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The realization of electroluminescence (EL) of negatively charged nitrogen vacancy (NV−) centers is important toward all-electrical control of diamond quantum devices. In this study, we demonstrated electrical excitation and detection of EL of single NV− centers by using lateral diamond p+–i(n−)–n+ diodes. It had been grown by homoepitaxy using the plasma enhanced chemical vapor deposition technique. We introduced a lightly phosphorus doped i(n−) layer to stabilize the negative state of NV centers. It was estimated that the efficiency of the electrical excitation rate of the NV center was more than 30 times enhanced by introducing lateral diamond p+–i(n−)–n+ diodes structure compared with the previous vertical diode. Furthermore, the EL of a single NV− center embedded in the i(n−) layer region was characterized. The results show that the charge state of the single NV centers can be manipulated by the voltage applied to the p+–i(n−)–n+ diode, where the emission of EL is increasingly dominated by NV− in the range of 30 to 50 V.

Background Current isolation techniques for spotted fever group Rickettsia from clinical samples are laborious and are limited to tissue, blood and blood derivatives with volumes ideally greater than 1 mL. We validated the use of simplified methodologies for spotted fever group Rickettsia culture isolation that overcome sample volume limitations and provide utility in clinical diagnostics and research studies. Methodology/Principal findings A modified cell culture method is evaluated for the isolation of Rickettsia ssp. from human diagnostic samples. Culture sampling method, culture platform, and growth phase analysis were evaluated to determine best practices for optimal culture isolation conditions. Rickettsial isolates (R. conorii, R. rickettsii, and R. parkeri) were grown in Vero E6 cells over a course of 5 to 7 days at low inoculum treatments (~40 bacterial copies) to standardize the sampling strategy at a copy number reflective of the bacteremia in acute diagnostic samples. This methodology was verified using small volumes (50 μL) of 25 unprocessed clinical whole blood, plasma, and serum samples from acute samples of patients suspected of having Rocky Mountain Spotted Fever, of which 10 were previously confirmed positive via the PanR8 qPCR assay, 13 had no detectable Rickettsia DNA by the PanR8 qPCR assay, and 2 were not previously tested; these samples resulted in the cultivation of 7 new R. rickettsii isolates. Conclusions/Significance We observed that rickettsial isolate growth in culture is reproducibly identified by real-time PCR testing of culture media within 72 hours after inoculation. Additionally, specimen sedimentation prior to isolation to remove red blood cells was found to decrease the amount of total organism available in the inoculum. A small volume culture method was established focusing on comparative qPCR detection rather than bacterial visualization, taking significantly shorter time to detect, and requiring less manipulation compared to traditional clinical isolate culture methods.

Estimada Editora: La infección por Rickettsia felis (R. felis) es considerada una amenaza para la salud humana. La R. felis, una bacteria gramnegativo considerada como un patógeno emergente que ha sido identificada en numerosos casos humanos a nivel global, representa una causa importante de enfermedades febriles, asociada generalmente con Ctenocephalides felis encontrada en gatos y perros1. Las manifestaciones clínicas tempranas incluyen fiebre, dolor de cabeza, mialgia, sarpullido, tos y vómitos, que pueden parecerse a otras enfermedades febriles como dengue y malaria, complicando así el diagnóstico clínico1,2. Sin tratamiento podrían desarrollarse síntomas severos potencialmente letales. La vigilancia centinela de enfermedades febriles agudas, a través de la Vigilancia Integrada Colaborativa que se desarrolló en Guatemala entre los años 2013 y 20183, permitió el hallazgo del primer caso de Rickettsia felis en Guatemala. Se eligieron 612 pacientes que cumplieron con los criterios de la definición de caso de síndrome febril agudo: consulta médica u hospitalización por fiebre sin causa aparente con evolución menor a siete días, o fiebre cuantificada mayor o igual a 38 °C durante la consulta o durante las primeras 24 horas de hospitalización. Se tomaron las muestras de sangre para el análisis de los agentes causantes de malaria, leptospirosis, dengue y rickettsiosis, que fueron procesadas en los laboratorios de la Universidad del Valle de Guatemala. La muestra positiva para Rickettsia spp. fue analizada por reacción en cadena de la polimerasa (PCR) convencional para la detección del gen de antígeno de Rickettsia 17 kDa, encontrado en el grupo de rickettsias productoras de fiebres maculosas (SFGR) y en el grupo de tifus Rickettsia ADN. Se usó la amplificación semianidada del fragmento nucleótido 70–602 del gen de proteína transmembranal A OmpA de Rickettsia para la identificación de SFGR. Finalmente, el hallazgo fue confirmado por la División de Zoonosis de Rickettsia de los Centros para el Control y Prevención de Enfermedades; donde se confirmó Rickettsia spp., a través de la PCR en tiempo real en la que se utilizó el ensayo PanR8 y por la PCR anidada enfocada en el gen SFG 17 kDa. La secuenciación del producto de amplificación identificó R. felis. La muestra pertenecía a un niño de tres años tratado en diciembre de 2017 en un centro de salud del Municipio de Nueva Santa Rosa, Santa Rosa, en Guatemala. Al momento de la toma de la muestra, el paciente reportaba dos días de fiebre, tos, disnea, vómitos, dolor abdominal y fatiga. Se reportó como factor de riesgo de exposición que su mascota era un gato. La infección por R. felis puede causar un síndrome febril agudo con síntomas variados1. En algunos casos, es una enfermedad leve sin fiebre; además, se han registrado casos aislados de niños que presentaron erupciones o costras1. La presentación afebril también puede contribuir a la no detección4. La identificación de esta infección en estudios de vigilancia de enfermedad febril en África y Asia sugiere que produce una enfermedad clínicamente relevante en individuos con inmunosupresión2. La baja disponibilidad de pruebas diagnósticas es una limitante. Además, al existir una reactividad cruzada de la serología entre las fiebres maculosas de las Montañas Rocosas, hace difícil interpretar los resultados, lo cual limita la utilidad del diagnóstico1. Estudios demuestran evidencia serológica de una exposición diseminada a fiebre de las Montañas Rocosas, coincidiendo con el aislamiento de R. felis5. Por su parte, las pruebas moleculares dan un resultado de especie específica, pero la sensibilidad podría disminuirse con el tiempo y el tratamiento1. Una alta proporción de casos de ensayos de inmunofluorescencia nunca reciben un diagnóstico definitivo. Los mamíferos no humanos son los reservorios asintomáticos. La escasez de casos humanos notificados en Centroamérica, a pesar de la amplia evidencia documentada de R. felis en vectores artrópodos, sugiere que la enfermedad no está siendo detectada5. Dada la conocida prevalencia en la región de R. felis en pulgas, es probable que las infecciones humanas por R. felis no estén siendo diagnosticadas y pueden estar entre las causas de ensayos de inmunofluorescencia no diferenciadas. Los ensayos moleculares pueden distinguir entre varias especies de rickettsias, lo que permite una mejor caracterización de estas infecciones4,5. Este hallazgo señala a considerar a R. felis como una etiología en el diagnóstico diferencial de pacientes febriles con síntomas respiratorios, digestivos o no específicos, que puede orientar el tratamiento y la atención médica adecuados. Además, se deben evaluar factores de riesgo potenciales, como el contacto con portadores de pulgas infectadas5. Aunque en este estudio se detectó solo un caso de R. felis, la carga real en Centroamérica podría estar subregistrada. Se considera importante proponer que las técnicas de laboratorio molecular estén accesibles en la región para brindar una mejor caracterización de la carga de enfermedades por rickettsiosis4. A pesar de la falta de una muestra de suero convaleciente para confirmar que la respuesta inmune coincidía con la enfermedad aguda, la proximidad a los síntomas agudos, la falta de otra etiología después de realizar pruebas exhaustivas y el resultado positivo en un ensayo con un alto límite de detección, respaldó que la etiología fuera R. felis en la enfermedad febril de este niño. Además, existe una conocida circulación de infección por R. felis en animales domésticos en la misma área geográfica y cada vez hay más evidencia en la literatura de que es una importante fuente de enfermedad febril aguda en niños en África y Asia. Ampliar la vigilancia permitiría una mejor descripción de la distribución de las enfermedades por rickettsiosis en la población, con las consiguientes mejoras en el manejo clínico y el tratamiento de estas infecciones emergentes. Por tanto, se sugiere una mayor conciencia de la presentación y diagnóstico de este patógeno en Centroamérica, lo cual puede contribuir a una comprensión más completa de la verdadera carga de estas enfermedades en la región.

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.

At the Fermilab Tevatron proton-antiproton ($p\bar{p}$) collider, high-mass electron-neutrino ($e\nu$) pairs are produced predominantly in the process $p \bar{p} \rightarrow W(\rightarrow e\nu) + X$. The asymmetry of the electron and positron yield as a function of their pseudorapidity constrain the slope of the ratio of the $u$- to $d$-quark parton distributions versus the fraction of the proton momentum carried by the quarks. This paper reports on the measurement of the electron-charge asymmetry using the full data set recorded by the Collider Detector at Fermilab in 2001--2011 and corresponding to 9.1~fb$^{-1}$ of integrated luminosity. The measurement significantly improves the precision of the Tevatron constraints on the parton-distribution functions of the proton. Numerical tables of the measurement are provided.

Background and objective Percutaneous coronary intervention (PCI) with metallic coronary stent (bare-metal stents [BMS] and drug-eluting stents [DES]) implantation is most frequently performed therapeutic procedures for coronary artery disease. In-stent restenosis (ISR) is a critical drawback of metallic coronary stents. Incidence of ISR has been reported in up to 30% after BMS implantation. The use of DES has greatly reduced the proportion of restenosis compared with the BMS. However, ISR still remains the primary concern after PCI even in the contemporary DES era, and thought to be associated with worse clinical outcomes. However, comparative data on ISR and de novo lesions are rare. Purpose The aim of the present study was to compare the clinical outcomes after PCI for the de novo lesion and the ISR lesion. Methods We performed a retrospective analysis of patients who underwent PCI between 2013 and 2020. The incidences of major adverse cardiac and cerebrovascular events (MACCE) and all-cause death were evaluated. MACCE was defined as composite of cardiovascular death, non-fatal myocardial infarction, and stroke. Results In this study, 1538 patients were enrolled and divided into two groups: PCI for de novo lesion group (n=1258, 81.8%), and PCI for ISR lesion group (n=280, 18.2%). Patients in the ISR lesion group were significantly older and had higher prevalence of hypertension, diabetes mellitus, dyslipidemia and chronic kidney disease than patients in the de novo lesion group. During a median follow-up period of 1.9 years, Kaplan-Meier curves showed no significant differences in the incidences of MACCE (log-rank, p=0.86) and all-cause death (p=0.84) between two groups. After adjustment for other covariates, PCI for ISR lesion were not significantly associated with MACCE (hazard ratio [HR], 1.10; 95% confidential interval [CI], 0.61–1.97; p=0.76) and all-cause death (HR, 0.93; 95% CI, 0.56–1.56; p=0.79) Conclusion PCI for the ISR lesion was not associated with worse clinical outcomes compared with PCI for the de novo lesion. Funding Acknowledgement Type of funding sources: None.

Background Near-infrared spectroscopy (NIRS) and intravascular ultrasound (IVUS) are useful imaging modalities to identify lipid-rich plaque (LRP) which is associated with an increased risk of future cardiovascular events in individuals undergoing PCI. Pathological studies have raised concerns that treating LRP with stents may impair vascular healing. However, the impact of stent implantation to LRP lesions was less known. Moreover, little information is available about changes in the extent of LRP at before and after PCI. Purpose The aim of this study was to investigate changes in LRP by NIRS between pre- and post-stent implantation, and to evaluate an association among impact of LRP by NIRS at pre- and post-stenting and late lumen loss (LLL) by angiography. Methods We studied 175 lesions in 149 patients who underwent PCI under NIRS-IVUS guidance and follow-up angiography at 8-month later from 2017 to 2020. Plaque characteristics on IVUS, the extent of LRP [defined as a long segment with a 4-mm maximum lipid core burden index (maxLCBI4mm)] on NIRS, and quantitative coronary angiography measurements were analyzed. We evaluated a change of the extent of LRP between pre- and post-stenting at index PCI procedure, and association between the extent of LRP and a 8-month LLL at follow-up coronary angiography. A large LRP was defined as maxLCBI4mm>400 at pre-stenting. Results Mean age was 64.5 years old, and 123 (82%) patients were male. The prevalence of large LRP was 51% and median plaque burden at minimum lumen area was 81%. The extent of LRP at culprit lesion significantly decreased from pre- to post-stenting (median maxLCBI4mm [interquartile range (IQR)]: 407 [199, 580] to 133 [13, 319], p0.05). Median LLL at follow-up angiogram was 0.17 [0.07–0.35] mm. Both the extent of pre- and post-stenting LRP were not associated with LLL (r=0.018, p=0.80 and r=0.022, p=0.76, respectively) (Figure 2). In addition, there was no significant difference in LLL between the post-stenting large and non-large LRP (median [IQR] 0.18 [0.08–0.35] vs. 0.17 [0.07–0.35]; P=0.95). Conclusions This study showed coronary stent implantation significantly reduced the NIRS-derived LRP in patients undergoing PCI. Although the extent of pre-stenting LRP and IVUS plaque burden predicted the reduction of LRP, the extent of pre- and post-stenting LRP were not associated with LLL. These findings suggest that stent implantation for LRP, even in a large LRP, is safe and does not affect LLL. Funding Acknowledgement Type of funding sources: None. Figure 1. Scatter plotsFigure 2. CENTRAL Figure

Background Sarcoidosis is a systemic granulomatous disease that affects multiple organs. Among these, the presence of cardiac involvement is recognised as a determinant of worse clinical outcomes. Soluble interleukin 2 receptor (sIL-2R) is a potentially useful biomarker in the diagnosis and evaluation of disease severity in patients with sarcoidosis. However, it remains to be seen whether sIL-2R is associated with the severity and activity of disease in patients with cardiac sarcoidosis (CS). Purpose The aims of this study were to investigate whether sIL-2R was associated with clinical outcomes and to clarify the relationship between sIL-2R levels and disease activity evaluated by 18F-fluorideoxyglucose in positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with CS. Methods We examined 101 consecutive patients with CS who were admitted to our University HospitalbetweenMay 2003 and February 2020. Patients who had no data of serum sIL-2R levels before initiation of immunosuppressive therapy (n=18) were excluded. Ultimately, 83 patients were examined in this study. The primary outcome was a composite of advanced atrioventricular block (AVB), ventricular tachycardia or ventricular fibrillation (VT/VF), heart failure hospitalisation, and all-cause death. Inflammatory activity in the myocardium and lymph nodes were assessed by18F-FDG PET/CT. We used a published program to analyse the cardiac metabolic activity (CMA), and total lymph node glycolysis (TLyG), which are quantitative measures of FDG volume-intensity. Results During a median follow-up period of 2.96 (interquartile range 2.24–4.27) years, the primary outcome occurred in 24 patients (29%), including 1 advanced AVB, 13 VT/VF, 5 hospitalisations for heart failure, and 5 all-cause deaths. Kaplan-Meier analyses showed that the primary outcome occurred more frequently in patients with higher sIL-2R levels (>538 U/mL, the median) than in those with lower sIL-2R levels (Figure). A multivariable Cox regression analysis revealed that a higher sIL-2R level was independently associated with an increased subsequent risk of adverse events (hazard ratio 3.71, 95% confidence interval 1.63–8.44, p=0.002), even after adjustments for age, plasma B-type natriuretic peptide, estimated glomerular filtration rate, left ventricular ejection fraction, and late gadolinium enhancement, which are known to be strong determinants of worse clinical outcomes in patients with CS (Table). Furthermore, sIL-2R levels were significantly correlated with TLyG, the inflammatory activity in lymph nodes (r=0.346, p=0.003) but not with CMA, the inflammatory activity in myocardium (r=0.131, p=0.27). Conclusions Increased sIL-2R is associated with worse long-term clinical outcomes accompanied by increased systemic inflammatory activity in CS patients. These findings suggest the importance of assessing sIL-2R as a surrogate marker for further risk stratification in these patients. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Japan Society for the Promotion of Science

Background Asians have a much lower incidence of adverse coronary events than Caucasians, and the characteristics of vulnerable plaque might be different among the ethnics. Purpose The aim of this study was to investigate the clinical characteristics of lipid-rich plaque (LRP) in the Asian population and we also aimed to distinguish the characteristics of an acute coronary syndrome (ACS) culprit lesion and a chronic coronary syndrome (CCS) culprit lesion. Furthermore, we evaluated the association between lipid core burden index (LCBI) and cardiovascular risk factors, lipid profiles, and inflammatory biomarkers, as determined in vivo by near infrared spectroscopy intravascular ultrasound (NIRS-IVUS) imaging in patients undergoing percutaneous coronary intervention (PCI). Methods We evaluated 207 patients (ACS, n=75; CCS, n=132) who underwent PCI under NIRS-IVUS. Plaque characteristics and the extent of LRP [defined as a long segment with a 4-mm maximum LCBI (maxLCBI4mm)] on NIRS in de-novo culprit and non-culprit segments were analyzed. Results The mean age was 65 years old and 82% of patients were male. The ACS culprit lesions had a significantly higher maxLCBI4mm (median [interquartile range (IQR)]: 533 [385–745] vs. 361 [174–527], p Conclusions We confirmed that NIRS-IVUS plaque assessment could be useful to differentiate ACS from CCS culprit lesions, and that a threshold maxLCBI4mm ≥400 was clinically suitable in Japanese patients. No systemic surrogate markers were found to be associated with the extent of LRP by NIRS in culprit and non-culprit segments. Consequently, we believe that direct intravascular evaluation of coronary plaque characteristics remains important for identification of high-risk LRP. Funding Acknowledgement Type of funding sources: None. Figure 1. The difference of maxLCBI4mmFigure 2. ROC curve

Using data samples of 89.5 and 711fb$^{-1}$ recorded at energies of $\sqrt{s}$=10.52 and 10.58 GeV, respectively, with the Belle detector at the KEKB e$^{+}$e$^{-}$ collider, we report measurements of branching fractions of semileptonic decays Ξ$_{c}$$^{0}$ → Ξ$^{-}$l$^{+}$ν$_{l}$(l=e or μ) and the CP-asymmetry parameter of Ξ$_{c}$$^{0}$ → Ξ$^{-}$π$^{+}$ decay. The branching fractions are measured to be B(Ξ$_{c}$$^{0}$ → Ξ$^{-}$e$^{+}$ν$_{e}$)= 1.31±0.04±0.07±0.38)% and B(Ξ$_{c}$$^{0}$ → Ξ$^{-}$μ$^{+}$ν$_{μ}$ = (1.27±0.06±0.10±0.37)% , and the decay parameter α$_{Ξπ}$ is measured to be 0.63±0.03±0.01 with much improved precision compared with the current world average. The corresponding ratio B(Ξ$_{c}$$^{0}$ → Ξ$^{-}$e$^{+}$ν$_{e}$) /B(Ξ$_{c}$$^{0}$ → Ξ$^{-}$μ$^{+}$ν$_{μ}$) is 1.03±0.05±0.07, which is consistent with the expectation of lepton flavor universality. The first measured asymmetry parameter A$_{CP}$=(α$_{Ξ^{-}π^{+}}$+α$_{Ξ^{+}π^{-}}$)/(α$_{Ξ^{-}π^{+}}$+α$_{Ξ^{+}π^{-}}$) = 0.024±0.052±0.014 is found to be consistent with zero. The first and the second uncertainties above are statistical and systematic, respectively, while the third ones arise due to the uncertainty of the Ξ$_{c}$$^{0}$ → Ξ$^{-}$π$^{+}$ branching fraction.

Murine typhus, which is caused byRickettsia typhi, has a wide range of clinical manifestations. It has a low mortality rate but may result in meningoencephalitis and interstitial pneumonia in severe cases. Comparisons of complete genome sequences ofR.typhiisolates from North Carolina, USA (Wilmington), Myanmar (B9991PP), and Thailand (TH1527) identified only 26 single nucleotide polymorphism (SNP) and 7 insertion-deletion (INDEL) sites in these highly syntenic genomes. Assays were developed to further define the distribution of these variant sites among 15 additional isolates ofR.typhiwith different histories from Asia, the USA, and Africa. Mismatch amplification mutation assays (MAMA) were validated for 22 SNP sites, while the 7 INDEL sites were analyzed directly on agarose gels. Six SNP types, 9 INDEL types, 11 total types were identified among these 18 isolates. Replicate DNA samples as well as comparisons of isolates with different passage and source histories gave consistent genetic typing profiles. Comparison of the SNP and INDEL markers toR.typhi’snearest neighborRickettsia prowazekiidemonstrated that the majority of the SNPs represent intra-species variation that arose post divergence of these two species while several INDEL sites also exhibited intraspecies variability among theR.prowazekiigenomes that have been completely sequenced. The assays for the presence of these SNP and INDEL sites, particularly the latter, comprise a low technology gel method for consistently distinguishingR.typhi and R.prowazekiias well as for differentiating genetic types ofR.typhi.

Using 980 ${\rm fb}^{-1}$ of data {collected} with the Belle detector operating at the KEKB asymmetric-energy $e^+e^-$ collider, we report the measurements of the masses, and the first measurements of the instrinsic widths, of the $\Sigma_c(2455)^+$ and $\Sigma_c(2520)^+$ charmed baryons. We find $M(\Sigma_c(2455)^+)-M(\Lambda_c^+) = 166.17\pm 0.05^{+0.16}_{-0.07}\ {\rm MeV}/c^2$, $\Gamma(\Sigma_c(2455)^+) = 2.3 \pm 0.3 \pm 0.3\ {\rm MeV/c^2}$, $M(\Sigma_c(2520)^+)-M(\Lambda_c^+) = 230.9 \pm 0.5 ^{+0.5}_{-0.1}\ {\rm MeV}/c^2$, and $\Gamma(\Sigma_c(2520)^+) = 17.2^{+2.3\ +3.1}_{-2.1\ -0.7}\ {\rm MeV}/c^2$, where the uncertainties are statistical and systematic, respectively. These measurements can be used to test models of the underlying quark structure of the $\Sigma_c$ states.

Objective To conduct detailed measurements of site-specific radiation doses in 36 sections plotted on the surface of the prostate after brachytherapy (BT), to conduct a comprehensive analysis of the regions associated with erectile dysfunction (ED). Subjects and methods The subjects were 81 patients selected from among patients who underwent BT between 2004 and 2016 because they were able to complete the International Index of Erectile Function (IIEF)-6 questionnaire pre-treatment and 12 months post-treatment. Post-planning was done by inputting CT images made over a four-week period after treatment into a radiotherapy planning system, dividing the surface of the prostate into 36 equal sections, and measuring the D90 radiation dose (Gy) at each site. The soft tissue surrounding the corpus cavernosum was set as the ROI for the uretheral bulb spongy tissue, and the radiation dose to this region was similarly calculated. Results We selected 56 of the 81 patients who did not have ED or who had mild ED prior to treatment. 23 patients who scored 22 or higher on the IIEF-6 at 12 months post-treatment were assigned to the non-ED group, and 11 patients who scored under 11 were assigned to the ED group. Statistical inter-group comparison of the site-specific radiation doses indicated that the doses were significantly higher in the ED group in the following sections: Center of right lobe at 3 o'clock, center of left lobe at 2-4 o'clock, apex of left lobe at 2-4 o'clock. No significant difference in radiation dose was found for the corpus cavernosum. Conclusion In the group of patients with high radiation doses to the middle and apex at 2 – 4 o'clock the IIEF-6 score was significantly lower at 12 months post-treatment. This suggests that excessive radiation exposure to these sections may have an effect on post-BT ED. Disclosure Work supported by industry: no.

Clinical and laboratory diagnosis of rickettsial diseases is challenging because of the undifferentiated symptoms (commonly fever, headache, and malaise) and low bacteremia (< 100 genomic copies [gc]/mL) during the early acute stage of illness. Early treatment with doxycycline is critical for a positive outcome, especially in Rickettsia rickettsii (Rocky Mountain spotted fever) infections where cases may be fatal within 5 to 10 days from symptom onset, emphasizing the need for more sensitive diagnostics. A real-time reverse transcriptase polymerase chain reaction (PCR) assay, RCKr, was developed and validated for Rickettsia spp. nucleic acid detection in human clinical samples. The limit of detection for RCKr was determined to be 20 gc/mL, compared with our 2013 (Kato et al.) laboratory developed test, PanR8 at 1,800 to 2,000 gc/mL. Inclusivity, exclusivity, accuracy, and precision results correlated as expected. From an evaluation of 49 banked clinical samples, RCKr detected 35 previously positive samples, as well as two specimens that were PanR8 real-time PCR negative yet clinically diagnosed as possible rickettsiosis. Ct values from RCKr clinical sample testing show a 100-fold increase relative to PanR8. Additional testing is needed to understand the clinical sensitivity of RCKr; however, this study demonstrates RCKr to have high analytical specificity and sensitivity for Rickettsia detection.

We report results from a study of the spin and parity of $\Xi_{c}(2970)^+$ using a $980~\mathrm{fb^{-1}}$ data sample collected by the Belle detector at the KEKB asymmetric-energy $e^{+}e^{-}$ collider. The decay angle distributions in the chain $\Xi_{c}(2970)^+ \to \Xi_c(2645)^{0}\pi^{+} \to \Xi_c^{+}\pi^{-}\pi^{+}$ are analyzed to determine the spin of this charmed-strange baryon. The angular distributions strongly favor the $\Xi_{c}(2970)^+$ spin $J =1/2$ over $3/2$ or $5/2$, under an assumption that the lowest partial wave dominates in the decay. We also measure the ratio of $\Xi_{c}(2970)^+$ decay branching fractions $R={\mathcal{B}[ \Xi_{c}(2970)^+ \to \Xi_c(2645)^{0}\pi^{+} ]} / { \mathcal{B}[ \Xi_{c}(2970)^+ \to \Xi_c^{\prime0}\pi^{+} ]} =1.67 \pm 0.29\mathrm{(stat.)}^{ +0.15}_{ -0.09}\mathrm{(syst.)} \pm 0.25\mathrm{(IS)}$, where the last uncertainty is due to possible isospin-symmetry-breaking effects. This $R$ value favors the spin-parity $J^P=1/2^+$ with the spin of the light-quark degrees of freedom $s_{l}=0$. This is the first determination of the spin and parity of a charmed-strange baryon.

Background Human epidermal growth factor 2 (HER2) is a potential driver oncogene. Although HER2-targeted precision therapy has been tested in non-small cell lung cancer (NSCLC), the demographic characteristics of HER2-positive NSCLC have not been systematically defined. Methods Patients with pathologically confirmed stage IIIB/IV or recurrent NSCLC, Eastern Cooperative Oncology Group performance status 0 to 2, were prospectively registered. HER2 immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assays were performed to screen patients. HER2 mutations were identified by using direct gene sequencing. The aim of this study was to clarify the frequency, characteristics, and outcome of HER2-positive NSCLC. HER2 was defined as positive if the tumor harbored IHC3+, IHC2+/FISH+, or exon 20 insertion mutations. Results Of the 1,126 tumors screened, 34 (3.0%) were IHC3+, and 34 (3.0%) were IHC2+/FISH+. Among the 724 epidermal growth factor receptor wild-type tumors, 21 (2.9%) were HER2-mutant tumors, including A775-G776insYVMA (n = 15). Interestingly, the IHC3+ tumors and mutant tumors were entirely exclusive. Female patients had HER2-mutant tumors more frequently, whereas both IHC3+ and IHC2+/FISH+ tumors were detected more often in male subjects and smokers. Patients with an HER2-aberrant tumor had a significantly worse prognosis than those with epidermal growth factor receptor-positive and anaplastic lymphoma kinase-positive tumors, possibly due to the low proportion that received HER2-targeted therapies (n = 15 [26%]) and low response rates of 0% and 14% in patients with HER2-overexpressing and HER2-mutant tumors, respectively. Conclusions This prospective large-scale cohort study is the first to show comprehensively the frequency and clinical demographic characteristics of those with HER2-positive advanced lung tumors in detail, providing critical historical data for future drug development against HER2-positive NSCLC. Future treatment strategies would be developed stratified according to the types of HER2 aberrations. Trial Registry UMIN Registration No. 000017003; URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000019691

In this work, the MgO-CO2 working pair has been adapted for thermochemical energy storage (TCES) at medium temperatures by the MgO modification with inorganic salts to promote the TCES dynamics. Brief screening of modifying salts showed that lithium acetate (LiOAc) and mixed lithium-potassium nitrate (Li0.42K0.58NO3) additives could considerably promote the MgO carbonation at P(CO2) ≤10 bar and T ≥300 °C. The de- and re-carbonation kinetics, as well as cycling stability of the doped MgO/MgCO3, was reported to outline possible TCES operating conditions (T = 280 °C–380 °C, P(CO2) = 0–1 bar). The heat storage capacity of the salt-promoted MgO was estimated to be 1.6 GJ/m3. A concept of chemical heat pump utilizing the MgO-CO2 working pair was discussed. The salt-promoted MgO-CO2 working pair was concluded to be promising for TCES.

Recipients of organ transplants are immunosuppressed and at high risk of oral infection. Oral diseases are often neglected compared with infections of other organs that typically confer higher morbidity. However, severe local symptoms hinder oral intake, decrease quality of life, and are sometimes lethal. Here we describe a case of a 57-year-old woman who developed recurrent aphthous stomatitis after kidney transplantation; the cause of the infection was complex and included cytomegalovirus, herpes simplex virus, and Candida species. Since misdiagnosis of oral diseases impairs patient quality of life and increases morbidity, clinicians should be aware of possible etiologies of oral infections in renal transplant recipients.

We observed a distinct peak in the Λp invariant mass spectrum of He 3 ( K − , Λ p ) n , well below m K + 2 m p , i.e., the mass threshold of the K − to be bound to two protons. By selecting a relatively large momentum-transfer region q = 350 ∼ 650 MeV/c, one can kinematically separate the peak from the quasi-free process, K ‾ N → K ‾ N followed by the non-resonant absorption by the two spectator-nucleons K ‾ N N → Λ N . We found that the simplest fit to the observed peak gives us a Breit–Wigner pole position at B Kpp = 47 ± 3 ( s t a t . ) − 6 + 3 ( s y s . ) MeV having a width Γ Kpp = 115 ± 7 ( s t a t . ) − 20 + 10 ( s y s . ) MeV, and the S-wave Gaussian reaction form-factor parameter Q Kpp = 381 ± 14 ( s t a t . ) − 0 + 57 ( s y s . ) MeV/c, as a new form of the nuclear bound system with strangeness – “ K − p p ”.

The effect of romosozumab is affected by previous osteoporosis treatment. Here we showed that the duration of the previous treatment just before romosozumab affects the therapeutic effect of romosozumab. Using denosumab and oral bisphosphonates for more than 1 year attenuates the effect of romosozumab.As an anti-sclerostin antibody, romosozumab suppresses bone resorption and stimulates bone formation. We investigated whether the effectiveness of 12 months of romosozumab treatment depended on the duration of previous treatment with teriparatide, denosumab, or oral bisphosphonates.In total, 259 osteoporosis patients received subcutaneous injections of romosozumab (210 mg) every 4 weeks during 2019 and 2020. This study was designed as a pre-post comparison. The end points were the percent changes of bone mineral density (BMD) after 12 months of romosozumab treatment. The patients were divided into seven groups depending on the type and duration of previous treatment before starting romosozumab as follows: non-previous treatment group, change from teriparatide used for 1 year or less/more than 1 year, change from denosumab used for 1 year or less/more than 1 year, and change from oral bisphosphonates used for 1 year or less/more than 1 year.The effects of previous treatment with teriparatide on the effectiveness of 12-month romosozumab did not clearly depend on the duration of treatment (p 0.05). In contrast, the effects of previous treatments with denosumab or oral bisphosphonates on the effectiveness of 12-month romosozumab depended on the previous treatment duration, which was reflected by the differences in percent change of the spine BMD (both p 0.05), however, there were no significant differences in the percent change of the total hip BMD (both p 0.05).The duration of the previous treatment affected the effectiveness of romosozumab. Using denosumab and oral bisphosphonate for more than 1 year attenuated the effect of romosozumab.

International Ocean Discovery Program (IODP) Expedition 382, Iceberg Alley and Subantarctic Ice and Ocean Dynamics, investigated the long-term climate history of Antarctica, seeking to understand how polar ice sheets responded to changes in insolation and atmospheric CO2 in the past and how ice sheet evolution influenced global sea level and vice versa. Five sites (U1534–U1538) were drilled east of the Drake Passage: two sites at 53.2°S at the northern edge of the Scotia Sea and three sites at 57.4°–59.4°S in the southern Scotia Sea. We recovered continuously deposited late Neogene sediments to reconstruct the past history and variability in Antarctic Ice Sheet (AIS) mass loss and associated changes in oceanic and atmospheric circulation. The sites from the southern Scotia Sea (Sites U1536–U1538) will be used to study the Neogene flux of icebergs through “Iceberg Alley,” the main pathway along which icebergs calved from the margin of the AIS travel as they move equatorward into the warmer waters of the Antarctic Circumpolar Current (ACC). In particular, sediments from this area will allow us to assess the magnitude of iceberg flux during key times of AIS evolution, including the middle Miocene glacial intensification of the East Antarctic Ice Sheet, the mid-Pliocene warm period, the late Pliocene glacial expansion of the West Antarctic Ice Sheet, the mid-Pleistocene transition (MPT), and the “warm interglacials” and glacial terminations of the last 800 ky. We will use the geochemical provenance of iceberg-rafted detritus and other glacially eroded material to determine regional sources of AIS mass loss. We will also address interhemispheric phasing of ice sheet growth and decay, study the distribution and history of land-based versus marine-based ice sheets around the continent over time, and explore the links between AIS variability and global sea level. By comparing north–south variations across the Scotia Sea between the Pirie Basin (Site U1538) and the Dove Basin (Sites U1536 and U1537), Expedition 382 will also deliver critical information on how climate changes in the Southern Ocean affect ocean circulation through the Drake Passage, meridional overturning in the region, water mass production, ocean–atmosphere CO2 transfer by wind-induced upwelling, sea ice variability, bottom water outflow from the Weddell Sea, Antarctic weathering inputs, and changes in oceanic and atmospheric fronts in the vicinity of the ACC. Comparing changes in dust proxy records between the Scotia Sea and Antarctic ice cores will also provide a detailed reconstruction of changes in the Southern Hemisphere westerlies on millennial and orbital timescales for the last 800 ky. Extending the ocean dust record beyond the last 800 ky will help to evaluate dust-climate couplings since the Pliocene, the potential role of dust in iron fertilization and atmospheric CO2 drawdown during glacials, and whether dust input to Antarctica played a role in the MPT. The principal scientific objective of Subantarctic Front Sites U1534 and U1535 at the northern limit of the Scotia Sea is to reconstruct and understand how intermediate water formation in the southwest Atlantic responds to changes in connectivity between the Atlantic and Pacific basins, the “cold water route.” The Subantarctic Front contourite drift, deposited between 400 and 2000 m water depth on the northern flank of an east–west trending trough off the Chilean continental shelf, is ideally situated to monitor millennial- to orbital-scale variability in the export of Antarctic Intermediate Water beneath the Subantarctic Front. During Expedition 382, we recovered continuously deposited sediments from this drift spanning the late Pleistocene (from ~0.78 Ma to recent) and from the late Pliocene (~3.1–2.6 Ma). These sites are expected to yield a wide array of paleoceanographic records that can be used to interpret past changes in the density structure of the Atlantic sector of the Southern Ocean, track migrations of the Subantarctic Front, and give insights into the role and evolution of the cold water route over significant climate episodes, including the most recent warm interglacials of the late Pleistocene and the intensification of Northern Hemisphere glaciation.

The COBAND is a project of an experimental search for the cosmic background neutrino decay [1] – [9] . The existence of the cosmic background neutrino is predicted as a relic of the big bang in the theoretical cosmology. Since the neutrino is found to have mass generations and mixing between them, a heavier neutrino is possible to decay to a lighter neutrino with a far-infrared photon, even though its lifetime is expected to be much longer than the age of the universe [10] . However, neither the cosmic background neutrino nor the neutrino decay is yet established experimentally. Only a lower limit in the order of 10 12 years is given on the heaviest neutrino lifetime. We, thus, search for photons which come from the cosmic background neutrino decays. The photons from the cosmic background neutrino decays are expected to shape a spectrum of a unique signature with a sharp edge at a wavelength of around 50μm depending on the heaviest neutrino mass. To identify the signature against the overwhelming zodiacal emission foreground as well as the cosmic infrared background, the photodetectors are required to have an ability to measure the FIR spectrum around 50pm with sufficient precision. Thus, we aim at developing a photodetector with capability of FIR photon-by-photon spectrometry. We employ superconducting tunnel junction (STJ) sensors in combination with cryogenic amplifiers for signal readout to maximize the potential of STJ.

We report measurements of the branching fractions of singly Cabibbo-suppressed decays Λc+→pη and Λc+→pπ0 using the full Belle data sample corresponding to an integrated luminosity of 980.6 fb-1. The data were collected by the Belle detector at the KEKB e+e- asymmetric energy collider. A clear Λc+ signal is seen in the invariant mass distribution of pη. The fitted number of signal events of the Λc+→pη process is 7734±263; from this, we measure the ratio of branching fractions B(Λc+→pη)/B(Λc+→pK-π+)=[2.258±0.077(stat)±0.122(syst)]×10-2, from which we infer the branching fraction B(Λc+→pη)=[1.42±0.05(stat)±0.11(syst)]×10-3. In addition, no significant signal for Λc+→pπ0 is found, so an upper limit on the branching fraction of B(Λc+→pπ0)

A neutron decays into a proton, an electron, and an anti-neutrino through the beta-decay process. The decay lifetime ($\sim$880 s) is an important parameter in the weak interaction. For example, the neutron lifetime is a parameter used to determine the |$V_{\rm ud}$| parameter of the CKM quark mixing matrix. The lifetime is also one of the input parameters for the Big Bang Nucleosynthesis, which predicts light element synthesis in the early universe. However, experimental measurements of the neutron lifetime today are significantly different (8.4 s or 4.0$\sigma$) depending on the methods. One is a bottle method measuring surviving neutron in the neutron storage bottle. The other is a beam method measuring neutron beam flux and neutron decay rate in the detector. There is a discussion that the discrepancy comes from unconsidered systematic error or undetectable decay mode, such as dark decay. A new type of beam experiment is performed at the BL05 MLF J-PARC. This experiment measured neutron flux and decay rate simultaneously with a time projection chamber using a pulsed neutron beam. We will present the world situation of neutron lifetime and the latest results at J-PARC., Comment: 8 pages, 6 figures, Proceedings of J-PARC Symposium 2019

We report the first evidence for $X(3872)$ production in two-photon interactions by tagging either the electron or the position in the final state, exploring the highly virtual photon region. The search is performed in $e^+e^- \rightarrow e^+e^-J/\psi\pi^+\pi^-$, using 825 fb$^{-1}$ of data collected by the Belle detector operated at the KEKB $e^+e^-$ collider. We observe three $X(3872)$ candidates with an expected background of $0.11\pm 0.10$ events, with a significance of 3.2$\sigma$. We obtain an estimated value for $\tilde{\Gamma}_{\gamma\gamma}{\cal B}(X(3872)\rightarrow J/\psi\pi^+\pi^-$) assuming the $Q^2$ dependence predicted by a $c\bar{c}$ meson model, where $-Q^2$ is the invariant mass-squared of the virtual photon. No $X(3915)\rightarrow J/\psi\pi^+\pi^-$ candidates are found.

Using data samples of 89.5 and 711 fb^{-1} recorded at energies of sqrt[s]=10.52 and 10.58 GeV, respectively, with the Belle detector at the KEKB e^{+}e^{-} collider, we report measurements of branching fractions of semileptonic decays Ξ_{c}^{0}→Ξ^{-}ℓ^{+}ν_{ℓ} (ℓ=e or μ) and the CP-asymmetry parameter of Ξ_{c}^{0}→Ξ^{-}π^{+} decay. The branching fractions are measured to be B(Ξ_{c}^{0}→Ξ^{-}e^{+}ν_{e})=(1.31±0.04±0.07±0.38)% and B(Ξ_{c}^{0}→Ξ^{-}μ^{+}ν_{μ})=(1.27±0.06±0.10±0.37)%, and the decay parameter α_{Ξπ} is measured to be 0.63±0.03±0.01 with much improved precision compared with the current world average. The corresponding ratio B(Ξ_{c}^{0}→Ξ^{-}e^{+}ν_{e})/B(Ξ_{c}^{0}→Ξ^{-}μ^{+}ν_{μ}) is 1.03±0.05±0.07, which is consistent with the expectation of lepton flavor universality. The first measured asymmetry parameter A_{CP}=(α_{Ξ^{-}π^{+}}+α_{Ξ[over ¯]^{+}π^{-}})/(α_{Ξ^{-}π^{+}}-α_{Ξ[over ¯]^{+}π^{-}})=0.024±0.052±0.014 is found to be consistent with zero. The first and the second uncertainties above are statistical and systematic, respectively, while the third ones arise due to the uncertainty of the Ξ_{c}^{0}→Ξ^{-}π^{+} branching fraction.

Ehrlichiosis, caused by Gram-negative bacteria of the genus Ehrlichia , is considered an emerging infectious disease due to the increasing number of reported cases. Symptoms are non-specific and occur within 1 to 2 weeks following the bite of an infected tick. Confirmatory laboratory diagnostic methods vary in sensitivity and specimen requirements, which can lead to delayed diagnosis. PCR testing serves as an efficient approach to Ehrlichia confirmation in the acute stage of illness. Published assays have been effectively used to detect human ehrlichiosis at limit of detections ranging from 10 to 50 genomic copies (GC) of Ehrlichia DNA. With the discovery of new species capable of human infection, we wanted to develop assays that are sensitive and encompass a wide range of Ehrlichia. Here we developed and validated two sensitive and specific real-time PCR assays (PanE1 and PanE2) for the detection of Ehrlichia species, as well as two real-time PCR assays (ECh2 and ECh4) for the detection of Ehrlichia chaffeensis , specifically. The limit of detection was determined to be 10 GC per reaction with 100% confidence, and as little as 1 GC with lower efficiencies. Accuracy was assessed at 100% correlation. Specificity from exclusivity testing demonstrated that neither the Ehrlichia species assays (n = 60), nor the E. chaffeensis specific assays (n = 64) had cross reactivity with near neighbors or environmental bacteria. A positive predictive value of 100% and a negative predictive value of ≥93% was determined by evaluating banked clinical specimens from 62 patients with the assays. These real-time PCR assays are effective tools to detect human Ehrlichia species during the acute stage of illness. Early detection of Ehrlichia infection by these real-time PCR assays can facilitate diagnosis and treatment.

$\bar K$-nuclear bound systems, kaonic nuclei, have been widely discussed as products of the strongly attractive $\bar K N$ interaction in $I = 0$ channels. Recently, we demonstrated that kaonic nuclei can be produced via in-flight $(K^-,N)$ reactions using the low-momentum DC kaon beam at the J-PARC E15 experiment. We observed the simplest kaonic nuclei, $K^-pp$, having a much deeper binding energy than normal nuclei. For further studies, we have proposed a series of experimental programs for the systematic investigation of light kaonic nuclei, from $\bar K N$ ($\Lambda(1405)$) to $\bar K NNNN$. In the new experiment approved as J-PARC E80, we will measure the $\bar K NNN$ ($A=3$) system as a first step toward a comprehensive study., Comment: 10 pages, 5 figures, proceedings of the 8th Asia-Pacific Conference on Few-Body Problems in Physics (APFB2020), accepted for publication in Fwe-Body Systems

Charged lepton flavor violation is forbidden in the Standard Model but possible in several new physics scenarios. In many of these models, the radiative decays τ± → ℓ±γ (ℓ = e, μ) are predicted to have a sizeable probability, making them particularly interesting channels to search at various experiments. An updated search via τ± → ℓ±γ using full data of the Belle experiment, corresponding to an integrated luminosity of 988 fb−1, is reported for charged lepton flavor violation. No significant excess over background predictions from the Standard Model is observed, and the upper limits on the branching fractions, $$ \mathcal{B} $$ B (τ± → μ±γ) ≤ 4.2 × 10−8 and $$ \mathcal{B} $$ B (τ± → e±γ) ≤ 5.6 × 10−8, are set at 90% confidence level.