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Abstract Background Blast transformation is a rare but well-recognized event in Philadelphia-negative myeloproliferative neoplasms associated with a poor prognosis. Secondary acute myeloid leukemias evolving from myeloproliferative neoplasms are characterized by a unique set of cytogenetic and molecular features distinct from de novo disease. t(8;21) (q22;q22.1); RUNX1::RUNX1T1, one of the most frequent cytogenetic abnormalities in de novo acute myeloid leukemia, is rarely observed in post-myeloproliferative neoplasm acute myeloid leukemia. Here we report a case of secondary acute myeloid leukemia with t(8;21) evolving from JAK2-mutated essential thrombocythemia. Case presentation The patient was a 74-year-old Japanese woman who was referred because of thrombocytosis (platelets 1046 × 109/L). Bone marrow was hypercellular with increase of megakaryocytes. Chromosomal analysis presented normal karyotype and genetic test revealed JAK2 V617F mutation. She was diagnosed with essential thrombocythemia. Thrombocytosis had been well controlled by oral administration of hydroxyurea; 2 years after the initial diagnosis with ET, she presented with leukocytosis (white blood cells 14.0 × 109/L with 82% of blasts), anemia (hemoglobin 91 g/L), and thrombocytopenia (platelets 24 × 109/L). Bone marrow was hypercellular and filled with 80% of myeloperoxidase-positive blasts bearing Auer rods. Chromosomal analysis revealed t(8;21) (q22;q22.1) and flow cytometry presented positivity of CD 13, 19, 34, and 56. Molecular analysis showed the coexistence of RUNX1::RUNX1T1 chimeric transcript and heterozygous JAK2 V617F mutation in leukemic blasts. She was diagnosed with secondary acute myeloid leukemia with t(8;21)(q22;q22.1); RUNX1::RUNX1T1 evolving from essential thrombocythemia. She was treated with combination chemotherapy with venetoclax and azacytidine. After the first cycle of the therapy, blasts disappeared from peripheral blood and decreased to 1.4% in bone marrow. After the chemotherapy, RUNX1::RUNX1T1 chimeric transcript disappeared, whereas mutation of JAK2 V617F was still present in peripheral leukocytes. Conclusions To our best knowledge, the present case is the first one with JAK2 mutation preceding the acquisition of t(8;21). Our result suggests that t(8;21); RUNX1::RUNX1T1 can be generated as a late event in the progression of JAK2-mutated myeloproliferative neoplasms. The case presented typical morphological and immunophenotypic features associated with t(8;21) acute myeloid leukemia.

Abstract Background The human induced pluripotent stem cells (hiPSCs) can generate all the cells composing the human body, theoretically. Therefore, hiPSCs are thought to be a candidate source of stem cells for regenerative medicine. The major challenge of allogeneic hiPSC-derived cell products is their immunogenicity. The hypoimmunogenic cell strategy is allogenic cell therapy without using immune suppressants. Advances in gene engineering technology now permit the generation of hypoimmunogenic cells to avoid allogeneic immune rejection. In this study, we generated a hypoimmunogenic hiPSC (HyPSC) clone that had diminished expression of human leukocyte antigen (HLA) class Ia and class II and expressed immune checkpoint molecules and a safety switch. Methods First, we generated HLA class Ia and class II double knockout (HLA class Ia/II DKO) hiPSCs. Then, a HyPSC clone was generated by introducing exogenous β-2-microglobulin (B2M), HLA-G, PD-L1, and PD-L2 genes, and the Rapamycin-activated Caspase 9 (RapaCasp9)-based suicide gene as a safety switch into the HLA class Ia/II DKO hiPSCs. The characteristics and immunogenicity of the HyPSCs and their derivatives were analyzed. Results We found that the expression of HLA-G on the cell surface can be enhanced by introducing the exogenous HLA-G gene along with B2M gene into HLA class Ia/II DKO hiPSCs. The HyPSCs retained a normal karyotype and had the characteristics of pluripotent stem cells. Moreover, the HyPSCs could differentiate into cells of all three germ layer lineages including CD45+ hematopoietic progenitor cells (HPCs), functional endothelial cells, and hepatocytes. The HyPSCs-derived HPCs exhibited the ability to evade innate and adaptive immunity. Further, we demonstrated that RapaCasp9 could be used as a safety switch in vitro and in vivo. Conclusion The HLA class Ia/II DKO hiPSCs armed with HLA-G, PD-L1, PD-L2, and RapaCasp9 molecules are a potential source of stem cells for allogeneic transplantation.

Abstract A multicenter study of nonmetastatic castration-resistant prostate cancer (nmCRPC) was conducted to identify the optimal cut-off value of prostate-specific antigen (PSA) doubling time (PSADT) that correlated with the prognosis in Japanese nmCRPC. Of the 515 patients diagnosed and treated for nmCRPC at 25 participating Japanese Urological Oncology Group centers, 450 patients with complete clinical information were included. The prognostic values of clinical factors were evaluated with respect to prostate specific antigen progression-free (PFS), cancer-specific survival (CSS), and overall survival (OS). The optimal cutoff value of PSADT was identified using survival tree analysis by Python. The Median PSA and PSADT at diagnosis of nmCRPC were 3.3 ng/ml, and 5.2 months, respectively. Patients treated with novel hormonal therapy (NHT) showed significantly longer PFS (HR: hazard ratio 0.38, p

Subclavian artery injuries during internal jugular vein puncture when attempting central venous catheter insertion are rare. A 60-year-old man undergoing treatment for neuromyelitis optica with paralysis and sensory loss developed a complication during catheter placement into his right internal jugular vein for plasmapheresis. His previous physician felt resistance and discontinued the procedure. The patient later developed mild dyspnea and dysphagia. Computed tomography scans indicated thrombus formation and tracheal deviation. Contrast-enhanced computed tomography scans showed right subclavian artery injury with extravasation and a large pseudoaneurysm.Following transferal to our hospital, he was stable and asymptomatic; however, contrast-enhanced computed tomography scans showed a pseudoaneurysm located proximal to the right subclavian artery. Considering challenges with compression hemostasis and the invasiveness of open surgery, endovascular treatment was selected using a VIABAHN stent graft. A balloon occlusion test of the right vertebral artery was performed to assess stroke risk. Prophylactic embolization of the right vertebral artery, internal thoracic artery, and thyrocervical trunk were performed to prevent a type 2 endoleak. On hospital day 5, our patient showed no postoperative complications and was transferred to the referring hospital. Follow-up imaging showed the graft was intact with no pseudoaneurysm, confirming successful treatment. Endovascular treatment with a stent graft is highly effective for peripheral artery injuries. Using a balloon occlusion test to assess collateral blood flow and stroke risk is essential pretreatment, especially when a graft might occlude the vertebral artery. Balloon occlusion tests are recommended when planning treatment for iatrogenic and other types of subclavian artery injuries.

Abstract The prognostic significance of unconventional histology (UH) subtypes including intraductal carcinoma of the prostate (IDC-P), ductal adenocarcinoma, and cribriform pattern has been investigated for prostate cancer (PCa). However, little is known about magnetic resonance imaging (MRI) features and the oncological impact of tumor localization in localized PCa with UH. Clinical data of 211 patients with acinar adenocarcinoma (conventional histology [CH]) and 82 patients with UH who underwent robotic-assisted radical prostatectomy (RARP) were reviewed. Patients with UH are more likely to be older and have higher Gleason grade group, higher Prostate Imaging-Reporting and Data System (PI-RADS) v2.1 score, and larger tumor volume (TV) than those with CH. Multivariate analysis identified the presence of UH as an independent prognostic factor for progression-free survival (PFS) (hazard ration (HR) 2.41, 95% confidence interval (CI) 0.22–0.79, P = 0.0073). No significant difference in PFS was seen regarding tumor localization (transition zone [TZ] or peripheral zone [PZ]) in patients with UH (P = 0.8949), whereas PZ cancer showed shorter PFS in patients with CH (P = 0.0174). PCa with UH was associated with higher progression than PCa with CH among resection margin (RM)-negative cases (P

Abstract We show how effects of compositeness emerging in a Composite 2-Higgs Doublet Model can enter Standard Model (SM)-like Higgs boson pair production at the Large Hadron Collider in both resonant and non-resonant mode. Such effects can arise from modified trilinear Higgs self-couplings and top-Yukawa couplings, as well as from loops of new heavy quarks and additional quartic Higgs-fermion interactions. In the resonant case, significant distortions of the Breit-Wigner shape of a new scalar state decaying into the two SM-like Higgs states may occur due to interference effects amongst not only the SM-like diagrams but also those involving the new heavy quarks. In the non-resonant case, a modification of the underlying line-shape and a local maximum at twice a new heavy quark mass appear simultaneously. We quantify these effects by taking into account the relevant theoretical and latest experimental bounds.

Abstract This study aimed to elucidate the relationship between joint structures of the first tarsometatarsal and articular facet degeneration. A total of 100 feet from 50 cadavers were examined. The articular facets of the first metatarsal and medial cuneiform were categorized into four types based on the superior and inferior facets' separation, and the formation of the inferior lateral facet on the lateral plantar prominence: Type I, a single facet with no separation or inferior lateral facet; Type II-a, two facets with separation but no inferior lateral facet; Type II-b, two facets, no separation, but with an inferior lateral facet; Type III, three facets with separation and an inferior lateral facet. When both bone types matched, they were defined as Type I, Type II-a, Type II-b, and Type III joints, respectively; unmatched types were classified as Unpair joints. The severity of articular cartilage degeneration on both bones was assessed using a 5-point scale. The degeneration grade was compared among joint types. Type III joints exhibited significantly milder articular cartilage degeneration in medial cuneiform compared to Type II-a, II-b, Unpair joints. The formation of inferior lateral facet and separation of the superior and inferior facets might be crucial for the joint's stability.

Introduction: Young adults are hesitant to receive the coronavirus disease 2019 (COVID-19) vaccination owing to concerns regarding adverse events despite the effectiveness of vaccines in preventing SARS-CoV-2 infection-associated serious illness, hospitalization, and death. Methods: A retrospective cohort study was conducted in Gifu University students receiving the mRNA-1273 vaccine and boosters to elucidate the real incidence of adverse events and factors that prevent them. We examined the adverse events and identified potential risk factors through a self-administered questionnaire on the participants’ physical condition after COVID-19 vaccination. Results: Focal/systemic adverse events were highly frequent among university students after receiving the COVID-19 vaccine; however, there were no life-threatening cases or hospitalizations over two years. A higher number of vaccinations (p

Abstract Anterior ankle impingement syndrome (AAIS) has been reported to account for a high percentage of complications following ankle fracture surgery. The soft tissue etiology of AAIS is thought to be thickening and inflammation of the anterior ankle soft tissues intervening anteriorly at the tibiotalar joint, causing pain and functional limitation during dorsiflexion. However, the effects of anterior ankle soft tissue dynamics and stiffness on AAIS have yet to be clarified. This study aimed to determine the relationship between AAIS and the anterior ankle soft tissue thickness change ratio and shear modulus using ultrasonography (US). The participants were 20 patients with ankle joint fractures (AO classification A, B) who had undergone open reduction and internal fixation and 20 healthy adults. The evaluation periods were 3 months and 6 months postoperatively. US was used to delineate the tibialis anterior tendon, extensor hallucis longus tendon, and the extensor digitorum longus tendon over the talus and tibia on a long-axis image. Anterior ankle soft tissue thickness was measured as the shortest distance from the most convex part of the talus to the tendon directly above it. The Anterior ankle soft tissue thickness change ratio was determined by dividing the value at 0° dorsiflexion by the value at 10° plantarflexion. The same images as for the anterior soft tissue thickness measurement were drawn for the shear modulus measurement, and the average shear modulus (kPa) was calculated using shear-wave elastography. There was no significant difference in the thickness change ratio between the postoperative and healthy groups. Compared with the healthy group, the shear modulus was significantly higher at 3 and 6 months in the postoperative group (p

Abstract Background Rhabdomyolysis is characterized by the destruction and necrosis of skeletal muscle tissue, resulting in acute kidney injury (AKI). Recombinant antithrombin (rAT) has DNA repair and vascular endothelial-protection properties. Herein, we investigated whether rAT therapy has beneficial effects against rhabdomyolysis-induced AKI. Ten-week-old male B6 mice were injected with 5 mL/kg of 50% glycerol intramuscularly in the left thigh after 24 h of fasting to create a rhabdomyolysis mouse model. Further, 750 IU/kg rAT was injected intraperitoneally at 24 and 72 h after the rhabdomyolysis model was established. The mice were euthanized after 96 h for histological analysis. Saline was administered to mice in the control group. Results Blood tests show elevated serum creatinine, urea nitrogen, and neutrophil gelatinase-associated lipocalin levels in rhabdomyolysis. Loss of tubular epithelial cell nuclei and destruction of the tubular luminal surface structure was observed in the untreated group, which improved with rAT treatment. Immunostaining for Ki-67 showed increased Ki-67-positive nuclei in the tubular epithelial cells in the rAT group, suggesting that rAT may promote tubular epithelial cell regeneration. The microvilli of the brush border of the renal tubules were shed during rhabdomyolysis, and rAT treatment reduced this injury. The vascular endothelial glycocalyx, which is usually impaired by rhabdomyolysis, became functional following rAT treatment. Conclusions Treatment with rAT suppressed rhabdomyolysis-induced AKI, suggesting that rAT therapy may be a novel therapeutic approach.

Abstract Intradialytic hypotension and arrhythmias are complications of hemodialysis. They are associated with decreased intravascular volume due to reduced ultrafiltration volume, cardiac function, and arterial tone. The vascular endothelial glycocalyx, which exists on the surface of healthy vascular endothelial cells and maintains vascular permeability, has been suggested to be impaired by hemodialysis. This single-center retrospective study evaluated the association between syndecan-1, an endothelial glycocalyx dysfunction marker, and complications of hemodialysis. We enrolled 92 patients who underwent outpatient hemodialysis at Gifu Seiryu Hospital from April to July 2022 (346 hemodialysis sessions). The median duration and time of hemodialysis were 40 months and 4.1 h, respectively. Median serum syndecan-1 levels were 67.7 ng/mL before and 98.3 ng/mL after hemodialysis. Hemodialysis complications were noted in 68 sessions, all of which were hypotension. No correlation between pre-hemodialysis syndecan-1 levels and the incidence of complications was observed. However, a positive correlation between the amount of change in syndecan-1 levels before and after hemodialysis and the incidence of hemodialysis complications was noted. Conversely, syndecan-1 levels did not correlate with brain or atrial natriuretic peptides, suggesting that impairment of the vascular endothelial glycocalyx may be a possible cause of intradialytic hypotension and may be useful in preventing intradialytic hypotension.

IntroductionAcute kidney injury (AKI), with a fatality rate of 8.6%, is one of the most common types of multiorgan failure in the intensive care unit (ICU). Thus, AKI should be diagnosed early, and early interventions should be implemented. Urinary liver-type fatty acid-binding protein (L-FABP) could aid in the diagnosis of AKI.MethodsIn this prospective, single-center, observational study, we included 100 patients with trauma. Urinary L-FABP levels were measured using a semi-quantitative rapid assay kit 6 and 12 h after injury. Negative, weakly positive, and strongly positive urinary L-FABP levels were examined using two protocols. Using protocol 1, measurements were performed at 6 h after injury negative levels were considered “negative,” and weakly positive and strongly positive levels were considered “positive.” Using protocol 2, strongly positive levels at 6 h after injury were considered “positive,” and negative or weakly positive levels at 6 h after injury were considered “positive” if they were weakly positive or positive at 12 h after injury.ResultsFifteen patients were diagnosed with AKI. Using protocol 1, the odds ratio (OR) was 20.55 (p = 0.001) after adjustment for the injury severity score (ISS), contrast media use, and shock index. When the L-FABP levels at 6 and 12 h were similarly adjusted for those three factors, the OR was 18.24 (p < 0.001). The difference in ORs for protocols 1 and 2 was 1.619 (p = 0.04).DiscussionAssociations between urinary L-FABP and AKI can be examined more precisely by performing measurements at 6 and 12 h after injury than only one time at 6 h.

BackgroundStress-transthoracic Doppler echocardiography (S-TDE) provides a noninvasive assessment of coronary flow parameters in the left anterior descending artery (LAD). However, the association between morphological characteristics and coronary flow changes after elective percutaneous coronary intervention (PCI) remains unclear. We aimed to evaluate the relationships between periprocedural coronary flow changes observed on S-TDE and lesion-specific plaque characteristics obtained by optical coherence tomography (OCT) in the interrogated vessels in patients with chronic coronary syndrome (CCS).Methods and resultsPatients with CCS who underwent pre- and post-PCI S-TDE and elective fractional flow reserve (FFR)-guided PCI under OCT guidance for de novo single LAD lesions were included. S-TDE-derived hyperemic diastolic peak flow velocity (hDPV) was used as a surrogate for coronary flow. Lesions were categorized into two groups based on the %hDPV increase or decrease. The baseline clinical, physiological, and OCT findings were compared between the groups. In total, 103 LAD lesions were studied in 103 patients. After PCI, hDPV significantly increased from 55.6 cm/s to 69.5 cm/s (PConclusionsIn patients who underwent successful uncomplicated elective PCI for de novo single LAD lesions, the presence of layered plaques was independently associated with hyperemic coronary flow decrease as assessed by S-TDE.

A correction to this paper has been published: https://doi.org/10.1007/JHEP07(2022)124

Abstract This study sought to evaluate the prognostic implications of the presence of preprocedural unrecognized myocardial infarction (UMI) and periprocedural myocardial injury (PMI) evaluated by delayed gadolinium enhancement cardiac magnetic resonance (DE-CMR) in patients with chronic coronary syndrome (CCS) undergoing elective percutaneous coronary intervention (PCI). We enrolled 250 CCS patients scheduled for elective PCI. UMI was defined as the presence of late gadolinium enhancement (LGE) detected by pre-PCI CMR in the region without medical history of revascularization and/or MI. Periprocedural new occurrence or increased volume of LGE in the target territory detected by post-PCI CMR (PPL) were used to assess PMI. In the final analysis of 235 patients, UMI and PPL were detected in 43 patients (18.3%) and 45 patients (19.1%), respectively. During follow-up for a median of 2.2 years, major adverse cardiac events (MACE) occurred in 31 (13.2%) patients. On multivariable analysis, UMI and PPL remained as significant predictors of MACE after adjusting confounding factors (HR 4.62, 95% CI 2.24–9.54, P

Weather Report is an initiative from Weathernews Inc. to obtain sky images and current weather conditions from the users of its weather app. This approach can provide supplementary weather information to radar observations and can potentially improve the accuracy of forecasts However, since the time and location of the contributed images are limited, gathering data from different sources is also necessary. This study proposes a system that automatically submits weather reports using a dash cam with communication capabilities and image recognition technology. This system aims to provide detailed weather information by classifying rainfall intensities and cloud formations from images captured via dash cams. In models for fine-grained image classification tasks, there are very subtle differences between some classes and only a few samples per class. Therefore, they tend to include irrelevant details, such as the background, during training, leading to bias. One solution is to remove useless features from images by masking them using semantic segmentation, and then train each masked dataset using EfficientNet, evaluating the resulting accuracy. In the classification of rainfall intensity, the model utilizing the features of the entire image achieved up to 92.61% accuracy, which is 2.84% higher compared to the model trained specifically on road features. This outcome suggests the significance of considering information from the whole image to determine rainfall intensity. Furthermore, analysis using the Grad-CAM visualization technique revealed that classifiers trained on masked dash cam images particularly focused on car headlights when classifying the rainfall intensity. For cloud type classification, the model focusing solely on the sky region attained an accuracy of 68.61%, which is 3.16% higher than that of the model trained on the entire image. This indicates that concentrating on the features of clouds and the sky enables more accurate classification and that eliminating irrelevant areas reduces misclassifications.

Abstract The Higgs portal interaction to a singlet sector of the standard model (SM) gauge group is widely-studied. In this paper, we show that a quantum effect is important if the Higgs field mixes with another singlet scalar field whose decay rate is larger than the mass difference between the two mass eigenstates. This effect may be interpreted as the “quantum Zeno effect” by defining the (would-be) decay process of the singlet scalar as the measurement. In either the quantum mechanics or the quantum field theory, we show that the resulting propagating mode is not the eigenstate of the mass matrix, but it is approximately the eigenstate of the interaction. As a consequence, the decoupling of the mixing effect happens at the infinity limit of the decay width of the exotic scalar even if the naïve mixing parameter is not small. With a finite decay width of the exotic scalar, we derive the effective mass of the propagating mode in the SM sector, its decay rate, and the couplings at the 1-loop level. It turns out that the mixed mass eigenstates can mimic the discovered 125 GeV Higgs boson. This fuzzy Higgs boson can be obtained in a simple perturbative renormalizable model when the mass difference is smaller than O(0.1)GeV (O(1) GeV, O(10)GeV) for O(1) (O(0.01), O(0.001)) mixing to be consistent with the 125 GeV SM Higgs boson. We argue the possible natural scenario for the tiny mass splitting and the possibility that the upper bound of the mass difference is larger for a strongly-coupled singlet sector. To probe the fuzzy Higgs boson scenario, it is difficult to directly produce the singlet sector particles. Nevertheless, the future Higgs factories may probe this scenario by precisely measuring the Higgs boson invisible decay rate and the deviation of the Higgs coupling. Applications of the mechanism are also mentioned.

Abstract Background Drug-induced hypersensitivity syndrome (DIHS), including Stevens-Johnson syndrome (SJS), is a severe rash that often develops 2–6 weeks after the intake of the causative drug; however, its diagnosis is sometimes difficult. This article describes a case in which a patient with DIHS-induced multiple organ failure was successfully treated with blood purification therapy. Case presentation A male patient in his 60s was admitted to our hospital with autoimmune encephalitis. The patient was treated with steroid pulse therapy, acyclovir, levetiracetam, and phenytoin. From the 25th day, he presented with fever (≥ 38 °C) as well as miliary-sized erythema on the extremities and trunk, followed by erosions. DIHS and SJS were suspected; accordingly, levetiracetam, phenytoin, and acyclovir were discontinued. On the 30th day, his condition further deteriorated, and he was admitted to the intensive care unit for ventilatory management. The next day, he developed multi-organ failure and was started on hemodiafiltration (HDF) for acute kidney injury. Although he presented with hepatic dysfunction and the appearance of atypical lymphocytes, he did not meet the diagnostic criteria for DIHS or SJS/toxic epidermal necrolysis. Therefore, he was diagnosed with multi-organ failure caused by severe drug eruption and underwent a 3-day treatment with plasma exchange (PE) in addition to HDF. Accordingly, the patient was diagnosed with atypical DIHS. After being started on blood purification therapy, the skin rash began to disappear; moreover, the organ damage improved, with a gradual increase in urine output. Eventually, the patient was weaned off the ventilator and transferred to the hospital on the 101st day. Conclusions HDF + PE could effectively treat multi-organ failure caused by atypical DIHS, which is difficult to diagnose.

Abstract Machine learning technology is expected to support diagnosis and prognosis prediction in medicine. We used machine learning to construct a new prognostic prediction model for prostate cancer patients based on longitudinal data obtained from age at diagnosis, peripheral blood and urine tests of 340 prostate cancer patients. Random survival forest (RSF) and survival tree were used for machine learning. In the time-series prognostic prediction model for metastatic prostate cancer patients, the RSF model showed better prediction accuracy than the conventional Cox proportional hazards model for almost all time periods of progression-free survival (PFS), overall survival (OS) and cancer-specific survival (CSS). Based on the RSF model, we created a clinically applicable prognostic prediction model using survival trees for OS and CSS by combining the values of lactate dehydrogenase (LDH) before starting treatment and alkaline phosphatase (ALP) at 120 days after treatment. Machine learning provides useful information for predicting the prognosis of metastatic prostate cancer prior to treatment intervention by considering the nonlinear and combined impacts of multiple features. The addition of data after the start of treatment would allow for more precise prognostic risk assessment of patients and would be beneficial for subsequent treatment selection.

Dysregulation of T cell homeostasis is known to contribute to the immunopathology of autoimmune diseases. Here the authors show that itaconate impacts autoimmune pathology by altering T cells via modulation of metabolic and epigenetic programs.

Abstract Background Spinal ankylosing disorders (SADs) refer to a group of conditions resulting in spontaneous or postsurgical ossification and fusion of the spinal segments. The spine becomes increasingly susceptible to injury over time such that even low-energy trauma can cause a spinal injury. We report two cases of SADs, associated with massive thoracic hemorrhage. Case presentation The first patient was an 85-year-old male, who suffered from a vehicular crash. He was diagnosed with a fracture of the first lumbar vertebra, accompanied by SADs. Intubation was required, and thoracic drainage tubes were inserted. The patient underwent a massive transfusion and thoracotomy with packing. Despite prompt treatment, the hemorrhage from the vertebral fracture was uncontrolled, and the patient died 180 min after the injury. The second case features an 88-year-old male who fell from a height. He was diagnosed with flail chest, hemothorax, pneumothorax, and a fracture of the eighth thoracic vertebra with SADs. After intubation, four thoracic drainage tubes were placed, and a massive transfusion was conducted. He died after 3 days due to hypoxemia secondary to persistent bleeding of the vertebral fracture for 24 h. Conclusions The patients died of persistent thoracic hemorrhage, and the sources of bleeding were the fracture site of the spine fractures. Controlling spinal hemorrhage is difficult due to the absence of a bleeding artery, which is managed via trans-arterial embolization. This report emphasized that fracture of SADs could be a fatal disease that requires prompt intervention.

Background: Since gastric cancers (GCs) detected after Helicobacter pylori (HP) eradication present with different morphological characteristics from conventional HP-positive GCs, delayed detection of early-stage GCs may be observed. This study aimed to investigate the clinical impact of HP eradication on diagnosing GC during screening endoscopy. Methods: Eleven health checkup institutions in Japan participated in the present study. All GC cases newly diagnosed by screening endoscopy between January 2016 and December 2020 were included. After propensity score matching, multivariable regression analysis was performed to estimate the effect of HP eradication on deep tumor invasion among HP-eradicated and HP-positive GC cases. Results: A total of 231 patients with GCs (134 HP-eradicated and 97 HP-positive cases) were enrolled. After propensity score matching, there were 81 cases in each group. The distribution of the depth of tumor invasion (pT1a, pT1b1, pT1b2, and pT2) between the HP-eradicated group and HP-positive group was similar (p = 0.82). In the propensity analysis, with HP-positive as the reference value, HP eradication was not significantly associated with T1b–T4-GCs and T1b2–T4-GCs, with odds ratios (95% confidence intervals) of 1.16 (0.48–2.81) and 1.16 (0.42–3.19), respectively. Conclusions: HP eradication does not adversely affect the clinical course of GCs, supporting the recommendation of HP eradication in screening programs to reduce the total number of GC cases without delaying diagnosis.

Lithium–air batteries (LABs) have a theoretically high energy density. However, LABs have some issues, such as low energy efficiency, short life cycle, and high overpotential in charge–discharge cycles. To solve these issues electrocatalytic materials were developed for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), which significantly affect battery performance. In this study, we aimed to synthesize electrocatalytic N-doped carbon-based composite materials with solution plasma (SP) using Co or Ni as electrodes from organic solvents containing cup-stacked carbon nanotubes (CSCNTs), iron (II) phthalocyanine (FePc), and N-nethyl-2-pyrrolidinone (NMP). The synthesized N-doped carbon-based composite materials were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS). TEM observation and XPS measurements revealed that the synthesized carbon materials contained elemental N, Fe, and electrode-derived Co or Ni, leading to the successful synthesis of N-doped carbon-based composite materials. The electrocatalytic activity for ORR of the synthesized carbon-based composite materials was also evaluated using electrochemical measurements. The electrochemical measurements demonstrated that the electrocatalytic performance for ORR of N-doped carbon-based composite material including Fe and Co showed superiority to that of N-doped carbon-based composite material including Fe and Ni. The difference in the electrocatalytic performance for ORR is discussed regarding the difference in the specific surface area and the presence ratio of chemical bonding species.

Grain yield of rice consists of sink capacity and grain filling. There are some genes known to contribute to sink capacity, but few genes associated with grain filling are known. We conducted a genetic analysis on yield-related traits by using a chromosome segment substitution line population that have introgression from DV85, an aus variety of rice, in the background of T65, a japonica variety. Refined whole-genome genotypes of the 43 TD-CSSLs were obtained by genotyping-by-sequencing. The effects of previously detected quantitative trait loci (QTLs), qNSC1 and qNSC2, were confirmed by the amount of non-structural carbohydrate (NSC) at 5 days after heading (DAH). The CSSL for qSWTR11, the QTL for decrease in shoot weight during the maturity stage, showed the highest NSC at 5 DAH and lowest at 35 DAH. The brown rice yield of these lines were not stably significant. Most of the sink-related traits correlated between the 2 tested years, but most of the grain-filling traits did not show correlation between the 2 years. Correlation analysis revealed that the sink capacity is stable and primarily determines the yield, and grain filling is more affected by the environment. In addition, biomass production before heading and during the maturity stage contributes to higher yield in TD-CSSLs, and the amount of translocation of stem reserve does not affect much to the yield. We conclude that higher NSC at the heading stage and rapid decrease in shoot biomass during the maturity stage did not directly contribute to the yield formation in the japonica genetic background.

Immune responses are orchestrated by controlling the initiation, magnitude, and duration of various signaling pathways. Adaptor proteins act as positive or negative regulators by targeting critical molecules of signaling cascades. Signal-transducing adaptor protein-2 (STAP-2) contains typical features of adaptor proteins, like a pleckstrin homology (PH) domain in the N-terminal region and a Src homology 2 (SH2) domain in the central region. STAP-2 binds to a variety of signaling or transcriptional molecules to control multiple steps of inflammatory/immune responses. STAP-2 enhances T-cell receptor (TCR)-mediated signaling via the association with TCR-proximal CD3ζ immunoreceptor tyrosine-based activation motifs (ITAMs) and lymphocyte-specific protein tyrosine kinase (Lck). STAP-2 decreases adherence of T-cells to fibronectin (FN) through an association with focal adhesion kinase (Fak) and Casitas B-lineage Lymphoma (c-Cbl), and increases chemotaxis of T-cells toward stromal cell-derived factor-1α (SDF-1α) through interactions with Vav1 and Ras-related C3 botulinum toxin substrate 1 (Rac1). STAP-2 positively regulates activation-induced cell deathrough the association with Fas and caspase-8. This review describes the current knowledge of the roles of STAP-2 in T-cell-dependent immune responses and the possible clinical utility of STAP-2-targeting therapies.

Abstract Unrecognized myocardial infarction (UMI) is associated with adverse outcomes. This prospective, single-center study elucidated the prevalence and prognostic significance of UMI before elective percutaneous coronary intervention (PCI) using delayed-enhancement cardiac magnetic resonance (DE-CMR). We enrolled 236 patients with stable coronary artery disease who underwent DE-CMR before elective PCI. The prevalence of UMI and the association of clinical and CMR-derived variables with major adverse cardiac events (MACE), defined as cardiovascular death, nonfatal MI, hospitalization for congestive heart failure, and unplanned late revascularization, were assessed. Final analysis revealed that 63/213 (29.6%) patients had UMI. Target territory UMI was observed in 38 patients (17.8% of the total cohort, 60.3% of patients with UMI). UMI was significantly associated with sex, diabetes mellitus, left ventricular ejection fraction, SYNTAX score, and fractional flow reserve in the target vessels. During follow-up (median, 23 months), MACE occurred in 17 (27.0%) patients with UMI and 17 (11.3%) without UMI (P = 0.001). Multivariable modeling revealed that UMI (hazard ratio: 2.18, 95%CI, 1.10–4.33, P = 0.001) was an independent predictor of MACE. Kaplan–Meier analysis indicated that the presence of UMI was significantly associated with a higher incidence of MACE. UMI was independently associated with a greater risk of MACE after successful PCI.

Artificial intelligence (AI) technology leads to new insights into the manipulation of quantum systems in the Noisy Intermediate-Scale Quantum (NISQ) era. Classical agent-based artificial intelligence algorithms provide a framework for the design or control of quantum systems. Traditional reinforcement learning methods are designed for the Markov Decision Process (MDP) and, hence, have difficulty in dealing with partially observable or quantum observable decision processes. Due to the difficulty of building or inferring a model of a specified quantum system, a model-free-based control approach is more practical and feasible than its counterpart of a model-based approach. In this work, we apply a model-free deep recurrent Q-network (DRQN) reinforcement learning method for qubit-based quantum circuit architecture design problems. This paper is the first attempt to solve the quantum circuit design problem from the recurrent reinforcement learning algorithm, while using discrete policy. Simulation results suggest that our long short-term memory (LSTM)-based DRQN method is able to learn quantum circuits for entangled Bell–Greenberger–Horne–Zeilinger (Bell–GHZ) states. However, since we also observe unstable learning curves in experiments, suggesting that the DRQN could be a promising method for AI-based quantum circuit design application, more investigation on the stability issue would be required.

Introduction Generally, renal transplantation is contraindicated in cancer patients, and a certain follow‐up period is required. We report a case of late recurrence of renal cell carcinoma in a patient who underwent simultaneous radical nephrectomy and cadaver renal transplantation due to renal cell carcinoma observed during renal transplantation after 12 years. Case presentation Incidental renal cell carcinoma was found in a 48‐year‐old man during kidney transplantation who subsequently underwent simultaneous cadaver kidney transplantation and radical nephrectomy. Twelve years after transplantation, he developed an anterior mediastinal tumor, a lung tumor which was resected and a right adrenal gland mass which was resected along with the right kidney. Currently, he is being treated with tyrosine kinase inhibitors owing to the metastasis in the left adrenal gland. Conclusion In patients with metastatic carcinoma undergoing renal transplant, the indications for surgical procedures and choice of immunosuppressants should be carefully considered.

Abstract We study phenomenological implications of an axion that arises as a pseudo Nambu-Goldstone boson due to the spontaneous breaking of anomaly-free global flavor symmetry. One interesting possibility for such anomaly-free axion to explain dark matter (DM) is when it has a mass of order keV and an intermediate scale decay constant, since it can be explored through direct search experiments, X-ray observations, various stellar cooling processes, and the misalignment mechanism naturally explains the DM abundance. As a concrete renormalizable model of such axion, we consider an extended Higgs sector with global flavor symmetry, which consists of three Higgs doublet fields and three singlet Higgs fields with U(1)B−L charges. We identify viable parameter regions that satisfy theoretical bounds on the Higgs potential and various experimental limits on this model, and evaluate the mass spectra of the axion and extra Higgs bosons. We find that even an anomaly-free axion can generally couple to photons through mixing with CP-odd Higgs, and that its strength depends on the vacuum expectation values of the Higgs doublets as well as the axion mass. As a result, the ratios of the vacuum expectation values of the Higgs doublets are tightly constrained to satisfy the X-ray constraints. We show the favored parameter region where axion DM explains the XENON1T excess. We also demonstrate that the axion-electron coupling is correlated with the extra Higgs boson masses and mixing angles for CP-even Higgs bosons. Thus, if the axion is detected in future observations, the extra Higgs boson masses and the coupling of the standard model-like Higgs boson with the weak gauge bosons are restricted. This is a good example of the synergy between searches for the axion DM and the BSM around the electroweak scale.

In this work, a novel device concept for improving the efficiency and field operation of conventional InAs/GaAs quantum dot (QD) based intermediate band solar cell (IBSC) with the feature of current constraint (CC-QD-IBSC) was proposed and evaluated from both theoretical simulations and experimental demonstrations. The advantages of the proposed device concept including increasing efficiency, obtaining higher suitability for operation under concentrated photovoltaic (CPV) condition and more robust efficiency stability against intermediate band fluctuation were rigorously identified using the detailed balance theorem by comparing with conventional InAs/GaAs QD-IBSC. Furthermore, a hybrid molecular beam epitaxy (MBE) and metal organic chemical vapor deposition (MOCVD) shuttle growth of the proposed CC-QD-IBSC were adopted in this work for better preserving QD induced intermediate band feature and overcoming practical growth difficulties. By introducing a InGaP top cell for constraining the current of InAs/GaAs QD-IBSC, the short circuit current density of CC-QD-IBSC decreased to 13.0mA/cm2 under 1 sun illumination, a near 50 % reduction compared to the conventional InAs/GaAs QD-IBSC. On the contrary, by well adjusting the regrowth interface between MBE and MOCVD, we managed to reach the highest conversion efficiency of 22.8 % measured at an UL certified laboratory under light concentration ratio of 93 suns for the proposed CC-QD-IBSC with well-functioning QD and IB feature. It is our belief that our results pave the road for developing techniques geared towards higher efficiency and more practical field applications.

Background A previous coronary computed tomography (CT) angiographic study failed to discriminate optical coherence tomography‐defined intact fibrous cap culprit lesions (IFC group) from those with ruptured fibrous caps (RFC group) in patients with coronary artery disease. This study aimed to evaluate the diagnostic efficacy of preprocedural coronary CT imaging in identifying subsequently performed optical coherence tomography‐defined plaque rupture or erosion at culprit lesions in patients with non–ST‐segment–elevation acute myocardial infarction. Methods and Results This study used data from 2 recently published studies that tested the hypothesis that coronary CT angiography (CCTA) before percutaneous coronary intervention may provide diagnostic information on the high‐risk atherosclerotic burden in patients with non–ST‐segment–elevation acute myocardial infarction. In the analysis of 186 patients, optical coherence tomography identified 106 RFC plaques and 80 IFC plaques as the culprit lesions. On CT, the prevalence of low‐attenuation plaque, positive remodeling, napkin‐ring sign, and spotty calcification were all significantly lower in the IFC group. The culprit vessel pericoronary adipose tissue inflammation and coronary artery calcium scores were significantly lower in the IFC group than in the RFC group. The absence of low‐attenuation plaque, napkin‐ring sign, zero coronary artery calcium, and low pericoronary adipose tissue inflammation were independent predictors of IFC. When stratified into 5 subgroups according to the number of these 4 CT factors, the prevalence of IFC was 8.3%, 20.8%, 44.6%, 75.6%, and 100% (P

The rapid advancement of climate change and global warming have widespread impacts on society, including ecosystems, water security, food production, health, and infrastructure. To achieve significant global emission reductions, approximately 74% is expected to come from cutting carbon dioxide (CO2) emissions in energy supply and demand. Carbon Capture and Storage (CCS) has attained global recognition as a preeminent approach for the mitigation of atmospheric carbon dioxide levels, primarily by means of capturing and storing CO2 emissions originating from fossil fuel systems. Currently, geological models for storage location determination in CCS rely on limited sampling data from borehole surveys, which poses accuracy challenges. To tackle this challenge, our research project focuses on analyzing exposed rock formations, known as outcrops, with the goal of identifying the most effective backbone networks for classifying various strata types in outcrop images. We leverage deep learning-based outcrop semantic segmentation techniques using hybrid backbone networks, named OutcropHyBNet, to achieve accurate and efficient lithological classification, while considering texture features and without compromising computational efficiency. We conducted accuracy comparisons using publicly available benchmark datasets, as well as an original dataset expanded through random sampling of 13 outcrop images obtained using a stationary camera, installed on the ground. Additionally, we evaluated the efficacy of data augmentation through image synthesis using Only Adversarial Supervision for Semantic Image Synthesis (OASIS). Evaluation experiments on two public benchmark datasets revealed insights into the classification characteristics of different classes. The results demonstrate the superiority of Convolutional Neural Networks (CNNs), specifically DeepLabv3, and Vision Transformers (ViTs), particularly SegFormer, under specific conditions. These findings contribute to advancing accurate lithological classification in geological studies using deep learning methodologies. In the evaluation experiments conducted on ground-level images obtained using a stationary camera and aerial images captured using a drone, we successfully demonstrated the superior performance of SegFormer across all categories.

Sepsis leads to organ dysfunction. Acute kidney injury, a common type of organ dysfunction, is associated with a high mortality rate in patients with sepsis. Kidney replacement therapy can correct the metabolic, electrolyte, and fluid imbalances caused by acute kidney injury. While this therapy can improve outcomes, evidence of its beneficial effects is lacking. Herein, we review the indications for blood purification therapy, including kidney replacement therapy, and the current knowledge regarding acute kidney injury in terms of renal and non-renal indications. While renal indications have been well-documented, indications for blood purification therapy in sepsis (non-renal indications) remain controversial. Excessive inflammation is an important factor in the development of sepsis; blood purification therapy has been shown to reduce inflammatory mediators and improve hemodynamic instability. Given the pathophysiology of sepsis, blood purification therapy may decrease mortality rates in these patients. Further trials are needed in order to establish the effectiveness of blood purification therapy for sepsis.

The hot-carrier effect and hot-carrier dynamics in GaAs solar cell device performance were investigated. Hot-carrier solar cells based on the conventional operation principle were simulated based on the detailed balance thermodynamic model and the hydrodynamic energy transportation model. A quasi-equivalence between these two models was demonstrated for the first time. In the simulation, a specially designed GaAs solar cell was used, and an increase in the open-circuit voltage was observed by increasing the hot-carrier energy relaxation time. A detailed analysis was presented regarding the spatial distribution of hot-carrier temperature and its interplay with the electric field and three hot-carrier recombination processes: Auger, Shockley–Read–Hall, and radiative recombinations.

Abstract Axion or axion-like particle (ALP) has been usually considered as a CP-odd Nambu-Goldstone boson (NGB) from the spontaneous breakdown of a global U(1) symmetry. In this paper, we point out that the NGB behaves as a CP-even particle coupled to the SM particles in a large class of simple (or perhaps the simplest) renormalizable models. We provide a first study of the collider phenomenology and cosmology of the CP-even ALP. In a natural parameter region, the CP-even ALP can be produced from the Higgs boson decay in colliders. When the mass is not very light, the signals will be Higgs exotic decays, Higgs decay to displaced vertex ×2, Higgs decay to displaced vertex + missing energy. The signal can be discriminated from other models, e.g. hidden photon, by measuring the decay length and the decay products of the light new particle. In addition, when m a ≲ MeV, in which case the Higgs boson invisible decay may be probed in the colliders, the CP-even ALP is a nice Dark matter (DM) candidate. The DM can be probed by 21cm line measurement, the future measurement of the Milky way mass halo function in the Vera Rubin Observatory, as well as X- or γ-ray observations. The DM production mechanisms are discussed.

Abstract Cyclin-dependent kinase 5 (Cdk5) /p35 is involved in many developmental processes of the central nervous system. Cdk5/p35 is also implicated in synaptic plasticity, learning and memory. Several lines of conditional Cdk5 knockout mice (KO) have been generated and have shown different outcomes for learning and memory. Here, we present our analysis of p35 conditional KO mice (p35cKO) in hippocampal pyramidal neurons or forebrain GABAergic neurons using electrophysiological and behavioral methods. In the fear conditioning task, CamKII-p35cKO mice showed impaired memory retention. Furthermore, NMDAR-dependent long-term depression (LTD) induction by low-frequency stimuli in hippocampal slices from CamkII-p35cKO mice was impaired compared to that in control mice. In contrast, Dlx-p35cKO mice showed no abnormalities in behavioral tasks and electrophysiological analysis in their hippocampal slices. These results indicated that Cdk5/p35 in excitatory neurons is important for the hippocampal synaptic plasticity and associative memory retention.

Abstract In the presence of functionally significant epicardial lesions, microvascular resistance reserve (MRR) calculation needs incorporation of collateral flow. Coronary fractional flow reserve (FFRcor) requiring coronary wedge pressure (Pw), which is an essential part of the true MRR calculation, is reportedly estimated by myocardial FFR (FFRmyo) not requiring Pw measurement. We sought to find an equation to calculate MRR without the need for Pw. Furthermore, we assessed changes in MRR after percutaneous coronary intervention (PCI). An equation to estimate FFRcor was developed from a cohort of 230 patients who underwent physiological measurements and PCI. Corrected MRR was calculated using this equation and compared with true MRR in 115 patients of the different set of the validation cohort. True MRR was calculated using FFRcor. FFRcor and FFRmyo showed a strong linear relationship (r2 = 0.86) and an equation was FFRcor = 1.36 × FFRmyo – 0.34. This equation provided no significant difference between corrected MRR and true MRR in the validation cohort. Pre‐PCI lower coronary flow reserve and higher index of microcirculatory resistance were independent predictors of pre‐PCI decreased true MRR. True MRR significantly decreased after PCI. In conclusion, MRR can be accurately corrected using an equation for FFRcor estimation without Pw.

BackgroundHemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome occurs in pregnant and postpartum individuals. We observed serum syndecan-1 (SDC-1) levels, which is a component of the glycocalyx, in a patient with HELLP syndrome from admission to the postpartum period and examined their association as reflecting the pathophysiology related to endothelial injury.Case presentationA 31-year-old primiparous female patient without a previous medical history at a gestational age of 37 weeks and 6 days was transferred to our hospital the morning after a visit to a previous hospital with headache and nausea. Elevated transaminase, platelet count, and proteinuria were noted. Head magnetic resonance imaging revealed a caudate nucleus hemorrhage and posterior reversible encephalopathy syndrome. After she delivered her newborn through an emergency cesarean section, she was admitted to the intensive care unit. On day 4 post-delivery, the patient’s D-dimer concentration was elevated, and contrast-enhanced computed tomography was performed. The results indicated pulmonary embolism, and heparin administration was initiated. The serum SDC-1 level was highest on day 1 post-delivery and quickly decreased subsequently; however, it remained elevated during the postpartum period. Her condition gradually improved, and she was extubated on day 6 and discharged from the ICU on day 7 post-delivery.ConclusionWe measured SDC-1 concentration in a patient with HELLP syndrome and found that the clinical course correlated with SDC-1 levels, indicating that SDC-1 is elevated immediately before and after pregnancy termination in patients with HELLP syndrome. Therefore, SDC-1 fluctuations, combined with the elevation of the D-dimer level, may be a potential marker for the early detection of HELLP syndrome and estimation of the syndrome’s severity in the future.

Purpose: Cerebral fat embolism (CFE) is a rare syndrome caused by the embolization of fat particles into the brain circulation. This prospective single-center observational study investigated the incidence of CFE in long-bone or pelvic fractures based on magnetic resonance imaging (MRI) findings. The purpose of this study was to investigate the incidence of CFE by MRI findings with or without symptoms suggestive of CFE. Methods: Eligible patients were consecutive, aged 15 years or older, with high-energy traumas, including pelvic or femur fractures. Excluded patients were those who died, could not undergo MRI resulting from medical conditions, or had insufficient mental capacity and no consultee to provide consent. The MRI was scheduled within 4 weeks of the injury, and the images were reviewed by one of the three neuroradiologists who were unaware of the patient's clinical information. Patient data regarding demographics, preceding trauma, injury severity score (ISS), presentation and examination timing of MRI, management including surgery, and outcome were collected. Results: Sixty-two patients were recruited, and three patients were excluded. All patients were injured by blunt trauma. The median patient age was 44 years. The median ISS was 13, and 53 patients needed surgical fixation. There were 22 patients with long-bone fractures, all of whom received external fixation or intramedullary nailing on admission day. MRI was performed after a median hospital day of 18 days. Using MRI imaging, three (5.0%) patients were diagnosed with CFE, and three patients were suspected of CFE. Conclusions: This is the first study to prospectively examine the probability of CFE based on MRI. Since fat embolism syndrome (FES) is confirmed in patients without clinical symptoms, CFE may be more common in patients with trauma than currently believed. Therefore, studies to determine the diagnostic criteria combined with symptoms, MRI, or other objective findings are required in the future.

Abstract The endothelial glycocalyx covers the lumen of blood vessels throughout the body and plays an important role in endothelial homeostasis. Advances in electron microscopy techniques have provided clues to better understand the structure and composition of identical vascular endothelial glycocalyx. The morphology and thickness of the endothelial glycocalyx differ from organ to organ. The content of the endothelial glycocalyx covering the vascular lumen differs even in the brain, heart, and lungs, which have the same continuous capillaries. Various types of inflammation are known to attenuate the endothelial glycocalyx; however, we found that the morphology of the glycocalyx damaged by acute inflammation differed from that damaged by chronic inflammation. Acute inflammation breaks the endothelial glycocalyx unevenly, whereas chronic inflammation leads to the overall shortening of the endothelial glycocalyx. The same drug has different effects on the endothelial glycocalyx, depending on the location of the target blood vessels. This difference in response may reflect not only the size and shape of the endothelial glycocalyx but also the different constituents. In the cardiac tissue, the expression of glypican‐1, a core protein of the endothelial glycocalyx, was enhanced. By contrast, in the pulmonary tissue, the expression of heparan sulfate 6‐O‐sulfotransferase 1 and endothelial cell‐specific molecule‐1 significantly increased in the treatment group compared with that in the no‐treatment group. In this review, we present the latest findings on the evolution of the vascular endothelial glycocalyx and consider the microstructural differences.

Myocardial infarction (MI) can result in fatal myocardial rupture or heart failure due to adverse remodeling and dysfunction of the left ventricle. Although recent studies have shown that exogenous interleukin (IL)-22 shows cardioprotective effect after MI, the pathophysiological significance of endogenous IL-22 is unknown. In this study, we investigated the role of endogenous IL-22 in a mouse model of MI. We produced MI model by permanent ligation of the left coronary artery in wild-type (WT) and IL-22 knock-out (KO) mice. The post-MI survival rate was significantly worse in IL-22KO mice than in WT mice due to a higher rate of cardiac rupture. Although IL-22KO mice exhibited a significantly greater infarct size than WT mice, there was no significant difference in left ventricular geometry or function between WT and IL-22KO mice. IL-22KO mice showed increase in infiltrating macrophages and myofibroblasts, and altered expression pattern of inflammation- and extracellular matrix (ECM)-related genes after MI. While IL-22KO mice showed no obvious changes in cardiac morphology or function before MI, expressions of matrix metalloproteinase (MMP)-2 and MMP-9 were increased, whereas that of tissue inhibitor of MMPs (TIMP)-3 was decreased in cardiac tissue. Protein expression of IL-22 receptor complex, IL-22 receptor alpha 1 (IL-22R1) and IL-10 receptor beta (IL-10RB), were increased in cardiac tissue 3 days after MI, regardless of the genotype. We propose that endogenous IL-22 plays an important role in preventing cardiac rupture after MI, possibly by regulating inflammation and ECM metabolism.

BackgroundThe relationship of layered plaque detected by optical coherence tomography (OCT) with coronary inflammation and coronary flow reserve (CFR) remains elusive. We aimed to investigate the association of OCT-defined layered plaque with pericoronary adipose tissue (PCAT) inflammation assessed by coronary computed tomography angiography (CCTA) and global (G)-CFR assessed by cardiac magnetic resonance imaging (CMR) in patients with acute coronary syndrome (ACS).MethodsWe retrospectively investigated 88 patients with first ACS who underwent preprocedural CCTA, OCT imaging of the culprit lesion prior to primary/urgent percutaneous coronary intervention (PCI), and postprocedural CMR. All patients were divided into two groups according to the presence and absence of OCT-defined layered plaque at the culprit lesion. Coronary inflammation was assessed by the mean value of PCAT attenuation (-190 to -30 HU) of the three major coronary vessels. G-CFR was obtained by quantifying absolute coronary sinus flow at rest and during maximum hyperemia. CCTA and CMR findings were compared between the groups.ResultsIn a total of 88 patients, layered plaque was detected in 51 patients (58.0%). The patients with layered plaque had higher three-vessel-PCAT attenuation value (-68.58 ± 6.41 vs. -71.60 ± 5.21 HU, P = 0.021) and culprit vessel-PCAT attenuation value (-67.69 ± 7.76 vs. -72.07 ± 6.57 HU, P = 0.007) than those with non-layered plaque. The patients with layered plaque had lower G-CFR value (median, 2.26 [interquartile range, 1.78, 2.89] vs. 3.06 [2.41, 3.90], P = 0.003) than those with non-layered plaque.ConclusionsThe presence of OCT-defined layered plaque at the culprit lesion was associated with high PCAT attenuation and low G-CFR after primary/urgent PCI in patients with ACS. OCT assessment of culprit plaque morphology and detection of layered plaque may help identify increased pericoronary inflammation and impaired CFR, potentially providing the risk stratification in patients with ACS and residual microvascular dysfunction after PCI.

ObjectiveThis study aimed to compare outcomes among patients who sustained major trauma from injury with and without receiving antiplatelet therapy (APT) or anticoagulant therapy (ACT) to test the hypothesis that APT does not increase the risk of mortality. However, ACT increases the mortality risk in the acute phase of trauma.MethodsPatients registered in the Japanese Observational body for Coagulation and Thrombolysis in Early Trauma 2 between April 2017 and March 2018 who had sustained a severe injury in any anatomic region of the body, as determined using an injury severity score (ISS) ≥ 16 were included in this retrospective cohort study. We analyzed the mortality within 24 h from the arrival using a multivariable linear regression analysis adjusted for several confounding variables.ResultsWe identified 1,186 eligible participants who met the inclusion criteria for this study: 105 in the APT (cases), 1,081 in the non-antiplatelet therapy (nAPT) group (controls), 65 in the ACT (cases), and 1,121 in the non-anticoagulant therapy (nACT) group (controls). The mortality within 24 h in the ACT group was significantly higher than in the nACT group (odds ratio 4.5; 95%CI: 1.2–16.79; p = 0.025); however, there was no significant difference between the two groups with or without the antiplatelet drug (odds ratio 0.32; 95%CI: 0.04–2.79; p = 0.3) administration. Other outcomes, like the 28-day mortality, mortality at discharge, and surgery for hemostasis, were not significantly different between regular users and non-users of either antiplatelet or anticoagulant drugs.ConclusionRegular antiplatelet medications did not increase mortality within 24 h, 28 days, or at discharge in patients with major trauma, suggesting that standard treatment, including surgery, is sufficient.

We calculate radiative corrections to decay rates of CP-odd Higgs boson A for various decay modes in the four types of two Higgs doublet models with the softly broken discrete Z2 symmetry. The decay branching ratios are evaluated at the next-to-leading order for electroweak corrections and the next-to-next-to-leading order for QCD corrections. We comprehensively study the impact of the electroweak corrections on the decay rates and the branching ratios. We find that the radiative corrections can sizably modify the branching ratios, especially for the A→Zh decay mode in the nearly alignment scenario, where coupling constants of the SM-like Higgs boson h are close to those in the standard model. We also show correlations between the branching ratios of A and the scaling factor of the SM-like Higgs boson coupling including higher-order corrections. In addition, we show characteristic predictions on the decay pattern depending on the types of Yukawa interaction, by which we can discriminate the types of Yukawa interaction in future collider experiments.

Abstract The Higgs invisible decay width may soon become a powerful tool to probe extensions of the Standard Model with dark matter candidates at the Large Hadron Collider. In this work, we calculate the next-to-leading order (NLO) electroweak corrections to the 125 GeV Higgs decay width into two dark matter particles. The model is the next-to-minimal 2-Higgs-doublet model (N2HDM) in the dark doublet phase, that is, only one doublet and the singlet acquire vacuum expectation values. We show that the present measurement of the Higgs invisible branching ratio, BR(H → invisible < 0.11), does not lead to constraints on the parameter space of the model at leading order. This is due to the very precise measurements of the Higgs couplings but could change in the near future. Furthermore, if NLO corrections are required not to be unphysically large, no limits on the parameter space can be extracted from the NLO results.

Introduction: Myocardial dysfunction occurs in patients with sepsis due to vascular endothelial injury. Recombinant human thrombomodulin (rhTM) attenuates vascular endothelial injuries through endothelial glycocalyx (eGC) protection. Hypothesis: We hypothesized that rhTM attenuates myocardial dysfunction via the inhibition of vascular endothelial injury during sepsis. Methods: Ten-week-old male C57BL6 mice were injected intraperitoneally with 20 mg/kg of lipopolysaccharide (LPS). In rhTM-treated mice, rhTM was injected intraperitoneally at 3 and 24 h after LPS injection. Saline was injected intraperitoneally as control. To assess for eGC injury, intensity score was measured 48 h after the LPS injection. To confirm vascular endothelial injuries, ultrastructural analysis was performed using scanning (SEM) and transmission electron microscopy (TEM). Results: The survival rate of the rhTM group at 48 h after LPS injection was significantly higher than that of the control group (68% vs. 17%, p < 0.05). The serum level of troponin I in the rhTM group was lower than that in the control (2.2 ± 0.4 ng/dL vs 9.4 ± 1.1 ng/dL, p < 0.05). The expression of interleukin-6 (IL-6) was attenuated in the rhTM-treated group than in the control (65.3 ± 15.3 ng/mL vs 226.3 ± 19.4 ng/mL, p < 0.05). The serum concentration of syndecan-1, a marker of glycocalyx damage, was significantly decreased 48 h post-administration of LPS in the rhTM-treated group than in the control group. In ultrastructural analysis using SEM and TEM, eGC peeled off from the surface of the capillary lumen in the control. Conversely, the eGC injury was attenuated in the rhTM group. Gene set enrichment analysis revealed that osteomodulin, osteoglycin proline/arginine-rich end leucine-rich repeat protein, and glypican-1, which are proteoglycans, were preserved by rhTM treatment. Their protein expression was retained in endothelial cells. Conclusion: rhTM attenuates sepsis-induced myocardial dysfunction via eGC protection.