Search for Periodic Time Variations of the Solar

We report a search for time variations of the solar ^{8}B neutrino flux using 5804 live days of Super-Kamiokande data collected between May 31, 1996, and May 30, 2018. Super-Kamiokande measured the precise time of each solar neutrino interaction over 22 calendar years to search for solar neutrino flux modulations with unprecedented precision. Periodic modulations are searched for in a dataset comprising five-day interval solar neutrino flux measurements with a maximum likelihood method. We also applied the Lomb-Scargle method to this dataset to compare it with previous reports. The only significant modulation found is due to the elliptic orbit of the Earth around the Sun. The observed modulation is consistent with astronomical data: we measured an eccentricity of (1.53±0.35)%, and a perihelion shift of (-1.5±13.5) days.

Majorana quantization and half-integer thermal quantum Hall effect in a Kitaev spin liquid.

The quantum Hall effect in two-dimensional electron gases involves the flow of topologically protected dissipationless charge currents along the edges of a sample. Integer or fractional electrical conductance is associated with edge currents of electrons or quasiparticles with fractional charges, respectively. It has been predicted that quantum Hall phenomena can also be created by edge currents with a fundamentally different origin: the fractionalization of quantum spins. However, such quantization has not yet been observed. Here we report the observation of this type of quantization of the Hall effect in an insulating two-dimensional quantum magnet1, α-RuCl3, with a dominant Kitaev interaction (a bond-dependent Ising-type interaction) on a two-dimensional honeycomb lattice2-7. We find that the application of a magnetic field parallel to the sample destroys long-range magnetic order, leading to a field-induced quantum-spin-liquid ground state with substantial entanglement of local spins8-12. In the low-temperature regime of this state, the two-dimensional thermal Hall conductance reaches a quantum plateau as a function of the applied magnetic field and has a quantization value that is exactly half of the two-dimensional thermal Hall conductance of the integer quantum Hall effect. This half-integer quantization of the thermal Hall conductance in a bulk material is a signature of topologically protected chiral edge currents of charge-neutral Majorana fermions (particles that are their own antiparticles), which have half the degrees of freedom of conventional fermions13-16. These results demonstrate the fractionalization of spins into itinerant Majorana fermions and Z2 fluxes, which is predicted to occur in Kitaev quantum spin liquids1,3. Above a critical magnetic field, the quantization disappears and the thermal Hall conductance goes to zero rapidly, indicating a topological quantum phase transition between the states with and without chiral Majorana edge modes. Emergent Majorana fermions in a quantum magnet are expected to have a great impact on strongly correlated quantum matter, opening up the possibility of topological quantum computing at relatively high temperatures.

Assessing parosmia patients: a study on the evaluation method using a self-administered odor questionnaire for parosmia.

BACKGROUND: Parosmia symptoms are difficult to quantify due to their heterogeneity among patients, and thus a clinical challenge. This study aimed to assess parosmia with Self-Administered Odor Questionnaire for Parosmia (SAOQ-P), a modification of the widely used SAOQ in Japan. The primary objective was to assess the effectiveness of SAOQ-P in identifying parosmia symptoms and its potential integration into the clinical assessment process. The study also explored traditional olfactory test differences between patients with and without parosmia. METHODS: Patients at Jikei Smell Clinic that presented between May 2022 and November 2022 were recruited and administered the SAOQ-P, which had an added question about changes in the perception of 20 daily odors compared to the original SAOQ. Traditional olfactory tests utilized T&T olfactometry and Open Essence. RESULTS: Of 279 patients, 81 had parosmia, while 198 did not exhibit parosmic symptoms. Parosmia prevalence was influenced by the cause of olfactory dysfunction, with post-infectious and post-COVID-19 patients showing higher parosmia rates. Among parosmia patients, 87% reported changes in their perception of at least one odor assessed by SAOQ-P, with coffee, stool, and perfume most commonly affected. Traditional olfactory tests showed no significant differences between parosmia and non-parosmia groups. The number of odors causing parosmia was negatively correlated with age. CONCLUSION: SAOQ-P offers a promising approach to assess and quantify parosmia symptoms, seamlessly integrating into clinical assessments. SAOQ-P identified parosmia in 87% of patients and revealed insights into triggering factors. Traditional olfactory tests' limitations underscore the need for more accurate, patient-centric diagnostic approaches for parosmia.

Search for Cosmic-Ray Boosted Sub-GeV Dark Matter Using Recoil Protons at Super-Kamiokande.

We report a search for cosmic-ray boosted dark matter with protons using the 0.37 megaton×years data collected at Super-Kamiokande experiment during the 1996-2018 period (SKI-IV phase). We searched for an excess of proton recoils above the atmospheric neutrino background from the vicinity of the Galactic Center. No such excess is observed, and limits are calculated for two reference models of dark matter with either a constant interaction cross section or through a scalar mediator. This is the first experimental search for boosted dark matter with hadrons using directional information. The results present the most stringent limits on cosmic-ray boosted dark matter and exclude the dark matter-nucleon elastic scattering cross section between 10^{-33}cm^{2} and 10^{-27}cm^{2} for dark matter mass from 1 MeV/c^{2} to 300 MeV/c^{2}.

Erratum: Search for Cosmic-Ray Boosted Sub-GeV Dark Matter Using Recoil Protons at Super-Kamiokande [Phys. Rev. Lett. 130, 031802 (2023)].

This corrects the article DOI: 10.1103/PhysRevLett.130.031802.

Analysis of COVID-19 mRNA Vaccine-induced Mouth Ulcers Using the Japanese Adverse Drug Event Report Database.

There are case reports of mouth ulcers caused by the coronavirus disease 2019 (COVID-19) messenger ribonucleic acid (mRNA) vaccine; however, the actual number and characteristics of cases are unknown. Therefore, we examined this issue using the Japanese Adverse Drug Event Report (JADER), a large Japanese database. We calculated the reported odds ratio (ROR) of drugs that may be specifically associated with mouth ulcers and assumed that a signal was present if the lower limit of the calculated ROR's 95% confidence interval (CI) was > 1. In addition, the time to symptom onset after administration of the COVID-19 mRNA and influenza HA vaccines was investigated. We found that the JADER database contained 4,661 mouth ulcer cases between April 2004 and March 2022. The COVID-19 mRNA vaccine was the eighth most common causative drug for mouth ulcers, with 204 reported cases. The ROR was 1.6 (95% CI, 1.4-1.9) and a signal was detected. There were 172 mouthulcer cases associated with the Pfizer-BioNTech's COVID-19 mRNA vaccine, 76.2% of which were female. The outcome was no unrecovered cases with the influenza HA vaccine, whereas the COVID-19 mRNA vaccine showed unrecovered cases (Pfizer-BioNTech: 12.2%, Moderna: 11.1%). The median time-to-onset of the mouth ulcers was two days for the COVID-19 mRNA vaccine and one day for the influenza HA vaccine, indicating that mouth ulcers caused by the COVID-19 mRNA vaccine were delayed adverse events. In this study, the COVID-19 mRNA vaccine was shown to cause mouth ulcers in a Japanese population.

Effect of acid suppressant medications on the laxative action of magnesium preparations in patients with opioid-induced constipation: A pharmacovigilance analysis of the FDA Adverse Event Reporting System.

Objective: Magnesium oxide is widely used for treating opioid-induced constipation, a serious analgesic-associated problem. Opioid analgesic users are often prescribed non-steroidal anti-inflammatory drugs, which are sometimes combined with acid suppressants to prevent gastrointestinal adverse events. Magnesium preparations combined with acid suppressants may diminish magnesium preparations' laxative effect. This study was aimed at evaluating the effect of magnesium preparations combined with acid suppressants on the incidence of opioid-induced constipation by using the Food and Drug Administration Adverse Event Reporting System. Methods: Adverse events were defined per the Medical Dictionary for Regulatory Activities; the term 'constipation (preferred term code: 10010774)' was used for analysis. After adjusting for patient background factors using propensity score matching, acid suppressants' effect on constipation incidence was evaluated in opioid users prescribed magnesium preparations alone as laxatives by using a test for independence. Key Findings: The Food and Drug Administration Adverse Event Reporting System contains 14,475,614 reports for January 2004 to December 2021. Significantly increased constipation incidence was related to magnesium preparations combined with acid suppressants, especially proton pump inhibitors (P < 0.0001, McNemar's test). Conclusion: Magnesium preparations combined with acid suppressants may diminish magnesium preparations' laxative effect; healthcare professionals should pay attention to this issue.

Occurrence of voriconazole-induced cutaneous squamous cell carcinoma in Japan: data mining from different national pharmacovigilance databases.

Long-term voriconazole use may increase the risk of cutaneous squamous cell carcinoma (cSCC), especially in immunocompromised patients. However, relatively little is known regarding voriconazole-induced cSCC in Japan. Thus, the purpose of this study was to evaluate the association between voriconazole use and cSCC in Japan using different national pharmacovigilance databases. First, using the Japanese Adverse Drug Event Report (JADER) database, we evaluated the association between voriconazole use and cSCC in Japan. Second, using the U. S. Food and Drug Administration Adverse Event Reporting System (FAERS) database, we examined regional differences in the occurrence of voriconazole-induced cSCC between Japan and other countries. We calculated reporting odds ratios (RORs) as disproportionality analysis to evaluate voriconazole-induced cSCC. In this study, cases in which one or more of "Bowen's disease", "Carcinoma in situ of skin", "Keratoacanthoma", "Squamous cell carcinoma in skin", or "Squamous cell carcinoma" were reported as adverse events were considered to be cSCC cases. The analysis based on the JADER database showed an association between voriconazole use and cSCC in Japan, with a ROR (95% confidence interval) of 35.37 (25.60-48.87). Further, the analysis based on the FAERS database revealed that signals were detected in Japan as well as in Western countries and Australia. This study is the first in which the association between voriconazole use and cSCC in Japan is assessed using national pharmacovigilance databases. Healthcare providers need to be fully aware of the potential for cSCC development owing to voriconazole use and in all countries, including Japan, ensure careful follow-up of patients' skin.

Utility of the Berlin Initiative Study-1 equation for the prediction of serum vancomycin concentration in elderly patients aged 75 years and older.

Accurate assessment of renal function is essential for determining serum vancomycin (VCM) concentration. Creatinine clearance (Ccr)-calculated using the Cockcroft and Gault (CG) equation-can be used to evaluate renal function for determining VCM dosage. However, Ccr-based evaluation may not be an accurate representation of the renal function in the elderly. Herein, we examine the effectiveness of estimated glomerular filtration rate (eGFR) calculated using the Berlin Initiative Study-1 (BIS1) equation, for predicting the serum VCM concentration. Herein, we retrospectively analyzed patients (aged ≥ 75 years) who had received VCM. Serum VCM concentration was predicted based on Ccr and eGFR. eGFR was calculated using the Japanese equation for eGFR (eGFRJAP), Modification of Diet in Renal Disease (MDRD) equation (eGFRMDRD), chronic kidney disease epidemiology collaboration (CKD-EPI) equation (eGFRCKD-EPI), and BIS1 equation (eGFRBIS1). The predicted serum VCM concentration was compared with the measured values. Prediction bias, accuracy, and precision were evaluated by calculating the mean prediction error (ME), mean absolute prediction error (MAE), and root mean squared prediction error (RMSE). Our results showed that the ME between the measured and the predicted values calculated using Ccr and each eGFR was the largest and smallest when calculated based on Ccr and eGFRMDRD, respectively. MAE and RMSE were the largest and smallest when calculated based on Ccr and eGFRBIS1, respectively. A significant difference was observed in the MAE associated with eGFRJAP, eGFRMDRD, and eGFRCKD-EPI compared to that associated with eGFRBIS1. In conclusion, our results suggest that the BIS1 equation might be useful for determining the VCM dosage in the elderly.

Nivolumab with carboplatin, paclitaxel, and bevacizumab for first-line treatment of advanced nonsquamous non-small-cell lung cancer.

BACKGROUND: This international, randomized, double-blind phase III study (ONO-4538-52/TASUKI-52) evaluated nivolumab with bevacizumab and cytotoxic chemotherapy as first-line treatment for nonsquamous non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between June 2017 and July 2019, this study enrolled treatment-naïve patients with stage IIIB/IV or recurrent nonsquamous NSCLC without sensitizing EGFR, ALK, or ROS1 alterations. They were randomly assigned in a 1 : 1 ratio to receive nivolumab or placebo in combination with carboplatin, paclitaxel, and bevacizumab every 3 weeks for up to six cycles, followed by nivolumab/placebo with bevacizumab until progressive disease or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) assessed by an independent radiology review committee (IRRC). RESULTS: Overall, 550 patients from Japan, Korea, and Taiwan were randomized; of these patients, 273 and 275 received the nivolumab and placebo combinations, respectively. In the present preplanned interim analysis with a median follow up of 13.7 months, the IRRC-assessed median PFS was significantly longer in the nivolumab arm than in the placebo arm (12.1 versus 8.1 months; hazard ratio 0.56; 96.4% confidence interval 0.43-0.71; P < 0.0001). The PFS benefit was observed across all patients with any programmed death-ligand 1 (PD-L1) expression levels including PD-L1-negative patients. The IRRC-assessed objective response rates were 61.5% and 50.5% in the nivolumab and placebo arms, respectively. The incidence of treatment-related adverse events of grade 3 or 4 was comparable between the two arms; treatment-related adverse events leading to death were observed in five and four patients in the nivolumab and placebo arms, respectively. CONCLUSION: The TASUKI-52 regimen should be considered a viable new treatment strategy for treatment-naïve patients with advanced nonsquamous NSCLC.

Time-to-onset of diabetes with everolimus use: analysis of a spontaneous reporting system database.

The incidence of hyperglycemia and diabetes induced by everolimus has been shown in previous studies. Our study analyzed diabetes time-to-onset profiles after everolimus use in patients who underwent transplantation and patients with cancer. Using data from April 2007 to December 2018 in the Japanese Adverse Drug Event Report database, the reports with everolimus were classified according to its use as an immunosuppressant or anticancer drug. The median (25%-75%) days of diabetes time-to-onset in patients who underwent transplantation and patients with cancer were 172 (56-315) and 32 (18.5-57), respectively. There were no significant variations among patients with breast cancer, neuroendocrine tumor, and renal cell carcinoma. By conducting a Weibull shape parameter test, the lower limits of the 95% confidence intervals of the shape parameter ß values for the indications of the cancer types were >1, indicating the wear out failure type profile, whereas those for transplantation data indicated a random failure type profile. The diabetes time-to-onset profiles after everolimus use differed between usage as an anticancer drug and immunosuppressant and there were no significant variations among the type of cancer. It was suggested that the incidence of diabetes should be monitored for 1-2 months in patients with cancer, whereas continuous monitoring is needed in patients who undergo transplantation.

Cartilage and subchondral bone distributions of the distal radius: a 3-dimensional analysis using cadavers.

OBJECTIVE: To quantify the spatial distributions of cartilage and subchondral bone thickness of the distal radius. DESIGN: Using 17 cadaveric wrists, three types of 3-dimensional models were created: a cartilage-bone model, obtained by laser scanning; a bone model, rescanned after dissolving the cartilage; and a subchondral bone model, obtained using computed tomography. By superimposing the bone model onto the cartilage-bone and the subchondral bone models, the cartilage and subchondral bone thickness were determined. Measurements along with the spatial distribution were made at fixed anatomic points including the scaphoid and lunate fossa, sigmoid notch and interfossal ridge, and compared at each of these four regions. RESULTS: Cartilage thickness of the interfossal ridge (0.89 ± 0.23 mm) had a larger average thickness compared to that of the scaphoid fossa (0.70 ± 0.18 mm; p = 0.004), lunate fossa (0.75 ± 0.17 mm; p = 0.044) and sigmoid notch (0.64 ± 0.13 mm; p < 0.001). Subchondral bone was found to be thickest at the scaphoid (2.18 ± 0.72 mm) and lunate fossae (1.94 ± 0.93 mm), which were both thicker than that of sigmoid notch (1.63 ± 1.06 mm: vs scaphoid fossa, p = 0.020) or interfossal ridge (1.54 ± 0.84 mm: vs scaphoid fossa, p = 0.004; vs lunate fossa, p = 0.048). In the volar-ulnar sub-regions of the scaphoid and lunate fossa, the subchondral bone thickened. CONCLUSIONS: Our data can be applied when treating distal radius fractures. Cartilage thickness was less than 1 mm across the articular surface, which may give an insight into threshold for an acceptable range of step-offs. The combined findings of subchondral bone appreciate the importance of the volar-ulnar corner of the distal radius in the volar locking plate fixation.

Morphological characterisation of glial and neuronal tau pathology in globular glial tauopathy (Types II and III).

AIMS: Globular glial tauopathy (GGT) is a new category within the 4-repeat tauopathies that is characterised neuropathologically by tau-positive globular glial inclusions (GGIs), namely, globular oligodendrocytic and astrocytic inclusions (GOIs and GAIs). Occurrence of tau-positive neuronal cytoplasmic inclusions (NCIs) is also a feature. GGT is classified into three pathological subtypes (Types I, II and III). We studied the tau pathology in 6 cases of GGT (Type II, n = 3; Type III, n = 3), with special reference to GAIs and NCIs. METHODS: Neuropathological examinations were conducted, along with immunohistochemistry, morphometry and three-dimensional imaging, and biochemical and genetic analysis of tau. RESULTS: The cortical GAIs in Type II and those in Type III were distinguishable from each other. In the motor cortex, GAIs were much more numerous in Type III than in Type II. Prominent occurrence of perikaryal globular structures was a feature of GAIs in Type III. By contrast, prominent occurrence of radiating process-like structures was a feature of GAIs in Type II. Overall, the GAIs were significantly smaller in Type III than in Type II. NCIs were divisible into three subgroups in terms of shape: diffuse granular, thick cord-like, and round/horseshoe-shaped structures. In all cases, NCIs were a feature of the upper and lower motor neurons. Interestingly, the round/horseshoe-shaped NCIs were observed only in Type III cases. CONCLUSIONS: These findings, which characterised GAIs and NCIs, indicated that Type II and Type III constitute two distinct pathological subtypes, and also further strengthen the concept of GGT as a distinct entity.

UV-pumped visible Tb3+-lasers.

We report on continuous-wave laser operation of Tb3+:LiLuF4 under UV pumping. More than five times higher absorption cross sections in the UV allow for shorter gain media, which are required for future high-power diode pumping. The cross-relaxation process is found to efficiently populate the upper laser level 5D4 at doping concentrations typically used in Tb3+-doped gain media. Pumping with a frequency doubled Ti:sapphire laser at 359 nm enables laser operation in the green and yellow spectral range with slope efficiencies of 41% and 20%, respectively, at optical-to-optical efficiencies a factor of two higher than under cyan-blue pumping.

Particle-Hole Symmetry Breaking in a Spin-Dimer System TlCuCl_{3} Observed at 100 T.

The entire magnetization process of TlCuCl_{3} has been experimentally investigated up to 100 T employing the single-turn technique. The upper critical field H_{c2} is observed to be 86.1 T at 2 K. A convex slope of the M-H curve between the lower and upper critical fields (H_{c1} and H_{c2}) is clearly observed, which indicates that a particle-hole symmetry is broken in TlCuCl_{3}. By quantum Monte Carlo simulation and the bond-operator theory method, we find that the particle-hole symmetry breaking results from strong interdimer interactions.

Cross Sections and Asymmetry Parameters for Formic Acid in the Vacuum-Ultraviolet Energy Range.

We present an experimental and theoretical investigation of the photon interaction with formic acid in the vacuum-ultraviolet energy range. The absolute absorption cross sections and ionization efficiencies were measured in the 11.2-21.4 and 13.5-21.4 eV ranges, respectively, using a double-ion chamber technique. Photoionization and neutral-decay cross sections were derived from these results. From the present ionization cross sections and previously reported ionic dissociative branching ratios, the partial cross sections for dissociating processes were obtained. Theoretically, the photoionization cross sections and the asymmetry parameters of the photoelectron angular distributions for ionization out of the six outermost valence orbitals (10a', 2a″, 9a', 1a″, 8a', and 7a') were obtained in the energy range from near-threshold to 35 eV. For that, the Padé approximant technique along with the single-center partial-wave expansion method was applied to solve the Lippmann-Schwinger equation in the static-exchange-polarization level of approximation. This is the first theoretical investigation concerning the determination of the asymmetry parameters and photoionization cross sections of formic acid in the vacuum-ultraviolet energy range. Comparison is made between our results and the previous ones.

In-vitro fertilisation-embryo-transfer complicates the antenatal diagnosis of placenta accreta spectrum using MRI: a retrospective analysis.

AIM: To evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) for the antenatal diagnosis of placenta accreta spectrum (PAS). MATERIALS AND METHODS: Data from 95 patients with placenta previa or low-lying placenta who underwent MRI at Osaka University Hospital for the antenatal diagnosis of PAS between January 2013 and December 2018 were reviewed retrospectively. The antenatal MRI signs suggesting PAS were assessed. Patients were divided into two groups depending on whether they were diagnosed with PAS. Factors that affected PAS diagnosis were identified using multivariate analysis. RESULTS: The diagnostic accuracy of MRI for detecting PAS was as follows: 71.4% sensitivity, 96.4% specificity, and area under the curve (AUC) of 0.839 (95% confidence interval [CI]: 0.73-0.91). The diagnostic accuracy was lower in patients with in-vitro fertilisation with embryo transfer (IVF-ET): 22.2% sensitivity, 93.3% specificity, and AUC=0.578 (95% CI: 0.417-0.724). On multivariate analysis, only IVF-ET showed a significant association with false-positive or -negative MRI diagnosis of PAS (adjusted odds ratio: 26.5; 95% CI: 2.42-289.4; p=0.007). CONCLUSION: IVF-ET affects the antenatal diagnosis of PAS using MRI.

Cartilage wear patterns in severe osteoarthritis of the trapeziometacarpal joint: a quantitative analysis.

OBJECTIVE: The present quantitative study aimed to assess the three-dimensional (3-D) cartilage wear patterns of the first metacarpal and trapezium in the advanced stage of osteoarthritis (OA) and compare cartilage measurements with radiographic severity. DESIGN: Using 19 cadaveric trapeziometacarpal (TMC) joints, 3-D cartilage surface models of the first metacarpal and trapezium were created with a laser scanner, and 3-D bone surface model counterparts were similarly created after dissolving the cartilage. These two models were superimposed, and the interval distance on the articular surface as the cartilage thickness was measured. All measurements were obtained in categorized anatomic regions on the articular surface of the respective bone, and we analyzed the 3-D wear patterns on the entire cartilage surface. Furthermore, we compared measurements of cartilage thickness with radiographic OA severity according to the Eaton grading system using Pearson correlation coefficients (r). RESULTS: In the first metacarpal, the cartilage thickness declined volarly (the mean cartilage thickness of the volar region was 0.32 ± 0.16 mm, whereas that of the dorsal region was 0.53 ± 0.18 mm). Conversely, the cartilage evenly degenerated throughout the articular surface of the trapezium. Measurements of the categorized regions where cartilage thinning was remarkable exhibited statistical correlations with radiographic staging (r = -0.48 to -0.72). CONCLUSIONS: Our findings indicate that cartilage wear patterns differ between the first metacarpal and trapezium in the late stage of OA. There is a need for further studies on cartilage degeneration leading to symptomatic OA in the TMC joint.

Photoabsorption and Photoionization Cross Sections of Pyridine in the Vacuum-Ultraviolet Energy Range.

We have performed an experimental investigation into the interaction of vacuum-ultraviolet synchrotron radiation with pyridine molecules in the gas phase. Specifically, a double-ion chamber spectrometer was used to measure the absolute photoabsorption cross sections and the photoionization quantum yields from the ionization threshold to 21.5 eV. Moreover, photoionization and neutral-decay cross sections in absolute scale were derived from these data. In addition, the fragmentation pattern was investigated as a function of the photon energy by using a time-of-flight mass spectrometer and the photoelectron-photoion coincidence technique. Thus, the absolute partial ionization cross sections for each ionic fragment were obtained. Comparisons are made with experimental data available in the literature.