Miracle-dz/UniFAR-FTUs huggingface dataset:
A novel approach to extraction of a large thrombus on the intraventricular guide‐wire during transcatheter aortic valve replacement

For appropriate patients with severe symptomatic aortic stenosis with a prohibitively high surgical risk, trans‐catheter aortic valve replacement (TAVR) is now established as a viable option. Thrombosis on the intra‐ventricular guide‐wire during TAVR is a recognized complication (Wiper et al., Cardiovasc Revasc Med 2014). There is an obvious potential for embolization with particular concern for stroke in this situation. We describe a case in which a >1cm thrombus was noted on the intra‐ventricular guide‐wire by trans‐esophageal echocardiogram (TEE) during a TAVR procedure. Balloon aortic valvuloplasty was still performed and an Edwards Sapien valve was deployed. After valve deployment a multi‐purpose guiding catheter was advanced with continuous suction. The guide‐wire and thrombus were withdrawn inside the guiding catheter. The guide‐wire and catheter were removed as a single unit, allowing the thrombus to be safely retrieved. We believe that this is a novel technique of aspiration thrombectomy in this potentially hazardous clinical circumstance. As our experience with TAVR increases, so does our experience with the complications. In the PARTNER trial there was a higher rate of neurological events in TAVR patients than those who had open aortic valve replacement (Smith et al. N Engl J Med 2011;364:2187–2198.). This may be related to peri‐procedural formation of thrombus and subsequent embolization. We report a case where a large guide‐wire thrombus identified during TAVR was successfully removed using a novel approach, preventing a potentially major stroke in this high‐risk patient. © 2015 Wiley Periodicals, Inc.
Application of flower pollination algorithm to parameter identification of DC motor model

Flower pollination algorithm (FPA) is one of the most efficient population-based nature-inspired metaheuristic optimization algorithms based on the flower pollination process of flowering plants. With Lévy distribution, the FPA can control the balance of exploration and exploitation properties with a proposed switch probability. This leads the FPA efficiently escape from local entrapment and reach global optimal rapidly. In this paper, the application of FPA to parameter identification of a direct current (DC) motor model is proposed. Under testing, the DC motor system was excited by the step input to generate the specific level of the motor speed considered as the output of the system. As results of parameter identification and validation, it was found that the FPA can provide the optimal parameters of DC motor model representing system dynamics accurately. Very good agreement between actual system dynamics behavior and model parameters obtained by the FPA is completely confirmed.
Sequence Motifs in Transit Peptides Act as Independent Functional Units and Can Be Transferred to New Sequence Contexts1[OPEN]

Various sequence motifs in diverse transit peptides act as independent functional units and can be transferred to new sequence contexts with the possibility of a change in their functionality. A large number of nuclear-encoded proteins are imported into chloroplasts after they are translated in the cytosol. Import is mediated by transit peptides (TPs) at the N termini of these proteins. TPs contain many small motifs, each of which is critical for a specific step in the process of chloroplast protein import; however, it remains unknown how these motifs are organized to give rise to TPs with diverse sequences. In this study, we generated various hybrid TPs by swapping domains between Rubisco small subunit (RbcS) and chlorophyll a/b-binding protein, which have highly divergent sequences, and examined the abilities of the resultant TPs to deliver proteins into chloroplasts. Subsequently, we compared the functionality of sequence motifs in the hybrid TPs with those of wild-type TPs. The sequence motifs in the hybrid TPs exhibited three different modes of functionality, depending on their domain composition, as follows: active in both wild-type and hybrid TPs, active in wild-type TPs but inactive in hybrid TPs, and inactive in wild-type TPs but active in hybrid TPs. Moreover, synthetic TPs, in which only three critical motifs from RbcS or chlorophyll a/b-binding protein TPs were incorporated into an unrelated sequence, were able to deliver clients to chloroplasts with a comparable efficiency to RbcS TP. Based on these results, we propose that diverse sequence motifs in TPs are independent functional units that interact with specific translocon components at various steps during protein import and can be transferred to new sequence contexts.
The cost of an additional disability-free life year for older Americans: 1992-2005.

OBJECTIVE To estimate the cost of an additional disability-free life year for older Americans in 1992-2005. DATA SOURCE This study used 1992-2005 Medicare Current Beneficiary Survey, a longitudinal survey of Medicare beneficiaries with a rotating panel design. STUDY DESIGN This analysis used multistate life table model to estimate probabilities of transition among a discrete set of health states (nondisabled, disabled, and dead) for two panels of older Americans in 1992 and 2002. Health spending incurred between annual health interviews was estimated by a generalized linear mixed model. Health status, including death, was simulated for each member of the panel using these transition probabilities; the associated health spending was cross-walked to the simulated health changes. PRINCIPAL FINDINGS Disability-free life expectancy (DFLE) increased significantly more than life expectancy during the study period. Assuming that 50 percent of the gains in DFLE between 1992 and 2005 were attributable to increases in spending, the average discounted cost per additional disability-free life year was $71,000. There were small differences between gender and racial/ethnic groups. CONCLUSIONS The cost of an additional disability-free life year was substantially below previous estimates based on mortality trends alone.
Division of Comparative Physiology and Biochemistry , Society for Integrative and Comparative Biology Measuring Oxidative Stress : The Confounding Effect of Lipid Concentration in Measures of Lipid Peroxidation

Lipid peroxidation products are widely used as markers of oxidative damage in the organism. To properly interpret the information provided by these markers, it is necessary to know potential sources of bias and control confounding factors. Here, we investigated the relationship between two indicators of lipid mobilization (circulating levels of triglycerides and cholesterol) and two common markers of oxidative damage (plasma levels of malondialdehyde and hydroperoxides; the latter estimated from the d-ROMs assay kit). The following five avian specieswere studied: red-leggedpartridge (Alectoris rufa), zebra finch (Taeniopygia guttata), spotless starling (Sturnus unicolor), marsh harrier (Circus aeroginosus), and Montagu’s harrier (Circus pygargus). In all cases, plasma triglyceride lev*Corresponding author; e-mail: lorenzoperezrodriguez@gmail.com, lorenzo
Phase I/II study of decitabine in patients with myelodysplastic syndrome: A multi‐center study in Japan

The management of myelodysplastic syndrome (MDS) remains challenging. We performed a phase I/II study to evaluate the safety and efficacy of decitabine in patients with MDS in Japan. Patients with MDS with red cell transfusion dependence or 5–30% blasts in marrow and with an International Prognostic Scoring System score of intermediate‐1 or higher were eligible. Patients received intravenous decitabine at 15 or 20 mg/m2 daily for 5 days every 4 weeks. A total of 37 patients were enrolled. Three patients received 15 mg/m2 and experienced no dose limiting toxicity during the first cycle. Thirty‐four patients received 20 mg/m2. Grade 3 or greater non‐hematologic toxicities included cerebral infarction (n = 1), subdural hematoma (n = 1), elevated blood glucose (n = 1), and pulmonary hypertension (n = 1). At 20 mg/m2, complete response, partial response, and hematologic improvement were observed in 7 (20.6%), 2 (5.9%), and 7 (20.6%) patients, respectively. Complete cytogenetic response was observed in 30% of evaluable 20 patients. The median number of cycles to clinical response was 4 (range 4–8), and duration of remission was 474+ days (range 294–598+). The 2‐year rate of acute myeloid leukemia‐free survival was 52%. Correlative studies revealed hypomethylation in multiple genes in peripheral blood cells after treatment. Hypomethylation was generally more profound in CD15 + peripheral blood cells, which reflects myeloid cells, than in peripheral blood mononuclear cells. In summary, decitabine was safe and demonstrated efficacy in Japanese patients with high‐risk MDS. This trial was registered at ClinicalTrials.gov (NCT00796003).
Do lower cuff pressures reduce damage to the tracheal mucosa? A scanning electron microscopy study in neonatal pigs

Modern high volume–low pressure (HVLP) endotracheal tubes (ETT) cuffs can seal the trachea using baseline cuff pressures (CP) lower than peak inspiratory airway pressures (PIP). The aim of the study was to determine whether this technique reduces the damage to the tracheal mucosa compared to constant CP of 20 cmH2O.
Crystal structure of 1-methyluracil from neutron diffraction at 15, 60 and 123 K.

The crystal structure of 1-methylpyrimidine-2,4-dione (1-methyluracil, C5H6N2O2) has been determined at 15, 60 and 123 K from neutron diffraction data. Molecules lie in the eightfold special positions (symmetry m) of space group Ibam, with a = 13.213 (2), b = 13.172 (2), c = 6.163 (1) A at 15 K. Full-matrix least-squares refinements based on 807 (15 K), 805 (60 K) and 815 (123 K) reflections with sin theta/lambda less than 0.69 A-1 converged with R(F2) = 0.023, 0.024 and 0.024 respectively. Bond lengths and angles have e.s. d. 's less than 0.002 A and 0.2 degrees. Detailed analysis of the anisotropic thermal parameters gives estimates of the zero-point internal vibrations for all nuclei and also for molecular rigid-body thermal vibrations at 15, 60 and 123 K. With thermal-vibration corrections there is good agreement in bond lengths and angles at the three temperatures.
Margatoxin‐bound quantum dots as a novel inhibitor of the voltage‐gated ion channel Kv1.3

Venom‐derived ion channel inhibitors have strong channel selectivity, potency, and stability; however, tracking delivery to their target can be challenging. Herein, we utilized luminescent quantum dots (QDs) conjugated to margatoxin (MgTx) as a traceable vehicle to target a voltage‐dependent potassium channel, Kv1.3, which has a select distribution and well‐characterized role in immunity, glucose metabolism, and sensory ability. We screened both unconjugated (MgTx) and conjugated MgTx (QD‐MgTx) for their ability to inhibit Shaker channels Kv1.1 to Kv1.7 using patch‐clamp electrophysiology in HEK293 cells. Our data indicate that MgTx inhibits 79% of the outward current in Kv1.3‐transfected cells and that the QD‐MgTx conjugate is able to achieve a similar level of block, albeit a slightly reduced efficacy (66%) and at a slower time course (50% block by 10.9 ± 1.1 min, MgTx; vs. 15.3 ± 1.2 min, QD‐MgTx). Like the unbound peptide, the QD‐MgTx conjugate inhibits both Kv1.3 and Kv1.2 at a 1 nM concentration, whereas it does not inhibit other screened Shaker channels. We tested the ability of QD‐MgTx to inhibit native Kv1.3 expressed in the mouse olfactory bulb (OB). In brain slices of the OB, the conjugate acted similarly to MgTx to inhibit Kv1.3, causing an increased action potential firing frequency attributed to decreased intraburst duration rather than interspike interval. Our data demonstrate a retention of known biophysical properties associated with block of the vestibule of Kv1.3 by QD‐MgTx conjugate compared to that of MgTx, inferring QDs could provide a useful tool to deliver ion channel inhibitors to targeted tissues in vivo.
A solver-aided language for test input generation

Developing a small but useful set of inputs for tests is challenging. We show that a domain-specific language backed by a constraint solver can help the programmer with this process. The solver can generate a set of test inputs and guarantee that each input is different from other inputs in a way that is useful for testing. This paper presents Iorek: a tool that empowers the programmer with the ability to express to any SMT solver what it means for inputs to be different. The core of Iorek is a rich language for constraining the set of inputs, which includes a novel bounded enumeration mechanism that makes it easy to define and encode a flexible notion of difference over a recursive structure. We demonstrate the flexibility of this mechanism for generating strings. We use Iorek to test real services and find that it is effective at finding bugs. We also build Iorek into a random testing tool and show that it increases coverage.
Robot-Assisted Vertebral Body Augmentation: A Radiation Reduction Tool

Study Design. Retrospective. Objective. To assess radiation exposure time during robot-guided vertebral body augmentation compared with other published findings. Summary of Background Data. Rising incidence of vertebral compression fractures in the aging population result in widespread use of vertebral body cement augmentation with significant radiation exposure to the surgeon, operating room staff, and patient. Radiation exposure leads to higher cancer rates among orthopedic and spine surgeons and patients. Methods. Thirty-three patients with 60 vertebral compression fractures underwent robot-guided vertebral body augmentation performed by 2 surgeons simultaneously injecting cement at 2 levels under pulsed fluoroscopy. The age of patients was in the range from 29 to 92 (mean, 67 yr). One to 6 vertebrae were augmented per case (average 2). Twenty-five patients had osteoporotic fractures and 8 had pathological fractures. Robotic guidance data included execution rate, accuracy of guidance, total surgical time, and time required for robotic guidance. Radiation-related data included the average preoperative computed tomographic effective dose, radiation time for calibration, registration, placement of Kirschner wires, and total procedure radiation time. Radiation time per level and surgeon's exposure were calculated. Results. Kyphoplasty was performed in 15 patients (1 sacroplasty), vertebroplasty in 13, and intravertebral expanding implants in 5. The average preoperative computed tomographic effective dose was 50 mSv (18–81). Average operative time was 118 minutes (49–350). Mean robotic guidance took 36 minutes. Average operative radiation time was 46.1 seconds per level (33–160). Average exposure time of the surgeons and the operating room staff per augmented level was 37.6 seconds. The execution rate was 99%, with an accuracy of 99%. Two complications (hemothorax and superficial wound infection) occurred. Conclusion. The radiation exposure of the surgeon and the operating room staff in a series of robot-assisted vertebral body augmentation was 74% lower than published results on fluoroscopy guidance and approximately 50% lower than the literature on navigated augmentation. Level of Evidence: 4
Beta and alpha cell function in metabolically healthy but obese subjects: Relationship with entero‐insular axis

Obesity is widely acknowledged as a critical risk factor for metabolic complications. Among obese subjects, there is a phenotype of metabolically healthy but obese (MHO) individuals that shows a favorable cardiometabolic risk profile. We aimed to evaluate the potential mechanisms underlying the metabolic profile of this subset, including alpha and beta cell function and entero‐insular axis.
AIR POLLUTION AND BIRTH WEIGHT IN NORTHERN NEVADA, 1991-1999

This study examined the association between particulate matter ≤ 10 µm in aerodynamic size (PM 10), carbon monoxide (CO), and ozone (O 3), and birth weight in Washoe County, NV, from 1991 through 1999. In total, 39,338 single births were included in this study. The mean birth weight was 3383 ± 460 g and prevalence of low birth weight (LBW) was 2.46% for single births with a gestational age of 37-44 wk. After controlling for cofactors including infant sex, maternal residential city, education, medical risk factors, active tobacco use, drug use, alcohol use, prenatal care, mother's age, race and ethnicity of mothers, and weight gain of mothers, we found PM 10 exposure in the third trimester of pregnancy to be a significant predictor of birth weight of newborns. A 10-µg/m 3 increase in the 24-h PM 10 level in the third trimester of pregnancy can be associated with a birth-weight reduction of 11 g (95% CI: 2.3-19.8 g) using multiple linear regression; however, PM 10 was not found to be related with the risk of LBW from logistic regression. CO and O 3 were not found to be associated with birth weight or risk of LBW of newborns by the same modeling procedure. The results suggest PM 10 could be a risk factor associated with birth-weight reduction of newborns in urban northern Nevada; however, the current level of PM 10 is not a risk factor to increase the chance of LBW newborns.
Birth weight and psychological distress at age 45-51 years: results from the Aberdeen Children of the 1950s cohort study.

BACKGROUND It is unclear whether the effect of low birth weight on common affective disorders in later life is direct or mediated through childhood factors. AIMS To determine whether birth weight has a direct effect on psychological distress in adulthood not mediated by childhood IQ or behavioural problems. METHOD Participants (n=5572) of the Aberdeen Children of the 1950s study had data on birth weight for gestational age and adult psychological distress. Logistic regression was used to examine the association between these factors, with adjustment for confounders and potential childhood mediators. RESULTS Children born full term but weighing less than 5.5 lb had increased odds of psychological distress in later life after adjustment for potential confounders (OR=1.49, 95% CI 1.01-2.20). Further adjustment for childhood IQ and behaviour did not attenuate the association. A 1 s.d. decrease in birth weight for gestational age was associated with a 4% increased odds of psychological distress in adulthood (OR=1.04, 95% CI 0.97-1.12). CONCLUSIONS Low birth weight for gestational age, particularly at term, was associated with adult psychological distress. This was not mediated by childhood factors, suggesting a direct effect of early life factors on adult mental health. A neurodevelopmental pathway may therefore be implicated.
Systemic complement activation and complement gene analysis in enterohaemorrhagic Escherichia coli-associated paediatric haemolytic uraemic syndrome.

BACKGROUND In contrast to atypical haemolytic uraemic syndrome (aHUS), only single case reports and limited data have been published on systemic activation of the complement system and mutations in complement genes in paediatric enterohaemorrhagic Escherichia coli-induced HUS (EHEC-HUS). METHODS Complement activation (CH50, APH50, C3d, sC5b-9) was analysed at four timepoints (Week 1, Week 2, Month 3 and Month 6 after primary diagnosis of HUS) in 25 children with EHEC-HUS. Seven patients received the complement C5 inhibitor eculizumab. Targeted next generation sequencing for a total of 89 genes involved in complement regulation and coagulation and haemostasis was performed in all patients. RESULTS Activity of classical (CH50) and alternative (APH50) complement pathways was normal or even elevated throughout the observation time, except for patients under eculizumab treatment. In contrast, the mean concentration of the soluble terminal complement complex (sC5b-9) was significantly elevated at the first timepoint (mean 498 ng/mL), dropping to normal values after 2 weeks. Initially elevated (42 mU/L) median C3d concentration reached normal levels from Week 2. Levels of sC5b-9 >320 ng/mL at the time of HUS diagnosis were associated with arterial hypertension, oedema and lower platelet counts, but not with the duration of dialysis. Genetic analysis revealed various changes that may have had a modifying impact on the clinical course. CONCLUSIONS Complement activation at the acute phase of EHEC-HUS, indicated by increased levels of sC5b-9, predicts a poor outcome. Complement alterations appear to be more frequent in patients with EHEC-HUS than previously thought and are suspected to have a role in the severity of the disease.
Ceramide mediates acute oxygen sensing in vascular tissues.

AIMS A variety of vessels, such as resistance pulmonary arteries (PA) and fetoplacental arteries and the ductus arteriosus (DA) are specialized in sensing and responding to changes in oxygen tension. Despite opposite stimuli, normoxic DA contraction and hypoxic fetoplacental and PA vasoconstriction share some mechanistic features. Activation of neutral sphingomyelinase (nSMase) and subsequent ceramide production has been involved in hypoxic pulmonary vasoconstriction (HPV). Herein we aimed to study the possible role of nSMase-derived ceramide as a common factor in the acute oxygen-sensing function of specialized vascular tissues. RESULTS The nSMase inhibitor GW4869 and an anticeramide antibody reduced the hypoxic vasoconstriction in chicken PA and chorioallantoic arteries (CA) and the normoxic contraction of chicken DA. Incubation with interference RNA targeted to SMPD3 also inhibited HPV. Moreover, ceramide and reactive oxygen species production were increased by hypoxia in PA and by normoxia in DA. Either bacterial sphingomyelinase or ceramide mimicked the contractile responses of hypoxia in PA and CA and those of normoxia in the DA. Furthermore, ceramide inhibited voltage-gated potassium currents present in smooth muscle cells from PA and DA. Finally, the role of nSMase in acute oxygen sensing was also observed in human PA and DA. INNOVATION These data provide evidence for the proposal that nSMase-derived ceramide is a critical player in acute oxygen-sensing in specialized vascular tissues. CONCLUSION Our results indicate that an increase in ceramide generation is involved in the vasoconstrictor responses induced by two opposite stimuli, such as hypoxia (in PA and CA) and normoxia (in DA).
Neural stem/progenitor cells display a low requirement for oxidative metabolism independent of hypoxia inducible factor‐1alpha expression

Neural stem/progenitor cells (NSPCs) are multipotent cells within the embryonic and adult brain that give rise to both neuronal and glial cell lineages. Maintenance of NSPC multipotency is promoted by low oxygen tension, although the metabolic underpinnings of this trait have not been described. In this study, we investigated the metabolic state of undifferentiated NSPCs in culture, and tested their relative reliance on oxidative versus glycolytic metabolism for survival, as well as their dependence on hypoxia inducible factor‐1alpha (HIF‐1α) expression for maintenance of metabolic phenotype. Unlike primary neurons, NSPCs from embryonic and adult mice survived prolonged hypoxia in culture. In addition, NSPCs displayed greater susceptibility to glycolytic inhibition compared with primary neurons, even in the presence of alternative mitochondrial TCA substrates. NSPCs were also more resistant than neurons to mitochondrial cyanide toxicity, less capable of utilizing galactose as an alternative substrate to glucose, and more susceptible to pharmacological inhibition of the pentose phosphate pathway by 6‐aminonicotinamide. Inducible deletion of exon 1 of the Hif1a gene improved the ability of NSPCs to utilize pyruvate during glycolytic inhibition, but did not alter other parameters of metabolism, including their ability to withstand prolonged hypoxia. Taken together, these data indicate that NSPCs have a relatively low requirement for oxidative metabolism for their survival and that hypoxic resistance is not dependent upon HIF‐1α signaling.