Accelerated free-breathing liver fat and R 2 * quantification using multi-echo stack-of-radial MRI with motion-resolved multidimensional regularized reconstruction: Initial retrospective evaluation.

PURPOSE: To improve image quality, mitigate quantification biases and variations for free-breathing liver proton density fat fraction (PDFF) and R 2 * $$ {\mathrm{R}}_2^{\ast } $$ quantification accelerated by radial k-space undersampling. METHODS: A free-breathing multi-echo stack-of-radial MRI method was developed with compressed sensing with multidimensional regularization. It was validated in motion phantoms with reference acquisitions without motion and in 11 subjects (6 patients with nonalcoholic fatty liver disease) with reference breath-hold Cartesian acquisitions. Images, PDFF, and R 2 * $$ {\mathrm{R}}_2^{\ast } $$ maps were reconstructed using different radial view k-space sampling factors and reconstruction settings. Results were compared with reference-standard results using Bland-Altman analysis. Using linear mixed-effects model fitting (p < 0.05 considered significant), mean and SD were evaluated for biases and variations of PDFF and R 2 * $$ {\mathrm{R}}_2^{\ast } $$ , respectively, and coefficient of variation on the first echo image was evaluated as a surrogate for image quality. RESULTS: Using the empirically determined optimal sampling factor of 0.25 in the accelerated in vivo protocols, mean differences and limits of agreement for the proposed method were [-0.5; -33.6, 32.7] s-1 for R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and [-1.0%; -5.8%, 3.8%] for PDFF, close to those of a previous self-gating method using fully sampled radial views: [-0.1; -27.1, 27.0] s-1 for R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and [-0.4%; -4.5%, 3.7%] for PDFF. The proposed method had significantly lower coefficient of variation than other methods (p < 0.001). Effective acquisition time of 64 s or 59 s was achieved, compared with 171 s or 153 s for two baseline protocols with different radial views corresponding to sampling factor of 1.0. CONCLUSION: This proposed method may allow accelerated free-breathing liver PDFF and R 2 * $$ {\mathrm{R}}_2^{\ast } $$ mapping with reduced biases and variations.

Protocol for nanoscale thermal mapping of electronic devices using atomic force microscopy with phase change material.

In this protocol, we present a facile nanoscale thermal mapping technique for electronic devices by use of atomic force microscopy and a phase change material Ge2Sb2Te5. We describe steps for Ge2Sb2Te5 thin film coating, Ge2Sb2Te5 temperature calibration, thermal mapping by varying heater power, and thermal mapping by varying heating time. The protocol can be applied for resolving surface temperatures of various operational microelectronic devices with a nanoscale precision. For complete details on the use and execution of this protocol, please refer to Cheng et al.1.

Growth differentiation factor-15 as a negative predictor for microvascular obstruction in ST-segment elevation myocardial infarction after primary percutaneous coronary intervention.

Growth differentiation factor-15 (GDF-15) is an anti-inflammatory cytokine with cardioprotective effects, but circulating GDF-15 concentration predicts adverse cardiovascular outcomes in clinical settings. Microvascular obstruction (MVO) formation contributed to poor prognosis in patients with ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (pPCI). We aimed to investigate GDF-15 concentration in relation to cardiac magnetic resonance (CMR)-derived MVO in STEMI patients after pPCI, which might help better understand the role of GDF-15 in STEMI. GDF-15 levels at 6 h after pPCI and MVO extent at day 5 ± 2 after pPCI were measured in 74 STEMI patients (mean age 60.3 ± 12.8 years, 86.5% men). The adjusted association of GDF-15 with MVO was analyzed with MVO treated as a categorized variable (extensive MVO, defined as MVO extent ≥ 2.6% of left ventricular (LV)) and a continuous variable (MVO mass, % of LV), respectively, in multivariate logistic and linear regression models. 41.9% of the patients developed extensive MVO after pPCI. In multivariate analysis, the odds ratio (95% confidential interval (CI)) of each standard deviation (SD) increase in GDF-15 for developing extensive MVO was 0.46 (0.21, 0.82), p = 0.02). Consistently, when MVO was used a continuous variable, each SD increase in GDF-15 was associated with a substantially lower MVO mass (ß - 0.42, standard error 0.19, p = 0.03). GDF-15 was a negative predictor for MVO in STEMI patients after pPCI. The observation was consistent with results from experiment studies, suggesting a potential protective effect of GDF-15 against cardiac injury.

Effective Management of Acute Oral Chemical Burns After NaOH Ingestion: A Case Report.

BACKGROUND Chemical burns in the oral cavity, although rare, cause more severe tissue damage than thermal burns, continuing tissue destruction even after removing the causative substance. Prompt identification of the substance, exposure extent, time from injury to treatment, and the injured area are imperative for effective management. This report details severe oral burns in an elderly woman from accidental NaOH ingestion. CASE REPORT A 70-year-old female patient was presented to our hospital approximately 15 h after inadvertent consumption of approximately 20 ml of NaOH (sodium hydroxide) solution. This incident led to oral discomfort and restricted mouth opening. The ingested solution, erroneously assumed to be a beverage, was later identified as a potent alkaline substance typically employed in grease removal. Initial manifestations included intense burning sensation, oral edema, and heightened salivation, which exacerbated on the following day, adversely impacting her alimentation and verbal communication. Clinical examination disclosed extensive damage to the oral mucosa. The diagnosis encompassed a chemical burn in the oral cavity coupled with chronic gastritis. The treatment regimen comprised dietary limitations, administration of famotidine for gastric acid suppression, intravenous hydration, nutritional support, oral care with Kangfuxin liquid, and nebulization therapy. Six months after therapy, she exhibited complete recovery, with the absence of discomfort and restored normal oral functions. CONCLUSIONS Timely and targeted treatment strategies, particularly nebulization medication and Kangfuxin liquid, are effective in managing chemical burns in the oral cavity, promoting wound healing, and preventing complications.

Large rectangular cross-section tunnel undercrossing urban road by micro pipe jacking and joint assembly structure (MPJ & JAS) method in soft soils.

With the continuous construction of urban traffic roads, more and more new roads are cut off by existing roads to form "dead end roads". There is an urgent need for a trenchless method suitable for urban ultra-shallow overburden to build the undercrossing tunnel. To solve this problem, this paper proposed the micro pipe jacking and joint assembly structure (MPJ & JAS) method, which has the characteristics of shallow burial depth, low cost, short construction time, flexible cross-section setting and high space utilization. The MPJ & JAS method construct a large cross-section tunnel through assembling small cross-section elements, quite different from traditional methods. Therefore, this paper designed a CT-shaped integrated joint, the mechanical performance of which was verified and clarified by tensile test. The bending test and finite element (FE) analysis proved the reliability of MPJ & JAS tunnel structure, and confirmed the structure performances such as the failure models, crack behaviors, load-deflection response and stress-strain distribution. Moreover, the influences of the steel plate thickness, concrete strength and shear connector spacing were determined by the FE analysis. On the basis of test results and reasonable assumptions, a theoretical design method considering the influence of the CT-shaped integrated joint was proposed, which can effectively predict the bending strength of the MPJ & JAS tunnel structure with an error of less than 10%. Finally, in view of the characteristics of the MPJ & JAS method, the suitable micro pipe jacking machine, soil reinforcement measure, hydraulic traction construction technology, high-precision guidance system and concrete construction quality detection method based on the phased array ultrasonic imaging technology were developed, supporting the accurate and efficient construction of the MPJ & JAS tunnel.

Quantification of tRNA m1A modification by templated-ligation qPCR.

N1-methyladenosine (m1A) is a widespread modification in all eukaryotic, many archaeal, and some bacterial tRNAs. M1A is generally located in the T loop of cytosolic tRNA and between acceptor and D stems of mitochondrial tRNAs, it is involved in tertiary interaction that stabilizes tRNA. Human tRNA m1A levels are dynamically regulated that fine-tune translation and can also serve as biomarkers for infectious disease. Although many methods have been used to measure m1A, a PCR method to assess m1A levels quantitatively in specific tRNAs has been lacking. Here we develop a templated-ligation followed by qPCR method (TL-qPCR) that measures m1A levels in target tRNAs. Our method uses the SplintR ligase that efficiently ligates two tRNA complementary DNA oligonucleotides using tRNA as the template followed by qPCR using the ligation product as the template. M1A interferes with the ligation in specific ways, allowing for the quantitative assessment of m1A levels using sub-nanogram amounts of total RNA. We identify the features of specificity and quantitation for m1A modified model RNAs and apply these to total RNA samples from human cells. Our method enables easy access to study the dynamics and function of this pervasive tRNA modification.

Chemical manipulation of m1A mediates its detection in human tRNA.

N 1-methyl adenosine (m1A) is a widespread RNA modification present in tRNA, rRNA, and mRNA. m1A modification sites in tRNAs are evolutionarily conserved and its formation on tRNA is catalyzed by methyltransferase TRMT61A and TRMT6 complex. m1A promotes translation initiation and elongation. Due to its positive charge under physiological conditions, m1A can notably modulate RNA structure. It also blocks Watson-Crick-Franklin base-pairing and causes mutation and truncation during reverse transcription. Several misincorporation-based high-throughput sequencing methods have been developed to sequence m1A. In this study, we introduce a reduction-based m1A sequencing (red-m1A-seq). We report that NaBH4 reduction of m1A can improve the mutation and readthrough rates using commercially available RT enzymes to give a better positive signature, while alkaline-catalyzed Dimroth rearrangement can efficiently convert m1A to m6A to provide good controls, allowing the detection of m1A with higher sensitivity and accuracy. We applied red-m1A-seq to sequence human small RNA, and we not only detected all the previously reported tRNA m1A sites, but also new m1A sites in mt-tRNAAsn-GTT and 5.8S rRNA.

Electron/infrared-phonon coupling in ABC trilayer graphene.

Stacking order plays a crucial role in determining the crystal symmetry and has significant impacts on electronic, optical, magnetic, and topological properties. Electron-phonon coupling, which is central to a wide range of intriguing quantum phenomena, is expected to be intricately connected with stacking order. Understanding the stacking order-dependent electron-phonon coupling is essential for understanding peculiar physical phenomena associated with electron-phonon coupling, such as superconductivity and charge density waves. In this study, we investigate the effect of stacking order on electron-infrared phonon coupling in graphene trilayers. By using gate-tunable Raman spectroscopy and excitation frequency-dependent near-field infrared nanoscopy, we show that rhombohedral ABC-stacked trilayer graphene has a significant electron-infrared phonon coupling strength. Our findings provide novel insights into the superconductivity and other fundamental physical properties of rhombohedral ABC-stacked trilayer graphene, and can enable nondestructive and high-throughput imaging of trilayer graphene stacking order using Raman scattering.

Multifunctional two-dimensional perovskite based solar cells for photodetectors and resistive switching.

The escalating interest in low-dimensional perovskites stems from their tunable optoelectronic traits and robust stability. The pursuit of multifaceted optoelectronic devices holds substantial importance for energy-efficient and space-constrained systems. This investigation showcases the realization of multifunctional two-dimensional perovskite solar cells, incorporating transient light detection and resistive switching functions within a single device, achievable by facile external bias adjustments. Serving as a photodetector, the device exhibits commendable self-powered photodetection attributes, including an exceptionally low dark current density of 1 nA mm-2, a remarkable specific detectivity of 7.67 × 1012 Jones, a swift response time of 0.60 µs, and an expansive linear dynamic range of 72 dB. As a memristor, it showcases enduring performance across 4 × 102 cycles, a substantial on/off ratio of 106, and a rapid operation time of less than 1 µs. This endeavor unveils a pioneering avenue for advancing high-performance, air-stable multifunctional two-dimensional perovskite electronics.

Compensating losses in polariton propagation with synthesized complex frequency excitation.

Surface plasmon polaritons and phonon polaritons offer a means of surpassing the diffraction limit of conventional optics and facilitate efficient energy storage, local field enhancement and highsensitivity sensing, benefiting from their subwavelength confinement of light. Unfortunately, losses severely limit the propagation decay length, thus restricting the practical use of polaritons. While optimizing the fabrication technique can help circumvent the scattering loss of imperfect structures, the intrinsic absorption channel leading to heat production cannot be eliminated. Here, we utilize synthetic optical excitation of complex frequency with virtual gain, synthesized by combining the measurements made at multiple real frequencies, to compensate losses in the propagations of phonon polaritons with dramatically enhanced propagation distance. The concept of synthetic complex frequency excitation represents a viable solution to the loss problem for various applications including photonic circuits, waveguiding and plasmonic/phononic structured illumination microscopy.

Therapeutic drug monitoring of imipenem/cilastatin and meropenem in critically ill adult patients.

OBJECTIVES: To investigate the factors influencing imipenem/cilastatin (IMI) and meropenem (MEM) concentrations in critically ill adult patients and the role of these concentrations in the clinical outcome. METHODS: Plasma trough concentrations of IMI and MEM were detected by high-performance liquid chromatography. A target value of 100%-time above MIC was used for the drugs. RESULTS: A total of 186 patients were included, with 87 receiving IMI and 99 receiving MEM. The percentages of patients reaching the target IMI and MEM concentrations were 44.8% and 38.4%, respectively. The proportions of patients infected with drug-resistant bacteria were 57.5% and 69.7% in the IMI group and MEM group, respectively. In the multivariate analysis, the risk factors for an IMI concentration that did not reach the target were infection with drug-resistant bacteria, and those for MEM were infection with drug-resistant bacteria, estimated glomerular filtration rate, and diabetes mellitus. A total of 47.1% of patients had good outcomes in the IMI cohort, and 38.1% of patients had good outcomes in the MEM cohort. The duration of mechanical ventilation and IMI concentration were associated with ICU stay in patients in the IMI cohort, while MEM concentration and severe pneumonia affected the clinical outcome of patients in the MEM cohort. CONCLUSION: Infection with drug-resistant bacteria is an important factor influencing whether IMI and MEM concentrations reach the target. Furthermore, IMI and MEM concentrations are associated with the clinical outcome, and elevated doses of IMI and MEM should be given to patients who are infected with drug-resistant bacteria.

Ultrafast bisulfite sequencing detection of 5-methylcytosine in DNA and RNA.

Bisulfite sequencing (BS-seq) to detect 5-methylcytosine (5mC) is limited by lengthy reaction times, severe DNA damage, overestimation of 5mC level and incomplete C-to-U conversion of certain DNA sequences. We present ultrafast BS-seq (UBS-seq), which uses highly concentrated bisulfite reagents and high reaction temperatures to accelerate the bisulfite reaction by ~13-fold, resulting in reduced DNA damage and lower background noise. UBS-seq allows library construction from small amounts of purified genomic DNA, such as from cell-free DNA or directly from 1 to 100 mouse embryonic stem cells, with less overestimation of 5mC level and higher genome coverage than conventional BS-seq. Additionally, UBS-seq quantitatively maps RNA 5-methylcytosine (m5C) from low inputs of mRNA and allows the detection of m5C stoichiometry in highly structured RNA sequences. Our UBS-seq results identify NSUN2 as the major 'writer' protein responsible for the deposition of ~90% of m5C sites in HeLa mRNA and reveal enriched m5C sites in 5'-regions of mammalian mRNA, which may have functional roles in mRNA translation regulation.

Manipulating hyperbolic transient plasmons in a layered semiconductor.

Anisotropic materials with oppositely signed dielectric tensors support hyperbolic polaritons, displaying enhanced electromagnetic localization and directional energy flow. However, the most reported hyperbolic phonon polaritons are difficult to apply for active electro-optical modulations and optoelectronic devices. Here, we report a dynamic topological plasmonic dispersion transition in black phosphorus via photo-induced carrier injection, i.e., transforming the iso-frequency contour from a pristine ellipsoid to a non-equilibrium hyperboloid. Our work also demonstrates the peculiar transient plasmonic properties of the studied layered semiconductor, such as the ultrafast transition, low propagation losses, efficient optical emission from the black phosphorus's edges, and the characterization of different transient plasmon modes. Our results may be relevant for the development of future optoelectronic applications.

Base-Resolution Sequencing Methods for Whole-Transcriptome Quantification of mRNA Modifications.

ConspectusRNA molecules are not merely a combination of four bases of A, C, G, and U. Chemical modifications occur in almost all RNA species and play diverse roles in gene expression regulation. The abundant cellular RNAs, such as ribosomal RNA (rRNA) and transfer RNA (tRNA), are known to have the highest density of RNA modifications, which exert critical functions in rRNA and tRNA biogenesis, stability, and subsequent translation. In recent years, modifications on low-abundance RNA species in mammalian cells, such as messenger RNA (mRNA), regulatory noncoding RNA (ncRNA), and chromatin-associated RNA (caRNA), have been shown to contain multiple different chemical modifications with functional significance.As the most abundant mRNA modification in mammals, N6-methyladenosine (m6A) affects nearly every stage of mRNA processing and metabolism, with the antibody-based m6A-MeRIP-seq (methylated RNA immunoprecipitation sequencing) followed by high-throughput sequencing widely employed in mapping m6A distribution transcriptome-wide in diverse biological systems. In addition to m6A, other chemical modifications such as pseudouridine (Ψ), 2'-O-methylation (Nm), 5-methylcytidine (m5C), internal N7-methylguanosine (m7G), N1-methyladenosine (m1A), N4-acetylcytidine (ac4C), etc. also exist in polyA-tailed RNA in mammalian cells, requiring effective mapping approaches for whole-transcriptome profiling of these non-m6A mRNA modifications. Like m6A, the antibody-based enrichment followed by sequencing has been the primary method to study distributions of these modifications. Methods to more quantitatively map these modifications would dramatically improve our understanding of distributions and modification density of these chemical marks on RNA, thereby bettering informing functional implications. In this Account, aimed at both single-base resolution and modification fraction quantification, we summarize our recent advances in developing a series of chemistry- or biochemistry-based methods to quantitatively map RNA modifications, including m6A, Ψ, m5C, m1A, 2'-O-methylation (Nm), and internal m7G, in mammalian mRNA at base resolution. These new methods, including m6A-SAC-seq, eTAM-seq, BID-seq, UBS-seq, DAMM-seq, m1A-quant-seq, Nm-Mut-seq, and m7G-quant-seq, promise to conduct base-resolution mapping of most major mRNA modifications with low RNA input and uncover dynamic changes in modification stoichiometry during biological and physiological processes, facilitating future investigations on these RNA modifications in regulating cellular gene expression and as potential biomarkers for clinical diagnosis and prognosis. These quantitative sequencing methods allow the mapping of most mRNA modifications with limited input sample requirements. The same modifications on diverse RNA species, such as caRNA, ncRNA, nuclear nascent RNA, mitochondrial RNA, cell-free RNA (cfRNA), etc., could be sequenced using the same methods.

Hypokalemia and Hyponatremia in Adult Patients Receiving Voriconazole Therapeutic Drug Monitoring.

Hypokalemia and hyponatremia are common but easily ignored adverse events in treatment with voriconazole (VCZ) that can lead to serious consequences. We intend to investigate the incidence of VCZ-induced hypokalemia and hyponatremia and their risk factors based on real-world data. A prospective study was conducted. A total of 272 patients with 414 VCZ plasma trough concentrations (C0) and VCZ N-oxide concentrations (CN) were included. The incidence of hypokalemia was 18.0% (48/266). A total of 81.2% (39/48) of patients developed hypokalemia within 14 days, whereas 56.2% (27/48) of patients developed hypokalemia within 1 week. The proportion of female patients in the hypokalemia group was higher than that in the nonhypokalemia group, as was the proportion of patients receiving intravenous VCZ. In the multivariate analysis, the independent risk factors for hypokalemia were sex, combined use of antibiotics, and VCZ CN/C0. The incidence of hyponatremia was 7.9% (21/266). The proportion of patients over 47 years of age in the hyponatremia group was 71.4% (15/21). The number of days of VCZ use in the hyponatremia group was greater than that in the nonhyponatremia group. A total of 47.6% (10/21) of patients in the hyponatremia group had supratherapeutic VCZ C0 (>5.0 µg/mL). In conclusion, hypokalemia is more likely to occur in females, in patients receiving intravenous VCZ, and in patients with the combined use of antibiotics. Hyponatremia is more likely to occur in patients older than 47 years who have been using VCZ for a long time and have higher VCZ C0 values.