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Abstract Introduction To diagnose sinusoidal obstruction syndrome/veno‐occlusive disease (SOS/VOD), transabdominal ultrasonography is usually used to detect hemodynamic changes, but we tried to detect the changes using four‐dimensional computed tomography (4D‐CT). A 42‐year‐old Japanese woman was diagnosed with late‐onset SOS/VOD with transabdominal ultrasonography and was also assessed using 4D‐CT. Method We analyzed the portal vein (PV) contrast effect every 1.5 seconds and plotted the values of the contrast effect. With this graph, we analyzed three hemodynamic parameters. Result We found that these parameters correlated with the patient's status and indicated stasis due to sinusoid constriction. Conclusion 4D‐CT may become a helpful tool to diagnose and follow up with SOS/VOD.

There is a lack of data regarding the safety and effectiveness of implanting the Pipeline Embolization Device with Shield technology (PED-Shield) compared with the previous generation of Pipeline (PED-Flex). This retrospective single-center study aimed to compare treatment outcomes between the PED-Shield and PED-Flex for treating unruptured internal carotid artery aneurysms. The PED-Flex was used in 62 procedures (67 aneurysms, 59 patients) and the PED-Shield in 53 procedures (59 aneurysms, 58 patients). The mean aneurysm diameter was significantly lower in the PED-Shield group than in the PED-Flex group (11.9 ± 7.0 mm vs. 15.2 ± 6.9 mm, p < 0.001). At the 12-month follow-up, the complete angiographic occlusion rate was 72.1% and 72.3% in the PED-Flex and PED-Shield groups, respectively (p = 0.9808). Limited to aneurysms larger than 10 mm, 70.6% and 68.0%, respectively (p = 0.8175). The incidence of more than three high signal intensity areas on diffusion-weighted imaging after treatment was significantly lower in the PED-Shield group than in the PED-Flex group (27.7% vs. 67.7%; p < 0.001). Limited to aneurysms larger than 10 mm, 41.1% and 69.6%, respectively (p < 0.0117). Symptomatic ischemic complications occurred within 30 days of four PED-Flex procedures (6.5%) and one PED-Shield procedure (2.0%) (p = 0.2315). Limited to aneurysms larger than 10 mm, 1.8% and 3.2%, respectively (p = 0.6677). The incidence of mRS score worsening at 6 months was 3.2% and 1.9% in the PED-Flex and PED-Shield groups, respectively (p = 0.6534). The PED-Shield can achieve outcomes equivalent to or better than the PED-Flex. Further large-scale studies are warranted to confirm our findings.

Abstract The germinal centers (GCs) are structure found within secondary lymphoid organs and are important for the antibody-producing response against foreign antigens. In GCs, antigen-specific B cells proliferate intensely, inducing immunoglobulin class switching. Recent studies have shown that GCs are also an important site for class switching to IgE, which is implicated in allergy. However, the mechanisms by which IgE production is regulated in GCs remain unclear. Here, we found impairment in IgE-specific production and a reduction of GC B cells after immunization in mice deficient in the Aps/Sh2b2 gene encoding the Lnk/Sh2b family adaptor protein Aps. GC B cells express higher levels of the Aps gene than non-GC B cells, and cell death of Aps -/- GC B cells is enhanced compared to wild-type GC B cells. An in vitro culture system with purified Aps -/- B cells induced the same level of IgE production and frequencies of IgE+ B cells as wild-type B cells. We found that Aps deficiency in B cells resulted in augmented depletion of IgE+ blasts by B cell receptor crosslinking with anti-CD79b antibodies compared to wild-type IgE+ cells. These results suggest that Aps regulates IgE production by controlling the survival of GC B cells and IgE+ plasma cells and may serve as a potential therapeutic target to control IgE production.

Abstract Background Hypophosphatemia due to excessive carbohydrate administration is considered the primary pathogenesis of refeeding syndrome. However, its association with liver injury and hypoglycemia, often seen in severe malnutrition before re-nutrition, remains unclear. Autophagy reportedly occurs in the liver of patients with severe malnutrition. This study aimed to clarify the pathophysiology of liver injury and hypoglycemia by focusing on liver volume. Methods Forty-eight patients with anorexia nervosa with a body mass index (BMI) of

Economic impact estimates of the initial lockdowns due to the COVID-19 pandemic showed a significant reduction in economic activities globally. However, the succeeding impacts and their spatiotemporal distribution within countries remain unknown. Studies showed that nighttime light data (NTL) has effectively revealed the spatiotemporal dimensions of the economic effects of COVID-19. Thus, this study used NTL data to determine the medium-term regional monthly economic impacts of the pandemic in the Philippines in terms of the Economic Activity Reduction (EAR) index. We generated a spatial error model, regressing pre-pandemic NTL on mean temperature, maximum rainfall, and built-up area. This model explained 81.6% of the pre-pandemic NTL and was used to estimate the counterfactual NTL. We subtracted the actual from the counterfactual to compute the EAR. Then, the EAR was regressed on regional factors to determine which ones influence the impacts. Results showed uneven distribution of EAR across space and time. The EAR was generally higher in urban regions than in rural ones. Overall, more regions in the south had higher EAR. Temporally, the EAR showed a dynamic pattern, increasing in less urban regions and decreasing in highly urbanized regions. Regional analysis showed that urbanization level, population density, and poverty incidence had a significant positive relationship with the EAR. Beyond the immediate impacts, NTL effectively revealed spatiotemporal dimensions of the economic effects of a long-term global hazard.

Background: Recent studies suggested an expected survival benefit associated with anticoagulant therapies for sepsis in patients with disseminated intravascular coagulation (DIC). However, anticoagulant therapies for overt DIC are no longer assumed to regulate pathologic progression as overt DIC is a late-phase coagulation disorder. Therefore, methods for early prediction of sepsis-induced DIC before its progression to an overt stage are strongly required. Objectives: We aimed to develop a prediction model for overt DIC using machine learning. Methods: This retrospective, observational study included adult septic patients without overt DIC. The objective variable was binary classification of whether patients developed overt DIC based on International Society on Thrombosis and Haemostasis (ISTH) overt DIC criteria. Explanatory variables were the baseline and time series data within 7 days from sepsis diagnosis. Light Gradient Boosted Machine method was used to construct the prediction model. For controls, we assessed sensitivity and specificity of Japanese Association for Acute Medicine DIC criteria and ISTH sepsis-induced coagulopathy criteria for subsequent onset of overt DIC. Results: Among 912 patients with sepsis, 139 patients developed overt DIC within 7 days from diagnosis of sepsis. Sensitivity, specificity, and area under the receiver operating characteristic curve for predicting onset of overt DIC within 7 days were 84.4%, 87.5%, and 0.867 in the test cohort and 95.0%, 75.9%, and 0.851 in the validation cohort, respectively. Sensitivity and specificity by the diagnostic thresholds were 54.7% and 74.9% for Japanese Association for Acute Medicine DIC criteria and 63.3% and 71.9% for ISTH sepsis-induced coagulopathy criteria, respectively. Conclusion: Compared with conventional DIC scoring systems, a machine learning model might exhibit higher prediction accuracy.

Objective: A cardiopulmonary exercise test provides information regarding appropriate exercise intensity, but there have been few reports on its use in patients over 80 years of age. Design: Retrospective observational study. Patients: A total of 511 cardiovascular disease patients who performed a cardiopulmonary exercise test from February 2011 to January 2020 were investigated. Methods: Patients were stratified according to age:

Abstract Numerous COVID-19 diagnostic imaging Artificial Intelligence (AI) studies exist. However, none of their models were of potential clinical use, primarily owing to methodological defects and the lack of implementation considerations for inference. In this study, all development processes of the deep-learning models are performed based on strict criteria of the “KAIZEN checklist”, which is proposed based on previous AI development guidelines to overcome the deficiencies mentioned above. We develop and evaluate two binary-classification deep-learning models to triage COVID-19: a slice model examining a Computed Tomography (CT) slice to find COVID-19 lesions; a series model examining a series of CT images to find an infected patient. We collected 2,400,200 CT slices from twelve emergency centers in Japan. Area Under Curve (AUC) and accuracy were calculated for classification performance. The inference time of the system that includes these two models were measured. For validation data, the slice and series models recognized COVID-19 with AUCs and accuracies of 0.989 and 0.982, 95.9% and 93.0% respectively. For test data, the models’ AUCs and accuracies were 0.958 and 0.953, 90.0% and 91.4% respectively. The average inference time per case was 2.83 s. Our deep-learning system realizes accuracy and inference speed high enough for practical use. The systems have already been implemented in four hospitals and eight are under progression. We released an application software and implementation code for free in a highly usable state to allow its use in Japan and globally.

This study developed a fibre-optic laser Doppler velocimetry sensor for use in opaque, high-temperature, and high-pressure fluid flows by inserting the fibre perpendicular to the main flow. The tip of the optical fibre was obliquely polished and chemically etched using a buffered hydrofluoric acid solution, and a reflective mirror was deposited on the surface of the oblique fibre tip. Based on the results of the verification test using the rotating annular open channel, the fabrication conditions of the fibre tip were optimized for measuring the lubricating oil flow. The flow velocity profiles in the engine’s oil flow of the lubrication system during engine bench testing were measured. These velocity profiles were influenced by variations in the measurement position, oil temperature, and engine speed. The measurement accuracy of this sensor was compared with the volumetric flow rate obtained by cross-sectional area integration of the flow velocity profile, as measured using a Coriolis flowmeter, and the difference was within 1%. By combining computational simulation for flow and optical attenuation and particle scattering in light transmission through a working fluid, this fibre-optic sensor achieved a measurement volume of 200 microns in length and 200 microns in width at a distance of 900–1000 microns from the sensor.

Physical training changes the metabolic state, but such changes are difficult to quantify directly and non-invasively in humans. This study therefore used breath tests with 13C stable isotope glucose to assess glucose metabolism in endurance athletes. Our breath test measured the ratio of 13C to 12C in CO2 from expired air to derive 13C excretion per unit time. We compared 13C excretion levels between long-distance runners (runner group) and non-trained healthy males (control group), in both conditions with and without 50 g oral glucose loading (OGL). The 13C excretion was lower in the runner group than in the control group throughout the 6-hour period, regardless of OGL. Therefore, the area under the curve, which indicates total excretion, was lower in the runner group. There are many reports related to the adaptation of glucose metabolism in training (including gluconeogenesis, glucose transport to the liver and muscle, and glycogen synthesis). Our study showed that this breath test could be a simple and convenient way to monitor the overall glucose metabolic adaptation state in the athlete body.

Abstract Background Varicella-Zoster virus (VZV) vasculopathy occasionally occurs in immunocompromised patients and is difficult to treat. The risk factor and optimal therapy remain unclear. Patients with human immunodeficiency virus (HIV) and dysphagia or difficulty in oral intake receive antiretroviral therapy (ART) suspension. However, there remains little evidence regarding ART suspension. Case presentation We experienced a case of a 55-year-old man diagnosed with HIV and severe multiple cerebral infarctions due to VZV vasculopathy. We started on bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) and acyclovir (ACV), and prednisone. He was started on BIC/TAF/FTC suspension because of deteriorated swallowing. The HIV viral load was increased; however, no drug-resistance genes were detected. We successfully treated him with doltegravir/abacavir/lamibudine suspension. We performed two literature reviews of the administration of BIC/TAF/3TC suspension and VZV vasculopathy in patients with HIV. Three cases of BIC/TAF/3TC suspension were considered treatment failures. Recent history of VZV infection and a CD4 count under 200 μL may be risk factors for VZV vasculopathy. The effective treatment may be using steroid and ACV; however, treatment duration could differ. Conclusions BIC/TAF/FTC suspension administration may be unstable, and treating ACV and steroid may be optimal therapy for VZV vasculopathy; however, the evidence level is low.

IntroductionEconomic loss estimation is critical for policymakers to craft policies that balance economic and health concerns during pandemic emergencies. However, this task is time-consuming and resource-intensive, posing challenges during emergencies.MethodTo address this, we proposed using electricity consumption (EC) and nighttime lights (NTL) datasets to estimate the total, commercial, and industrial economic losses from COVID-19 lockdowns in the Philippines. Regression models were employed to establish the relationship of GDP with EC and NTL. Then, models using basic statistics and weather data were developed to estimate the counterfactual EC and NTL, from which counterfactual GDP was derived. The difference between the actual and the counterfactual GDP from 2020 to 2021 yielded economic loss.ResultsThis paper highlights three findings. First, the regression model results established that models based on EC (adj-R2 ≥ 0.978) were better at explaining GDP than models using NTL (adj-R2 ≥ 0.663); however, combining both EC and NTL improved the prediction (adj-R2 ≥ 0.979). Second, counterfactual EC and NTL could be estimated using models based on statistics and weather data explaining more than 81% of the pre-pandemic values. Last, the estimated total loss amounted to 2.9 trillion PhP in 2020 and 3.2 trillion PhP in 2021. More than two-thirds of the losses were in the commercial sector as it responded to both policies and the COVID-19 case surge. In contrast, the industrial sector was affected primarily by the lockdown implementation.DiscussionThis method allowed monitoring of economic losses resulting from long-term and large-scale hazards such as the COVID-19 pandemic. These findings can serve as empirical evidence for advocating targeted strategies that balance public health and the economy during pandemic scenarios.

A 31-year-old woman who had unprotected sexual intercourse with multiple partners presented to our hospital with bilateral leg edema, weight gain, and eyelid edema. One month before her visit, she had a fever of 38.0 ℃ for 2 days, and 1 week before her visit, she experienced fatigue. The presence of hypoalbuminemia, proteinuria, and leg edema raised the suspicion of nephrotic syndrome along with syphilis. She was treated with doxycycline for secondary nephrotic syndrome caused by secondary syphilis. Secondary syphilis is a well-known but rare cause of secondary nephrotic syndrome, and the occurrence rate, risk factors, and timing of occurrence are unknown. Therefore, we have supplemented this case report with a concise review of the relevant literature that delineates the use of appropriate antibiotic therapy in the management of secondary nephrotic syndrome derived from secondary syphilis.

Oral immunotherapy (OIT) is an effective approach to controlling food allergy. Although the detailed molecular and cellular mechanisms of OIT are unknown currently, they must be understood to advance the treatment of allergic diseases in general. To elucidate the mechanisms of OIT, especially during the immunological transition from desensitization to allergy regulation, we generated a clinical OIT murine model and used it to examine immunological events of OIT. We found that in mice that completed OIT successfully, desensitized mast cells (MCs) showed functionally beneficial alterations, such as increased induction of regulatory cytokines and enhanced expansion of regulatory T cells. Importantly, these regulatory-T-cell-mediated inhibitions of allergic responses were dramatically decreased in mice lacking OIT-induced desensitized MC. Collectively, these findings show that the desensitization process modulates the activation of MCs, leading directly to enhanced induction of regulatory-T-cell expansion and promotion of clinical allergic unresponsiveness. Our results suggest that efficiently inducing regulatory MCs is a novel strategy for the treatment of allergic disease.

Abstract Background Diagnosis of aortic graft infections (AGI) is challenging. Here, we report a case of AGI with splenomegaly and splenic infarction. Case presentation A 46-year-old man who underwent total arch replacement for Stanford type A acute aortic dissection one year prior presented to our department with fever, night sweat, and a 20-kg weight loss over several months. Contrast-enhanced computed tomography (CT) revealed splenic infarction with splenomegaly, fluid collection, and thrombus around the stent graft. Positron emission tomography-CT (PET-CT) revealed abnormal 18F-fluorodeoxyglucose uptake in the stent graft and spleen. Transesophageal echocardiography revealed no vegetations. The patient was diagnosed with an AGI and underwent graft replacement. Blood and tissue cultures in the stent graft yielded Enterococcus faecalis. After the surgery, the patient was successfully treated with antibiotics. Conclusions Splenic infarction and splenomegaly are the clinical findings of endocarditis but are rare in graft infection. These findings could be helpful to diagnose graft infections, which is often challenging.

Increases in adhesive and invasive commensal bacteria, such as Escherichia coli, and subsequent disruption of the epithelial barrier is implicated in the pathogenesis of inflammatory bowel disease (IBD). However, the protective systems against such barrier disruption are not fully understood. Here, we show that secretion of luminal glycoprotein 2 (GP2) from pancreatic acinar cells is induced in a TNF-dependent manner in mice with chemically induced colitis. Fecal GP2 concentration is also increased in Crohn's diease patients. Furthermore, pancreas-specific GP2-deficient colitis mice have more severe intestinal inflammation and a larger mucosal E. coli population than do intact mice, indicating that digestive-tract GP2 binds commensal E. coli, preventing epithelial attachment and penetration. Thus, the pancreas-intestinal barrier axis and pancreatic GP2 are important as a first line of defense against adhesive and invasive commensal bacteria during intestinal inflammation.

Mesenchymal cells in the crypt play indispensable roles in the maintenance of intestinal epithelial homeostasis through their contribution to the preservation of stem cells. However, the acquisition properties of the production of stem cell niche factors by the mesenchymal cells have not been well elucidated, due to technical limitations regarding the isolation and subsequent molecular and cellular analyses of cryptal mesenchymal cells. To evaluate the function of mesenchymal cells located at the large intestinal crypt, we established a novel method through which cells are harvested according to the histologic layers of mouse colon, and we compared cellular properties between microenvironmental niches, the luminal mucosa and crypts. The gene expression pattern in the cryptal mesenchymal cells showed that receptors of the hormone/cytokine leptin were highly expressed, and we found a decrease in Wnt2b expression under conditions of leptin receptor deficiency, which also induced a delay in cryptal epithelial proliferation. Our novel stratified layer isolation strategies thus revealed new microenvironmental characteristics of colonic mesenchymal cells, including the intrinsic involvement of leptin in the control of mucosal homeostasis.

Muscle regeneration requires the contribution and communication of various different cell types. Here, Nawaz et al. show that CD206+ macrophages inhibit the secretion of the promyogenic factor follistatin by fibro-adipogenic progenitor cells, impeding myogenesis and muscle regeneration.

Abstract Background Toxic shock syndrome (TSS) caused by Staphylococcus aureus in the postpartum period is a rare but life-threatening disease. We present a case of acute heart failure as the initial presentation of TSS due to methicillin-susceptible Staphylococcus aureus (MSSA) and describe its clinical characteristics with a systematic literature review. Case presentation A 34-year-old woman, 8 days after a normal vaginal delivery presented to our hospital with dyspnea and fever. She had jugular venous distension, bilateral leg edema, and erythema. Laboratory examinations revealed elevated NT-pro-BNP level of 3,233 pg/mL. Transthoracic echocardiography showed elevated tricuspid regurgitation peak gradient, with decreased respiratory variability of the inferior vena cava diameter and bilateral pleural effusions. The patient was hospitalized with suspicion of congestive heart failure. MSSA positive for toxic shock syndrome exotoxin-1 was detected in the culture of the perineal incision wound, and we diagnosed TSS caused by MSSA. Intravenous diuretics were administered, along with eventual cefazolin plus clindamycin. After 2 weeks of antimicrobial therapy, the patient showed improvement and was discharged. No recurrence was observed at the 24-month follow-up. Conclusion This is a rare case report of acute heart failure being the initial manifestation of TSS due to MSSA in the postpartum period. Clinicians should consider TSS as a possibility in postpartum patients with acute heart failure. This systematic review provides insights into its clinical features, treatment regimens, and prognosis of TSS by S. aureus in the postpartum period. TSS requires an appropriate, prompt diagnosis, because delayed treatment can be fatal.

Besides hepatocytes, resident immune cells of the liver are also contributing to the body’s energy homeostasis. Here authors show that group 2 innate lymphoid cells interact with a specific set of hepatocytes in suppressing gluconeogenesis and regulate blood glucose levels via Interleukin-13 signalling.

A giant vesicle system combines fatty acid synthesis pathways, CoA recycling, and cell-free acyltransferase gene expression to perform phospholipid synthesis inside.

Abstract Disseminated intravascular coagulation (DIC) is one of the major organ dysfunctions associated with sepsis. This retrospective secondary analysis comprised data from a prospective multicenter study to investigate the age-related differences in the survival benefit of anticoagulant therapy in sepsis according to the DIC diagnostic criteria. Adult patients with severe sepsis based on the Sepsis-2 criteria were enrolled and divided into the following groups: (1) anticoagulant group (patients who received anticoagulant therapy) and (2) non-anticoagulant group (patients who did not receive anticoagulant therapy). Patients in the former group were administered antithrombin, recombinant human thrombomodulin, or their combination. The increases in the risk of hospital mortality were suppressed in the high-DIC-score patients aged 60–70 years receiving anticoagulant therapy. No favorable association of anti-coagulant therapy with hospital mortality was observed in patients aged 50 years and 80 years. Furthermore, anticoagulant therapy in the lower-DIC-score range increased the risk of hospital mortality in patients aged 50–60 years. In conclusion, anticoagulant therapy was associated with decreased hospital mortality according to a higher DIC score in septic patients aged 60–70 years. Anticoagulant therapy, however, was not associated with a better outcome in relatively younger and older patients with sepsis.