Clinical significances of several fibrotic markers for prognosis in hepatocellular carcinoma patients who underwent hepatectomy.

Background: Progression of chronic liver fibrosis and related increased fibrotic markers are associated with functional liver reserves or patient prognosis as well as tumor factors in hepatocellular carcinoma (HCC) patients. The aim of this study was to newly clarify the relationship between fibrotic markers and HCC malignant behaviors or its long-term postoperative prognosis by the retrospective cohort study. Methods: We examined the relationship between tumor-related factors or six liver fibrosis-associated parameters, including platelet count, hyaluronic acid (HA), Mac-2 binding protein glycosylation isomer (M2BPGi), type IV collagen 7S (T4C7), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 (Fib-4) index, and clinicopathological parameters, surgical records, and postoperative prognosis in 130 HCC who underwent curative hepatectomy. Results: Histological fibrosis stage 4 as cirrhosis was in 31%. The platelet count significantly decreased in stage 4 fibrosis and correlated with grade B liver damage (P<0.01). HA levels were significantly increased in multiple HCC, stage 4 fibrosis, and grade B liver damage (P<0.01). T4C7 was significantly increased in patients with post-hepatectomy tumor recurrence compared to those without (P<0.01). Additionally, M2BPGi was significantly higher in stage 4 fibrosis and liver damage grade B, and was significantly associated with poor prognosis (P<0.05). Fib-4 index was significantly higher in patients with liver damage B (P<0.05), and T4C7 alone did not correlate with other five fibrosis markers. Stage 4 fibrosis, higher T4C7, higher M2BPGi, and increased tumor size were significantly associated with shorter cancer-free, overall, and cancer-specific survivals. Higher T4C7, non-met Milan criteria, liver damage B, blood transfusion, and curability C were independently associated with cancer-specific survivals (P<0.05). Conclusions: Type IV collagen 7S (T4C7) may reflect not only impaired liver function but also HCC malignant behaviors and patient survivals.

Reactivation of hepatitis C virus caused by steroid monotherapy for sudden deafness.

Hepatitis C virus (HCV) reactivation has been reported to be caused due to several anticancer drugs and immunosuppressive agents; however, HCV reactivation after steroid monotherapy has rarely been reported. Here, we report the case of a 65-year-old Japanese man with HCV infection who developed HCV reactivation after the administration of prednisolone (PSL) for 6 days for sudden deafness. In the patient history, the positivity for anti-HCV antibody was observed, but serum level of HCV RNA was not measured. Two months after PSL administration, the patient experienced an alanine aminotransferase (ALT) flare and the serum level of HCV RNA was observed to be 6.2 log IU/mL; then, the patient was admitted to our hospital for hepatitis treatment. Based on the clinical course and laboratory findings, the patient was diagnosed with HCV reactivation. Although the ALT levels decreased spontaneously during follow-up, they did not drop to normal range; subsequently, sofosbuvir and ledipasvir treatments were started. A sustained virological response 24 weeks after the end of treatment was achieved. This case study suggests that HCV reactivation with hepatitis flare can occur even after a steroid monotherapy, and doctors should pay attention to HCV reactivation when administering PSL for patients with HCV infection.

A new surgical approach for the treatment of a refractory foveal microaneurysm: A case report.

Purpose: To report a case of a refractory foveal microaneurysm (MA) that was successfully treated by use of a new surgical procedure. Observations: This study involved a 79-year-old female with an active foveal MA associated with branch retinal vein occlusion in her left eye. Despite anti-vascular endothelial growth factor treatments, the MA remained active without closure, and best-corrected visual acuity (VA) gradually decreased from 20/20 to 20/200. After our new surgical procedure was explained in detail to the patient, written informed consent was obtained from the patient and the surgery was performed. Briefly, following pars plana vitrectomy, the internal limiting membrane in her left eye was peeled and the retina of the external wall of the MA was then gently incised. The exposed MA was then directly grabbed and pulled up onto the retina using 27-gauge microforceps, and photocoagulation was performed. At 3-months postoperative, closure of the MA and improvement in the retinal findings were observed, and best-corrected VA improved to 20/67. Conclusions and importance: We report a case of a refractory foveal MA that was successfully treated with a novel surgical technique that closed the MA, avoided thermal damage to the surrounding tissue, and resulted in improved postoperative VA.

Association of immune-related adverse events with durvalumab efficacy after chemoradiotherapy in patients with unresectable Stage III non-small cell lung cancer.

BACKGROUND: Immune-related adverse events (irAEs) have been found to predict PD-L1 inhibitor efficacy in metastatic NSCLC. However, the relation of irAEs to clinical outcome for nonmetastatic NSCLC has remained unknown. METHODS: In this multicenter prospective study of Stage III NSCLC treated with PACIFIC regimen, the relation of irAEs to PFS was evaluated by 8-week landmark analysis to minimise lead-time bias as well as by multivariable analysis adjusted for baseline factors. irAEs were categorised as mild or nonmild according to whether they were treated with systemic steroid. RESULTS: Median PFS was 16.0 months, not reached, and 9.7 months for patients without (85 cases) or with mild (21 cases) or nonmild (21 cases) irAEs, respectively. Multivariable analysis indicated that nonmild irAEs were associated with poor PFS, with HRs of 3.86 (95% CI, 1.31-11.38) compared with no irAEs and 11.58 (95% CI, 2.11-63.63) compared with mild irAEs. This pattern was consistent after irAE grade, the number of durvalumab doses and immune profiles (PD-L1 score, CD8+ tumour-infiltrating lymphocyte density, and tumour mutation burden) were taken into consideration. CONCLUSIONS: The development of mild irAEs might predict a better survival outcome, whereas immunosuppressive steroid-treated irAEs were associated with a worse outcome, regardless of baseline clinical and immune profiles.

Bayesian active learning with model selection for spectral experiments.

Active learning is a common approach to improve the efficiency of spectral experiments. Model selection from the candidates and parameter estimation are often required in the analysis of spectral experiments. Therefore, we proposed an active learning with model selection method using multiple parametric models as learning models. Important points for model selection and its parameter estimation were actively measured using Bayesian posterior distribution. The present study demonstrated the effectiveness of our proposed method for spectral deconvolution and Hamiltonian selection in X-ray photoelectron spectroscopy.

The successful posterior sectionectomy accompanied with caudate lobectomy for hepatocellular carcinoma located in segment 1 after LEN-TACE: a case report.

Nowadays, the novel molecular targeting chemotherapy provides possibility of safe hepatectomy for progressive hepatocellular carcinoma (HCC). Further, combination of the conventional transarterial chemoembolization (TACE) may add an effect of tumor shrink. We present a successful radical hepatectomy for a large HCC located in segment 1 accompanied with the preoperative Lenvatinib (LEN)-TACE sequential treatment. We present a woman patient without any complaints who had a 7 cm-in-size of solitary HCC compressing vena cava and right portal pedicle. To achieve radical hepatectomy by tumor shrinking, LEN-TACE for 2 months. After confirming downsizing or devascularization of the HCC, we scheduled radical posterior sectionectomy combined with caudate lobectomy according to tumor location and expected future remnant liver volume from three-dimensional computed tomography simulation before surgery. Under the thoraco-abdominal incision laparotomy, we safely achieved scheduled radical hepatectomy without any vascular injuries. The postoperative course was uneventful and no tumor recurrence were observed for 1 year. Histological findings showed the Japan TNM stage III HCC with 70% necrosis. The multi-modal strategy of LEN-TACE followed by radical hepatectomy by confirming downsizing or devascularization in tumor is supposed to be useful and would be a preoperative chemotherapy option, and promising for curative treatment in HCC patients with progressive or large HCC, which may lead to safety by prevention surrounding major vascular injury.

Characterization and anti-tumor activities of polysaccharide isolated from Brassica rapa L. via activation of macrophages through TLR2-and TLR4-Dependent pathways.

We have previously shown the immunostimulatory effects by Nozawana (Brassica rapa L.). In this report, we determined the characteristics of Nozawana polysaccharide (NPS) and evaluated the immunomodulatory effects and anti-tumor activity of NPS mediated by macrophage activation. The molecular weight of NPS was determined by gel filtration chromatography with an average molecular weight of approximately 100.6 kDa. HPLC analysis showed that NPS contained glucose, galacturonic acid, galactose, and arabinose. NPS increased cytokine and nitric oxide (NO) production by macrophages in a Toll-like receptor (TLR)2 and TLR4-dependent manner. Furthermore, NPS induced apoptosis significantly against 4T1 murine breast cancer cells cultured in conditioned medium from NPS-treated macrophages through tumor necrosis factor-α. In tumor-bearing mouse model, tumor growth was significantly reduced in NPS-treated mice compared with control mice. These results support the potential use of NPS as an immunotherapeutic material found in health food products.

Structural Basis of Amide-Forming Adenylation Enzyme VinM in Vicenistatin Biosynthesis.

Adenylation enzymes activate amino acid substrates to aminoacyl adenylates and generally transfer this moiety onto the thiol group of the phosphopantetheine arm of a carrier protein for the selective incorporation of aminoacyl building blocks in natural product biosynthesis. In contrast to the canonical thioester-forming adenylation enzymes, the amide-forming adenylation enzyme VinM transfers an l-alanyl group onto the amino group of the aminoacyl unit attached to the phosphopantetheine arm of the carrier protein VinL to generate dipeptidyl-VinL in vicenistatin biosynthesis. It is unclear how VinM distinguishes aminoacyl-VinL from VinL for amide bond formation. Herein we describe structural and biochemical analyses of VinM. We determined the crystal structure of VinM in complex with VinL using a designed pantetheine-type cross-linking probe. The VinM-VinL complex structure in combination with site-directed mutagenesis analysis revealed that the interactions with both the phosphopantetheine arm and VinL are critical for the amide-forming activity of VinM.

Construction of the lactate-sensing fibremats by confining sensor fluorescent protein of lactate inside nanofibers of the poly(HPMA/DAMA)/ADH-nylon 6 core-shell fibremat.

The development of a new materials platform capable of sustaining the functionality of proteinous sensor molecules over an extended period without being affected by biological contaminants in living systems, such as proteases, is highly demanded. In this study, our primary focus was on fabricating new core-shell fibremats using unique polymer materials, capable of functionalizing encapsulated sensor proteins while resisting the effects of proteases. The core-fibre parts of core-shell fibremats were made using a newly developed post-crosslinkable water-soluble copolymer, poly(2-hydroxypropyl methacrylamide)-co-poly(diacetone methacrylamide), and the bifunctional crosslinking agent, adipic dihydrazide, while the shell layer of the nanofibers was made of nylon 6. Upon encapsulating the lactate-sensor protein eLACCO1.1 at the core-fibre part, the fibremat exhibited a distinct concentration-dependent fluorescence response, with a dynamic range of fluorescence alteration exceeding 1000% over the lactate concentration range of 0 to 100 mM. The estimated dissociation constant from the titration data was comparable to that estimated in a buffer solution. The response remained stable even after 5 cycles and in the presence of proteases. These results indicates that our core-shell fibremat platform could serve as effective immobilizing substrates for various sensor proteins, facilitating continuous and quantitative monitoring of various low-molecular-weight metabolites and catabolites in a variety of biological samples.

Establishment and validation of an electron inelastic mean free path database for narrow bandgap inorganic compounds with a machine learning approach.

Narrow bandgap inorganic compounds are extremely important in many areas of physics. However, their basic parameter database for surface analysis is incomplete. Electron inelastic mean free paths (IMFPs) are important parameters in surface analysis methods, such as electron spectroscopy and electron microscopy. Our previous research has presented a machine learning (ML) method to describe and predict IMFPs from calculated IMFPs for 41 elemental solids. This paper extends the use of the same machine learning method to 42 inorganic compounds based on the experience in predicting elemental electron IMFPs. The in-depth discussion extends to including material dependence discussion and parameter value selections. After robust validation of the ML method, we have produced an extensive IMFP database for 12 039 narrow bandgap inorganic compounds. Our findings suggest that ML is very efficient and powerful for IMFP description and database completion for various materials and has many advantages, including stability and convenience, over traditional methods.

[A case of invasive liver abscess syndrome caused by Klebsiella pneumoniae causing endophthalmitis-induced blindness].

An 82-year-old female patient was admitted to our hospital for visual acuity loss in both eyes. The patient was diagnosed with invasive liver abscess syndrome and bilateral endophthalmitis due to Klebsiella pneumoniae 4 days after the onset of ocular symptoms. The liver abscess improved by broad-spectrum antibiotics and intravitreal injection, but bilateral blindness occurred. Most literature reported fever as the first symptom of invasive abscess syndrome, but this case had no fever at the onset of ocular symptoms. Delayed invasive liver abscess syndrome diagnosis might cause poor visual acuity prognosis.

Reply to Marino et al. Does Subretinal Fluid Influence Choroidal Thickness (ChT) and Structure in Preeclampsia with Serous Retinal Detachment? Comment on "Fukui et al. Changes in Choroidal Thickness and Structure in Preeclampsia with Serous Retinal Detachment. J. Clin. Med. 2023, 12, 609".

We thank the authors for the interesting comments [...].

Inflammatory Hepatocellular Adenoma Mimicking Focal Nodular Hyperplasia That Grew during Pregnancy and Changed Its Appearance on Magnetic Resonance Imaging after Delivery.

We reported a notable case of inflammatory hepatocellular adenoma that grew during pregnancy, consequently changing its appearance on magnetic resonance imaging remarkably. A 5-months-pregnant 35-year-old woman presented with a 37-mm liver nodule that had been diagnosed as focal nodular hyperplasia 3 years earlier. She had never used oral contraceptives. After 2 months, the nodule grew to 57 mm. The patient delivered a full-term infant without complications. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging performed after delivery revealed markedly different findings compared with the first images. A liver biopsy was performed, and the tumor was diagnosed as inflammatory hepatocellular adenoma.

Palladium-Catalyzed para-Selective Allylation of 1-(Cyanomethyl)arenes with Allyl Acetates.

The Pd/PMe3-catalyzed allylation of 1-(cyanomethyl)naphthalenes with allyl acetates proved to be para- rather than α-regioselective. This reaction is thought to proceed through ligand attack of the para-carbon in the arenes, electronically enriched by a cyano-stabilized α-carbanion, to the (π-allyl)palladium and a 1,5-hydrogen shift of the para-hydrogen from the dearomatized intermediate.

A conserved mechanism determines the activity of two pivotal transcription factors that control epidermal cell differentiation in Arabidopsis thaliana.

The surface of plants is covered by the epidermis, which protects the plant's body from the external environment and mediates inter-cell layer signaling to regulate plant development. Therefore, the manifestation of epidermal traits at a precise location is a prerequisite for their normal growth and development. In Arabidopsis thaliana, class IV homeodomain-leucine zipper transcription factors PROTODERMAL FACTOR2 (PDF2) and ARABIDOPSIS THALIANA MERISTEM LAYER1 (ATML1) play redundant roles in epidermal cell differentiation. Nevertheless, several pieces of evidence suggest that the activity and/or function of PDF2 and ATML1 are regulated differently. The role of the steroidogenic acute regulatory protein-related lipid transfer (START) domain of ATML1 in restricting this protein's activity has been demonstrated; however, whether this lipid-dependent mechanism regulates PDF2 expression is unknown. In this study, we demonstrated that the START domains of PDF2 and ATML1, regulate protein turnover in a position-dependent manner and affect the dimeric proteins. Our results show that a conserved mechanism provides the basis for the functional redundancy of PDF2 and ATML1 in epidermal cell differentiation and that an unidentified regulatory layer specific to PDF2 or ATML1 is responsible for the difference in the activity and/or function of PDF2 and ATML1.

Changes in Choroidal Thickness and Structure in Preeclampsia with Serous Retinal Detachment.

Preeclampsia is a pregnancy-specific syndrome characterized by hypertension and proteinuria. We retrospectively investigated the clinical features, including choroidal layer thickness and luminal area to stromal area ratio, in a case series of preeclampsia with serous retinal detachment (SRD). The subjects were pregnant women with SRD during hospitalization for preeclampsia from October 2014 to June 2021. Based on medical records, affected eyes, time of onset, fundus examination findings, and subfoveal choroidal thickness (SCT), the choroidal layer thickness and choroidal vascular index (CVI) in each patient was examined. Thirteen eyes from seven patients (mean age 30.7 ± 4.7 years) were included in the study. In all cases, SRD improved without topical ocular treatment. The mean SCT at the initial visit was 424.4 ± 70.5 µm, and all patients had choroidal thickening, which significantly decreased to 286.0 ± 57.9 µm (p < 0.01) at the last visit. The mean choroidal inner layer was 162.7 ± 69.4 µm at the initial visit and 122.3 ± 35.5 µm at the final follow-up visit (p = 0.06), showing no significant difference; however, the mean choroidal outer layer was 261.7 ± 47.6 µm at the initial visit and 163.7 ± 37.1 µm at the final follow-up visit (p < 0.01), thus showing a significant decrease. The mean CVI was 67.2 ± 1.3% at the initial visit, yet it had significantly decreased to 65.4 ± 1.1% (p < 0.01) at the final follow-up visit. The findings of this study show that SRD with preeclampsia is associated with increased thickening of the choroidal outer layer, especially in the choroidal luminal area.

Radiotherapy for ductal carcinoma of the prostate: an analysis based on the Japanese radiation oncology study group survey.

BACKGROUND: The clinical characteristics of prostate ductal carcinoma is still unclear, and treatment strategy has not yet been established due to its rarity. Therefore, we conducted a multicenter survey of radiation therapy for prostate ductal carcinoma in Japan. METHOD: Data of patients with ductal carcinoma of the prostate treated with radiation therapy between 1996 and 2018 were extracted from the database of each facility. RESULTS: Fifty-two treatment records of 41 patients were collected from nine institutions. The treatment purpose and situations were varied curative intent to palliation. Twenty-eight patients received curative treatments. The median follow-up period of these patients was 68 months. Androgen deprivation therapy was combined with radiation therapy in 26 cases (93%). X-ray and particle irradiation was used. Radiation dose range was 63-78 Gy; 5-year overall survival, progression-free survival and biochemical relapse-free survival were 87.0, 79.3 and 79.3%, respectively. One patient experienced Grade 3 radiation proctitis and one experienced Grade 3 radiation cystitis. There were no Grade 4 or worse adverse events. CONCLUSION: Most patient received similar treatment with adenocarcinoma of prostate, and the clinical results were compatible. For more reliable evidence, further studies are required.

A multicenter study of ocular inflammation after COVID-19 vaccination.

PURPOSE: To report the characteristics of a case series of ocular inflammatory events following COVID-19 vaccination in Japan. STUDY DESIGN: Retrospective multicenter study METHODS: In this retrospective multicenter survey, a questionnaire was sent to 16 Japanese hospitals that had uveitis specialty clinics. Information on patients who developed ocular inflammatory events within 14 days of COVID-19 vaccination between February 2021 and December 2021 was collected. RESULTS: Thirty-seven patients were diagnosed with ocular inflammatory events following COVID-19 vaccination. The mean age was 53.4 ± 16.4 years (range, 26-86 years), and the mean time to onset after vaccination was 6.3 ± 4.2 days (range, 1-14 days). Vogt-Koyanagi-Harada disease (VKH) was the most common event (n = 17 patients, 46%), followed by anterior uveitis (n = 6), infectious uveitis (n = 3), acute zonal occult outer retinopathy (AZOOR) (n = 2), sarcoidosis-associated uveitis (n = 1), acute posterior multifocal placoid pigment epitheliopathy (APMPPE) (n = 1), optic neuritis (n = 1), multiple evanescent white dot syndrome (MEWDS) (n = 1), Posner-Schlossman syndrome (n = 1), and unclassified uveitis (n = 4). Twenty-eight cases occurred after BNT162b2 vaccination (Pfizer-BioNTech) and 8 after mRNA-1273 vaccination (Moderna), whilst 1 patient had no information about vaccine type. CONCLUSIONS: COVID-19 vaccination can be related to various types of ocular inflammatory events. When we encounter patients with ocular inflammatory disease, we should consider that it may be an adverse effect of COVID-19 vaccination.

Core-shell fibremats comprising a poly(AM/DAAM)/ADH nanofibre core and nylon6 shell layer are an attractive immobilization platform for constructing immobilised enzymes.

Core-shell fibremats, comprising poly(acrylamide)-co-poly(diacetone-acrylamide)/adipic dihydrazide [poly(AM/DAAM)/ADH] core-nanofibres and hydrophobic polymer shell layers, are a new class of platforms for constructing various immobilised enzymes. In this study, to elucidate the impacts of the shell-layer material on fibremat properties and enzymatic activities, we synthesised core-shell fibremats with shell layers comprising nylon6 or acetyl cellulose (AcCel) instead of poly(ε-caprolactone) (PCL), as in our previous study. Transmission and scanning electron microscopy images revealed that the lactase-encapsulated poly(AM/DAAM)/ADH-nylon6 and -AcCel fibremats were both constructed like the poly(AM/DAAM)/ADH-PCL one. Leakage measurements of the beforehand loaded molecules inside the core-nanofibres revealed that both fibremats exhibited efficient permeability for low-molecular-weight molecules and stable retention of enzyme molecules inside the core-nanofibres. Meanwhile, the fibremats' mechanical properties considerably depended on the choice of shell-layer material. The thermal analyses of the lactase-encapsulated fibremats revealed residual water inside the core nanofibres. The core-shell fibremats fabricated with a nylon6 or PCL shell exhibited excellent enzymatic activities (102 and 114%, respectively, compared to that of free lactase), superior to that of the same amount of free enzyme in a buffer. Furthermore, both core-shell fibremats retained over 95% of their initial enzymatic activities, even after they were re-used 10 times.

Liver abscess in advanced hepatocellular carcinoma after atezolizumab plus bevacizumab treatment: A case report.

RATIONALE: Hepatocellular carcinoma (HCC) is the sixth most common type of cancer globally. Since 2020, combination treatment with atezolizumab and bevacizumab were approved in patients with unresectable HCC in Japan, and atezolizumab plus bevacizumab is the first-line treatment for unresectable HCC. PATIENT CONCERNS: A 73-year-old Japanese man diagnosed with a large HCC was treated with atezolizumab plus bevacizumab. After 2 cycles, he had fever and fatigue and was admitted to the hospital. DIAGNOSIS: Abdominal contrast-enhanced computed tomography revealed tumor necrosis in HCC with gas formation in the necrotic area. Laboratory examination revealed a white blood cell (WBC) count of 16,340/µL and C-reactive protein (CRP) level of 33.0 mg/dL. Based on the above findings, he was diagnosed with a liver abscess. INTERVENTIONS: Percutaneous transhepatic liver abscess drainage and broad-spectrum antibiotics treatment were performed. OUTCOMES: Despite liver abscess drainage, persistent fever and no improvement in the WBC count or CRP level was observed. The patient's respiratory condition and renal function gradually worsened; The patient's general condition did not improve despite the ventilator support and continuous hemodiafiltration, and he died on day 37. LESSONS: We report the first case of liver abscess after atezolizumab plus bevacizumab treatment for unresectable HCC.