Miracle-dz/UniFAR-FTUs huggingface dataset:
The Mirasol Pathogen Reduction Technology system and quality of platelets stored in platelet additive solution.

BACKGROUND The Mirasol Pathogen Reduction Technology system for platelets and plasma uses riboflavin and UV light to introduce irreparable lesions into nucleic acids thereby inhibiting pathogen and white blood cell replication and reducing the load of infectious pathogens. The aim of the present study was to evaluate low plasma buffy coat platelet concentrates obtained from the OrbiSac System and to examine the effects on the development of platelet storage lesion during storage in platelet additive solution. MATERIAL AND METHODS Twenty buffy coat platelet concentrates were generated by pooling five individual units using the OrbiSac System. Riboflavin was added during the final pooling step, and the units were exposed to UV light. The bag was removed after the target energy of 6.24 J/mL had been delivered and 150 mL of platelet additive solution were added prior to storage. Platelet quality was assessed by pH, swirl, CD62P expression, lactate dehydrogenase, lactate production and glucose consumption rates over 7 days of storage. RESULTS Buffy coat platelet concentrates generated on the OrbiSac contained an average 3.5 +/- 0.6 x 10(11) platelets at a concentration of 2976+/- 406 x 10(6)/mL. After addition of 150 mL platelet additive solution the storage concentration was 1043 +/- 148x 10(6)/mL. Values obtained for pH, lactate production and glucose consumption rates were all within the limits of previously established correlations between in vitro cell quality and in vivo performance of Pathogen Reduction Technology-treated platelets in plasma. DISCUSSION In vitro studies show that OrbiSac-derived platelets treated with the Mirasol Pathogen Reduction Technology system preserve adequate function, which would indicate acceptable in vitro viability.
Circulating Nucleic Acids in Plasma and Serum

Abstract: Nucleic acids (DNA and RNA) have been detected in plasma, serum, urine, and other body fluids from healthy subjects as well as in patients. The ability to detect and quantitate specific DNA and RNA sequences has opened up the possibility of diagnosis and monitoring of diseases. With the recent developments in the field of circulating nucleic acids the application in the diagnostic field has increased. The recent discovery of epigenetic changes in placental/fetal DNA and the detection of fetal/placental‐specific RNAs have made it possible to use this technology in all pregnancies irrespective of the gender of the fetus. With the application of mass spectrometry and other techniques to this field, it is now possible to detect very small amounts of specific DNA in the presence of excess of other nonspecific nucleic acids (e.g., detection of mutations in fetal DNA in the presence of excess of maternal DNA). Circulating nucleic acids have now been shown to be useful in other conditions, such as diabetes mellitus, trauma, stroke, and myocardial infarction. In oncology, detection and monitoring of tumors is now possible by the detection of tumor‐derived nucleic acids. In spite of these advances questions regarding the origin and biologic significance of circulating nucleic acids remain to be answered. Furthermore preanalytical and analytical aspects of this field remain to be standardized.
Intraarterial versus intravenous adriamycin in the rabbit Vx‐2 tumor system

Intraarterial (IA) chemotherapy can theoretically result in a high tissue level of the drug with reduced systemic toxicity compared with intravenous (IV) administration. The authors compared these two modes of therapy using Adriamycin (doxorubicin) in the rabbit Vx‐2 tumor system. Vx‐2 was implanted in hind limb muscle, and silastic catheters were placed in the jugular vein and femoral artery. Nuclear imaging of technetium‐99m‐labeled autologous erythrocytes in nine animals was used to measure the kinetics of tumor blood flow. Presence of tumor increased flow through the involved limb up to threefold. One minute following injection there was no difference in concentration of 99mTc in tumor whether labeled cells were introduced IA or IV. Twelve rabbits received IA (N = 6) or IV (N = 6) Adriamycin (3 mg/ kg), while eight animals received normal saline IA or IV as controls. Tumor progressed in all control rabbits, whereas there was an objective or complete response in 83% of animals receiving Adriamycin. One hundred percent of those treated IA responded compared with 67% for IV (P = 0.04). Median time to initial response in animals treated IA was 7 days versus 21 days for those treated IV (P = 0.02). Thus, IA Adriamycin achieves a more complete and more rapid response than the drug given IV. This occurs despite a large tumor blood flow and rapid equilibration using both methods. Cancer 53:1397‐1404, 1984.
Differentiation of Bordetella avium and related species by cellular fatty acid analysis

The fatty acids of 18 strains of Bordetella avium, 3 strains of Alcaligenes faecalis, 5 strains of Bordetella bronchiseptica, and 12 strains of a B. avium-like organism were examined by gas chromatography-mass spectrometry. The presence of a significant amount of the acid 2-OH C14:0 characterized B. avium and the B. avium-like organism. B. avium and the B. avium-like organism differed in their relative concentrations of C16:1 and 3-OH C14:0 acids. B. bronchiseptica and A. faecalis were distinguishable by comparison of the relative concentrations of C18:0 and C18:1 acids.
Functional Analysis of N-Terminal Residues of Ty1 Integrase

ABSTRACT The Ty1 retrotransposon of Saccharomyces cerevisiae is comprised of structural and enzymatic proteins that are functionally similar to those of retroviruses. Despite overall sequence divergence, certain motifs are highly conserved. We have examined the Ty1 integrase (IN) zinc binding domain by mutating the definitive histidine and cysteine residues and thirteen residues in the intervening (X32) sequence between IN-H22 and IN-C55. Mutation of the zinc-coordinating histidine or cysteine residues reduced transposition by more than 4,000-fold and led to IN and reverse transcriptase (RT) instability as well as inefficient proteolytic processing. Alanine substitution of the hydrophobic residues I28, L32, I37 and V45 in the X32 region reduced transposition 85- to 688-fold. Three of these residues, L32, I37, and V45, are highly conserved among retroviruses, although their effects on integration or viral infectivity have not been characterized. In contrast to the HHCC mutants, all the X32 mutants exhibited stable IN and RT, and protein processing and cDNA production were unaffected. However, glutathione S-transferase pulldowns and intragenic complementation analysis of selected transposition-defective X32 mutants revealed decreased IN-IN interactions. Furthermore, virus-like particles with in-L32A and in-V45A mutations did not exhibit substantial levels of concerted integration products in vitro. Our results suggest that the histidine/cysteine residues are important for steps in transposition prior to integration, while the hydrophobic residues function in IN multimerization.
Two forms of the nucleoside diphosphate kinase of Pseudomonas aeruginosa 8830: altered specificity of nucleoside triphosphate synthesis by the cell membrane-associated form of the truncated enzyme

Nucleoside diphosphate kinase (EC 2.7.4.6) (Ndk) is a ubiquitous enzyme functioning in the intracellular distribution of terminal phosphate bond energy among the various nucleotides used in synthetic and regulatory functions in cells. We have previously reported that in Pseudomonas aeruginosa, this important enzyme is transcriptionally regulated by the gene algR2 and posttranslationally regulated by a phosphoprotein phosphatase for the phosphorylated form of Ndk. We report here that an intracellular protease cleaves the 16-kDa form of Ndk to a 12-kDa form that undergoes autophosphorylation with an efficiency almost identical to that of the 16-kDa form. The 12-kDa form was found to be predominantly associated with the P. aeruginosa cell membrane fraction, whereas the 16-kDa form was predominantly cytoplasmic. In the membrane-associated state, the 12-kDa form of Ndk was found to synthesize GTP in preference to other nucleoside triphosphates. The specificity toward GTP synthesis could be abolished by the addition of Tween 20 or Triton X-100. The activity itself could be abolished by the addition of anti-Ndk antibody to the assay mixture. The formation of the 12-kDa form of Ndk and its association with the cell membrane were found to be related to the growth stage of P. aeruginosa, with less than 1% of the 12-kDa Ndk detectable in the membrane fraction at early log phase in comparison with the levels present at late stationary phase.
The HIV and AIDS academic curriculum in higher education

While a university's core business of teaching, research and engagement is underpinned by national and global imperatives, the purpose of the university is embedded in students' realities of living, learning and working in the world. A key challenge for all academics, therefore, is to keep their academic project, whether in engineering or health sciences, 'embedded in the students', while at the same time, preparing them for work in the world. The purpose of this article is to argue that the university academic curriculum should be harnessed more vigorously to address HIV and AIDS - a reality impacting the student corps. The article, therefore, seeks to persuade, but also to ensure, that the work of higher education institutions (HEIs) remains 'embedded in its students', and that the curriculum is responsive and engaged, and contributes to the public good of South African society as a whole.
Differential effects of severe vs mild GBA mutations on Parkinson disease

Objective: To better define the genotype-phenotype correlations between the type of GBA (glucosidase, beta, acid) mutation, severe or mild, and the risk and age at onset (AAO), and potential mechanism of Parkinson disease (PD). Methods: We analyzed 1,000 patients of Ashkenazi-Jewish descent with PD for 7 founder GBA mutations, and conducted a meta-analysis of risk and AAO according to GBA genotype (severe or mild mutation). The meta-analysis included 11,453 patients with PD and 14,565 controls from worldwide populations. The statistical analysis was done with and without continuity correction (constant or empirical), considering biases that could potentially affect the results. Results: Among Ashkenazi-Jewish patients with PD, the odds ratios for PD were 2.2 and 10.3 for mild and severe GBA mutation carriers, respectively. The observed frequency of severe GBA mutation carriers among patients with PD was more than 4-fold than expected (4.4% vs 0.9%, respectively, p < 0.0001, Fisher exact test). In the different models of the meta-analysis, the odds ratios for PD ranged between 2.84 and 4.94 for mild GBA mutation carriers and 9.92 and 21.29 for severe GBA mutation carriers (p < 1 × 10−6 for all analyses). Pooled analysis demonstrated AAO of 53.1 (±11.2) and 58.1 (±10.6) years for severe and mild GBA mutation carriers, respectively (p = 4.3 × 10−5). Conclusions: These data demonstrate that mild and severe heterozygous GBA mutations differentially affect the risk and the AAO of PD. Our results have important implications for genetic counseling and clinical follow-up.
A Note on the Sources of Portfolio Returns: Underlying Stock Returns and the Excess Growth Rate

A portfolioâ€™s compound return over time is not simply the weighted sum of the compound returns of its underlying stocks. Instead, it is due to (a) the underlying constituent stocksâ€™ compound returns, and (b) a component induced by constituent covariances. This can be important. The average smallest-cap decile portfolio outperformed its largest-cap counterpart by 44 basis points per month (bps/mo), but the smallest-cap decile stock constituents on average underperformed their largest-cap counterparts by 74 bps/mo. Thus, the â€œsize effect" is not a small-firm effect, but a small-firm portfolio effect. In contrast, our high-minus-low (HML) and up-minus-down (UMD) portfolios outperformed because their individual stock constituents outperformed on average. Value and momentum are simultaneously portfolio and individual stock effects.
Kinematics of a Cylindrical Particle at Low Reynolds Numbers in
 Asymmetrical Conditions

This paper concerns the hydrodynamic interactions on a cylindrical particle in non-dilute regime at low Reynolds numbers. The particle moves between two parallel walls with its axis parallel to the boundaries. A numerical finite-volume procedure is implemented and a generalized resistance matrix is built by means of the superposition principle. Three problems are solved: the settling of the particle, the transport of a neutrally and of a non-neutrally buoyant particle in a Poiseuille flow. Concerning sedimentation, the settling velocity is maximal off the symmetry plane and decreases when the confinement increases. The particle rotates in the direction opposite to that of contact rolling. The particle induces a high pressure zone in the front and a low pressure zone in the back, the difference of which is maximal in the symmetry plane. For a neutrally-buoyant particle, the hydrodynamic interactions lead to a velocity lag between the particle and the undisturbed flow. The magnitude of the velocity lag increases with confinement and eccentricity. The angular velocity and pressure difference are opposite to the previous case. For a non-neutrally buoyant particle, three situations are found depending on a dimensionless parameter similar to an inverse Shields number. For its extreme low and high values, the particle is respectively either carried by the flow or settles against it whatever its position. For intermediate values, the particle either settles close to the walls or is dragged by the flow close to the symmetry plane. Similar results are obtained for the angular velocity and the pressure difference. All these results question the assumption usually met in particulate transport in which the kinematics of the particle is often supposed to be that of the flow.
Perceived coercion in persons with mental disorder in India: A cross-sectional study

Background: Little is known about how patients in India perceive coercion in psychiatric care. Aims: To assess perceived coercion in persons with mental disorder admitted involuntarily and correlate with sociodemographic factors and illness variables. Materials and Methods: We administered the short MacArthur Admission Experience Interview Questionnaire to all consecutive involuntary psychiatric patients admitted in 2014 in Mysore, India. Multivariate linear regression was used. Results: Three hundred and one patients participated. “Perceived coercion” subscale scores increased with female gender, nuclear family status, Muslim and Christian religion, lower income, and depressive disorder. It decreased with former coercion, forensic history, and longer illness duration. Drug use increased total scores; the extended family item decreased them. “Negative pressure” increased with male gender, extended family, lower income, forensic history, and longer illness duration. Conclusions: The study shows perceived coercion is a reality in India. Levels of perceived coercion and the populations affected are similar to high-income countries.
Boosting: An Ensemble Learning Tool for Compound Classification and QSAR Modeling

A classification and regression tool, J. H. Friedman's Stochastic Gradient Boosting (SGB), is applied to predicting a compound's quantitative or categorical biological activity based on a quantitative description of the compound's molecular structure. Stochastic Gradient Boosting is a procedure for building a sequence of models, for instance regression trees (as in this paper), whose outputs are combined to form a predicted quantity, either an estimate of the biological activity, or a class label to which a molecule belongs. In particular, the SGB procedure builds a model in a stage-wise manner by fitting each tree to the gradient of a loss function: e.g., squared error for regression and binomial log-likelihood for classification. The values of the gradient are computed for each sample in the training set, but only a random sample of these gradients is used at each stage. (Friedman showed that the well-known boosting algorithm, AdaBoost of Freund and Schapire, could be considered as a particular case of SGB.) The SGB method is used to analyze 10 cheminformatics data sets, most of which are publicly available. The results show that SGB's performance is comparable to that of Random Forest, another ensemble learning method, and are generally competitive with or superior to those of other QSAR methods. The use of SGB's variable importance with partial dependence plots for model interpretation is also illustrated.
A New Model for the Study of Mild Diabetes During Pregnancy: Syngeneic Islet-Transplanted STZ-Induced Diabetic Rats

Diabetes during pregnancy carries short- and long-term consequences for the offspring. Improved obstetrical and diabetic care has resulted in decreased morbidity and mortality in the neonate of the diabetic mother. Mild hyperglycemia is still found in both IDDM pregnant women and women with GDM. The long-term consequences of exposure to mild hyperglycemia in utero remain to be determined. In an effort to develop an appropriate animal model of mild diabetes during pregnancy, we mated female STZ-induced diabetic rats previously transplanted with specific numbers of islets of Langerhans (2500,1000, 700, or 500 islets). Diabetic and nondiabetic sham-transplanted control groups also were studied. During pregnancy, the plasma glucose levels in the diabetic rats and the group receiving 500 islets (26.5 ± 1.1 and 10.0 ± 0.8 mM, respectively) were significantly greater than in control animals (5.4 ± 0.5 mM, P < 0.0001). The mean glucose levels in rats receiving 700 or 1000 transplanted islets (6.8 ± 0.2 and 6.5 ± 0.2 mM) also were significantly greater than in control animals (P < 0.001). No difference was evident between control rats and the group receiving 2500 islets (5.8 ± 0.2 mM). No gross congenital abnormalities were apparent in the offspring. The pup plasma glucose was significantly greater in the offspring of dams receiving either none (diabetic) or 500 islets (10.6 ± 0.7 and 11.1 ± 1.1 mM, respectively) compared with the offspring of nondiabetic control dams (4.4 ± 0.3 mM, P < 0.0001). The pup pancreatic insulin content was lower in the offspring of diabetic animals than in control animals (4.9 ± 0.3 vs. 15.2 ± 0.5 nM/mg, P < 0.0001), but no difference was found between the offspring of islet-transplanted dams compared with control offspring. In summary, the STZ-induced diabetic rat transplanted with a specified number of islets of Langerhans is a promising new animal model for the study of mild to moderate hyperglycemia during pregnancy. This model should be useful for study of the longer term consequences of diabetes during pregnancy.
The Social Stigma and the Challenges of Raising a Child with Autism Spectrum Disorders (ASD) in Greece

This paper describes the social stigma and the challenges some Greek parents of children with autism spectrum disorders (ASD) faced in Athens, Greece. The sample consisted of seventy-four parents of children with ASD and a mixed methods approach was used; (seventy - four parents completed a semi - structured questionnaire and twenty had semi-structured interviews). The quantitative and qualitative findings show these parents and families of ASD children experienced stigma in various ways which played a major role in making their lives difficult. This study offers a lens through which to view attitudes towards disability, stigmatisation, especially when resources are scarce. It was conducted in Greece during the period of austerity, affecting the delivery of education within social – cultural restraints. So studies at a different time or in another place could produce other findings.
Chirality and neuropsychiatric drugs: an update on stereoselective disposition and clinical pharmacokinetics of bupropion

Abstract 1. Bupropion, an antidepressant drug has been approved as a racemate containing equal amounts of R- and S-enantiomers. Recently, the chirality of bupropion has received significant attention in the delineation of stereoselective pharmacokinetic (PK) and disposition data. Although the non-stereoselective metabolism of bupropion was well established, the emerging data suggest that bupropion exhibits complex stereoselective metabolism, leading to the formation of various stereoisomeric metabolites. Along with the chiral PKs of bupropion, hydroxybupropion, threohydrobupropion and erythrohydrobupropion, the metabolism data also provided insights into the roles of both CYP2B6 and CYP2C19 enzymes in the stereoselective disposition. Furthermore, the metabolism studies also suggested specific involvement of CYP2B6 pathway in the stereoselective hydroxylation of bupropion to R,R-hydroxybupropion, which was considered as a better marker for CYP2B6 activity. 2. Other significant learnings were: (1) understanding the in vivo CYP2D6 inhibitory potential of bupropion with respect to the chirality of parent drug and the metabolites; (2) the potential involvement of bupropion and metabolites towards significant down regulation of CYP2D6 mRNA; (3) significant in vivo CYP2D6 inhibitory activity (86%) exhibited by R,R-hydroxybupropion and threohydrobupropion. 3. The newly published data on chiral PKs and disposition of bupropion and its metabolites can be used to gauge the drug–drug interaction potential when bupropion is combined in clinical therapy. Moreover, such data would be useful to understand the consequences (if any), due to the combination of bupropion with other drugs both from a safety and efficacy perspective because of the prevalence of polypharmacy situations in many therapeutic areas including CNS indications.
The Effect of Rapid Thoracoabdominal Compressions on Intracranial Pressure in Newborn Lambs

ABSTRACT: Measurements of forced expiratory flow in infants can be obtained with the rapid thoracoabdominal compression (RTC) technique. To assess the transmission of the chest wall compression pressure into the cerebrum, we have performed intracranial pressure (ICP) measurements during RTCs in newborn lambs. Thirteen lambs were studied during the first 8 d of life. An epidural pressure transducer was implanted under general anesthesia. Respiratory measurements were performed under sedation with ketamine. RTCs were induced through an inflatable jacket wrapped around the lamb's trunk. RTCs were started with a pressure of 30 cm H2O. The compression pressure was increased in steps of 20 cm H2O up to 250 cm H2O. Flow and volume were determined with a pneumotachograph attached to a face mask. Transpulmonary pressure (Ptp) was measured with an esophageal balloon placed in the lower esophagus. RTCs resulted in proportional increases of Ptp and ICP. ICP was lower or equal to Ptp in all measurements. No changes in baseline ICP occurred throughout the study period. The maximal ICP observed during RTCs was within the range of pressures observed during crying in newborn infants. These data suggest that the RTC technique can be considered safe even at high compression pressures.