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In this study, poundo yam flour was supplemented with cassava flour (5, 15, 30 and 50%) and the functionality of the flour and quality of the cooked dough were determined. The composite flours and yam flour (approx. 56%) were more dispersible than the cassava flour (approx. 50%). Cassava flour addition significantly (p ≤ 0.05) increased the lightness of poundo yam flour (75.65–84.67) and the ability of the flours to absorb water, but the lightness values (61.60–64.79) of the cooked dough did not change significantly (p > 0.05). Samples with cassava flour were firmer (7.56–22.87 N), stickier (2.51–5.92 Ns) and gummier (2.57–5.48 N) than the control dough. Sensory ratings were similar across the cooked poundo yam samples. This study demonstrated that cassava flour can be used to supplement yam flour for poundo yam flour production.

Background: This study aimed to elucidate the clinical value of combined pancreaticoduodenectomy (PD) for advanced gallbladder cancer according to the mode of cancer spread in the pancreaticoduodenal region., Methods: Patients who underwent combined PD for advanced gallbladder cancer were retrospectively reviewed. The mode of cancer spread in the pancreaticoduodenal region was defined as involvement of peripancreatic organs/structures alone, peripancreatic nodal metastasis alone, or both. Surgical outcomes were compared among these modes of spread., Results: Fifty-seven patients were included. Rates of severe morbidity and mortality were 52.6% and 3.5%, respectively. The mode of cancer spread was involvement of peripancreatic organs/structures alone in 16 patients, peripancreatic nodal metastasis alone in 17, and both in 24; R0 resection rates differed significantly among the groups (87.5% vs. 94.1% vs. 37.5%; p < 0.001). Overall survival (OS) was significantly worse in patients with both modes of spread (5-year OS, 8.3%) than in those with involvement of peripancreatic organs/structures alone (5-year OS, 37.9%; p < 0.001) and those with peripancreatic nodal metastasis alone (5-year OS, 29.4%; p = 0.011). OS was similar between pM0 patients with both modes of spread and pM1 patients (5-year OS, 16.7% vs. 8.7%; p = 0.605). Multivariate analysis identified mode of cancer spread as an independent prognostic factor (p = 0.006)., Conclusions: Combined PD could be oncologically justified for advanced gallbladder cancer with involvement of peripancreatic organs/structures alone or peripancreatic nodal metastasis alone in the pancreaticoduodenal region. This procedure would not be indicated in patients with both modes of spread., Competing Interests: Declaration of competing interest No specific funding was received for this study and the authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and influenza virus are responsible for acute respiratory tract infections (ARTIs) in adults. We assessed the clinical burden of RSV, hMPV and influenza virus infection among Japanese adults hospitalized with ARTIs., Methods: The Hospitalized Acute Respiratory Tract Infection (HARTI) study was a multinational, prospective cohort study in adults with ARTIs across the 2017-2019 epidemic seasons. Enrolment in Japan began in Sept 2018 and ran until Oct 2019. The clinical diagnosis of ARTI and the decision to hospitalize the patient were made according to local standard of care practices. Viral testing was performed by reverse transcription polymerase chain reaction., Results: Of the 173 adults hospitalized with ARTI during this period at the Japan sites, 7 (4.0%), 9 (5.2%), and 11 (6.4%) were positive for influenza virus, RSV, and hMPV, respectively. RSV season was observed from Oct 2018 to Jan 2019, followed by influenza from Dec 2018 to Apr 2019. hMPV was detected across both the RSV and influenza seasons. Two patients with RSV and 1 patient with hMPV required ICU admission whereas none with influenza. Use of antibiotics, bronchodilators and inhaled corticosteroids was high amongst patients with RSV and hMPV at 1, 2, and 3 months' post-discharge compared with patients with influenza, with few exceptions., Conclusion: These findings highlight the need for a high degree of clinical suspicion for RSV and hMPV infection in adults hospitalized with ARTIs., Competing Interests: Declaration of competing interest MS received research funding to conducts clinical trials from Genova Inc., Shionogi & Co., Ltd., Sanofi K.K., AstraZeneca K.K., GlaxoSmithKline K.K., Kyorin Pharmaceutical Co., Ltd., Fujifilm Corporation, Gilead Sciences Inc., Insmed G.K., and Guerbet K.K., and received lecture fees from GlaxoSmithKline K.K., AstraZeneca K.K., Kyorin Pharmaceutical Co., Ltd., and Sanofi K.K. SO, NI, TT, HS, SA have no conflict of interest. YV, YN, YM: Employees of Janssen Pharmaceutical Companies of Johnson & Johnson at the time of the study., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Objective: We aimed to investigate the impact of preceding seasonal influenza on the clinical characteristics of adult patients with invasive pneumococcal disease (IPD) in Japan., Methods: Data for 1722 adult patients with IPD were analyzed before (2017-2019) and during the COVID-19 pandemic (2020-2022)., Results: The seasonal influenza epidemic disappeared soon after the emergence of the pandemic. Compared with that before the pandemic (66.7%), we observed a lower bacteremic pneumonia proportion in patients with IPD during the pandemic (55.6%). The clinical presentations of IPD cases significantly differed between those with and without preceding influenza. The proportion of bacteremic pneumonia was higher in IPD patients with preceding influenza than in those without in both younger (44.9% vs 84.2%) and older adults (65.5% vs 87.0%) before the pandemic. The case fatality rate was significantly higher in IPD patients with preceding influenza (28.3%) than in those without (15.3%) in older adults before the pandemic (P = 0.020). Male and aging are high risk factors for death in older patients with IPD who had preceding influenza., Conclusion: Our study reveals that preceding seasonal influenza plays a role in the development of bacteremic pneumococcal pneumonia, increasing the risk of death in older adults., Competing Interests: Declaration of competing interest The authors have no competing interests relevant to this article to disclose., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Adenovirus is a major pathogen causing febrile illness among children. It may also cause acute encephalitis/encephalopathy. This study aimed to elucidate the clinical features of adenovirus-associated encephalitis/encephalopathy (AdVE) among children in Japan., Methods: A nationwide survey of children with AdVE was conducted. An initial survey was distributed among pediatricians to obtain information about children with AdVE treated between January 2014 and March 2019. A second survey was used to obtain the clinical information of children with AdVE from hospitals that responded to the initial survey and those identified from a literature search of the reported cases. We collected demographic data and information about symptoms of infection, neurological symptoms, laboratory parameters, treatment, and outcomes. Outcomes were determined using the Pediatric Cerebral Performance Category Score., Results: Clinical information was available for 23 children with a median age of 39 months. Two had preexisting neurological disorders and six had a history of febrile seizures. The outcome was good in 15 patients and poor in eight patients. Serum lactate dehydrogenase, glucose, and ammonia levels were higher among children with a poor outcome compared to those with a good outcome. Clinically mild encephalitis/encephalopathy with a reversible splenial lesion was the most common type (n = 8), followed by acute encephalopathy with biphasic seizures and late reduced diffusion (n = 7)., Conclusion: A prior history of febrile seizures was frequent in children with AdVE. Several different subtypes of acute encephalopathy were seen in children with AdVE, and the outcome was poor in those with acute encephalopathy with biphasic seizures and late reduced diffusion and hemorrhagic shock and encephalopathy syndrome. Elevated lactate dehydrogenase, glucose, and ammonia levels on admission were found to correlate with a poor outcome., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

In-cell protein crystals which spontaneously crystallize in living cells, have recently been analyzed in investigations of their structures and biological functions. The crystals have been challenging to analyze structurally because of their small size. Therefore, the number of in-cell protein crystals in which the native structure has been determined is limited because most of the structures of in-cell crystals have been determined by recrystallization after dissolution. Some proteins have been reported to form intermolecular disulfide bonds in natural protein crystals that stabilize the crystals. Here, we focus on Cry1Aa, a cysteine-rich protein that crystallizes in Bacillus thuringiensis (Bt) and forms disulfide bonds. Previously, the full-length structure of 135 kDa Cry1Ac, which is the same size as Cry1Aa, was determined by recrystallization of dissolved protein from crystals purified from Bt cells. However, the formation of disulfide bonds has not been investigated because it was necessary to replace cysteine residues to prevent aggregation of the soluble protein. In this work, we succeeded in direct X-ray crystallographic analysis using crystals purified from Bt cells and characterized the cross-linked network of disulfide bonds within Cry1Aa crystals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

High-throughput sequencing has identified vast numbers of variants in genetic disorders. However, the significance of variants at the exon-intron junction remains controversial. Even though most cases of Mowat-Wilson syndrome (MOWS) are caused by heterozygous loss-of-function variants in ZEB2, the pathogenicity of variants at exon-intron junction is often indeterminable. We identified four intronic variants in 5/173 patients with clinical suspicion for MOWS, and evaluated their pathogenicity by in vitro analyses. The minigene analysis showed that c.73+2T>G caused most of the transcripts skipping exon 2, while c.916+6T>G led to partial skipping of exon 7. No splicing abnormalities were detected in both c.917-21T>C and c.3067+6A>T. The minigene analysis reproduced the splicing observed in the blood cells of the patient with c.73+2T>G. The degree of the exon skipping was concordant with the severity of MOWS; while the patient with c.73+2T>G was typical MOWS, the patient with c.916+6T>G showed milder phenotype which has been seldom reported. Our results demonstrate that mRNA splicing assays using the minigenes are valuable for determining the clinical significance of intronic variants in patients with not only MOWS but also other genetic diseases with splicing aberrations and may explain atypical or milder cases, such as the current patient., Competing Interests: Disclosure of conflict of interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Masson SAS.)

Background: This study aimed to evaluate the adequate extent of regional lymphadenectomy according to tumor location and the impact of number-based nodal classification on survival in patients with non-ampullary duodenal adenocarcinoma (NADAC)., Methods: A total of 85 patients with NADAC who underwent surgery were enrolled. The frequency of metastasis was calculated for each node group in the respective tumor locations for 63 patients who underwent lymphadenectomy for pT2-pT4 tumor., Results: The frequency of metastasis in the pancreaticoduodenal (nos. 13 and 17) and superior mesenteric artery (no. 14) nodes was high (16.7 %-52.3 %) regardless of tumor location. Metastasis in the perigastric (nos. 3 and 4d) and right celiac artery (no. 9) nodes was not uncommon (14.3 %-22.2 %) for tumors in the first portion. The frequency of metastasis in the pyloric (nos. 5 and 6) and the other peripancreaticoduodenal (nos. 8 and 12) nodes varied depending on tumor location but could not be ignored for staging. When these nodes were classified as regional nodes, the 5-year survival in patients with pN0, pN1 (1-2 positive nodes), and pN2 (≥3 positive nodes) were 82.9 %, 51.7 %, and 19.2 %, respectively (p < 0.001). pN classification independently predicted survival (pN1, p = 0.022; pN2, p < 0.001)., Conclusions: Nos. 5, 6, 8, 12, 13, 14, and 17 nodes in all advanced NADAC and nos. 3, 4d, and 9 nodes in advanced NADAC in the first portion should be considered as regional nodes for accurate staging. The number-based nodal classification allows good patients' prognostic stratification., (© 2023 Published by Elsevier Ltd.)

Background: /Objective: FOLFIRINOX therapy (FFX) for locally advanced pancreatic cancer (LAPC) is increasingly recognized as a potent neoadjuvant therapy that enables transition to conversion surgery (CS). However, predictors of CS achievement after chemotherapy are controversial. This study aimed to demonstrate the efficacy of CS after modified FFX (mFFX) in patients with LAPC and to identify and score predictors of CS., Methods: From January 2014 to December 2018, patients with LAPC who received mFFX as a first-line treatment were screened. Patients' overall survival was compared with and without CS. Moreover, the predictors for CS were analyzed to create scores for the CS factors., Results: Forty-three patients received mFFX, including 20 patients who underwent CS (CS group, 46.5%). R0 resection was achieved in 16 patients (80%). The median survival time was 39.2 months (95% confidence interval [CI] 17.3-53.8) for the CS group and 16 months (95% CI 10.5-22.6) for the non-CS group (P < 0.001; hazard ratio 0.25, 95% CI 0.12-0.54). Since an average relative dose intensity of ≥90%, tumor reduction of ≥35%, and carbohydrate antigen 19-9 reduction of ≥70% or normalization were associated with successful transition to CS in the multivariate analysis, these factors were scored (CS score, range 0-3). All of the patients in the CS group fell into the 2-3 category, compared with 2 of 23 patients in the non-CS group (P < 0.001)., Conclusion: CS after FFX contributes to the long-term survival of patients with LAPC. The CS score could be an indicator for transition to CS., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Background & Aims: This study aimed to investigate the associations of pre-existing sarcopenia with swallowing function, oral intake level, and aspiration pneumonia in patients with acute stroke., Methods: This observational study included patients (≥60 years of age) with acute ischemic stroke or intracerebral hemorrhage within 7 days of onset who were screened for sarcopenia, malnutrition, and swallowing difficulties in a stroke-care unit within 48 h of admission. Sarcopenia was defined by the Asian Working Group on Sarcopenia 2019 as having a low calf circumference, handgrip strength, and appendicular muscle mass index. The primary outcome was impaired oral intake (functional oral intake scale <5 points) at 3, 7, and 14 days after admission, and the secondary outcome was aspiration pneumonia during hospitalization., Results: We enrolled 350 patients (median age of 77 years; 63% males) who underwent the aforementioned screening. Sarcopenia was diagnosed in 34% of patients, and malnutrition was found in 66% of patients with sarcopenia. When compared with the comparison group (defined as patients with either or both normal calf circumference and handgrip strength), the sarcopenia group had significantly lower tongue pressure and a higher prevalence of dysphagia. Sarcopenia was associated with functional oral intake scale <5 at 7 days (adjusted odds ratio [OR], 4.72; 95% confidence interval [CI], 1.91-11.71); p = 0.002) and 14 days (adjusted OR, 3.93; 95% CI, 1.47-10.53; p = 0.006) and with aspiration pneumonia during hospitalization (adjusted OR, 6.12; 95% CI, 1.63-22.94; p = 0.007)., Conclusion: Acute stroke patients with sarcopenia may have weakness of the swallowing-related muscles which may lead to impaired oral intake and aspiration pneumonia., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Objectives: We investigated the occurrence of non-respiratory bacterial and fungal secondary infections, causative organisms, impact on clinical outcomes, and association between the secondary pathogens and mortality in hospitalized patients with coronavirus disease 2019 (COVID-19)., Methods: This was a retrospective cohort study that included data from inpatients with COVID-19 from multiple centers participating in the Japan COVID-19 Taskforce (April 2020 to May 2021). We obtained demographic, epidemiological, and microbiological data throughout the course of hospitalization and analyzed the cases of COVID-19 complicated by non-respiratory bacterial infections., Results: Of the 1914 patients included, non-respiratory bacterial infections with COVID-19 were diagnosed in 81 patients (4.2%). Of these, 59 (3.1%) were secondary infections. Bacteremia was the most frequent bacterial infection, occurring in 33 cases (55.9%), followed by urinary tract infections in 16 cases (27.1%). Staphylococcus epidermidis was the most common causative organism of bacteremia. Patients with COVID-19 with non-respiratory secondary bacterial infections had significantly higher mortality, and a multivariate logistic regression analysis demonstrated that those with bacteremia (aOdds Ratio = 15.3 [5.97-39.1]) were at higher risk of death. Multivariate logistic regression analysis showed that age, male sex, use of steroids to treat COVID-19, and intensive care unit admission increased the risk for nosocomial bacteremia., Conclusions: Secondary bacteremia is an important complication that may lead to poor prognosis in cases with COVID-19. An appropriate medical management strategy must be established, especially for patients with concomitant predisposing factors., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2023 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: In order to improve cancer care in Japan further, it is now required for orthopaedic surgeons to get actively involved in managing locomotive organs such as bones, muscles and nerves in cancer patients. In 2018, the Japanese Orthopaedic Association (JOA) conducted a questionnaire survey to investigate the current status of cancer treatment at the orthopaedic training facilities certified by the JOA. We analyzed the results of that questionnaire survey, focusing on the data from the core hospitals for cancer care (designated cancer hospitals), to clarify the involvement of orthopaedic surgeons in cancer treatment., Materials and Methods: A nationwide survey was conducted in the orthopaedic training facilities certified by the JOA using an online questionnaire from March 15th to 31st, 2018. To clarify the involvement of orthopaedic surgeons in cancer treatment, we analyzed the results of that questionnaire survey, focusing on the data from the designated cancer hospitals in Japan., Results: From the questionnaire survey, it became clear that 24% of the orthopaedic training facilities certified by the JOA are designated cancer hospitals. There were significant differences concerning cancer treatment and the prospect of orthopaedic surgeons' involvement in the treatment for bone metastases between institutions classified according to number of both certified orthopaedic surgeons by the JOA and specialists for bone and soft tissue tumors. In addition, in 45% of the designated cancer hospitals, orthopaedic surgeons treated bone metastases that occur in cancer patients, but in the rest of the institutions, orthopaedic surgeons did not yet adequately respond., Conclusion: In order to further improve the locomotive function and quality of life (QOL) in cancer patients, it was seemed to be necessary that all medical professionals engaged in cancer treatment, including orthopaedic surgeons, recognize the importance of locomotive management for cancer patients. In addition, the results of this study suggested that the presence of more than six certified orthopaedic surgeons by the JOA, including one or more specialists for bone and soft tissue tumors, may be able to create an environment conducive to the involvement of orthopaedic surgeons in cancer treatment at the facility., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest relevant to the submitted work., (Copyright © 2021 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Objective: This study evaluated the clinical implications of sarcopenia for patients with rectal cancer according to cancer progression., Summary Background Data: The negative impact of body composition on long-term outcome has been demonstrated for various malignancies., Methods: We retrospectively reviewed 708 patients with rectal cancer who underwent curative resection at our institution between 2003 and 2020. Factors contributing to long-term outcomes and the incidence of secondary cancer (ISC) were analyzed. Psoas muscle mass index (PMI) was assessed using preoperative computed tomography. Sarcopenia was defined using the PMI cut-off values for Asian adults (6.36 cm 2 /m 2 for males and 3.92 cm2/m2 for females)., Results: Sarcopenia was identified in 306 patients (43.2%). Sarcopenia was associated with advanced age, low body mass index, smoking history, and advanced T-stage. Multivariate analysis showed sarcopenia was an independent poor prognostic factor for OS (HR 1.71; P = .0102) and cancer-specific survival (HR 1.64; P = .0490). Patients with sarcopenia had significantly higher mortality due to cancer-related death in stages III and IV, whereas non-rectal cancer-related death, including secondary cancer, was markedly increased in stage 0-II sarcopenic rectal patients. Five-year cumulative ISC in patients with and without sarcopenia was 11.8% and 5.9%, respectively. Multivariate analysis revealed that sarcopenia was an independent predictive factor for ISC (HR 2.05; P = .0063)., Conclusions: Sarcopenia helps predict survival outcomes and cause of death according to cancer stage for patients with middle/lower rectal cancer who underwent radical surgery. Furthermore, sarcopenia increased the development of secondary cancer in those patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The monkeypox virus is excreted in the feces of infected individuals. Therefore, there is an interest in using viral load detection in wastewater for sentinel early surveillance at a community level and as a complementary approach to syndromic surveillance. We collected wastewater from 63 sewered and non-sewered locations in Bangkok city center between May and August 2022. Monkeypox viral DNA copy numbers were quantified using real-time polymerase chain reaction (PCR) and confirmed positive by Sanger sequencing. Monkeypox viral DNA was first detected in wastewater from the second week of June 2022, with a mean copy number of 16.4 copies/ml (n = 3). From the first week of July, the number of viral DNA copies increased to a mean copy number of 45.92 copies/ml. Positive samples were Sanger sequenced and confirmed the presence of the monkeypox virus. Our study is the first to detect monkeypox viral DNA in wastewater from various locations within Thailand. Results suggest that this could be a complementary source for detecting viral DNA and predicting upcoming outbreaks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: This study aimed to evaluate the association between the preoperative Controlling Nutritional Status (CONUT) score, survival outcomes, and recurrence pattern in patients with resectable biliary tract cancer (BTC)., Methods: A total of 224 BTC patients (gallbladder, n = 69; intrahepatic bile ducts, n = 26; perihilar bile ducts, n = 72; distal bile duct, n = 57) who underwent surgery with curative intent were enrolled. The best cutoff point of the preoperative CONUT score in discriminating survival was determined using χ 2 scores. The sites of recurrence were subclassified as locoregional or distant., Results: Patients were subdivided into the CONUT-low (score ≤ 3, n = 156) and the CONUT-high (score > 3; n = 68) groups. In-hospital mortality occurred more frequently in the CONUT-high group than in the CONUT-low group (7.4% vs. 1.3%; p = 0.028). A high preoperative CONUT score was independently associated with worse overall survival (hazard ratio [HR] 1.906, p = 0.001), worse disease-specific survival (HR 1.840, p = 0.006), and worse recurrence-free survival (HR 1.680, p = 0.005). Recurrence developed in 110 (49.1%) patients. A high preoperative CONUT score was independently associated with a higher risk of distant recurrence (HR 2.245, p = 0.001), but not locoregional recurrence. The incidences of distant recurrence at 5 years were 55.4% and 34.2% in the CONUT-high and CONUT-low groups, respectively (p = 0.001)., Conclusions: The preoperative CONUT score independently predicts survival outcomes and may serve as a surrogate marker of aggressive systemic disease recurrence in patients with resectable BTC., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Purpose: Obstructive colitis (OC) is a risk factor of anastomotic leakage in colorectal cancer resection. We aimed to clarify the relationship between the severity of OC and clinicopathological findings and to detect predictive factors of OC., Methods: We retrospectively reviewed 43 cases of colectomy after self-expandable metallic stent placement for left-sided colorectal cancer. Preoperative diagnosis of OC was made by multiple modalities (initial computed tomography (CT), presurgical CT, and colonoscopy). We classified OC macroscopically in resected specimens into five groups (Grade 0: none, 1: mild [mild edema], 2: moderate [severe edema, redness, erosion], 3: severe [ulceration, bleeding], 4: very severe [necrosis, perforation]), and investigated the relationship between the preoperative assessment, surgical findings and the severity of OC., Results: OC of Grade 2 or more (53.5%) was significantly correlated with severe edema in initial CT. There was no significant correlation between OC and anastomosis rate. The creation of covering stoma was significantly higher in the Grade 2 or more OC group. No leakage was observed in either group., Conclusions: Initial CT may be most useful for prediction of OC. It is important to make a preoperative diagnosis of OC by combining multiple modalities, which enables to determine the appropriate location for resection, anastomosis, and construction of a covering stoma., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Steroid hormones, especially glucocorticoids, androgens, and estrogens, have profound influence on immunity. Recent studies using cell-type specific steroid hormone receptor-deficient mice have revealed the precise roles of some of these hormones in the immune system. Glucocorticoids are known to have strong anti-inflammatory and immunosuppressive effects and pleiotropic effects on innate and adaptive immune responses. They suppress the production of inflammatory cytokines by macrophages and DCs and the production of IFN-γ by NK cells, thus inhibiting innate immunity. By contrast, glucocorticoids enhance the immune response by inducing the expression of IL-7R and CXCR4 in T cells and the accumulation of T cells in lymphoid organs in accordance with the diurnal change of the glucocorticoid concentration. Thus, glucocorticoids suppress innate immunity but enhance adaptive immunity. Androgens suppress the homeostasis and activation of ILC2s and the differentiation of Th2 and Th17 cells and enhance the suppressive function of Tregs, thereby alleviating allergic airway inflammation. Thus, these steroid hormones have pleiotropic functions in the immune system. Further investigations are awaited on the regulation of immunity and allergy by estrogens using cell-specific steroid hormone receptor-deficient mice., (Copyright © 2022 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Patients with acute coronary syndrome complicated with cardiogenic shock (ACS-CS) frequently require mechanical circulatory support. In addition to veno-arterial extracorporeal membrane oxygenation (VA-ECMO), use of the Impella® (ECpella) (Abiomed Inc., Danvers, MA, USA) heart pump may improve the prognosis of such patients. In this study, we compared the efficacy of VA-ECMO plus intra-aortic balloon pumping (ECMO-IABP) with that of the ECpella for add-on circulatory support of VA-ECMO., Methods: Clinical outcomes of 64 patients with ACS-CS treated with ECMO-IABP (n = 41) or ECpella (n = 23) between January 2013 and April 2021 were retrospectively analyzed. The primary outcomes were 30-day and 365-day mortality. In addition, patients resuscitated after cardiopulmonary arrest (CPA) were evaluated separately., Results: The ECpella group showed significantly lower mid-term mortality than the ECMO-IABP group [30-day mortality (39.1% vs 56.1%, respectively; p = 0.193) and 365-day mortality (43.5% vs 75.6%, respectively; p = 0.010)], with significantly higher rates of new hemodialysis and bleeding at the vascular access site. Also, among the limited number of patients resuscitated from CPA, mortality was significantly lower in the ECpella group than the ECMO-IABP group [30-day mortality (28.6% vs 65.4%, respectively; p = 0.026) and 365-day mortality (28.6% vs 84.6%, respectively; p < 0.001)]. Among the resuscitated patients, ECMO weaning period and the incidence of neurological complications were related to 30-day mortality; The incidence of neurological complications was related to 365-day mortality. The use of ECpella was strongly associated with both 30-day and 365-day survival., Conclusions: The ECpella heart pump may provide a survival advantage over ECMO-IABP in patients with ACS-CS., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Bleeding risk in heart failure (HF) patients with coronary artery disease (CAD) has not yet been fully investigated., Methods: We analyzed the data of 677 patients with a previous history of CAD who were hospitalized for HF. The patients were divided into three groups based on the tertiles of B-type natriuretic peptide (BNP) levels: Low, Middle, and High BNP groups (n = 225, 226, and 226, respectively). The primary endpoint was post-discharge bleeding events, which was defined as hemorrhagic stroke and gastrointestinal bleeding., Results: The High BNP group was the oldest (Low, Middle, High, 67.0, 74.0, and 75.0 years, respectively; p < 0.001), showed the lowest left ventricular ejection fraction (56.0%, 50.7%, and 40.3%, respectively; p < 0.001), and contained more patients at high bleeding risk (HBR) defined by the simplified version of the Academic Research Consortium for High Bleeding Risk (ARC-HBR) definition (65.3%, 85.4%, and 93.8%, respectively, p < 0.001). Kaplan-Meier analysis demonstrated that post-discharge bleeding events occurred most frequently in the High BNP group (log-rank p = 0.008). In the Cox proportional hazard analysis, compared to the Low BNP group as a reference, the High BNP group was independently associated with bleeding events after adjustment for age, sex, simplified ARC-HBR definition, and left ventricular ejection fraction (hazard ratio 3.208, 95% confidence interval 1.078-9.544, p = 0.036)., Conclusions: High BNP is associated with bleeding events in HF patients with a history of CAD., (Copyright © 2022. Published by Elsevier Ltd.)

Objective: The purpose of this study was to investigate the effectiveness of Diamour®, a newly developed vitrification device, for the ultra-rapid frozen storage of human blastocysts., Materials and Methods: Surplus blastocysts obtained using assisted reproductive technology at our clinic during a 2-year period (2018-2019) were assigned for vitrification with the Diamour® device in 2019 or a comparator device in 2018. We retrospectively compared outcomes (clinical pregnancy rate, abortion rate, live birth rate, and perinatal outcomes) between the two vitrification devices., Results: We obtained 228 blastocysts from 178 patients, and 118 blastocysts were cryopreserved using the Diamour® vitrification device and the other 110 were cryopreserved using a Cryotop®, the comparator device. We found no significant difference between the Diamour®-vitrified and comparator-vitrified blastocysts in clinical pregnancy rate (32.2% vs. 30.9%; p = 0.83), abortion rate (17.0% vs. 9.1%; p = 0.08), and live birth rate (25.4% vs. 26.4%; p = 0.87). The Diamour®-vitrified blastocysts yielded 30 live births, and the comparator-vitrified blastocysts 29. The two devices yielded no significant difference in birth weight (Diamour®: 3049 ± 337 g, comparator: 3008 ± 340 g; p = 0.65) and congenital abnormalities, with just 1 case (cleft lip) noted with Diamour® vitrification (p = 0.33). The devices also showed no significant differences in the incidence of gestational diabetes mellitus, hypertensive disorders of pregnancy, placenta previa, preterm birth, macrosomia, low birth weight, and delivery method., Conclusion: The Diamour® device achieves outcomes similar to those of the currently widely used Cryotop® device for clinical pregnancy with frozen-thawed human blastocysts., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2022. Published by Elsevier B.V.)

Purpose: This study aimed to measure the angles between the screw and plate in 16 commercially available volar locking plates (VLPs) to determine the fixable intra-articular fragment size., Methods: Ulnar orientation angles (axial plane) and elevation angles (sagittal plane) between the distal ulnar screw and plate were measured for 14 fixed-angle VLPs and 2 variable-angle VLPs. Each VLP was simulated by 2 surgeons to sit distally and ulnarly in 10 normal distal radius models. The distance between the screw and distal/ulnar end of the distal radius on both the volar and dorsal sides, designated as the longitudinal/lateral distance, was measured to identify the fixable size of the 2 intra-articular fragments: volar lunate fragment and dorsoulnar fragment. Relationships between the ulnar orientation angle and dorsal-side lateral length as well as the elevation angle and dorsal-side longitudinal distance were analyzed., Results: The ulnar orientation and elevation angles ranged from 6.5° to 16.9° and -5.8° to 34.3°, respectively, for fixed-angle VLPs and -12.5° to 32.2° and 3.1° to 42.1°, respectively, for variable-angle VLPs. The minimal longitudinal distances on the volar side with the fixed- and variable-angle VLPs were 4.3-10.9 mm and 5.8-5.9 mm, respectively. On the dorsal side, the lateral distance negatively correlated with the ulnar orientation angle (R = -0.74), and the longitudinal distance negatively correlated with the elevation angle (R = -0.89)., Conclusions: The Depuy Synthes variable-angle VLP provides an advantage for fixating small intra-articular fragments. For fixed-angle VLPs, the Mizuho VLP provides an advantage for fixating small volar lunate fragments. A narrow dorsoulnar fragment can be fixated using a plate with a large ulnar orientation angle, such as the Zimmer Biomet or Mizuho VLP., Clinical Relevance: The ability of each individual commercially available plate to capture specific intra-articular fragments should be known., (Copyright © 2022 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Background: Analysis of long-term clinical outcomes of patients with familial adenomatous polyposis is critical in reducing or preventing the incidence of extracolonic malignancies after initial surgery. The aim of the present study was to clarify the long-term outcomes, and establish a surveillance strategy for surgically treated familial adenomatous polyposis patients., Methods: Between January 1967 and March 2020, retrospective data were collected from 37 patients with familial adenomatous polyposis treated or monitored in our department. Occurrence of metachronous cancers, including rectal cancers and extracolonic malignancies, and other diseases was analyzed., Results: The median follow-up duration after the first surgery was 13.8 years. Initially, 16 patients underwent total proctocolectomy with ileal pouch-anal anastomosis, 18 underwent total colectomy with ileorectal anastomosis, and three underwent other procedures. A secondary proctectomy was performed for 9 of the 18 patients who underwent ileorectal anastomosis. Rectal cancer was diagnosed in 6 patients who underwent ileorectal anastomosis. In addition, 5 gastric cancer, 2 duodenal cancer, 1 gallbladder cancer, and 1 thyroid cancer cases were diagnosed. The age at which the extracolonic malignancies were diagnosed was >50 years. 4 patients died due to metachronous rectal cancer, gastric cancer, or gallbladder cancer., Conclusion: Careful consideration should be paid before choosing ileorectal anastomosis as the treatment procedure for familial adenomatous polyposis patients because completion proctectomy was eventually necessary for half of the patients. Long-term surveillance, with more frequent gastric surveillance for patients over 50 years, is important for the prevention and treatment of extracolonic malignancies in familial adenomatous polyposis patients., Competing Interests: Declaration of competing interest The authors have no conflicts to disclose., (Copyright © 2021. Published by Elsevier Taiwan LLC.)

The genus Gambierdiscus is a marine benthic/epiphytic dinoflagellate considered the causative agent of ciguatera poisoning (CP). Clarifying the geographical distribution of this genus to understand the potential risk of CP is important. Many studies have focused only on the species/phylotype composition of Gambierdiscus in shallow waters, but no study has investigated the species/phylotype composition of the genus in deep waters. In the present study, the distributions of Gambierdiscus species/phylotypes at two depths (2-8 and 30 m) and two sampling sites (temperate and subtropical) in Japan was investigated using high throughput sequencing (HTS) with a newly developed primer set that preferentially amplifies the 18S rDNA V8-V9 region of Alveolata. A phylogenetic analysis using 89 samples collected over three years revealed of ten Gambierdiscus species/phylotypes including not only two species that have not been reported in Japan (G. caribaeus and G. silvae) but also four novel phylotypes (Gambierdiscus spp. Clade II&#95;1, Clade II&#95;2, Clade II&#95;3, and Clade VI&#95;1). Uncorrected genetic distances also supported that these new phylotypes clearly diverged from other Gambierdiscus species. All four new phylotypes, G. caribaeus, and G. silvae were distributed in the subtropical region. Among them, Clade II&#95;2, Clade VI&#95;1, and G. silvae were also distributed in the temperate region. Four species/phylotypes previously reported from Japan showed a similar distribution as reported previously. Among the ten species/phylotypes, Gambierdiscus sp. type 3 and Clade VI&#95;1 were found only in deep waters, whereas five species/phylotypes were observed only in shallow waters. The other three species/phylotypes were found in both deep and shallow waters. The results of the horizontal and vertical distribution suggest that the growth characteristics of each species/phylotypes found in Japan might adapt to the ambient environmental conditions. This study revealed an inclusive assemblage of Gambierdiscus species/phylotypes in Japan through metabarcoding using the Alveolata primer set. In the future, the abundance and toxicities/toxin productions of the newly reported species/phylotypes need to be clarified to understand the mechanism of CP outbreaks in Japan., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Two classes of replication intermediates have been observed from mitochondrial DNA (mtDNA) in many mammalian tissue and cells with two-dimensional agarose gel electrophoresis. One is assigned to leading-strand synthesis in the absence of synchronous lagging-strand synthesis (strand-asynchronous replication), and the other has properties of coupled leading- and lagging-strand synthesis (strand-coupled replication). While strand-asynchronous replication is primed by long noncoding RNA synthesized from a defined transcription initiation site, little is known about the commencement of strand-coupled replication. To investigate it, we attempted to abolish strand-asynchronous replication in cultured human cybrid cells by knocking out the components of the transcription initiation complexes, mitochondrial transcription factor B2 (TFB2M/mtTFB2) and mitochondrial RNA polymerase (POLRMT/mtRNAP). Unexpectedly, removal of either protein resulted in complete mtDNA loss, demonstrating for the first time that TFB2M and POLRMT are indispensable for the maintenance of human mtDNA. Moreover, a lack of TFB2M could not be compensated for by mitochondrial transcription factor B1 (TFB1M/mtTFB1). These findings indicate that TFB2M and POLRMT are crucial for the priming of not only strand-asynchronous but also strand-coupled replication, providing deeper insights into the molecular basis of mtDNA replication initiation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Alkali treatment and bioactive glass (BG) sol dip-coating are well-known individual methods for titanium (Ti) surface modification. In this study, a unique combination of alkali treatment and bioactive glass sol dip coating was applied to the Ti substrate, then the mechanical properties and cell responses were investigated., Methods: Based on the methods introduced above, the Ti substrate was treated by 6 mL of an NaOH 5 M aqueous solution for 24 h at 60 ̊C; this was followed by adding 1.2 mL of a BG 58S sol to form a novel combined nanostructure network covered by a thin BG layer. For the assessment of the formed coating layer, the morphology, elemental analysis, phase structure, adhesion property and the cell response of the untreated and treated surfaces were investigated., Results: The BG coating layer was reinforced by the nanostructure, fabricated through the alkali treatment. The results obtained by applying the combined modification method confirmed that the mechanical and biological properties of the fabricated surface demonstrated the highest performance compared to that of the unmodified and individually modified surfaces., Significance: The achieved upgrades for this method could be gained from the demanded porous nanostructure and the apatite transformation ability of the alkali treatment. Therefore, the hybridized application of the alkali-BG treatment could be introduced as a promising surface modification strategy for hard-tissue replacement applications., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The incidence of syphilis infection among pregnant women is persistently high in Japan and in several developed countries. Here, we report the utility of intravenous benzylpenicillin in 13 infants born to mothers with syphilis infection. Because the recommended treatment (intramuscular benzathine benzylpenicillin) is not available in Japan, we intravenously administered benzylpenicillin for 10 days, which is used for treatment in high-risk cases. The administration of benzylpenicillin in low-risk infants resulted in an extended duration of parent-to-infant separation and increased the infants' exposure to invasive procedures. Thus, establishing evidence of the adequacy of no-treatment follow-up in low-risk groups and introducing intramuscular injections of benzathine benzylpenicillin may improve the management of infants suspected with congenital syphilis in Japan., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: SARS-CoV-2 RNA is excreted in feces of most patients, therefore viral load in wastewater can be used as a surveillance tool to develop an early warning system to help and manage future pandemics., Methods: We collected wastewater from 24 random locations at Bangkok city center and 26 nearby suburbs from July to December 2020. SARS-CoV-2 RNA copy numbers were measured using real-time polymerase chain reaction (PCR)., Results: SARS-CoV-2 RNA was detected in wastewater from both the city center and suburbs. Except for July, there were no significant differences in copy numbers between the city center and suburbs. Between October and November, a sharp rise in copy number was observed in both places followed by two to three times increase in December, related to SARS-CoV-2 cases reported for same month., Conclusions: Our study provided the first dataset related to SARS-CoV-2 viral RNA in the wastewater of Bangkok. Our results suggest that wastewater could be used as a complementary source for detecting viral RNA and predicting upcoming outbreaks and waves., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Although natriuretic peptide receptor-C (NPR-C) is involved in the clearance of natriuretic peptides from plasma, it also possesses other physiological functions, such as inhibition of adenylyl cyclase activity through Gαi. However, the physiological roles and intracellular signaling pathways of NPR-C have yet been not fully elucidated. In this study, we identified a RhoA-specific guanine nucleotide-exchange factor, GEF-H1, as a novel binding protein of NPR-C. We demonstrated that endogenous NPR-C interacted with GEF-H1 in HeLa cells, and that the interaction between NPR-C and GEF-H1 was dependent on a 37-amino acid cytoplasmic region of NPR-C. In contrast, another natriuretic peptide receptor, NPR-A, which includes the kinase homology and guanylyl cyclase domains in the intracellular region, did not interact with GEF-H1. We also revealed that the ligands of NPR-C (i.e., ANP, CNP, and osteocrin) caused dissociation of GEF-H1 from NPR-C. Furthermore, osteocrin treatment induced phosphorylation of GEF-H1 at Ser-886, enhanced the interaction of GEF-H1 with 14-3-3, and increased the amount of activated GEF-H1. These findings strongly supported that NPR-C may be involved in diverse physiological roles by regulating GEF-H1 signaling., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Postoperative severe respiratory adverse events (SRAEs) are the major cause of perioperative morbidity in patients after thoracic surgery. In particular, SRAEs often occur in lung cancer patients concomitant with chronic inflammatory lung diseases (CILDs) such as interstitial lung disease, emphysema, infectious disease, and asthma. We aimed to clarify whether the measurement of the maximum of standardized uptake value in the noncancerous lung area (NCA-SUVmax) and CILDs on high-resolution computed tomography were useful for predicting the risk of SRAEs., Methods: A total of 984 patients with lung cancer undergoing preoperative computed tomography, F-18 fluorodeoxyglucose-positron emission tomography/computed tomography followed by surgery between July 2012 and March 2019 were assessed. NCA-SUVmax was measured using a 3-dimensional workstation. We extracted the records of patients with CILDs and their disease history. Predictive factors associated with SRAEs were identified., Results: SRAEs were observed in 75 patients (7.6%), and 7 patients (9.3%) died of SRAEs within 90 days after surgery. NCA-SUVmax in patients with CILDs (n = 325; emphysema = 161, interstitial lung disease = 134, infectious disease = 17, asthma = 13) were higher than that in patients without CILDs (n = 659; 1.3 ± 0.7 vs 1.1 ± 0.4, respectively; P < .001). On multivariate analysis, CILDs, percent vital capacity, and NCA-SUVmax were independently associated with SRAEs (P < .001). Rate of SRAEs in patients with CILDs, NCA-SUVmax ≥1.3, and percent vital capacity ≤ 110 was 31.8%., Conclusions: NCA-SUVmax was independently associated with the incidence of SRAEs in patients with resected lung cancer and was significantly increased in patients with CILDs., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Adequate improvement in fractional flow reserve (FFR) is not necessarily achieved in some cases of drug-eluting stent (DES) implantation, even when imaging confirms successful placement. We hypothesized that post-stent FFR may be associated with advanced diffuse atherosclerotic condition. We explored the relationships between FFR values after DES implantation (post-stent FFR)., Methods: A total of 218 patients were included in this prospective, multicenter study and were divided into two groups: adequate FFR group (post-stent FFR >0.80, n=176) and inadequate FFR group (post-stent FFR ≤0.80, n=42). The primary endpoint was a major adverse cardiovascular event (MACE) including cardiac death, non-fatal myocardial infarction (MI), unplanned coronary revascularization, and hospitalization for heart failure. The secondary endpoints were event rate of all-cause death, non-fatal MI, unplanned coronary revascularization, non-fatal stroke, and hospitalization for heart failure., Results: During follow-up of 31.4±8.7 months, 34 patients (16%) had cardiovascular events. Inadequate FFR group was significantly associated with higher risk of MACE (hazard ratio: 3.86; 95% confidence interval: 1.17-12.76, p=0.026; log-rank p=0.027). In particular, the incidence of unplanned coronary revascularization on non-target lesions was significantly higher in the inadequate FFR group (log-rank p=0.031)., Conclusions: Post-stent FFR ≤0.80 was associated with a high incidence of non-target lesion revascularization and could be a surrogate marker for advanced atherosclerotic condition in the vessels of the entire coronary artery., (Copyright © 2020. Published by Elsevier Ltd.)

Escherichia coli is one of the most popularly used hosts to produce recombinant proteins. Most recombinant proteins are produced in the cytoplasm and periplasm, requiring multiple steps to extract and purify recombinant proteins. The Serratia marcescens Lip system (LipB-LipC-LipD) is a type 1 secretion system that selectively secretes LipA from the intracellular to extracellular space in a single step. This study aimed to establish a secretory production system for nanobodies, camelid-derived small molecule antibody fragments, using the S. marcescens Lip system. Surprisingly, E. coli harboring only LipC, a membrane fusion protein of the Lip system, could secrete an anti-green fluorescent protein (GFP)-Nb, a nanobody against GFP, without the addition of a long amino acid sequence. The LipC-based secretion system recognized the Val-Thr-Val sequence at the C-terminus of the nanobody. Finally, Strep-tagged anti-GFP-Nb was purified from culture supernatants of E. coli harboring LipC by Strep-affinity chromatography at a final yield of >5 mg per liter of culture supernatant. These results potently supported that the S. marcescens LipC-based secretion system has the potential to establish an efficient secretory production system for nanobodies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Favipiravir, an antiviral agent, is undergoing clinical trials for treating novel coronavirus disease 2019 (COVID-19). Here, we report two cases of COVID-19 with favipiravir-induced fever. In both cases, pyrexia was observed following the administration of favipiravir despite improvements in symptoms of COVID-19. No other cause for fever was evident after careful physical examination and laboratory investigation. The fever subsided in both patients after the discontinuation of favipiravir. To the best of our knowledge, this is the first report of favipiravir-induced fever in COVID-19 patients., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Supplementation with medium-chain triglycerides (MCTs) was previously shown to increase muscle function in frail elderly individuals., Objective: We aimed to assess effects of MCTs on cognition in such individuals., Methods: We enrolled 64 elderly nursing home residents (85.5 ± 6.8 y; 13 men, 51 women; BMI 18.6 ± 2.5 kg/m2) in a 3-mo randomized, controlled, single-blinded, intervention trial. Participants were randomly allocated to 3 groups: the first group received supplemental L-leucine (1.2 g) and cholecalciferol (20 μg) enriched with 6 g/d of MCTs (LD + MCT group) as a positive control, the second group received 6 g/d of MCTs (MCT group) as the test nutrient, and the third group received 6 g/d of long-chain triglycerides (LCT group) as a negative control. Cognition (secondary outcome) was monitored 4 times: baseline, 1.5 and 3 mo after initiation of the intervention (intervention), and 1.5 mo after termination of the intervention (postintervention follow-up). Cognition scores were assessed by a linear mixed model (intention-to-treat analysis)., Results: MCT supplementation increased the Mini-Mental State Examination (MMSE) score by 3.5 points at the 3-mo intervention from baseline (P < 0.001) [intention-to-treat adjusted means: baseline 17.5 points (95% CI: 14.9, 20.2), 3-mo intervention 21.0 points (18.3, 23.7)], whereas LCT supplementation decreased the MMSE score by -0.7 points [baseline 17.0 points (95% CI: 14.4, 19.6), 3-mo intervention 16.3 points (13.6, 18.9)]. At the 3-mo intervention, the difference in MMSE score between the MCT (21.0 points) and LCT (16.3 points) groups became significant (P < 0.05). The increase in MMSE score in response to MCTs was 2.1-fold greater at 3 mo than at 1.5 mo and had returned to baseline value at the 4.5-mo postintervention follow-up visit., Conclusion: Supplementation with 6 g MCTs/d may improve the cognition of frail elderly individuals. This trial was registered at umin.ac.jp as UMIN000023302., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)