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A laparoscopia, também conhecida como cirurgia de buraco da fechadura, é a arte de realizar cirurgias por meio de pequenas incisões de 0,5 a 1,5 cm, usando pequenos instrumentos telescópicos especializados. Um laparoscópio é um tubo estreito com uma câmera e lentes acopladas a ele. As vantagens da cirurgia laparoscópica sobre a tradicional cirurgia de incisão aberta incluem diminuição da dor pós-operatória, diminuição do sangramento, menor tempo de internação, convalescença e recuperação mais precoces, com complicações como infecções pulmonares, coágulos nas pernas e pulmões minimizados com a mobilização precoce. Este estudo teve como objetivo analisar os benefícios da laparoscopia na cirurgia urológica em caso de patologia benigna. Para isso, foi desenvolvida uma revisão integrativa de literatura, realizando-se a seleção de fontes de estudo nas bases de dados Medline e Lilacs. Com base na análise qualitativa de dados, concluiu-se que a laparoscopia na cirurgia urológica em patologias benignas apresenta uma série de benefícios ao serem comparadas a cirurgias abertas convencionais, tais como: menor sangramento, diminuição da morbidade operatória, alta hospitalar precoce, menor dor no pós-operatório, efeitos estéticos mais adequados e retomada precoce das atividades habituais. No caso de pessoas Testemunhas de Jeová, registram-se menores níveis de sangramento e redução da necessidade de transfusão.

In the global trend towards decarbonization, peer-to-peer (P2P) energy trading is garnering increasing attention. Furthermore, energy management on the demand side plays a crucial role in decarbonization efforts. The authors have previously developed an automated bidding agent that considers user preferences for renewable energy (RE), assuming users own electric vehicles (EVs). In this study, we expand upon this work by considering users who own not only EVs but also heat pump water heaters, and we develop an automated bidding agent that takes into account their preferences for RE. We propose a method to control the start time and presence of daytime operation shifts for heat pump water heaters, leveraging their daytime operation shift function. Demonstration experiments were conducted to effectively control devices such as EVs and heat pumps using the agent. The results of the experiments revealed that by controlling the daytime operation of heat pumps with our method, the RE utilization rate can be improved compared to scenarios without daytime operation shifts. Furthermore, we developed a simulator to verify the outcomes under different scenarios of demand-side resource ownership rates, demonstrating that higher ownership rates of EVs and heat pumps enable more effective utilization of renewable energy, and that this effect is further enhanced through P2P trading. Based on these findings, we recommend promoting the adoption of demand-side resources such as EVs and heat pumps and encouraging P2P energy trading to maximize the utilization of renewable energy in future energy systems.

Body weight change resulting from once-daily oral administration of TAS6417

Activated HER2 is a promising therapeutic target for various cancers. Although several reports have described HER2 inhibitors in development, no covalent-binding inhibitor selective for HER2 has been reported. Here, we report a novel compound TAS0728 that covalently binds to HER2 at C805 and selectively inhibits its kinase activity. Once TAS0728 bound to HER2 kinase, the inhibitory activity was not affected by a high ATP concentration. A kinome-wide biochemical panel and cellular assays established that TAS0728 possesses high specificity for HER2 over wild-type EGFR. Cellular pharmacodynamics assays using MCF10A cells engineered to express various mutated HER2 genes revealed that TAS0728 potently inhibited the phosphorylation of mutated HER2 and wild-type HER2. Furthermore, TAS0728 exhibited robust and sustained inhibition of the phosphorylation of HER2, HER3, and downstream effectors, thereby inducing apoptosis of HER2-amplified breast cancer cells and in tumor tissues of a xenograft model. TAS0728 induced tumor regression in mouse xenograft models bearing HER2 signal–dependent tumors and exhibited a survival benefit without any evident toxicity in a peritoneal dissemination mouse model bearing HER2-driven cancer cells. Taken together, our results demonstrated that TAS0728 may offer a promising therapeutic option with improved efficacy as compared with current HER2 inhibitors for HER2-activated cancers. Assessment of TAS0728 in ongoing clinical trials is awaited (NCT03410927).

Methods for in vitro kinase assay, genome sequence, and immunoblotting analysis

Establishment of a cell line tool with an EGFR exon 20 insertion mutation

Inhibitory activity and kinase selectivity of TAS6417 in biochemical assays

The list of 68 non-kinase targets tested in a panel of binding assays

Synthesis procedures and characterization data for the synthesis of TAS6417

Assignment of MSE fragmentation data for protease-digested peptide with TAS6417

IC50 values of TAS0728 against kinases

Synthetic procedures

Activating mutations in the EGFR gene are important targets in cancer therapy because they are key drivers of non–small cell lung cancer (NSCLC). Although almost all common EGFR mutations, such as exon 19 deletions and the L858R point mutation in exon 21, are sensitive to EGFR-tyrosine kinase inhibitor (TKI) therapies, NSCLC driven by EGFR exon 20 insertion mutations is associated with poor clinical outcomes due to dose-limiting toxicity, demonstrating the need for a novel therapy. TAS6417 is a novel EGFR inhibitor that targets EGFR exon 20 insertion mutations while sparing wild-type (WT) EGFR. In cell viability assays using Ba/F3 cells engineered to express human EGFR, TAS6417 inhibited EGFR with various exon 20 insertion mutations more potently than it inhibited the WT. Western blot analysis revealed that TAS6417 inhibited EGFR phosphorylation and downstream molecules in NSCLC cell lines expressing EGFR exon 20 insertions, resulting in caspase activation. These characteristics led to marked tumor regression in vivo in both a genetically engineered model and in a patient-derived xenograft model. Furthermore, TAS6417 provided a survival benefit with good tolerability in a lung orthotopic implantation mouse model. These findings support the clinical evaluation of TAS6417 as an efficacious drug candidate for patients with NSCLC harboring EGFR exon 20 insertion mutations. Mol Cancer Ther; 17(8); 1648–58. ©2018 AACR.

Purpose Laparoscopic colectomy for transverse colon cancer (TCC) can be technically demanding due to the anatomical complexity of the region. In Japan, the Endoscopic Surgical Skill Qualification System (ESSQS) was established to improve the skill of laparoscopic surgeons and further develop surgical teams. We examined the safety and feasibility of laparoscopic colectomy for TCC, and evaluated the effects of the Japanese ESSQS in facilitating this approach. Methods We retrospectively reviewed 136 patients who underwent laparoscopic colectomy for TCC between April 2016 and December 2021. Patients were divided into an expert group (surgery performed by an ESSQS-qualified surgeon, n = 52) and a non-expert group (surgery performed by an ESSQS-unqualified surgeon, n = 84). Clinicopathological and surgical features were compared between groups. Results Postoperative complications occurred in 37 patients (27.2%). The proportion of patients who developed postoperative complications was lower in the expert group (8.0%) than in the non-expert group (34.5%; p

The violent 2022 Tonga submarine volcanic eruption produced globally propagating atmospheric disturbance. The short explosive eruption generated a leading Lamb wave pulse that are recorded as a pressure pulse worldwide. A weather station network in Japan recorded the pressure pulse as well as temperature and winds during the passage of the Lamb pressure pulse. Individual temperature and wind records indicate little simultaneous change. However, after aligning temperature and wind records at the timing of pressure pulse arrivals and stacking, we obtain clear temperature and wind changes synchronized with the pressure change. By assuming Lamb wave propagation synthesized temperature and wind changes from the pressure record match well the observed waveforms. Observed wind speed and pressure change of the Lamb pulse directly yield the total energy transported by the pulse to be 4.2 x 10 J.

Background Esophageal duplication cyst (EDC) is a type of gastrointestinal duplication cyst that involves congenital malformations of the gastrointestinal tract. EDCs are frequently found in the mediastinum and thoracoabdominal region, but rarely occur in the abdominal cavity. However, intra-abdominal EDCs are frequently found in the upper abdomen near the abdominal esophagus. Here, we report, for the first time, a case of intra-abdominal EDC that occurred in the ileum. Case presentation A 14-year-old female patient presented to our hospital with complaints of epigastric pain and vomiting. Abdominal computed tomography (CT) revealed a cystic tumor in the pelvis, suspected of ovarian origin. She was admitted to our gynecology department and underwent emergency surgery. The laparoscopic examination revealed that both ovaries were intact and that a primary tumor had developed from the ileal mesentery. Since the patient’s condition was not urgent at the time of the gynecological surgery, the procedure was completed by only performing exploratory laparotomy; the patient was admitted to our department after the surgery. Pelvic magnetic resonance imaging performed on the next day revealed a cystic mass measuring 90 × 65 mm with a smooth margin and homogeneous signal intensity, arising posterior to the uterus. The mass was suspected as an intestinal duplication cyst. On another day, after the examinations were completed, we resected the portion of the small intestine containing the tumor by laparoscopy. The patient had a successful postoperative course and was discharged on the 5th postoperative day. Histological examination showed that the cyst was lined by stratified squamous epithelium, contained esophageal glands, and had a two-layer muscularis propria. Therefore, a diagnosis of intra-abdominal EDC was performed. Conclusions An intra-abdominal EDC cyst is relatively rare; this is the first case reported at the distal ileum.

We report the unusual case of a 68-year-old man with coral reef aorta complicated with severe calcified valvular heart disease who has been undergoing dialysis for 21 years. This report highlights the etiology and the unusual manifestations of coral reef aorta in a long-term dialysis patient. (Level of Difficulty: Intermediate.), Central Illustration

There has been a growing interest in transdisciplinary approaches to improve the added value of cities, such as smart cities. To add value to a city, not only the hard infrastructure but also the soft systems are important. Systematic distribution of incentives such as the holding of events and the issuing of coupons is significant as a means of creating liveliness in cities. This paper proposes a system that supports effective incentive selection using a human flow simulator. A part of the city, including a station and commercial facilities, is reproduced on the simulator by modeling the customer behavior based on actual data. We simulate the behavioral paths of individual customers with different incentives. The list of the incentives is proposed and the result of the simulation suggests insights for the selection of the appropriate incentive to improve sales and the liveliness of the city as a whole.

In last mile delivery, to manage delivery default risks and ensure delivery completion, reserve personenel are placed. This is due to driver procurement having to be planned and executed about one-month ahead, when delivery demands could only be roughly predicted. Although reserve drivers occasionally work as final defense, it regularly lowers driver utility, and a method to place reserve drivers balancing delivery default risk and driver utility is required. Previous work tackled this problem by stochastic staffing problem approaches, but there existed a limit in feature modelling and result interpretability, which created a gap in algorithms and procurement manager decision making. The proposed method aims to fill this gap, by taking a transdisciplinary approach of traditional scheduling, probability modelling, and explainable AI. In doing so, a flow of first creating a staffing schedule based on fixed staffing number demands, and then determining a fixed number of reserve personnel required for each staffing window, was designed. A probablity distribution of required personnel number per delivery is calculated in doing so, and this distribution is used as a easy to understand decision support tool for delivery managers. Through a case study using delivery demand data of a Japanese EC-logistics company, the proposed method was shown capable of lowering reserve drivers, with having a high potential of no delivery defaults.

In recent years, with the expansion of the e-commerce market and the improvement of customer requirements and service levels, express operators have fallen into a shortage of truck drivers. The operator’s distribution channel optimization reaches its limit, and an e-commerce system assisted by customers is needed. Through SDGs and other goals, people pay more attention to social problems. Thus, customers are highly likely to cooperate. However, the indicators of e-commerce operators’ contribution to social issues have not been established yet. Operators have set different goals, and customers can not compare various operators. What impact will it bring to the logistics industry with the cooperation of consumers with high environmental awareness? Therefore, the purpose of this study is “logistics operators set common goals related to social issues, and consumers can also evaluate logistics operators” and “logistics operators propose customer cooperative e-commerce to achieve this goal and test its effectiveness.” As a method to achieve these purposes, “adopting the concept definition of ethical e-commerce and making evaluation indicators,” “establishing a system for calculating the latest excess load when new orders arrive,” and “inspired by China’s logistics, what SDGs goals can logistics operators achieve with the help of consumers” are introduced.

Decarbonisation of social infrastructures such as airports have attracted wide attention. In commiting to the global decarbonisation target, introduction of renewable energy is important. However, few research has focused on the specifications of renewable energy facilities for airports. Thus, it is vital to enable airport operators to determine the necessary facility specifications for installing renewable energy systems. Moreover, the efficiency of battery operation influences the necessary facility specifications. Yet, many previous studies have proposed linear battery optimisation, even though forecasts for renewable energy supply include uncertainties derived from natural factors, and demand forecasts can also fluctuate due to future uncertainties. This study provides a framework for analysing the cost efficiency of photovoltaic systems, wind systems, and batteries to determine the optimal specifications for each hardware to achieve 100% renewable electricity. Further, it proposes a novel battery operation algorithm considering uncertainties of supply and demand forecasts. A case study on Chubu Centrair International Airport was conducted. The results show practical steps for the airport to achieve decarbonisation. In addition, battery operation based on the proposed algorithm outperformed the linear optimisation in the unpredicted rain weather scenario. It can be said that the proposed method performs well in considering uncertainties.

Objective: Fibroblast growth factor (FGF)23 suppresses erythropoiesis and is implicated in iron metabolism. It was investigated whether high levels of FGF23 was associated with hepcidin levels of iron metabolism markers in hemodialysis patients. Methods: The serum hepcidin, erythroferrone, and intact-FGF23 or total-FGF23 level as well as iron-related parameters at pre-dialysis in 70 hemodialysis (HD) patients was measured and performed a regression analysis. Results: Each measurement for FGF23, including the intact-/total-FGF23 ratio, correlated strongly with both serum inorganic phosphate and calcium-phosphate product concentrations. Serum hepcidin levels showed a positive correlation with TSAT or serum ferritin concentration. In addition, a negative correlation was found between serum of hepcidin and erythroferrone levels, but no correlation was found between FGF23-related measurements and serum hepcidin levels. Both serum FGF23 levels and erythroferrone levels correlated with erythropoietin-stimulating agent treatment. Conclusion: It was strongly suggested that both serum phosphate concentrations and calcium-phosphate products were associated with FGF23 production in HD patients. As previously reported, the association between hepcidin and iron metabolism markers was reconfirmed, but a simple linear relationship between hepcidin and FGF23 was not observed even after adjusting FGF23. However, a significant negative correlation between erythroferrone and serum hepcidin levels was confirmed in HD patients.

The emergence of multicellularity is a key event in the evolution of life and is an attractive challenge among researchers, including those investigating the artificial design of cellular behavior1. Multicellular organisms are widely distributed on Earth, and retracing the specific conditions conducive for the initial transition from unicellularity to multicellularity is difficult. However, by examining organisms that inhabit unique (e.g., isolated) environmental niches, we may be able to get a glimpse into primitive multicellularity in the context of a given environment. Here we report the discovery of a new bacterium that displayed multicellular-like characteristics and behavior. The bacterium, which was isolated adjacent to an underground stream in a limestone cave, is to be named Jeongeupia sacculi sp. nov. HS-3. On a solid surface, HS-3 self-organizes its filamentous cells to form an appearance similar to the nematic phase of a liquid crystal2. Mature colonies produce and accommodate clusters of coccobacillus progeny, and release them upon contact with water. HS-3 demonstrated novel, spatiotemporally regulated multicellularity that can resolve the so-called ‘competition-dispersal trade-off’ problem3. This study illustrates a hypothetical missing link on the emergence of multicellularity.

Anaerobic digestion is an energy-generating, ecologically friendly waste/wastewater treatment process. However, treatment of anaerobic digestion effluent (ADE) and purification of carbon dioxide in the biogas, commonly called biogas upgrading, are two issues that prevent propagation of this process. Since ADE contains high concentrations of nutrients, it can be utilized for microalgal cultivation if the chemical composition is optimized for the purpose. Microalgal cultivation is at the same time a promising platform to capture and utilize carbon dioxide in biogas. Therefore, simultaneous ADE utilization and biogas upgrading can be possible by coupling microalgal culture. Previous studies using the simultaneous process adopted open pond systems with algal-bacterial consortium. Although these processes were effective in treatment of both ADE and biogas, the volumetric productivity and economic value of the microalgal biomass are low in such systems. Thus, this study aimed to establish a simultaneous algal pure culture and biogas upgrading using centrifuged supernatant of anaerobic digestion effluent from an activated sludge treatment facility. To achieve this goal, the ADE concentration, pH, dissolved inorganic carbon, and metal composition were adjusted by batch optimization tests with Chlorella sorokiniana. The optimized ADE media was then scaled up to 4-L photobioreactor (PBR) coupled with a 1.8-L gas/liquid exchange column for simultaneous processing. Since the current study adopted algal pure culture in a closed PBR, gas/liquid transfer was expected to be different from previous studies, and thus, three liquid circulation flow rates (1, 2 and 4 L d-1) were tested, which resulted in liquid to gas ratio (L/G) of 0.1, 0.3 and 0.5. As a result, the ADE media was optimized to 10% ADE content, pH 8.0, 0.1 mol L-1 bicarbonate addition, and Mg + Mn addition. While the raw ADE did not allow the growth of Chlorella sorokiniana, the maximum algal specific growth rate using the optimized media reached more than 2 d-1, which equals a doubling time of less than 9 hours. The optimized media was then used for the simultaneous microalgae cultivation and biogas upgrading process. The average productivity in the PBR was 206 ±138 mg L-1 d-1. The carbon dioxide recovery rates for L/G 0.1, 0.3, and 0.5 were 90, 94, and 99%, respectively. On the other hand, O2 contents in the upgraded gas were 8.5, 8, and 14%, respectively. The content of carbon dioxide and O2 were in a reverse relationship over various L/G ratios. The current study demonstrated the effectiveness of carbon capture from the biogas, but also suggested further challenge in prevention of oxygen intrusion from algal pure culture. Comparisons with other studies suggest that optimization in gas/PBR volume may enhance the quality of biogas upgrading.

The efficacy of laparoscopic multivisceral resection (Lap-MVR) has been reported by several experienced high-volume centers. The Endoscopic Surgical Skill Qualification System (ESSQS) was established in Japan to improve the skill of laparoscopic surgeons and further develop surgical teams. We examined the safety and feasibility of Lap-MVR in general hospitals, and evaluated the effects of the Japanese ESSQS for this approach. We retrospectively reviewed 131 patients who underwent MVR between April 2016 and December 2019. Patients were divided into the laparoscopic surgery group (LAC group, n = 98) and the open surgery group (OPEN group, n = 33). The clinicopathological and surgical features were compared between the groups. Compared with the OPEN group, BMI was significantly higher (21.9 vs 19.3 kg/m2, p = 0.012) and blood loss was lower (55 vs 380 ml, p

A 61-year-old woman who underwent hemodialysis presented with heart failure. Echocardiography revealed multiple mobile masses in the left atrium. The masses were excised, and histopathologic examination revealed calcified amorphous tumors. Here, we present several echocardiography images, including 3-dimensional transesophageal echocardiography, demonstrating the revolving masses in the left atrium. (Level of Difficulty: Intermediate.), Central Illustration

Purpose Although the safety and comparable long-term outcomes after laparoscopic surgery (LAP) for advanced colon cancer versus open surgery (OP) were previously reported, the indications for highly advanced colon cancer are controversial. We aimed to assess long-term outcomes after LAP versus OP for pathological T4 (pT4) and/or N2 (pN2) colon cancer. Methods We retrospectively reviewed 255 primary tumor resections for pT4 and/or pN2 colon cancer performed from 2015 to 2020 at six hospitals, divided into LAP (n = 204) and OP groups (n = 51). After propensity score matching to minimize selection bias, 42 matched patients per group were assessed. Results Before matching, the rate of males (53.9% vs 37.3%, p = 0.042), left sided colon cancer (53.9% vs 37.3%, p = 0.042), D3 lymph node dissection (90.7% vs 68.6%, p

Background Conflicting results between bacterial mutagenicity tests (the Ames test) and mammalian carcinogenicity tests might be due to species differences in metabolism, genome structure, and DNA repair systems. Mutagenicity assays using human cells are thought to be an advantage as follow-up studies for positive results in Ames tests. In this collaborative study, a thymidine kinase gene mutation study (TK6 assay) using human lymphoblastoid TK6 cells, established in OECD TG490, was used to examine 10 chemicals that have conflicting results in mutagenicity studies (a positive Ames test and a negative result in rodent carcinogenicity studies). Results Two of 10 test substances were negative in the overall judgment (20% effective as a follow-up test). Three of these eight positive substances were negative after the short-term treatment and positive after the 24 h treatment, despite identical treatment conditions without S9. A toxicoproteomic analysis of TK6 cells treated with 4-nitroanthranilic acid was thus used to aid the interpretation of the test results. This analysis using differentially expressed proteins after the 24 h treatment indicated that in vitro specific oxidative stress is involved in false positive response in the TK6 assay. Conclusions The usefulness of the TK6 assay, by current methods that have not been combined with new technologies such as proteomics, was found to be limited as a follow-up test, although it still may help to reduce some false positive results (20%) in Ames tests. Thus, the combination analysis with toxicoproteomics may be useful for interpreting false positive results raised by 24 h specific reactions in the assay, resulting in the more reduction (> 20%) of false positives in Ames test.

The use of Q-switched erbium:yttrium-aluminum-garnet laser (Er:YAG laser), which have much less thermal effects than conventional Er:YAG lasers, has been proposed mainly in the medical field. The purpose of this study was to evaluate the bonding ability of dentin after Q-switched Er:YAG laser irradiation.The effects of dentin irradiation with Q-switched and conventional lasers were evaluated in terms of dentin morphology, roughness, hardness, elemental content, and resin bonding strength. Q-switched Er:YAG laser at average power densities of 20, 40, and 60 W/cm

Although adjuvant chemotherapy (AC) using fluoro-pyrimidine and oxaliplatin (FU + oxaliplatin) is recommended after curative resection for locally advanced colon cancer patients, several randomized controlled trials have shown no additional effect of oxaliplatin in patients aged ≥ 70 years. Here, we examined the effectiveness of FU + oxaliplatin on the long-term outcome of old patients with a high risk of recurrence.This multicenter, retrospective study included 346 colon cancer patients diagnosed with pathological T4 and/or N2 disease from 2016 to 2020. They were divided into an old group (≥ 70 years, n = 197) and a young group ( 70 years, n = 167). Propensity score matching was used to minimize selection bias, and 126 patients per group were matched.Before matching, the rates of poor performance status (p 0.001) and the presence of comorbidities (76.1% vs. 47.9%, p 0.001) were higher in the old group. Although all baseline factors were similar between groups, after matching, the AC rate was lower in the old group (45.2% vs. 65.1%, p = 0.002). In the old group, relapse-free (82.2% vs. 55.6% and 69.6%, p 0.05) and overall survival (83.1% vs. 80.0% and 44.4%, p 0.05) rates were significantly higher in the AC patients with FU + oxaliplatin than in the AC patients with only FU and the non-AC patients.The selected old colon cancer patients with a high risk of recurrence gained an additional benefit with respect to prognosis from FU + oxaliplatin as AC.

Compact lasers capable of producing kilowatt class peak power are highly desirable for applications in various fields, including laser remote sensing, laser micromachining, and biomedical photonics. In this paper, we propose a high-peak-power chip-scale semiconductor/solid-state vertically integrated laser in which two cavities are optically coupled at the solid-state laser gain medium. The first cavity is for the intra-pumping of ytterbium-doped yttrium aluminum garnet (Yb:YAG) with an electrically driven indium gallium arsenide (InGaAs) quantum well, and the second cavity consists of Yb:YAG and chromium-doped yttrium aluminum garnet (Cr:YAG) for passive Q-switching. The proposed laser produces pulses as short as 450 ps, and an estimated peak power of 57.0 kW with a laser chip dimension of 1 mm3. To the best of our knowledge, this is the first monolithic integration of semiconductor and solid-state laser gain mediums to realize a compact high-peak-power laser.