Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of moclobemide N-oxidation in human liver microsomes

1. Moclobemide undergoes morpholine ring N-oxidation to form a major metabolite in plasma, Ro12-5637. 2. The kinetics of moclobemide N-oxidation in human liver microsomes (HLM) (n = 6) have been investigated and the mixed-function oxidase enzymes catalysing this reaction have been identified using inhibition, enzyme correlation, altered pH and heat pretreatment experiments. 3. N-oxidation followed single enzyme Michealis-Menten kinetics (0.02-4.0 mM). Km app and Vmax ranged from 0.48 to 1.35 mM (mean ± SD 0:77 ± 0:34 mM) and 0.22 to 2.15 nmol mg−1 min−1 (1:39 ± 0:80 nmol mg−1 min−1), respectively. 4. The N-oxidation of moclobemide strongly correlated with benzydamine N-oxidation, a probe reaction for flavin-containing monooxygenase (FMO) activity, (0.1 mM moclobemide, rS = 0:81; p < 0:005; 4 mM moclobemide, rS = 0:94; p = 0:0001). Correlations were observed between moclobemide N-oxidation and specific cytochrome P450 (CYP) activities at both moclobemide concentrations (0.1 mM moclobemide, CYP2C19 rS = 0:66; p < 0:05; 4 mM moclobemide, CYP2E1 rS = 0:56; p < 0:05). 5. The general P450 inhibitor, N-benzylimidazole, did not affect the rate of Ro12-5637 formation (0% inhibition versus control) at 1.3 mM moclobemide. Furthermore, the rate of Ro12-5637 formation in HLM was unaffected by inhibitors or substrates of specific P450s (<10% inhibition versus control). 6. Heat pretreatment of HLM in the absence of NADPH (inactivating FMOs) resulted in 97% inhibition of Ro12-5637 formation. N-oxidation activity was greatest when incubated at pH 8.5. These results are consistent with the reaction being FMO mediated. 7. In conclusion, moclobemide N-oxidation activity has been observed in HLM in vitro and the reaction is predominantly catalysed by FMOs with a potentially small contribution from cytochrome P450 isoforms.
Groupthink: Collective Delusions in Organizations and Markets

I develop a model of (individually rational) collective reality denial in groups, organizations and markets. Whether participants' tendencies toward wishful thinking reinforce or dampen each other is shown to hinge on a simple and novel mechanism. When an agent can expect to benefit from other's delusions, this makes him more of a realist; when he is more likely to suffer losses from them this pushes him toward denial, which becomes contagious. This general "Mutually Assured Delusion" principle can give rise to multiple social cognitions of reality, irrespective of any strategic payoff interactions or private signals. It also implies that in hierachical organizations realism or denial will trickle down, causing subordinates to take their mindsets and beliefs from the leaders. Contagious "exuberance" can also seize asset markets, leading to evidence-resistant investment frenzies and subsequent deep crashes. In addition to collective illusions of control, the model accounts for the mirror case of fatalism and collective resignation. The welfare analysis differentiates valuable group morale from harmful groupthink and identifies a fundamental tension in organizations' attitudes toward free speech and dissent.
A refined theoretical model for mode I crack near the interface of strength and plasticity mismatched materials in K dominant regime

The paper investigates a cracked bi-material, comprising elastic-plastic materials that are elastically identical but strength and plasticity mismatched, under the action of monotonic and uniform far field tension in small scale yielding (SSY) or K dominant regime. A through, mode I, edge crack in weaker material is assumed to advance perpendicularly toward the interface of stronger material. The interface between the materials is considered to be thin, strong and perfect. A theoretical model is developed with the help of basic mathematical principles to account for the influence of non-linearity in plastic behavior of constituent materials during estimation of plastic energy transfer toward stronger interface material when the crack tip is near the interface. The criterion of the onset of yielding of interface material is included in the model. Energy transfer is represented by the component of energy release rate of the crack due to inhomogeneity caused by property mismatched interface. Shielding effect over the crack is quantified by energy release rate and stress intensity parameter at the crack tip. Two elastically similar steels with different yield strengths and plasticity properties are chosen for computational purpose under plane stress condition. Differences between fracture results of the proposed model and those of an available model based on Dugdale’s criterion that ignores material non-linearity and is valid for elastic-perfectly plastic materials are presented. The proposed model is validated.
Rhabdomyolysis reported for children and adolescents treated with antipsychotic medicines: a case series analysis.

OBJECTIVE Rhabdomyolysis is a rare and potentially serious adverse drug reaction (ADR) to antipsychotic medicines. The aim of this study was to investigate the clinical circumstances surrounding the diagnosis of rhabdomyolysis in children and adolescents treated with antipsychotic medicines. We also critically reviewed individual case safety reports (ICSRs) of suspected ADRs to evaluate how clinically useful they can be in a case series analysis. METHODS This was a descriptive and an exploratory study. Published case reports and ICSRs from the World Health Organization (WHO) Global ICSR database, VigiBase, reported with rhabdomyolysis and antipsychotic medicines for patients ≤17 years years of age were described. Reporting patterns of ICSRs with rhabdomyolysis and antipsychotic medicines were explored in VigiBase for children and adolescents and for adults. The VigiBase ICSRs were also systematically evaluated regarding the report content. RESULTS Of the 26 evaluated reports, 6 co-reported neuroleptic malignant syndrome (NMS) and 20 reports concerned rhabdomyolysis in the absence of NMS. The reported suspected antipsychotic medicines for these 20 reports were olanzapine, risperidone, haloperidol, paliperidone, quetiapine, clozapine, cyamemazine, and aripiprazole. In VigiBase, rhabdomyolysis (in the absence of NMS) was reported more frequently with olanzapine relative to all reports for children and adolescents with antipsychotic medicines. In the range of events that preceded rhabdomyolysis, muscle pains and abdominal pain were commonly recorded to have started during the week prior to the diagnosis. Other preceding symptoms were general weakness and dark urine. Onset of rhabdomyolysis for most patients occurred at any time within 2 months of starting antipsychotic treatment, in several cases triggered by changes to the patient's drug therapy or known risk factors of rhabdomyolysis. It was found that ICSRs can contribute with additional information, but that access to free text and narratives were crucial in order to capture clinically useful features of rhabdomyolysis. CONCLUSION Monitoring of children and adolescents needs to be intensified during dose increases, or when a new, added, or switched antipsychotic medicine is introduced to their drug regimen, and during exposure to known risk factors for rhabdomyolysis. The development of seemingly nonserious events, such as abdominal pain, muscle pain, weakness, and dark urine, should be followed up during antipsychotic use, as they might be precursory events to rhabdomyolysis that eventually could develop into acute renal failure.
Yield of Lumbar Puncture Among Children Who Present With Their First Complex Febrile Seizure

OBJECTIVE: To assess the rate of acute bacterial meningitis (ABM) among children who present with their first complex febrile seizure (CFS). DESIGN AND METHODS: This study was a retrospective, cohort review of patients aged 6 to 60 months who were evaluated in a pediatric emergency department (ED) between 1995 and 2008 for their first CFS. Cases were identified by using a computerized text search followed by a manual chart review. Exclusion criteria included prior history of nonfebrile seizures, an immunocompromised state, an underlying illness associated with seizures or altered mental status, or trauma. Data extracted included age, gender, seizure features, the number of previous simple febrile seizures, temperature, a family history of seizures, findings on physical examination, laboratory and imaging study results, and ED diagnosis and disposition. RESULTS: We identified 526 patients. The median age was 17 months (interquartile range: 13–24), and 44% were female. Ninety patients (17%) had a previous history of simple febrile seizures. Of the patients, 340 (64%) had a lumbar puncture (LP). The patients' median white blood cell count during a CFS was 1 cell per μL (interquartile range: 1–2), and 14 patients had CSF pleocytosis (2.7% [95% confidence interval [CI]: 1.5–4.5]). Three patients had ABM (0.9% [95% CI: 0.2–2.8]). Two had Streptococcus pneumoniae in a culture of their cerebrospinal fluid. Among these 2 patients, 1 was nonresponsive during presentation, and the other had a bulging fontanel and apnea. The third child appeared well; however, her blood culture grew S pneumoniae and failed the LP test. None of the patients for whom an LP was not attempted subsequently returned to the hospital with a diagnosis of ABM (0% [95% CI: 0, 0.9]). CONCLUSION: Few patients who experienced a CFS had ABM in the absence of other signs or symptoms.
A New Slow Releasing, H2S Generating Compound, GYY4137 Relaxes Spontaneous and Oxytocin-Stimulated Contractions of Human and Rat Pregnant Myometrium

Better tocolytics are required to help prevent preterm labour. The gaseotransmitter Hydrogen sulphide (H2S) has been shown to reduce myometrial contractility and thus is of potential interest. However previous studies used NaHS, which is toxic and releases H2S as a non-physiological bolus and thus alternative H2S donors are sought. GYY4137 has been developed to slowly release H2S and hence better reflect endogenous physiological release. We have examined its effects on spontaneous and oxytocin-stimulated contractility and compared them to NaHS, in human and rat myometrium, throughout gestation. The effects on contractility in response to GYY4137 (1 nM–1 mM) and NaHS (1 mM) were examined on myometrial strips from, biopsies of women undergoing elective caesarean section or hysterectomy, and from non-pregnant, 14, 18, 22 day (term) gestation or labouring rats. In pregnant rat and human myometrium dose-dependent and significant decreases in spontaneous contractions were seen with increasing concentrations of GYY4137, which also reduced underlying Ca transients. GYY4137 and NaHS significantly reduced oxytocin-stimulated and high-K depolarised contractions as well as spontaneous activity. Their inhibitory effects increased as gestation advanced, but were abruptly reversed in labour. Glibenclamide, an inhibitor of ATP-sensitive potassium (KATP) channels, abolished the inhibitory effect of GYY4137. These data suggest (i) H2S contributes to uterine quiescence from mid-gestation until labor, (ii) that H2S affects L-type calcium channels and KATP channels reducing Ca entry and thereby myometrial contractions, (iii) add to the evidence that H2S plays a physiological role in relaxing myometrium, and thus (iv) H2S is an attractive target for therapeutic manipulation of human myometrial contractility.
Tumor CE image classification using SVM-based feature selection

In this paper, we propose a new scheme aimed for gastrointestinal (GI) tumor capsule endoscopy (CE) images classification, which utilizes sequential forward floating selection (SFFS) together with support vector machine (SVM). To achieve this goal, candidate features related to texture characteristics of CE images are extracted. With these candidate features, SFFS based on SVM is applied to select the most discriminative features that can separate normal CE images from tumor CE images. Comprehensive experiments on our present CE image data verify that it is promising to employ the proposed scheme to recognize tumor CE images.
Characterization of laterally deformable elastomer membranes for microfluidics

This work presents experimental characterization and numerical modeling of laterally deflecting polydimethylsiloxane (PDMS) membranes under pneumatic actuation. The device for this study is a membrane valve seat that partially closes a perpendicular fluid microchannel, fabricated using single-layer soft lithography. Membranes with thickness between 8 and 14 µm have been experimentally tested up to 207 kPa, and maximum lateral displacement beyond 20 µm has been demonstrated. Investigation of geometric parameters by factorial design shows that the height of the membrane is more dominant than the width and thickness, and this is attributed to the zero-displacement boundary condition at the foot of the membrane where it is bonded to a flat substrate. A numerical model that incorporates hyperelastic material testing data shows close agreement with the deflection behavior of experimental samples, accurately predicting that a membrane of 10 µm thick, 100 µm wide and 45 µm tall deflects approximately 13 µm at 207 kPa. Simulation further shows that sidewall effects from bulk compression of the elastomer material in the actuation cavity have a significant effect, reducing maximum displacement by as much as 15% over predictions based on deformation that is limited strictly to the membrane only. Experimental yield, SEM imaging and stress simulations emphasize that the membrane foot region requires the greatest attention in terms of process development.
Early Postnatal Exposure to a Low Dose of Decabromodiphenyl Ether Affects Expression of Androgen and Thyroid Hormone Receptor-Alpha and Its Splicing Variants in Mouse Sertoli Cells

Decabromodiphenyl ether (decaBDE) adversely affects reproduction and development. Our previous study showed that postnatal exposure to a low dose of decaBDE (0.025 mg/kg body weight/day) by subcutaneous injection on postnatal days (PNDs) 1 through 5 leads to reductions in testicular size and number of Sertoli cells and sperm, while higher dose of decaBDE (2.5 mg/kg body weight/day) had no significant differences about these. In the present study, we examined the molecular mechanism of these effects on mouse testes following postnatal exposure to a low decaBDE dose. We hypothesized that postnatal exposure to decaBDE may alter levels of serum thyroid hormones (THs) and testosterone, or the level of TH receptor alpha (Thra) transcripts and its splicing variants and androgen receptor (Ar) in Sertoli cells, adversely affecting spermatogenesis. To test this hypothesis, we examined serum TH and testosterone levels and the levels of transcripts of the Ar, Thra and its splicing variants, and Thra splicing factors (Hnrnpa1, Srsf1, and Hnrnph1) with qPCR in isolated mouse Sertoli cells exposed postnatally to decaBDE (0.025, 0.25, and 2.5 mg/kg). Levels of serum testosterone and transcripts encoding Ar, Thra, and its variant, Thra1, declined significantly in Sertoli cells of mice exposed to 0.025 mg decaBDE/kg. No significant differences in serum TH level or Thra2, Hnrnph1, or Srsf1 transcript levels were observed between control and decaBDE-exposed mice. However, the Thra1:Thra2 and Hnrnpa1:Srsf1 ratios were altered in Sertoli cells of mice exposed to 0.025 mg decaBDE/kg but not in cells exposed to 0.25 or 2.5 mg decaBDE/kg. These results indicate that postnatal exposure to a low dose of decaBDE on PNDs 1 through 5 lowers the testosterone level and the levels of Ar and Thra transcripts in Sertoli cells, accompanied by an imbalance in the ratios of Thra splicing variants, resulting in smaller testicular size and impaired spermatogenesis.
Association between Refractive Errors and Ocular Biometry in Iranian Adults

Purpose: To investigate the association between ocular biometrics such as axial length (AL), anterior chamber depth (ACD), lens thickness (LT), vitreous chamber depth (VCD) and corneal power (CP) with different refractive errors. Methods: In a cross-sectional study on the 40 to 64-year-old population of Shahroud, random cluster sampling was performed. Ocular biometrics were measured using the Allegro Biograph (WaveLight AG, Erlangen, Germany) for all participants. Refractive errors were determined using cycloplegic refraction. Results: In the first model, the strongest correlations were found between spherical equivalent with axial length and corneal power. Spherical equivalent was strongly correlated with axial length in high myopic and high hyperopic cases, and with corneal power in high hyperopic cases; 69.5% of variability in spherical equivalent was attributed to changes in these variables. In the second model, the correlations between vitreous chamber depth and corneal power with spherical equivalent were stronger in myopes than hyperopes, while the correlations between lens thickness and anterior chamber depth with spherical equivalent were stronger in hyperopic cases than myopic ones. In the third model, anterior chamber depth + lens thickness correlated with spherical equivalent only in moderate and severe cases of hyperopia, and this index was not correlated with spherical equivalent in moderate to severe myopia. Conclusion: In individuals aged 40-64 years, corneal power and axial length make the greatest contribution to spherical equivalent in high hyperopia and high myopia. Anterior segment biometric components have a more important role in hyperopia than myopia.
Automatic image‐driven segmentation of the ventricles in cardiac cine MRI

To propose and to evaluate a novel method for the automatic segmentation of the heart's two ventricles from dynamic (“cine”) short‐axis “steady state free precession” (SSFP) MR images. This segmentation task is of significant clinical importance. Previously published automated methods have various disadvantages for routine clinical use.
Diffusion tensor spectroscopy (DTS) of human brain

The diffusion tensor of N‐acetyl aspartate (NAA), creatine and phosphocreatine (tCr), and choline (Cho) was measured at 3T using a diffusion weighted STEAM 1H‐MRS sequence in the healthy human brain in 6 distinct regions (4 white matter and 2 cortical gray matter). The Trace/3 apparent diffusion coefficient (ADC) of each metabolite was significantly greater in white matter than gray matter. The Trace/3 ADC values of tCr and Cho were found to be significantly greater than NAA in white matter, whereas all 3 metabolites had similar Trace/3 ADC in cortical gray matter. Fractional anisotropy (FA) values for all 3 metabolites were consistent with water FA values in the 4 white matter regions; however, metabolite FA values were found to be higher than expected in the cortical gray matter. The principal diffusion direction derived for NAA was in good agreement with expected anatomic tract directions in the white matter. Magn Reson Med, 2006. © 2005 Wiley‐Liss, Inc.
Matrix-Assisted Laser Desorption Ionization - Time of Flight Mass Spectrometry: An Emerging Tool for the Rapid Identification of Mosquito Vectors

Background The identification of mosquito vectors is typically based on morphological characteristics using morphological keys of determination, which requires entomological expertise and training. The use of protein profiling by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), which is increasingly being used for the routine identification of bacteria, has recently emerged for arthropod identification. Methods To investigate the usefulness of MALDI-TOF-MS as a mosquito identification tool, we tested protein extracts made from mosquito legs to create a database of reference spectra. The database included a total of 129 laboratory-reared and field-caught mosquito specimens consisting of 20 species, including 4 Aedes spp. , 9 Anopheles spp. , 4 Culex spp. , Lutzia tigripes, Orthopodomyia reunionensis and Mansonia uniformis. For the validation study, blind tests were performed with 76 specimens consisting of 1 to 4 individuals per species. A cluster analysis was carried out using the MALDI-Biotyper and some spectra from all mosquito species tested. Results Biomarker mass sets containing 22 and 43 masses have been detected from 100 specimens of the Anopheles, Aedes and Culex species. By carrying out 3 blind tests, we achieved the identification of mosquito vectors at the species level, including the differentiation of An. gambiae complex, which is possible using MALDI-TOF-MS with 1.8 as the cut-off identification score. A cluster analysis performed with all available mosquito species showed that MALDI-Biotyper can distinguish between specimens at the subspecies level, as demonstrated for An gambiae M and S, but this method cannot yet be considered a reliable tool for the phylogenetic study of mosquito species. Conclusions We confirmed that even without any specific expertise, MALDI-TOF-MS profiling of mosquito leg protein extracts can be used for the rapid identification of mosquito vectors. Therefore, MALDI-TOF-MS is an alternative, efficient and inexpensive tool that can accurately identify mosquitoes collected in the field during entomological surveys.
What Is the Accuracy of the High-Fidelity METI Human Patient Simulator Physiological Models During Oxygen Administration and Apnea Maneuvers?

BACKGROUND: A widely used physiological simulator is generally accepted to give valid predictions of oxygenation status during disturbances in breathing associated with anesthesia. We compared predicted measures with physiological measurements available in the literature, or derived from other models. METHODS: Five studies were selected from the literature which explored arterial oxygenation, with or without preoxygenation, in clinical situations or through mathematical modeling as well as the evolution of the fraction of expired oxygen (FEO2) during preoxygenation maneuvers. Scenarios from these studies were simulated on the METI-Human Patient Simulator™ simulator, and the data were compared with the results in the literature. RESULTS: Crash-induction anesthesia without preoxygenation induces an O2 pulse saturation (SpO2) decrease that is not observed on the METI simulator. In humans, after 8 minutes of apnea, SpO2 decreased below 90% while the worst value was 95% during the simulation. The apnea time to reach 85% was less with obese patients than with healthy simulated patients and was shortened in the absence of preoxygenation. However, the data in the literature include METI simulator confidence interval 95% values only for healthy humans receiving preoxygenation. The decrease in PaO2 during 35-second apnea started at end-expiration was slower on the METI simulator than the values reported in the literature. FEO2 evolution during preoxygenation maneuvers on the METI simulator with various inspired oxygen fractions (100%, 92%, 84%, and 68%) was very close to those reported in humans when perfect mask seal is provided. In practice, this seal is impossible to obtain on the METI simulator. CONCLUSIONS: SpO2 decreased much later during apnea on the METI simulator than in a clinical situation, whether preoxygenation was performed or not. The debriefing after simulation of critical situations or the use of the METI simulator to test a new equipment must consider these results.