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The objective of the cyclotron radiation emission spectroscopy (CRES) technology is to build precise particle energy spectra. This is achieved by identifying the start frequencies of charged particle trajectories which, when exposed to an external magnetic field, leave semi-linear profiles (called tracks) in the time–frequency plane. Due to the need for excellent instrumental energy resolution in application, highly efficient and accurate track reconstruction methods are desired. Deep learning convolutional neural networks (CNNs) - particularly suited to deal with information-sparse data and which offer precise foreground localization—may be utilized to extract track properties from measured CRES signals (called events) with relative computational ease. In this work, we develop a novel machine learning based model which operates a CNN and a support vector machine in tandem to perform this reconstruction. A primary application of our method is shown on simulated CRES signals which mimic those of the Project 8 experiment—a novel effort to extract the unknown absolute neutrino mass value from a precise measurement of tritium β ^− -decay energy spectrum. When compared to a point-clustering based technique used as a baseline, we show a relative gain of 24.1% in event reconstruction efficiency and comparable performance in accuracy of track parameter reconstruction.

In-plane polarized ferroelectric thin films typically exhibit complicated multidomain states, not desirable for optoelectronic device performance. Here, the authors combine interfacial symmetry engineering and anisotropic strain to design single-domain in-plane polarized ferroelectric BaTiO3 films.

Cyclotron radiation emission spectroscopy (CRES) is a modern approach for determining charged particle energies via high-precision frequency measurements of the emitted cyclotron radiation. For CRES experiments with gas within the fiducial volume, signal and noise dynamics can be modelled by a hidden Markov model. We introduce a novel application of the Viterbi algorithm in order to derive informational limits on the optimal detection of cyclotron radiation signals in this class of gas-filled CRES experiments, thereby providing concrete limits from which future reconstruction algorithms, as well as detector designs, can be constrained. The validity of the resultant decision rules is confirmed using both Monte Carlo and Project 8 data.

Objective To explore the significance of interleukin-17C(IL-17C)-mediated follicular helper T cell (Tfh) differentiation in atopic dermatitis (AD) model. Methods BALB/c mice were divided into control group, AD model group, low-dose MOR106 (anti-IL-17C huIgG1)(MDR106-L)treatment group and high-dose MOR106 (MOR106-H) treatment group, 8 mice in each group. Except for the control group, all the other groups were treated with 2, 4- dinitrochlorobenzene (DNCB) to establish AD models. The low-dose and high-dose MOR106 groups were treated with 5 mg/kg or 10 mg/kg MOR106 respectively. The differentiation of Tfh cell subsets in peripheral blood of mice was analyzed by flow cytometry, and the expression of Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3) signal pathway protein in skin tissue was detected by Western blot analysis. Results Compared with the control group, the dermatitis severity score, mass difference between two ears, spleen mass and spleen index of DNCB group increased significantly, while those of MOR106-L group and MOR106-H group decreased significantly. Compared with the control group, the Tfh subgroup of AD mice showed deregulated differentiation, resulting in a significant increase in the percentage of CD4 + CXCR5 + IFN-γ + Tfh1 cells, CD4 + CXCR5 + IL-17A + Tfh17 and CD4 + CXCR5 + IL-21 + Tfh21 cells, and a significant decrease in the percentage of CD4 + CXCR5 + IL-10 + Tfh10 cells and CD4 + CXCR5 + FOXP3 + Tfr cells in peripheral blood. The protein levels of phosphorylated JAK2(p-JAK2) and p-STAT3 were significantly increased. MOR106 effectively reversed these changes of Tfh1, Tfh10, Tfh17, Tfh21 and Tfr cells in peripheral blood of AD mice. Compared with AD group, the levels of p-JAK2 and p-STAT3 protein in low-dose and high-dose MOR106 treatment groups decreased significantly. Conclusion MOR106 can reduce the inflammatory response of AD mice by blocking JAK2/STAT3 signaling pathway and inhibiting the differentiation of Tfh cells mediated by IL-17C.

The absolute scale of the neutrino mass plays a critical role in physics at every scale, from the subatomic to the cosmological. Measurements of the tritium end-point spectrum have provided the most precise direct limit on the neutrino mass scale. In this Letter, we present advances by Project 8 to the cyclotron radiation emission spectroscopy (CRES) technique culminating in the first frequency-based neutrino mass limit. With only a cm^{3}-scale physical detection volume, a limit of m&#95;{β}<155  eV/c^{2} (152  eV/c^{2}) is extracted from the background-free measurement of the continuous tritium beta spectrum in a Bayesian (frequentist) analysis. Using ^{83m}Kr calibration data, a resolution of 1.66±0.19  eV (FWHM) is measured, the detector response model is validated, and the efficiency is characterized over the multi-keV tritium analysis window. These measurements establish the potential of CRES for a high-sensitivity next-generation direct neutrino mass experiment featuring low background and high resolution.

We present an apparatus for detection of cyclotron radiation yielding a frequency-based β^{±} kinetic energy determination in the 5 keV to 2.1 MeV range, characteristic of nuclear β decays. The cyclotron frequency of the radiating β particles in a magnetic field is used to determine the β energy precisely. Our work establishes the foundation to apply the cyclotron radiation emission spectroscopy (CRES) technique, developed by the Project 8 Collaboration, far beyond the 18-keV tritium endpoint region. We report initial measurements of β^{-}'s from ^{6}He and β^{+}'s from ^{19}Ne decays to demonstrate the broadband response of our detection system and assess potential systematic uncertainties for β spectroscopy over the full (MeV) energy range. To our knowledge, this is the first direct observation of cyclotron radiation from individual highly relativistic β's in a waveguide. This work establishes the application of CRES to a variety of nuclei, opening its reach to searches for new physics beyond the TeV scale via precision β-decay measurements.

Henagliflozin proline and metformin hydrochloride sustained-release tablets (HR20033) are a fixed-dose combination of the novel, highly selective, and effective sodium-glucose cotransporter-2 inhibitor henagliflozin, with a metformin sustained-release layer for the treatment of type 2 diabetes mellitus in conjunction with dietary control and exercise. The aims of this study were to investigate the effect of a high-fat diet on the pharmacokinetics of henagliflozin and metformin after a single administration of HR20033 and the effect of repeated oral administration of HR20033 on their pharmacokinetics in healthy volunteers. The food-effect clinical study involved 18 healthy subjects randomized to receive either HR20033 in the fasted condition followed by HR20033 in the fed condition or the reverse schedule, with the two doses separated by a washout period of at least 7 days. The multiple-dose clinical study was conducted on 10 healthy subjects. In the food-effect study, compared with those in the fasted condition, the area under the blood concentration curve (AUC) and peak concentration (C max ) of henagliflozin decreased by 12.64% and 40.89%, respectively, while the AUC of metformin increased by 31.13% and C max decreased by 7.09% in the fed state. There was no significant accumulation of HR20033 in the body after multiple oral doses. No serious adverse event was observed in either of the two clinical studies. Food did not have a clinically meaningful effect on the absorption of HR20033., (© 2022, The American College of Clinical Pharmacology.)

Objectives: To compare the efficacy of transarterial embolization (TAE) with polyvinyl alcohol (PVA) particles alone and lipiodol-bleomycin emulsion (LBE) plus PVA particles for patients with unresectable large symptomatic focal nodular hyperplasia (FNH)., Methods: We performed a retrospective analysis of patients who underwent TAE either with PVA particles alone (group A, n = 46) or LBE plus PVA particles (group B, n = 35) for large (≥ 7 cm) symptomatic FNH between January 2002 and February 2019. Propensity score matching (PSM) (1:1) was performed to adjust for potential baseline confounders. Technical success, adverse events (AEs), symptom relief, and changes in the lesion size after TAE were evaluated. Statistical analysis included Wilcoxon rank sum test and χ 2 test., Results: After PSM, no significant differences in baseline characteristics were found between the groups (31 in group A and 31 in group B, with a mean age of 31 years). Technical success was achieved in all patients (100%), without major AEs in both groups. Complete resolution of the abdominal symptoms was reported in 77.4% in group A and 100% in group B (p = 0.037) during a mean follow-up period of 72 months; complete resolution (CR) of the FNH rate was significantly higher in group B than in group A (93.6% vs. 67.7%; p = 0.019)., Conclusion: Compared with the use PVA particles alone, TAE with LBE plus PVA particles in the treatment of patients with large symptomatic FNH had a significantly higher rates of CR of the FNH and complete relief of the symptoms., Key Points: • Transarterial embolization (TAE) with lipiodol-bleomycin emulsion (LBE) plus PVA particles for the large symptomatic FNH yielded better results than with PVA particles alone, in terms of complete resolution of FNH lesions (93.6% vs 67.7%) and complete relief of the abdominal symptoms (100% vs 77.4%) during a mean follow-up period of 72 months (38-170 months). • No major complications were recorded in both groups, and no significant difference in the incidence of postembolization syndrome were observed between the two groups., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Background: Hypertension is a long-term medical condition. Mobile health (mHealth) services can help out-of-hospital patients to self-manage. However, not all management is effective, possibly because the behavior mechanism and behavior preferences of patients with various characteristics in hypertension management were unclear., Objective: The purpose of this study was to (1) explore patient multibehavior engagement trails in the pathway-based hypertension self-management, (2) discover patient behavior preference patterns, and (3) identify the characteristics of patients with different behavior preferences., Methods: This study included 863 hypertensive patients who generated 295,855 use records in the mHealth app from December 28, 2016, to July 2, 2020. Markov chain was used to infer the patient multibehavior engagement trails, which contained the type, quantity, time spent, sequence, and transition probability value (TP value) of patient behavior. K-means algorithm was used to group patients by the normalized behavior preference features: the number of behavioral states that a patient performed in each trail. The pages in the app represented the behavior states. Chi-square tests, Z-test, analyses of variance, and Bonferroni multiple comparisons were conducted to characterize the patient behavior preference patterns., Results: Markov chain analysis revealed 3 types of behavior transition (1-way transition, cycle transition, and self-transition) and 4 trails of patient multibehavior engagement. In perform task trail (PT-T), patients preferred to start self-management from the states of task blood pressure (BP), task drug, and task weight (TP value 0.29, 0.18, and 0.20, respectively), and spent more time on the task food state (35.87 s). Some patients entered the states of task BP and task drug (TP value 0.20, 0.25) from the reminder item state. In the result-oriented trail (RO-T), patients spent more energy on the ranking state (19.66 s) compared to the health report state (13.25 s). In the knowledge learning trail (KL-T), there was a high probability of cycle transition (TP value 0.47, 0.31) between the states of knowledge list and knowledge content. In the support acquisition trail (SA-T), there was a high probability of self-transition in the questionnaire (TP value 0.29) state. Cluster analysis discovered 3 patient behavior preference patterns: PT-T cluster, PT-T and KL-T cluster, and PT-T and SA-T cluster. There were statistically significant associations between the behavior preference pattern and gender, education level, and BP., Conclusions: This study identified the dynamic, longitudinal, and multidimensional characteristics of patient behavior. Patients preferred to focus on BP, medications, and weight conditions and paid attention to BP and medications using reminders. The diet management and questionnaires were complicated and difficult to implement and record. Competitive methods such as ranking were more likely to attract patients to pay attention to their own self-management states. Female patients with lower education level and poorly controlled BP were more likely to be highly involved in hypertension health education., (©Dan Wu, Xiaoyuan Huyan, Yutong She, Junbin Hu, Huilong Duan, Ning Deng. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 03.02.2022.)

Helminth infection induces Th2-biased immune responses and inhibitory/regulatory pathways that minimize excessive inflammation to facilitate the chronic infection of helminth in the host and in the meantime, prevent host hypersensitivity from autoimmune or atopic diseases. However, the detailed molecular mechanisms behind modulation on inflammatory diseases are yet to be clarified. Programmed death 1 (PD-1) is one of the important inhibitory receptors involved in the balance of host immune responses during chronic infection. Here, we used the murine model to examine the role of PD-1 in CD4 + T cells in the effects of Trichinella spiralis infection on collagen-induced arthritis (CIA). Mice infected with T. spiralis demonstrated higher expression of PD-1 in the spleen CD4 + T cells than those without infection. Mice infected with T. spiralis 2 weeks prior to being immunized with type II collagen displayed lower arthritis incidence and significantly attenuated pathology of CIA compared with those of uninfected mice. The therapeutic effect of T. spiralis infection on CIA was reversed by blocking PD-1 with anti-PD-1 antibody, associated with enhanced Th1/Th17 pro-inflammatory responses and reduced Th2 responses. The role of PD-1 in regulating CD4 + T cell differentiation and proliferation during T. spiralis infection was further examined in PD-1 knockout (PD-1 -/- ) C57BL/6 J mice. Interestingly, T. spiralis -induced alteration of attenuated Th1 and enhanced Th2/regulatory T cell differentiation in wild-type (WT) mice was effectively diminished in PD-1 -/- mice characterized by recovered Th1 cytokine levels, reduced levels of Th2 and regulatory cytokines and CD4 + CD25 + Foxp3 + cells. Moreover, T. spiralis -induced CD4 + T cell proliferation suppression in WT mice was partially restored in PD-1 -/- mice. This study introduces the first evidence that PD-1 plays a critical role in helminth infection-attenuated CIA in a mouse model by regulating the CD4 + T cell function, which may provide the new insights into the mechanisms of helminth-induced immunomodulation of host autoimmunity.