Adaptive beam forming across temperature variation in optical phased array enabled with deep neural network.

Integrated optical phased arrays (OPA) require calibration to account for mismatches amongst the channels. Furthermore, beams emitted from an OPA tend to distort when the chip's temperature changes. We propose to utilize a deep neural network (DNN) to adaptively control the phase modulator voltages of the OPA and create a desired beam pattern in the presence of process mismatches and temperature changes. As a proof of concept, adaptive beam forming was demonstrated with an integrated 128-channel OPA realized in a commercial foundry silicon photonics (SiP) process. Beam forming within 50° field of view (FoV) is demonstrated, while accuracy of 0.025° is achieved when the beam is swept in 0.1° step at a fixed temperature. The DNN is also used to create beams with multiple peaks at desired spatial angles. The DNN is shown to properly adjust the phase modulator voltages to keep the beam nearly intact as temperature changes within 20°C range.

ß-Catenin-activated inflammatory hepatocellular adenoma with pigmentation and atypical features: a case report.

Hepatocellular adenomas are rare diseases, defined as benign liver neoplasms composed of cells with hepatocellular differentiation. Differential diagnosis of hepatocellular adenoma from other lesions, including focal nodular hyperplasia and hepatocellular carcinoma, is crucial to determine treatment strategy. We describe a case of ß-catenin-activated inflammatory hepatocellular adenoma with malignant transformation. A 50-year-old man with a suspected liver tumor, based on abdominal ultrasonography findings, was referred to our hospital. Contrast-enhanced computed tomography and magnetic resonance imaging revealed a liver tumor in S2 which was enhanced in the arterial phase to the delayed phase. Based on diagnostic imaging findings, hepatocellular adenoma or focal nodular hyperplasia was suspected. We considered the possibility of malignant potential because of the enlargement of the lesion. Thus, we performed a laparoscopic hepatectomy. Histological examination showed pigment deposition in the hepatocytes, which was determined to be lipofuscin. Mild nuclear swelling and atypia in the tumor area indicated nodular growth. Based on the histological and immunohistochemical findings, the diagnosis was ꞵ-catenin-activated inflammatory hepatocellular adenoma with atypical features. The imaging features of hepatocellular adenoma and focal nodular hyperplasia are similar, but if the tumor tends to grow, surgical treatment should be performed because of the possibility of malignant hepatocellular adenoma.

Time-course analysis of pulmonary inflammation induced by intratracheal instillation of nanosized crystalline silica particles in F344 rats.

Crystalline silica is an important cause of serious pulmonary diseases, and its toxic potential is known to be associated with its surface electrical properties. However, in vivo data clarifying the relevance of silica's toxic potential, especially its long-term effects, remain insufficient. To investigate the contribution of physico-chemical property including surface potential on the hazard of nanocrystalline silica, we performed single intratracheal instillation testing using five different crystalline silicas in a rat model and assessed time-course changes in pulmonary inflammation, lung burden, and thoracic lymph node loads. Silica-nanoparticles were prepared from two commercial products (Min-U-Sil5 [MS5] and SIO07PB [SPB]) using three different pretreatments: centrifugation (C), grinding (G), and surface dissolving (D). The five types of silica particles-MS5, MS5_C, SPB_C, SPB_G, and SPB_D-were intratracheally instilled into male F344 rats at doses of 0 mg/kg (purified water), 0.22 mg/kg (SPB), and 0.67, 2, or 6 mg/kg (MS5). Bronchoalveolar lavage, a lung burden analysis, and histopathological examination were performed at 3, 28, and 91 days after instillation. Granuloma formation was present in MS5 group at 91 days after instillation, although granuloma formation was suppressed in MS5_C group, which had a smaller particle size. SPB_C induced severe and progressive inflammation and kinetic lung overload, whereas SPB_G and SPB_D induced only slight and transient acute inflammation. Our results support that in vivo toxic potential of nanosilica by intratracheal instillation may involve with surface electrical properties leading to prolonged effect and may not be dependent not only on surface properties but also on other physico-chemical properties.

[A Case of Stage â £ Gastric Cancer Treated with Conversion Surgery after Chemotherapy].

A case is a female of 61-year-old. She visited her local doctor with a chief complaint of frequent burping. She was hospitalized for gastric cancer with pyloric stenosis. Although open gastrectomy was planned the gastric cancer was unresectable due to pancreatic invasion and peritoneal dissemination. Cytology with abdominal lavage was CY0. She underwent gastrojejunostomy. She was treated by 19 courses of chemotherapy with SOX therapy for 2 years. The tumor reduced, and she underwent distal gastrectomy as conversion surgery. Pathological findings were por2>muc>tub2>tub1, ypT2(ypMP), INF c, int, Ly1a, V0, pPM0, pDM0, pN0(0/43), ypStage ⅠB, R0, Grade 2b. Adjuvant chemotherapy(S-1 and docetaxel)was administered after conversion surgery. She is alive without recurrence for 1 year and 6 months after gastrectomy. We report a case of Stage Ⅳ gastric cancer treated with conversion surgery after chemotherapy.

[Three Cases of Conversion Surgery for Unresectable Advanced Gallbladder Cancer with Distant Metastasis Treated with Gemcitabine plus CDDP].

All three patients were female, one in her 50s, and the other two in their 60s. The one in her 50s had liver metastasis and the other two had unresectable advanced cholecystic carcinomas with peritoneal dissemination. All three received 8-12 courses of gemcitabine plus CDDP(GC). After GC, all three were deemed to be candidates for R0 resection and underwent resection of two central liver segments. In addition, the second patient required an extrahepatic cholangiectomy; an extended cholecystectomy, plus an extrahepatic cholangiectomy, plus a complete omental resection; and the third needed an extended cholecystectomy, plus an extrahepatic cholangiectomy with a partial transverse colon resection, plus a partial duodenectomy. The pathologic response to chemotherapy was moderate in the patient with liver metastases, mild in the one who underwent the omental resection, and moderate in the patient who had the partial resection of the digestive tract. All three patients continued with postoperative chemotherapy. The patient with liver metastases and the one with the partial gastrointestinal tract resection have survived without recurrence for 52 months and 43 months, respectively, after the initial treatment. The patient with the omental resection has survived 44 months after the initial treatment with recurrent peritoneal dissemination and is continuing chemotherapy as an outpatient. Although further study is needed to accumulate more cases, the results suggest the usefulness of multidisciplinary treatment including conversion surgery in cases such as these.

Conversion surgery following gemcitabine plus cisplatin therapy for initially unresectable gallbladder cancer with peritoneal carcinomatosis: a case report.

BACKGROUND: Conversion surgery, which is defined as chemotherapy or chemoradiotherapy followed by radical surgery, may improve survival of patients with initially unresectable advanced biliary tract cancer, including gallbladder cancer. However, there are few reports on conversion surgery for advanced gallbladder cancer. CASE PRESENTATION: A 69-year-old woman was referred to our hospital with initially unresectable gallbladder cancer with peritoneal carcinomatosis. She underwent gemcitabine plus cisplatin therapy for 9 months. Extended cholecystectomy, resection of the extrahepatic bile duct with regional lymph node dissection, and total omentectomy were then performed as conversion surgery. The patient has survived without recurrence for 19 months postoperatively (31 months after the initial diagnosis) while continuing chemotherapy. CONCLUSIONS: This case suggests that conversion surgery for advanced gallbladder cancer is effective and may be curative for locally advanced disease and distant metastasis such as peritoneal carcinomatosis.

Time-course comparison of pulmonary inflammation induced by intratracheal instillation of four different nickel oxide nanoparticles in male Fischer rats.

Occupational exposure to nickel oxide (NiO) is an important cause of respiratory tract cancer. Toxicity is known to be associated with the dissociated component, i.e. nickel (II) ions. To address the relationship between physicochemical properties, including solubility in artificial lysosomal fluid, of NiO and time-course changes in the pulmonary response, we conducted an intratracheal instillation study in male Fischer rats using four different well-characterized NiO products, US3352 (NiO A), NovaWireNi01 (NiO B), I small particle (NiO C), and 637130 (NiO D). The NiOs were suspended in purified water and instilled once intratracheally into male F344 rats (12 weeks old) at 0 (vehicle control), 0.67, 2, and 6 mg/kg body weight. The animals were euthanized on days 3, 28, or 91 after instillation, and blood analysis, bronchoalveolar lavage fluid (BALF) testing, and histopathological examination were performed. The most soluble product, NiO B, caused the most severe systemic toxicity, leading to a high mortality rate, but the response was transient and surviving animals recovered. The second-most-soluble material, NiO D, and the third, NiO A, caused evident pulmonary inflammation, and the responses persisted for at least 91 days with collagen proliferation. In contrast, NiO C induced barely detectable inflammation in the BALF examination, and no marked changes were noted on histopathology. These results indicate that the early phase toxic potential of NiO products, but not the persistence of pulmonary inflammation, is associated with their solubility.

[Gallbladder Cancer with Multiple Liver Metastases Completely Responding to Gemcitabile plus Cisplatin Chemotherapy-A Case Report].

A 59-year-old man was diagnosed with cholecystolithiasis and cholecystitis and underwent cholecystectomy. The pathological findings were moderately differentiated adenocarcinoma(pT2)in the gallbladder fundus. Sixteen days after surgery, he visited our hospital due to jaundice. Abdominal enhanced CT and EOB-MRI revealed multiple liver metastases and lymph node metastases in the hepatoduodenal ligament that we deemed to be unresectable. A metallic stent was inserted for bile duct obstruction, and he underwent chemotherapy with gemcitabine plus cisplatin(GC). After 12 courses of GC, the metastatic lesions disappeared, and the patient showed complete response. FDG-PET/CT showed FDG uptake in the hepatoduodenal ligament and we subsequently decided to perform surgery. He underwent resection of the extrahepatic bile duct and regional lymphadenectomy. The pathological findings revealed no residual carcinomas in the bile duct or lymph nodes. We are continuing chemotherapy at present, and the patient is alive with no signs of recurrence at 1 year and 3 months following the diagnosis of multiple liver metastases.

[Transcriptomics-driven Evaluation on Liver Toxicity Using Adverse Outcome Pathways (AOP)].

Because the liver is the primary target organ for chemicals and pharmaceuticals, evaluation of these substances' liver toxicity is of critical importance. New evaluation methods without animal testing (i.e., in vitro and/or in silico) are eagerly anticipated, both for animal welfare and for decreasing cost. Also, the importance of mechanistic interpretation of the output derived from non-animal testing has been increasing. Accordingly, we investigated the potential for evaluating liver toxicity by applying the adverse outcome pathway (AOP) concept using gene set enrichment analysis (GSEA) from gene expression (GEx) data. A case study targeting hepatocellular fatty degeneration (HFD) is reported and discussed. We first identified the events detectable in an in vitro system by comparing the GEx data from the rat primary hepatocyte (in vitro) and rat liver (in vivo) treated with a chemical with the ability to induce HFD as one of the phenotypes in a 28-day repeated-dose toxicity test. Then, the scores based on GSEA were calculated after establishing the gene sets for each event leading to HFD. As a result, the mechanistic information leading to HFD was obtained from the score calculated based on the GSEA and the usefulness of the transcriptome-driven evaluation using AOP was demonstrated.

Low-power thermo-optic silicon modulator for large-scale photonic integrated systems.

Silicon platform enables the monolithic realization of large-scale photonic integrated systems. Many emerging applications facilitated by silicon photonics such as optical biosensing, optical neurostimulation, optical phased arrays, holographic displays, 3D cameras, optical machine learning, and optical quantum information processing systems require the integration of a large number of optical phase modulators with modest modulation speed. Classical optical modulators are not suitable for such large-scale integration because of their inability to provide low optical loss, compact size, high efficiency, and wide optical bandwidth, all at the same time. We report a thermo-optic silicon modulator realized in a 0.0023-mm2 silicon footprint of a commercial foundry silicon photonics process. The optical modulator consumes 2.56 mW for 180° phase modulation over 100-nm optical bandwidth while achieving 1.23-dB optical loss without air-gap trench or silicon undercut post-processing. Geometrical design optimization, at the core of this demonstration, is applicable to the realization of compact thermo-optic devices for large-scale programmable photonic integrated systems, with a potential to reduce power consumption roughly by an order of magnitude without sacrificing scalability and optical modulation bandwidth.

[A Case of Liver Recurrence of Choriocarcinoma and AFP-Producing Carcinoma of the Stomach Showing a Complete Histological Response after Chemotherapy].

A 65-year-old man was hospitalized for gastric cancer. Abdominal computed tomography detected lower gastric cancer and invasion of the liver. Initial laboratory data showed high levels of serum AFP(2,688.6 ng/mL). He underwent distal gastrectomy with left lobectomy of the liver and cholecystectomy. Histology confirmed that the tumor consisted of 2 components: primary gastric choriocarcinoma and AFP-producing carcinoma. The pathological staging was pT4b(liver), N3aM0, Stage ⅢC. After surgery, AFP levels decreased to within the normal limits. Adjuvant chemotherapy(S-1)was administered for 1 year after the operation. Fourteen months later, PET-CT and EOB-MRI detected liver recurrence. He was treated with weekly paclitaxel(PTX)chemotherapy for the liver recurrence. After 12 courses, the tumor had disappeared. The patient was continuously treated with weekly PTX and is doing well without recurrence 24 months after the resection of the liver tumor. Co-existence of primary gastric choriocarcinoma and AFP-producing carcinoma is very rare. We report a case of liver recurrence of choriocarcinoma and AFP-producing carcinoma of the stomach showing a complete histological response after chemotherapy.

Basic eluent for rapid and comprehensive analysis of fatty acid isomers using reversed-phase high performance liquid chromatography/Fourier transform mass spectrometry.

Comprehensive separation of fatty acids, including various isomers, is very important for chemical analyses associated with detailed physiological function investigations. We found that a basic eluent is effective for realizing clear separation of double-bond regioisomers by reversed-phase high-performance liquid chromatography. We carried out a comprehensive analysis of fatty acids, including double-bond positional isomers, trans-fatty acids, and iso-fatty acids using reversed-phase high-performance liquid chromatography coupled with Fourier transform mass spectrometry (LC/FTMS). Clear separation of these fatty acids was achieved using a C18 column and a basic eluent. A three-pump gradient system using acetone provided rapid elution within 22 min. In a single run, 184 fatty acid molecular species contained in a dietary fish oil supplement were detected by the FTMS full scan. A previously unreported peak was also detected, which was assigned as tetratriacontadecaenoic acid by comparison with the MS2 profiles of fatty acids with known chemical structures. This result demonstrates that the developed method is useful for clarifying the composition of fatty acid molecular species in target samples, providing a promising approach to discover unreported fatty acids.

[A Case of Multiple Lymph Node Metastases Treated with Nivolumab after an Adrenalectomy for Solitary Adrenal Metastasis of Gastric Cancer after a Gastrectomy].

A 69-year-old man was hospitalized for gastric cancer. He underwent total gastrectomy with distal pancreatectomy, splenectomy, and cholecystectomy. Pathological staging was pT3N3aM0 and Stage ⅢB. Adjuvant chemotherapy(S-1)was administered postoperatively. Ten months later, left adrenal metastasis was detected on computed tomography(CT)scans. He was then treated with 4 courses of chemotherapy with SOX therapy and 2 courses of PTX plus RAM therapy for the left adrenal metastasis. However, the tumor size increased. He underwent adrenalectomy with left nephrectomy and partial resection of the transverse colon for the solitary adrenal metastasis. His pathological diagnosis was metastatic carcinoma of the left adrenal gland and lymph nodes, which invaded the left renal vein and originated from gastric carcinoma. Three months after the adrenalectomy, CT scans identified paraaortic, porta hepatis, and left supraclavicular lymph node metastases. The patient was continuously treated with nivolumab, for 20 courses, and is doing well with good PS. Adrenalectomy for solitary adrenal metastasis of gastric cancer very rarely occurs. We report a case of multiple lymph node metastases treated with nivolumab after an adrenalectomy for solitary adrenal metastasis of gastric cancer after a gastrectomy.

[Successful Treatment of Necrotizing Fasciitis Due to Ascending Colon Cancer-A Case Report].

A 70-year-old woman was brought to our hospital by ambulance because of severe groin pain on the right side. Computed tomography scan revealed a tumor in the ascending colon, intraperitoneal abscess spread to the subcutaneous tissues, and a large amount of pneumoderma. She was diagnosed with necrotizing fasciitis caused by penetration of ascending colon cancer and underwent lavage and drainage, right hemicolectomy, end ileostomy, and debridement of necrotic tissues on emergency. Postoperatively, she underwent debridement and irrigation at the bedside every day, but the necrotizing tissues spread. Debridement under general anesthesia was repeated on postoperative day 8. On postoperative day 20, negative pressure wound therapy(NPWT)was initiated to manage the exudates and wound condition, and healthy granulation tissues formed gradually. After 4 weeks, she underwent split-thickness skin graft implantation. The postoperative course was uneventful, and she was discharged from the hospital. She is currently on chemotherapy and has been alive for 1 year and 3 months after the first operation.

Applicability of an Integrated Testing Strategy consisting of in silico, in chemico and in vitro assays for evaluating the skin sensitization potencies of isocyanates.

The skin sensitization potential of chemicals has been traditionally assessed using regulatory accepted in vivo methods, such as guinea pig maximization test or mouse local lymph node assays (LLNAs). A huge effort to reduce and replace the use of animals for safety assessments of chemicals because of regulatory requirements and ethical issues is presently underway, and alternative non-animal methods have been greatly developed. So far, a few studies have investigated the sensitization potencies of isocyanates which is a group of highly reactive chemicals that are known to be occupational allergens. The present study evaluated nine commonly used isocyanates using an in vivo LLNA and assessed the applicability of an Integrated Testing Strategy (ITS) consisting of an in silico Derek Nexus prediction, an in chemico direct peptide reactivity assay (DPRA), and an in vitro human Cell Line Activation Test (h-CLAT) to isocyanates. All nine isocyanates were evaluated as positive using the LLNA, Derek Nexus and DPRA, whereas seven chemicals tested positive using the h-CLAT: hexamethylene diisocyanate tested negative, and 1,5-diisocyanatonaphthalene could not be examined because of a solubility issue. When assessed using the ITS, the positive/negative evaluations of skin sensitization hazard were consistent with those assessed using the LLNA for all nine chemicals. However, the potency prediction results of the ITS tended to be underestimated, compared with those of the LLNA. The data presented in this work provide insights into the performance of non-animal testing approaches for evaluating the skin sensitization potencies of isocyanates.

Kinetics and dissolution of intratracheally administered nickel oxide nanomaterials in rats.

BACKGROUND: The toxicokinetics of nanomaterials are an important factor in toxicity, which may be affected by slow clearance and/or distribution in the body. METHODS: Four types of nickel oxide (NiO) nanoparticles were single-administered intratracheally to male F344 rats at three doses of 0.67-6.0 mg/kg body weight. The rats were sacrificed under anesthesia and the lung, thoracic lymph nodes, bronchoalveolar lavage fluid, liver, and other organs were sampled for Ni burden measurement 3, 28, and 91 days post-administration; Ni excretion was measured 6 and 24 h after administration. Solubility of NiO nanoparticles was determined using artificial lysosomal fluid, artificial interstitial fluid, hydrogen peroxide solution, pure water, and saline. In addition, macrophage migration to trachea and phagosome-lysosome-fusion rate constants were estimated using pulmonary clearance and dissolution rate constants. RESULTS: The wire-like NiO nanoparticles were 100% dissolved by 24 h when mixed with artificial lysosomal fluid (dissolution rate coefficient: 0.18/h); spherical NiO nanoparticles were 12% and 35% dissolved after 216 h when mixed with artificial lysosomal fluid (1.4 × 10-3 and 4.9 × 10-3/h). The largest irregular-shaped NiO nanoparticles hardly dissolved in any solution, including artificial lysosomal fluid (7.8 × 10-5/h). Pulmonary clearance rate constants, estimated using a one-compartment model, were much higher for the NiO nanoparticles with a wire-shape (0.069-0.078/day) than for the spherical and irregular-shaped NiO nanoparticles (0-0.012/day). Pulmonary clearance rate constants of the largest irregular-shaped NiO nanoparticles showed an inverse correlation with dose. Translocation of NiO from the lungs to the thoracic lymph nodes increased in a time- and dose-dependent manner for three spherical and irregular-shaped NiO nanoparticles, but not for the wire-like NiO nanoparticles. Thirty-five percent of the wire-like NiO nanoparticles were excreted in the first 24 h after administration; excretion was 0.33-3.6% in that time frame for the spherical and irregular-shaped NiO nanoparticles. CONCLUSION: These findings suggest that nanomaterial solubility differences can result in variations in their pulmonary clearance. Nanoparticles with moderate lysosomal solubility may induce persistent pulmonary inflammation.

Effects of pentobarbital, isoflurane, or medetomidine-midazolam-butorphanol anesthesia on bronchoalveolar lavage fluid and blood chemistry in rats.

Bronchoalveolar lavage fluid (BALF) is commonly examined for pulmonary toxicity in animal studies. Two common means of anesthesia before euthanasia and bronchoalveolar lavage in rats are intraperitoneal injection of pentobarbital and inhalation of isoflurane. Medetomidine-midazolam-butorphanol is an alternative anesthesia to pentobarbital for animal welfare; however, the effect of this combination on BALF and blood chemistry is unknown. Here, we compared the effects of anesthesia by intraperitoneal injection of pentobarbital or one of two combinations of medetomidine-midazolam-butorphanol (dose, 0.375-2.0-2.5 or 0.15-2.0-2.5 mg/kg) or by inhalation of isoflurane on BALF and blood chemistry in rats with or without pulmonary inflammation. In BALF, we determined total protein, albumin, lactate dehydrogenase, total cell count and neutrophil count. In serum, we conducted a general chemistry screen. After anesthesia with pentobarbital or isoflurane, there were no significant differences between any of the BALF or blood chemistry parameters with or without inflammation. After anesthesia with either of the combinations of medetomidine-midazolam-butorphanol, lactate dehydrogenase, total cell count, neutrophil count, and almost all of the blood chemistry parameters were comparable with those observed after pentobarbital or isoflurane; however, BALF albumin and serum glucose were significantly increased in rats without inflammation. After the combination of low-dose medetomidine in rats with inflammation, BALF parameters were comparable with those observed after pentobarbital or isoflurane. Our results show that, of the anesthetics examined, inhalation of isoflurane is the most appropriate means of anesthesia when examining BALF or serum for toxicity studies in rats.

Effects of dose volume and delivery device on bronchoalveolar lavage parameters of intratracheally administered nano-sized TiO2 in rats.

The intratracheal (IT) test is useful for screening the pulmonary toxicity of inhaled materials, including nanomaterials. However, a standard procedure has not yet been authorized internationally, and the effects of different test parameters are unknown. To determine appropriate experimental conditions for the IT test, we intratracheally administered nano-sized TiO2 to male F344 rats at 3.0 mg/kg body weight by using two delivery devices (gavage needle or microaerosolizer) and dose volumes of 0.5-3.0 mL/kg (gavage needle) or 0.5-2.0 mL/kg (microaerosolizer). We evaluated the pulmonary deposition and interlobar distribution of TiO2 at both 30 min and 3 days after administration. In addition, the inflammatory components in bronchoalveolar lavage (BAL) fluid were measured 3 days after administration of TiO2. At dose volumes of 0.5-2.0 mL/kg, the BAL values were comparable regardless of the device used. In addition, pulmonary TiO2 burden and lobar concentration patterns were equivalent at all combinations of dose volume and delivery device. In conclusion, the acute pulmonary toxicity of nanomaterials can be assessed effectively by using an IT test in which the test agent is provided to rats at a dose volume of 0.5-2.0 mL/kg with either a gavage needle or microaerosolizer.

[A Case of Mesenteric Fibromatosis after Robot-Assisted Total Gastrectomy for Gastric Cancer].

The patient underwent robot-assisted total gastrectomy for an early gastric cancer. Thirty-four months later, he was admitted to another hospital because of abdominal discomfort. Computed tomography scans showed a giant solid mass approximately 13 cm in diameter in the lower abdomen. We performed a resection of the tumor; operative findings showed a giant solid tumor, without adhesion, in the mesentery of the jejunum. The tumor did not involve other parts of the small intestine. The resected tumor had a smooth surface with an elastic hard consistency. Pathological examination revealed that the tumor was immunohistochemically positive for a-SMA and b-catenin and negative for S-100, CD34, and c-kit. The tumor was diagnosed as a mesenteric fibromatosis. The patient did not show any incidence of recurrence for five months after resection. Mesenteric fibromatosis is a very rare condition and has been reported in association with Gardner's syndrome, abdominal traumas such as surgery and injury, and with pregnancy. This report describes a case of mesenteric fibromatosis after robotassisted laparoscopic surgery.