Miracle-dz/UniFAR-FTUs huggingface dataset:
Childhood Outcomes Following Parechovirus Infections in a US Young Infant Cohort

Background: Parechovirus A type 3 (PeV-A3) is associated with central nervous system infection in young infants. There are limited data regarding long-term outcomes, mostly reported from Australia and European populations. The objective of this study was to assess frequency of neurodevelopmental impairment (NDI) following PeV-A3 infection in our US cohort. Methods: Infants hospitalized during the 2014 outbreak with laboratory-confirmed PeV-A3 infection were evaluated with medical history, neurologic examination, parental completion of Ages and Stages Questionnaire and developmental assessment using Bayley Scales of Infant and Toddler Development, Third Edition cognitive, motor and language quotients. Determination of NDI was based on published criteria. Relationship of severity of PeV disease to outcome measures was determined using Fisher exact, χ2 and Mann-Whitney U test as appropriate. Results: Nineteen children, term gestation, were evaluated at ~3 years of age; PeV-A3 illness was uncomplicated for 6 (32%), complex, non-neurologic for 9 (47%) and encephalitis/seizures for 4 (21%). No differences were noted in mean Bayley Scales of Infant and Toddler Development, Third Edition quotients between infants by clinical presentation. Quotients for all were within 1 SD of population norms. Two (11%) children had mild NDI; 1 with mild cerebral palsy. Ages and Stages Questionnaire results included 11% at referral level and 37% suspect concern. Parents of 6 (32%) noted behavior concerns. These findings were unrelated to severity of the PeV-A3 illness. Conclusions: Parent concerns were identified frequently following infant PeV-A3 disease. Eleven percent had neurodevelopmental impairment at 3 years of age. Severity at presentation did not correlate with adverse childhood outcomes. Longitudinal developmental monitoring following infantile PeV-A3 disease is warranted.
Engineering Transcriptional Interference through RNA Polymerase Processivity Control

Antisense transcription is widespread in all kingdoms of life and has been shown to influence gene expression through transcriptional interference (TI), a phenomenon in which one transcriptional process negatively influences another in cis. The processivity, or uninterrupted transcription, of an RNA Polymerase (RNAP) is closely tied to levels of antisense transcription in bacterial genomes, but its influence on TI, while likely important, is not well-characterized. Here we show that TI can be tuned through processivity control via three distinct antitermination strategies: the antibiotic bicyclomycin, phage protein Psu, and ribosome-RNAP coupling. We apply these methods toward TI and tune ribosome-RNAP coupling to produce 38-fold gene repression due to RNAP collisions. We then couple protein roadblock and RNAP collisions to design minimal genetic NAND and NOR logic gates. Together these results show the importance of processivity control for strong TI and demonstrate the potential for TI to create sophisticated switching responses.
Personalized Therapy for Mycophenolate: Consensus Report by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology.

ABSTRACT When mycophenolic acid (MPA) was originally marketed for immunosuppressive therapy, fixed doses were recommended by the manufacturer. Awareness of the potential for a more personalized dosing has led to development of methods to estimate MPA area under the curve based on the measurement of drug concentrations in only a few samples. This approach is feasible in the clinical routine and has proven successful in terms of correlation with outcome. However, the search for superior correlates has continued, and numerous studies in search of biomarkers that could better predict the perfect dosage for the individual patient have been published. As it was considered timely for an updated and comprehensive presentation of consensus on the status for personalized treatment with MPA, this report was prepared following an initiative from members of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT). Topics included are the criteria for analytics, methods to estimate exposure including pharmacometrics, the potential influence of pharmacogenetics, development of biomarkers, and the practical aspects of implementation of target concentration intervention. For selected topics with sufficient evidence, such as the application of limited sampling strategies for MPA area under the curve, graded recommendations on target ranges are presented. To provide a comprehensive review, this report also includes updates on the status of potential biomarkers including those which may be promising but with a low level of evidence. In view of the fact that there are very few new immunosuppressive drugs under development for the transplant field, it is likely that MPA will continue to be prescribed on a large scale in the upcoming years. Discontinuation of therapy due to adverse effects is relatively common, increasing the risk for late rejections, which may contribute to graft loss. Therefore, the continued search for innovative methods to better personalize MPA dosage is warranted.
CLP290 promotes the sedative effects of midazolam in neonatal rats in a KCC2-dependent manner: A laboratory study in rats

Immature neurons dominantly express the Na+-K+-2Cl- cotransporter isoform 1 (NKCC1) rather than the K+-Cl- cotransporter isoform 2 (KCC2). The intracellular chloride ion concentration ([Cl-]i) is higher in immature neurons than in mature neurons; therefore, γ-aminobutyric acid type A (GABAA) receptor activation in immature neurons does not cause chloride ion influx and subsequent hyperpolarization. In our previous work, we found that midazolam, benzodiazepine receptor agonist, causes less sedation in neonatal rats compared to adult rats and that NKCC1 blockade by bumetanide enhances the midazolam-induced sedation in neonatal, but not in adult, rats. These results suggest that GABA receptor activation requires the predominance of KCC2 over NKCC1 to exert sedative effects. In this study, we focused on CLP290, a novel KCC2-selective activator, and found that midazolam administration at 20 mg/kg after oral CLP290 intake significantly prolonged the righting reflex latency even in neonatal rats at postnatal day 7. By contrast, CLP290 alone did not exert sedative effects. Immunohistochemistry showed that midazolam combined with CLP290 decreased the number of phosphorylated cAMP response element-binding protein-positive cells in the cerebral cortex, suggesting that CLP290 reverted the inhibitory effect of midazolam. Moreover, the sedative effect of combined CLP290 and midazolam treatment was inhibited by the administration of the KCC2-selective inhibitor VU0463271, suggesting indirectly that the sedation-promoting effect of CLP290 was mediated by KCC2 activation. To our knowledge, this study is the first report showing the sedation-promoting effect of CLP290 in neonates and providing behavioral and histological evidence that CLP290 reverted the sedative effect of GABAergic drugs through the activation of KCC2. Our data suggest that the clinical application of CLP290 may provide a breakthrough in terms of midazolam-resistant sedation.
Synthesis and Characterization of Iron/Iron Oxide Core/Shell Nanocubes

A simple method for the preparation of iron/iron oxide nanoparticles with core/shell cubic morphology is presented. The synthesis of the nanocubes was carried out through decomposition of a preformed iron oleate complex at high temperature. Although this procedure has been shown previously to produce monodisperse magnetite spheres,[1] the use of squalene as a solvent and the presence of sodium oleate was found to induce cube formation. A detailed high-resolution transmission electron microscopy (HRTEM) analysis of the nanocubes was performed for structural characterization. The core/shell structure, an iron core surrounded by magnetite (Fe3O4) shell, was confirmed by fast Fourier transform (FFT) filtering analysis. The results obtained by HRTEM analysis are in agreement with X-ray Photoelectron Spectroscopy (XPS) and magnetic analysis. The Fe nanocubes are superparamagnetic at room temperature with a saturation magnetization MS = 101 A m2 kg–1 and magnetic anisotropy density Keff = 1.6 × 105 J m–3 at low temperatures.
Citizens, Research Ethics Committee Members and Researchers’ Attitude Toward Information and Consent for the Secondary Use of Health Data: Implications for Research Within Learning Health Systems

A survey was conducted to assess citizens, research ethics committee members, and researchers’ attitude toward information and consent for the secondary use of health data for research within learning health systems (LHSs). Results show that the reuse of health data for research to advance knowledge and improve care is valued by all parties; consent regarding health data reuse for research has fundamental importance particularly to citizens; and all respondents deemed important the existence of a secure website to support the information and consent processes. This survey was part of a larger project that aims at exploring public perspectives on alternate approaches to the current consent models for health data reuse to take into consideration the unique features of LHSs. The revised model will need to ensure that citizens are given the opportunity to be better informed about upcoming research and have their say, when possible, in the use of their data.
Acceleration mechanics during forward and backward running: A comparison of step kinematics and kinetics over the first 20 m

ABSTRACT Backward running (BR) and forward running (FR) are unique movements utilized by athletes in many sports. Importantly, this investigation provides further insights on BR and benchmarking against more commonly researched FR capacity. Twenty-one collegiate soccer players (age 20.0 ± 0.8 years, body mass 65.6 ± 7.7 kg, body height 1.70 ± 0.07 m) performed maximal effort BR and FR along 20 m of in-ground force platforms. Step kinematics and kinetics were compared between BR and FR over four relative acceleration phases (BR = steps 1–6, 7–12, 13–18 and 19–23; FR = steps 1–4, 5–8, 9–12, 13–15). The primary findings of this study were that BR speeds were 29% slower than FR (p < 0.001), all step kinematics differed between BR and FR (p < 0.01), except contact time from the second to fourth step phases (p > 0.05), and most step kinetics were lower during BR (p < 0.05), with the exceptions of peak vertical force (p > 0.05). These findings indicate that lower running speeds over the acceleration phases of BR appear to be primarily due to lower horizontal ground reaction force application, resulting in shorter stride lengths and decreased flight times compared to FR.
Novel Glutamine Antagonist JHU395 Suppresses MYC-Driven Medulloblastoma Growth and Induces Apoptosis.

Medulloblastoma is the most common malignant pediatric brain tumor. Amplification of c-MYC is a hallmark of a subset of poor-prognosis medulloblastoma. MYC upregulates glutamine metabolism across many types of cancer. We modified the naturally occurring glutamine antagonist 6-diazo-5-oxo-l-norleucine (DON) by adding 2 promoeities to increase its lipophilicity and brain penetration creating the prodrug isopropyl 6-diazo-5-oxo-2-(((phenyl (pivaloyloxy) methoxy) - carbonyl) amino) hexanoate, termed JHU395. This prodrug was shown to have a 10-fold improved CSF-to-plasma ratio and brain-to-plasma ratio relative to DON. We hypothesized that JHU395 would have superior cell penetration compared with DON and would effectively and more potently kill MYC-expressing medulloblastoma. JHU395 treatment caused decreased growth and increased apoptosis in multiple human high-MYC medulloblastoma cell lines at lower concentrations than DON. Parenteral administration of JHU395 in Nu/Nu mice led to the accumulation of micromolar concentrations of DON in brain. Treatment of mice bearing orthotopic xenografts of human MYC-amplified medulloblastoma with JHU395 increased median survival from 26 to 45 days compared with vehicle control mice (p < 0.001 by log-rank test). These data provide preclinical justification for the ongoing development and testing of brain-targeted DON prodrugs for use in medulloblastoma.
Clinical Implications of Horizontal Beating Nystagmus Induced by Dix-Hallpike Test in the Diagnosis of Horizontal Canal Benign Paroxysmal Positional Vertigo

Objectives: The purpose of this study was to identify the diverse patterns of nystagmus during the Dix-Hallpike test (DHT) and analyze their clinical significance in horizontal canal benign paroxysmal positional vertigo (HC-BPPV). Study Design: Retrospective medical records review. Patients: Two hundred ninety-five patients diagnosed with HC-BPPV. Methods: Various nystagmus patterns identified during the DHT in patients with HC-BPPV were analyzed. The correlation between the affected side of HC-BPPV and the direction of the horizontal beating nystagmus (HBN) during the DHT was also analyzed. Results: The nystagmus pattern during the DHT in 128 patients with geotropic HC-BPPV demonstrated, direction-changing positional nystagmus on both sides in 48 (37.5%) patients, HBN toward one side in 25 (19.6%) patients, and no nystagmus in 55 (42.9%) patients. In 144 patients with apogeotropic HC-BPPV, 54 (37.5%) patients presented with direction-changing positional nystagmus on both sides, 27 (18.8%) patients presented with HBN toward one side, and 63 (43.7%) patients did not show nystagmus during the DHT. The direction of HBN provoked by the DHT was significantly correlated with the affected side in each subtype of HC-BPPV (geotropic type, p = 0.049; apogeotropic type, p = 0.040; respectively). Conclusion: More than half of the patients with HC-BPPV (56.6%) showed HBN during the DHT. When HBN was present during the DHT, it may provide a clue for determining the subtype and affected side in diagnosis of HC-BPPV before performing the supine roll test.
Diagnostic Contribution of Contrast-Enhanced CT as Compared with Unenhanced Low-Dose CT in PET/CT Staging and Treatment Response Assessment of 18F-FDG–Avid Lymphomas: A Prospective Study

Visual Abstract The aim of this study was to assess the added diagnostic value of contrast-enhanced CT (CECT) as compared with unenhanced CT (UECT) in PET/CT staging and treatment response assessment of 18F-FDG–avid lymphomas. Methods: 170 PET/UECT scans followed by CECT scans were prospectively performed for staging (n = 85) and for treatment response assessment (n = 85) of 18F-FDG–avid lymphomas, during a single session using an integrated 64-slice PET/CT scanner. CECT and UECT images were evaluated separately by 2 radiologists, whereas PET images were evaluated by 2 nuclear physicians. Nodal and extranodal UECT and CECT findings were classified according to the Lugano criteria and were successively compared with PET/CT results, considered the gold standard. In the analyzed groups, the agreement rate with the disease status determined via PET was calculated separately for UECT and CECT using the McNemar test on paired data. The added value of the contrast medium was shown by the agreement between the PET and CECT results and the lack of agreement between UECT and PET. Results: CECT enabled the identification of additional extranodal lesions (hepatic, muscular, and gastric) in only 3 staging group cases (3.5%), indicating different stages as compared with UECT, whereas there was absolute agreement between CECT and UECT in terms of treatment response assessment. The added diagnostic value of CECT was lower than the established threshold for clinical relevance (15%). The McNemar test indicated no statistical significance in either group. The incidental findings detected by CECT but not UECT were important for clinical management but not sufficient to alter lymphoma treatment strategy. Conclusion: According to our results, it might be possible to exclude CECT examination of 18F-FDG–avid lymphoma from staging and treatment response assessment, with the consequent advantages of reducing radiation exposure and potential contrast-related risks.
Regeneration potential of decellularized periodontal ligament cell sheets combined with 15-deoxy-Δ12,14-prostaglandin J2 nanoparticles in a rat periodontal defect

Periodontitis is a chronic inflammatory disease characterized by loss of attachment and destruction of the periodontium. Decellularized sheet, as an advanced tissue regeneration engineering biomaterial, has been researched and applied in many fields, but its effects on periodontal regeneration remain unclear. In this study, the biological properties of decellularized human periodontal ligament cell (dHPDLC) sheets were evaluated in vitro. Polycaprolactone/gelatin (PCL/GE) nanofibers were fabricated as a carrier to enhance the mechanical strength of the dHPDLC sheet. 15-deoxy- Δ12,14 -prostaglandin J2 (15d-PGJ2) nanoparticles were added for anti-inflammation and regeneration improvement. For in vivo analysis, dHPDLC sheets combined with 15d-PGJ2 nanoparticles, with or without PCL/GE, were implanted into rat periodontal defects. The periodontal regeneration effects were identified by microcomputed tomography (micro-CT) and histological staining, and immunohistochemistry. The results revealed that DNA content was reduced by 96.6%. The hepatocyte growth factor, vascular endothelial growth factor, and basic fibroblast growth factor were preserved but reduced. The expressions or distribution of collagen I and fibronectin were similar in dHPDLC and nondecellularized cell sheets. The dHPDLC sheets maintained the intact structure of the extracellular matrix. It could be recellularized by allogeneic human periodontal stem ligament cells and retain osteoinductive potential. Newly formed bone, cementum, and PDL were observed in dHPDLC sheets combined with 15d-PGJ2 groups, with or without PCL/GE nanofibers, for four weeks post-operation in vivo. Bringing together all these points, this new construct of dHPDLC sheets can be a potential candidate for periodontal regeneration in an inflammatory environment of the oral cavity.
Quality and physiological changes of film packaged malvasio' mandarins during long term storage

Abstract Malvasio mandarins were packaged in fibreboard cartons (approximately 2.5 kg per box) using three different plastic films: film A (the least permeable), film B (medium permeability) and film C (perforated). Fruits were stored for 6 or 12 weeks at 4 °C plus 1 week at 20 °C and 75% relative humidity (shelf-life). Film C had only a slight influence on quality maintenance, negligible from the practical point of view. Film A and film B preserved visual appearance and inhibited weight loss. Chemical and sensory quality of wrapped fruits were substantially similar to controls, when kept at 4 °C, while nutritional and taste characteristics deteriorated severely upon transfer to shelf-life conditions. The best results were achieved with fruit sealed with film B and unwrapped at the end of cold storage, when transferred to 20 °C.
Recent Advances in H2/O2 High Pressure Coaxial Injector Performance Analysis.

Theoretical and experimental studies have been performed on propellant injection problems in high pressure H2/O2 combustors using coaxial injector configurations with liquid (LOX) core and surrounding parallel (GH2) gas stream. The aim based on previous experiences in the field of atomization has been to identify some of the fundamental processes in liquid jet break-up, droplet generation, evaporation, mixing and/or transport under supercritical pressure conditions, in order to be able to define, beyond empirical knowledge, the physical boundary conditions for subsequent combustion and expansion regimes and to establish and verify corresponding mathematical laws for integration into global combustor models.
Dependence of Interface State Density on Silicon Thermal Oxidation Process Variables

The structural or intrinsic type of interface state charge, related to thermal oxidation and annealing processes, has been characterized with respect to silicon thermal oxidation variables using quasistatic C‐V techniques. Those variables include oxidation ambient (, , ), annealing/cooling ambient (, , Ar), oxidation temperature (800°–1200°C), silicon type (p‐ and n‐type), and orientation [(111) and (100)]. Oxides (1200–2200A thick) annealed and cooled from any oxidation temperature in nitrogen or argon exhibit large interface state densities as oxidized. However after a low temperature hydrogen anneal these densities are lower than those of comparable oxygen‐cooled oxides. Interface state densities of oxides cooled in oxygen vary inversely with oxidation temperature before and after postmetallization anneals. This temperature relationship is very similar to that reported previously for oxide fixed charge and helps to substantiate a model based on a common origin of interface states and oxide fixed charge.
Envirocat (K10-MX)–Catalyzed Regioselective Transformation of Alkenes into Iodohydrins and β-Iodo Ethers and Further Conversion of Iodohydrins to Epoxides Using Al2O3-Na2CO3 Under MWI

Abstract Commercial K10 clay was converted to extremely efficient and environmentally friendly catalyst K10-MX for the preparation of iodohydrins and β-iodo ethers from alkenes (terminal as well as internal) using microwave irradiation. This method was further extended for the conversion of alkenes to epoxides via iodohydrin intermediate in a one-pot reaction system. GRAPHICAL ABSTRACT
Dielectric response of disordered Pb(Sc1/2Ta1/2)O3 single crystal under hydrostatic pressure

The effect of hydrostatic pressure on the dielectric response of Pb(Sc1/2Ta1/2)O3 single crystal with the degree of order S = 0.16 has been studied. At elevated pressures the dielectric anomaly characteristic of ferroelectric relaxors is shifted to lower temperatures, its amplitude decreases and the relaxor peak becomes more diffused. In the pressure range studied up to 0.75 GPa, the temperature dependencies of the characteristic relaxation time obey the Vogel–Fulcher law. It has been found that the Vogel–Fulcher temperature decreases with increasing pressure while the activation energy of the dipolar entities increases. This increase can be ascribed to the pressure-induced changes in the atom–atom and dipolar interactions, resulting in the increased energy barriers for dipolar fluctuations.
Diverse bacterial profile in extraradicular biofilms and periradicular lesions associated with persistent apical periodontitis.

AIM To characterize the bacterial community present in the extraradicular biofilm and periradicular lesions associated with persistent apical periodontitis. METHODOLOGY Eighteen adult patients who presented with persistent periradicular lesions after root canal treatment and scheduled for endodontic surgery were selected. During surgery, extraradicular samples of biofilms and periradicular lesions were collected. Ten pairs of periradicular lesions and extraradicular biofilm samples were randomly selected for ribosomal 16S rRNA cloning and sequencing. A Wilcoxon's rank-sum test was used to compare total bacterial counts and the levels of individual genera and species between the two groups (P < 0.05). RESULTS Overall, seventy-three phylotypes belonging to 6 different phyla were identified from 1000 sequenced clones. M. timidum, S. intermedius and E. faecalis predominated in both extraradicular biofilm and periapical lesions. P. propionicus, A. adiacens, P. prevotii, C. gracilis and P. aeruginosa were found in significantly higher levels in the extraradicular biofilm than periapical lesions, while P. micra and A. rimae were more abundant in periapical lesions (P < 0.05). CONCLUSIONS The microbial profile of extraradicular biofilms differed from periapical lesions, indicating the presence of diverse bacterial populations in these regions. Several genera and species were significantly associated with the formation of extraradicular biofilm.