Miracle-dz/UniFAR-FTUs huggingface dataset:
A model for ultrasound contrast agent in a phantom vessel

A theoretical framework to model the dynamics of Ultrasound Contrast Agent (UCA) inside a phantom vessel is presented. The model is derived from the reduced Navier-Stokes equation and is coupled with the evolving flow field solution inside the vessel by a similarity transformation approach. The results are computed, and compared with experiments available in literature, for the initial UCA radius of Ro=1.5 μm and 2 μm for the vessel diameter of D=12 μm and 200 μm with the acoustic parameters as utilized in the experiments. When compared to other models, better agreement on smaller vessel diameter is obtained with the proposed coupled model. The model also predicts, quite accurately, bubble fragmentation in terms of acoustic and geometric parameters.
Toll‐like receptor 4 polymorphism is associated with coronary stenosis but not with the occurrence of acute or old myocardial infarctions

Objective. Atherosclerosis is considered to be a chronic inflammatory disease. Toll‐like receptor 4 (TLR‐4), a key mediator in activating inflammatory cascade, has an A‐to‐G functional polymorphism that changes aspartic acid to glycine at position 299. TLR‐4 is activated by, for example, lipopolysaccharides. The purpose of this study was to investigate the role of a common Asp299Gly polymorphism of the TLR‐4 gene in atherosclerosis. Material and methods. The study comprised autopsy material from 657 men (the Helsinki Sudden Death Study; mean age 53, range 33–70 years). Results. Fewer G‐allele carriers had 3‐vessel coronary artery disease compared with AA homozygotes (OR 0.32; 95 % CI, 0.12–0.88, p = 0.027), and they also had a lower mean value for maximal coronary stenosis (p = 0.019). TLR‐4 polymorphism was not significantly associated with the occurrence of acute or old myocardial infarction (MI). Conclusions. The G allele of the TLR‐4 gene, which is associated with a lower inflammation response, was associated with a lower risk of coronary stenosis but not with the occurrence of MI and hence is not a major factor in the development of coronary atherosclerosis.
Effects of stressor predictability on escape learning and sleep in mice.

STUDY OBJECTIVES Controllable stress, modeled by escapable shock (ES), can produce significant alterations in post-stress sleep, including increased rapid eye movement (REM) sleep. Recent work has demonstrated that post-stress sleep may be influenced by stressor predictability, modeled by predictive auditory cues. In this study, we trained mice with ES, either signaled (SES) or unsignaled (UES) by auditory cues, and investigated the effects of predictability on escape learning and sleep associated with ES. DESIGN Adult male BALB/cJ mice were implanted for recording electroencephalography and activity via telemetry. After the mice recovered from surgery, baseline sleep recordings were obtained. The mice were then randomly assigned to SES and UES conditions. Both groups had control over the duration of footshocks (0.5 mA; 5.0 sec maximum duration) by moving to the non-occupied chamber in a shuttlebox. SES mice were presented tones (90 dB, 2 kHz, 10 sec maximum duration) that started 5.0 sec prior to and co-terminated with footshocks. UES mice were presented identical tones that were not synchronized to shock presentation. ES training continued for 2 consecutive days (EST1 and EST2) with 20 footshock presentations (1 min inter-stimulus intervals). Seven days after EST2, the animals were re-exposed to the training chamber (context) alone for 30 min. MEASUREMENTS AND RESULTS Escape latency was used to determine successful or unsuccessful escape learning. Sleep was scored for 20 h for baseline and on each treatment day. Freezing in the training context was scored as a behavioral index of fear. Nine of 14 SES mice successfully learned escape (SESl), and 5 failed to learn escape (SESf). Compared with baseline, SESl mice, but not SESf mice, showed significantly increased post-shock REM. All UES mice learned escape and showed enhanced post-shock REM. Freezing and sleep did not differ among groups on the context re-exposure day. CONCLUSIONS The results indicate that information available in a stressful situation can affect an animal's ability to learn an appropriate response and post-stress sleep. CITATION Machida M; Yang L; Wellman LL; Sanford LD. Effects of stressor predictability on escape learning and sleep in mice. SLEEP 2013;36(3):421-430.
Age, abdominal obesity, and glycated hemoglobin are associated with carotid atherosclerosis in type 2 diabetes patients with nonalcoholic fatty liver disease.

AIM The aim of this study was to evaluate the impact of clinical parameters and indices of body composition on the relation between non-alcoholic fatty liver disease (NAFLD) and carotid intima-media thickness (cIMT), in a type 2 diabetes mellitus population (T2DM). MATERIAL AND METHODS We retrospectively enrolled 336 T2DM outpatients who regularly attended Regina Maria Clinic in Cluj. Clinical, anthropometric and biochemical parameters were measured. Ultrasonography (US) was used to assess hepatic steatosis (HS) in all patients and cIMT in 146 subjects. Body composition was assessed by bioelectric impedance (BIA, InBody 720) in all patients. RESULTS cIMT was correlated with age (r=0.25; p=0.004), systolic blood pressure (r=0.18; p=0.041), glycated haemoglobin A1C (HbA1C, r=0.20; p=0.04), and with coronary artery disease (r=0.20; p=0.007). HS did not correlate with cIMT (r=0.04; p=0.64). cIMT was correlated with visceral fatty area (VFA, r=0.18; p=0.014) but not with other indices of body composition. Homeostasis model assessment for insulin resistance (HOMA-IR) was not correlated with cIMT (r=0.17; p=0.086). After multivariate analysis, age, HbA1c, and VFA were good independent predictors of cIMT (r=0.45; p < 0.001). CONCLUSIONS These results are suggestive that in T2DM patients, fatty liver is not a direct mediator of early carotid atherosclerosis. Our data indicate that visceral fat accumulation and HbA1C are determinant factors of cIMT sugesting that controlling abdominal obesity and hyperglicemia might reduce atherosclerotic disease risk in NAFLD-T2DM subjects.
Applicability of mitochondrial DNA for the identification of Arvicolid species from faecal samples: a case study from the threatened Cabrera’s vole

Arvicolid mitochondrial genomes evolve faster than in any other mammalian lineage. The genetic diversity exhibited by these rodents contrasts sharply with their phenotypic homogeneity. Furthermore, faecal droppings from Arvicolid rodents of similar body size are almost undistinguishable on the basis of pellet morphology and content. In this study, we advantaged from their high genetic diversity vs. phenotypic homogeneity to document the applicability of mtDNA extraction from vole droppings for latter identification of such via a rapid and efficient nested PCR‐based technique using the threatened Microtus cabrerae as a model species. We sequenced the mitochondrial control region from 75 individuals belonging to 11 species of Arvicolinae from Spain, Portugal, Greece and Italy, and an additional 19 sequences from ten Microtus species from other countries were downloaded from Genbank. Based on these control region sequences, we successfully designed and applied a nested PCR for M. cabrerae‐specific and arvicolid‐generic mtDNA markers to differentiate Cabrera’s vole faecal samples among other species of the Arvicolinae subfamily. Although this study used Cabrera’s vole as a model species, similar techniques based on mtDNA sequences may find a broader applicability for noninvasive genetic conservation of vole species and their populations.
Managing work life with systemic sclerosis.

OBJECTIVE To explore how individuals with SSc manage their work life. METHODS We conducted four focus group interviews, which included 17 patients currently working at least 20 h per week. The interviews were recorded and transcribed verbatim. The transcribed texts were analysed according to thematic content analysis. Relevant statements that generated preliminary categories were identified, after which themes and underlying subthemes were generated. RESULTS The participants perceived their work role as being important, giving them a structure in everyday life and a sense of being useful members of society. Work and private life were interacting, and different adjustments had been developed to create a satisfactory balance of activities in daily life. Three themes emerged: adjustment of work situation, adapting to own resources and disclosing limitations. Reduced working hours, flexibility in the workplace concerning time schedule, room and tasks were all valuable adjustments, and were dependent on the employer, fellow workers as well as the individual's attitude towards informing employer and colleagues about his/her limitations. The participants had simplified and rationalized a lot of household chores and pointed to the importance of prioritizing meaningful activities, as well as the necessity of having time for rest and recovery. CONCLUSIONS Reduced working hours, work flexibility and prioritizing meaningful activities and recovery were important factors in order to manage work life. Intervention, including problem-solving techniques and re-designing of activities in daily life, could be useful to coach individuals towards finding a balance in their work life.
Development of a Robust, Versatile, and Scalable Inoculum Train for the Production of a DNA Vaccine

For many microbial fermentation processes, the inoculum train can have a substantial impact on process performance in terms of productivity, profitability, and process control. In general, it is understood that a well‐characterized and flexible inoculum train is essential for future scale‐up and implementation of the process in a pilot plant or manufacturing setting. A fermentation process utilizing E. coli DH5 for the production of plasmid DNA carrying the HIV gag gene for use as a vaccine is currently under development in our laboratory. As part of the development effort, we evaluated inoculum train schemes that incorporate one, two, or three stages. In addition, we investigated the effect of inoculum viable‐cell concentrations, either thawed or actively growing, over a wide range (from 2.5 × 104 to 1.0 × 108 viable cells/mL or approximately 0.001% to 4% of final working volume). The various inoculum trains were evaluated in terms of final plasmid yield, process time, reproducibility, robustness, and feasibility at large scale. The results of these studies show that final plasmid yield remained in the desired range, despite the number of stages or inoculation viable‐cell concentrations comprising the inoculum train. On the basis of these observations and because it established a large database, the first part of these investigations supports an exceptional flexibility in the design of scalable inoculum trains for this DNA vaccine process. This work also highlighted that a slightly higher level of process reproducibility, as measured by the time for the culture to reach mid‐exponential growth, was observed when using actively growing versus frozen cells. It also demonstrated the existence of a viable‐cell concentration threshold for the one‐stage process, since we observed that inoculation of the production stage with very low amounts of viable cells from a frozen source could lead to increased process sensitivity to external factors such as variation in the quality of the raw materials used in the medium formulation. However, our analysis indicates that, despite this slight disadvantage, a one‐stage inoculum train was a viable option in many situations, especially if the inoculation viable‐cell concentration was kept above 4.8 × 106 viable cells/mL. Because it leads to a reduction in process steps and eliminates some capital investments (i.e., inoculum fermenter), when feasible a one‐stage process configuration will positively impact process economics.
Identification of noncytopathic equine rhinovirus 1 as a cause of acute febrile respiratory disease in horses

Equine rhinovirus 1 (ERhV1) is a recognized cause of acute febrile respiratory disease in horse, although the virus is rarely isolated from such animals, despite seroprevalence rates as high as 50% in some horse populations. Recently, ERhV1 has been shown to be most closely related to foot-and-mouth disease virus, raising questions as to its disease associations in horses. We report that ERhV1 infection was the likely cause of two separate outbreaks of severe febrile respiratory disease which involved more than 20 horses. Attempts to isolate ErhV1 from nasopharyngeal swabs by conventional cell culture methods were unsuccessful, in that cytopathology was not observed. Viral antigen was detected by immunofluorescence assay in the cytoplasm of cells infected with 10 of 15 nasopharyngeal swab samples, indicating the presence and presumably replication of ERhV1. A rise in serum neutralizing antibody titer between acute- and convalescent-phase sera confirmed that ERhV1 was causatively associated with one of the outbreaks. ERhV1 RNA was detected in nasopharyngeal swabs collected from all horses during the acute phase of disease by reverse transcription-PCR. Nucleotide sequencing of amplified products showed that within each outbreak a single strain of ERhV1 was involved but that distinct viruses were involved in each outbreak. A retrospective study of samples from nine other outbreaks of respiratory disease in horses suggested ERhV1 etiology in at least two of these. We conclude that the relative importance of ERhV1 as a cause of acute febrile respiratory disease in horses has been underestimated due to failure in many instances to isolate virus by conventional cell culture methods.
Liposomal amphotericin B (AmBisome) compared with amphotericin B both followed by oral fluconazole in the treatment of AIDS‐associated cryptococcal meningitis

Objective:Amphotericin B deoxycholate initial therapy and fluconazole maintenance therapy is the treatment of choice for AIDS-associated cryptococcal meningitis. However, the administration of amphotericin B is associated with considerable toxicity. A potential strategy for reducing the toxicity and increasing the therapeutic index of amphotericin B is the use of lipid formulations of this drug. Design and methods:HIV-infected patients with cryptococcal meningitis were randomized to treatment with either liposomal amphotericin B (AmBisome) 4 mg/kg daily or standard amphotericin B 0.7 mg/kg daily for 3 weeks, each followed by fluconazole 400 mg daily for 7 weeks. During the first 3 weeks, clinical efficacy was assessed daily. Mycological response was primarily evaluated by cerebrospinal fluid (CSF) cultures at days 7, 14, 21 and 70. Results:Of the 28 evaluable patients, 15 were assigned to receive AmBisome and 13 to receive amphotericin B. Baseline characteristics were comparable. The time to and the rate of clinical response were the same in both arms. AmBisome therapy resulted in a CSF culture conversion within 7 days in six out of 15 patients versus one out of 12 amphotericin B-treated patients (P = 0.09), within 14 days in 10 out of 15 AmBisome patients versus one out of nine amphotericin B patients (P = 0.01), and within 21 days in 11 out of 15 AmBisome patients versus three out of eight amphotericin B patients (P = 0.19). When Kaplan-Meier estimates were used to compare time to CSF culture conversion, AmBisome was effective more (P < 0.05; median time between 7 and 14 days for AmBisome versus > 21 days for amphotericin B). AmBisome was significantly less nephrotoxic. Conclusions:A 3-week course of 4 mg/kg AmBisome resulted in a significantly earlier CSF culture conversion than 0.7 mg/kg amphotericin B, had equal clinical efficacy and was significantly less nephrotoxic when used for the treatment of primary episodes of AIDS-associated cryptococcal meningitis.
Vitamin D and cardiometabolic health: a review of the evidence

The cardiometabolic syndrome (MetS) is a clustering of related metabolic abnormalities including abdominal adiposity, insulin resistance, hypertension, dyslipidaemia and increased inflammatory and thrombotic markers, which is linked to increased risk of type 2 diabetes, CVD and overall mortality. Several cross-sectional and prospective studies have shown an association between low vitamin D status, as indicated by concentrations of serum 25-hydroxyvitamin D (s25(OH)D), and increased prevalence of the MetS and individual CVD risk factors. These epidemiological observations are supported by mechanistic studies but experimental data are limited. The available data from intervention studies are largely confounded as most vitamin D supplementation trials were mainly carried out to explore the role of Ca in CVD and include Ca in the treatment arms. Inadequate consideration of seasonal effects on s25(OH)D concentrations is also a common design flaw in most studies. Further complications arise from shared risk factors such as adiposity and ageing, which predispose individuals to exhibit both a more pronounced risk profile and relatively lower s25(OH)D concentrations. In conclusion, while epidemiological associations are promising and a rationale for low vitamin D status as a potentially modifiable risk factor for CVD is supported by mechanistic data, suitable experimental data from appropriately designed trials are just beginning to emerge. As yet, this body of literature is too immature to draw firm conclusions on the role of vitamin D in CVD prevention. Carefully controlled vitamin D trials in well-described population groups using intervention doses that are titrated against target s25(OH)D concentrations could yield potentially valuable outcomes that may have a positive impact on CVD risk modification.
Model forecast skill and sensitivity to initial conditions in the seasonal Sea Ice Outlook

We explore the skill of predictions of September Arctic sea ice extent from dynamical models participating in the Sea Ice Outlook (SIO). Forecasts submitted in August, at roughly 2 month lead times, are skillful. However, skill is lower in forecasts submitted to SIO, which began in 2008, than in hindcasts (retrospective forecasts) of the last few decades. The multimodel mean SIO predictions offer slightly higher skill than the single‐model SIO predictions, but neither beats a damped persistence forecast at longer than 2 month lead times. The models are largely unsuccessful at predicting each other, indicating a large difference in model physics and/or initial conditions. Motivated by this, we perform an initial condition sensitivity experiment with four SIO models, applying a fixed −1 m perturbation to the initial sea ice thickness. The significant range of the response among the models suggests that different model physics make a significant contribution to forecast uncertainty.
Reduction in endogenous parkin levels renders glial cells sensitive to both caspase‐dependent and caspase‐independent cell death

Mutations in the parkin gene give rise to a familial form of Parkinson's disease, autosomal recessive juvenile Parkinsonism (AR‐JP). Although the exact mechanisms are unclear, it is thought that these ‘loss‐of‐function’ mutations contribute to the pathological process by interfering with parkin's E3 ubiquitin ligase activity. In order to mimic the in vivo loss‐of‐function, we produced tet‐inducible glial cell lines that, in the presence of doxycycline, were able either to under‐ or to over‐express the parkin protein. Using this cell‐culture system, we found that the induced alteration of parkin levels in glial cell lines caused different responses compared with their un‐induced counterparts under conditions of stress (staurosporine, hydrogen peroxide and dopamine). In particular, reduction in the levels of parkin within the transfected cells rendered them more susceptible to both apoptotic and necrotic cell death. Interestingly, blocking the cell death pathway with caspase inhibitors rescued the cells under‐expressing parkin from only some of the stress‐induced death. These findings implicate a pathogenic role of glial cells in the pathogenesis of AR‐JP caused by mutations in the parkin gene.
Atrophy mainly affects the limbic system and the deep grey matter at the first stage of multiple sclerosis

Background The existence of grey matter (GM) atrophy right after the first clinical event suggestive of multiple sclerosis (MS) remains controversial. The aim of this study was therefore to establish whether regional GM atrophy is already present in the earliest stage of MS assessing regional GM atrophy in a large group of patients. Methods Sixty-two patients with a clinically isolated syndrome (CIS) were examined on a 1.5 T MR imager within 6 months after their first clinical events. A group of 37 matched healthy control subjects were also included in the study. An optimised voxel-based morphometry (VBM) method customised for MS was applied on volumetric T1-weighted images. The functional status of patients was assessed using the Expanded Disability Status Scale (EDSS) and the Brief Repeatable Battery. Results VBM analysis (p<0.005, familywise error corrected) on patients versus control subjects showed the presence of significant focal GM atrophy in patients involving the bilateral insula, the bilateral orbitofrontal cortices, the bilateral internal and inferior temporal regions, the posterior cingulate cortex, the bilateral thalami, the bilateral caudate nuclei, the bilateral lenticular nuclei and the bilateral cerebellum. EDSS was slightly correlated (ρ=−0.37 p=0.0027) with the atrophy of the right cerebellum. No correlations have been evidenced between the cognitive status of patients and the regional GM atrophy. Conclusion The present study performed on a large group of CIS patients demonstrated that regional GM atrophy is present right after the first clinical event of multiple sclerosis and mainly affects the deep GM and the limbic system.
Clinico-pathological characteristics of BRCA1- and BRCA2-related breast cancer.

Approximately 2% to 5% of all breast cancers are hereditary, meaning that the cancer predisposition is carried as a monogenic trait. Several highly penetrant breast cancer predisposing genes have been identified. These discoveries will permit a refined description of breast cancer occurring as part of the different genetic syndromes. We reviewed the medical literature on the clinico-pathological features of breast cancer associated with the major breast cancer susceptibility genes BRCA1 and BRCA2. BRCA1-associated breast cancers are more frequently ductal invasive, high-grade carcinomas with an important lymphocytic infiltration. They are aneuploid, estrogen and progesterone receptors negative, and p53 positive. BRCA2-related breast cancers tend to be higher-grade tumors than are non-hereditary cases, although this association is less strong then for BRCA1 cases. These tumors exhibit substantially less tubule formation, but mitotic count and cellular pleomorphism do not differ significantly from those of sporadic cases. The overall pattern of the identified pathological characteristics suggests a carcinogenic pathway in BRCA1- and BRCA2-related breast cancers different from that found in sporadic cases. The probability of finding a BRCA1/2 germ-line mutation is partly determined by these characteristics. In addition, these features will likely influence the behavior of BRCA1/2-related breast cancer.