Development of a novel fluorogenic assay method for screening inhibitors of bovine leukemia virus protease and identification of mitorubrinic acid as an anti-BLV compound.

Bovine leukemia virus (BLV) causes enzootic bovine leukosis, a fatal cattle disease that leads to significant economic losses in the livestock industry. Currently, no effective BLV countermeasures exist, except testing and culling. In this study, we developed a high-throughput fluorogenic assay to evaluate the inhibitory activity of various compounds on BLV protease, an essential enzyme for viral replication. The developed assay method was used to screen a chemical library, and mitorubrinic acid was identified as a BLV protease inhibitor that exhibited stronger inhibitory activity than amprenavir. Additionally, the anti-BLV activity of both compounds was evaluated using a cell-based assay, and mitorubrinic acid was found to exhibit inhibitory activity without cytotoxicity. This study presents the first report of a natural inhibitor of BLV protease-mitorubrinic acid-a potential candidate for the development of anti-BLV drugs. The developed method can be used for high-throughput screening of large-scale chemical libraries.

Pi-Class Glutathione S-transferase (GSTP1)-Selective Fluorescent Probes for Multicolour Imaging with Various Cancer-Associated Enzymes.

Pi-class glutathione S-transferase (GSTP1) is highly expressed in a wide variety of human cancer tissues compared to the corresponding normal counterpart. Therefore, GSTP1 is a potential target enzyme for overcoming resistance to chemotherapeutic agents or visualizing specific lesions such as cancer. Here, we present orange and red fluorescence-emitting probes selective for GSTP1. Carbofluorescein and TokyoMagenta fluorophores were modified with a previously described GSTP1-selective chromogenic compound to generate orange and red fluorescence probes, respectively. Of these probes, Ps-CF, the orange fluorescence-emitting probe, was confirmed to be highly specific for detecting GSTP1 exogenously or endogenously expressed in various cancer cells. Additionally, it was demonstrated that Ps-CF is applicable for the simultaneous detection of GSTP1 and another cancer-associated enzyme by using a green fluorescence emitting γ-glutamyl transpeptidase (GGT) probe. In conclusion, the fluorescent probes developed in this study enable the simultaneous detection of multiple tumour markers such as GSTP1 with other cancer-associated enzymes by concurrently using spectrally distinguished fluorescent probes, potentially broadening the scope of cancer detection.

Rapidly progressive miliary brain metastasis of lung cancer after EGFR tyrosine kinase inhibitor discontinuation: An autopsy report.

Miliary brain metastasis is a rare type of brain metastasis, in which carcinoma cells disseminate to numerous foci confined to Virchow-Robin/subpial spaces. Symptoms usually progress within several months, and magnetic resonance imaging (MRI) shows multiple small contrast-enhancing lesions. We report an autopsy case of a patient who rapidly deteriorated within a week due to miliary brain metastasis after epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) discontinuation, without contrast-enhancing lesions on MRI. A 74-year-old woman was diagnosed with stage IV lung adenocarcinoma with EGFR L868R mutation 2 years before presentation. Gefitinib, an EGFR-TKI was started. After 7 months, multiple new punctate contrast-enhancing lesions in the cerebral cortex appeared. After switching to another EGFR-TKI, erlotinib, these lesions disappeared. One year later, erlotinib was discontinued because of disease progression in the lung and docetaxel was initiated. Sixteen days later, cognitive decline appeared which rapidly progressed to bedridden state in 4 days. MRI showed multiple cortical small fluid-attenuated inversion recovery high intensity lesions which lacked contrast enhancement. The patient exhibited a state of akinetic mutism within a few days, and died 52 days after the appearance of neurological symptoms. The rapid progression indicated disease flare after EGFR-TKI discontinuation. Autopsy revealed numerous foci of metastasis in the cerebral cortex, basal ganglia, thalamus, and cerebellum, in which cancer cells were mostly confined to the Virchow-Robin/subpial spaces. These pathological findings were compatible with previous reports of miliary brain metastasis. Recent reports suggest that early disseminated cancer cells can survive for a long time and even remain after chemotherapy in supportive niches, and Virchow-Robin spaces are the niches in the brain. Our case suggests that these cancer cells may rapidly proliferate as a withdrawal burst after discontinuation of molecular targeted drugs, and show pathological findings of miliary brain metastasis.

Pulmonary Tumor Thrombotic Microangiopathy due to Advanced Gastric Cancer with Virchow's Node Metastasis.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal cancer-related complication characterized by severe progressive pulmonary hypertension. Antemortem diagnosis is difficult owing to the rapid progression of the condition, especially when the patient has no known malignancies and initially presents with pulmonary hypertension. Here we report a case of PTTM due to occult gastric cancer with metastasis in the left supraclavicular lymph node, also known as Virchow's node. Enlarged Virchow's node is an important indicator of advanced gastric cancer. In patients with progressive pulmonary hypertension of unknown origin, enlarged Virchow's node can be an important indicator for the diagnosis of PTTM.

Histopathological characteristics of renal changes in human renin-angiotensinogen double transgenic rats.

The human renin-angiotensinogen double transgenic rat (dTGR) is a model of hypertension. The aim of this short report was to describe the histopathological characteristics of the renal changes in this rat strain in detail. Seven to nine-week-old male dTGRs were euthanized, and their kidneys were histopathologically examined. At the time of sacrifice, the average systolic blood pressure of the dTGRs was 258 mmHg, while that of age-matched, normal Sprague-Dawley rats was 135 mmHg. In the kidney, histopathological changes were observed mainly in blood vessels, tubules and glomeruli. In blood vessels, changes including medial hypertrophy, intimal thickening, hyaline change and/or fibrinoid necrosis were observed in arteries and arterioles. In tubules, changes including tubular basophilia were observed radially, mainly around interlobular arteries with lesions. In glomeruli, changes including hyaline droplet accumulation in podocytes, which was accompanied by increased expression of desmin, were observed. These changes were similar to those reported in other hypertension models, such as the spontaneously hypertensive rat (SHR). We hope that this short report will be helpful in histopathological examination of renal changes in this or other hypertension models.

[How Long Are Unstained Sections Available for Immunostaining? -A Study of Antigenicity Preservation Time-].

It is well known that the antigenicity of unstained sections put on a slide glass decreases when the slides are stored at room temperature. Several methods have been reported to prevent reduced antigenicity, such as storing in a dark place at 4°C, covering sections with paraffin or a sheet, and storing in a deep freezer at -80°C. The aim of the present study is to determine how long unstained sections can be stored in a refriger- ator (ie, 1 week, 2 weeks, 1 month and 2 months). Each section was well stained and equal to the day 0 section for CD3, CD20, bcl-2, bcl-6, ER, PgR, HER2, Ki-67, chromogranin-A, synaptophysin, CK5, CK7, CK20, and TTF-1. In conclusion, unstained sections can be used for immunostaining after at least 2 months of storage, and preparing several control sections and storing them in a refrigerator is useful for minimizing control block loss. [Original].

DSR-71167, a novel mineralocorticoid receptor antagonist with carbonic anhydrase inhibitory activity, separates urinary sodium excretion and serum potassium elevation in rats.

Mineralocorticoid receptor (MR) antagonists, such as spironolactone (SPI) and eplerenone (EPL), are useful for treating hypertension and heart failure. However, these two agents have the serious side effect of hyperkalemia. We hypothesized that adding the ability to inhibit carbonic anhydrase (CA) would reduce the risk of hyperkalemia associated with MR antagonists. We investigated the profiles of DSR-71167 [2-([(2,2-difluoroethyl)amino]methyl)-2'-fluoro-N-(3-methoxy-4-sulfamoylphenyl)biphenyl-4-carboxamide hydrochloride; an MR antagonist with weak CA inhibitory activity] with regard to antimineralocorticoid actions by examining relationships between the urinary excretion of sodium (index of antimineralocorticoid action) in deoxycorticosterone acetate-treated rats and elevation of serum levels of potassium in potassium-loaded rats compared with a DSR-71167 derivative without CA inhibition (2-(hydroxymethyl)-N-[4-(methylsulfonyl)phenyl]-2'-(trifluoromethyl)biphenyl-4-carboxamide), SPI, and EPL. DSR-71167 dose-dependently increased urinary excretion of sodium in deoxycorticosterone acetate-treated rats without elevating serum levels of potassium in potassium-loaded rats. 2-(Hydroxymethyl)-N-[4-(methylsulfonyl)phenyl]-2'-(trifluoromethyl)biphenyl-4-carboxamide, SPI, and EPL elevated serum levels of potassium significantly in potassium-loaded rats at doses that increased MR inhibitory activity. We confirmed that DSR-71167 significantly increases urinary bicarbonate and decreases blood bicarbonate, as pharmacodynamic markers of CA inhibition, in intact rats. Chronic DSR-71167 administration showed antihypertensive effects in high salt-loaded Dahl hypertensive rats. These results demonstrate that DSR-71167 is a novel type of MR antagonist, with CA inhibitory activity, which is expected to become a safer MR antagonist with a low potential risk for hyperkalemia.

Dialysis Amyloid Deposition in the Aortic Valve and Its Association with Aortic Stenosis.

BACKGROUND: The relationship between dialysis amyloid (DA) deposition in the aortic valve (AV) and aortic stenosis (AS) is unknown. METHODS: This was a cross-sectional study. AV specimens of dialysis patients (median vintage: 8.8 years) consecutively collected from cardiac surgeries (n = 56) or autopsies (n = 13) were examined by a board-certified pathologist blinded to clinical data. DAs were considered to be present if deposits were stained both by Congo red with apple-green birefringence under polarized light and by anti-ß2-microblobulin antibody. Degree of deposition was graded as follows: Amyloid (-), no deposit; Amyloid (1+), occasional small deposits; Amyloid (2+), multiple small to large deposits or a single large deposit. Calcification was defined as a calcified deposit with a diameter >1 mm in the specimen. Severe AS (sAS) was defined as a mean gradient >50 mm Hg by echocardiogram. We examined the proportion of DAs and the association between DAs and the sAS. RESULTS: DAs were present in 71% (n = 49) of specimens and primarily co-localized with calcification. Non-dialysis related amyloid was found in one specimen. After excluding this specimen, sAS was associated with 'Amyloid (1+) and Calcification >1 mm' and 'Amyloid (2+) and Calcification >1 mm' (vs. 'Amyloid (-) and Calcification ≤1 mm', odds ratios (ORs): 13.5 and 34.2, respectively). Furthermore, after adjustment for covariates, sAS was found to be associated with 'Amyloid (2+) and Calcification >1 mm' (OR: 24.3). CONCLUSIONS: DA deposition in the AV was prevalent among dialysis patients. DA deposition with accompanying calcification might contribute to the severity of AS.

An analysis of initial and follow-up CT findings in intramural hematoma, aortic double-lumen dissection, and mixed type lesions.

BACKGROUND: Although the clinical presentation of intramural hematoma (IMH) and aortic double-lumen dissection (AD) is similar, the imaging results and subsequent clinical course of the two lesions differ. PURPOSE: To compare the clinical and radiological findings of IMH, AD, and mixed type lesions. MATERIAL AND METHODS: Forty-two patients with IMH, 38 with AD, and 10 with mixed type lesions were imaged with post-contrast-enhanced CT. The most proximal ulcer-like lesions and entry tears and the distal ends of the IMH and AD were evaluated. The interval change of the intramural hematoma, ulcer-like lesion, and false lumen was observed. The pathological findings of the aorta were evaluated in 15 patients. RESULTS: The most proximal ulcer-like lesion and entry tear were located in the arch to the descending aorta in 27 (64.2%) of the 42 patients with IMH and in 24 (63.1%) of the 38 patients with AD. The distal extension was located at the iliac arteries in six (14.3%) patients with IMH and in 31 (81.6%) patients with AD (P < 0.001). The intramural hematomas regressed in 29 (93.5%) of 31 patients, and the ulcer-like lesion progressed in 14 (70%) of 20 patients with IMH. The clinical features of the mixed type lesions resembled those of AD, rather than IMH. The intramural hematoma or dissection was observed within the outer media in all lesion types on histopathology. CONCLUSION: There is a distinct difference between IMH and AD in distal extension; however, the locations of the lesions are pathologically the same in the media of the aorta.

[A Surgical Case of Intrapulmonary Bronchogenic Cyst Treated by Left Lower Lobectomy for Hemopneumothorax and Repeated Hemoptysis].

A 79-year-old female visited a hospital because of high fever and computed tomography(CT)showed a cystic lesion with fluid accumulation in her left lung. She had hemoptysis and left chest pain 3 days after antibiotic therapy was started. Chest CT demonstrated the cystic lesion rupturing and causing hemopneumothorax. Then she was referred to our department and thoracic drainage was performed. However, a week after the drainage, she had hemoptysis and chest pain again, and the left lower lobectomy was performed. Histopathological findings showed the cystic lesion was intrapulmonary bronchogenic cyst. We describe a rare case of the hemopneumothorax due to the hemorrhage in the bronchogenic cyst.

A case of more than 20 years survival with glioblastoma, and development of cavernous angioma as a delayed complication of radiotherapy.

Glioblastoma (GBM) is the most common malignant CNS neoplasm, the prognosis of which remains poor even after multidisciplinary treatment. The 5-year overall survival rate of GBM is less than 10% and has remained unchanged for more than 50 years. Because GBM patients rarely survive over a decade, only very few cases of delayed complications caused by therapy have been reported. Here, we report the case of a 24-year-old man who is still alive 21 years after surgical resection and chemoradiotherapy for GBM. This patient developed a cavernous angioma 19 years after the initial surgery as a delayed complication of radiotherapy. The diagnosis of the initial tumor was confirmed by histopathological review, which indicated that the tumor had immunohistochemical and genetic profiles consistent with GBM. Long-term survival in the case of this GBM patient likely resulted from a combination of factors, including hypermethylation of the MGMT (O(6)-methyl guanine methyl transferase) CpG island, young age at diagnosis, good performance status, and complete surgical resection of the tumor. To the best of our knowledge, this case report describes one of the longest-surviving GBM patients and is the first on radiation-induced cavernous angioma in a GBM patient.

Characterization of extended-spectrum ß-lactamase-producing Escherichia coli isolated from municipal and hospital wastewater in Japan.

OBJECTIVES: The purpose of this study was to characterize the strains of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (ESBL-EC) isolated from municipal and hospital wastewater by detecting antibiotic resistance genes (ARGs) as well as antibiotic susceptibility. To identify the source of ESBL-EC, multi-locus sequence typing and typing plasmids that may carry ESBL-producing genes were conducted. METHODS: Wastewater was sampled twice a month from February 2019 to February 2020 from a municipal wastewater treatment plant and hospital located in a city in northeastern Japan. Throughout the study period, 279 and 37 strains of ESBL-EC were isolated from municipal and hospital wastewater, respectively. RESULTS: All 316 isolates were resistant to ampicillin and cefotaxime and susceptible to imipenem and tigecycline. Almost all (98.1%) of the ESBL-EC isolates possessed blaCTX-M, and the blaCTX-M-9 group was detected most frequently (62.3%). Multi-locus sequence typing revealed a higher diversity of sequence types (STs) in the isolates from municipal wastewater than in those from hospital wastewater; although ST131, which recently caused nosocomial- and community-associated infections worldwide, was dominant in both types of wastewater. All ST131 isolates possessed the IncFII plasmid, which is often reported to carry blaCTX-M. CONCLUSIONS: These results demonstrated that healthy people carry clinically important antibiotic-resistant bacteria and ARGs, motivating routine monitoring of municipal wastewater to detect such antibiotic-resistant bacteria and ARGs from a variety of sources supported by the high diversity of STs in the present study.

Design and synthesis of versatile GSTP1-specific fluorogenic substrates for the highly sensitive detection of GSTP1 activity in living cells.

Pi-class glutathione S-transferase (GSTP1) is a detoxification enzyme that is highly expressed in various types of cancer cells and is a promising target for cancer imaging and therapy. Ps-TAc, an acetylated derivative of the GSTP1-specific fluorogenic substrate Ps-TG, is attracting attention as an effective GSTP1 fluorescent probe, and has been successfully used to visualize intracellular GSTP1 activity. Ps-TAc is a prodrug type fluorescent probe in which the phenolic hydroxyl group of Ps-TG is acetylated and thus is susceptible to nonspecific hydrolysis, potentially compromising its ability to detect GSTP1 activity. Here, we describe the development of a highly selective fluorogenic GSTP1 substrate that is membrane permeable and does not involve esterification and show its application to live-cell imaging and FACS analysis. We designed and synthesized several compounds with benzylsulfone substituents instead of the mesyl group of Ps-TG and tested their fluorescence activation by GSTP1 catalysis in vitro and in cellulo. Of the test compounds, Ps-TG3 was the most suitable for the visualization of intracellular GSTP1 activity because the signal from living cells increased significantly when MK-571, an inhibitor of multidrug resistance proteins (MRPs), was simultaneously loaded. The results obtained by co-loading Ps-TG3 and MK571 into GSTP1-nonexpressing cells suggest that Ps-TG3 can be a substrate for MRPs. The usefulness of Ps-TG3 was demonstrated by fluorescence imaging of several cancer cell cultures and FACS analysis of lymphoma cells. The results presented here suggest that Ps-TG3, in combination with MK571, is useful for visualizing and detecting intracellular GSTP1 activity in cancer cells that highly express GSTP1.

Delayed rupture of the iliac artery after endovascular therapy.

Iliac artery rupture during endovascular therapy (EVT) is a life-threatening complication requiring prompt diagnosis and treatment. However, delayed rupture of the iliac artery after EVT is rare, and its predictive value remains unknown. Herein, we present the case of a 75-year-old woman who developed delayed iliac artery rupture 12 h after balloon angioplasty and placement of a self-expandable stent in the left iliac artery. Hemostasis was achieved with a covered stent graft. However, the patient died of hemorrhagic shock. From the review of previous case reports and the pathological findings of the current case, increased radial force due to overlapping stent and kinking of the iliac artery may be associated with delayed iliac artery rupture. Learning objective: Delayed iliac artery rupture after endovascular therapy is rare but with a poor prognosis. Hemostasis can be achieved using a covered stent; however, the outcome could be fatal. Based on pathological findings and previous case reports, increased radial force at the stent site and kinking of the iliac artery may be associated with delayed iliac artery rupture. Self-expandable stent probably should not be overlapped at the site where kinking is likely to occur, even if long stenting is needed.

SM-368229, a novel promising mineralocorticoid receptor antagonist, shows antihypertensive efficacy with minimal effect on serum potassium level in rats.

The purpose of this study was to evaluate the effects of SM-368229, a novel mineralocorticoid receptor (MR) antagonist with partial agonistic activity, and spironolactone (SPI) on systolic blood pressure (SBP) and serum potassium in spontaneously hypertensive rats. SM-368229 given for 2 weeks prevented the increase in SBP without serum potassium elevation, but the treatment with SPI prevented SBP increase with serum potassium elevation. To elucidate the contribution of partial agonistic activity of SM-368229 for MR in the mitigation of serum potassium elevation, we studied the relationships between sodium balance decrease, as an index of antimineralocorticoid action, and serum potassium elevation in adrenalectomized and/or potassium-loaded rats, using SM-368229 and its derivatives (DSR-11861 and DSR-14397) showing different partial agonist activities for MR (12%, 0%, and 36%, respectively). DSR-11861 and SPI reversed sodium balance and increased serum potassium. SM-368229 also reversed sodium balance but did not show apparent serum potassium increase. Although DSR-14397 did not show serum potassium increase, its antimineralocorticoid action was very weak. These findings indicate that serum potassium elevation is negatively related to partial agonistic activities for MR, and SM-368229 shows antihypertensive efficacy with minimal effect on serum potassium level, probably due to its partial agonistic property.

Antihypertensive and cardiorenal protective effects of SM-368229, a novel mineralocorticoid receptor antagonist, in aldosterone/salt-treated rats.

The purpose of this study was to evaluate the effects of SM-368229, a novel mineralocorticoid receptor (MR) antagonist, on the blood pressure and cardiorenal injury markers in aldosterone/salt-treated hypertensive rats, in comparison to those of spironolactone (SPI). Uninephrectomized rats, given 1% NaCl to drink, were infused with aldosterone (0.75 µg/h, s.c.). In experiment 1, SM-368229 (10, 30 mg/kg) or SPI (100 mg/kg) were administered for 14 days immediately after aldosterone/salt loading. In experiment 2, SM-368229 (10 mg/kg) or SPI (100 mg/kg) were administered for 10 days after 10 days of aldosterone/salt loading. In both experiments, SM-368229 prevented the increase in systolic blood pressure, heart/kidney weights, and urinary protein/N-acetyl-ß-D- glucosaminidase excretion caused by aldosterone infusion. In real-time polymerase chain reaction analysis, SM-368229 abolished aldosterone-induced gene expression levels for inflammatory, fibrosis and oxidative stress markers in hearts and kidneys. The antihypertensive effect of SM-368229 (30 mg/kg) was superior to that of SPI, and the antihypertensive and cardiorenal protective effects of SM-368229 (10 mg/kg) were similar to those of SPI (100 mg/kg) in both experiments. These results clearly demonstrated that SM-368229 strongly attenuated the progression of hypertension and exerted cardiorenal protection in aldosterone/salt-treated hypertensive rats.

Use of a Deep Learning Approach for the Sensitive Prediction of Hepatitis B Surface Antigen Levels in Inactive Carrier Patients.

Deep learning is a subset of machine learning that can be employed to accurately predict biological transitions. Eliminating hepatitis B surface antigens (HBsAgs) is the final therapeutic endpoint for chronic hepatitis B. Reliable predictors of the disappearance or reduction in HBsAg levels have not been established. Accurate predictions are vital to successful treatment, and corresponding efforts are ongoing worldwide. Therefore, this study aimed to identify an optimal deep learning model to predict the changes in HBsAg levels in daily clinical practice for inactive carrier patients. We identified patients whose HBsAg levels were evaluated over 10 years. The results of routine liver biochemical function tests, including serum HBsAg levels for 1, 2, 5, and 10 years, and biometric information were obtained. Data of 90 patients were included for adaptive training. The predictive models were built based on algorithms set up by SONY Neural Network Console, and their accuracy was compared using statistical analysis. Multiple regression analysis revealed a mean absolute percentage error of 58%, and deep learning revealed a mean absolute percentage error of 15%; thus, deep learning is an accurate predictive discriminant tool. This study demonstrated the potential of deep learning algorithms to predict clinical outcomes.

Orbital Intravascular Natural Killer/T-cell Lymphoma: An Unusual Cause of Ocular Symptoms.

Orbital intravascular lymphoma is rare and typically of B-cell lineage. In this study, we report a patient who developed orbital lesions of intravascular natural killer/T-cell lymphoma (IVNKL), an extremely rare lymphoma. An 88-year-old man presented with rapidly progressive right vision loss and double vision. A neurological examination revealed that he had decreased visual acuity and severe oculomotor impairment in the right eye. Magnetic resonance imaging showed right-dominant, nonmass lesions in both orbits. No lesions were found in the lymph nodes, skin, or brain. The patient received immunosuppressive and antifungal therapy, but his clinical condition rapidly deteriorated, and he died of multiple organ failure. Autopsy revealed natural killer/T-cell lymphoma proliferation within the lumina of small blood vessels in multiple organs, including the ocular adnexa of the right orbit. These findings show that he was ultimately diagnosed with IVNKL. IVNKL could initially cause ocular symptoms due to the involvement of the ocular adnexa. Ocular involvements have not been described previously. Even if patients initially present with only ocular symptoms, IVNKL should be considered.

Prediction of Microcystis Occurrences and Analysis Using Machine Learning in High-Dimension, Low-Sample-Size and Imbalanced Water Quality Data.

Machine learning, Deep learning, and water quality data have been used in recent years to predict the outbreak of harmful algae, especially Microcystis, and analyze outbreak causes. However, for various reasons, water quality data are often High-Dimension, Low-Sample- Size (HDLSS), meaning the sample size is lower than the number of dimensions. Moreover, imbalance problems may arise due to bias in the occurrence frequency of Microcystis. These problems make predicting the occurrence of Microcystis and analyzing its causes with machine learning difficult. In this study, a machine learning model that applies Feature Engineering (FE) and Feature Selection (FS) algorithms are used to predict outbreaks of Microcystis and analyze the outbreak factors from imbalanced HDLSS water quality data. The prediction performance was verified with binary classification to determine whether Microcystis would occur in the future by applying three machine learning models to four data patterns. The cause analysis of Microcystis occurrence was performed by visualizing the results of applying FE and FS. For the test data, the predictive performance of FE and FS methods was significantly better than that of the conventional method, with an accuracy of .108 points and an F-value of .691 points higher than the conventional method. A prediction performance increase was observed with a smaller model capacity. Data-driven analysis suggested that total nitrogen, chemical oxygen demand, chlorophyll-a, dissolved oxygen saturation, and water temperature are associated with Microcystis occurrences. The results also indicated that basic statistics of the water quality distribution (especially mean, standard deviation, and skewness) over a year, not the concentrations of water components, are related to the occurrence of Microcystis. These are new findings not found in previous studies and are expected to contribute significantly to future studies of algae. This study provides a method for analyzing water quality data with high-dimensionality and small samples, imbalance problems, or both.

Autopsy findings of left atrial appendage closure device.

We report an autopsy case of an 80-year-old woman who underwent left atrial appendage closure with a WATCHMAN (Boston Scientific, St. Paul, MN, USA) device. This is the first report of histologic assessment following left atrial appendage closure with a WATCHMAN device at 3 months. Gross and histopathological examinations revealed neoendocardial coverage of the WATCHMAN device. Partial endothelialization was verified by CD34 staining; however, it remains unclear when complete endothelialization is likely to occur.