Biophysical mechanisms underlying tefluthrin-induced modulation of gating changes and resurgent current generation in the human Nav1.4 channel.

Human skeletal muscle contraction is triggered by activation of Nav1.4 channels. Nav1.4 channels can generate resurgent currents by channel reopening at hyperpolarized potentials through a gating transition dependent on the intracellular Navß4 peptide in the physiological conditions. Tefluthrin (TEF) is a pyrethroid insecticide that can disrupt electrical signaling in nerves and skeletal muscle, resulting in seizures, muscle spasms, fasciculations, and mental confusion. TEF can also induce tail currents through other voltage-gated sodium channels in the absence of Navß4 peptide, suggesting that muscle spasms may be caused by resurgent currents. Further, intracellular Navß4 peptide and extracellular TEF may show competitive or synergistic effects; however, their binding sites are still unknown. To address these issues, electrophysiological recordings were performed on CHO-K1 cells expressing Nav1.4 channels with intracellular Navß4 peptide, extracellular TEF, or both. TEF and Navß4 peptide induced a hyperpolarizing shift of activation and inactivation curves in the Nav1.4 channel. TEF also substantially prolonged the inactivation time constants, while simultaneous application of Navß4 peptide partially reversed this effect. Resurgent currents were enhanced by TEF and Navß4 peptide at negative potentials, but TEF more potently enhances resurgent currents and dampens decay of resurgent currents. With longer depolarization, peak resurgent currents decay was fastest with the TEF alone. Molecular docking suggested that TEF and Navß4 peptide binding site(s) are not in the narrowest part of the channel pore, but rather in the bundle-crossing regions and in the domain linkers, respectively. TEF can induce resurgent currents independently and synergistically with Navß4 peptide, which may explain the muscle spasms observed in TEF intoxication.

Oral Dexmedetomidine Achieves Superior Effects in Mitigating Emergence Agitation and Demonstrates Comparable Sedative Effects to Oral Midazolam for Pediatric Premedication: A Systematic Review and Meta-Analysis of Randomized Controlled Studies.

Background: Oral midazolam is the most commonly used sedative premedication agent in pediatric patients. While effective, oral midazolam cannot reduce the incidence of emergence agitation. Oral dexmedetomidine may be effective in providing satisfactory sedation and reduce the incidence of emergence agitation, although the results of different randomized controlled trials are conflicting. Methods: This study enrolled randomized controlled trials (RCTs) examining premedication with oral dexmedetomidine versus oral midazolam in pediatric patients undergoing general anesthesia. PubMed, the Cochrane Library, Embase, and the Web of Science database were searched from their inception until June 2023. The outcomes were the incidence of satisfactory preoperative sedation, satisfactory sedation during separation from parents, satisfactory sedation during anesthesia induction using an anesthesia mask, and the incidence of emergence agitation. Results: A total of 9 RCTs comprising 885 patients were analyzed. Our data revealed comparable effects of dexmedetomidine and midazolam with respect to satisfactory preoperative sedation and a satisfactory incidence of sedation during parental separation and mask acceptance before anesthesia induction. Notably, our data revealed that the rate of emergence agitation was significantly lower in pediatric patients receiving dexmedetomidine (n = 162) than in those receiving midazolam (n = 159) (odds ratio = 0.16; 95% confidence interval: 0.06 to 0.44; p < 0.001; I2 = 35%). Conclusions: Data from this meta-analysis revealed comparable effects for premedication with oral dexmedetomidine or oral midazolam with respect to satisfactory sedation; furthermore, premedication with oral dexmedetomidine more effectively mitigated emergence agitation in pediatric patients receiving general anesthesia compared with oral midazolam.

Quantum oscillations evidence for topological bands in kagome metal ScV6Sn6.

Metals with kagome lattice provide bulk materials to host both the flat-band and Dirac electronic dispersions. A new family of kagome metals is recently discovered inAV6Sn6. The Dirac electronic structures of this material needs more experimental evidence to confirm. In the manuscript, we investigate this problem by resolving the quantum oscillations in both electrical transport and magnetization in ScV6Sn6. The revealed orbits are consistent with the electronic band structure models. Furthermore, the Berry phase of a dominating orbit is revealed to be aroundπ, providing direct evidence for the topological band structure, which is consistent with calculations. Our results demonstrate a rich physics and shed light on the correlated topological ground state of this kagome metal.

Neural Architecture Search using Covariance Matrix Adaptation Evolution Strategy.

Evolution-based neural architecture search methods have shown promising results but they require high computational resources since these methods involve training each candidate architecture from scratch and then evaluating its fitness which results in long search time. Covariance Matrix Adaptation Evolution Strategy (CMA-ES) has shown promising results in tuning hyperparameters of neural networks but has not been used for neural architecture search. In this work, we propose a framework called CMANAS which applies the faster convergence property of CMA-ES to the deep neural architecture search problem. Instead of training each individual architecture seperately, we used the accuracy of a trained one shot model (OSM) on the validation data as a prediction of the fitness of the architecture resulting in reduced search time. We also used an architecture-fitness table (AF table) for keeping record of the already evaluated architecture, thus further reducing the search time. The architectures are modelled using a normal distribution, which is updated using CMA-ES based on the fitness of the sampled population. Experimentally, CMANAS achieves better results than previous evolution-based methods while reducing the search time significantly. The effectiveness of CMANAS is shown on 2 different search spaces for datasets: CIFAR-10, CIFAR-100, ImageNet and ImageNet16-120. All the results show that CMANAS is a viable alternative to previous evolution-based methods and extends the application of CMA-ES to the deep neural architecture search field.

Resonant torque differential magnetometry with high frequency quartz oscillators.

Sensitive magnetometry has been a powerful probe for investigating quantum materials. Extreme conditions, such as sub-kelvin cryogenic temperatures and ultrahigh magnetic fields, demand further durability for sensitive magnetometry. However, significant mechanical vibrations and rapid magnetic field changes give enormous challenges to conventional magnetometry. This article presents a possible solution to this problem by developing a new magnetometry technique using high-frequency quartz oscillators. The technique takes advantage of the symmetry and geometry of mechanical vibration configurations of standard commercially available MHz quartz oscillators, and the setup keeps the high quality factor resonance with the sample mounted on the oscillator. We further demonstrate the sensitivity of the technique using bismuth single crystals and a Fe0.25TaS2 ferromagnetic material. Quantum oscillations are observed in the magnetometry response below 1 T, and the detected oscillation frequency is shown to come from the electron pockets of the bismuth.

Low Vertebrobasilar Velocity Is Associated with a Higher Risk of Posterior Circulation Ischemic Lesions.

Background: Transcranial color-coded sonography (TCCS) is used as a real-time tool to evaluate patients suspected of having vertebrobasilar insufficiency (VBI). However, the sonographic criteria for VBI remain inconclusive. The purpose of this study was to analyze the velocity in the vertebrobasilar system, which links the risk for posterior circulation infarction (POCI) and total ischemic stroke (TIS) in patients with VBI. Methods: Patients' data were retrospectively reviewed if they were suspected of having VBI within a 2-year period. Baseline characteristics, brain images, and a series of sonography data were recorded and analyzed. We compared vertebrobasilar (VB) velocities in different age groups and in patients with infarctions. Results: A total of 875 patients were enrolled, with 112 and 427 candidates in the POCI and TIS groups, respectively. The mean velocity (MV)s of BA and bilateral VAs were all negatively correlated with age (all p < 0.001). The adjusted odds ratio was 2.55 (1.58−4.13, p < 0.001) in POCI and 1.75 (1.15−2.67, p = 0.009) in TIS if the mean velocity of the VB arteries was below 15 cm/s. Conclusions: Low VB velocity detected in TCCS was more commonly associated with ageing-related changes and a higher risk of both POCI and TIS. Recognition and aggressive treatment for these patients are necessary.

Prediction Model for Pancreatic Cancer-A Population-Based Study from NHIRD.

(1) Background: Cancer has been the leading cause of death in Taiwan for 39 years, and among them, pancreatic cancer has been ranked seventh in the top ten cancer mortality rates for the past three years. While the incidence rate of pancreatic cancer is ranked at the bottom of the top 10 cancers, the survival rate is very low. Pancreatic cancer is one of the more difficult cancers to detect early due to the lack of early diagnostic tools. Early screening is important for the treatment of pancreatic cancer. Only a few studies have designed predictive models for pancreatic cancer. (2) Methods: The Taiwan Health Insurance Database was used in this study, covering over 99% of the population in Taiwan. The subset sample was not significantly different from the original NHIRD sample. A machine learning approach was used to develop a predictive model for pancreatic cancer disease. Four models, including logistic regression, deep neural networks, ensemble learning, and voting ensemble were used in this study. The ROC curve and a confusion matrix were used to evaluate the accuracy of the pancreatic cancer prediction models. (3) Results: The AUC of the LR model was higher than the other three models in the external testing set for all three of the factor combinations. Sensitivity was best measured by the stacking model for the first factor combinations, and specificity was best measured by the DNN model for the second factor combination. The result of the model that used only nine factors (third factor combinations) was equal to the other two factor combinations. The AUC of the previous models for the early assessment of pancreatic cancer ranged from approximately 0.57 to 0.71. The AUC of this study was higher than that of previous studies and ranged from 0.71 to 0.76, which provides higher accuracy. (4) Conclusions: This study compared the performances of LR, DNN, stacking, and voting models for pancreatic cancer prediction and constructed a pancreatic cancer prediction model with accuracy higher than that of previous studies. This predictive model will improve awareness of the risk of pancreatic cancer and give patients with pancreatic cancer a simpler tool for early screening in the golden period when the disease can still be eradicated.

Quantitative Measurement of Breast Tumors Using Intravoxel Incoherent Motion (IVIM) MR Images.

Breast magnetic resonance imaging (MRI) is currently a widely used clinical examination tool. Recently, MR diffusion-related technologies, such as intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI), have been extensively studied by breast cancer researchers and gradually adopted in clinical practice. In this study, we explored automatic tumor detection by IVIM-DWI. We considered the acquired IVIM-DWI data as a hyperspectral image cube and used a well-known hyperspectral subpixel target detection technique: constrained energy minimization (CEM). Two extended CEM methods-kernel CEM (K-CEM) and iterative CEM (I-CEM)-were employed to detect breast tumors. The K-means and fuzzy C-means clustering algorithms were also evaluated. The quantitative measurement results were compared to dynamic contrast-enhanced T1-MR imaging as ground truth. All four methods were successful in detecting tumors for all the patients studied. The clustering methods were found to be faster, but the CEM methods demonstrated better performance according to both the Dice and Jaccard metrics. These unsupervised tumor detection methods have the advantage of potentially eliminating operator variability. The quantitative results can be measured by using ADC, signal attenuation slope, D*, D, and PF parameters to classify tumors of mass, non-mass, cyst, and fibroadenoma types.

Primary Tumor Radiotherapy During EGFR-TKI Disease Control Improves Survival of Treatment Naïve Advanced EGFR-Mutant Lung Adenocarcinoma Patients.

BACKGROUND: Whether radiotherapy only for primary lung tumor (RTPLT) after epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy improves survival of treatment naïve advanced EGFR-mutant lung adenocarcinoma (LAD) patients with/without polymetastasis. MATERIALS AND METHODS: This was a retrospective, single-center, observational study. Patients with stage IIIB-IV EGFR-mutant LAD with disease control by EGFR-TKI therapy were divided into curative RTPLT, and control, without radiotherapy (WRTPLT) groups. RESULTS: A total of 138 patients were enrolled; 46 in the RTPLT group and 92 in the WRTPLT group. Amongst them, 37% had oligometastasis, and 26.1% brain metastasis. The RTPLT group had both significantly longer progression-free survival (PFS) (27.5 months [95% CI 18.1-36.9] vs 10.9 months [95% CI 6.3-15.5], P<0.001) and overall survivor (OS) (NR [95% CI NR-NR] vs 38.0 months [95% CI 31.2-44.8], P<0.001), respectively, when compared to the WRTPLT group. In multivariate analysis, the adjusted HR of radiotherapy on PFS was 0.30 (0.19-0.47) and on OS, 0.11 (0.04-0.30). Patients with oligometastasis had significantly longer PFS than those with polymetastasis with an HR of 0.35 (0.14-0.85), P=0.02. Patients with either oligometastasis or polymetastasis had significant longer PFS when undergoing radiotherapy than those without (both P<0.05). An EGFR-TKI to radiotherapy interval <24 weeks seemed more beneficial (P=0.097). Radiation pneumonitis comprised 32 (69.6%), 12 (26.1%), and two (4.3%) cases of common terminology criteria grade I, II, and III, respectively. CONCLUSION: Curative RTPLT can prolong survival in patients with LAD following EGFR-TKI disease control, both involving oligometastasis and polymetastasis. RTPLT within 24 weeks after EGFR-TKI initiation appeared to be more beneficial with tolerable radiation pneumonitis.

Bilateral Vertebral Artery Hypoplasia and Fetal-Type Variants of the Posterior Cerebral Artery in Acute Ischemic Stroke.

Aim: Unilateral vertebral artery hypoplasia is considered a risk factor for posterior circulation infarction. Despite the increasing attention on unilateral vertebral artery hypoplasia, few studies have discussed bilateral vertebral artery hypoplasia, its influence on stroke, or its collateral supply from the circle of Willis. We aimed to identify its characteristics, stroke pattern, and unique ultrasonographic and brain imaging findings. Materials and Methods: Of the 1,301 consecutive in-patients diagnosed with acute ischemic stroke from January 2013 to December 2015, medical and laboratory data and stroke or transient ischemic attack history were recorded. We enrolled patients who underwent both brain magnetic resonance imaging and sonography examinations. Vertebral artery and posterior cerebral artery analyses were conducted in accordance with clinical criteria. Results: Adequate imaging data were available for 467 patients. Of these, eight patients met the criteria for bilateral vertebral artery hypoplasia. The mean age was 62.9 ± 12.1 years. There were six male (75.0%) and two female patients (25.0%). A high prevalence of hypertension (7/8, 87.5%) was noted. Sonograms displayed a very low net flow volume in the vertebral arteries, with the average net flow volume being 28.9 ± 9.7 mL/min. A high frequency (6/8; 75.0%) of the fetal variant posterior cerebral artery from the carotids was found. The infarction patterns in these patients were all bilateral, scattered, and in multiple vascular territories. Conclusion: Patients with bilateral vertebral hypoplasia displayed a unique collateral supply, special stroke pattern, and younger stroke onset. Early recognition and stroke prevention should be considered critical in clinical practice.

Electronic transport properties of a lithium-decorated ZrTe5 thin film.

Through a combination of single crystal growth, experiments involving in situ deposition of surface adatoms, and complimentary modeling, we examine the electronic transport properties of lithium-decorated ZrTe5 thin films. We observe that the surface states in ZrTe5 are robust against Li adsorption. Both the surface electron density and the associated Berry phase are remarkably robust to adsorption of Li atoms. Fitting to the Hall conductivity data reveals that there exist two types of bulk carriers: those for which the carrier density is insensitive to Li adsorption, and those whose density decreases during initial Li depositions and then saturates with further Li adsorption. We propose this dependence is due to the gating effect of a Li-adsorption-generated dipole layer at the ZrTe5 surface.

Adjuvant whole breast radiotherapy with simultaneous integrated boost to tumor bed with intensity modulated radiotherapy technique in elderly breast cancer patients.

BACKGROUND: Adjuvant whole breast radiotherapy is the standard of care for breast cancer patients after partial mastectomy. Intensity-modulated radiation therapy (IMRT) has been reported to reduce acute toxicities compared to conventional radiotherapy. IMRT with simultaneous integrated boost (SIB) technique can deliver higher doses to tumor bed and irradiate whole breast with a lower dose level to shorten overall treatment duration. This study presents the long-term results of adjuvant IMRT with SIB in elderly breast cancer patients who received partial mastectomy. METHODS: From January 2007 to January 2018, 93 elder breast cancer patients (≥65-year-old) who received IMRT with SIB technique after partial mastectomy were reviewed retrospectively. The axillary areas were managed with either sentinel lymph node biopsies or axillary lymph node dissection. The dose to whole breast was 50.4 Gy in 28 fractions in all patients and the dose to tumor bed was 61.6 to 66.4 Gy in 28 fractions. The primary end point is locoregional control. Secondary end points include: overall survival, breast cancer-specific survival, distant-metastases-free survival, disease-free survival, and acute and chronic toxicities. RESULTS: The median follow-up was 56.1 months. One patient had ipsilateral breast tumor recurrence, 3 patients had regional lymph node recurrence, and 9 patients had distant metastases. Death occurred in 5 patients, including 3 patients died of breast cancer progression. Five-year overall survival is 96.3% and 5-year locoregional recurrence-free survival is 96.4%. The 5-year breast cancer specific survival and 5-year distant metastases-free survival is 97.5% and 87.2%, respectively. Seven patients developed second primary cancer after RT. Eighty-one point seven percent patients had acute grade 1 dermatitis while 18.3% suffered from grade 2 dermatitis. The incidence of grade 1 pneumonitis and grade 1 stomatitis was 4.3% and 8.6%, respectively. CONCLUSIONS: Adjuvant IMRT with SIB technique is a safe and effective treatment strategy for elderly breast cancer patients after partial mastectomy.

Cyclodehydration of 1,4-butanediol over Zr-Al Catalysts: Effect of Reaction Medium.

The conversion of 1,4-butanediol (BDO) to tetrahydrofuran (THF) in aqueous phase is desirable because BDO production technology is shifting to bio-based aqueous fermentation routes. In this study, liquid-phase cyclodehydration of BDO to THF was studied in two reaction media (pure BDO and aqueous BDO feeds) at 200-240 °C using ZrO2-Al2O3 (ZA) mixed oxides, which were made with a co-precipitation method and were characterized with XRD, BET, SEM/EDX, pyridine and n-butylamine adsorptions. The maximum acidity and the largest surface area occurred at Zr/Al atomic ratios of 1/1 (ZA11) and 1/3 (ZA13), respectively. The reaction exhibited pseudo-first-order; aqueous BDO feed had much greater rate constant than pure BDO feed, ascribed to the acidic properties of adsorbed water molecules (coordinated to surface metal cations) for the former case. For pure BDO feed, linear relation was observed between rate constant and catalyst acidity, and ZA11 reached a THF yield of 90.1% at 240 °C. With aqueous BDO feed, rate constant increased linearly with increasing surface area and ZA13 reached a THF yield of 97.1% at 220 °C. The change of optimum catalyst composition with reaction medium suggests that active sites for catalyzing BDO cyclodehydration changed with the reaction environment.

Enhanced thermoelectric performance of heavy-fermion compounds YbTM 2Zn20 (TM = Co, Rh, Ir) at low temperatures.

Thermoelectricity allows direct conversion between heat and electricity, providing alternatives for green energy technologies. Despite these advantages, for most materials the energy conversion efficiency is limited by the tendency for the electrical and thermal conductivity to be proportional to each other and the Seebeck coefficient to be small. Here we report counter examples, where the heavy fermion compounds YbTM 2Zn20 (TM = Co, Rh, Ir) exhibit enhanced thermoelectric performance including a large power factor (PF = 74 µW/cm-K2; TM = Ir) and a high figure of merit (ZT = 0.07; TM = Ir) at 35 K. The combination of the strongly hybridized electronic state originating from the Yb f-electrons and the novel structural features (large unit cell and possible soft phonon modes) leads to high power factors and small thermal conductivity values. This demonstrates that with further optimization these systems could provide a platform for the next generation of low temperature thermoelectric materials.

Ultrasound Findings Disclose the Mutual Impact of Vertebrobasilar Dolichoectasia and Vertebral Artery Hypoplasia.

OBJECTIVES: Vertebrobasilar dolichoectasia (VBD) and vertebral artery hypoplasia (VAH) are known predisposing factors of posterior circulation stokes. These vascular conditions have unique hemodynamic patterns in neuroimaging studies; however, they have been presented as a single entity in some reports. The aim of this retrospective study was to clarify the relationship between these conditions with regard to ultrasound (US) findings. METHODS: A total of 465 patients with strokes were recruited. Brain magnetic resonance imaging of vertebrobasilar arteries and differences in extracranial side-to-side vertebral artery (VA) flow were recorded by US and compared in groups. RESULTS: The mean age of the 465 patients ± SD was 67.23 ± 12.13 years; 296 were men. The prevalence of VBD was 13.5% (n = 63), and 10.8% (n = 50) of the patients had coexisting VAH and VBD. These patients also had the highest prevalence of posterior circulation strokes (58% [n = 29]). A cutoff value of 55.65 mL/min and a ratio discrepancy of 5.28 (group median) for the side-to-side extracranial VA flow volume as detected by conventional US were also observed in the patients with both VAH and VBD. CONCLUSIONS: Our study revealed a higher prevalence of posterior circulation strokes in the patients with both VBD and VAH. Chronic asymmetric hemodynamic shear force in extracranial VAs leading to deformity of the vertebrobasilar system may explain our observations. Accordingly, the blood flow volume and the ratio difference could potentially be used to detect patients at risk of VBD and reduce stroke risk factors.

Antibacterial activity of ovatodiolide isolated from Anisomeles indica against Helicobacter pylori.

Helicobacter pylori infection is associated with high incidence of gastric diseases. The extensive therapy of H. pylori infection with antibiotics has increased its resistance rates worldwide. Ovatodiolide, a pure constituent isolated from Anisomeles indica, has been demonstrated to possess bactericidal activity against H. pylori. In this study, ovatodiolide inhibited the growth of both H. pylori reference strain and clinical multidrug-resistant isolates. Docking analysis revealed that ovatodiolide fits into the hydrophobic pocket of a ribosomal protein, RpsB. Furthermore, ovatodiolide inhibited bacterial growth by reducing levels of RpsB, which plays a crucial role in protein translation. Our results demonstrate that ovatodiolide binds to a ribosomal protein and interferes with protein synthesis. This study provides evidence that ovatodiolide has the potential to be developed into a potent therapeutic agent for treating H. pylori infection.

Electronic Structure and Properties of Berkelium Iodates.

The reaction of 249Bk(OH)4 with iodate under hydrothermal conditions results in the formation of Bk(IO3)3 as the major product with trace amounts of Bk(IO3)4 also crystallizing from the reaction mixture. The structure of Bk(IO3)3 consists of nine-coordinate BkIII cations that are bridged by iodate anions to yield layers that are isomorphous with those found for AmIII, CfIII, and with lanthanides that possess similar ionic radii. Bk(IO3)4 was expected to adopt the same structure as M(IO3)4 (M = Ce, Np, Pu), but instead parallels the structural chemistry of the smaller ZrIV cation. BkIII-O and BkIV-O bond lengths are shorter than anticipated and provide further support for a postcurium break in the actinide series. Photoluminescence and absorption spectra collected from single crystals of Bk(IO3)4 show evidence for doping with BkIII in these crystals. In addition to luminescence from BkIII in the Bk(IO3)4 crystals, a broad-band absorption feature is initially present that is similar to features observed in systems with intervalence charge transfer. However, the high-specific activity of 249Bk (t1/2 = 320 d) causes oxidation of BkIII and only BkIV is present after a few days with concomitant loss of both the BkIII luminescence and the broadband feature. The electronic structure of Bk(IO3)3 and Bk(IO3)4 were examined using a range of computational methods that include density functional theory both on clusters and on periodic structures, relativistic ab initio wave function calculations that incorporate spin-orbit coupling (CASSCF), and by a full-model Hamiltonian with spin-orbit coupling and Slater-Condon parameters (CONDON). Some of these methods provide evidence for an asymmetric ground state present in BkIV that does not strictly adhere to Russel-Saunders coupling and Hund's Rule even though it possesses a half-filled 5f 7 shell. Multiple factors contribute to the asymmetry that include 5f electrons being present in microstates that are not solely spin up, spin-orbit coupling induced mixing of low-lying excited states with the ground state, and covalency in the BkIV-O bonds that distributes the 5f electrons onto the ligands. These factors are absent or diminished in other f7 ions such as GdIII or CmIII.