Miracle-dz/UniFAR-FTUs huggingface dataset:
MicroRNA expression profiles discriminate childhood T‐ from B‐acute lymphoblastic leukemia

MicroRNAs (miRNAs) play a critical role on biological and cellular processes; the search for functional markers may be of importance for differential diagnosis, prognosis, and development of new therapeutic regimens. In this context, we evaluated the bone marrow miRNA profile of Brazilian children exhibiting T‐ or B‐cell acute lymphoblastic leukemia (T‐ALL or B‐ALL), using massive parallel sequencing, using the HiSeq 2500 platform (Illumina). The differential expression analysis was conducted considering a leave‐one‐out approach and FDR ≤ 0.05. Machine learning algorithms were applied to search for the disease subset biomarkers. Target prediction, functional enrichment, and classification of biological categories were also performed. Sixteen miRNAs were differentially expressed between T‐ and B‐ALL, of which 10 (miR‐708‐5p, miR‐497‐5p, miR‐151a‐5p, miR‐151b, miR‐371b‐5p, miR‐455‐5p, miR‐195‐5p, miR‐1266‐5p, miR‐574‐5p, and miR‐425‐5p) were downregulated and six (miR‐450b‐5p, miR‐450a‐5p, miR‐542‐5p, miR‐424‐5p, miR‐629‐5p, and miR‐29c‐5p) were upregulated in childhood T‐ALL. These miRNAs may be used for distinguishing childhood lymphoblastic leukemia subtypes, since it provided the clear separation of patients in these two distinct groups. Six relevant biological pathways were identified according to their role in leukemia, namely, viral carcinogenesis, cell cycle, and B‐cell receptor signaling pathways for induced miRNAs and TGF‐beta signaling, apoptosis, and NF‐kappa B signaling for the repressed miRNAs, of which several miRNA gene targets participate in cell differentiation and hematopoiesis processes. Machine learning analysis pointed out miR‐29c‐5p expression as the best discriminator between childhood T‐ and B‐ALL, which is involved in calcium signaling, critical for B‐cell lymphocyte fate. Further studies are needed to assure the role of the 16 miRNAs and miR‐29c‐5p on acute lymphoblastic leukemia subtypes and on disease prognosis.
Thoughts on the Future: The Perspectives of Elderly People with Early-Stage Alzheimer's Disease and the Implications for Advance Care Planning

Background: Early diagnosis in dementia is promoted to allow patients to engage in advance care planning (ACP) while still competent to do so and thereby to extend their autonomy into futures in which they lack decision-making capacity. However, engagement of people with dementia in ACP lags behind. The aim of this study was to investigate the thoughts of people with early-stage Alzheimer's disease (AD) with regard to future care and treatment and the implications for ACP. Methods: A qualitative study using explorative semistructured interviews was conducted with 24 individuals diagnosed with early-stage AD. Results: Participants were found to be very capable of sharing their experiences, often becoming more open and talkative in the course of the interview. For participants, thinking about the future involved an ongoing process of balancing feelings of fear and hope, but the overall tendency among this group was to try to live one day at a time and avoid worrying about the future. Conclusions: Although ACP is considered to be a key element of high-quality palliative and end-of-life care, engagement in ACP by people with early-stage AD on their own initiative is limited. Additional interventions are essential in order to stimulate and support people with early-stage AD to initiate actions with regard to ACP. The development of alternative models for ACP in dementia care is recommended. However, the advisability of ACP in early-stage AD is not without dispute. Ethical issues, such as whether steering people toward ACP is justified, should be addressed in further research and the role of advance directives needs to be reconsidered.
Variation in innate immunity genes and risk of multiple myeloma

Multiple myeloma (MM) is a B‐cell lymphoid malignancy suspected to be associated with immunologic factors. Given recent findings associating single‐nucleotide polymorphisms (SNPs) in innate immunity genes with non‐Hodgkin lymphoma, we conducted an investigation of innate immune gene variants using specimens from a population‐based case‐control study of MM conducted in Connecticut women. Tag SNPs (N = 1461) summarizing common variation in 149 gene regions were genotyped in non‐Hispanic Caucasian subjects (103 cases, 475 controls). Odds ratios (OR) and 95% confidence intervals (CI) relating SNP associations with MM were computed using unconditional logistic regression, while the MinP test was used to investigate associations with MM at the gene level. We calculated permutation‐adjusted P‐values and false discovery rates (FDR) to account for the number of comparisons performed in SNP‐level and gene‐level tests, respectively. Three genes were associated with MM when controlling for a FDR of ≤10%: SERPINE1 (PMinP < 0.0001; FDR = 0.02), CCR7 (PMinP = 0.0006; FDR = 0.06) and HGF (PMinP = 0.001; FDR = 0.08). Two SNPs demonstrated robust associations: SERPINE1 rs2227667 (P = 2.1 × 10−5, Ppermutation = 0.03) and HGF rs17501108 (P = 5.0 × 10−5, Ppermutation = 0.07). Our findings suggest that genetic variants in SERPINE1 and HGF, and possibly CCR7, are associated with MM risk, and warrant further investigation in other studies. Copyright © 2010 John Wiley & Sons, Ltd.
Assessing the representativeness of Canadian Hospitals Injury Reporting and Prevention Programme (CHIRPP) sport and recreational injury data in Calgary, Canada

The objective of this study was to assess the representativeness of sport and recreational injury data from Canadian Hospital Injury Reporting and Prevention Programme (CHIRPP) in Calgary. Internal representativeness was assessed by comparing CHIRPP and regional health administrative data (ambulatory care classification system-ACCS) at Alberta Children's Hospital (ACH). External representativeness was assessed by comparing CHIRPP with ACCS at all hospitals. Comparisons were performed using descriptive statistics for top injury-producing sports and sports that produced severe injuries. Stratified distributions of injury-producing sports by gender, age group and severity of injury in CHIRPP and ACCS were compared. The proportion of all injuries in Calgary captured by CHIRPP was 64.8% (99%CI: 64.02–65.54%) (16,977/26,206). CHIRPP captured more cases of top injury-producing sports than ACCS at ACH. Rankings of top injury-producing sports in CHIRPP and ACCS at ACH were remarkably consistent (ρ = 0.92, p < 0.0001). Rankings of top injury-producing sports in CHIRPP and ACCS at all hospitals were almost identical (ρ = 0.98, p < 0.0001). Stratified distributions of top injury-producing sports by gender, age group and the severity of injury showed strong consistency between CHIRPP and ACCS. It is concluded that CHIRPP in Calgary provides a representative profile of injuries compared to regional health administrative data. This project supports the use of CHIRPP for establishing injury prevention priorities.
Analysis of EEG activity during sleep - brain hemisphere symmetry of two classes of sleep spindles

Analysis of EEG activity during sleep - brain hemisphere symmetry of two classes of sleep spindles This paper presents automatic analysis of some selected human electroencephalographic patterns during deep sleep using the Matching Pursuit (MP) algorithm. The periodicity of deep sleep EEG patterns was observed by calculating autocorrelation functions of their percentage contributions. The study confirmed the increasing trend of amplitude-weighted average frequency of sleep spindles from frontal to posterior derivations. The dominant frequencies from the left and the right brain hemisphere were strongly correlated.
Motala Municipality – a sustainable Safe Community in Sweden

An extensive research project concerning injury prevention was planned and initiated in Motala Municipality in the early 1980s. This article summarises 25 years of work for injury prevention and safety promotion in Motala. Evaluation of both process and effect were conducted based on a quasi-experimental study design, as well as cost-effectiveness and cost-benefit analyses of interventions. Initial evaluations results showed an annual incidence of injuries of 118.9/1000 citizens in 1983/1984 consisting of injuries at home (35%), sports injuries (18.9%), injuries at work (13.7%), traffic-related injuries (12.8%) and other injuries (19.5%). The annual social economic costs of injuries were estimated at 116 million Swedish crowns (SEK). By 1989, after two years of preventive work, the incidence of injuries was reduced by 13%. The greatest decrease was among the moderate severity category of injuries (41%). The social economic costs were thereby reduced by 21 million SEK per year. Since then, work with injury prevention has continued and annual evaluations have shown that the incidence of injuries, with some fluctuation, has continued to decrease up to the latest evaluation in 2008. The total decrease during the study period was 37%. This study shows that community-based injury prevention work according to the Safe Community model is a successful and cost-effective way of reducing injuries in the local community.
Injuries from falling objects in the United Arab Emirates

Our aim was to study the demography, anatomical regions injured, severity, and outcome of hospitalised trauma patients who were injured by falling objects in order to give recommendations regarding their prevention in the UAE. All trauma patients who were injured by falling objects and were admitted to Al Ain Hospital for more than 24 hours, or died after arrival to the hospital were studied for over 3 years. One hundred forty nine patients having a mean age (SD) > 34 (12.1) years were studied. The annual incidence of hospitalisation was 10.7/100,000 persons per year. Majority (97.3%) were males and 73.2% from the Indian subcontinent. The most common location for injury was work (88.6%), followed by home (9.4%). Patients injured at home were younger (p < 0.0001), and were more females (p < 0.0001). Extremities and head/neck were the most common injured regions; 1.3% of patients died. Males from the Indian subcontinent are at a higher risk of being injured by falling objects especially at work. Safety education and programs, environmental changes, use of protective devices including helmets or special shoes, and proper enforcement of the safety guidelines could reduce hospitalisations, disability, and death from these injuries.
Changes in plasma adiponectin, IL-6, TNF-α and free fatty acid concentrations in obese Japanese men.

The risk of developing metabolic syndrome, hypertension, type 2 diabetes, and hyperlipidemia increases with obesity, and an elevated visceral fat content has been associated with a higher incidence of metabolic risk factors. We investigated differences in IL-6 (Interleukin-6), TNF-α (tumor necrosis factor-α), adiponectin and FFA (free fatty acid) levels in obese and non-obese Japanese men. Five obese men (BMI: 32.4±4.9 kg/m) and five non-obese men (BMI: 23.2±2.9 kg/m 2 ) participated in this study.IL-6 levels were significantly higher in obese than in non-obese subjects, whereas no significant differences were observed in TNF-α, adiponectin, or FFA levels. These results suggested that IL-6 levels may be affected more by obesity in Japanese men than TNF-α and adiponectin levels, which may, in turn, influence the pathophysiology of obesity in Japanese individuals. Short Communication Sato et al.; BJMMR, 7(2): 131-137, 2015; Article no.BJMMR. 2015.316 132
The Alberta Stroke Program Early CT Score in Clinical Practice: What have We Learned?

The introduction of brain imaging with computed tomography revolutionised the treatment of patients with acute ischaemic stroke. With the visual differentiation of haemorrhagic stroke from ischaemic stroke, thrombolytic therapy became feasible. The Alberta Stroke Program Early CT Score was devised to quantify the extent of early ischaemic changes in the middle cerebral artery territory on noncontrast computed tomography. With its systematic approach, the score is simple and reliable. However, the assessment of early ischaemic changes and Alberta Stroke Program Early CT scoring require training. The Alberta Stroke Program Early CT Score is a strong predictor of functional outcome. Furthermore, the effectiveness of intraarterial thrombolysis in patients with middle cerebral artery occlusion shows effect modification by the Alberta Stroke Program Early CT Score. This review summarises the Alberta Stroke Program Early CT Score methodology. We illustrate current knowledge regarding Alberta Stroke Program Early CT Score applied to clinical trials and comment on how Alberta Stroke Program Early CT Score may facilitate clinical treatment decision making and future trial design. Moreover, we introduce a modification of the Alberta Stroke Program Early CT Score methodology that disregards isolated cortical swelling, i.e. focal brain swelling without associated parenchymal hypoattenuation, as early ischaemic changes in the Alberta Stroke Program Early CT Score system.
Safety legislation, public health policy and drowning prevention

The article presents a study on drowning as the major cause of mortality and morbidity of the children in Brisbane, Queensland. It states that the drowning death rates of young children, aging 0-4 years old, had decreased after the introduction of safety legislation. The study has shown that the drowning incidents of young children will continue to reduce with the introduction of safety legislation and enforced compliance, in combination with education for safety and ongoing advocacy.
AACCI Approved Methods Technical Committee Report: Collaborative Study on the Immunochemical Determination of Intact Gluten Using an R5 Sandwich ELISA

In 2008, the AACC International Protein Technical Committee (now the Protein and Enzymes Technical Committee) initiated a collaborative study of a method for determining gluten in selected foods using an R5 antibody sandwich ELISA system. The method has been approved as AACCI Approved Method 38-50.01. The new method has been validated for testing foods to determine that they conform to the newly defined Codex threshold of 20 mg of gluten/kg in total for gluten-free products.
Situational factors associated with road traffic crashes: A case–control study on the Yaoundé–Douala road section, Cameroon

Our aim was to identify situational factors associated with road traffic crash sites on a heavy traffic 243 km road section in Cameroon. We conducted a case–control study on Yaoundé–Douala road section. Cases were sites where an injury crash was reported to one of the 13 police stations on this road section over a period from 2004 to 2007. Control sites were randomly selected on same road section where no crash was reported. A total of 474 crash sites and 509 control sites were included. Results showed statistically significant associations with injury crash risk for flat road profile (adjusted odds ratio (aOR) = 1.52, 95% confidence interval (CI) = 1.15–2.01), irregular road surface conditions (aOR = 1.43, 95% CI = 1.04–1.99), roadside obstacle situated less than 4 m from the road edge (aOR = 1.99, 95% CI = 1.09–3.63), three-legged intersections (aOR = 3.11, 95% CI = 1.15–8.39) and four-legged intersections (aOR = 3.23, 95% CI = 1.15–6.92). Built-up areas were significantly associated with injury crash sites where verge depth was 0 m (aOR = 2.33; 95% CI = 1.97–2.77). Our results suggest that traffic calming and speed enforcement measures in built-up areas, intersections and on flat sections of this road should be strongly encouraged.
The Fundamentals of Clinical Neuropsychiatry

Increasingly, psychiatrists make little distinction between psychiatric and neurologic disorders, considering them all as dysfunctions of the central nervous system. In a clear and engaging style, the author explains what to do and how to do it, giving the rationale for each step, and synthesizing neuropsychiatric principles with practical guidelines for diagnosis and management of adult patients. Many tables are included for quick reference and to help the reader to quickly see the big picture of a given topic. The book covers personality and personality disorders, depression, bipolar disorder, psychiatric disorders, alcohol and substance abuse, epilepsy, traumatic brain injury and stroke, anxiety disorders, obsessive compulsive disorders, headache and violence. It can be used as an introductory text for psychiatric residents, medical students, and others who care for persons with behavioral disorders. It can also be used as a clinical manual or reference by practitioners in psychiatry and neurology.
Patterns of missplicing caused by RB1 gene mutations in patients with retinoblastoma and association with phenotypic expression

We have analyzed RNA from retinoblastoma patients and unaffected carriers with various RB1 gene mutations to determine the patterns of missplicing and associations with phenotypic expression. Most sequence alterations in or in the neighborhood of conserved splice signals that we tested resulted in simple exon skipping (15 mutations) or intron inclusion (new acceptor AG‐sites, four mutations) as expected. Two mutations resulted in skipping of a neighboring exon (exon 11), a complex pattern indicating competition for correct lariat formation. We observed no activation of a cryptic splice site but found that a recurrent missense mutation in exon 7 creates a new splice site (two families). RT‐PCR analysis enabled us to confirm the presence and to characterize the transcriptional consequences of gross insertions and deletions in the RB1 gene in six patients, including two patients with mutational mosaicism. We also used RT‐PCR analysis to search for unknown mutations in 15 patients and identified three oncogenic point mutations deep in introns. Two of these mutations are recurrent thus indicating that, despite the vast extent of the introns of the RB1 gene, few bases are effective targets for oncogenic mutations. When analyzing associations between phenotypic expression (16 families) and mutational consequences we observed no link to the presence or absence of a premature termination codon in the mutant transcript. However, the location of a mutation relative to the splice sequence has a strong and consistent influence on phenotypic expression. Hum Mutat 29(4), 475–484, 2008. © 2008 Wiley‐Liss, Inc.
Glycated haemoglobin (HbA1C) as an indicator of job strain

As a part of the WHO-initiated MONICA project 248, 50- and 60-year-old men participated in a study on the relations between HbA1C (glycated haemoglobin) and job stress indicators. The participants answered a questionnaire on work, social and health conditions and underwent clinical examinations which included measurements of blood pressure, serum cholesterol, triglycerides, HDL and HbA1C. Using the demand—control model for measuring job strain suggested by Karasek, we classified the employed participants according to those who had suffered job strain and those who had not. This was done in two different ways. The subjective classification was based on the participants' statements regarding demand and control in their job, whereas the objective one was based on job title, mode of payment, etc. The levels of HbA1C were significantly higher among participants with objective job strain, high daily coffee consumption and low alcohol consumption. Coronary risk factors and subjective job strain did not correlate significantly with the level of HbA1C.
New routes in frontotemporal dementia drug discovery

ABSTRACT Introduction: Research into the pathogenic mechanisms behind frontotemporal dementia (FTD) has yielded several new targets for therapeutic intervention; such targets include specific new pathways uncovered by mutations as well as targets involving the modulation, formation and degradation of protein aggregates. Areas covered: Herein, the authors outline the principal molecular causes underlying FTD to date and the research that has been performed in these areas with respect to an eventual corrective strategy. Expert opinion: While it is worthwhile targeting pathways affected by specific mutations with a causative loss of function linked to FTD, research still has to contend with issues including the remaining presence of protein aggregates or that treatments are rarely universally applicable. Aiming to recover function in a downstream target caused by the protein aggregates will likely be insufficient due to the large cascade of events affected. It is our belief that the clearance of these aggregates and the inhibition of protein misfolding are more appropriate and direct routes to an eventual therapy.
An overview of hydrogen deuterium exchange mass spectrometry (HDX-MS) in drug discovery

ABSTRACT Introduction: Hydrogen deuterium exchange mass spectrometry (HDX-MS) is a powerful methodology to study protein dynamics, protein folding, protein-protein interactions, and protein small molecule interactions. The development of novel methodologies and technical advancements in mass spectrometers has greatly expanded the accessibility and acceptance of this technique within both academia and industry. Areas covered: This review examines the theoretical basis of how amide exchange occurs, how different mass spectrometer approaches can be used for HDX-MS experiments, as well as the use of HDX-MS in drug development, specifically focusing on how HDX-MS is used to characterize bio-therapeutics, and its use in examining protein-protein and protein small molecule interactions. Expert opinion: HDX-MS has been widely accepted within the pharmaceutical industry for the characterization of bio-therapeutics as well as in the mapping of antibody drug epitopes. However, there is room for this technique to be more widely used in the drug discovery process. This is particularly true in the use of HDX-MS as a complement to other high-resolution structural approaches, as well as in the development of small molecule therapeutics that can target both active-site and allosteric binding sites.
Functional analysis of an ADAMTS10 signal peptide mutation in Weill‐Marchesani syndrome demonstrates a long‐range effect on secretion of the full‐length enzyme

We report the identification and functional analysis of the first missense ADAMTS10 mutation (c.73G>A; p.Ala25Thr) causing recessive Weill‐Marchesani syndrome (WMS). The Ala25 residue affected by the missense mutation is at the −1 position relative to the ADAMTS10 signal peptidase cleavage site. p.Ala25Thr substituted full‐length ADAMTS10 showed consistent and significantly diminished secretion in both HEK293F and Cos‐1 cells. However, a C‐terminally truncated construct lacking the ancillary domain and containing only the signal peptide, the propeptide and the catalytic domain (p.Ala25Thr Pro‐Cat) was efficiently secreted in both HEK293F cells and Cos‐1 cells. Edman degradation of purified p.Ala25Thr Pro‐Cat and p.Ala25Thr substituted full‐length ADAMTS10 from HEK293F cells demonstrated correct signal peptide processing. Thus, the p.Ala25Thr substitution hinders secretion of full‐length ADAMTS10, but not Pro‐Cat from cells, yet permits signal peptide removal. We infer that folding of the complex C‐terminal ancillary domain is the rate‐limiting step in biosynthesis of ADAMTS10, and that it (but not Pro‐Cat) is sensitive to subtle changes in efficiency of signal peptide cleavage. These observations represent an unprecedented effect of a signal peptide mutation and support a model in which the initial cotranslational processing events during protein biosynthesis can have long‐range effects on protein folding and secretion. Hum Mutat 0, l–10, 2008. © 2008 Wiley‐Liss, Inc.