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Amyand's hernia is a rare type of inguinal hernia characterized by the presence of the vermiform appendix within the hernia sac. It was named after Claudius Amyand who performed the world's first successful appendectomy on an 11-year-old boy with a right inguinal hernia in 1735 and discovered a herniated appendix during surgery.This condition warrants urgent surgical treatment, with the type of surgical intervention depending on the appendix's condition. However, the nonspecific clinical presentation often complicates the preoperative diagnosis, emphasizing the critical role of imaging in surgical planning.Herein, we present the case of a 74-year-old male who presented with fever, inguinal swelling, and discomfort. Clinical suspicion of inguinal and scrotal inflammation prompted us to perform a prompt CT scan. This radiological evaluation led to a preoperative diagnosis of a Type 3 Amyand's hernia.This case highlights the significance of CT scans in the accurate and timely diagnosis of Amyand's hernia. Distinguishing between various types of Amyand's hernia is pivotal as it profoundly influences surgical decision-making and postoperative outcomes. By sharing this case, we contribute to current knowledge about Amyand's hernia, increase clinical awareness of the condition, and emphasize the crucial role of imaging in its management.

Summary: Membrane-less subcellular compartments play important roles in various cellular functions. Although techniques exist to identify components of cellular bodies, a comprehensive method for analyzing both static and dynamic states has not been established. Here, we apply an antibody-based in situ biotinylation proximity-labeling technique to identify components of static and dynamic nuclear bodies. Using this approach, we comprehensively identify DNA, RNA, and protein components of Cajal bodies (CBs) and then clarify their interactome. By inhibiting transcription, we capture dynamic changes in CBs. Our analysis reveals that nascent small nuclear RNAs (snRNAs) transcribed in CBs contribute to CB formation by assembling RNA-binding proteins, including frontotemporal dementia-related proteins, RNA-binding motif proteins, and heterogeneous nuclear ribonucleoproteins.

This study examined the association between human activities and precipitation in dry areas, focusing on nomadic people in Djibouti. Nomadic communities often lack access to essential social services, and water resource management is crucial for their survival and social welfare. Understanding how they respond to variations in water availability could contribute to effective policy implementation. Using satellite-derived information, this study found that nighttime light brightness increased in response to precipitation around wadis, with potential water spring locations, and decreased with distance from a wadi. Specifically, we observed no effect when the distance was more than 5 km. Furthermore, no effect of precipitation was found in urban areas, while a positive effect was found in remote areas. These findings suggest that the activity of nomadic people increases around wadis in response to increased water resource availability, indicating that water supply is important for settlement projects because it can reduce water-seeking costs and improve social welfare. This study provides the first empirical evidence using satellite data and statistical analysis to show that water availability is critical for nomadic communities which can inform better resource management and policy decisions in African countries.

Purpose: Although good mid-term results of the first- and second-generation cementless stems have been reported, no study has compared outcomes between generations. This study aimed to compare the mid-term results of Accolade Ti–12Mo–6Zr–2Fe (TMZF) and Accolade II over a 5-year period. Methods: This retrospective, single-institution, single-surgeon observational study included patients who underwent primary total hip arthroplasty using the Accolade TMZF (n ​= ​71, group I) or Accolade II (n ​= ​73, group II) between January 2009 and July 2015. Revision and conversion cases were excluded. Functional evaluations were performed using the Japanese Orthopaedic Association hip (JOA) score. Radiographic evaluations were performed using anteroposterior radiographs. Spot welds, radiolucency, cortical hypertrophy, and stress shielding around the stem were assessed for each Gruen zone. Subsidence and stem alignment were evaluated. Results: The 5-year postoperative stem survival rate was 100% in both groups. The JOA score improved from 44.0 ​± ​10.2 to 90.6 ​± ​7.6 in group I and from 49.1 ​± ​10.1 to 91.7 ​± ​6.6 in group II. There were no significant differences in preoperative and postoperative JOA scores and subscale scores in either group. Significant spot welds were observed in group II in Gruen zones 3 and 5. Stress shielding progressed over time in both groups, and the prevalence of grade 3 shielding was significantly lower in group II (p ​= ​0.028). Conclusion: Both stems had a survival rate of 100%. The incidence of severe stress shielding seemed to be lower with Accolade II, but further investigations should be needed.

We report a rare case of a primary renal neuroendocrine tumor. The patient was a 64-year-old woman. The patient's chief complaint was gross hematuria. Dynamic contrast-enhanced computed tomography (CT) revealed a hypovascular mass 13 cm in diameter in the right kidney. The border of the mass was clear. A grossly contrast-impaired area and internal granular calcification were observed. A right radical nephrectomy was performed. Macroscopically, the mass was hemorrhaged and necrotic. It was diagnosed as a neuroendocrine tumor (NET) (Grade 2) histologically. Findings, such as hypovascularity, calcification, and necrosis, in our case were similar to those in previous reports. These findings are considered relatively characteristic of primary renal NETs.

Glycosylation of biopharmaceuticals can affect their safety and efficacy. Glycans can occur on recombinant adeno-associated viruses (rAAVs) that are used for gene therapy; however, the types of glycans that attach to rAAVs are controversial. Here, we conducted lectin microarray analyses on six rAAV serotype 6 (rAAV6) preparations that were produced differently. We demonstrate that O-glycans considered to be attached to rAAV6 were recognized by Agaricus bisporus agglutinin (ABA) and that N-glycans were detected in rAAV6 purified without affinity chromatography. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis showed that the N-glycans detected in rAAV6 were derived from host cell proteins. A combination of ABA-based fractionation and LC-MS/MS revealed that rAAV6 was O-glycosylated with the mucin-type glycans, O-GalNAc (Tn antigen), and mono- and di-sialylated Galβ1-3GalNAc (T antigen) at S156, T162, T194, and T201 in viral protein (VP) 2 and with O-GlcNAc at T242 in VP3. The mucin-type O-glycosylated rAAV6 particles were 0.1%–1% of total particles. Further physicochemical and biological analyses revealed that mucin-type O-glycosylated rAAV6 had a lower ratio of VP1 to VP2/VP3, resulting in a lower transduction efficiency both in vitro and in vivo compared with rAAV6 without mucin-type O-glycans. This report details conclusive evidence of rAAV glycosylation and its impact on rAAV-based therapeutics.

Background: SARS-CoV-2 mRNA vaccination, recognized for high immunogenicity, frequently induces adverse reactions, especially fever. We previously reported a correlation between post-vaccination fever and specific antibody responses to the primary series and first booster. We herein report changes in adverse reactions and the correlation between post-vaccination fever and antibody responses across successive vaccinations, from monovalent to bivalent mRNA vaccines. Methods: This cohort study was conducted at a Japanese hospital to investigate adverse reactions to the monovalent primary, first booster, and BA.4/5 bivalent BNT162b2 vaccinations. Local and systemic reactions were reported through a self-reporting diary after each dose. The spike-specific IgG titers were measured following each vaccination. Results: Across 727 vaccinations in the vaccine series, the bivalent booster induced fewer adverse reactions than earlier doses. Fever ≥ 38.0 °C was significantly less frequent in the bivalent booster (12.3 %) compared to the primary series and monovalent booster (22.0 %, 26.2 %, p

Summary: Aurora A is a critical kinase that functions in centrosome maturation and bipolar spindle assembly. On the other hand, Aurora A has E3 ubiquitin ligase activity and polyubiquitinates Breast cancer gene 1 (BRCA1)-interacting protein Obg-like ATPase 1 (OLA1), targeting it for proteasomal degradation. Here, we present a protocol to detect OLA1 ubiquitination. We describe steps for recovering frozen cells and protein purification. We then detail assays for both in vivo and in vitro ubiquitination of OLA1 by Aurora A.For complete details on the use and execution of this protocol, please refer to Fang et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Recurrent mastitis poses a common challenge on dairy farms. While the impact of repeated mastitis within the same lactation has been investigated, the difference from one lactation to the next, particularly concerning the change of milk and blood metabolites, remains unclear. This study aimed to examine the difference in milk yield, milk composition, and metabolic status in the subsequent lactation between healthy and repeated mastitis in the previous lactation. The study population comprised 50 cows chosen from 400 cows, with 25 having no history of mastitis and 25 experiencing mastitis more than three times during the last lactation. Following dry-off and calving, all cows initiated a new lactation, during which no mastitis was diagnosed until the sample collection period. In the group exposed to repeated mastitis, a significant decrease in milk fat levels was observed in the subsequent lactation, while no change was observed in milk somatic cell count (SCC). Milk collected from cows that had experienced repeated mastitis in the previous lactation exhibited significant increases in the levels of free amino acids, namely valine, proline, and alanine. However, no difference in plasma levels of these amino acids was noted. These results indicate that individuals exposed to repeated mastitis have persistent milk quality changes even after dry-off. Biomarker analysis suggested that the milk valine and proline showed a moderate biomarker potential on Kappa coefficients to characterize cows that have experienced repeated mastitis. Furthermore, the results of biomarker combinations for valine and proline provided the highest specificity (100 %), positive likelihood ratio (infinity), and substantial biomarker potential on kappa coefficients (0.68). These findings significantly enhance our understanding of the pathobiology and etiology of recurrent mastitis and provide a biomarker to characterize cows that have experienced repeated mastitis in the past.

We study the effect of self-gravity on entropy by directly solving the 4D semi-classical Einstein equation. In particular, we focus on whether the Bekenstein-Hawking formula holds when self-gravity is extremely strong. As an example, we consider a simple spherically symmetric static configuration consisting of many quanta and construct a self-consistent non-perturbative solution for ħ in which the entropy exactly follows the area law for many local degrees of freedom of any kind. This can be a candidate for black holes in quantum theory. It represents a compact dense configuration with near-Planckian curvatures, and the interior typically behaves like a local thermal state due to particle creation inside. Here, the information content is stored in the interior bulk, and the self-gravity plays an essential role in changing the entropy from the volume law to the area law. We finally discuss implications to black holes in quantum gravity and a speculative view of entropy as a gravitational charge.

Background: Constipation has been recently recognized as a complication associated with motor and autonomic dysfunction in patients with motor neuron disease (MND), typified by amyotrophic lateral sclerosis (ALS). However, the long-term characteristics of constipation remain unclear in patients with MND. We longitudinally investigated the prevalence and risk factors of constipation in a consecutive cohort of patients with MND. Methods: Data from Japanese patients with MND enrolled in a single-center registry from June 2017 to December 2021 were retrospectively investigated. The diagnosis of ALS was based on the updated Awaji criteria, and other MND subtypes were also included. The presence or absence of constipation symptoms was determined by referring to the Rome III criteria. The clinical backgrounds and symptoms of patients with and without constipation were compared. Results: Among 155 consecutive patients (female, 63; age, 66.5 ± 12.4 years), 30.3% had constipation at diagnosis and 52.9% after a median follow-up of 18 months. Univariate analysis showed that female sex, use of tracheostomy and invasive ventilation, and delivery of enteral nutrition were more frequent in the constipation group. The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale score was significantly lower in the constipation group, especially for the sub-items related to physical motor function. Multivariate analysis showed that the use of enteral nutrition was an independent risk of constipation, with an odds ratio of 3.69 (95% CI, 1.49–9.17; p = 0.005). Conclusion: Constipation had a high prevalence in patients with MND with impaired motor function. Controlling defecation is important in patients with MND, especially during enteral nutrition.

Pulmonary amyloidosis is characterized by extracellular deposition of fibrous protein called amyloid in the lungs and has three subtypes: nodular, diffuse, and tracheobronchial amyloidosis. Pulmonary nodular amyloidosis can mimic other lung diseases including infectious diseases, metastatic lung tumors, sarcoidosis, and pulmonary hyalinizing granuloma. A biopsy of the lesion is essential for a definitive diagnosis. Herein, we report the case of a 66-year-old man who presented for shortness of breath on exertion and was diagnosed with nodular pulmonary amyloidosis on ultrasound-guided percutaneous needle biopsy. A chest X-ray and computed tomography (CT) revealed bilateral slowly growing multiple calcified pulmonary nodules and cavities. Malignancy was suspected based on 18F-fluoro-deoxyglucose (18F-FDG) positron emission tomography/CT (PET/CT) images. An ultrasound-guided percutaneous needle biopsy was performed, and histopathologic examination of the lesion confirmed nodular pulmonary amyloidosis. This case highlights the importance of considering nodular pulmonary amyloidosis in the differential diagnosis of pulmonary nodules with increased uptake of 18F-FDG on PET/CT and the utility of ultrasound-guided needle biopsy in the definitive diagnosis.

The posterior circumflex humeral artery, a branch of the axillary artery, is compressed by the humeral head during repeated abduction and external rotation of the shoulder joint owing to its anatomical structure. This damages the vascular endothelium, resulting in thrombi, arterial dissection, and aneurysms, a condition known as posterior, circumflex humeral artery pathological lesions. A thrombus may form at the site and becomes a peripheral embolus, resulting in peripheral arterial occlusion.A 21-year-old right-handed elite man college volleyball player noticed coldness and pain in his right hand during a game. Cyanosis was present except in the middle finger, and the beating radial artery was palpable; however, the ulnar artery was not. Doppler ultrasound examination revealed thrombus occlusion of the ulnar artery and common palmar artery of the index finger. Peripheral arterial occlusion was diagnosed due to embolization of a thrombus from this site. The patient stopped practicing volleyball immediately after the onset of symptoms and was started on cilostazol 200 mg and rivaroxaban 15 mg. Subjective coldness of the fingers improved one week after the start of treatment. The patient resumed practice four weeks after the start of treatment and participated in a game by the seventh week.Posterior circumflex humeral artery pathological lesions are caused by overhead motions such as pitching. They are most commonly reported in athletes playing volleyball, although rare, and many cases of aneurysm formation have been reported.Observing a cold sensation in the periphery after practice is necessary for screening.

Background: Nursing shortage is a global and priority issue. Affective commitment has been identified as a key to retention in the workplace. Exploring the way to promote the nurse's affective commitment is necessary to maintain the nursing workforce and care quality. The staff nurse's organizational justice (procedural and interactional justice) and the manager's condition of mental health have the potential to be related to the staff nurse's affective commitment. Objective: To explore the impact on the nurse's affective commitment from procedural and interactional justices at individual and unit levels and the manager's mental health. Design: A multi-site longitudinal design. Setting(s): Nine Japanese hospitals with more than 200 beds and located in an area with more than 150,000 people. Participants: 385 staff nurses and their 42 nurse managers who completed both surveys in 2016 and 2017. Methods: We analyzed the data from a two-year national survey of the Work Environment for hospital Nurses in Japan part II. Nurse staff and their managers completed the surveys. This multilevel analysis performed four random intercept models on affective commitment and entered the variables of procedural and interactional justices and manager mental health into the models. Results: The staff nurse's affective commitment was positively associated with procedural justice climate (unit level), interactional justice climate (unit-level), and the perception of interactional justice (individual justice). The manager's mental health (psychological distress) had a negative relationship with affective commitment. Conclusions: The climates of procedural and interactional justice, the individual perception of interactional justice, and the manager's mental health impacted the nurses’ affective commitment as a predictor of retention. Moreover, the perception of interactional justice and the organizational contexts (organizational justice climates and managers’ psychological distress) were mediated by affective commitment. Thus, support to maintain the manager's mental health is required to promote staff's affective commitment related to retention. Registration: None. Tweetable abstract: Nurse staff's affective commitment was stimulated by interactional justice, two types of organizational justice climate, and the manager's mental health.

An immunochromatographic kit using antibodies against recombinant N protein of an omicron B.1.1.529 of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was developed to detect SARS-CoV-2 omicron variants. The kit detected omicron variants (BA.1.18, BA.1.1, BA.2, BA.2.12.1, BA.2.75, BA.4.1, BA.4.6, BE.1, BA.5.2.1, XE, BF.7, BF.7.4.1, XBB.1, XBB.1.5 and BQ.1.1) as well as Wuhan strain and a delta variant.

Summary: Interstitial lung disease (ILD) represents a large group of diseases characterized by chronic inflammation and fibrosis of the lungs, for which therapeutic options are limited. Among several causative genes of familial ILD with autosomal dominant inheritance, the mutations in the BRICHOS domain of SFTPC cause protein accumulation and endoplasmic reticulum stress by misfolding its proprotein. Through a screening system using these two phenotypes in HEK293 cells and evaluation using alveolar epithelial type 2 (AT2) cells differentiated from patient-derived induced pluripotent stem cells (iPSCs), we identified Cryptotanshinone (CPT) as a potential therapeutic agent for ILD. CPT decreased cell death induced by mutant SFTPC overexpression in A549 and HEK293 cells and ameliorated the bleomycin-induced contraction of the matrix in fibroblast-dependent alveolar organoids derived from iPSCs with SFTPC mutation. CPT and this screening strategy can apply to abnormal protein-folding-associated ILD and other protein-misfolding diseases.

The current coronavirus disease 2019 (COVID-19) pandemic that is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a significant threat to public health. Although vaccines based on the mRNA of the SARS-CoV-2 spike protein have been developed to induce both cellular and humoral immunity against SARS-CoV-2, there have been some concerns raised about their high cost, particularly in developing countries. In the present study, we aim to identify an immunogenic peptide in the SARS-CoV-2 spike protein to activate cellular immunity, particularly CD4+ helper T lymphocytes (Th cells), which are a commander of immune system. SARS-CoV-2 spike protein-derived peptides Spike448-477 and Spike489-513(N501Y)-specific CD4+ Th cell lines were generated by repetitive stimulation of healthy donor-derived CD4+T-cells with each peptide. Their HLA-restrictions were addressed by using blocking antibodies against HLA and HLA-transfected L-cells. The epitopes of Spike448-477-specific CD4+ Th cell lines were defined using a series of 7–14-mer overlapping truncated peptides and alanine-substituted epitope peptides. To address responsiveness of these CD4+ Th cell lines to several SARS-CoV-2 variants, we stimulated the CD4+ Th cell lines with mutated peptides. We addressed whether these identified peptides were useful for monitoring T-cell-based immune responses in vaccinated donors using the IFN-γ ELISpot assay. The Spike448-477 peptide was found to be a promiscuous peptide presented by HLA- DRB1*08:02, DR53, and DPB1*02:02. Although HLA-DPB1*02:02-restricted CD4+ Th cells did not response to some peptides with the L452R and L452Q mutations, the other CD4+ Th cells were not affected by any mutant peptides. We developed two tetramers to detect HLA-DRB1*08:02/Spike449-463- and Spike449-463(L452R/Y453F)-recognizing CD4+ Th cells. Spike489-513(N501Y) peptide was also a promiscuously presented to HLA-DRB1*09:01 and DRB1*15:02. The T-cell responses specific to both peptides Spike448-477 and Spike489-513 were detected in PBMCs after vaccinations. In addition, we observed that the Spike448-477 peptide activated both CD8+ T-cells and CD4+ Th cells in individuals receiving mRNA vaccines. SARS-CoV-2 spike protein-derived peptides, Spike448-477 and Spike489-513, include several epitopes that are presented by multiple HLA-class II alleles to activate CD4+ Th cells, which are considered useful for monitoring the establishment of acquired immunity after vaccination.

Summary: Prion-like protein propagation is considered a common pathogenic mechanism in neurodegenerative diseases. Here we investigate the in vivo propagation pattern and aggregation state of mutant α-synuclein by injecting adeno-associated viral (AAV)-α-synuclein-A53T-EGFP into the mouse olfactory cortex. Comparison of aggregation states in various brain regions at multiple time points after injection using western blot analyses shows that the monomeric state of the mutant/misfolded protein propagates to remote brain regions by 2 weeks and that the propagated proteins aggregate in situ after being incorporated into neurons. Moreover, injection of Alexa 488-labeled α-synuclein-A53T confirms the monomeric propagation at 2 weeks. Super-resolution microscopy shows that both α-synuclein-A53T proteins propagate via the lymphatic system, penetrate perineuronal nets, and reach the surface of neurons. Electron microscopy shows that the propagated mutant/misfolded monomer forms fibrils characteristic of Parkinson’s disease after its incorporation into neurons. These findings suggest a mode of propagation different from that of aggregate-dependent propagation.

The chemokine CCL21 regulates immune and cancer cell migration through its receptor CCR7. The Ccl21a gene encodes the isoform CCL21-Ser, predominantly expressed in the thymic medulla and the secondary lymphoid tissues. This study examined the roles of CCL21-Ser in the antitumor immune response in Ccl21a-knockout (KO) mice. The Ccl21a-KO mice showed significantly decreased growth of B16–F10 and YUMM1.7 melanomas and increased growth of MC38 colon cancer, despite no significant difference in LLC lung cancer and EO771 breast cancer. The B16–F10 tumor in Ccl21a-KO mice showed melanoma-specific activated CD8+ T cell and NK cell infiltration and higher Treg counts than wild-type mice. B16–F10 tumors in Ccl21a-KO mice showed a reduction in the positive correlation between the ratio of regulatory T cells (Tregs) to activated CD8+ T cells and tumor weight. In Ccl21a-KO tumor, the intratumoral Tregs showed lower co-inhibitory receptors TIM-3 and TIGIT. Taken together, these results suggest that endogenous CCL21-Ser supports melanoma growth in vivo by maintaining Treg function and suppressing antitumor immunity by CD8+ T cells.

Summary: The intricate interplay between gut microbes and the onset of experimental autoimmune encephalomyelitis (EAE) remains poorly understood. Here, we uncover remarkable similarities between CD4+ T cells in the spinal cord and their counterparts in the small intestine. Furthermore, we unveil a synergistic relationship between the microbiota, particularly enriched with the tryptophan metabolism gene EC:1.13.11.11, and intestinal cells. This symbiotic collaboration results in the biosynthesis of kynurenic acid (KYNA), which modulates the recruitment and aggregation of GPR35-positive macrophages. Subsequently, a robust T helper 17 (Th17) immune response is activated, ultimately triggering the onset of EAE. Conversely, modulating the KYNA-mediated GPR35 signaling in Cx3cr1+ macrophages leads to a remarkable amelioration of EAE. These findings shed light on the crucial role of microbial-derived tryptophan metabolites in regulating immune responses within extraintestinal tissues.

Summary: The BRCA1-interacting protein Obg-like ATPase 1 (OLA1) functions in centriole duplication. In this study, we show the role of the mitotic kinase Aurora A in the reduction of centrosomal OLA1. Aurora A binds to and polyubiquitinates OLA1, targeting it for proteasomal degradation. NIMA-related kinase 2 (NEK2) phosphorylates the T124 residue of OLA1, increases binding of OLA1 to Aurora A and OLA1 polyubiquitination by Aurora A, and reduces centrosomal OLA1 in G2 phase. The kinase activity of Aurora A suppresses OLA1 polyubiquitination. The decrease in centrosomal OLA1 caused by Aurora A-mediated polyubiquitination promotes the recruitment of pericentriolar material proteins in G2 phase. The E3 ligase activity of Aurora A is critical for centrosome amplification induced by its overexpression. The results suggest a dual function of Aurora A as an E3 ubiquitin ligase and a kinase in the regulation of centrosomal OLA1, which is essential for proper centrosome maturation in G2 phase.

Background/purpose: The number of patients with oral hypofunction is increasing with the aging of the population, and such hypofunction increases their risk for dysphagia and malnutrition. The purpose of this study was to measure the hardness of commercially available confectioneries, select a confectionery with a hardness suitable for masticatory training for elderly patients, and evaluate the effects of 1-week masticatory training on oral function (occlusal force, masticatory ability, and tongue pressure). Materials and methods: The average hardness values of 25 confectioneries were determined. Among them, one of the softest confectioneries that the patients felt as “chewable but difficult to chew” was selected as the training confectionery for each patient. The patients in the training group continued training, which involved eating of approximately 5 g of one selected confectionery daily for 7 days. The patients in the control group did not undergo any training. Oral function (occlusal force, masticatory ability, and tongue pressure) on the first day and after 7 days was evaluated and compared between the groups. Results: The occlusal force of the patients in the training group increased significantly. However, their masticatory ability and tongue pressure did not change significantly. Conclusion: Patients aged 65 years and older underwent masticatory training, which involved eating of a confectionery with its hardness adjusted individually for a week. A significant increase in the occlusal force was observed, suggesting that masticatory training using confectioneries with a hardness suitable for each patient is effective.

The development of three-dimensional printers has facilitated the creation of patient-specific hollow vessel models. Preoperative simulations using these types of models have improved our ability to select appropriate devices and embolic materials before performing complex endovascular procedures. This report describes 2 cases of high-flow renal arteriovenous fistulas (r-AVFs) that were successfully treated via short-segment embolization using the preloading coil-in-plug (p-CIP) technique. To our knowledge, this is the first report of r-AVF being treated using the p-CIP technique. Our findings demonstrate that preoperative simulation has the potential to improve the safety and reliability of complex vascular embolization procedures.

Indoor vertical farming using artificial light has gained popularity as one solution to food problems. However, prior studies have shown that some consumers have a negative impression that crops are grown in an artificial environment. The increased use of purple Light-Emitting Diode (LED) lighting, which would make the growing environment look more artificial, may exacerbate that negative perception, leading to low acceptance of vertically farmed produce. Given that consumers are increasingly seeing indoor vertical farming directly, for example, in supermarkets and office buildings, it is important to understand how they perceive the use of purple LED lighting to grow crops and whether these perceptions can be improved by learning more about the scientific basis for artificial light cultivation. This study aimed to determine whether purple LED lighting reduces consumers’ perceptions of indoor vertical farming compared to traditional white lighting, and to examine whether providing information on plant growth and artificial light changes those perceptions. We administered a web-based questionnaire to 961 Japanese respondents, and analyzed the response data using analysis of variance and an ordered probit model to explore the factors that define the likability for indoor vertical farming. The results revealed that the color of LED lighting had a limited influence on consumers' perceptions of indoor vertical farming, whereas explaining the principle of plant growth under artificial light improves their perceptions. Additionally, personal factors, such as resistance to novel food technology, trust in food safety, and awareness of indoor vertical farming, had a significant impact on the perceptions. It is crucial to expand opportunities for people to interact with artificial light cultivation and disseminate information about its scientific mechanisms.

Background & Aims: The albumin-bilirubin (ALBI) score is calculated using serum levels of total bilirubin and albumin as a simple method to assess liver function. This study investigated the ability of baseline ALBI score/grade measurements to assess histological stage and disease progression in individuals with primary biliary cholangitis (PBC) in a large Japanese nationwide cohort. Methods: A total of 8,768 Japanese patients with PBC were enrolled between 1980 and 2016 from 469 institutions, among whom 83% received ursodeoxycholic acid (UDCA) only, 9% received UDCA and bezafibrate, and 8% were given neither drug. Baseline clinical and laboratory parameters were retrospectively retrieved and reviewed from a central database. Associations of ALBI score/grade with histological stage, mortality, and need for liver transplantation (LT) were evaluated using Cox proportional hazards models. Results: During the median follow-up period of 5.3 years, 1,227 patients died (including 789 from liver-related causes) and 113 underwent LT. ALBI score and ALBI grade were significantly associated with Scheuer’s classification (both p

Vaginoscopy has been mainly used diagnostically due to the lack of adequate equipment for performing complicated surgeries (Johary et al., 2015). However, herein, we report therapeutic vaginal endoscopic surgery (pneumovaginoscopy) for secondary malignant vaginal tumors using the vNOTES technique and devices (Kita et al., 2021; Yokoe et al., 2022).To our knowledge, this report and surgical video demonstrate the first case of successful fertility-sparing R0 tumor resection of a rare primary cervical clear cell adenocarcinoma using pneumovaginoscopy.A 12-year-old girl was referred to our outpatient clinic with a chief complaint of a genital tumor and possible clear cell carcinoma on biopsy. There was no history of diethylstilbestrol exposure. MRI and CT images suggested a polypoid cervical tumor without metastatic lesions. Therefore, we performed therapeutic pneumovaginoscopic surgery with diagnostic laparoscopy and hysteroscopy.The cervical tumor was resected completely, and hysteroscopy and laparoscopy revealed no abnormalities. The total surgical time was 123 min, and the blood loss volume was minimal. R0 resection was achieved microscopically.Postoperatively, we performed a partial cervical resection around the first surgical scar to confirm no residual tumor.There were no postoperative complications, and a 2-year follow-up revealed no recurrence.The standard treatment for early-stage cervical cancer (IA2-IB1) remains radical hysterectomy with pelvic lymphadenectomy. However, fertility-sparing minimally invasive surgery has recently been introduced for clear cell adenocarcinoma of the cervix (Su et al., 2020). Our report supports the possibility of this minimally invasive surgery under exceptional conditions. This study was approved by the ethics committee of Kansai Medical University. Written and signed informed consent was obtained from the patient’s legal guardian.

Background/purpose: Baicalin, a natural bioactive flavonoid extracted from Scutellaria baicalensis Georgi, mediates bone metabolism, and recent studies have revealed that it has cell signaling properties. However, its biological functions in cementoblasts still remain unclear. This study therefore aimed to investigate the effects of baicalin on bone resorption markers, including osteoprotegerin (OPG) and receptor activator of nuclear factor-κβ ligand (RANKL), in human cementoblast-lineage cells, as well as their proliferation ability. Materials and methods: Human cementoblast cell line (HCEM) cells were cultured and treated with 0, 0.01, 0.1, or 1 μM of baicalin. The proliferative capacity of cultured HCEM cells was analyzed using bromodeoxyuridine immunoassay and cell counting. The baicalin effect on OPG and RANKL expression was determined using quantitative polymerase chain reaction (qPCR) and western blotting. Furthermore, OPG expression was measured in 1 μM baicalin-treated HCEM cells in the presence or absence of the Wnt signaling pathway inhibitor, Dickkopf (Dkk)-1, using qPCR and western blotting. Results: The addition of 0.01, 0.1, and 1 μM of baicalin did not significantly change the proliferative capacity of cultured HCEM cells. Compared with the non-supplemented group, baicalin increased and suppressed OPG and RANKL gene and protein expression, respectively, in a concentration-dependent manner. OPG mRNA and protein expression levels were increased by 1 μM baicalin, which was suppressed by Dkk-1 addition. Conclusion: Baicalin enhanced OPG expression in HCEM cells through the Wnt/beta-catenin signaling pathway, which could contribute to periodontal tissue regeneration.

The relation between pre-vaccination antipyretic use and antibody responses to SARS-CoV-2 vaccination has been unclear. We measured the pre- and post-BNT162b2 booster spike-specific IgG titers and recorded antipyretic use and adverse reactions for SARS-CoV-2-naive hospital healthcare workers. The data of 20 cases who used antipyretics within 24 h before vaccination were compared to that of 281 controls. The post-booster geometric mean IgG titers were 15,559 AU/mL (95 % CI, 11,474–21,203) for the cases and 16,850 AU/mL (95 % CI, 15,563–18,243) for the controls (p = 0.622). No significant reduction in the frequency or severity of any of the solicited adverse reactions was found for the cases. Similar results were obtained after adjustment with propensity-score matching for demographic characteristics, baseline IgG titer, and post-vaccination antipyretic use. Antipyretic use within 24 h before vaccination would not affect mRNA COVID-19 vaccine-induced specific antibody responses and that postponement of vaccination due to pre-vaccination antipyretic use would be unnecessary.

A 40-year-old female (gravida 3 para 1) presented with menstrual, urinary, and anal pain. Computed tomography revealed type II acquired uterine arteriovenous malformation, a common dilated venous sac with bilateral uterine arteries, and multiple branches of iliac arteries draining to the bilateral ovarian veins. Venous sac transvenous embolization via the left ovarian vein of dominant outflow was planned, since complete arteriovenous malformation occlusion was difficult with super-selective transarterial embolization of multiple feeders. Therefore, transarterial embolization of the minor feeder was performed before completing transvenous embolization using coils and 50% glue under left iliac artery flow control. Immediately thereafter, angiography confirmed the complete disappearance of the uterine arteriovenous malformation, and all pain symptoms remitted. In conclusion, transvenous embolization combined with adjunctive transarterial embolization can be an effective and radical treatment for type II uterine arteriovenous malformations.

Background/purpose: Facial asymmetry is relatively common in the general population. Here, we propose a fully automated annotation system that supports analysis of mandibular deviation and detection of facial asymmetry in posteroanterior (PA) cephalograms by means of a deep learning-based convolutional neural network (CNN) algorithm. Materials and methods: In this retrospective study, 400 PA cephalograms were collected from the medical records of patients aged 4 years 2 months–80 years 3 months (mean age, 17 years 10 months; 255 female patients and 145 male patients). A deep CNN with two optimizers and a random forest algorithm were trained using 320 PA cephalograms; in these images, four PA landmarks were independently identified and manually annotated by two orthodontists. Results: The CNN algorithms had a high coefficient of determination (R2), compared with the random forest algorithm (CNN-stochastic gradient descent, R2 = 0.715; CNN-Adam, R2 = 0.700; random forest, R2 = 0.486). Analysis of the best and worst performances of the algorithms for each landmark demonstrated that the right latero-orbital landmark was most difficult to detect accurately by using the CNN. Based on the annotated landmarks, reference lines were defined using an algorithm coded in Python. The CNN and random forest algorithms exhibited similar accuracy for the distance between the menton and vertical reference line. Conclusion: Our findings imply that the proposed deep CNN algorithm for detection of facial asymmetry may enable prompt assessment and reduce the effort involved in orthodontic diagnosis.

[Purpose]: We used a near-infrared ray catheter (NIRC) in a child with cloacal exstrophy presenting with hematometra and assessed whether the NIRC could help with complicated adhesiolysis during hemi-hysterectomy in children. [Method]: A 6-French pig tail-type NIRC was inserted into the left ureter with guidance from a cystoscope. Laparoscopic hemi-hysterectomy with fluorescence observation was performed using the VISERA ELITE 2 system. [Result]: NIRC insertion into the left ureter was not as difficult as expected despite the eccentric position of the left ureter orifice. When we found an enlarged left uterus and fallopian tube, adhesion was extremely severe around them due to chronic inflammation caused by hematometra. When near-infrared rays were applied, a fluorescent ureteral catheter that emitted bright green excitation light was observed on the dorsal side of the enlarged left uterus and fallopian tube. Under ureteral navigation with an NIRC, dissection of the adhesions was performed safely and smoothly. Hemi-hysterectomy and adnexectomy were performed successfully. The patient was doing well 2 years postoperatively without any complications. [Conclusion]: An NIRC can provide useful real-time visualization of the ureter course and reduce the risk of ureteral damage in children with advanced adhesions.

Background: Cerebral hyperperfusion syndrome (CHS) is a relatively rare but critical perioperative complication after CEA and CAS. We herein report a case with a preoperative increase in CBV, not OEF, in a patient who suffered from CHS both after CEA and after CAS for the same lesion. Case description: An 82-year-old female with a history of transient right hemiparesis was admitted to our hospital. 3DCTA demonstrated severe stenosis of the left neck ICA with severe calcification. 15O-PET indicated an increase of CBV was observed, but an increase of OEF was not observed in the left MCA territory. She underwent left CEA and suffered from CHS. After four months of left CEA, she suffered from right hemiparesis and was admitted to our hospital. MRI DWI revealed a spotty high signal lesion in the left frontal subcortex due to re-stenosis of the left neck ICA following CEA. She underwent CAS and suffered from CHS again. Finally, she was discharged home with mRS1. Conclusion: To our knowledge, no previous reports have described CHS after CEA and CAS for the same lesion, as occurred in our case. This case could suggest that regardless of CEA and CAS procedures, an increase of CBV was related to CHS rather than the longstanding chronic ischemia, which might increase OEF.

Hydatidiform moles can be fatal because of the risk of massive bleeding or thyroid storm; however, they rarely occur concomitantly with sepsis. We present herein the case of a woman with a hydatidiform mole with septic shock. A 30-year-old multiparous woman with Basedow's disease presented with fever, amenorrhea, and vaginal bleeding. Transvaginal ultrasonography revealed an enlarged uterus with an intrauterine vesicular mass (74.3 × 93.0 mm). Human chorionic gonadotropin level was 994,000 mIU/mL. C-reactive protein was elevated, and blood cultures were positive (gram-negative rods), indicating infection. After administering antibiotics (tazobactam and piperacillin), blood pressure suddenly decreased (69/45 mmHg), requiring stabilization with noradrenaline and albumin. The uterine contents were naturally expelled, followed by dilatation and curettage after her vital signs and general condition gradually improved. The pathological diagnosis was a complete hydatidiform mole. Culture of the intrauterine contents revealed Escherichia coli, leading to the potentially fatal diagnosis of septic shock associated with a hydatidiform mole.

Purpose: We applied indocyanine green fluorescence angiography (ICG-FA) to a child with intestinal volvulus and assessed if ICG-FA could help judge bowel resection. Method: ICG with a dose of 0.5 mg/kg was injected and decision of intestinal resection was made by means of the degrees of fluorescent intensity in fluorescence system. Result: An 8-year-old girl was diagnosed as intestinal volvulus due to mesenteric defect with 200 cm of the strangulated intestine. ICG-FA revealed no fluorescence was observed at the entire strangulated intestine, thus we planned to re-evaluate the viability of intestine. ICG-FA at second look operation showed three patterns of fluorescent intensity including WHITE; strong fluorescence at mesentery and intestinal wall, GRAY; weak mosaic fluorescence at bowel wall, and BLACK; no fluorescence. We decided to resect 100 cm of BLACK fluorescent bowel and preserve WHITE and GRAY fluorescent intestine with double-barreled stoma. The 3rd ICG-FA reveled GRAY pattern changed to WHITE fluorescence, thus stoma was closed successfully. The patient is doing well 2 years after surgery without any complication Conclusion: ICG-FA can provide useful real-time visualization of intestinal perfusion intraoperatively, and help surgeon judge the necessity and its area of bowel resection.

Background & Aims: The reason why small intestinal cancer is rarer than colorectal cancer is not clear. We hypothesized that intraepithelial lymphocytes (IELs), which are enriched in the small intestine, are the closest immune cells to epithelial cells, exclude tumor cells via cell-to-cell contact. Methods: We developed DPE-green fluorescent protein (DPE-GFP) × adenomatous polyposis coli; multiple intestinal neoplasia (APCmin ) mice, which is a T-cell–reporter mouse with spontaneous intestinal tumors. We visualized the dynamics of IELs in the intestinal tumor microenvironment and the interaction between IELs and epithelial cells, and the roles of cell-to-cell contact in anti-intestinal tumor immunity using a novel in vivo live-imaging system and a novel in vitro co-culture system. Results: In the small intestinal tumor microenvironment, T-cell movement was restricted around blood vessels and the frequency of interaction between IELs and epithelial cells was reduced. Genetic deletion of CD103 decreased the frequency of interaction between IELs and epithelial cells, and increased the number of small intestinal tumors. In the co-culture system, wild-type IELs expanded and infiltrated to intestinal tumor organoids from APCmin mice and reduced the viability of them, which was cell-to-cell contact and CD103 dependent. Conclusions: The abundance of IELs in the small intestine may contribute to a low number of tumors, although this system may not work in the colon because of the sparseness of IELs. Strategies to increase the number of IELs in the colon or enhance cell-to-cell contact between IELs and epithelial cells may be effective for the prevention of intestinal tumors in patients with a high cancer risk.

Primary rhabdomyosarcoma (RMS) of the diaphragm, especially alveolar RMS, is extremely rare. Because of its rarity, no treatment for it has yet been established, but previous studies have reported long-term survival in recipients of a combination therapy with local control, including a total resection and/or radiation therapy concomitant with multiagent chemotherapy. We experienced a case of primary alveolar rhabdomyosarcoma of the diaphragm surrounding the gastric cardia in a 15-year-old, female patient. After administering chemotherapy consisting of vincristine, actinomycin D, and cyclophosphamide (VAC) to shrink the tumor, tumor resection was performed with a proximal gastrectomy and partial resection of the diaphragm, pericardium, and left lung. After receiving postoperative adjuvant chemotherapy with VAC and radiotherapy at a total of 41.4 Gy, the patient has been relapse-free for 18 months. The tumor-induced stenosis at the hilum was corrected, allowing oral intake and markedly improving the patient's nutritional status. Tumor resection with a proximal gastrectomy for primary diaphragmatic RMS surrounding the lower esophagus is recommended both for its efficacy in local control and for allowing the preservation of postoperative gastrointestinal function.

Background: Preeclampsia (PE) is hallmarked by dysfunction of various organs; therefore, its diagnosis can be challenging, especially when patients present with right upper abdominal pain. Herein, we present a case of postpartum gallbladder wall thickening (GBWT) that led to a diagnosis of PE, rather than hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome or gallbladder and biliary disease. Case Presentation: A 31-year-old postpartum woman presented with a fever, hypertension, headache, and right upper abdominal pain. HELLP syndrome and intracranial hemorrhage were initially suspected, due to the combination of symptoms and elevated levels of aspartate transaminase, alanine transaminase, and lactate dehydrogenase. However, hemolysis and thrombocytopenia were absent, and a computed tomography (CT) scan of the head did not indicate the presence of intracranial hemorrhage. Further, transabdominal ultrasound and CT revealed GBWT (edematous gallbladder); CT also revealed an enlarged heart, lung edema, pleural effusion, and ascites. Thus, PE, rather than HELLP syndrome or gallbladder or biliary disease, was diagnosed based on gestational hypertension and proteinuria, new-onset headache, liver dysfunction, and edema in several organs, including the lung. Nicardipine treatment quickly improved hypertension and headache, and, over time, the patient's urination increased, and edema subsided throughout the body. Furthermore, laboratory results improved, and the patient was discharged on postpartum day 11. Conclusion: Postpartum gallbladder wall thickening can be a diagnostic sign of PE.

Lipopolysaccharide (LPS), an outer component of Gram-negative bacteria, induces a strong response of innate immunity via microglia, which triggers a modulation of the intrinsic excitability of neurons. However, it is unclear whether the modulation of neurophysiological properties is similar among neurons. Here, we found the hypoexcitability of layer 5 (L5) pyramidal neurons after exposure to LPS in the medial prefrontal cortex (mPFC) of juvenile rats. We recorded the firing frequency of L5 pyramidal neurons long-lastingly under in vitro whole-cell patch-clamp, and we found a reduction of the firing frequency after applying LPS. A decrease in the intrinsic excitability against LPS-exposure was also found in L2/3 pyramidal neurons but not in fast-spiking interneurons. The decrease in the excitability by immune-activation was underlain by increased activity of small-conductance Ca2+-activated K+ channels (SK channels) in the pyramidal neurons and tumor necrosis factor (TNF)-α released from microglia. We revealed that the reduction of the firing frequency of L5 pyramidal neurons was dependent on intraneuronal Ca2+ and PP2B. These results suggest the hypoexcitability of pyramidal neurons caused by the upregulation of SK channels via Ca2+-dependent phosphatase during acute inflammation in the mPFC. Such a mechanism is in contrast to that of cerebellar Purkinje cells, in which immune activation induces hyperexcitability via downregulation of SK channels. Further, a decrease in the frequency of spontaneous inhibitory synaptic transmission reflected network hypoactivity. Therefore, our results suggest that the directionality of the intrinsic plasticity by microglia is not consistent, depending on the brain region and the cell type.

Background: Pulmonary hyalinizing granuloma (PHG) is a very rare pulmonary disease characterized by multiple fibrosclerotic inflammatory lung nodules. The disease is supposedly caused by an unusual immune response. Case presentation: We present a case involving a 53-year-old female with a history of lumpectomy surgery due to invasive ductal carcinoma who was admitted for slowly progressive pulmonary nodules. The patient's elevated serum IgG4 level and the pathological findings obtained in surgical biopsy indicated IgG4-related lung disease. The nodules continued to enlarge despite administration of corticosteroid therapy, and we performed a second surgical biopsy to obtain a correct diagnosis. The pathological findings obtained in the second biopsy were different and consistent with the features of PHG. Conclusions: In this report, the radiological follow-up data obtained after lumpectomy surgery demonstrate the very early stage of PHG and the following radiological changes over a decade, and the two surgical biopsies support us to realize the pathological change from previous diagnosed disease before PHG.

An expression of concern (EoC) alerts readers to new considerations or concerns about a paper, usually at the post-publication stage. Authors and readers are left in a state of uncertainty as they await a resolution. This uncertainty might create a state of stress or anxiety for some authors. The paper's findings may be either validated and confirmed, resolving the EoC, or the paper's validity or loss of integrity is confirmed, leading to an erratum or retraction. Academics wanting to cite a paper to which an EoC is associated might decide not to cite it. If an EoC is reversed, i.e., if the post-publication findings annul the initial concerns, then the authors and journal may suffer a “loss” of citations. Conversely, if concerns are confirmed post-publication, and the EoC develops into a retraction, then any citations that were rewarded while the paper was in a state of uncertainty were rewarded unfairly. In such a case, both author- and journal-based metrics should be adjusted. Using the Retraction Watch database until April 20, 2021, we assessed 20 cases of EoCs in the neuroscience literature to appreciate how EoCs have been processed. After excluding one author-issued EoC, from 19 editor-issued EoCs, 10 were resolved in an average of 220 days while nine remain unresolved. In this article, we suggest the need to make the processes associated with an EoC more visible and transparent to the academic community, allowing editors to make the correct decisions regarding its resolution.

Tardigrades are microscopic animals of which terrestrial species are capable of tolerating extreme environments by entering a desiccated ametabolic state known as anhydrobiosis. Intriguingly, they survive high dosage gamma rays (>4,000 Gy), possibly through a mechanism known as cross-tolerance. We hypothesized that anhydrobiosis genes are also regulated during cross-tolerance, thus we submitted Ramazzottius varieornatus to 500 Gy 60Co gamma-ray and conducted time-course low-input RNA-Seq. The gene expression was quantified with RSEM and differential expression was determined with DEseq2. Differentially expressed genes were submitted to gene ontology enrichment analysis with GOStat. The transcriptome dynamically shifted nine hours post-exposure.

Morphine, fentanyl, and oxycodone are widely used as analgesics, and recently hydromorphone has been approved in Japan. Although all of these are selective for μ-opioid receptors (MORs) and have similar structures, their analgesic potencies and adverse effects (AEs) are diverse. Recent molecular analyses of MOR signaling revealed that the G protein-mediated signaling pathway causes analgesic effects and the β-arrestin-mediated signaling pathway is responsible for AEs. We used several cell-based analyses that selectively measure cellular responses activated by either G protein- or β-arrestin-mediated pathways. GloSensor™ cAMP, CellKey™, and receptor internalization assays were performed with four different types of cells stably expressing differentially labelled MOR. EC50 values measured by cAMP and CellKey™ assays had potencies in the order fentanyl ≤ hydromorphone

We developed a novel chemically modified miR-143 (miR-143#12), and with it we investigated the contribution of miR-143 to the pathogenesis of bladder cancer (BC), in which miR-143 is extremely downregulated. Since miR-143 silenced K-RAS and RAS effector-signaling molecules Erk and Akt, we performed the ectopic expression of miR-143 in human BC 253J-BV cells, and we examined the growth inhibition and the mechanism of it in vitro and in orthotopic model mice. As a result, miR-143#12 induced a marked growth inhibition with apoptosis through impairing RAS-signaling networks, including SOS1, which exchanges guanosine diphosphate (GDP)/RAS for active guanosine triphosphate (GTP)/RAS. In the in vivo study, miR-143#12 exhibited a marked anti-tumor activity by either systemic or intravesical administration with polyionic copolymer (PIC) as the carrier, compared with the activity obtained by use of lipofection. These findings raised the possibility that the chemically modified miR-143#12 would be a candidate of microRNA (miRNA) medicine for BC delivered by intravesical infusion. Keywords: miR-143, K-RAS, SOS1, bladder cancer, PI3K/Akt, MEK/Erk signaling, intravesical infusion

Summary: Thalidomide is a teratogen that causes multiple malformations in the developing baby through its interaction with cereblon (CRBN), a substrate receptor subunit of the CRL4 E3 ubiquitin ligase complex. CRBN was originally reported as a gene associated with autosomal recessive non-syndromic mild mental retardation. However, the function of CRBN during brain development remains largely unknown. Here we demonstrate that CRBN promotes brain development by facilitating the proliferation of neural stem cells (NSCs). Knockdown of CRBN in zebrafish embryos impaired brain development and led to small brains, as did treatment with thalidomide. By contrast, overexpression of CRBN resulted in enlarged brains, leading to the expansion of NSC regions and increased cell proliferation in the early brain field and an expanded expression of brain region-specific genes and neural and glial marker genes. These results demonstrate that CRBN functions in the determination of brain size by regulating the proliferation of NSCs during development. : Cellular Neuroscience; Developmental Neuroscience; Molecular Neuroscience Subject Areas: Cellular Neuroscience, Developmental Neuroscience, Molecular Neuroscience

Summary: It has been challenging to generate in vitro models of alveolar lung diseases, as the stable culture of alveolar type 2 (AT2) cells has been difficult. Methods of generating and expanding AT2 cells derived from induced pluripotent stem cells (iPSCs) have been established and are expected to be applicable to disease modeling. Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by dysfunction of lysosome-related organelles, such as lamellar bodies (LBs), in AT2 cells. From an HPS type 2 (HPS2) patient, we established disease-specific iPSCs (HPS2-iPSCs) and their gene-corrected counterparts. By live cell imaging, the LB dynamics were visualized and altered distribution, enlargement, and impaired secretion of LBs were demonstrated in HPS2-iPSC-derived AT2 cells. These findings provide insight into the AT2 dysfunction in HPS patients and support the potential use of human iPSC-derived AT2 cells for future research on alveolar lung diseases. : Pulmonary surfactant secretion by alveolar type 2 (AT2) cells is crucial for alveolar homeostasis. Gotoh and colleagues generated Hermansky-Pudlak syndrome type 2 (HPS2) patient-derived iPSCs and their gene-corrected counterparts and differentiated them into alveolar organoids (AOs). In HPS2-AOs, aberrant lamellar bodies and impaired surfactant secretion were demonstrated. Human iPSC-derived AOs might be useful for investigating alveolar lung diseases. Keywords: iPSC, Hermansky-Pudlak syndrome, HPS, lamellar body, alveolar type 2 cell, pulmonary surfactant, pluripotent stem cell, pulmonary fibrosis, alveolar organoid, MX35

Summary: Recent studies have profiled the innate immune signatures in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and suggest that cellular responses to viral challenge may affect disease severity. Yet the molecular events that underlie cellular recognition and response to SARS-CoV-2 infection remain to be elucidated. Here, we find that SARS-CoV-2 replication induces a delayed interferon (IFN) response in lung epithelial cells. By screening 16 putative sensors involved in sensing of RNA virus infection, we found that MDA5 and LGP2 primarily regulate IFN induction in response to SARS-CoV-2 infection. Further analyses revealed that viral intermediates specifically activate the IFN response through MDA5-mediated sensing. Additionally, we find that IRF3, IRF5, and NF-κB/p65 are the key transcription factors regulating the IFN response during SARS-CoV-2 infection. In summary, these findings provide critical insights into the molecular basis of the innate immune recognition and signaling response to SARS-CoV-2.

Background: Multi-virus real-time polymerase chain reaction (PCR) system is able to simultaneously detect 163 viruses using a multiplex Taqman real-time PCR system. We present a case of acute liver failure (ALF) of unknown etiology diagnosed with echovirus 30 infection via multi-virus real-time PCR. Case presentation: A previously healthy 66-year-old man had a persistent fever and developed ALF of unclear etiology. Although viral infection was suspected, serological screening showed no evidence of acute viral infections such as hepatitis A, B, C and E, Epstein-Barr virus, herpes simplex virus, and varicella zoster virus. Multi-virus real-time PCR revealed the presence of enterovirus and echovirus 30 genomes, and reverse transcription-PCR using enterovirus-specific primers confirmed the presence of enterovirus genome in serum samples at the time of admission. Anti-echovirus antibody titers showed an increase in paired sera. In spite of multimodality treatment, the patient died due to multiple organ failure. Histological analysis in autopsy revealed extensive coagulative necrosis of the hepatocytes and immunohistochemical analysis showed the expression of enterovirus antigens in necrotic hepatocytes. Conclusions: We present here a case of echovirus 30 associated with ALF. Multi-virus real-time PCR is useful for detection of virus for patients with ALF of unknown etiology suspected of harboring a viral infection.

Pulmonary mucoepidermoid carcinoma (PMEC) are rare, accounting for 0.1–0.2% of all malignant lung tumors. Furthermore, endobronchial lesions are rare and are more commonly found in the segmental or lobar bronchi. We present, to the best of our knowledge, the first case of successful treatment with photodynamic therapy (PDT) for PMEC. A 77-year-old male presented with cough and hemosputum for 4 months. Chest computed tomography showed a mass in the right intermediate bronchus. Endobronchial biopsy revealed a diagnosis of PMEC. An optimal surgical technique to preserve respiratory function was desirable as most of the tumor emerged from the bronchial glands in the central airways and was of low-grade type. Hence, PDT was performed. Repeat bronchoscopies were performed 5 years after the PDT and showed no evidence of tumor recurrence. PDT is more likely to be effective for low-grade PMECs that are visible on bronchoscopy.