Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of Gene Expression Phenotype in Amyotrophic Lateral Sclerosis Monocytes

Importance Amyotrophic lateral sclerosis (ALS) is a common adult-onset neurodegenerative disease characterized by selective loss of upper and lower motor neurons. Patients with ALS have persistent peripheral and central inflammatory responses including abnormally functioning T cells and activated microglia. However, much less is known about the inflammatory gene profile of circulating innate immune monocytes in these patients. Objective To characterize the transcriptomics of peripheral monocytes in patients with ALS. Design, Setting, and Participants Monocytes were isolated from peripheral blood of 43 patients with ALS and 22 healthy control individuals. Total RNA was extracted from the monocytes and subjected to deep RNA sequencing, and these results were validated by quantitative reverse transcription polymerase chain reaction. Main Outcomes and Measures The differential expressed gene signatures of these monocytes were identified using unbiased RNA sequencing strategy for gene expression profiling. Results The demographics between the patients with ALS (mean [SD] age, 58.8 [1.57] years; 55.8% were men and 44.2% were women; 90.7% were white, 4.65% were Hispanic, 2.33% were black, and 2.33% were Asian) and control individuals were similar (mean [SD] age, 57.6 [2.15] years; 50.0% were men and 50.0% were women; 90.9% were white, none were Hispanic, none were black, and 9.09% were Asian). RNA sequencing data from negative selected monocytes revealed 233 differential expressed genes in ALS monocytes compared with healthy control monocytes. Notably, ALS monocytes demonstrated a unique inflammation-related gene expression profile, the most prominent of which, including IL1B, IL8, FOSB, CXCL1, and CXCL2, were confirmed by quantitative reverse transcription polymerase chain reaction (IL8, mean [SE], 1.00 [0.18]; P = .002; FOSB, 1.00 [0.21]; P = .009; CXCL1, 1.00 [0.14]; P = .002; and CXCL2, 1.00 [0.11]; P = .01). Amyotrophic lateral sclerosis monocytes from rapidly progressing patients had more proinflammatory DEGs than monocytes from slowly progressing patients. Conclusions and Relevance Our data indicate that ALS monocytes are skewed toward a proinflammatory state in the peripheral circulation and may play a role in ALS disease progression, especially in rapidly progressing patients. This increased inflammatory response of peripheral immune cells may provide a potential target for disease-modifying therapy in patients with ALS.
Use of antipsychotics and risk of myocardial infarction: a systematic review and meta-analysis.

AIM There is emerging concern that antipsychotics may be associated with an increased risk of myocardial infarction (MI). A previous review identified five observational studies that did not provide an accurate estimate of the association between antipsychotic drug use and MI risk. More recent studies have produced variable results. METHODS We performed a systematic review and meta-analysis of observational studies to determine whether antipsychotic use affects the risk for MI. Our analysis included all observational studies that compared MI incidence among patients receiving antipsychotics vs. no treatment. RESULTS Nine observational studies were included in the analysis. The odds for developing MI were 1.88-fold higher (odds ratio (OR) 1.88, 95% confidence interval (CI) 1.39, 2.54) in antipsychotic users compared with individuals who had not taken antipsychotics. Subgroup analyses found an OR of 2.48 (95% CI 1.66, 3.69) among patients with schizophrenia and an OR of 2.64 (95% CI 2.48, 2.81) among short term (<30 days) antipsychotic users. CONCLUSION The findings of this meta-analysis support an increased risk of MI in antipsychotic drug users. The present systematic review expands previous knowledge by demonstrating an increased and more pronounced risk in short term users.
Identifying the Rehabilitative Potential of Electronically Monitored Release Preparation: A Randomized Controlled Study in Germany

As one of many fields of application, electronic monitoring (EM) of offenders can be used—in conjunction with other measures—for release preparation. Using such measures, policymakers expect an alleviation of the negative effects of imprisonment and the promotion of positive rehabilitative effects by adding structure and social support. At the same time, policymakers are willing to maintain community safety through the close supervision provided by EM. The present study examines participants’ psychological and psychosocial changes during two measures of electronically monitored release preparation, namely, home detention and early work release. These findings are compared with a randomized group of participants who remained in custody. In sum, we found no distinctive positive effects of the tested measures. Because most participants already displayed functional psychological characteristics at pretest, there was only a small margin for improvement through electronically monitored release preparation. We conclude that if rehabilitation is sought by the use of such measures, it is important to select a target group that is actually in need of rehabilitative support and equally important to conduct further research on the rehabilitative potential of EM measures.
Construction and Analysis of Weighted Brain Networks from SICE for the Study of Alzheimer's Disease

Alzheimer's Disease (AD) is the most common neurodegenerative disease in elderly people, and current drugs, unfortunately, do not represent yet a cure but only slow down its progression. This is explained, at least in part, because the understanding of the neurodegenerative process is still incomplete, being sometimes mistaken, particularly at the first steps of the illness, with the natural aging process. A better identification of how the functional activity deteriorates is thus crucial to develop new and more effective treatments. Sparse inverse covariance estimates (SICE) have been recently employed for deriving functional connectivity patterns from Positron Emission Tomography (PET) of brains affected by Alzheimer's Disease. SICE, unlike the traditional covariance methods, allows to analyze the interdependencies between brain regions factoring out the influence of others. To analyze the effects of the illness, connectivity patterns of brains affected by AD are compared with those obtained for control groups. These comparisons are, however, carried out for binary (undirected and unweighted) adjacency matrices with the same number of arcs. Additionally, the effect of the number of subjects employed or the validity of the regularization parameter used to compute the SICE have been not hitherto analyzed. In this paper, we delve into the construction of connectivity patterns from PET using SICE. In particular, we describe the effect that the number of subjects employed has on the results and identify, based on the reconstruction error of linear regression systems, a range of valid values for the regularization parameter. The amount of arcs is also proved as a discriminant value, and we show that it is possible to pass from unweighted (binary) to weighted adjacency matrices, where the weight of a connection corresponding to the existence of a relationship between two brain areas can be correlated to the persistence of this relationship when computed for different values of the regularization parameter and sets of subjects. Finally, network measures are computed for the connectivity patterns confirming that SICE may be particularly apt for assessing the efficiency of drugs, since it produces reliable brain connectivity models with small sample sizes, and that connectivity patterns affected by AD seem much less segregated, reducing the small-worldness.
Publication rate of abstracts of papers and posters presented at Medical Library Association annual meetings.

OBJECTIVES This study sought to ascertain the publication rate of abstracts presented at the annual meetings of the Medical Library Association (MLA) for the years of 2002 and 2003. The secondary objectives were to examine possible reasons for non-publication and factors influencing publication. METHODS A total of 442 abstracts from both meeting years, consisting of presented papers and posters, were examined. The 2 methods used to obtain a publication rate were literature searches and an online questionnaire sent to first authors. The questionnaire also asked abstract authors about reasons for non-publication and other factors that might have influenced their decisions about whether or not to submit the project for publication. RESULTS The overall publication rate from the survey was 26.5%, and the publication rate found via literature searching was 27.6%. The most common reason given for non-publication was time restrictions. Also notable was the large proportion of abstracts written by librarians working at universities and those having 25 or more years in the library profession. DISCUSSION Publication rates for abstracts presented at the Medical Library Association meetings for the years studied rank at the low end in comparison with other medical professional associations. Further research into factors affecting publication may reveal ways to increase this rate.
Associations of serum leptin, ghrelin and peptide YY levels with physical activity and cardiorespiratory fitness in adolescent boys with different BMI values

The aim of this study was to investigate the differences in associations of serum acylated and des-acylated ghrelin, peptide YY (PYY) and leptin levels with physical activity (PA) and cardiorespiratory fitness (CReF) in adolescent boys (mean age of 14.0 years) with overweight (OWB; n=55) and with normal weight (NWB; n=154). Methods: Total PA was measured by 7-day accelerometry (counts/min) and CReF by peak oxygen consumption (VO2peak/kg). Results: No differences were found in serum PYY, acylated ghrelin or des-acyl ghrelin levels, whereas mean leptin (11.6±10.6 vs. 2.0±2.7 ng/ml; p<0.05) and insulin (18.1±8.7 vs. 11.0±6.2 mU/l; p<0.05) levels were significantly higher in OWB compared to NWB. Mean CReF was significantly lower in OWB compared to NWB (39.7±8.7 vs. 50.5±6.8 ml/min/kg; p<0.05). Leptin was negatively correlated with CReF in both groups (r=-0.43; p<0.05), des-acylated ghrelin with CReF only in OWB (r =-0.36; p<0.05). In OWB leptin was negatively correlated with total PA (r=-0.32; p<0.05) and positively with sedentary time of PA (r=0.35; p<0.05). In NWB 28.1% of the variability of CReF was determined by leptin and insulin resistance index (HOMA-IR), whereas in OWB 71.9% was determined by trunk FM and BMI. Conclusions: Leptin concentration was inversely associated with CReF in adolescent boys independently of BMI in both groups, while des-acylated ghrelin was associated with CReF only in OWB. Low PA in OWB was associated with high serum leptin level.
An ontology for secure socio-technical systems

Security is often compromised by exploiting vulnerabilities in the interface between the organization and the information systems that support it. This reveals the necessity of modeling and analyzing information systems together with the organizational setting where they will operate. In this chapter we address this problem by presenting a modeling language tailored to analyze the problem of security at an organizational level. This language proposes a set of concepts founded on the notions of permission, delegation, and trust. The chapter also presents a semantics for these concepts, based on Datalog. A case study from the bank domain is employed to illustrate the proposed language.
The Effect of CuO Nanoparticles on Antimicrobial Effects and Shear Bond Strength of Orthodontic Adhesives

Statement of the Problem: Orthodontic appliances facilitate microbial plaque accumulation and increase the chance of white spot lesions. There is a need for new plaque control methods independent of patient's cooperation. Purpose: The aim of this study was to determine the effects of incorporating copper oxide (CuO) nanoparticles on antimicrobial properties and bond strength of orthodontic adhesive. Materials and Method: CuO nanoparticles were added to the composite transbond XT at concentrations of 0.01, 0.5 and 1 wt. %. To evaluate the antimicrobial properties of composites containing nanoparticles, the disk agar diffusion test was used. For this purpose, 10 discs from each concentration of nano-composites (totally 30 discs) and 10 discs from conventional composite (as the control group) were prepared. Then the diameter of streptococcus mutans growth inhibition around each disc was determined in blood agar medium. To evaluate the shear bond strength, with each concentration of nano-composites as well as the control group (conventional composite), 10 metal brackets were bonded to the human premolars and shear bond strength was determined using a universal testing machine. Results: Nano-composites in all three concentrations showed significant antimicrobial effect compared to the control group (p< 0.001). With increasing concentration of nanoparticles, antimicrobial effect showed an upward trend, although statistically was not significant. There was no significant difference between the shear bond strength of nano-composites compared to control group (p= 0.695). Conclusion: Incorporating CuO nanoparticles into adhesive in all three studied concentrations added antimicrobial effects to the adhesive with no adverse effects on shear bond strength.
Generic imatinib in the treatment of chronic myeloid leukemia: two years' experience in Latvia.

BACKGROUND Imatinib is tyrosine kinase inhibitor (TKI) and as a targeted anti-cancer agent has significantly changed chronic myeloid leukemia (CML) prognosis and patient survival. Currently TKI is the main therapy in CML Philadelphia chromosome-positive (Ph-positive) cases. When generics of imatinib appeared in the pharmaceuticals market, reimbursement policies in many countries switched to using generics or encouraged use of generic imatinib to lower the expenses. Cost savings were substantial; however, for doctors and CML patients the efficacy, safety and quality of generic imatinib were an issue of concern. OBJECTIVE Since the global number of CML patients, who in the future will have to switch from original imatinib to generic imatinib, is high, the aim of study was to monitor, whether during 24 months of generic imatinib usage patients maintain the achieved major molecular response (MMR) or whether the treatment results are inferior. METHODS We conducted a retrospective study, which included CML patients, who were above 18 years of age and who until May 2013 had used at least for 2 years (24 months) the original imatinib, and following that used at least for 24 months one of the generic imatinib medicines. In 2013, before switching to generic imatinib, all patients had reached MMR in accordance with European LeukemiaNet (ELN) Guidelines. Every three months blood count, BCR-ABL fusion gene (BCR-ABL), biochemical analysis and side effect were monitored. RESULTS Our study proved that CML patients, who had achieved MMR by original imatinib therapy, retained MMR during 24 months of generic imatinib therapy. Nobody was switched to second line generation TKI. During observation period neither haematological, nor non-hematological toxicity was found. CONCLUSION Our study proved that CML patients, who had achieved MMR by original imatinib therapy, retained MMR during 24 months of generic imatinib therapy. This demonstrates that generic imatinib is not inferior to original imatinib. As to expenses, the annual costs of generic imatinib are lower by 96%, which is a significant benefit to health-care financing.
The JmjN Domain of Jhd2 Is Important for Its Protein Stability, and the Plant Homeodomain (PHD) Finger Mediates Its Chromatin Association Independent of H3K4 Methylation*♦

Histone lysine methylation is a dynamic process that plays an important role in regulating chromatin structure and gene expression. Recent studies have identified Jhd2, a JmjC domain-containing protein, as an H3K4-specific demethylase in budding yeast. However, important questions regarding the regulation and functions of Jhd2 remain unanswered. In this study, we show that Jhd2 has intrinsic activity to remove all three states of H3K4 methylation in vivo and can dynamically associate with chromatin to modulate H3K4 methylation levels on both active and repressed genes and at the telomeric regions. We found that the plant homeodomain (PHD) finger of Jhd2 is important for its chromatin association in vivo. However, this association is not dependent on H3K4 methylation and the H3 N-terminal tail, suggesting the presence of an alternative mechanism by which Jhd2 binds nucleosomes. We also provide evidence that the JmjN domain and its interaction with the JmjC catalytic domain are important for Jhd2 function and that Not4 (an E3 ligase) monitors the structural integrity of this interdomain interaction to maintain the overall protein levels of Jhd2. We show that the S451R mutation in human SMCX (a homolog of Jhd2), which has been linked to mental retardation, and the homologous T359R mutation in Jhd2 affect the protein stability of both of these proteins. Therefore, our findings provide a mechanistic explanation for the observed defects in patients harboring this SMCX mutant and suggest the presence of a conserved pathway involving Not4 that modulates the protein stability of both yeast Jhd2 and human SMCX.
CATaDa reveals global remodelling of chromatin accessibility during stem cell differentiation in vivo

Regulation of eukaryotic gene expression is coordinated by dynamic changes to chromatin states throughout development. Measurements of accessible chromatin are used extensively to identify genomic regulatory elements. Whilst the chromatin landscapes of pluripotent stem cells are well characterised, chromatin accessibility changes in the development of somatic stem cell lineages are not well defined. Here we show that tissue specific chromatin accessibility data can be produced via ectopic expression of E. coli Dam methylase in vivo, without the requirement for cell-sorting. We have profiled chromatin accessibility in individual cell types of the Drosophila neural and midgut stem cell lineages. Functional cell-type specific enhancers were identified, as well as novel motifs enriched at diferent stages of development. Finally, we show global changes in the accessibility of chromatin between stem-cells and their diferentiated progeny. Our results demonstrate the dynamic nature of chromatin accessibility in somatic tissues during stem cell diferentiation and provide a novel approach to understanding the gene regulatory mechanisms underlying development.
Be tick aware: when and where to check cats and dogs for ticks

Tickborne disease represents a long established risk to human and pet populations. Increasing pet travel and importation is occurring concurrently with an expanding distribution of tick vectors and tickborne diseases, bringing new challenges for veterinarians. In the UK, the most common tick species, Ixodes ricinus , bites humans and companion animals, and can put both groups at risk of endemic diseases such as Lyme disease.1–5 The prevalence of Lyme disease-causing Borrelia in ticks removed from dogs and cats in the UK is low, approximately 2 per cent.1 4 5 Recent large-scale incidence data for Lyme disease in cats and dogs are lacking but the presence of causative agents in ticks attached to cats and dogs demonstrates that they are being exposed to infection. The wide range of non-pathognomonic ways in which Lyme disease can present also means it is likely to be underdiagnosed. Dogs and cats may also act as transport hosts for infected ticks, moving them into new locations. Other tickborne diseases may also pose a risk. For example, Babesia canis has recently been reported for the first time in the UK6 and increasing numbers of Rhipicephalus sanguineus ticks are being found on recently travelled or imported dogs.7 These threats make tick surveillance and accurate tick prevention advice for people and their companion animals vital for both human and animal health. Veterinary professionals should recommend licensed tick preventive products that rapidly kill or repel ticks for pets whose lifestyle puts them at increased risk of tick exposure or for pets travelling abroad (ESCCAP UK & Ireland). In addition, owners should check themselves and their pets regularly and safely remove any ticks found. …
Estimation of ultrasound reference values for the upper limb peripheral nerves in adults

Abstract The objective of this study is to estimate the reference values for the upper limb peripheral nerves in adults. The demographics and physical characteristics of 69 adult healthy volunteers were evaluated and recorded. In addition, the side to side differences of the estimated reference values and their correlations with the age, weight, height, and body mass index (BMI) were evaluated. Cross-sectional area reference values of the upper limb nerves did not correlate with height; however, they correlated with age, weight, and BMI in some scanned sites. The data obtained in this study could be helpful in future diagnosis of peripheral nerve disorders of the upper limb.
Recolonizing gray wolves increase parasite infection risk in their prey

Abstract The recent recolonization of Central Europe by the European gray wolf (Canis lupus) provides an opportunity to study the dynamics of parasite transmission for cases when a definitive host returns after a phase of local extinction. We investigated whether a newly established wolf population increased the prevalence of those parasites in ungulate intermediate hosts representing wolf prey, whether some parasite species are particularly well adapted to wolves, and the potential basis for such adaptations. We recorded Sarcocystis species richness in wolves and Sarcocystis prevalence in ungulates harvested in study sites with and without permanent wolf presence in Germany using microscopy and DNA metabarcoding. Sarcocystis prevalence in red deer (Cervus elaphus) was significantly higher in wolf areas (79.7%) than in control areas (26.3%) but not in roe deer (Capreolus capreolus) (97.2% vs. 90.4%) or wild boar (Sus scrofa) (82.8% vs. 64.9%). Of 11 Sarcocystis species, Sarcocystis taeniata and Sarcocystis grueneri occurred more often in wolves than expected from the Sarcocystis infection patterns of ungulate prey. Both Sarcocystis species showed a higher increase in prevalence in ungulates in wolf areas than other Sarcocystis species, suggesting that they are particularly well adapted to wolves, and are examples of “wolf specialists”. Sarcocystis species richness in wolves was significantly higher in pups than in adults. “Wolf specialists” persisted during wolf maturation. The results of this study demonstrate that (1) predator–prey interactions influence parasite prevalence, if both predator and prey are part of the parasite life cycle, (2) mesopredators do not necessarily replace the apex predator in parasite transmission dynamics for particular parasites of which the apex predator is the definitive host, even if meso‐ and apex predators were from the same taxonomic family (here: Canidae, e.g., red foxes Vulpes vulpes), and (3) age‐dependent immune maturation contributes to the control of protozoan infection in wolves.