Anisotropy of upper critical fields and interface superconductivity in FeSe/SrTiO3grown by PLD.

In this study, we grow FeSe/SrTiO3with thicknesses of 4-19 nm using pulsed laser deposition and investigate their magneto-transport properties. The thinnest film (4 nm) exhibit negative Hall effect, indicating electron transfer into FeSe from the SrTiO3substrate. This is in agreement with reports on ultrathin FeSe/SrTiO3grown by molecular beam epitaxy. The upper critical field is found to exhibit large anisotropy (γ>11.9), estimated from the data near the transition temperature (Tc). In particular, the estimated coherence lengths in the perpendicular direction are 0.15-0.27 nm, which are smaller than thec-axis length of FeSe, and are found to be almost independent of the total thicknesses of the films. These results indicate that superconductivity is confined at the interface of FeSe/SrTiO3.

Impact of the early phase of COVID-19 on the trends of isolated bacteria in the national database of Japan: an interrupted time-series analysis.

OBJECTIVES: During the coronavirus disease 2019 (COVID-19) pandemic, a change in the trend of infections was observed. However, there are few reports comprehensively assessing the impact of the early phase of COVID-19 on the trend of bacteria isolated. METHODS: We extracted the number of positive cultures of hospitalized patients for approximately 200 institutions using the Japanese national database. The outcome was the ratio of 10 species isolated in comparison to the total isolates for each month. Interrupted time-series analyses were conducted between 13 (from Jan-2019 to Jan-2020) and 8 (from May-2020 to Dec-2020) monthly data points. RESULTS: A total of 369,210 isolates were involved. Differences in the level change for Streptococcus pneumoniae, Haemophilus influenzae, and Streptococcus pyogenes decreased significantly by 0.272 (95% confidence interval [CI]:0.192-0.352), 0.244 (95%CI:0.174-0.314), and 0.324 (95%CI:0.06-0.589), respectively. Bacteria transmitted by contact infection, such as Staphylococcus aureus, did not decrease. Differences in slope change were not significant in all species. CONCLUSIONS: The ratios of isolated bacteria transmitted by droplet infection decreased immediately after the early phase of COVID-19 and maintained the same level. The awareness and behavioral changes toward increased COVID-19 prevention might have a substantial impact on the prevention of bacterial infections, especially droplet infections.

Virtual reality as a learning tool for improving infection control procedures.

BACKGROUND: Hand hygiene and donning personal protective equipment (PPE) are essential techniques for infection control; however, low compliance is an issue. The effectiveness of virtual reality (VR) in learning infection control procedures is unknown. METHODS: To verify the effectiveness of VR, medical students were categorized into VR or lecture groups (n=21 each). Each group was given the same curricular content; one group received the training through VR learning using a fully-immersive 360-degree video and the other was conventional lecture-style learning. Before and after the training, they were evaluated for the implementation of hand hygiene and PPE using an Objective Structured Clinical Examination method. Post-test questionnaires were administered. RESULTS: The scores for hand hygiene, donning PPE, and the total score increased after learning in both groups. There was no difference between the pre-test total scores of the two groups (7 [5-9] vs 6 [5-7.5], P=.352); however, the VR group had significantly higher post-test total scores than the lecture group (12 [9.5-12] vs 9 [8-12], P=.024). More students in the VR group responded that they enjoyed the training and would like to use the same learning method next time. CONCLUSIONS: VR can be a useful tool for learning and practicing appropriate infection control procedures.

Depletion of hepatic stellate cells inhibits hepatic steatosis in mice.

BACKGROUND AND AIM: Hepatic stellate cells (HSCs), the main source of extracellular matrix in hepatic fibrogenesis, produce various cytokines, growth factors, and morphogenetic proteins. Among these, several factors are known to promote hepatocyte lipid accumulation, suggesting that HSCs can be efficient therapeutic targets for non-alcoholic steatohepatitis (NASH). This study aimed to investigate the effects of HSC depletion on the development of hepatic steatosis and fibrosis in a murine NASH model. METHODS: C57BL/6 mice were treated with gliotoxin (GTX), an apoptosis inducer of activated HSCs under the feeding of a choline-deficient l-amino acid-defined high-fat diet for 4 weeks. For in vitro study, Hc3716 cells, immortalized human hepatocytes, were treated with fatty acids in the presence or absence of LX2, immortalized HSCs. RESULTS: Choline-deficient l-amino acid-defined high-fat diet increased pronounced hepatic steatosis, which was attenuated by GTX treatment, together with a reduction in the number of activated HSCs. This change was associated with the downregulation of the peroxisome proliferator-activated receptor gamma (PPARγ) and its downstream genes, including adipocyte protein 2, cluster of differentiation 36 (CD36), and fatty acid transport protein 1, all of which increase the fatty acid uptake into hepatocytes. As expected, GTX treatment improved hepatic fibrosis. Co-culture of hepatocytes with HSCs enhanced intracellular lipid accumulation, together with the upregulation of PPARγ and CD36 protein expressions. CONCLUSIONS: In addition to the improvement in hepatic fibrogenesis, depletion of HSCs had a favorable effect on hepatic lipid metabolism in a mouse NASH model, suggesting that HSCs are potentially efficient targets for the treatment of NASH.

Investigation of Degradation Mechanism of Y6-Based Inverted Organic Solar Cells and Their Utilization in Durable Near-Infrared Photodetection.

The device durability of inverted organic solar cells (OSCs) is investigated based on Y6, which is an effective nonfullerene acceptor for high-performance OSCs. The durability of Y6-based inverted OSCs is poor and it can be caused by aggregation of Y6 in the bulk-heterojunction layer due to heating by continuous photo-irradiation (≈65 °C, 100 mW cm-2 , and 72 h). It is found that the aggregation of Y6 is suppressed at a low temperature (≈50 °C), and that the Y6-based devices can be useful as a photodurable near-infrared detector upon continuous laser irradiation.

Granulocyte Colony-stimulating Factor-induced Aortitis with Lung Injury, Splenomegaly, and a Rash During Treatment for Recurrent Extraosseous Mucinous Chondrosarcoma.

We herein report a case of aortitis induced by granulocyte colony-stimulating factor (G-CSF) that coincided with lung injury, splenomegaly, and cutaneous manifestations during treatment for recurrent extraosseous mucinous chondrosarcoma. Computed tomography revealed large-vessel vasculitis, splenomegaly, and pulmonary interstitial changes. Treatment with prednisolone was successful. Because sarcoma is a rare disease, this case is valuable for showing clinicians that G-CSF preparations could cause aortitis regardless of the patient's underlying diseases or therapeutic pharmacological backgrounds.

Senescent hepatic stellate cells caused by deoxycholic acid modulates malignant behavior of hepatocellular carcinoma.

PURPOSE: Deoxycholic acid (DCA), a secondary bile acid, is reportedly increased in the serum of patients with nonalcoholic steatohepatitis and animals with experimentally induced hepatocellular carcinoma (HCC), but its contribution to malignant behaviors of HCC has not been precisely clarified. This study aimed to examine the effect of DCA on hepatic stellate cells (HSCs), a major component of nonparenchymal cells in the liver, and its subsequent indirect effect on HCC cells. METHODS: LX2 cells, a human HSC line, were treated with DCA in vitro. Then, HuH7 cells, a human hepatoma cell line, were incubated in conditioned media of DCA-treated LX2 to investigate the subsequent effect focusing on malignant behaviors. RESULTS: DCA resulted in cellular senescence in LX2 with the decreased cell proliferation via cell cycle arrest at G0/1 phase, together with the induction of senescence-associated secretory phenotype (SASP) factors. To investigate the influence of SASP factors secreted by HSCs in response to DCA, HCC cells were treated with conditioned media that promoted cell migration and invasion via induction of epithelial mesenchymal transition. These changes were attenuated in the presence of neutralizing antibody against IL8 or TGFß. Pathological analysis of surgical specimens from HCC patients revealed that senescent HSCs were detected in the stroma surrounding HCC. CONCLUSION: Our data suggest an important role of HSC senescence caused by DCA for the malignant biological behaviors of HCC via induction of SASP factors, particularly IL8 and TGFß.

Two Patients with Paget-Schroetter Syndrome That Were Successfully Diagnosed by Doppler Ultrasonography: Case Studies with a Literature Review.

We herein report on two male patients (age, 22 and 44 years) who were referred to our department with swelling of the upper right arm after attending other hospitals. Right subclavian vein thrombosis was demonstrated by ultrasonography and they were then further evaluated by contrast-enhanced computed tomography (CT). Successful treatment involved venous thrombectomy in one patient and anticoagulant therapy in the other. Paget-Schhroetter syndrome was confirmed using standard vascular ultrasonography. Despite the accuracy of this method for diagnosing Paget-Schroetter syndrome, some cases are difficult to confirm. We reviewed 29 previously published case reports of Paget-Schroetter syndrome and analyzed the patient baseline characteristics, time to diagnosis, and the diagnostic methods used.

[Long-Term Survival for a Patient with Stageâ £ Gastric Cancer with Multiple Liver Metastases for Ten Years Who Was Treated with Only S-1Chemotherapy].

An 82-year-old woman presented with a dull feeling in her stomach and anemia. The gastroscopy and abdominal CT scan showed a progressive gastric tumor with multiple liver metastases, and a biopsy specimen revealed moderately differentiated tubular adenocarcinoma. A subtotal gastrectomy with D1 plus lymph node dissection was performed. The final diagnosis was as follows: H1, P0, CY0, M1, pT3, pN2, and fStageⅣ. We considered her age, and postoperative chemotherapy with of an oral anticancer drug, S-1, was initiated at a daily dose of 100 mg, with a 2-week administration and 1-week suspension schedule. The multiple liver metastases obviously reduced in size(PR)by 3 months, and the CT scan revealed complete response(CR)by 8 months after beginning S-1 administration. However, grade 2 anorexia and general malaise developed, so the S-1 administration was changed to a daily dose of 80 mg, with a 2-week administration and 2-week suspension schedule. However, an adverse event of nausea appeared again, and the patient needed a 2-month discontinuation. Therefore, S-1 administration was changed to alternate-day administration, at a daily dose of 100 mg. Subsequently, no side effects were observed, and we continued the S-1 administration for 4 years. She has maintained a complete response(CR) for 10 years, with no obvious cancer recurrence.

Periostin antisense oligonucleotide prevents hepatic steatosis and fibrosis in a mouse model of non-alcoholic steatohepatitis.

BACKGROUND AND AIM: Non-alcoholic steatohepatitis (NASH) is characterized by hepatic steatosis, inflammation, and hepatocellular injury with varying degrees of fibrosis. There are currently no established treatment approaches for NASH other than lifestyle interventions. Periostin, a matricellular protein required for tissue remodeling and fibrosis, plays an important role in hepatic steatosis and fibrosis and could be a potential target for NASH treatment. Advances in molecular biology and biochemical engineering have led to the development of antisense oligonucleotides (ASOs) that can inhibit target genes with no significant toxic effects. Herein, we investigated the therapeutic effects of periostin-targeting ASO (PNASO) in NASH. METHODS: C57BL/6J mice were fed a choline-deficient, l-amino acid-defined, high-fat diet (CDAHFD) to induce NASH with or without intraperitoneal injection of mouse PNASO. To explore the role of periostin in hepatocellular steatosis, Hc3716 cells, an immortalized human hepatocyte line, were treated with recombinant periostin in vitro. RESULTS: The induced periostin expression in the liver of CDAHFD-fed mice was significantly suppressed by PNASO. The deletion of hepatic periostin by PNASO significantly ameliorated hepatic steatosis while restoring the expression levels of peroxisome proliferator-activated receptor-alpha (PPAR-α) and its target genes. PNASO also inhibited hepatic fibrosis, reflected by the reduction of alpha-smooth muscle actin, collagen type I, and other fibrotic markers. In vitro experiments demonstrated that treatment with recombinant periostin increased cellular lipid accumulation in Hc3716 cells accompanied with the downregulation of PPAR-α. CONCLUSIONS: Periostin-targeting ASO is a potential therapeutic approach for the efficient treatment of hepatic steatosis and fibrosis in NASH.

Plant-derived smoke enhances plant growth through ornithine-synthesis pathway and ubiquitin-proteasome pathway in soybean.

To investigate the mechanism of promotive effect of plant-derived smoke on the soybean growth, a gel-free/label-free proteomics was performed. Smoke solutions were irrigated on soybean or supplied simultaneously with flooding stress. Morphological and physiological analyses were performed for the confirmation of proteomic result. Metabolomic change was investigated to correlate proteomic change with metabolism regulation. Under normal condition, the length of root including hypocotyl increased in soybean treated with 2000 ppm plant-derived smoke within 4 days, as well as nitric oxide content. Proteins related to protein synthesis especially arginine metabolism were altered; metabolites related to amino acid, carboxylic acids, and sugars were mostly altered. Integrated analysis of omics data indicated that plant-derived smoke regulated nitrogen­carbon transformation through ornithine synthesis pathway and promoted soybean normal growth. Under flooding, the number of lateral roots increased with root tip degradation in soybean treated with smoke solutions. Proteins related to ubiquitin-proteasome pathway were altered and led to sacrifice-for-survival-mechanism-driven degradation of root tip in soybean, which enabled accumulation of metabolites and guaranteed lateral root development during soybean recovery after flooding. These findings suggest that plant-derived smoke improves early stage of growth in soybean with regulation of ornithine-synthesis pathway and ubiquitin-proteasome pathway. BIOLOGICAL SIGNIFICANCE: Plant-derived smoke plays a key role in crop growth, however, the understanding of soybean in response to smoke treatment remains premature. Therefore, gel-free/label-free proteomic analysis was used for comprehensive study on the dual effect of smoke to soybean under normal and flooding conditions. Under normal condition, plant-derived smoke regulated nitrogen­carbon transformation through ornithine synthesis pathway and resulted in the increase of the length of root including hypocotyl in soybean within 4 days. Under flooding condition, plant-derived smoke induced inhibition of ubiquitin-proteasome pathway and led to sacrifice-for-survival-mechanism-driven degradation of root tip in soybean, which enabled accumulation of metabolites and promoted lateral root development during soybean recovery after flooding.

Protective effect of phosphatidylcholine on lysophosphatidylcholine-induced cellular senescence in cholangiocyte.

BACKGROUND: Pancreaticobiliary maljunction and intrahepatic gallstones are at a high risk for biliary malignancy. Lysophosphatidylcholine (LPC) is increased in the bile of these patients, and we have previously reported that LPC-induced cytotoxicity causes senescence-associated secretory phenotype (SASP) in cholangiocytes. We aimed to determine the protective effect of phosphatidylcholine (PC) on LPC-induced cholangiocyte cytotoxicity. METHODS: MMNK-1, a human immortalized cholangiocyte cell line was treated with LPC with or without PC. To assess the biological effects of SASP components on cholangiocarcinoma, HuH28 and HuCCT1 (human cholangiocarcinoma cell lines) were cultured in the conditioned media where MMNK-1 cells treated with LPC. RESULTS: The presence of PC reduced reactive oxygen species generation and oxidative DNA damage in MMNK-1 treated with LPC. Moreover, SA-ß-gal activity was markedly downregulated by PC. The secretion of SASP components, including interleukin (IL)-8, IL-6, and C-C motif chemokine ligand 2 was also substantially reduced in the presence of PC. Cellular proliferation and migration were enhanced in HuCCT1 and HuH28 cells when cultured in the conditioned media, and these observations were suppressed by simultaneous addition of PC. CONCLUSION: PC protects cholangiocytes against LPC-induced cytotoxicity and cellular senescence, suggesting its potential as a target for inhibiting LPC-related carcinogenesis and its promotion.

Successful Treatment of Acute Chest Syndrome with Manual Exchange Transfusion in a Patient with Sickle Beta+-thalassemia.

Acute chest syndrome (ACS), characterized by fever, respiratory symptoms, and new pulmonary infiltration, is a serious complication of sickle cell disease (SCD). Regardless of the etiology, the conventional treatment options for ACS include empirical antibiotic therapy, the administration of analgesics, and red cell transfusion. The indications and methods of red cell transfusion are critical. We herein report the case of a 26-year-old African-American man with SCD who developed ACS and who was successfully treated with manual exchange transfusion. Despite increasing globalization, SCD remains extremely rare in Japan. Manual exchange transfusion can be performed easily anywhere and should be considered for treating SCD patients presenting with ACS.

An Atypical Case of Non-asthmatic Eosinophilic Granulomatosis with Polyangiitis Finally Diagnosed by Tissue Biopsy.

A 78-year-old woman with fever of unknown origin that had persisted for 3 months, systemic edema, and cervical lymphadenopathy was admitted to our hospital. Skin purpura and jaw claudication were subsequently observed. Histopathological examinations of the lymph nodes, skin, and temporal artery revealed findings characteristic of eosinophilic granulomatosis with polyangiitis (EGPA). However, she had no past medical history of asthma with modest eosinophilia. Although EGPA is a systemic vasculitis characterized by asthma and eosinophilia, various limited forms have been described. This was therefore considered to be an atypical form of non-asthmatic EGPA complicating with temporal arteritis (TA) diagnosed by tissue biopsy.

A case of giant cell arteritis simultaneously diagnosed with chronic subdural hematoma.

Here, we describe a case of giant cell arteritis (GCA) simultaneously diagnosed with chronic subdural hematoma. In this case, head to chest computed tomography angiography was useful for the diagnosis and treatment of GCA.

Comparison of hepatic arterial infusion chemotherapy between 5-fluorouracil-based continuous infusion chemotherapy and low-dose cisplatin monotherapy for advanced hepatocellular carcinoma.

AIM: The aim of this study is to compare the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) between 5-fluorouracil (5-FU)-based continuous infusion chemotherapy and low-dose cisplatin (CDDP) monotherapy in patients with advanced hepatocellular carcinoma (HCC). METHODS: Patients were grouped according to HAIC regimen (5-FU group, n = 317/CDDP group, n = 66). A two-to-one match was created using propensity score analysis (5-FU group, n = 102/CDDP group, n = 51). After matching, response rate (RR) and adverse events as primary end-points, and survival and progression-free survival as secondary end-points, were analyzed. RESULTS: In the analysis of primary end-points, the RR in the 5-FU group was significantly higher than in the CDDP group (32.4% vs. 15.7%, P = 0.033). In patients with a Child-Pugh (CP) score of 5-7, the RR in the 5-FU group was significantly higher than that in the CDDP group (36.1% vs. 15.4%, P = 0.020). In those with a CP score of 8-9, there was no significant difference in RR between the two groups (15.8% vs. 16.6%, P = 1.000). The reservoir system-related complications were 9.8% in the 5-FU group, and there was no significant difference in the incidence of grade 3/4 adverse events between the two matched groups (P > 0.05). In terms of secondary end-points, the median survival time was 9.1 and 8.7 months for the 5-FU and CDDP groups, respectively (P = 0.4917). Progression-free survival was 3.9 months for the 5-FU group and 4.9 months for the CDDP group (P = 0.4). CONCLUSIONS: 5-Fluorouracil-based continuous infusion chemotherapy could be suitable for advanced HCC patients with a CP score of 5-7 considering the treatment response.

Evaluation of glycemic variability in chronic liver disease patients with type 2 diabetes mellitus using continuous glucose monitoring.

BACKGROUND AND AIMS: The feature of blood glucose dynamics in patients with chronic liver disease (CLD) is marked blood glucose fluctuations. However, the detail of blood glucose dynamics is not well known. The aim of the present study was to evaluate glycemic fluctuations by continuous glucose monitoring (CGM). MATERIALS AND METHODS: A total of 105 CLD patients with type 2 diabetes mellitus (T2DM) were enrolled in this study. Various parameters of glycemic variability were evaluated. The association of these parameters with liver functional reserve was examined. The parameters were also evaluated according to glycated hemoglobin A1c (HbA1c) levels. RESULTS AND DISCUSSION: Data of all patients showed that mean blood glucose (MBG) levels and the difference between highest and lowest blood glucose (ΔBG) increased significantly with worsening of liver functional reserve (P < 0.001 and P = 0.005, respectively). Although many of the cases were being treated for diabetes, postprandial hyperglycemia was seen in 92% of patients. Nocturnal hypoglycemia was seen in 22% of patients. In non-anemic patients with HbA1c levels of < 7.0%, the percentage of patients with mean amplitude of glycemic excursion (MAGE) of ≥ 77.4 mg/dL and that of MBG levels of > 145 mg/dL were higher in liver cirrhosis (LC) patients than in chronic hepatitis (CH) patients. In them, homeostasis model assessment for insulin resistance (HOMA-IR) of > 2.5 and LC were significantly associated with the increase in MAGE. LC was also significantly associated with increased MBG levels. CONCLUSION: The CGM systems were useful in finding hidden abnormalities of blood glucose fluctuations in CLD patients with T2DM, especially in non-anemic CLD patients with HbA1c levels of < 7.0%.

Five Cases of Familial Mediterranean Fever in Japan: The Relationship with MEFV Mutations.

Familial Mediterranean fever (FMF) is the most common genetic autoinflammatory disease, but it has been considered a rare disease in Japan. We herein describe five patients with FMF who were diagnosed both clinically and genetically at a single Japanese institute. A genetic investigation of Mediterranean fever (MEFV) detected heterozygosity for the compound mutations L110P/E148Q (n=2) and L110P/148Q/P369S/R406Q (n=1), and heterozygosity for M694I (n=1) and S503C (n=1). Colchicine prevented febrile attacks and accompanying symptoms in four patients. One patient with an S503C mutation showed resistance. Physicians should be aware of the characteristic symptoms, as well as the more unusual symptoms such as headache, when diagnosing FMF.

Primary Signet Ring Cell Carcinoma of Rectum Diagnosed by Boring Biopsy in Combination with Endoscopic Mucosal Resection.

A 46-year-old man with severe back pain visited our hospital. Magnetic resonance imaging revealed extensive bone metastasis and rectal wall thickness. Colonoscopy revealed circumferential stenosis with edematous mucosa, suggesting colon cancer. However, histological findings of biopsy specimens revealed inflammatory cells but no malignant cells. The patient underwent endoscopic ultrasound, which demonstrated edematous wall thickness without destruction of the normal layer structure. After unsuccessful detection of neoplastic cells by boring biopsies, we performed endoscopic mucosal resection followed by boring biopsies that finally revealed signet ring cell carcinoma. Herein, we present a case and provide a review of the literature.