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Abstract Background Aspergillus spp. are rare causes of surgical site infections (SSIs). Specifically, Aspergillus section Nigri, commonly identified as Aspergillus niger through morphological findings, has infrequently been reported as an abdominal SSI pathogen. Case presentation An 86-year-old woman with a history of hypertension, chronic kidney disease, and atrial fibrillation who was taking 6 mg of prednisolone daily for rheumatoid arthritis was admitted to our hospital because of sudden abdominal pain. She was diagnosed with sigmoid colon perforation and underwent an open Hartmann operation on the day of admission. Subsequently, a superficial abdominal SSI was detected. Through analysis of the calmodulin gene, Aspergillus welwitschiae, which is classified within the Aspergillus section Nigri, was identified as the responsible pathogen. The minimum inhibitory concentration of voriconazole (VRCZ) was 2 mg/L. Surgical removal of the infected tissue and VRCZ administration was effectively used to treat the infection. Conclusions Given the reported low susceptibility of Nigri section species to azoles, identification and drug susceptibility testing of these fungi are highly important.

Abstract This study aims to elucidate the clinical and molecular characteristics, treatment outcomes and prognostic factors of patients with histone H3 K27-mutant diffuse midline glioma. We retrospectively analyzed 93 patients with diffuse midline glioma (47 thalamus, 24 brainstem, 12 spinal cord and 10 other midline locations) treated at 24 affiliated hospitals in the Kansai Molecular Diagnosis Network for CNS Tumors. Considering the term “midline” areas, which had been confused in previous reports, we classified four midline locations based on previous reports and anatomical findings. Clinical and molecular characteristics of the study cohort included: age 4–78 years, female sex (41%), lower-grade histology (56%), preoperative Karnofsky performance status (KPS) scores ≥ 80 (49%), resection (36%), adjuvant radiation plus chemotherapy (83%), temozolomide therapy (76%), bevacizumab therapy (42%), HIST1H3B p.K27M mutation (2%), TERT promoter mutation (3%), MGMT promoter methylation (9%), BRAF p.V600E mutation (1%), FGFR1 mutation (14%) and EGFR mutation (3%). Median progression-free and overall survival time was 9.9 ± 1.0 (7.9–11.9, 95% CI) and 16.6 ± 1.4 (13.9–19.3, 95% CI) months, respectively. Female sex, preoperative KPS score ≥ 80, adjuvant radiation + temozolomide and radiation ≥ 50 Gy were associated with favorable prognosis. Female sex and preoperative KPS score ≥ 80 were identified as independent good prognostic factors. This study demonstrated the current state of clinical practice for patients with diffuse midline glioma and molecular analyses of diffuse midline glioma in real-world settings. Further investigation in a larger population would contribute to better understanding of the pathology of diffuse midline glioma.

Abstract Aim Laparoscopic segmentectomy (LS) using indocyanine green (ICG) fluorescence navigation with negative staining method has potential for performing accurate and safe anatomical excision. This study aimed to evaluate the significance of LS using ICG fluorescence navigation compared with open segmentectomy (OS). Methods Eighty‐seven patients who underwent anatomical segmentectomies were evaluated for OS (n = 44) and LS (n = 43). The Glissonean pedicle approach was performed using either extra‐ or intrahepatic method, depending on the location of segment in LS. After clamping pedicle, negative staining method was performed. Liver transection was done along intersegmental plane visualizing by overlay mode of ICG camera. Surgical outcomes were compared between two groups. Correlation between predicted resecting liver volume (PRLV) calculated using volumetry and actual resected liver volume (ARLV) was assessed in two groups. Results Patients who underwent LS showed better outcomes in operative time, blood loss, and length of hospital stay. There were significantly fewer Grade II and Grade III or higher postoperative complications in LS group. Both values of AST (p

Abstract Background Ocular manifestations are known for non-Hodgkin lymphoma, but are rare for Hodgkin lymphoma. We report a case of Vogt-Koyanagi-Harada (VKH) disease presenting as serous retinal detachment and uveitis in both eyes in a child undergoing chemotherapy for Hodgkin lymphoma. Case presentation The patient was a 7-year-old boy with stage IIB Hodgkin lymphoma (nodular lymphocyte predominant type) who was undergoing chemotherapy, including 2 cycles of the OEPA regimen and 1 cycle of the COPDAC regimen. Two days after the end of the COPDAC regimen, the patient complained of headache and of blurred and decreased vision in both eyes. On the basis of optic symptoms, such as uveitis and serous retinal detachment in both eyes, increased cell counts in cerebrospinal fluid, and positivity for human leukocyte antigen (HLA)-DR4 in peripheral blood cells, incomplete VKH disease was diagnosed. Intravenous treatment with high-dose prednisolone (60mg/m2/day) for 7 days improved both visual acuity and serous retinal detachment and enabled the remains of the COPDAC chemotherapy cycle to be administered. With prednisolone treatment, visual acuity improved from 20/500 to 20/20 in the right eye and from 20/63 to 20/25 in the left eye. Because multiple vitiligo lesions later appeared in the abdomen, complete VKH disease was finally diagnosed. Conclusion The onset of VKH disease occurred during chemotherapy for Hodgkin lymphoma. The patient was HLA-DR4-positive and might have had a predisposition to develop autoimmune diseases, including VKH disease. However, the anticancer drugs administered to this patient have not been reported to cause uveitis. Whether Hodgkin lymphoma triggered the development of VKH remains unclear. Early diagnosis of VKH disease and prompt treatment with high-dose prednisone enabled the patient to maintain good visual function despite chemotherapy for Hodgkin lymphoma.

Abstract Aspergillus fumigatus is a pathogenic fungus with a global distribution. The emergence of azole-resistant A. fumigatus (ARAf) other than the TR-mutants is a problem in Japan. Additionally, the genetic diversity of A. fumigatus strains in Japan remains relatively unknown. Here we show the diversity in the A. fumigatus strains isolated in Japan as well as the complexity in the global distribution of the pathogenic strains. First, we analyzed the genome sequences of 171 strains from Japan as well as the antifungal susceptibility of these strains. Next, we conducted a population analysis of 876 strains by combining the available genomic data for strains isolated worldwide, which were grouped in six clusters. Finally, a genome-wide association study identified the genomic loci associated with ARAf strains, but not the TR-mutants. These results highlight the complexity of the genomic mechanism underlying the emergence of ARAf strains other than the TR-mutants.

Abstract Schizophyllum commune is the third most common causative fungus of allergic bronchopulmonary mycosis(ABPM). Two‐thirds of ABPM caused by S. commune can be positive for Aspergillus fumigatus‐specific IgE, which can be difficult to diagnose. Our patient presented to our hospital with wet cough for 3 months and chest pain for 3 days. Blood tests showed IgE 1522 IU/mL, eosinophils 688/mm3, A. fumigatus ‐specific IgE 2.24 UA/mL, and chest computed tomography showed high‐attenuation mucus. Bronchoscopy showed mucus plugs and speculum examination showed filamentous fungi, but various culture tests did not detect A. fumigatus, Asp f 1‐specific IgE was negative, and S. commune was detected in the culture of bronchial washing. Since he was positive for S. commune‐specific IgE and IgG, he diagnosed ABPM caused by S. commune. These findings demonstrate the importance of identifying the causative fungus in ABPM by detailed examination.

[Abstract]: Purpose: We report a rare case of microbial keratitis caused by Nigrospora oryzae. Observations: A 72-year-old Japanese woman was injured by plant debris and developed oval corneal ulcers and hypopyon in the anterior chamber. After 5 days, she complained of pain, redness, and vision loss in her left eye and was treated with antibacterial eye drops and an ointment (1.5 % levofloxacin hydrate, cefmenoxime hydrochloride, and sterilization and disinfection eye drops; SAN-IODE and ofloxacin ophthalmic ointment). Examination revealed a worsening oval corneal ulcer with Descemet's folds and a faint hypopyon. Considering the infection from soil or plants and the poor response to intensive antibacterial eye drops, topical antifungal eye drops, i.e., 1 % voriconazole eye drops, and 1 % natamycin ointment were applied. Direct microscopy of the corneal scraping with Gram staining was performed and the result was negative. Cultures from corneal scrapings showed the growth of dark colonies after several days. The colony was identified as Nigrospora oryzae by sequencing of the fungal internal transcribed spacer region. Pain and vision loss improved with improvement in corneal ulcers. The antifungal treatment was administered for 37 days. Discontinuation of the eye drops after 1 month did not result in keratitis recurrence. At the final follow-up at 70 days, the best-corrected visual acuity was 20/25, with persistent small corneal opacity. Conclusions and importance: Here, we report a case of fungal keratitis caused by Nigrospora oryzae. Microbiological identification of the causes of rare infections is difficult in clinical laboratories, necessitating the use of advanced molecular techniques based on amplification and sequencing of appropriate phylogenetic markers. Nigrospora oryzae responds to topical voriconazole and natamycin.

ABSTRACTInvasive aspergillosis (IA) and mucormycosis are life-threatening diseases, especially among immunocompromised patients. Drug-resistant Aspergillus fumigatus strains have been isolated worldwide, which can pose a serious clinical problem. As IA mainly occurs in patients with compromised immune systems, the ideal therapeutic approach should aim to bolster the immune system. In this study, we focused on Vγ9Vδ2 T cells that exhibit immune effector functions and examined the possibility of harnessing this unconventional T cell subset as a novel therapeutic modality for IA. A potent antifungal effect was observed when A. fumigatus (Af293) hyphae were challenged by Vγ9Vδ2 T cells derived from peripheral blood. In addition, Vγ9Vδ2 T cells exhibited antifungal activity against hyphae of all Aspergillus spp., Cunninghamella bertholletiae, and Rhizopus microsporus but not against their conidia. Furthermore, Vγ9Vδ2 T cells also exhibited antifungal activity against azole-resistant A. fumigatus, indicating that Vγ9Vδ2 T cells could be used for treating drug-resistant A. fumigatus. The antifungal activity of Vγ9Vδ2 T cells depended on cell-to-cell contact with A. fumigatus hyphae, and degranulation characterized by CD107a mobilization seems essential for this activity against A. fumigatus. Vγ9Vδ2 T cells could be developed as a novel modality for treating IA or mucormycosis.IMPORTANCEInvasive aspergillosis (IA) and mucormycosis are often resistant to treatment with conventional antifungal agents and have a high mortality rate. Additionally, effective antifungal treatment is hindered by drug toxicity, given that both fungal and human cells are eukaryotic, and antifungal agents are also likely to act on human cells, resulting in adverse effects. Therefore, the development of novel therapeutic agents specifically targeting fungi is challenging. This study demonstrated the antifungal activity of Vγ9Vδ2 T cells against various Aspergillus spp. and several Mucorales in vitro and discussed the mechanism underlying their antifungal activity. We indicate that adoptive immunotherapy using Vγ9Vδ2 T cells may offer a new therapeutic approach to IA.

Abstract The total and differential cross sections of the elastic proton–neutron and antiproton–neutron scattering are studied in a holographic QCD model, focusing on the Regge regime. Taking into account the Pomeron and Reggeon exchange, which are described by the Reggeized spin-2 glueball and vector meson propagator respectively, those cross sections are obtained. It is presented that the currently available experimental data of the total cross sections can be well described within the model. Once a single adjustable parameter is determined with the total cross section data, the differential cross sections can be calculated without any additional parameters. Although the available differential cross section data are limited, it is found that our predictions are consistent with those.

Abstract Background Fibrolamellar hepatocellular carcinoma (HCC) (FL-HCC) is rare in Japan. FL-HCC develops in young patients with no history of cirrhosis and tends to manifest lymphatic metastasis with clinical features similar to those of HCC. We present a case of FL-HCC in a young male patient. Case presentation A 14-year-old male patient underwent abdominal computed tomography (CT) to diagnose appendicitis, wherein a hepatic tumor was detected. Dynamic enhanced CT revealed a 35-mm solid tumor, which contrasted at the early phase of dynamic enhanced study of the right hepatic segments, with occlusion of the right portal vein. We performed right hepatectomy for these lesions. The patient experienced a single lymphatic recurrence on the hepatoduodenal ligament 12 months after the initial surgery. We performed lymphadenectomy for the recurrent tumor. We performed RNA sequencing (RNA-seq) and targeted DNA sequencing of the resected specimens (primary tumor, lymphatic metastasis, and normal liver). RNA-seq detected DNAJB1-PRKACA in both primary and metastatic lesions as previously reported. Furthermore, The Cancer Genome Atlas (TCGA) database was used to compare other gene expressions in this case with those of previously reported cases of FL-HCC and HCC in young patients. Principal component analysis of differentially expressed genes in the top 10% revealed that the gene expression in our case was similar to that of previous FL-HCC cases but was a different cluster from that in HCC cases in young patients. Mutational analysis did not detect any somatic mutations associated with carcinogenesis, including previously reported mutations (Kastenhuber et al. in Proc Natl Acad Sci USA 114: 13076–84, 2017). Conclusion We encountered a case of FL-HCC, a rare hepatic tumor in an adolescent patient, and evaluated the genetic background. Our findings could contribute to the elucidation of the mechanisms underlying carcinogenesis and progression in patients with FL-HCC and thereby contribute to the development of new therapeutic strategies in the future that may improve patient prognosis.

Abstract Aim This study aimed to evaluate the usefulness of the serum creatinine/cystatin C (Cr/CysC) ratio as a prognostic factor after pancreatic surgery in patients with pancreatic cancer. Methods We retrospectively analyzed the data of 88 patients with pancreatic ductal carcinoma who underwent pancreatic surgery from January 2017 to December 2020. CysC measured from frozen serum samples and circulating Cr levels were used to calculate the Cr/CysC ratio. The cutoff value of the Cr/CysC ratio was determined using receiver operating characteristic curves. Cox proportional hazards model analysis and survival curves were applied to identify the prognostic factors. Results The optimal cutoff value of the Cr/CysC ratio for predicting mortality after surgery was 1.05. This study included 20 (22.7%) and 68 (77.3%) patients with high and low Cr/CysC ratios, respectively. The low Cr/CysC ratio was significantly associated with female sex (p = 0.020) and higher levels of C‐reactive protein (p = 0.020). The postoperative length of stay was significantly longer in patients with low Cr/CysC rates (p = 0.044). Patients with low Cr/CysC ratio showed poorer prognosis in relapse‐free survival (hazard ratio [HR] = 3.33; 95% confidence interval [CI]: 1.54–4.20; p = 0.002) and overall survival (HR = 2.52, 95% CI: 1.04–6.10, p = 0.041), respectively, which were significantly worse than in those with high Cr/CysC ratios (p = 0.003 and 0.049, respectively). Conclusion The Cr/CysC ratio could be a useful screening tool for predicting the prognosis of patients with pancreatic ductal carcinoma undergoing pancreatic surgery.

Abstract The ubiquitin‒proteasome system (UPS) and autophagy are the two primary cellular pathways of misfolded or damaged protein degradation that maintain cellular proteostasis. When the proteasome is dysfunctional, cells compensate for impaired protein clearance by activating aggrephagy, a type of selective autophagy, to eliminate ubiquitinated protein aggregates; however, the molecular mechanisms by which impaired proteasome function activates aggrephagy remain poorly understood. Here, we demonstrate that activation of aggrephagy is transcriptionally induced by the transcription factor NRF1 (NFE2L1) in response to proteasome dysfunction. Although NRF1 has been previously shown to induce the expression of proteasome genes after proteasome inhibition (i.e., the proteasome bounce-back response), our genome-wide transcriptome analyses identified autophagy-related p62/SQSTM1 and GABARAPL1 as genes directly targeted by NRF1. Intriguingly, NRF1 was also found to be indispensable for the formation of p62-positive puncta and their colocalization with ULK1 and TBK1, which play roles in p62 activation via phosphorylation. Consistently, NRF1 knockdown substantially reduced the phosphorylation rate of Ser403 in p62. Finally, NRF1 selectively upregulated the expression of GABARAPL1, an ATG8 family gene, to induce the clearance of ubiquitinated proteins. Our findings highlight the discovery of an activation mechanism underlying NRF1-mediated aggrephagy through gene regulation when proteasome activity is impaired.

Uridine diphosphate glucuronosyltransferases (UGTs) are highly expressed in the liver and are involved in the metabolism of many drugs. In particular, UGT1A1 has a genetic polymorphism that causes decreased activity, leading to drug-induced hepatotoxicity. Therefore, an in vitro evaluation system that accurately predicts the kinetics of drugs involving UGT1A1 is required. However, there is no such evaluation system because of the absence of the UGT1A1-selective inhibitor. Here, using human induced pluripotent stem (iPS) cells, genome editing technology, and organoid technology, we generated UGT1A1-knockout human iPS hepatocyte-derived liver organoids (UGT1A1-KO i-HOs) as a model for UGT1A1-specific kinetics and toxicity evaluation. i-HOs showed higher gene expression of many drug-metabolizing enzymes including UGT1A1 than human iPS cell-derived hepatocyte-like cells (iPS-HLCs), suggesting that hepatic organoid technology improves liver functions. Wild-type (WT) i-HOs showed similar levels of UGT1A1 activity to primary human (cryopreserved) hepatocytes, while UGT1A1-KO i-HOs completely lost the activity. Additionally, to evaluate whether this model can be used to predict drug-induced hepatotoxicity, UGT1A1-KO i-HOs were exposed to SN-38, the active metabolite of irinotecan, an anticancer drug, and acetaminophen and confirmed that these cells could predict UGT1A1-mediated toxicity. Thus, we succeeded in generating model cells that enable evaluation of UGT1A1-specific kinetics and toxicity.

Background: Approximately 60% of individuals with cystic fibrosis (CF) are affected by Aspergillus fumigatus infection. This condition is correlated with a decline in lung function and is identified as an independent risk factor contributing to hospital admissions among CF patients. This study investigates the dynamic interplay of A. fumigatus within the context of CF patients, tracing its evolution over time, with a specific emphasis on colonization dynamics. Methods: An analysis was conducted on 83 sequential A. fumigatus isolates derived from sputum samples of six patients receiving care at a renowned CF hospital in Brazil. Employing microsatellite genotyping techniques, alongside an investigation into cyp51A gene mutations, this research sheds light on the genetic variations, colonization, and resistance of A. fumigatus within the CF respiratory environment. Results: Our research findings indicate that CF patients can harbor A. fumigatus strains from the same clonal complexes for prolonged periods. Additionally, we identified that clinical isolates have the potential to spread among patients in the same healthcare facility, evidencing hospital contamination. Two patients who underwent long-term Itraconazole treatment did not show phenotypic resistance. However, one of these patients exhibited mutations in the cyp51A gene, indicating the need to monitor resistance to azoles in these patients colonized for long periods by A. fumigatus. We also observed co-colonization or co-infection involving multiple genotypes in all patients over time. Conclusion: This comprehensive examination offers valuable insights into the pathogenesis of A. fumigatus infections in CF patients, potentially shaping future therapeutic strategies and management approaches. This enhanced understanding contributes to our knowledge of A. fumigatus impact on disease progression in individuals with cystic fibrosis. Additionally, the study provides evidence of cross-contamination among patients undergoing treatment at the same hospital.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is one of the most common chronic liver diseases worldwide. Some patients with MAFLD develop metabolic dysfunction-associated steatohepatitis (MASH), which can lead to severe liver fibrosis. However, the molecular mechanisms underlying this progression remain unknown, and no effective treatment for MASH has been developed so far. In this study, we performed a longitudinal detailed analysis of mitochondria in the livers of choline-deficient, methionine-defined, high-fat-diet (CDAHFD)-fed mice, which exhibited a MASH-like pathology. We found that FoF1–ATPase activity began to decrease in the mitochondria of CDAHFD-fed mice prior to alterations in the activity of mitochondrial respiratory chain complex, almost at the time of onset of liver fibrosis. In addition, the decrease in FoF1–ATPase activity coincided with the accelerated opening of the mitochondrial permeability transition pore (PTP), for which FoF1–ATPase might be a major component or regulator. As fibrosis progressed, mitochondrial permeability transition (PT) induced in CDAHFD-fed mice became less sensitive to cyclosporine A, a specific PT inhibitor. These results suggest that episodes of fibrosis might be related to the disruption of mitochondrial function via PTP opening, which is triggered by functional changes in FoF1–ATPase. These novel findings could help elucidate the pathogenesis of MASH and lead to the development of new therapeutic strategies.

A 61-year-old woman, hospitalized for a persistent cough and dyspnea, had no history of bronchial asthma, but was undergoing chemotherapy for methotrexate-related lymphoproliferative disorder due to rheumatoid arthritis. Her peripheral blood eosinophil count was significantly increased, and chest CT revealed left lower lobe atelectasis and high-attenuation mucus. Bronchoscopy revealed mucous plugs and pathological examination revealed numerous eosinophils and filamentous fungi. Allergic bronchopulmonary mycosis (ABPM) caused by Scedosporium apiospermum was diagnosed using culture and genetic analyses. Treatment with corticosteroids and antifungal drugs led to improvement. ABPM caused by S. apiospermum is extremely rare, emphasizing the importance of species identification.

Lomentospora prolificans is a rare, filamentous fungus, that causes a disseminated infection in immunocompromised individuals. Disseminated infections caused by the fungus are difficult to diagnose early. It is resistant to multiple antifungal agents and has a high mortality rate. We encountered a case in which the involvement of this fungus was indicated by a history of antifungal prophylaxis and an elevated serum 1,3-beta-D-glucan (BDG) level. A 76-year-old female with myelodysplastic syndrome that developed into overt leukemia was administered oral posaconazole as antifungal prophylaxis. She was admitted to the hospital to determine the cause of her fever, where no new abnormalities other than an elevated serum BDG level were observed. Unfortunately, the patient died due to acute respiratory failure on the same day of admission. The day after her death, L. prolificans was detected in a blood culture taken upon her admission. L. prolificans should be suspected based on the history of antifungal prophylaxis and an elevated serum BDG level, as these are risk factors for infection by this pathogen. Blood cultures are useful to provide a diagnosis. If treated early, before it is detected in culture, the mortality rate can be decreased.

We investigate the elastic photon-proton and photon-photon scattering in a holographic QCD model, focusing on the Regge regime. Considering contributions of the Pomeron and Reggeon exchange, the total and differential cross sections are calculated. While our model involves several parameters, by virtue of the universality of the Pomeron and Reggeon, for most of them the values determined in the preceding study on the proton-proton and proton-antiproton scattering can be employed. Once the two adjustable parameters, the Pomeron-photon and Reggeon-photon coupling constant, are determined with the experimental data of the total cross sections, predicting the both cross sections in a wide kinematic region, from the GeV to TeV scale, becomes possible. We show that the total cross section data can be well described within the model, and our predictions for the photon-proton differential cross section are consistent with the data.

We hereby make the first report of a case of mycosis caused by Purpureocillium lilacinum in CARD9 deficiency. A 40-year-old woman complained of lymph node swellings in the left cervical area. She also had chronic mucocutaneous candidiasis (CMC), and was found to have CARD9 deficiency. Lymphadenitis by P. lilacinum was confirmed. The diagnosis was difficult, as culturing the biopsy specimen at a cautiously selected temperature (25 °C) and genetic analysis were both required. Oral administration of voriconazole improved her lymphadenopathy.

Tropical peatlands serve as huge carbon (C) pools in the global C balance, and degradation due to agricultural use is a major concern. The objective of the present study was to examine the relationship between the C loss rate in agriculturally drained tropical peat soils in relation to groundwater level (GWL) and the chemical structure of the resulting soil organic matter (SOM). Soil mesocosms containing three peat soils collected from three forest types in Malaysia, Mixed peat swamp (MPS), Alan Batu (ABt), and Alan Bunga (ABg) forests, which are classified based on dominant plant species, species diversity, and forest structure, were buried in an oil palm plantation for a period of five years. Soil samples packed in the top layer (0–20 cm depth) and the bottom (60–80 cm depth) layer were then analyzed and the results were compared with the initial values for these soils. Weight loss, total C and N contents, ash content, and pyrophosphate solubility index (PSI; an index of the degree of humification) were measured. Changes in the chemical structure of the SOC were investigated using solid-state 13C nuclear magnetic resonance (NMR) spectroscopy with phase-adjusted spinning side bands and thermally assisted hydrolysis and methylation-gas chromatography/mass spectrometry (THM-GC/MS). The C loss in the MPS forest soil, 2–12%, was smaller than that in the ABt and ABg forest soils, 20–37%, especially in the bottom layer. The higher C loss in the ABt and ABg soils, without significant difference between the top and bottom layers, can be attributed to the greater accumulation of less decomposed plant components as evidenced by the larger yields of lignin-derived phenols and polysaccharide-related compounds in THM-GC/MS analysis. The C composition as estimated by 13C NMR did not vary during incubation of the ABt and ABg soils while the yields of lignin-derived and other phenols as well as polysaccharide-related compounds in THM-GC/MS were decreased, especially in the top layer. These findings suggest that plant components with a low degree of decomposition are susceptible to drainage regardless of their structure. The progression of the oxidative degradation of lignin in the top layer of all soils was also suggested by the increases in PSI and the vanillic acid/vanillin ratio. The % O-alkyl C and % alkyl C may control the rate of C loss positively and negatively, respectively. PSI also appears to be useful for roughly estimating the decomposability of tropical peat SOM in various GWLs.

ABSTRACT Azole resistance in Aspergillus fumigatus is a worldwide concern and new antifungal drugs are required to overcome this problem. Statin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, has been reported to suppress the growth of A. fumigatus, but little is known about its in vivo antifungal effect against A. fumigatus. In this study, we evaluated the in vivo efficacy of pitavastatin (PIT) combined with itraconazole (ITC) against azole-susceptible and azole-resistant strains with silkworm models. Prolongation of survival was confirmed in the combination-therapy (PIT and ITC) group compared to the no-treatment group in both azole-susceptible and azole-resistant strain models. Furthermore, when the azole-susceptible strain was used, the combination-therapy resulted in a higher survival rate than with ITC alone. Histopathological analysis of the silkworms revealed a reduction of the hyphal amount in both azole-susceptible and azole-resistant strain models. Quantitative evaluation of fungal DNA by qPCR in azole-susceptible strain models clarified the reduction of fungal burden in the combination-therapy group compared with the no-treatment group and ITC-alone group. These results indicate that the efficacy of PIT was enhanced when combined with ITC in vivo. As opposed to most statins, PIT has little drug–drug interaction with azoles in humans and can be used safely with ITC. This combination therapy may be a promising option as an effective treatment in clinical settings in the future. IMPORTANCE Azole resistance among A. fumigatus isolates has recently been increasingly recognized as a cause of treatment failure, and alternative antifungal therapies are required to overcome this problem. Our study shows the in vivo efficacy of PIT combined with ITC against A. fumigatus using silkworm models by several methods including evaluation of survival rates, histopathological analysis, and assessment of fungal burden. Contrary to most statins, PIT can be safely administered with azoles because of less drug–drug interactions, so this study should help us to verify how to make use of the drug in clinical settings in the future.

Abstract Six years ago, a 60‐year‐old man presented to our hospital with a cough and sputum. Upon suspicion of nontuberculous mycobacterial (NTM) infection, he was followed up at our hospital. Because the abnormal shadows in the bilateral lung fields deteriorated slightly over 6 years, bronchoscopy was performed. Exophiala dermatitidis and Mycobacterium intracellulare were detected in the bronchial lavage fluid. The patient underwent follow‐up examinations without drug administration. Currently, the patient's condition remains stable. E. dermatitidis is regulatory found in the lungs of patients with cystic fibrosis, but only rarely is it found in respiratory samples from patients without cystic fibrosis. However, NTM complications have been reported more frequently in recent years. Due to the increasing number of NTM patients, E. dermatitidis pulmonary infections may also increase. Additional research is required to develop strategies for treating this infection.

Abstract Although the formation of bone-like nodules is regarded as the differentiation process from stem cells to osteogenic cells, including osteoblasts and osteocytes, the precise biological events during nodule formation are unknown. Here we performed the osteogenic induction of human induced pluripotent stem cells using a three-dimensional (3D) culture system using type I collagen gel and a rapid induction method with retinoic acid. Confocal and time-lapse imaging revealed the osteogenic differentiation was initiated with vigorous focal proliferation followed by aggregation, from which cells invaded the gel. Invading cells changed their morphology and expressed osteocyte marker genes, suggesting the transition from osteoblasts to osteocytes. Single-cell RNA sequencing analysis revealed that 3D culture-induced cells with features of periosteal skeletal stem cells, some of which expressed TGFβ-regulated osteoblast-related molecules. The role of TGFβ signal was further analyzed in the transition from osteoblasts to osteocytes, which revealed that modulation of the TGFβ signal changed the morphology and motility of cells isolated from the 3D culture, suggesting that the TGFβ signal maintains the osteoblastic phenotype and the transition into osteocytes requires down-regulation of the TGFβ signal.

Abstract Chronic infection with Kaposi’s sarcoma-associated herpes virus (KSHV) in B lymphocytes causes primary effusion lymphoma (PEL), the most aggressive form of KSHV-related cancer, which is resistant to conventional chemotherapy. In this study, we report that the BCBL-1 KSHV+ PEL cell line does not harbor oncogenic mutations responsible for its aggressive malignancy. Assuming that KSHV viral oncogenes play crucial roles in PEL proliferation, we examined the effect of cyclin-dependent kinase 9 (CDK9) inhibitor FIT-039 on KSHV viral gene expression and KSHV+ PEL proliferation. We found that FIT-039 treatment impaired the proliferation of KSHV+ PEL cells and the expression of KSHV viral genes in vitro. The effects of FIT-039 treatment on PEL cells were further evaluated in the PEL xenograft model that retains a more physiological environment for the growth of PEL growth and KSHV propagation, and we confirmed that FIT-039 administration drastically inhibited PEL growth in vivo. Our current study indicates that FIT-039 is a potential new anticancer drug targeting KSHV for PEL patients.

In multicellular organisms, endocrine factors such as hormones and cytokines regulate development and homoeostasis through communication between different organs. For understanding such interorgan communications through endocrine factors, the fruit fly Drosophila melanogaster serves as an excellent model system due to conservation of essential endocrine systems between flies and mammals and availability of powerful genetic tools. In Drosophila and other insects, functions of neuropeptides or peptide hormones from the central nervous system have been extensively studied. However, a series of recent studies conducted in Drosophila revealed that peptide hormones derived from peripheral tissues also play critical roles in regulating multiple biological processes, including growth, metabolism, reproduction, and behaviour. Here, we summarise recent advances in understanding target organs/tissues and functions of peripherally derived peptide hormones in Drosophila and describe how these hormones contribute to various biological events through interorgan communications.

A 36-year-old primigravid woman with suspected gestational hypertension was referred to our hospital for further examination and treatment of bilateral serous retinal detachment (SRD). At the previous hospital immediately after the onset of visual symptoms (decreased visual acuity), the best-corrected visual acuity (BCVA) had been 0.1 in the right eye (RE) and 0.08 in the left eye (LE). Funduscopy revealed diffuse SRD and white discoloration at the posterior pole but no retinal tear in both eyes (BE). Optical coherence tomography (OCT) also revealed SRD. One day after the onset, we diagnosed bilateral SRD due to preeclampsia with HELLP syndrome because of elevated blood pressure, hemolysis, elevated liver enzymes, and low platelet and performed an emergency cesarean section. One week after the onset, BCVA improved to 0.3 in BE. Funduscopy showed resolution of SRD and the remaining white discoloration at the posterior pole. OCT showed complete resolution of SRD, blurred external limiting membrane, and an invisible ellipsoid zone. OCT angiography (OCTA) segmentation of the deep retinal layer (using en face imaging) revealed multiple white materials, mainly in the macula. Although funduscopy and OCT showed almost normal appearance by 2 months after the onset, BCVA was not completely improved. OCTA using en face imaging revealed shrinkage of multiple white materials but remnant material at the posterior pole. One year after the onset, BCVA was 0.9 in the RE and 0.8 in the LE. OCTA using en face imaging revealed remnant white materials but marked improvement overall.

Abstract Background Factor V (FV) deficiency is an extremely rare disease, with an incidence of 1 in 1 million. The bleeding symptoms are mild, and the prognosis is good; however, the safety of surgical treatment is unclear, because there are few available reports. Herein, we report a case of hepatocellular carcinoma with congenital FV deficiency in a patient who safely underwent laparoscopic hepatectomy. Case presentation A 79-year-old man, diagnosed with hepatocellular carcinoma of liver segment 5, with type C cirrhosis and sustained virological response visited our hospital. He had congenital FV deficiency, and blood tests showed coagulation deficiencies with an FV activity of

Abstract Aim The concept of Couinaud segmentation is widely used in clinical practice. However, there were no definite anatomical landmarks between segments V and VIII. Therefore, segmentation of the right anterior sector is still controversial. We aimed to investigate the portal segmentation of the right anterior sector using 3D image analysis, and to reveal the existence of the medial branch (PV8c), a unique, characteristic branch of the right anterior portal vein. Methods The ramification form and pattern of the tertiary portal branch of the right anterior portal vein were retrospectively analyzed, and the frequency of PV8c was evaluated in 261 patients between January 2016 and June 2020. Results The ramification pattern of tertiary portal branches of the right anterior portal vein was classified into four types: craniocaudal, 28.0% of patients; ventrodorsal, 21.8%; trifurcation, 39.5%; and quadfurcation, 5.7%, and each type was further subdivided into six patterns by focusing especially on the caudal branches. The ramification pattern in the remaining 5.0% of the livers did not belong to the above‐mentioned four types. The PV8c branch was identified in 140 of 261 livers (53.6%); the mean proportion of the feeding area of PV8c in the whole liver volume was 3.4%. Conclusion Since the ramification pattern of tertiary portal branches of the right anterior portal vein does not necessarily show a single pattern, it is important to confirm the portal vein branching in each case during hepatectomy. This is the first study of the details of PV8c by 3D computed tomography.

Background: Aspergillus fumigatus is an important concern for immunocompromised individuals, often resulting in severe infections. With the emergence of resistance to azoles, which has been the therapeutic choice for Aspergillus infections, monitoring the resistance of these microorganisms becomes important, including the search for mutations in the cyp51A gene, which is the gene responsible for the mechanism of action of azoles. We conducted a retrospective analysis covering 478 A. fumigatus isolates. Methods: This comprehensive dataset comprised 415 clinical isolates and 63 isolates from hospital environmental sources. For clinical isolates, they were evaluated in two different periods, from 1998 to 2004 and 2014 to 2021; for environmental strains, one strain was isolated in 1998, and 62 isolates were evaluated in 2015. Our primary objectives were to assess the epidemiological antifungal susceptibility profile; trace the evolution of resistance to azoles, Amphotericin B (AMB), and echinocandins; and monitor cyp51A mutations in resistant strains. We utilized the broth microdilution assay for susceptibility testing, coupled with cyp51A gene sequencing and microsatellite genotyping to evaluate genetic variability among resistant strains. Results: Our findings reveal a progressive increase in Minimum Inhibitory Concentrations (MICs) for azoles and AMB over time. Notably, a discernible trend in cyp51A gene mutations emerged in clinical isolates starting in 2014. Moreover, our study marks a significant discovery as we detected, for the first time, an A. fumigatus isolate carrying the recently identified TR46/F495I mutation within a sample obtained from a hospital environment. The observed cyp51A mutations underscore the ongoing necessity for surveillance, particularly as MICs for various antifungal classes continue to rise. Conclusions: By conducting resistance surveillance within our institution’s culture collection, we successfully identified a novel TR46/F495I mutation in an isolate retrieved from the hospital environment which had been preserved since 1998. Moreover, clinical isolates were found to exhibit TR34/L98H/S297T/F495I mutations. In addition, we observed an increase in MIC patterns for Amphotericin B and azoles, signaling a change in the resistance pattern, emphasizing the urgent need for the development of new antifungal drugs. Our study highlights the importance of continued monitoring and research in understanding the evolving challenges in managing A. fumigatus infections.

Facial asymmetry is often seen in patients with skeletal mandibular prognathism and is associated with deformities in the maxillofacial and head regions. The maxillofacial deviation is three-dimensional and affects not only the lateral deviation of the mandible and midface, but also the cranium. This study conducted a three-dimensional morphological evaluation of the cranial base morphology of patients with skeletal mandibular prognathism (ANB < 0°, Wits < 0 mm) with the aim of examining the relationship between deformities of the head region and facial asymmetry. Data obtained from computed tomography conducted during the initial examination of patients with and without skeletal mandibular prognathism with facial asymmetry were used. Differences in the position of structures present in the cranial base were measured, and the association between cranial deformities and mandibular deviation was assessed. The middle cranial base area and the lateral deviation of the mandibular fossa were significantly larger in patients with facial asymmetry compared to those without facial asymmetry. In addition, a correlation between the amount of mandibular deviation and the area of the anterior cranial base was identified in patients with significant cranial deformity (p = 0.012). Given the identified association between the structure of the head region and facial asymmetry, further studies are needed to determine the factors implicated in the growth process.

Non-albicans Candida infections have recently gained worldwide attention due to their intrinsic resistance to different antifungal agents and the limited therapeutic options for treating them. Although the Candida parapsilosis complex is reported to be the second or third most prevalent Candida spp., little information is available on the prevalence of antifungal resistance along with genotyping of the C. parapsilosis complex. In this study, we aimed to evaluate the prevalence of antifungal resistance, the genetic basis of such resistance, and the genotyping of C. parapsilosis complex isolates that were recovered from hospitalized patients in Japan from 2005 to 2019. Our results indicated that, with the exception of one single C. metapsilosis isolate that was dose-dependently susceptible to fluconazole, all other isolates were susceptible or showed wild phenotypes to all tested antifungals, including azoles, echinocandins, amphotericin B, and flucytosine. Molecular analyses for azole and echinocandin resistance via evaluating ERG11 mutation and FKS1 hotspot one (HS1) and hotspot two (HS2) mutations, respectively, confirmed the phenotypic results. Genotyping of our isolates confirmed that they belong to 53 different but closely related genotypes, with a similarity percentage of up to 90%. Our results are of significant concern, since understanding the genetic basis of echinocandin resistance in the C. parapsilosis complex as well their genotyping is essential for directing targeted therapy, identifying probable infection sources, and developing strategies for overcoming epidemic spread.

A combination of cobalt and dipicolinic acid-based metal organic complex was synthesized via deep eutectic solvent (DES) based ionothermal synthesis. The DES comprising of choline chloride and urea served as the solvent medium that cater the formation of novel 3-D layered motif as depicted by the crystallographic data of the complex. FESEM, TEM and EDX analysis verified the formation of unique, hollow morphology and homogeneous distribution of metal ions within the cobalt complex synthesized ionothermally. Based on BET surface area analysis, the presence of micro- and mesopores within the structure was verified. The structurally layered cobalt complex was then used as an electrode material for supercapacitor with a specific capacitance of 712 and 556 F g−1 at 1.0 and 5.0 A g−1 respectively. The energy density and power density were calculated to be 5.71 W h kg−1 and 60.09 W kg−1 when tested at the current density of 1 A g−1. The novel material also showed good cycling stability by retaining at 76% of initial value after over 500 cycles. These values demonstrate that ionothermally synthesized transition metal based organic complexes can serve as prospective electrode material in supercapacitors.

Abstract Background Although visceral aneurysms are relatively rare, it can be life-threatening in case it ruptures. We report a case of Mirizzi syndrome accompanied by a pseudoaneurysm that ruptured into the gallbladder. Case presentation The patient was a 73-year-old woman with persistent gastrointestinal bleeding and progressive jaundice. Examination revealed a pseudoaneurysm in the gallbladder artery or hepatic artery branch, and biliary hemorrhage due to gallbladder perforation was suspected. Urgent abdominal angiography revealed a pseudoaneurysm measuring 50 × 32 mm that had ruptured directly from the right hepatic artery or the cystic artery into the gallbladder. The pseudoaneurysm was successfully coiled and the bleeding was stopped. The presence of ongoing obstruction due to Mirizzi syndrome resulted in an emergency cholecystectomy being performed on the same day. On removing the impacted gallstone from the neck of the gallbladder, we found an obstruction between the lateral wall of the common bile duct and the gallbladder, this condition was diagnosed as Mirizzi syndrome with a biliobiliary fistula. After removing the impacted gallstone, a T-tube was inserted into the common bile duct. Bile leakage was observed postoperatively, but it improved with drainage. The patient fully recovered. Conclusions We present our experience with a case of Mirizzi syndrome accompanied by a ruptured pseudoaneurysm successfully treated with coil embolization followed by cholecystectomy. In this case, the pseudoaneurysm may have been caused by inflammation due to cholecystitis or compression of the arterial wall by a gallstone. To the best of our knowledge, Mirizzi syndrome associated with pseudoaneurysm rupture is rare. Our study suggested that cholecystectomy preceded by transcatheter arterial embolization is an effective strategy to control bleeding in patients with hemobilia due to aneurysm.

We present a case of a 55-year-old man with a heart transplant who acquired Invasive Aspergillosis by Aspergillus fumigatus with the focus in the kidney. During about two years of antifungal treatment, most of the time with voriconazole, it was possible to obtain nine isolates of A. fumigatus, with the same genotypic characteristics, but with an increase in MIC for several azoles. The two last isolates presented high MICs for Voriconazole (>8 μg/mL>). Sequencing of the CYP51A gene showed G448S amino acid substitution in the same two isolates. In long-term treatments with antifungals, it would be important to regularly evaluate the susceptibility of isolated strains, as resistance to azoles has been increasingly described around the world.

Objectives To examine the national, 6-year trends in in-hospital clinical outcomes of patients with subarachnoid haemorrhage (SAH) who underwent clipping or coiling and the prognostic influence of temporal trends in the Comprehensive Stroke Center (CSC) capabilities on patient outcomes in Japan.Design Retrospective study.Setting Six hundred and thirty-one primary care institutions in Japan.Participants Forty-five thousand and eleven patients with SAH who were urgently hospitalised, identified using the J-ASPECT Diagnosis Procedure Combination database.Primary and secondary outcome measures Annual number of patients with SAH who remained untreated, or who received clipping or coiling, in-hospital mortality and poor functional outcomes (modified Rankin Scale: 3–6) at discharge. Each CSC was assessed using a validated scoring system (CSC score: 1–25 points).Results In the overall cohort, in-hospital mortality decreased (year for trend, OR (95% CI): 0.97 (0.96 to 0.99)), while the proportion of poor functional outcomes remained unchanged (1.00 (0.98 to 1.02)). The proportion of patients who underwent clipping gradually decreased from 46.6% to 38.5%, while that of those who received coiling and those left untreated gradually increased from 16.9% to 22.6% and 35.4% to 38%, respectively. In-hospital mortality of coiled (0.94 (0.89 to 0.98)) and untreated (0.93 (0.90 to 0.96)) patients decreased, whereas that of clipped patients remained stable. CSC score improvement was associated with increased use of coiling (per 1-point increase, 1.14 (1.08 to 1.20)) but not with short-term patient outcomes regardless of treatment modality.Conclusions The 6-year trends indicated lower in-hospital mortality for patients with SAH (attributable to better outcomes), increased use of coiling and multidisciplinary care for untreated patients. Further increasing CSC capabilities may improve overall outcomes, mainly by increasing the use of coiling. Additional studies are necessary to determine the effect of confounders such as aneurysm complexity on outcomes of clipped patients in the modern endovascular era.

A myoepithelioma is a type of salivary gland tumor composed entirely of myoepithelial cells. Previously, this was considered a subtype of pleomorphic adenoma. Here, we report an extremely rare case of myoepithelioma of the upper lip. A 33-year-old female patient presented with a painless mass on her upper lip. Magnetic resonance imaging revealed a 23 mm × 18 mm well-defined tumor. We clinically suspected a benign minor salivary gland tumor and the patient underwent complete resection of the tumor under general anesthesia. Since the tumor was diagnosed as a myoepithelioma by rapid pathological examination, it was resected with a safety margin of approximately 5 mm. Pathologically, this tumor showed mild to moderate cell atypia, and focal invasion into the capsule. Immunohistochemical findings showed that the tumor was positive for the S-100 protein and vimentin. The Ki-67 labeling index was less than 1%, and there were no malignant findings. The postoperative clinical course has been good for approximately 5 years, and satisfactory results were obtained both functionally and esthetically. Herein, we also discussed the clinical and immunohistochemical features of myoepitheliomas.

Abstract Dyslipidemia is considered an essential component of the pathological process of amyotrophic lateral sclerosis (ALS), a fatal motor neuron disease. Although TAR DNA Binding Protein 43 kDa (TDP-43) links both familial and sporadic forms of ALS and cytoplasmic aggregates are a hallmark of most cases of ALS, the molecular mechanism and the in vivo relation of ALS dyslipidemia with TDP-43 have been unclear. To analyze the dyslipidemia-related gene expression by TDP-43, we performed expression microarray and RNA deep sequencing (RNA-Seq) using cell lines expressing high levels of TDP-43 and identified 434 significantly altered genes including sterol regulatory element-binding protein 2 (SREBP2), a master regulator of cholesterol homeostasis and its downstream genes. Elevated TDP-43 impaired SREBP2 transcriptional activity, leading to inhibition of cholesterol biosynthesis. The amount of cholesterol was significantly decreased in the spinal cords of TDP-43-overexpressed ALS model mice and in the cerebrospinal fluids of ALS patients. These results suggested that TDP-43 could play an essential role in cholesterol biosynthesis in relation to ALS dyslipidemia.

Mitochondrial calcium homeostasis plays critical roles in cell survival and aerobic metabolism in eukaryotes. The calcium uniporter is a highly selective calcium ion channel consisting of several subunits. Mitochondrial calcium uniporter (MCU) and essential MCU regulator (EMRE) are core subunits of the calcium uniporter required for calcium uptake activity in the mitochondria. Recent 3D structure analysis of the MCU‐EMRE complex reconstituted in nanodiscs revealed that the human MCU exists as a tetramer forming a channel pore, with EMRE bound to each MCU at a 1 : 1 ratio. However, the stoichiometry of MCU and EMRE in the mitochondria has not yet been investigated. We here quantitatively examined the protein levels of MCU and EMRE in the mitochondria from mouse tissues by using characterized antibodies and standard proteins. Unexpectedly, the number of EMRE molecules was lower than that of MCU; moreover, the ratios between MCU and EMRE were significantly different among tissues. Statistical calculations based on our findings suggest that a MCU tetramer binding to 4 EMREs may exist, but at low levels in the mitochondrial inner membrane. In brain mitochondria, the majority of MCU tetramers bind to 2 EMREs; in mitochondria in liver, kidney, and heart, MCU tetramers bind to 1 EMRE; and in kidney and heart, almost half of MCU tetramers bound to no EMRE. We propose here a novel stoichiometric model of the MCU‐EMRE complex in mitochondria.

Arch forms in orthodontics are considered to affect occlusal stability. This study’s subjects were 47 patients (Class III S group) who visited the Chiba Dental Center of Tokyo Dental College and were surgical orthodontic cases, and 60 patients with Class I malocclusion were selected as the control group. A mandibular model of each subject was plotted with each tooth on a digitizer. The clinical bracket points of each tooth were plotted, and intercanine and intermolar measurements were taken. The least squares method was used to fit a quartic equation, and the arch form was drawn. The Class IIIS group was divided by Wits appraisal and facial pattern into a dolichofacial or brachyfacial pattern, and arch forms were compared. The results show that the Class IIIS group had a significantly smaller intermolar width, canine depth, and molar depth and a significantly larger canine W/D ratio. In those with a dolichofacial pattern, the anterior curve of the arch form tended to be flat and the posterior curve narrower. This is because, in skeletal mandibular prognathism, the mandibular anterior shows lingual tipping, and the molars show palatal tipping due to dental compensation, and it was inferred that this tendency was higher in high-angle cases.

Abstract Background Mosquito control is a crucial global issue for protecting the human community from mosquito-borne diseases. There is an urgent need for the development of selective and safe reagents for mosquito control. Flavonoids, a group of chemical substances with variable phenolic structures, such as daidzein, have been suggested as potential mosquito larvicides with less risk to the environment. However, the mode of mosquito larvicidal action of flavonoids has not been elucidated. Results Here, we report that several flavonoids, including daidzein, inhibit the activity of glutathione S-transferase Noppera-bo (Nobo), an enzyme used for the biosynthesis of the insect steroid hormone ecdysone, in the yellow fever mosquito Aedes aegypti. The crystal structure of the Nobo protein of Ae. aegypti (AeNobo) complexed with the flavonoids and its molecular dynamics simulation revealed that Glu113 forms a hydrogen bond with the flavonoid inhibitors. Consistent with this observation, substitution of Glu113 with Ala drastically reduced the inhibitory activity of the flavonoids against AeNobo. Among the identified flavonoid-type inhibitors, desmethylglycitein (4′,6,7-trihydroxyisoflavone) exhibited the highest inhibitory activity in vitro. Moreover, the inhibitory activities of the flavonoids correlated with the larvicidal activity, as desmethylglycitein suppressed Ae. aegypti larval development more efficiently than daidzein. Conclusion Our study demonstrates the mode of action of flavonoids on the Ae. aegypti Nobo protein at the atomic, enzymatic, and organismal levels.

Abstract Background Excessive bleeding is a major intraoperative risk associated with orthognathic surgery. This study aimed to investigate the factors involved in massive bleeding during orthognathic surgeries so that safe surgeries can be performed. Patients (n=213) diagnosed with jaw deformities and treated with bimaxillary orthognathic surgery (Le Fort I osteotomy and bilateral sagittal split ramus osteotomy) in the Department of Oral and Maxillofacial Surgery at the Suidobashi Hospital, Tokyo Dental College between January 2014 and December 2016 were included. Using the patients’ medical and operative records, the number of cases according to sex, age at the time of surgery, body mass index (BMI), circulating blood volume, diagnosis of maxillary deformity, direction of maxillary movement, operative duration, incidence of bad split, injury of nasal mucosa, and blood type were analyzed. Results The results revealed that BMI, circulating blood volume, nasal mucosal injury, and operative time were associated with the risk of intraoperative massive bleeding in orthognathic surgeries. Chi-square tests and binomial logistic regression analyses showed significant differences in BMI, circulating blood volume, direction of maxillary movement, operative duration, and injury to the nasal mucosa. Operative duration emerged as the most important risk factor. Furthermore, a >4-mm upward migration of the posterior nasal spine predicted the risk of massive bleeding in orthognathic surgery. Conclusions The upward movement of the maxilla should be recognized during the preoperative planning stage as a risk factor for intraoperative bleeding, and avoiding damage to the nasal mucosa should be considered a requirement for surgeons to prevent massive bleeding during surgery.

ABSTRACT When Aspergillus, an ubiquitous, saprophytic fungus, is detected in respiratory tract specimens collected from chronic respiratory disease patients, it is important to determine whether it is a true infection or colonization. We investigated the usefulness of the Bio-Rad Platelia Aspergillus IgG (Platelia Aspergillus IgG) enzyme-linked immunosorbent assay (ELISA) method and the Aspergillus precipitin test to distinguish pulmonary aspergillosis from colonization. Between January 2017 and November 2021, 51 confirmed, untreated pulmonary aspergillosis (33 chronic pulmonary aspergillosis [CPA] and 18 allergic bronchopulmonary aspergillosis [ABPA]) and 77 colonization patients were included in this study. At first, the conventional cutoff value was utilized in assessing the validity of the two antibody tests for distinguishing pulmonary aspergillosis from colonization. The Platelia Aspergillus IgG cutoff value was then reevaluated to fit this situation. Finally, differences in test accuracy dependent on Aspergillus species were assessed for both antibody tests by comparing cases with Aspergillus fumigatus complex and those with non-fumigatus Aspergillus complex. Both antibody tests demonstrated significantly higher positive rates for pulmonary aspergillosis (P

Mitochondria play an important role in energy conversion as well as in intracellular calcium (Ca2+) storage. Ca2+ uptake from the cytosol to the mitochondria is mediated by the calcium uniporter, which functions as a Ca2+ ion channel. However, the molecular composition of this uniporter has remained unclear until recently. The Ca2+ ion channel consists of seven subunits. The yeast reconstitution technique revealed that the mitochondrial calcium uniporter (MCU) and essential MCU regulatory element (EMRE) are the core subunits of the complex. Furthermore, detailed structure-function analyses of the core subunits (MCU and EMRE) were performed. In this review, the regulatory mechanism of mitochondrial Ca2+ uptake is discussed.

Background: The prognosis of lymphnode positive breast cancer is worse than that of lymph node negative breast cancer but some cases may not require chemotherapy. We investigated the ability of the new multi-gene assays, 95GC and 155GC, to identify patients with lymphnode positive Luminal-type breast cancer whose chemotherapy can be omitted relatively safely. Patients and Methods: We extracted 1721 cases of lymphnode positive Luminal-type breast cancer from 22 public database Caucasoid cohorts and 3 Asian cohorts, and performed recurrence prognosis analysis with 95GC and 155GC. Results: Using 95GC, the cases were stratified as the high (n = 917) and low (n = 202) groups according to the prognosis of lymphnode positive Luminal-type endocrine only breast cancer. The 5 years DRFS in the low risk group was relatively good at 90%, and no additional effect of chemotherapy was observed, suggesting omission of chemotherapy. The recurrence prognosis was also significantly dichotomized into the high and low risks by 95GC in 21GC RS 0–25 cases. Here, we found a group with poor prognosis even in post-menopause RS 0–25 and requiring chemotherapy. Additionally, a group in which the prognosis was good in pre-menopause RS 0–25, and the omission of chemotherapy could be considered. Patients in the high-risk group at 155GC had poor prognosis after chemotherapy. 155GC also showed a group that chemotherapy alone was not sufficient. Conclusion: In this study, we demonstrated the possibility of accurately selecting patient groups for which chemotherapy can be omitted from lymphnode positive Luminal-type breast cancer.

Background: The nuclear laminar protein Lamin A and inner nuclear membrane protein Emerin plays important role in sustaining nuclear structure. However, They have not investigated the significance of these proteins for development of pancreatic intraductal papillary mucinous neoplasm (IPMN).Methods: We examined pancreatic IPMN specimens for nuclear morphology and nuclear protein expression pattern of Lamin A and Emerin. Forty-two IPMN specimens were included, with 30 classified as intraductal papillary mucinous adenoma (IPMA) and 12 as intraductal papillary mucinous carcinoma (IPMC).Results: Classification according to histological subtype revealed that 26 specimens were of the gastric subtype (1 IPMC case), 8 were pancreatobiliary (6 IPMC cases), 6 were intestinal (3 IPMC cases), and 2 were oncocytic (all cases were IPMC). The frequency of IPMN subtypes in this study seemed to agree with those in previous reports. We analyzed Feulgen staining sections for nuclear morphological analysis using computer-assisted image analysis. Nuclear area and perimeter were significantly larger in IPMC than in IPMA. Finally, we examined the positive ratios of Lamin A and Emerin in immunohistochemical staining sections by image analysis. We found a negative correlation between the nuclear size and Lamin A-positive ratio, which was significantly lower in IPMC than that in IPMA. However, no significant correlation was observed between nuclear size and Emerin expression was observed, and no differences were found in the Emerin-positive ratio between IPMA and IPMC.Conclusion: Our results suggest that a decreased Lamin A positive ratio induces nuclear enlargement in adenomas, which thereby induce promotion to carcinomas. Furthermore, Lamin A expression can be a reliable biomarker for distinguishing between IPMC and IPMA.

Dang Ngoc Anh Suong et al find that vertical mixing generates iPSC-derived brain organoids displaying an inverted structure with neurons localising at the centre and neural progenitors at the outside. This study illustrates the influence of fluid mechanics relevant to the direction of primary cilia on stem cell differentiation.

Summary: A mesenchymal cell activation is a hallmark event of pulmonary fibrosis. Alveolar type 2 (AT2) cells are progenitor cells that maintain alveolar homeostasis, and their damage is assumed to be an initiating event for pulmonary fibrosis. However, the interaction between the lung fibrogenic microenvironment and AT2 cell dynamics remains to be elucidated. Here, we report a unique role of the lung fibrogenic microenvironment, where cell type-specific tissue reconstruction is achieved by exogenous cell transplantation. We found that in the lung fibrogenic microenvironment the AT2 cell pool was depleted, whereas mesenchymal cells could promote intact AT2 cell proliferation in vitro. Furthermore, exogenously transplanted AT2 cells formed alveolar colonies and ameliorated pulmonary fibrosis. Exogenous tumor cells formed tumor nests with relevant histological and transcriptional properties. Human primary cells were adaptable to this microenvironment, facilitating epithelial cell-targeted therapy in pulmonary fibrosis and the establishment of patient-derived xenografts for precision medicine in lung cancer.