Miracle-dz/UniFAR-FTUs huggingface dataset:
Post-partum evaluation of maternal cardiac function after severe preeclampsia

Abstract Objective: To evaluate the post-partum maternal cardiac function in patients with history of severe preeclampsia. Methods: A series of women with previous singleton pregnancy complicated by severe preeclampsia underwent transthoracic echocardiography at 6–12 months from delivery. A group of women with previous uncomplicated pregnancy was selected as controls. Results: Sixteen women with history of severe preeclampsia were enrolled in the study group whereas 18 patients were selected as controls. In the study group systolic (p = 0.002) and diastolic blood pressure (p = 0.044) were significantly higher. Significant differences were observed in systolic left ventricular (LV) parameters, such as cardiac output (p = 0.034), LV mass indexed to BSA (p = 0.024) and longitudinal contraction, expressed by tissue Doppler (TD) S1 wave, which resulted relatively impaired in former preeclamptic women (p = 0.049). As regards as diastolic parameters, pulsed Doppler A-wave velocity was increased (p = 0.036). TD E-wave velocity was significantly lower in study group (p < 0.001) and E/E1 ratio (E = peak early diastole transmitral wave velocity/E1 = peak early diastolic velocity at mitral valve annulus at TD) was higher respect to controls (p < 0.001). Conclusions: LV contractility and diastolic function, although within normal reference ranges, show slight but significant impairment among women who experienced a severe preeclampsia. TD seems to be a sensible tool to identify these precocious signs of potential LV dysfunction.
In Vivo Pharmacological Characterization of TAK-063, a Potent and Selective Phosphodiesterase 10A Inhibitor with Antipsychotic-Like Activity in Rodents

Phosphodiesterase 10A (PDE10A) is a cAMP/cGMP phosphodiesterase highly expressed in medium spiny neurons (MSNs) in the striatum. We evaluated the in vivo pharmacological profile of a potent and selective PDE10A inhibitor, TAK-063 (1-[2-fluoro-4-(1H-pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)-pyridazin-4(1H)-one). TAK-063 at 0.3 and 1 mg/kg p.o. , increased cAMP and cGMP levels in the rodent striatum and upregulated phosphorylation levels of key substrates of cAMP- and cGMP-dependent protein kinases. TAK-063 at 0.3 and 1 mg/kg p.o. , strongly suppressed MK-801 [(5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine]–induced hyperlocomotion, which is often used as a predictive model for antipsychotic-like activity in rodents. Upregulation of striatal cAMP/cGMP levels and the antipsychotic-like effect of TAK-063 were not attenuated after 15 days of pretreatment with TAK-063 in mice. The potential side effect profile of TAK-063 was assessed in rats using the clinical antipsychotics haloperidol, olanzapine, and aripiprazole as controls. TAK-063 did not affect plasma prolactin or glucose levels at doses up to 3 mg/kg p.o. At 3 mg/kg p.o. , TAK-063 elicited a weak cataleptic response compared with haloperidol and olanzapine. Evaluation of pathway-specific markers (substance P mRNA for the direct pathway and enkephalin mRNA for the indirect pathway) revealed that TAK-063 activated both the direct and indirect pathways of MSNs. These findings suggest that TAK-063 represents a promising drug for the treatment of schizophrenia with potential for superior safety and tolerability profiles.
Lifestyle factors in people seeking infertility treatment – A review

Background: Clinical infertility is a prevalent problem with significant financial and psychosocial costs. Modifiable lifestyle factors exist that may affect a person’s time to conception and their chance of having a healthy, live birth. However, no guideline delineates what preconception advice should be offered to people presenting for infertility treatment.
In Vitro Screening of Tumoricidal Properties of International Medicinal Herbs

With growing use of anticancer complementary and alternative medicines (CAMs) worldwide, there is a need to assess, screen and rank commercially available herbal products for relative tumoricidal properties under standard experimental conditions. Moreover, high through‐put screening may provide information on potentially new plant resources for chemotherapy drugs. Previously, we screened and ranked 374 herbal extracts obtained from diverse international natural plants (Phytother Res. 2009 Mar; 23(3):385–98). In the current study, we screened an additional 307 extracts predominantly from plants used in traditional Chinese medicine (0.005–5.0 mg/ml), ranking them according to tumoricidal potency on malignant neuroblastoma. The results in this study show the greatest effects (LC50 < 0.08 mg/ml) for extracts of gromwell root also known as “Hong Tiao Zi Cao” (Lithospermum erythrorhizon root) (LER) < beth root (Trillium Pendulum Root) and Galbanum (Ferula galbaniflua). The reference standard: turmeric (Curcuma longa), a known anti‐tumor herb yielded an LC50 of . 269mg/ml displaying 7% the potency of LER. In conclusion, this study shows greatest efficacy for water soluble constituents within gromwell root, which is traditionally used as a Chinese tea. (Supported from NIH grant RR03020)
Novel Clade of Rickettsia spp. from Leeches

ABSTRACT Intracellular rickettsia-like structures were found in the tissues of a glossiphoniid leech, Torix tagoi, by transmission electron microscopy. Diagnostic PCR analysis using specific primers suggested that of the nine glossiphoniid species examined, two species, T. tagoi and Hemicrepsis marginata, harbored bacteria of the genus Rickettsia. A 1.5-kb eubacterial 16S rRNA gene segment obtained from each of these species was amplified by PCR, cloned, and sequenced. Phylogenetic analysis of the 16S rRNA gene demonstrated that the Rickettsia species found in the leeches constituted a novel clade that is distinct from the clade of arthropod-associated Rickettsia species. In natural populations, 97.7% (43 of 44) of T. tagoi leeches and 100% (9 of 9) of H. marginata leeches carried Rickettsia, suggesting that infection with Rickettsia is prevalent in these leeches. This is the first report of Rickettsia found in annelids.
Assessment of anthracycline-induced cardiotoxicity with electrocardiography.

AIM Monitoring of anthracycline-induced cardiotoxicity with electrocardiography (ECG) and comparing ECG changes with findings on echocardiography (ECHO). METHODS A total of 26 adult acute leukemia patients (mean age 46.2 -/+ 12.4 years, 15 males) treated with 2-6 cycles of anthracycline-based chemotherapy (CT) were studied. Cardiac evaluation was performed at the baseline (before CT), after first CT, after last CT (cumulative anthracycline dose 464.3 -/+ 117.5 mg/m2) and circa 6 months after CT. Time ECG parameters, QRS voltage, presence of repolarization changes, arrhythmias and other abnormalities were evaluated. RESULTS During treatment and follow-up, we found a statistical significant QTc interval prolongation - 414.7 -/+ 16.0 ms (before CT), 419.6 -/+ 21.6 ms (after first CT), 428.0 -/+ 16.2 ms (after last CT) and 430.1 -/+ 18.4 ms (6 months after CT). Significant QTc interval prolongation (> 450 ms) occurred in 3 patients after first CT, in 4 patients after last CT and in 5 patients within 6 months after CT. Significant total QRS voltage lowering in the limb leads (> 1.0 mV versus before CT) occurred in 3 patients after first CT, in 5 patients after last CT and in 6 patients within 6 months after CT. We found a statistically significant correlation between decreased QRS voltage, QTc interval prolongation and left ventricular (LV) dysfunction on ECHO. Repolarization changes associated with oncology treatment were present in 9 patients within 6 months after CT. CONCLUSION Anthracycline treatment is associated with changes in electrical activity of the myocardium. Prolonged QTc interval represents a risk for development of malignant ventricular arrhythmias. Decreased QRS voltage and prolonged QTc interval after anthracycline treatment could correlate with LV dysfunction on ECHO. Further studies will be needed to prove whether these ECG changes could serve as an accessible and non-invasive screening method indicating LV dysfunction after anthracycline treatment.
On Stabilization and Convergence of Clustered Ritz Values in the Lanczos Method

The Lanczos algorithm can be considered as an iterative method for finding a few eigenvalues and eigenvectors of large sparse symmetric matrices. In the present paper we solve a conjecture posed by Zdenek Strakos and Anne Greenbaum in [Open Questions in the Convergence Analysis of the Lanczos Process for the Real Symmetric Eigenvalue Problem, IMA Research Report, 1992] on the clustering of Ritz values, which occurs in finite precision computations. In particular, we prove that the conjecture is valid in most cases and describe the rare case when it is not. The established upper bounds measuring the quality of Ritz approximations imply also that Ritz values cluster only close to an eigenvalue.
Epidemiological analysis of data for scrapie in Great Britain

In recent years, the control or eradication of scrapie and any other transmissible spongiform encephalopathies (TSEs) possibly circulating in the sheep population has become a priority in Britain and elsewhere in Europe. A better understanding of the epidemiology of scrapie would greatly aid the development and evaluation of control and eradication strategies. Here we bound the range of key epidemiological parameters using a combination of relatively detailed pathogenesis and demography data, more limited data on susceptibility and incubation times, and recent survey data on scrapie incidence in Great Britain. These data are simultaneously analysed using mathematical models describing scrapie transmission between sheep and between flocks. Our analysis suggests that occurrence of scrapie in a flock typically provokes changes in flock management that promote termination of the outbreak, such as the adoption of selective breeding, and that a large fraction of cases (possibly over 80%) goes undetected. We show that the data analysed are consistent with the within-flock reproduction number of scrapie lying in the range 1·5–6, consistent with previous epidemiological studies.
Comparative Analysis of Galectins in Primary Tumors and Tumor Metastasis in Human Pancreatic Cancer

Galectins are galactoside-binding proteins that exhibit an important function in tumor progression by promoting cancer cell invasion and metastasis formation. Using Northern blotting and Western blotting analysis, in situ hybridization (ISH), and immunohistochemistry (IHC), we studied galectin-1 and galectin-3 in tissue samples of 33 primary pancreatic cancers and in tumor metastases in comparison to 28 normal pancreases. Furthermore, the molecular findings were correlated with the clinical and histopathological parameters of the patients. Northern blotting and Western blotting analysis showed significantly higher galectin-1 and galectin-3 mRNA and protein levels in pancreatic cancer samples than in normal controls. For galectin-1, no ISH signals and immunoreactivity were observed in acinar or ductal cells in the normal pancreas and in pancreatic cancer cells, whereas fibroblasts and extracellular matrix cells around the cancer mass exhibited strong mRNA signals and immunoreactivity. Galectin-3 mRNA signals and immunoreactivity were strongly present in most pancreatic cancer cells, whereas in the normal controls only faint ISH and IHC signals were seen in some ductal cells. Metastatic pancreatic cancer cells exhibited moderate to strong galectin-3 immunoreactivity but were negative for galectin-1. No relationship between the galectin-1 and galectin-3 mRNA levels and the tumor stage or between the IHC staining score and the tumor stage was found. However, galectin-1 mRNA levels and the IHC staining score were significantly higher in poorly differentiated tumors compared with well/moderately differentiated tumors, whereas for galectin 3 no differences were found. The expression pattern of galectin-1 and galectin-3 in pancreatic cancer tissues indicates that galectin-1 plays a role in the desmoplastic reaction that occurrs around pancreatic cancer cells, whereas galectin-3 appears to be involved in cancer cell proliferation. High levels of galectin-3 in metastatic cancer cells suggest an impact on metastasis formation.
Voluntary exercise does not ameliorate context memory and hyperarousal in a mouse model for post-traumatic stress disorder (PTSD)

Abstract Objectives. We investigated the effects of voluntary wheel running as model for intervention on the development of contextual fear and hyperarousal in a mouse model of post-traumatic stress disorder (PTSD). Physical exercise in general has been associated with improved hippocampus-dependent memory performance both in animals and humans. However, studies that have tried to link physical exercise and contextual conditioning in an animal model of PTSD, revealed mixed findings. Methods. Here we tested contextual fear conditioning, generalized fear response, acoustic startle response and emotionality in C57BL/6NCrl mice which had free access to a running wheel for 28 days, compared with control animals which did not run and mice which did not receive a shock during the conditioning phase. Results. We found no significant effects of voluntary running on the above-mentioned variables, except for enhanced anxiety levels in the Dark-Light-Box and O-Maze tests of running mice. Conclusions. Our results suggest that running as a model for intervention does not ameliorate contextual aversive learning but has the potency to change emotional behaviours.
The Subthalamic Nucleus in Parkinson's Disease and Progressive Supranuclear Palsy

The subthalamus has become a promising target for the neurosurgical treatment of parkinsonian symptoms. We have used unbiased counting techniques to quantify the neuronal populations of the subthalamic nucleus in patients with idiopathic Parkinson's disease and progressive supranuclear palsy. In addition, the type of calcium binding proteins contained within these subthalamic neurons was established using immunohistochemistry. Most of the 550,000 subthalamic neurons contain either parvalbumin or calretinin calcium binding proteins, and patients with idiopathic Parkinson's disease sustained no damage to this nucleus. This is consistent with current theories of basal ganglia circuitry, which postulate that overstimulation of this excitatory nucleus contributes to the inhibition of the motor thalamus via the activation of inhibitory relays. In contrast, we found that there was substantial cell loss in the subthalamus in progressive supranuclear palsy (45 to 85% neuronal reduction) and that both cell types were equally affected. Extracellular neurofibrillary tangles as well as tau-positive glia were observed in the subthalamus of these cases. As the patients, with Parkinson's disease and progressive supranuclear palsy all had overlapping parkinsonian symptoms, the loss of subthalamic stimulation within the basal ganglia of progressive supranuclear palsy cases is puzzling, unless their parkinsonian symptoms were generated by an alternate mechanism.
Pharmacokinetics and Pharmacodynamics of Vecuronium (ORG NC 45) in Patients with Cirrhosis

To evaluate the effect of liver cirrhosis on the pharmacokinetics and the pharmacodynamics of vecuronium, 12 patients with cirrhosis, aged (mean ± SD) 52 ± 12 yr, and 14 control patients, 42 ± 15 yr, undergoing elective surgery under general anesthesia were studied. The simultaneous time courses of the plasma concentration of vecuronium and of the neuromuscular blockade were studied after the administration of a bolus dose of 0.2 mg · kg−1. Vecuronium plasma concentration declined biexponentially in both groups. Vecuronium plasma clearance was reduced significantly (P < 0.01) from 4.26 ± 1.38 ml · min−1 · kg−1 in the controls to 2.73 ± 1.19 ml · min−1 · kg−1 in the patients with cirrhosis. The elimination half-life was 58 ± 19 min in the controls and was prolonged significantly to 84 ± 23 min (P < 0.01) in the patients with cirrhosis. The total apparent volume of distribution was unchanged in patients with cirrhosis (0.253 ± 0.086 1 · kg−1 vs. 0.246 ± 0.092 1 · kg−1 in the controls). Cirrhosis caused a prolongation of the neuromuscular blockade induced by vecuronium: the duration of effect from injection to 50% recovery of the twitch height was prolonged by 100% (P < 0.01) from 62 ± 16 min in the controls to 130 ± 52 min in patients with cirrhosis. The recovery rate (TH 25–75) also was prolonged (P < 0.05) from 21 ± 7 min in the controls to 44 ± 18 min in patients with cirrhosis. Vecuronium plasma concentration measured during recovery from paralysis indicates that cirrhosis did not alter the sensitivity to the relaxant, the plasma concentration corresponding to 50% of recovery (Cp 50) being unchanged between the two groups: 247 ± 60 ng · ml−1 in the controls versus 281 ± 129 ng · ml−1 in the cirrhotic patients. Thus, vecuronium seems to exert a prolonged neuromuscular blockade in patients with cirrhosis, and this change is mediated through its delayed elimination.
Mild Angelman syndrome phenotype due to a mosaic methylation imprinting defect

Angelman syndrome (AS) is a neurogenetic disorder causing severe to profound intellectual disability, absent or very limited speech and a high risk for seizures. AS is caused by a loss of function of the maternally‐derived UBE3A allele due to one of several mechanisms including imprinting defects (ImpDs). We present a girl with AS due to a mosaic ImpD who has relatively high developmental function (VABS‐II composite score of 76) and communication skills (as demonstrated in supplemental video links). Given the patient's relatively mild developmental impairment, without clinical evidence of seizures, gait disturbance or inappropriate laughter, the diagnosis of AS was not initially suspected. Initial laboratory testing for AS was inconclusive but additional studies suggested mosaic ImpD and characteristic EEG findings provided further support for the clinical diagnosis. Our patient, along with other case reports of children with AS and relatively mild phenotypes, raises the question as to whether there exists an undiagnosed group of individuals with mild intellectual disability and expressive speech delays due to mosaic methylation defects of the chromosome 15q11.2‐13 region. Population studies may be needed to determine if such an undiagnosed group exists. © 2015 Wiley Periodicals, Inc.
NuSTAR OBSERVATIONS OF HEAVILY OBSCURED QUASARS AT z ∼ 0.5

We present NuSTAR hard X-ray observations of three Type 2 quasars at z ≈ 0.4–0.5, optically selected from the Sloan Digital Sky Survey. Although the quasars show evidence for being heavily obscured, Compton-thick systems on the basis of the 2–10 keV to [O iii] luminosity ratio and multiwavelength diagnostics, their X-ray absorbing column densities (NH) are poorly known. In this analysis, (1) we study X-ray emission at >10 keV, where X-rays from the central black hole are relatively unabsorbed, in order to better constrain NH. (2) We further characterize the physical properties of the sources through broad-band near-UV to mid-IR spectral energy distribution analyses. One of the quasars is detected with NuSTAR at >8 keV with a no-source probability of <0.1%, and its X-ray band ratio suggests near Compton-thick absorption with NH ≳ 5 × 1023 cm−2. The other two quasars are undetected, and have low X-ray to mid-IR luminosity ratios in both the low-energy (2–10 keV) and high-energy (10–40 keV) X-ray regimes that are consistent with extreme, Compton-thick absorption (NH ≳ 1024 cm−2). We find that for quasars at z ∼ 0.5, NuSTAR provides a significant improvement compared to lower energy (<10 keV) Chandra and XMM-Newton observations alone, as higher column densities can now be directly constrained.
Extended cervicomediastinal thymectomy in the integrated management of myasthenia gravis.

OBJECTIVE The authors evaluated the response to extended cervicomediastinal thymectomy as a component of the integrated management of patients with myasthenia gravis in a large series of patients from a single institution. The authors evaluated the response to therapy with respect to a graded, multivariate, ordinal scale chosen to reflect the full range of the disease's manifestations. SUMMARY BACKGROUND DATA A number of series, of varying sizes, describe the response of patients with myasthenia gravis to thymectomy primarily with respect to the bivariate endpoint of the presence or absence of "remission. " These studies fail to describe the full spectrum of postoperative disease severity and have been unable to quantify definitively the influence of putative prognostic variables, nor to assess definitively the statistical significance of apparent improvements over time. METHODS The authors evaluated 202 consecutive patients who underwent trans-sternal thymectomy for symptomatic myasthenia gravis from 1969 through 1996 at the Johns Hopkins Hospital. The response to surgery, combined with postoperative medical therapy, was evaluated by a standardized scale reflecting the full spectrum of the disease. These data were analyzed by a novel mean multivariate regression analysis, which allowed the quantification of the statistical significance of apparent responses over time and the evaluation of the independent influence of each of nine putative prognostic indicators. RESULTS There was no perioperative mortality and a 33% perioperative morbidity. There was a marked clinical response at 6 months to 1 year after surgery that was sustained for at least 10 years thereafter. The median increment of improvement was two (of five) classes. Eighty-six percent and 83% of the patients had improved by at least one class at 5 and 10 years, respectively. These changes were statistically significant (p < 0.001). Whereas the use of extended cervicomediastinal thymectomy was associated with a greater than twofold chance of improvement, compared to conventional trans-sternal thymectomy, neither the pathologic diagnosis (presence of thymoma) nor the age at surgery proved to be negative predictors of postoperative response. CONCLUSIONS Extended cervicomediastinal thymectomy is the procedure of choice as a component of the integrated management of myasthenia gravis, with significant improvement seen in the group as a whole, as well as in subgroups of patients with thymoma and those older than 40 years of age.
Sooner or later? Young Australian men’s perspectives on timing of parenthood

Postponed parenthood has been identified as a significant driver of the trends towards smaller families and underachieved fertility aspirations. Understanding men’s preferred timing and circumstances for fatherhood is needed to complement existing research among young women and increase understanding of postponed parenthood. We collected quantitative and qualitative data on attitudes regarding the timing of parenthood from 382 young Australian men attending university. Participants valued having a stable relationship and personal maturity before having children, with completed studies, financial security and a permanent yet flexible job also important. Programmes and policies which facilitate the establishment of important ‘preconditions’ for parenthood would support individuals to achieve their reproductive aspirations.