Artificial intelligence for the automated single-shot assessment of psoriasis severity.

BACKGROUND: PASI score is globally used to assess disease activity of psoriasis. However, it is relatively complicated and time-consuming, and the score will vary due to the inconsistent subjectivity between dermatologists. Therefore, an AI system capable of assessing psoriasis severity will be useful. OBJECTIVES: To propose a simplified PASI system (Single-Shot PASI) and associated AI models capable of assessing psoriasis severity. METHODS: Overall, 705 psoriasis images of the trunk's front and back were used in our research. Considering the relatively small number of images, we used data augmentation techniques to expand the data. A psoriasis expert's scores were used as teacher data. Various convolutional neural network models and hyperparameters were adjusted using a fivefold cross-validation. From these adjustments, we discovered that fine-tuning Imagenet2012-pretrained InceptionV3 whose last linear layer was replaced by a two-layer perceptron (30 hidden units and five output units) exhibited the best performance. RESULTS: To validate our deep learning system, 10 images were selected as test sets and were excluded from the training sets. The AI assessment of Single-Shot PASI was almost consistent with the clinical severity. We examined whether AI assistance would affect human scoring. In this study, 13 dermatologists and 9 medical students were invited as evaluators. Mean absolute differences from AI scores and standard deviation among evaluators reduced with AI assistance. In addition, the evaluator's scores got close to the teacher's score with AI's assistance. CONCLUSIONS: We proposed a Single-Shot PASI system and developed an associated AI system capable of assessing psoriasis severity simply by uploading a single clinical image. An easy-to-use scoring system and our freely available AI software would help dermatologists and patients with psoriasis.

Punctate Administration of Ficin as a human and animal model of non-histaminergic itch.

BACKGROUND: Ficin, a cysteine protease derived from fig-tree latex, has been reported to elicit itch and nociceptive sensations, though quantitative sensory studies are lacking. Cowhage containing the pruritic cysteine Mucunain, on the contrary, has been widely studied as activating polymodal nociceptors and eliciting a histamine-independent itch. OBJECTIVES: We tested whether ficin in heat-inactivated cowhage spicules would elicit itch and nociceptive sensations in humans, and analogous behaviours in mice, which are similar to those evoked by native cowhage, and whether these behaviours in mice were dose-dependent when ficin was injected intradermally. METHODS: Human volunteers rated the magnitude of itch and nociceptive sensations evoked by either native cowhage spicules or heat-inactivated spicules soaked in 1, 10 or 100 mg/mL ficin (0.03, 0.3 and 3 ng of ficin in spicule tip), applied to forearm. In mice, itch-like scratching and nociceptive-like wiping were recorded in response to either native cowhage, to heat-inactivated spicules that were either inactive or contained 100 mg/mL ficin, or to intradermal injections of 1.25, 2.5 or 5 µg/ 5 µL, each treatment applied to the cheek. RESULTS: The dose of 100 mg/mL ficin in spicules evoked comparable magnitudes of itch, nociceptive sensations and areas of cutaneous dysesthesia as native cowhage in humans and comparable itch-like scratching and pain-like wiping behaviours in mice. But to elicit similar behaviours when injected intradermally in mice a greater amount of ficin (1.25 µg) was required. CONCLUSION: Spicule delivery or intradermal injection of ficin elicits behaviours in mice that model itch and nociceptive sensations in humans, suggesting that ficin may be useful in translating mechanistic research on the neural mechanisms of pruritic and nociceptive effects of cysteine proteases between the two species.

An outbreak of food poisoning due to Escherichia coli serotype O7:H4 carrying astA for enteroaggregative E. coli heat-stable enterotoxin1 (EAST1).

In June 2020, a large-scale food poisoning outbreak involving about 3000 elementary and junior high school students occurred in Yashio, Saitama, Japan. A school lunch was the only food stuff ingested by all of the patients. Escherichia coli serotype O7:H4 carrying the astA gene for enteroaggregative E. coli (EAggEC) heat-stable enterotoxin 1 (EAST1) was detected in faecal specimens from the patients, and sample inspection revealed its presence in a seaweed salad and red seaweed (Gigartina tenella) as one of the raw materials. Analysis of the antibiotic sensitivity of the isolates revealed resistance to ampicillin and cefotaxime. All isolates were confirmed to be of the same origin by pulsed-field gel electrophoresis after digestion with the restriction enzyme XbaI, and single nucleotide polymorphism analysis using whole genome sequencing. To our knowledge, this is the first report of a large-scale food poisoning caused by E. coli O7:H4, which lacks well-characterized virulence genes other than astA.

Cartilage and subchondral bone distributions of the distal radius: a 3-dimensional analysis using cadavers.

OBJECTIVE: To quantify the spatial distributions of cartilage and subchondral bone thickness of the distal radius. DESIGN: Using 17 cadaveric wrists, three types of 3-dimensional models were created: a cartilage-bone model, obtained by laser scanning; a bone model, rescanned after dissolving the cartilage; and a subchondral bone model, obtained using computed tomography. By superimposing the bone model onto the cartilage-bone and the subchondral bone models, the cartilage and subchondral bone thickness were determined. Measurements along with the spatial distribution were made at fixed anatomic points including the scaphoid and lunate fossa, sigmoid notch and interfossal ridge, and compared at each of these four regions. RESULTS: Cartilage thickness of the interfossal ridge (0.89 ± 0.23 mm) had a larger average thickness compared to that of the scaphoid fossa (0.70 ± 0.18 mm; p = 0.004), lunate fossa (0.75 ± 0.17 mm; p = 0.044) and sigmoid notch (0.64 ± 0.13 mm; p < 0.001). Subchondral bone was found to be thickest at the scaphoid (2.18 ± 0.72 mm) and lunate fossae (1.94 ± 0.93 mm), which were both thicker than that of sigmoid notch (1.63 ± 1.06 mm: vs scaphoid fossa, p = 0.020) or interfossal ridge (1.54 ± 0.84 mm: vs scaphoid fossa, p = 0.004; vs lunate fossa, p = 0.048). In the volar-ulnar sub-regions of the scaphoid and lunate fossa, the subchondral bone thickened. CONCLUSIONS: Our data can be applied when treating distal radius fractures. Cartilage thickness was less than 1 mm across the articular surface, which may give an insight into threshold for an acceptable range of step-offs. The combined findings of subchondral bone appreciate the importance of the volar-ulnar corner of the distal radius in the volar locking plate fixation.

Cartilage wear patterns in severe osteoarthritis of the trapeziometacarpal joint: a quantitative analysis.

OBJECTIVE: The present quantitative study aimed to assess the three-dimensional (3-D) cartilage wear patterns of the first metacarpal and trapezium in the advanced stage of osteoarthritis (OA) and compare cartilage measurements with radiographic severity. DESIGN: Using 19 cadaveric trapeziometacarpal (TMC) joints, 3-D cartilage surface models of the first metacarpal and trapezium were created with a laser scanner, and 3-D bone surface model counterparts were similarly created after dissolving the cartilage. These two models were superimposed, and the interval distance on the articular surface as the cartilage thickness was measured. All measurements were obtained in categorized anatomic regions on the articular surface of the respective bone, and we analyzed the 3-D wear patterns on the entire cartilage surface. Furthermore, we compared measurements of cartilage thickness with radiographic OA severity according to the Eaton grading system using Pearson correlation coefficients (r). RESULTS: In the first metacarpal, the cartilage thickness declined volarly (the mean cartilage thickness of the volar region was 0.32 ± 0.16 mm, whereas that of the dorsal region was 0.53 ± 0.18 mm). Conversely, the cartilage evenly degenerated throughout the articular surface of the trapezium. Measurements of the categorized regions where cartilage thinning was remarkable exhibited statistical correlations with radiographic staging (r = -0.48 to -0.72). CONCLUSIONS: Our findings indicate that cartilage wear patterns differ between the first metacarpal and trapezium in the late stage of OA. There is a need for further studies on cartilage degeneration leading to symptomatic OA in the TMC joint.

Surgical starting time in the morning versus the afternoon: propensity score matched analysis of operative outcomes following laparoscopic colectomy for colorectal cancer.

BACKGROUND: The number of colorectal cancer cases is increasing, and so the number of laparoscopic colectomy procedures being performed is also increasing, leading to an increased workload for surgeons. However, operating for prolonged time periods may cause surgeons to lose their concentration and develop fatigue. We hypothesized that there is a time-of-day variation in outcome for patients with colorectal cancer who undergo laparoscopic colectomy. The present study aimed to compare the operative outcome between laparoscopic colectomy for colorectal cancer performed in the morning versus the afternoon. METHODS: This was a single-center, retrospective study. All 1961 consecutive patients who underwent laparoscopic surgery for colorectal cancer between 2007 and 2017 were included; 1006 of these patients underwent morning surgery, while 955 underwent afternoon surgery. These patients were analyzed using propensity score matching, giving 791 patients in each group. The short- and long-term outcomes in both groups were compared. RESULTS: Before propensity score matching, the morning group had a larger mean tumor size than the afternoon group (30 cm vs 35 cm; P = 0.0035). After matching, the two groups did not significantly differ in any patient characteristics. Compared with the afternoon group, the morning group had a significantly lesser incidence of intra-operative organ injury (0.25% vs 1.13%; P = 0.027), and a significantly greater incidence of post-operative abdominal abscess (2.03% vs 0.75% P = 0.028). The incidences of other complications and morbidities were similar in both groups. The median operative time in the morning group (201 min) was significantly longer than that in the afternoon group (193 min; P = 0.0124). The two groups did not differ in 5-year overall survival rates and 5-year disease-free rates within any disease stage. CONCLUSIONS: Surgical start times are correlated with surgical outcomes. Our data will help to ensure the safest possible surgeries.

A novel 5HT3 receptor-IGF1 mechanism distinct from SSRI-induced antidepressant effects.

Depression is a common mental disorder affecting around 350 million people worldwide. Although selective serotonin reuptake inhibitors (SSRIs) are the most widely used antidepressants, a significant proportion of depressed patients do not achieve remission with SSRIs. In this study, we show that a serotonin type 3 receptor (5HT3R) agonist induces antidepressant effects as well as hippocampal neurogenesis independent of fluoxetine (a commonly used SSRI). Notably, our histological analysis reveals that 5HT3R and insulin-like growth factor 1 (IGF1) are expressed in the same neurons in the subgranular zone of the hippocampal dentate gyrus. Furthermore, our in vivo microdialysis analysis shows that 5HT3R regulates hippocampal extracellular IGF1 levels, and we also show that 5HT3R-dependent hippocampal neurogenesis is mediated by increased IGF1 levels. Altogether, our findings suggest a novel 5HT3R-IGF1 mechanism that is distinct from fluoxetine-induced responses and that provides a new therapeutic target for depression, especially bringing significant benefits for SSRI-resistant depressed patients.

Septin 9_i2 is downregulated in tumors, impairs cancer cell migration and alters subnuclear actin filaments.

Functions of septin cytoskeletal polymers in tumorigenesis are still poorly defined. Their role in the regulation of cytokinesis and cell migration were proposed to contribute to cancer associated aneuploidy and metastasis. Overexpression of Septin 9 (Sept9) promotes migration of cancer cell lines. SEPT9 mRNA and protein expression is increased in breast tumors compared to normal and peritumoral tissues and amplification of SEPT9 gene was positively correlated with breast tumor progression. However, the existence of multiple isoforms of Sept9 is a confounding factor in the analysis of Sept9 functions. In the present study, we analyze the protein expression of Sept9_i2, an uncharacterized isoform, in breast cancer cell lines and tumors and describe its specific impact on cancer cell migration and Sept9 cytoskeletal distribution. Collectively, our results showed that, contrary to Sept9_i1, Sept9_i2 did not support cancer cell migration, and induced a loss of subnuclear actin filaments. These effects were dependent on Sept9_i2 specific N-terminal sequence. Sept9_i2 was strongly down-regulated in breast tumors compared to normal mammary tissues. Thus our data indicate that Sept9_i2 is a negative regulator of breast tumorigenesis. We propose that Sept9 tumorigenic properties depend on the balance between Sept9_i1 and Sept9_i2 expression levels.

Donor Left-Sided Heptectomy by Use of the Real-Time Moving Windows Method With 8-Centimeter Transverse Skin Incision.

BACKGROUND: In this study, we demonstrated our new device for open donor liver surgery with left-sided heptectomy by use of the real-time moving windows (RTMW) method with 8-cm transverse skin incision for living donors from the viewpoints of cosmetic, economic, and safety procedures. METHODS: After the upper abdominal 8-cm transverse skin incision was made, the subcutaneous area was exfoliated and the reverse T-shaped-abdominal incision was made, as in open surgery. After that, the 2 Kent hooks for the upper region and the 2 surgical arms for the lower region were placed. The operative fields of hepatic vein, hepatic hilus, and common hepatic artery were explored, respectively, by use of the RTMW method with the use of the 4 surgical hooks. Hepatic parenchymal dissection was carried out with the use of CUSA and laparosonic coagulating shears. Manipulations of 3 hepatic vessels and the hepatic duct were done by the usual procedure of open surgery. RESULTS: This operative procedure could be performed without laparoscopic techniques. The operative time was 7 hours, without blood transfusion. The operative course was uneventful, and the patient was discharged on postoperative day 11. CONCLUSIONS: Our RTMW method for donor left-sided hepatectomy is considered to be a useful operative procedure from the viewpoints of donor safety, cosmetic advantage, and cost performance.

14-3-3ζ-Mediated Stimulation of Oxidative Phosphorylation Exacerbates Oxidative Damage Under Hypothermic Oxygenated Conditions in Human Renal Tubular Cells (HK-2).

Cellular survival and death are at least partially regulated by the phosphorylation of proteins. A chaperon protein, 14-3-3ζ, regulates the activity of many proteins by covering the phosphorylation site within a 14-3-3 binding motif. Therefore, regulation of 14-3-3ζ activity may affect the fate of cells subjected to cold preservation and/or hypothermic oxygenated conditions. The present study assessed whether 14-3-3ζ protects cells from hypothermic oxygenation-induced injury and clarified its role in mitochondrial functions. Human renal tubular cell line HK-2 or 14-3-3ζ-overexpressed HK-2 (ζHK-2) cells were subjected to 72 hours of normoxic cold preservation in UW solution with or without antioxidants and hydroperoxides. Cellular death, adenosine triphosphate (ATP) content, and MTT catabolism were evaluated. Deferoxamine treatment reduced cellular death and augmented ATP content in both cell types. These indices were higher in ζHK-2, regardless of deferoxamine treatment. Exposure to hydroperoxides did not affect cellular death in either cell type, whereas hydroperoxide supplementation significantly reduced ATP content, except for low-dose hydrogen peroxide in HK-2 cells. MTT assay at normal state showed higher values in ζHK-2 cells, whereas it was impaired by hydroperoxides in both cell types. These results suggest that accumulation of hydroperoxides as a byproduct of the augmented oxidative phosphorylation by 14-3-3ζ overexpression causes mitochondrial dysfunction. In conclusion, despite possessing many potentially protective functions, 14-3-3ζ exacerbates cellular injury under hypothermic oxygenated conditions. 14-3-3ζ accelerates mitochondrial functions together with iron-dependent oxidative damage. Although further investigations are necessary, upregulation of 14-3-3ζ could be a method to maintain mitochondrial function under hypothermic oxygenated conditions, as shown in hypothermic machine preservation of renal grafts, when appropriate antioxidant treatment is administered.

Olefin hydrosilylation catalyzed by cationic nickel(ii) allyl complexes: a non-innocent allyl ligand-assisted mechanism.

The arene-supported cationic nickel allyl complexes serve as good catalysts for olefin hydrosilylation at room temperature. Detailed mechanistic studies based on experiments and DFT calculations support the novel mechanism, which includes the facile Si-H bond cleavage and Si-C bond formation, assisted by a non-innocent allyl ligand.

Development and analysis of patient-derived xenograft mouse models in intravascular large B-cell lymphoma.

Intravascular large B-cell lymphoma (IVLBCL) is a distinct disease entity with the peculiar characteristic that tumor cells proliferate within vessels. Despite recent advances in understanding the disease from clinical aspects, the underlying pathogenesis remains unknown. Here we demonstrate analyses of IVLBCL biology using four xenograft mouse models established from primary IVLBCL samples. In all four models, the main characteristic of IVLBCL tumor cell proliferation within vessels was retained. Time-lapse engraftment analyses revealed that the tumor cells initially engrafted and proliferated in the sinusoids and vessels in the liver and then engrafted and proliferated in multiple organs. Intriguingly, serial passage of tumor cells from the adrenal gland of a transplanted mouse developed from primary patient bone marrow cells into a second mouse showed that the tumor cells mainly distributed into the adrenal gland in the second mouse, implying the existence of clonal selection and/or evolution at engraftment of a specific organ. Gene expression profiling analyses demonstrated that the gene set associated with cell migration was enriched for normal peripheral blood B cells, indicating that inhibition of cell migration might be involved in IVLBCL pathogenesis. In conclusion, the mouse xenograft models described here are essential tools for uncovering IVLBCL biology.

Allergen-specific basophil reactivity exhibits daily variations in seasonal allergic rhinitis.

It remains poorly understood how symptoms in allergic rhinitis are most severe during overnight or early in the morning. The circadian clock consisting of a network of several 'clock genes' including Clock drives daily rhythms in physiology. This study showed that allergen-induced surface CD203c expression on basophils in seasonal allergic rhinitis caused by Japanese cedar pollen exhibited a time-of-day-dependent variation associated with temporal variations in canonical circadian clock gene expression. We also found that bone-marrow-derived basophils (BM basophils) generated from wild-type mice exhibited a time-of-day-dependent variation in IgE-mediated IL-4 and histamine production, which was not observed in BM basophils generated from Clock-mutated mice. Therefore, allergen-specific basophil reactivity shows daily variations depending on the circadian clock activity in basophils, which could partly explain temporal symptomatic variations in allergic rhinitis. Additionally, circadian variations in CD203c expression should be considered for interpretation of this biomarker in clinical research.

The 5-HT3 receptor is essential for exercise-induced hippocampal neurogenesis and antidepressant effects.

Exercise has a variety of beneficial effects on brain structure and function, such as hippocampal neurogenesis, mood and memory. Previous studies have shown that exercise enhances hippocampal neurogenesis, induces antidepressant effects and improves learning behavior. Brain serotonin (5-hydroxytryptamine, 5-HT) levels increase following exercise, and the 5-HT system has been suggested to have an important role in these exercise-induced neuronal effects. However, the precise mechanism remains unclear. In this study, analysis of the 5-HT type 3A receptor subunit-deficient (htr3a(-/-)) mice revealed that lack of the 5-HT type 3 (5-HT3) receptor resulted in loss of exercise-induced hippocampal neurogenesis and antidepressant effects, but not of learning enhancement. Furthermore, stimulation of the 5-HT3 receptor promoted neurogenesis. These findings demonstrate that the 5-HT3 receptor is the critical target of 5-HT action in the brain following exercise, and is indispensable for hippocampal neurogenesis and antidepressant effects induced by exercise. This is the first report of a pivotal 5-HT receptor subtype that has a fundamental role in exercise-induced morphological changes and psychological effects.

Ganglioside disialosyl globopentaosylceramide is an independent predictor of PSA recurrence-free survival following radical prostatectomy.

BACKGROUND: Disialosyl globopentaosylceramide (DSGb5) is a ganglioside originally isolated from renal cell carcinoma (RCC) tissue that has been associated with RCC metastasis. However, in prostate cancer, the expression of DSGb5 has not yet been fully assessed. In this study, we investigated DSGb5 expression in prostate tissues and the relationship between DSGb5 expression and clinicopathological characteristics of prostate cancer patients. METHODS: A total of 130 patients who underwent radical prostatectomy (RP) at our hospital between January 2005 and December 2007 were analyzed in this study. The expression of DSGb5 in prostatectomy specimens was examined by immunohistochemical analysis with monoclonal antibody 5F3 (anti-DSGb5). Associations between 5F3 expression and clinicopathological findings were investigated and the factors that affected PSA failure-free survival were assessed by Kaplan-Meier analysis and a Cox regression model. RESULTS: When immunoreactivities of 5F3 were measured, negative to strong staining was observed in prostate cancer tissue, whereas strong staining was observed in benign prostate glands. These expression patterns suggest that DSGb5 may act as a differentiation antigen in cancerization. The PSA failure-free survival was significantly higher in the 5F3 intact expression group than in the 5F3 reduced expression group (log-rank P=0.0220). On multivariate analysis, 5F3 intact expression showed significantly worse PSA failure-free survival following RP. CONCLUSIONS: 5F3 expression reflects the clinical and pathological features of prostate cancer and is correlated with the outcomes following RP. Further studies are necessary to clarify the functional roles of DSGb5 and establish a novel biomarker for prostate cancer.