Observation of e

We study the processes e^{+}e^{-}→ωχ_{bJ}(1P) (J=0, 1, or 2) using samples at center-of-mass energies sqrt[s]=10.701, 10.745, and 10.805 GeV, corresponding to 1.6, 9.8, and 4.7 fb^{-1} of integrated luminosity, respectively. These data were collected with the Belle II detector during special operations of the SuperKEKB collider above the ϒ(4S) resonance. We report the first observation of ωχ_{bJ}(1P) signals at sqrt[s]=10.745 GeV. By combining Belle II data with Belle results at sqrt[s]=10.867 GeV, we find energy dependencies of the Born cross sections for e^{+}e^{-}→ωχ_{b1,b2}(1P) to be consistent with the shape of the ϒ(10753) state. These data indicate that the internal structures of the ϒ(10753) and ϒ(10860) states may differ. Including data at sqrt[s]=10.653 GeV, we also search for the bottomonium equivalent of the X(3872) state decaying into ωϒ(1S). No significant signal is observed for masses between 10.45 and 10.65 GeV/c^{2}.

Measurement of the Λ_{c}

An absolute measurement of the Λ_{c}^{+} lifetime is reported using Λ_{c}^{+}→pK^{-}π^{+} decays in events reconstructed from data collected by the Belle II experiment at the SuperKEKB asymmetric-energy electron-positron collider. The total integrated luminosity of the data sample, which was collected at center-of-mass energies at or near the ϒ(4S) resonance, is 207.2 fb^{-1}. The result, τ(Λ_{c}^{+})=203.20±0.89±0.77 fs, where the first uncertainty is statistical and the second systematic, is the most precise measurement to date and is consistent with previous determinations.

Search for Lepton-Flavor-Violating τ Decays to a Lepton and an Invisible Boson at Belle II.

We search for lepton-flavor-violating τ^{-}→e^{-}α and τ^{-}→µ^{-}α decays, where α is an invisible spin-0 boson. The search uses electron-positron collisions at 10.58 GeV center-of-mass energy with an integrated luminosity of 62.8 fb^{-1}, produced by the SuperKEKB collider and collected with the Belle II detector. We search for an excess in the lepton-energy spectrum of the known τ^{-}→e^{-}ν[over ¯]_{e}ν_{τ} and τ^{-}→µ^{-}ν[over ¯]_{µ}ν_{τ} decays. We report 95% confidence-level upper limits on the branching-fraction ratio B(τ^{-}→e^{-}α)/B(τ^{-}→e^{-}ν[over ¯]_{e}ν_{τ}) in the range (1.1-9.7)×10^{-3} and on B(τ^{-}→µ^{-}α)/B(τ^{-}→µ^{-}ν[over ¯]_{µ}ν_{τ}) in the range (0.7-12.2)×10^{-3} for α masses between 0 and 1.6 GeV/c^{2}. These results provide the most stringent bounds on invisible boson production from τ decays.

Search for an Invisible Z

The L_{µ}-L_{τ} extension of the standard model predicts the existence of a lepton-flavor-universality-violating Z^{'} boson that couples only to the heavier lepton families. We search for such a Z^{'} through its invisible decay in the process e^{+}e^{-}→µ^{+}µ^{-}Z^{'}. We use a sample of electron-positron collisions at a center-of-mass energy of 10.58 GeV collected by the Belle II experiment in 2019-2020, corresponding to an integrated luminosity of 79.7 fb^{-1}. We find no excess over the expected standard-model background. We set 90%-confidence-level upper limits on the cross section for this process as well as on the coupling of the model, which ranges from 3×10^{-3} at low Z^{'} masses to 1 at Z^{'} masses of 8 GeV/c^{2}.

Measurement of CP Violation in B

We report a measurement of the CP-violating parameters C and S in B^{0}→K_{S}^{0}π^{0} decays at Belle II using a sample of 387×10^{6} BB[over ¯] events recorded in e^{+}e^{-} collisions at a center-of-mass energy corresponding to the ϒ(4S) resonance. These parameters are determined by fitting the proper decay-time distribution of a sample of 415 signal events. We obtain C=-0.04_{-0.15}^{+0.14}±0.05 and S=0.75_{-0.23}^{+0.20}±0.04, where the first uncertainties are statistical and the second are systematic.

Search for a τ

We report the first search for a nonstandard-model resonance decaying into τ pairs in e^{+}e^{-}→µ^{+}µ^{-}τ^{+}τ^{-} events in the 3.6-10 GeV/c^{2} mass range. We use a 62.8 fb^{-1} sample of e^{+}e^{-} collisions collected at a center-of-mass energy of 10.58 GeV by the Belle II experiment at the SuperKEKB collider. The analysis probes three different models predicting a spin-1 particle coupling only to the heavier lepton families, a Higgs-like spin-0 particle that couples preferentially to charged leptons (leptophilic scalar), and an axionlike particle, respectively. We observe no evidence for a signal and set exclusion limits at 90% confidence level on the product of cross section and branching fraction into τ pairs, ranging from 0.7 to 24 fb, and on the couplings of these processes. We obtain world-leading constraints on the couplings for the leptophilic scalar model for masses above 6.5 GeV/c^{2} and for the axionlike particle model over the entire mass range.

Precise Measurement of the D_{s}

We measure the lifetime of the D_{s}^{+} meson using a data sample of 207 fb^{-1} collected by the Belle II experiment running at the SuperKEKB asymmetric-energy e^{+}e^{-} collider. The lifetime is determined by fitting the decay-time distribution of a sample of 116×10^{3} D_{s}^{+}→ϕπ^{+} decays. Our result is τ_{D_{s}^{+}}=(499.5±1.7±0.9) fs, where the first uncertainty is statistical and the second is systematic. This result is significantly more precise than previous measurements.

Tests of Light-Lepton Universality in Angular Asymmetries of B

We present the first comprehensive tests of the universality of the light leptons in the angular distributions of semileptonic B^{0}-meson decays to charged spin-1 charmed mesons. We measure five angular-asymmetry observables as functions of the decay recoil that are sensitive to lepton-universality-violating contributions. We use events where one neutral B is fully reconstructed in ϒ(4S)→BB[over ¯] decays in data corresponding to 189 fb^{-1} integrated luminosity from electron-positron collisions collected with the Belle II detector. We find no significant deviation from the standard model expectations.

Test of Light-Lepton Universality in the Rates of Inclusive Semileptonic B-Meson Decays at Belle II.

We present the first measurement of the ratio of branching fractions of inclusive semileptonic B-meson decays, R(X_{e/µ})=B(B→Xeν)/B(B→Xµν), a precision test of electron-muon universality, using data corresponding to 189 fb^{-1} from electron-positron collisions collected with the Belle II detector. In events where the partner B meson is fully reconstructed, we use fits to the lepton momentum spectra above 1.3 GeV/c to obtain R(X_{e/µ})=1.007±0.009(stat)±0.019(syst), which is the most precise lepton-universality test of its kind and agrees with the standard-model expectation.

Transition-metal decorated graphdiyne monolayer as an efficient sensor toward phosphide (PH3) and arsine (AsH3).

Graphdiyne (GDY), a two-dimensional (2D) carbon, uniquely possesses mixed sp-sp2 hybridization, uniform nano-sized porous structure, semiconducting character, and excellent electrical conductivity. These features beneficially promote its applications in many fields, especially gas sensing. Based on density functional theory (DFT) and statistical thermodynamics, this study reports the sensing capabilities of pristine and selected transition metal (i.e., Fe, Sc, and Ti)-decorated GDY to detect environmentally hazardous arsine (AsH3) and phosphide (PH3) gases. We discover that Fe-doped GDY is a high-performance sensing material for detecting AsH3 and PH3 because of its selectivity and ultra-high sensitivity at the part-per-million (ppm) level. The presence of these gases induces measurably drastic changes in the electronic properties of Fe-doped GDY. The promising detection capabilities are fundamentally rooted in the appropriate chemical binding energies (i.e., ranging from -0.80 to -1.80 eV), which are basically rooted in the prominent orbital overlap among Fe-3d and As(P)-4p states. This study has raised the need to design efficient nanosensors using GDY-based materials.

Precise Measurement of the D

We report a measurement of the D^{0} and D^{+} lifetimes using D^{0}→K^{-}π^{+} and D^{+}→K^{-}π^{+}π^{+} decays reconstructed in e^{+}e^{-}→cc[over ¯] data recorded by the Belle II experiment at the SuperKEKB asymmetric-energy e^{+}e^{-} collider. The data, collected at center-of-mass energies at or near the ϒ(4S) resonance, correspond to an integrated luminosity of 72 fb^{-1}. The results, τ(D^{0})=410.5±1.1(stat)±0.8(syst) fs and τ(D^{+})=1030.4±4.7(stat)±3.1(syst) fs, are the most precise to date and are consistent with previous determinations.

PIN1 is a new therapeutic target of craniosynostosis.

Gain-of-function mutations in fibroblast growth factor receptors (FGFRs) cause congenital skeletal anomalies, including craniosynostosis (CS), which is characterized by the premature closure of craniofacial sutures. Apert syndrome (AS) is one of the severest forms of CS, and the only treatment is surgical expansion of prematurely fused sutures in infants. Previously, we demonstrated that the prolyl isomerase peptidyl-prolyl cis-trans isomerase interacting 1 (PIN1) plays a critical role in mediating FGFR signaling and that Pin1+/- mice exhibit delayed closure of cranial sutures. In this study, using both genetic and pharmacological approaches, we tested whether PIN1 modulation could be used as a therapeutic regimen against AS. In the genetic approach, we crossbred Fgfr2S252W/+, a mouse model of AS, and Pin1+/- mice. Downregulation of Pin1 gene dosage attenuated premature cranial suture closure and other phenotypes of AS in Fgfr2S252W/+ mutant mice. In the pharmacological approach, we intraperitoneally administered juglone, a PIN1 enzyme inhibitor, to pregnant Fgfr2S252W/+ mutant mice and found that this treatment successfully interrupted fetal development of AS phenotypes. Primary cultured osteoblasts from Fgfr2S252W/+ mutant mice expressed high levels of FGFR2 downstream target genes, but this phenotype was attenuated by PIN1 inhibition. Post-translational stabilization and activation of Runt-related transcription factor 2 (RUNX2) in Fgfr2S252W/+ osteoblasts were also attenuated by PIN1 inhibition. Based on these observations, we conclude that PIN1 enzyme activity is important for FGFR2-induced RUNX2 activation and craniofacial suture morphogenesis. Moreover, these findings highlight that juglone or other PIN1 inhibitors represent viable alternatives to surgical intervention for treatment of CS and other hyperostotic diseases.

Association between time to treatment and functional outcomes according to the Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score in endovascular stroke therapy.

BACKGROUND AND PURPOSE: The rate at which the chance of a good outcome of endovascular stroke therapy (EVT) decays with time when eligible patients are selected by baseline diffusion-weighted magnetic resonance imaging (DWI-MRI) and whether ischaemic core size affects this rate remain to be investigated. METHODS: This study analyses a prospective multicentre registry of stroke patients treated with EVT based on pretreatment DWI-MRI that was categorized into three groups: small [Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS)] (8-10), moderate (5-7) and large (<5) cores. The main outcome was a good outcome at 90 days (modified Rankin Scale 0-2). The interaction between onset-to-groin puncture time (OTP) and DWI-ASPECTS categories regarding functional outcomes was investigated. RESULTS: Ultimately, 985 patients (age 69 ± 11 years; male 55%) were analysed. Potential interaction effects between the DWI-ASPECTS categories and OTP on a good outcome at 90 days were observed (Pinteraction  = 0.06). Every 60-min delay in OTP was associated with a 16% reduced likelihood of a good outcome at 90 days amongst patients with large cores, although no associations were observed amongst patients with small to moderate cores. Interestingly, the adjusted rates of a good outcome at 90 days steeply declined between 65 and 213 min of OTP and then remained smooth throughout 24 h of OTP (Pnonlinearity  = 0.15). CONCLUSIONS: Our study showed that the probability of a good outcome after EVT nonlinearly decreased, with a steeper decline at earlier OTP than at later OTP. Discrepant effects of OTP on functional outcomes by baseline DWI-ASPECTS categories were observed. Thus, different strategies for EVT based on time and ischaemic core size are warranted.

Protective effects of extracorporeal shockwave on rat chondrocytes and temporomandibular joint osteoarthritis; preclinical evaluation with in vivo99mTc-HDP SPECT and ex vivo micro-CT.

OBJECTIVE: Extracorporeal shockwave therapy (ESWT) has been shown to have chondroprotective effects on arthritic diseases. We investigated the effects of ESWT on temporomandibular joint osteoarthritis (TMJOA) using rat chondrocytes and TMJOA rat models. DESIGN: Cell viability and expression of pro-inflammatory cytokines, cartilage degradation, and apoptosis markers were measured in control, monosodium iodoacetate (MIA)-treated and ESWT plus MIA-treated chondrocytes in vitro, and intra-articular MIA injection (TMJOA) and ESWT on TMJOA rats in vivo. In vivo99mTc-hydroxymethylene diphosphonate (HDP) single-photon emission computerized tomography/computerized tomography (SPECT/CT) and ex-vivo micro-CT and histologic examinations were performed in rat models. RESULTS: ESWT plus MIA-treated chondrocytes showed increased cell viability significantly (P = 0.007), while decreased genetic expression of pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6); P < 0.001 for each] and cartilage degradation markers [matrix metalloproteinase-3 (MMP3), matrix metalloproteinase-13 (MMP13), and bone morphogenetic protein 7 (BMP7); P < 0.001 for each], and number of apoptotic cells (P < 0.001) compared to MIA-treated chondrocytes. Changes in cytochrome c and cleaved caspase-3 levels relative to procaspase-3 were decreased over MIA-treated chondrocytes. ESWT on TMJOA rat models was associated with a significant decrease in pro-inflammatory and cartilage degradation markers, as demonstrated by real-time PCR and immunohistochemistry stains (P < 0.001 for each). On 99mTc-HDP SPECT/CT, the ESWT group showed a significantly lower uptake ratio compared to the TMJOA group (P = 0.008). Micro-CT analysis revealed that the ESWT group showed improved structure and bone quality compared to the TMJOA control group. CONCLUSIONS: ESWT was associated with a protective effect on cartilage and subchondral bone structures of TMJOA by reducing inflammation, cartilage degradation, and chondrocyte apoptosis.

PI-RADS version 2: optimal time range for determining positivity of dynamic contrast-enhanced MRI in peripheral zone prostate cancer.

AIM: To analyse the optimal time cut-off for determining positivity of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in peripheral zone (PZ) prostate cancer (PCa). MATERIALS AND METHODS: A consecutive series of 89 patients with PZ PCa who had undergone diffusion-weighted imaging (DWI) and subtraction DCE MRI were included. An experienced reader visually analysed the earliest time after contrast medium injection to visualise the best contrast between an index tumour and normal PZ on DCE MRI (i.e., best contrast time). The best contrast time cut-off for clinically significant cancer (csPCa) according to Epstein criteria or International Society of Urological Pathology (ISUP) grade ≥2 was analysed by an experienced reader, and applied to a less-experienced reader. For the index lesion of DWI category 3, the added value of DCE MRI (increased true positive and negative rates of PI-RADSv2 for csPCa) was evaluated using the cut-off time. RESULTS: The best contrast time cut-off for csPCa was ≤72 seconds for Epstein criteria and ≤56 seconds for ISUP grade ≥2 by an experienced reader. The weighted kappa to determine positivity of DCE MRI was 0.622 for ≤72 seconds and 0.527 for ≤56 seconds between the two readers. The added value of DCE MRI was 55-75% by an experienced reader and 39.1-69.6% by a less-experienced reader. CONCLUSION: For interpreting PI-RADSv2, imaging findings within 60-72 seconds following contrast media injection seem to reliably determine positivity of DCE MRI in PZ, and have added value for detecting csPCa.

Short communication: Chia seed extract enhances physiochemical and antioxidant properties of yogurt.

Yogurt is a healthy dairy food fermented by lactic acid bacteria (LAB). Because consumers demand healthier and more nutritious yogurt, numerous substances have been used to supplement yogurt. Chia seed has been reported to contain abundant phenolic compounds, dietary fiber, and n-3 fatty acids and therefore is a potential functional food additive. The aim of this study was to investigate the influence of chia seed extracts on the physicochemical and bioactive properties of set-type yogurt. Yogurt was fortified with chia seed water extract (CSWE) or chia seed ethanol extract (CSEE) at 0.05 or 0.1% (vol/vol). Results showed that supplementation with CSWE or CSEE significantly accelerated the fermentation rate and growth of LAB. Both CSWE and CSEE improved the viscosity, syneresis, and water-holding capacity of yogurt. The radical scavenging activity of yogurt was increased with both extracts, and the 0.1% CSEE yogurt exhibited the highest radical scavenging activity. Furthermore, 0.1% CSEE yogurt significantly inhibited lipopolysaccharide-induced production of hydrogen peroxide in human colon cells. Addition of chia seed extract improves the growth of LAB, the physiochemical properties, and the health-beneficial effects of set-type yogurt.

Intraosseous basivertebral nerve ablation for the treatment of chronic low back pain: a prospective randomized double-blind sham-controlled multi-center study.

PURPOSE: To evaluate the safety and efficacy of radiofrequency (RF) ablation of the basivertebral nerve (BVN) for the treatment of chronic low back pain (CLBP) in a Food and Drug Administration approved Investigational Device Exemption trial. The BVN has been shown to innervate endplate nociceptors which are thought to be a source of CLBP. METHODS: A total of 225 patients diagnosed with CLBP were randomized to either a sham (78 patients) or treatment (147 patients) intervention. The mean age within the study was 47 years (range 25-69) and the mean baseline ODI was 42. All patients had Type I or Type II Modic changes of the treated vertebral bodies. Patients were evaluated preoperatively, and at 2 weeks, 6 weeks and 3, 6 and 12 months postoperatively. The primary endpoint was the comparative change in ODI from baseline to 3 months. RESULTS: At 3 months, the average ODI in the treatment arm decreased 20.5 points, as compared to a 15.2 point decrease in the sham arm (p = 0.019, per-protocol population). A responder analysis based on ODI decrease ≥ 10 points showed that 75.6% of patients in the treatment arm as compared to 55.3% in the sham control arm exhibited a clinically meaningful improvement at 3 months. CONCLUSION: Patients treated with RF ablation of the BVN for CLBP exhibited significantly greater improvement in ODI at 3 months and a higher responder rate than sham treated controls. BVN ablation represents a potential minimally invasive treatment for the relief of chronic low back pain. These slides can be retrieved under Electronic Supplementary Material.

Causal analysis of self-sustaining processes in the logarithmic layer of wall-bounded turbulence.

Despite the large amount of information provided by direct numerical simulations of turbulent flows, their underlying dynamics remain elusive even in the most simple and canonical configurations. Most common approaches to investigate the turbulence phenomena do not provide a clear causal inference between events, which is essential to determine the dynamics of self-sustaining processes. In the present work, we examine the causal interactions between streaks, rolls and mean shear in the logarithmic layer of a minimal turbulent channel flow. Causality between structures is assessed in a non-intrusive manner by transfer entropy, i.e., how much the uncertainty of one structure is reduced by knowing the past states of the others. We choose to represent streaks by the first Fourier modes of the streamwise velocity, while rolls are defined by the wall-normal and spanwise velocity modes. The results show that the process is mainly unidirectional rather than cyclic, and that the log-layer motions are sustained by extracting energy from the mean shear which controls the dynamics and time-scales. The well-known lift-up effect is also identified, but shown to be of secondary importance in the causal network between shear, streaks and rolls.

Adenovirus-mediated Foxp3 expression in lung epithelial cells ameliorates acute radiation-induced pneumonitis in mice.

Forkhead transcription factor 3 (Foxp3) has a critical role in regulatory T cells (Treg). There are an increasing number of researches concerning the functions of Foxp3 in other cells, including lung epithelial cells besides Treg. However, the roles of Foxp3 in lung epithelial cells remain poorly understood. To examine the potential therapeutic benefits of Foxp3 for lung inflammation, this study investigates the effect of adenovirus-mediated Foxp3 overexpression in a radiation-induced lung damage model. Foxp3-EGFP expressing adenovirus was administered by intratracheal injection three times over 14 days after focal X-ray irradiation. To evaluate effects of Foxp3 overexpression in radiation-induced lung inflammation, immune cell profiles of bronchoalveolar lavage (BAL) fluid were analyzed. Foxp3 gene-delivered mice showed significant inhibition of immune cell infiltration, such as eosinophils, lymphocytes, macrophages and neutrophils in BAL fluid. Histopathological analysis also showed that Foxp3 overexpression inhibits inflammatory cell recruitment and collagen deposition in lung tissues. In addition, expression of inflammatory and fibrosis-related genes was decreased in the Foxp3 expression adenovirus-infected group. These results suggest that Foxp3 expression in lungs holds considerable therapeutic potential for attenuating inflammation and fibrosis in radiation-induced lung injury.

Prognostic value of tumor-infiltrating lymphocytes in Epstein-Barr virus-associated gastric cancer.

BACKGROUND: This study explored the prognostic impact of tumor-infiltrating lymphocytes (TILs) and investigated whether three histologic subtypes (lymphoepithelioma-like carcinoma, carcinoma with Crohn's disease-like lymphoid reaction, and conventional-type adenocarcinoma) could stratify a prognostic subset for patients with Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC). MATERIALS AND METHODS: After reviewing 1318 consecutive cases of surgically resected or endoscopic submucosal dissected gastric cancers, 120 patients were identified as EBV-positive using EBV-encoded RNA in situ hybridization. The evaluation of the percentage of intratumoral (iTu-) and stromal (str-) TILs was carried out, and the cases were also subclassified into three histologic subtypes as noted above. RESULTS: Among the 120 patients, 73 patients (60.8%) and 60 patients (50.0%) were determined as str-TIL-positive and iTu-TIL-positive, respectively. In a univariate analysis, str-TIL-positivity was significantly associated with longer recurrence-free survival (RFS; P = 0.002) and disease-free survival (DFS; P = 0.008), yet not overall survival (OS; P = 0.145). While iTu-TIL-positivity has a tendency of favorable outcome indicator for DFS and OS, but statistically significant differences were not shown, respectively (RFS, P = 0.058; DFS, P = 0.151; OS, P = 0.191). In a multivariate analysis using a Cox proportional hazard model adjusted for age, pTNM stage, lymphatic invasion, perineural invasion, and venous invasion; histologic subtype, WHO classification, and str-TIL-positivity were independently or tentatively associated with favorable RFS (hazard ratio [HR] = 12.193, 95% confidence interval [95% CI] 1.039-143.055, P = 0.047) or DFS (HR = 4.836, 95% CI 0.917-25.525, P = 0.063). CONCLUSION: The histologic subclassification and TILs can be used to predict RFS and DFS for patients with EBVaGC.