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We present a measurement of the Cabibbo-Kobayashi-Maskawa unitarity triangle angle ϕ 3 (also known as γ) using a model-independent Dalitz plot analysis of B + → D ( K S 0 $$ {K}_S^0 $$ h + h − )h +, where D is either a D 0 or D ¯ $$ \overline{D} $$ 0 meson and h is either a π or K. This is the first measurement that simultaneously uses Belle and Belle II data, combining samples corresponding to integrated luminosities of 711 fb −1 and 128 fb −1, respectively. All data were accumulated from energy-asymmetric e + e − collisions at a centre-of-mass energy corresponding to the mass of the Υ(4S) resonance. We measure ϕ 3 = (78.4 ± 11.4 ± 0.5 ± 1.0)°, where the first uncertainty is statistical, the second is the experimental systematic uncertainty and the third is from the uncertainties on external measurements of the D-decay strong-phase parameters.

Background Endogenous sex hormones associated with both the left atrial (LA) and left ventricular (LV) structures in peri-menopausal women, but the association of menopause status with left atrioventricular coupling is not well established. Purpose To assess the prognostic value of a left atrioventricular coupling index (LACI) in pre- and post-menopausal women without a history of cardiovascular disease (CVD) at baseline in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods In women participating in the MESA study, the LACI was measured as the ratio of the left atrial (LA) end-diastolic volume to the left ventricular (LV) end-diastolic volume using cardiovascular magnetic resonance (CMR). Cox proportional hazard models were used to assess the association between the LACI and the outcomes of atrial fibrillation (AF), heart failure (HF), and hard CVD defined by myocardial infarction, resuscitated cardiac arrest, stroke, or coronary heart disease death. Results Among the 2,087 women participants (61±10 years), 485 cardiovascular events were observed during the mean follow-up period of 13.2±3.3 years. A higher LACI was independently associated with AF (HR 1.70; 95% CI [1.51–1.90]), HF (HR 1.62; [1.33–1.97]), and hard CVD (HR 1.30; [1.13–1.51], all p Conclusion In a multi-ethnic population of pre- and post-menopausal women, the LACI is an independent predictor of HF, AF, and hard CVD. In both pre- and post-menopausal women, the LACI has an incremental prognostic value for predicting cardiovascular events over traditional risk factors and sex hormone levels. ClinicalTrials: gov Identifier: NCT00005487 Funding Acknowledgement Type of funding sources: None.

Background In clinical practice, we often encounter the patients with sarcoidosis showing relatively high in the normal range of serum angiotensin-converting enzyme (ACE) value. Purpose We aimed to examine the serum ACE value of the patients with sarcoidosis and determine the new cut-off value for detecting the patients with sarcoidosis. Methods and results We retrospectively examined all 3781 subjects (51.1% men, 60.1±17.0 y.o.) in whom ACE was measured for any reasons including suspected sarcoidosis between 2009 and 2020 in our hospital. Of 293 patients with sarcoidosis, 101, 212, 84, and 88 were diagnosed as sarcoidosis in heart, lung, skin, and eyes, respectively. After excluding 477 patients taking ACE inhibitor and/or immunosuppression agent or those with any diseases affecting serum ACE levels, we analyzed 3304 subjects including 215 with sarcoidosis. Serum ACEs were 19.6 IU/L [IQR, 15.1–31.5] in the subjects with sarcoidosis and 10.7 [8.4–16.5] in those without (P Conclusion(s) In the current cut-off value of serum ACE, sensitivity for detecting sarcoidosis was comparatively low, though positive predictive value was low when the new-cut-off value was used in our study. Further examinations may be needed for the patients suspected sarcoidosis with relatively high ACE in the normal range. Funding Acknowledgement Type of funding sources: None.

The disaccharide galactose-α-1,3-galactose (alpha-gal) is expressed in mammals other than humans, apes, and old-world monkeys. In humans, elevated immunoglobulin-E (IgE) antibodies specific for alpha-gal can result in allergic hypersensitivity known as alpha-gal syndrome (AGS). Case reports and series suggest that tick bites can induce alpha-gal specific IgE antibodies.Evaluate tick exposure as a risk factor for AGS and elevated alpha-gal specific IgE (sIgE).We conducted a case-control study comparing AGS patients from a North Carolina allergy clinic with controls who were patients at a nearby internal medicine clinic. Cases and controls were administered a questionnaire to obtain information about demographics, home environment, outdoor activities, and recollection of tick bite. Serum samples taken at the time of enrollment were tested for total IgE, alpha-gal sIgE, and antibodies to other tickborne pathogens.AGS patients were more likely to recall finding a tick on themselves (OR=11.20, 95% CI 4.97-25.15), live near wooded forest (OR=2.27, 95% CI 0.92-5.55), and spend 17 or more hours per week outdoors in wooded areas (OR=5.58, 95% CI 2.56-12.19). AGS patients were also more likely to report 4 or more tick bites (OR=33.05, 95% CI 9.92-155.12) and reactions at the site of tick bites (OR=7.93, 95% CI 3.74-16.80). Elevated alpha-gal sIgE was also observed in 33% of controls and was also associated with tick exposure in the controls (OR=4.25, 95% CI 2.21-8.18).The results define tick bite as a risk factor for AGS and elevated alpha-gal sIgE.

Diabetes mellitus (DM) has wider neurological complications. They include upper gastrointestinal (GI) symptoms, impaired motility, impaired gastric emptying (GE) and diabetic gastroparesis (DG), which are usually found. The patient was a 64-year-old man with type 2 diabetes (T2D) for 22-years. The patient weighed 74 kg with body mass index (BMI) 23.6 kg/m2, hemoglobin A1C (HbA1c) 9.2%, ankle brachial index (ABI) 1.19/1.23, AST 25 U/L(7-38), ALT 23 U/L(4-44), GGT 48 U/L(

We have developed a novel technique for the measurement of the size of avalanche fluctuations of gaseous detectors using a gating device (gating foil) prepared for the time projection chamber in the international linear collider experiment (ILD-TPC). In addition to the gating function, the gating foil is capable of controlling the average fraction of drift electrons detected after gas amplification. The signal charge width and shape (skewness) for electron-ion pairs created by a pulsed UV laser as a function of the transmission rate of the gating foil can be used to determine the relative variance of gas gain for single electrons. We present the measurement principle and the result obtained using a stack of gas electron multipliers (GEMs) operated in a gas mixture of Ar-CF$_4$(3%)-isobutane(2%) at atmospheric pressure. Also discussed is the influence of the avalanche fluctuations on the spatial resolution of the ILD-TPC., 39 pages including 11 figures

The patient is a 56-year old (yo) female with type 2 diabetes mellitus (T2DM). Medical histories include persisting T2DM from 35yo, renal stone at 43yo, hypertension from 45yo, photocoagulation for retinopathy on 54yo. An incidentaloma was found in the left adrenal gland, where endocrinological exams were negative for functional tumor. Her diabetic control situation became worse with HbA1c > 10%, then the treatment has been changed from multiple daily injection (MDI), Dulaglutide to Xultophy which is combined agents of degludec and liraglutide (IDegLira). It was provided 10-18 doses daily, and then glucose variability profile was improved satisfactory, suggesting the dual synergistic effects.

Summary Romosozumab is an effective treatment for spine osteoporosis because it reduces the incidence of new fractures and significantly increases the percent change in the spine BMD at 12 months. The percent change in the spine BMD is higher in patients not previously treated with other anti-osteoporosis medications. Introduction Romosozumab appeared as a new osteoporosis medication in Japan in 2019. It is an anti-sclerostin antibody, which increases bone formation and suppresses bone resorption. The aim of our study was to elucidate the clinical effects, safety, and predictors of the effects of one-year romosozumab treatment. Methods This study was an observational study designed as a pre–post study in 262 patients. Romosozumab (210 mg) was administered subcutaneously once every 4 weeks during 12 months. We focused on incidence of new fractures, safety, bone mineral density (BMD) at the spine and total hip, and bone metabolism markers. Results There were five cases of new fractures during one-year romosozumab treatment. There were no fatal adverse events. Percent changes from baseline in the spine and total hip BMD after 12 months of romosozumab treatment were 10.67% and 2.04%, respectively. Romosozumab had better effects in cases of severe osteoporosis with low spine BMD, high TRACP-5b, and high iP1NP at the start of romosozumab treatment. The percent change in the spine BMD at 12 months was significantly lower in the group transitioning from bisphosphonates than in the group not previously treated with other anti-osteoporosis medications. Conclusion Romosozumab is an effective treatment for spine osteoporosis because it significantly increases the percent change in the spine BMD at 12 months. The percent change in the spine BMD is higher in patients not previously treated with other anti-osteoporosis medications.

Regarding the diet treatment of diabetic nephropathy, protein restriction has been recommended. American Diabetes Association (ADA) proposed protein restriction guidelines in the 2008 edition. However, this comment was deleted in the 2013/2019 edition, because of insufficient evidence. A recent report showed that the intake of plant protein has a protective effect on the decrease of estimated glomerular filtration rate (eGFR), and the intake of animal protein has neither protection nor deterioration. There are controversies about the relationship between protein intake and the reduction of renal function. Further research will be expected for diabetic nephropathy, diabetic kidney disease (DKD), and chronic kidney disease (CKD).

The daily profile of blood glucose can be detected by continuous glucose monitoring (CGM) using FreeStyle Libre. The case was a 51-year-old female with type 2 diabetes mellitus (T2DM) for uncontrolled glucose variability as HbA1c 10.3%. During CGM measurement, diabetic treatment was changed from multiple daily insulin injections (MDI) to Xultophy (insulin degludec and liraglutide). Xultophy starting from 10 to 18 doses has brought the improvement of glucose variability, such as decreased pre-prandial glucose from 268 mg/dL to 101 mg/dL. Consequently, detailed data of glucose variability on Xultophy using CGM would be beneficial and become some reference for further clinical diabetic research.

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Understanding the distribution of pathogens causing acute febrile illness (AFI) is important for clinical management of patients in resource-poor settings. We evaluated the proportion of AFI caused by specific pathogens among outpatients in Bangladesh. During May 2019-March 2020, physicians screened patients aged ≥2 years in outpatient departments of four tertiary level public hospitals. We randomly enrolled patients having measured fever (≥100.4°F) during assessment with onset within the past 14 days. Blood and urine samples were tested at icddr,b through rapid diagnostic tests, bacterial culture, and polymerase chain reaction (PCR). Acute and convalescent samples were sent to the Centers for Disease Control and Prevention (USA) for Rickettsia and Orientia (R/O) and Leptospira tests. Among 690 patients, 69 (10%) had enteric fever (Salmonella enterica serotype Typhi orSalmonella enterica serotype Paratyphi), 51 (7.4%) Escherichia coli, and 28 (4.1%) dengue detected. Of the 441 patients tested for R/O, 39 (8.8%) had rickettsioses. We found 7 (2%) Leptospira cases among the 403 AFI patients tested. Nine patients (1%) were hospitalized, and none died. The highest proportion of enteric fever (15%, 36/231) and rickettsioses (14%, 25/182) was in Rajshahi. Dhaka had the most dengue cases (68%, 19/28). R/O affected older children and young adults (IQR 8–23 years) and was detected more frequently in the 21–25 years age-group (17%, 12/70). R/O was more likely to be found in patients in Rajshahi region than in Sylhet (aOR 2.49, 95% CI 0.85–7.32) between July and December (aOR 2.01, 1.01–5.23), and who had a history of recent animal entry inside their house than not (aOR 2.0, 0.93–4.3). Gram-negative Enterobacteriaceae were the most common bacterial infections, and dengue was the most common viral infection among AFI patients in Bangladeshi hospitals, though there was geographic variability. These results can help guide empiric outpatient AFI management.

Background: Recent diabetic treatments include Insulin Degludec/ liraglutide (IDeg/Lira, Xultophy) in clinical practice. Authors have continued clinical research concerning diabetes, chronic renal failure, dialysis, and others. Subjects and Methods: Ten patients with type 2 diabetes mellitus (T2DM) undergoing hemodialysis were investigated. They showed that ages 74.5 ± 5.9 years, M/F=6/4, BMI 21.1± 3.8kg/m2, hemodialysis duration 8.1 ± 5.7 years. At the beginning, fundamental data were Cre 8.2 ± 1.9 mg/dL, HbA1c 6.5 ± 0.8%. Xultophy was started on 5-12 doses and continued for 6 months with the same or 1-4 increased doses for better glycemic variability. Results: Out of 10 subjects, the changes in HbA1c showed a decrease in 7, stable in 2, and an increase in 1. HbA1c value was 6.2 ± 0.8% in average at 6 months. There were no remarkable adverse effects by Xultophy for 6 months. Discussion and Conclusion: Xultophy was started at 5-12 doses, which were remarkably lower doses than usual doses with satisfactory efficacy. One of the reasons may be from the characteristic of the patients, who were diabetic with undergoing hemodialysis. Another factor is possibly from liraglutide, which has hepatic clearance with potential vascular protective effects. These results are expected to become reference data for future research.

Our 6-month study showed the usefulness of romosozumab for preventing fractures and its safety. It was effective in patients with low baseline spine BMD, high TRACP-5b, and high iP1NP. Percent change from baseline of TRACP-5b and iP1NP after 1 month correlated with that from baseline of BMD after four to 6-month treatment. Romosozumab appeared as a new osteoporosis medication in Japan in 2019. It is an anti-sclerostin antibody which increases bone formation and suppresses bone resorption. In this study, we analyzed the actual clinical effects, adverse effects, and the optimal way to evaluate the treatment. Romosozumab was administered as subcutaneous injection of 210 mg once every 4 weeks. We conducted pre-post study in 185 patients treated for 6 months. We focused on the incidence of new vertebral fractures, safety, bone mineral density (BMD) at the spine and total hip, and bone metabolism markers. We evaluated BMD before romosozumab treatment and after 4 to 6 months and performed the serum analysis before romosozumab treatment, after 1, 3, and 6 months. There was no new fracture during treatment, and there was no fatal adverse event including cardiovascular disease. Since percent changes from baseline of the spine and total hip BMD were 6.34% and 1.53% after 4- to 6-month treatment, the treatment was effective for spine osteoporosis. Tartrate-resistant acid phosphatase 5b (TRACP-5b) and intact type I procollagen N-terminal propeptide (iP1NP) had significant changes during romosozumab treatment (p

Maintenance of muscle mass and protein intake are closely related. Insufficient protein intake in each meal or a total of three meals causes a decrease in muscle mass. For the elderly, protein intake has been insufficient at breakfast and then a large amount of protein is necessary for stimulating muscle protein synthesis. Consequently, there is a need to more actively and consciously take protein in older age. There have been conflicting results concerning the effect of protein restriction diet on glomerular filtration rate (GFR) in patients with chronic kidney disease (CKD) from the data of various meta-analyses. A beneficial effect and also no significant effect was found. One of the perspectives suggested that protein restriction diet may make slower CKD progression in T1DM and non-DM subjects, but not for T2DM patients. However, further studies will be necessary in the future.

Objective Pulmonary arterial hypertension (PAH) is an intractable complication in connective tissue diseases, but the pathological mechanisms responsible for progression remain obscure. This study aims to test whether patient IgG possesses biological activity promoting the migration of pulmonary artery smooth muscle cells (PASMCs). Methods Cell migration was estimated by lamellipodia formation and by utilizing a Boyden chamber method. The specificity of autoantibodies was established by western blotting, ELISA, and immunocytochemistry. The target antigen was investigated by mass spectrometry. Results IgG obtained from a patient with systemic lupus erythematosus (SLE) accompanied by PAH was found to promote lamellipodia formation and migration of PASMCs. The IgG bound to a ∼50 kDa protein expressed on the cell membrane, and in the cytoplasm and nucleus. This molecule was identified as enolase 1. Removal of enolase 1-binding antibodies from the IgG fraction, or treatment of the cells with an enolase inhibitor, significantly suppressed the migration of PASMCs. Conclusion Patients with SLE may possess autoantibodies to enolase 1 which stimulate the migration of PASMCs and are likely to play a role in the progression of PAH.

Funding Acknowledgements Type of funding sources: None. BACKGROUND Recent studies have emphasized the incremental prognostic value of a novel left atrioventricular coupling index (LACI) and its 10-year annual change (ΔLACI) to predict cardiovascular events. However, no study has investigated the potential determinants of this index. PURPOSE To identify the determinants of LACI and ΔLACI, measured by cardiovascular magnetic resonance (CMR), and to better understand the parameters governing this left atrioventricular coupling in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS In the MESA, 2,112 study participants, free of cardiovascular disease at baseline, had LACI assessed by CMR imaging at baseline (LACIBaseline, Exam 1, 2000–2002) and 10 years later (Exam 5, 2010–2012). The LACI was defined as the ratio of left atrium to left ventricular (LV) end-diastolic volumes. Multivariable linear regression analyses were performed, adjusting for traditional risk factors and LV structure, to identify independent determinants of LACIBaseline or ΔLACI. RESULTS In the 2,112 participants (mean age 58.8 ± 9.1 years and 46.6% male), after adjustment for all covariates, age was independently associated with both LACIBaseline (R2 = 0.10) and ΔLACI (R2 = 0.15, both p CONCLUSIONS In a multi-ethnic population, age, sex, ethnicity, diabetes, and a higher body mass index were independent determinants of LACI. LACI was independently associated with LV myocardial fibrosis markers and NT-proBNP levels but not associated with inflammation biomarkers. ClinicalTrials.gov Identifier: NCT00005487 Abstract Figure. Relationship between LACI and Age Abstract Figure. Relationship between LACI and Gender

Funding Acknowledgements Type of funding sources: None. BACKGROUND Although endogenous sex hormones influence both left atrial (LA) and left ventricular (LV) structure in peri-menopausal women, no study has ever evaluated the interaction between sex hormones levels and the left atrioventricular coupling. PURPOSE This study aimed to assess the prognostic value of a left atrioventricular coupling index (LACI) in pre- and post-menopausal women without history of CVD at baseline. METHODS In all women participating in the Multi-Ethnic Study of Atherosclerosis (MESA) with baseline cardiovascular magnetic resonance (CMR) study, LACI was measured as the ratio of the LA end-diastolic volume divided by the LV end-diastolic volume. Cox proportional hazard models were used to assess the association between LACI and the outcomes of atrial fibrillation (AF), heart failure (HF), coronary heart disease (CHD) death, and hard CVD defined by myocardial infarction, resuscitated cardiac arrest, stroke, or CHD death. In multivariable analyses, the associations between LACI and the time-to-event were evaluated, adjusting for demographics, traditional cardiovascular risk factors, menopausal status and sex hormone levels. RESULTS Among the 2,087 women (61.2 ± 10.1 years), 485 cardiovascular events were observed during mean follow-up period of 13.2 ± 3.3 years. Greater LACI was independently associated with AF (HR 1.70; 95% CI [1.51-1.90]), HF (HR 1.62; 95% CI [1.33-1.97]), CHD death (HR 1.36; 95% CI [1.10-1.68]), and hard CVD (1.30; 95% CI [1.13-1.51], all p CONCLUSIONS In a multi-ethnic population of pre- and post-menopausal women, LACI is an independent predictor of HF, AF, CHD death and hard CVD. In both pre- and post-menopausal women, LACI has an incremental prognostic value to predict cardiovascular events over traditional risk factors and sex hormone levels. ClinicalTrials.gov Identifier: NCT00005487 Abstract Figure. Kaplan-Meier curves by LACI terciles Abstract Figure. Kaplan-Meier curves by LACI and Menop.

We present the development of neutron-tagging techniques in Super-Kamiokande IV using a neural network analysis. The detection efficiency of neutron capture on hydrogen is estimated to be 26%, with a mis-tag rate of 0.016 per neutrino event. The uncertainty of the tagging efficiency is estimated to be 9.0%. Measurement of the tagging efficiency with data from an Americium-Beryllium calibration agrees with this value within 10%. The tagging procedure was performed on 3,244.4 days of SK-IV atmospheric neutrino data, identifying 18,091 neutrons in 26,473 neutrino events. The fitted neutron capture lifetime was measured as 218±9 μs. We present the development of neutron-tagging techniques in Super-Kamiokande IV using a neural network analysis. The detection efficiency of neutron capture on hydrogen is estimated to be 26%, with a mis-tag rate of 0.016 per neutrino event. The uncertainty of the tagging efficiency is estimated to be 9.0%. Measurement of the tagging efficiency with data from an Americium-Beryllium calibration agrees with this value within 10%. The tagging procedure was performed on 3,244.4 days of SK-IV atmospheric neutrino data, identifying 18,091 neutrons in 26,473 neutrino events. The fitted neutron capture lifetime was measured as 218 \pm 9 \mu s.