Acyclovir Dosing Practices Across a Multicenter Cohort of Neonatal Intensive Care Units.

BACKGROUND: Acyclovir is the first-line therapy for neonatal herpes simplex virus infections. Therapy can mitigate morbidity and mortality but carries a risk for toxicity. We aimed to compare acyclovir dosing in neonatal intensive care units to published recommendations based on population pharmacokinetic (PopPK) analysis. METHODS: We performed a multicenter cohort study of infants in neonatal intensive care units managed by the Pediatrix Medical Group from 1997 to 2020. We included all infants who received acyclovir with complete dosing information. Our primary outcome was the proportion of courses with dosing within 80%-120% of the PopPK recommended daily dose and at the recommended dosing frequency. We compared dosing before and after the publication of the 2014 PopPK recommendations using linear probability modeling. RESULTS: We identified 6862 infants with complete dosing information across 308 centers. Dosing met PopPK recommendations for 41% of treatment courses for infants <30 weeks postmenstrual age (PMA), 71% for infants 30 to <36 weeks PMA and <1% for infants ≥ 36 weeks PMA. Comparison of dosing from 1997 to 2013 with that from 2015 to 2020 showed a significant increase in dosing meeting PopPK recommendations for infants <30 weeks PMA (P = 0.008) and infants 30 to <36 weeks PMA (P = 0.02) but not infants ≥ 36 weeks PMA (P = 0.29). No significant increase in dosing meeting PopPK recommendations was seen for any PMA group when comparison was limited to more recent years (2008-2013 vs. 2015-2020). CONCLUSIONS: Dosing meeting PopPK recommendations increased over time for some PMA groups, but dosing different than PopPK recommendations remains common. More research is needed to clarify optimal dosing strategies in these infants.

A deep learning-based approach for distinguishing different stress levels of human brain using EEG and pulse rate.

In today's world, people suffer from many fatal maladies, and stress is one of them. Excessive stress can have deleterious effects on the health, brain, mind, and nervous system of humans. The goal of this paper is to design a deep learningbased human stress level measurement technique using electroencephalogram (EEG), and pulse rate. In this research, EEG signals and pulse rate of healthy subjects are recorded while they solve four different question sets of increasing complexity. It is assumed that the subjects undergo through four different stress levels, i.e., 'no stress', 'low stress', 'medium stress', and 'high stress', while solving these question sets. An attention mechanism-based CNN-TLSTM (convolutional neural network-tanh long short-term memory) model is proposed to detect the mental stress level of a person. An attention layer is incorporated into the designed TLSTM network to increase the classification accuracy of the CNN-TLSTM model. The CNN network is used for the automated extraction of intricate features from the EEG signals and pulse rate. Then TLSTM is used to classify the stress level of a person into four different categories using the CNNextracted features. The obtained average accuracy of the proposed CNN-TLSTM model is 97.86%. Experimentally, it is found that the designed stress level measurement technique is highly effective and outperforms most existing state-of-the-art techniques. In the future, functional Near-Infrared Spectroscopy (fNIRS), ECG, and Galvanic Skin Response (GSR) can be employed with EEG and pulse rate to increase the effectiveness of the designed stress level measurement technique.

Insight into the biochemical and cell biological function of an intrinsically unstructured heat shock protein, Hsp12 of Ustilago maydis.

Small heat shock proteins (sHsps) play diverse roles in the stress response and maintenance of cellular functions. The Ustilago maydis genome codes for few sHsps. Among these, Hsp12 has previously been demonstrated to be involved in the pathogenesis of the fungus by our group. In the present study we further investigated the biological function of the protein in the pathogenic development of U. maydis. Analysis of the primary amino acid sequence of Hsp12 in combination with spectroscopic methods to analyse secondary protein structures revealed an intrinsically disordered nature of the protein. We also carried out detailed analysis on the protein aggregation prevention activity associated with Hsp12. Our data suggest Hsp12 has trehalose-dependent protein aggregation prevention activity. Through assaying the interaction of Hsp12 with lipid membranes in vitro we also showed the ability of U. maydis Hsp12 to induce stability in lipid vesicles. U. maydis hsp12 deletion mutants exhibited defects in the endocytosis process and delayed completion of the pathogenic life cycle. Therefore, U. maydis Hsp12 contributes to the pathogenic development of the fungus through its ability to relieve proteotoxic stress during infection as well as its membrane-stabilizing function.

Sarcosine Prostate Cancer Biomarker Detection by Controlling Oxygen in NiOx Membrane on Vertical Silicon Nanowires in Electrolyte-Insulator-Nanowire Structure.

Sarcosine prostate cancer biomarker with the low concentration of 1 pM has been detected by controlling oxygen from 1 to 15 sccm in a NiOx membrane on chemically etched vertical Si nanowires (SiNWs) in an electrolyte-insulator-nanowire (EIN) structure. The vertical Si nanowires with approximately 17 µm length and polycrystalline NiOx membrane are observed by both field-emission scanning electron microscope (FE-SEM) and high-resolution transmission electron microscope (HRTEM) images, respectively. The optimized NiOx membrane with oxygen content of 4 sccm on planar SiOx/Si substrate shows good pH sensitivity of approximately 50 mV/pH, low hysteresis of 3.4 mV, and low drift rate of 2.4 mV/h as compared to other oxygen content membranes of 1, 10, and 15 sccm. Further, uric acid with the concentration of 0.1 µM is detected directly by using the optimized NiOx membrane. In addition, repeatable H2O2 sensing with the low concentration of 10 pM as well as prostate cancer biomarker is detected, which is owing to the reduction-oxidation phenomena of the NiOx membranes. The sensing mechanism is owing to the Ni2+/Ni3+ oxidation states of the NiOx membrane, which is confirmed by X-ray photoelectron spectroscopy. The optimized NiOx membrane on vertical Si nanowire in the EIN structure shows a good drift rate of 3.84 mV/h and sarcosine detection with improvement of approximately 1000 times as compared to the planar Si in an electrolyte-insulator-semiconductor (EIS) structure. This sensor paves a way to detect early-stage diagnosis of prostate cancer rapidly in the near future.

Scalable cross-point resistive switching memory and mechanism through an understanding of H2O2/glucose sensing using an IrOx/Al2O3/W structure.

The resistive switching characteristics of a scalable IrOx/Al2O3/W cross-point structure and its mechanism for pH/H2O2 sensing along with glucose detection have been investigated for the first time. Porous IrOx and Ir3+/Ir4+ oxidation states are observed via high-resolution transmission electron microscope, field-emission scanning electron spectroscopy, and X-ray photo-electron spectroscopy. The 20 nm-thick IrOx devices in sidewall contact show consecutive long dc cycles at a low current compliance (CC) of 10 µA, multi-level operation with CC varying from 10 µA to 100 µA, and long program/erase endurance of >109 cycles with 100 ns pulse width. IrOx with a thickness of 2 nm in the IrOx/Al2O3/SiO2/p-Si structure has shown super-Nernstian pH sensitivity of 115 mV per pH, and detection of H2O2 over the range of 1-100 nM is also achieved owing to the porous and reduction-oxidation (redox) characteristics of the IrOx membrane, whereas a pure Al2O3/SiO2 membrane does not show H2O2 sensing. A simulation based on Schottky, hopping, and Fowler-Nordheim tunneling conduction, and a redox reaction, is proposed. The experimental I-V curve matches very well with simulation. The resistive switching mechanism is owing to O2- ion migration, and the redox reaction of Ir3+/Ir4+ at the IrOx/Al2O3 interface through H2O2 sensing as well as Schottky barrier height modulation is responsible. Glucose at a low concentration of 10 pM is detected using a completely new process in the IrOx/Al2O3/W cross-point structure. Therefore, this cross-point memory shows a method for low cost, scalable, memory with low current, multi-level operation, which will be useful for future highly dense three-dimensional (3D) memory and as a bio-sensor for the future diagnosis of human diseases.

Understanding of multi-level resistive switching mechanism in GeOx through redox reaction in H2O2/sarcosine prostate cancer biomarker detection.

Formation-free multi-level resistive switching characteristics by using 10 nm-thick polycrystalline GeOx film in a simple W/GeOx/W structure and understanding of switching mechanism through redox reaction in H2O2/sarcosine sensing (or changing Ge°/Ge4+ oxidation states under external bias) have been reported for the first time. Oxidation states of Ge0/Ge4+ are confirmed by both XPS and H2O2 sensing of GeOx membrane in electrolyte-insulator-semiconductor structure. Highly repeatable 1000 dc cycles and stable program/erase (P/E) endurance of >106 cycles at a small pulse width of 100 ns are achieved at a low operation current of 0.1 µA. The thickness of GeOx layer is found to be increased to 12.5 nm with the reduction of polycrystalline grain size of <7 nm after P/E of 106 cycles, which is observed by high-resolution TEM. The switching mechanism is explored through redox reaction in GeOx membrane by sensing 1 nM H2O2, which is owing to the change of oxidation states from Ge0 to Ge4+ because of the enhanced O2- ions migration in memory device under external bias. In addition, sarcosine as a prostate cancer biomarker with low concentration of 50 pM to 10 µM is also detected.

Negative voltage modulated multi-level resistive switching by using a Cr/BaTiOx/TiN structure and quantum conductance through evidence of H2O2 sensing mechanism.

Negative voltage modulated multi-level resistive switching with quantum conductance during staircase-type RESET and its transport characteristics in Cr/BaTiOx/TiN structure have been investigated for the first time. The as-deposited amorphous BaTiOx film has been confirmed by high-resolution transmission electron microscopy. X-ray photo-electron spectroscopy shows different oxidation states of Ba in the switching material, which is responsible for tunable more than 10 resistance states by varying negative stop voltage owing to slow decay value of RESET slope (217.39 mV/decade). Quantum conductance phenomenon has been observed in staircase RESET cycle of the memory devices. By inspecting the oxidation states of Ba+ and Ba2+ through measuring H2O2 with a low concentration of 1 nM in electrolyte/BaTiOx/SiO2/p-Si structure, the switching mechanism of each HRS level as well as the multi-level phenomenon has been explained by gradual dissolution of oxygen vacancy filament. Along with negative stop voltage modulated multi-level, current compliance dependent multi-level has also been demonstrated and resistance ratio up to 2000 has been achieved even for a thin (<5 nm) switching material. By considering oxidation-reduction of the conducting filaments, the current-voltage switching curve has been simulated as well. Hence, multi-level resistive switching of Cr/BaTiOx/TiN structure implies the promising applications in high dense, multistate non-volatile memories in near future.

Detection of pH and Enzyme-Free H2O2 Sensing Mechanism by Using GdO x Membrane in Electrolyte-Insulator-Semiconductor Structure.

A 15-nm-thick GdO x membrane in an electrolyte-insulator-semiconductor (EIS) structure shows a higher pH sensitivity of 54.2 mV/pH and enzyme-free hydrogen peroxide (H2O2) detection than those of the bare SiO2 and 3-nm-thick GdO x membranes for the first time. Polycrystalline grain and higher Gd content of the thicker GdO x films are confirmed by transmission electron microscopy (TEM) and X-ray photo-electron spectroscopy (XPS), respectively. In a thicker GdO x membrane, polycrystalline grain has lower energy gap and Gd(2+) oxidation states lead to change Gd(3+) states in the presence of H2O2, which are confirmed by electron energy loss spectroscopy (EELS). The oxidation/reduction (redox) properties of thicker GdO x membrane with higher Gd content are responsible for detecting H2O2 whereas both bare SiO2 and thinner GdO x membranes do not show sensing. A low detection limit of 1 µM is obtained due to strong catalytic activity of Gd. The reference voltage shift increases with increase of the H2O2 concentration from 1 to 200 µM owing to more generation of Gd(3+) ions, and the H2O2 sensing mechanism has been explained as well.