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The field of quantum technologies has garnered considerable interest and witnessed noteworthy progress in recent years. It is also anticipated that these technologies will continue to flourish and exert a considerable influence on society, i.e., a plethora of real-world problems that cannot be solved by classical algorithms are believed to benefit from the implementation of quantum algorithms. Meanwhile, as an alternative to cryptographic methods, physical layer security (PLS) has been extensively studied as a means to realize secure wireless communication that is resistant to attacks by both classical and quantum computers, i.e., quantum-safe. While the prevailing approach to PLS has been based on classical algorithms, this could potentially be accelerated by the application of quantum algorithms. This paper examines the potential applications of various quantum algorithms, including quantum annealing, hybrid quantum-classical algorithms, and Grover-based algorithms, to the the PLS problems. In particular, we begin with a concise overview of their applications to physical layer techniques and then proceed to discuss their use in addressing the challenges of secret message transmission and secret key generation from wireless channels.

Abstract The Fukushima Daiichi Nuclear Power Plant accident caused the release of large amounts of radioactive material into the environment. Radiation from radionuclides cause DNA lesions, mainly via oxidation, which adversely affect wild organisms by damaging their germ cells. Here, we investigated the effects of radiation on the reproductive organs of Japanese field mice (Apodemus speciosus) by estimating the dose rate of radiation exposure, the accumulation of DNA lesions, and the expression of DNA repair enzymes. In highly contaminated areas, mouse testes received a radiation dose rate > 0.1 mGy/d. According to the International Commission on Radiological Protection, there is a very low probability of effects in the reference rat species at this exposure level. The results of the current study do not definitively conclude that the expression of 8-oxoguanine DNA glycosylase 1 and superoxide dismutase in mouse testes increase with dose rate and lifetime dose. However, 8-hydroxy-2′-deoxyguanosine accumulation increases in a dose rate- and lifetime dose-dependent manner in mouse testes, but is not observed in the sperm of the cauda epididymis. These results suggest that, although DNA lesions occurred in male germ cells of Fukushima mice, most were successfully repaired by DNA repair enzymes at the observed gene expression level.

Abstract Genetic backgrounds of patients with pulmonary arterial hypertension (PAH) were not fully investigated. A variant of c.14429G > A (p.Arg4810Lys) in the ring finger protein 213 gene (RNF213) was recently identified as a risk allele for poor treatment response and poor clinical prognosis in patients with PAH. However, the molecular mechanisms of the RNF213 p.Arg4810Lys variant in development of PAH are unknown. We investigated the underlying molecular mechanisms of RNF213-associated vasculopathy using an in vivo mouse model. RNF213 +/p.Arg4828Lys mice, harboring the heterozygous RNF213 p.Arg4828Lys variant corresponding to the p.Arg4810Lys variant in humans, were created using the CRISPR-Cas9 system to recapitulate the genetic status of PAH patients. RNF213 +/p.Arg4828Lys mice had a significant elevation of the right ventricular systolic pressure, hypertrophy of the right ventricle, and increased thickness of the pulmonary arterial medial wall compared with wild-type mice after 3 months of exposure to a hypoxic environment. C-X-C motif chemokine ligand 12 (CXCL12), a C-X-C chemokine receptor type 4 (CXCR4) ligand, was significantly elevated in the lungs of RNF213 +/p.Arg4828Lys mice, and PAH was ameliorated by the administration of a CXCR4 antagonist. CXCL12-CXCR4 is an angiogenic chemokine axis, and immunohistochemistry demonstrated an increase in CXCR4 in vimentin-positive spindle-shaped cells in adventitia and interstitial lesions in RNF213 +/p.Arg4828Lys mice and lung specimens from severe PAH patients with the RNF213 p.Arg4810Lys variant. We confirmed a cause-and-effect relationship between the RNF213 p.Arg4810Lys variant and PAH via the CXCL12-CXCR4 pathway. The findings in this study suggest that targeting this pathway might be a novel therapeutic strategy for RNF213-associated vasculopathy.

Abstract A critical issue in laser powder bed fusion (LPBF) additive manufacturing is the selective vaporization of alloying elements resulting in poor mechanical properties and corrosion resistance of parts. The process also alters the part’s chemical composition compared to the feedstock. Here we present a novel multi-physics modeling framework, integrating heat and fluid flow simulations, thermodynamic calculations, and evaporation modeling to estimate and control the composition change during LPBF of nickel-based superalloys. Experimental validation confirms the accuracy of our model. Moreover, we quantify the relative vulnerabilities of different nickel-based superalloys to composition change quantitatively and we examine the effect of remelting due to the layer-by-layer deposition during the LPBF process. Spatial variations in evaporative flux and compositions for each element were determined, providing valuable insights into the LPBF process and product attributes. The results of this study can be used to optimize the LPBF process parameters such as laser power, scanning speed, and powder layer thickness to ensure the production of high-quality components with desired chemical compositions.

The serious problems of skin inflammations (dermatitides) observed in the users of rubber gloves caused by type I or type IV hypersensitivity strongly require their new manufacturing methods free from these irritations. This paper reports our novel approach to the production of rubber gloves addressing these problems. A synthetic rubber latex, carboxylated nitrile butadiene rubber (XNBR), was crosslinked using polyvalent epoxy compounds (PECs) without the utilization of accelerators that cause those dermatitides. Although epoxy compounds are generally hydrolyzable in alkaline latex solution, optimally hydrophobic PECs, especially a PEC with three epoxy groups derived from trimethylolpropane, were found to be effective crosslinking reagents for producing high performance XNBR films. The methyl isobutyl ketone (MIBK)-water partition coefficient is an advantageous index to select suitable PECs in this process. The XNBR film produced by the PEC from trimethylolpropane had a high durability to simulated perspiration liquid and the pot-life of the mixed latex solution was longer than 7 days. The XNBR films produced by our novel process that contain no substances causing type I and type IV hypersensitivity are potentially free from the skin inflammations.

Abstract Although sequence-based studies show that basal-like features lead to worse prognosis and chemotherapy-resistance compared to the classical subtype in advanced pancreatic ductal adenocarcinoma (PDAC), a surrogate biomarker distinguishing between these subtypes in routine diagnostic practice remains to be identified. We aimed to evaluate the utility of immunohistochemistry (IHC) expression subtypes generated by unsupervised hierarchical clustering based on staining scores of four markers (CK5/6, p63, GATA6, HNF4a) applied to endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) materials. EUS-FNAB materials taken from 190 treatment-naïve advanced PDAC patients were analyzed, and three IHC patterns were established (Classical, Transitional, and Basal-like pattern). Basal-like pattern (high co-expression of CK5/6 and p63 with low expression of GATA6 and HNF4a) was significantly associated with squamous differentiation histology (p

Porosity defects are inherently present in Ti–6Al–4V (Ti6-4) parts produced using additive manufacturing (AM) methods like laser powder-bed fusion (LPBF). This work aims to investigate different laser-inherent porosity defects at various LPBF parameter settings and assess their impact on the fatigue behaviour of Ti6-4 implants processed by LPBF. The presence of LPBF-inherent porosity defects with different shapes and sizes was established using microstructural examination and X-ray micro-CT analysis. These mostly comprise lack-of-fusion porosity (LoFP), gas-entrapped porosity (GeP), and pores-induced microcracks. Volumetric porosity defects were seen to range from 1.9 × 104 to 9.52 × 105 μm3. The L-1 specimen exhibited the lowest defect, while the L-6 specimen displayed the largest number of defects. While LoFP defects predominate in L-6, there was a notable presence of GeP defects in the specimens processed using the factory default condition (L-D). Upon examination of the majority of specimens, GeP and LoFP coalesced to form clusters, leading to the formation of pores-induced microcracks. This ultimately leads to a decrease in fatigue performance. By maintaining the power at the default setting and increasing the scan speed by 8% of the default value, a specimen (L-1) with minimal porosity defects and superior fatigue performance is achieved. L-6 exhibits defects with significant dimensions and irregular form. Consequently, it displays inferior fatigue characteristics.

Abstract Porosity in directed energy deposition (DED) deteriorates mechanical performances of components, limiting safety-critical applications. However, how pores arise and evolve in DED remains unclear. Here, we reveal pore evolution mechanisms during DED using in situ X-ray imaging and multi-physics modelling. We quantify five mechanisms contributing to pore formation, migration, pushing, growth, removal and entrapment: (i) bubbles from gas atomised powder enter the melt pool, and then migrate circularly or laterally; (ii) small bubbles can escape from the pool surface, or coalesce into larger bubbles, or be entrapped by solidification fronts; (iii) larger coalesced bubbles can remain in the pool for long periods, pushed by the solid/liquid interface; (iv) Marangoni surface shear flow overcomes buoyancy, keeping larger bubbles from popping out; and (v) once large bubbles reach critical sizes they escape from the pool surface or are trapped in DED tracks. These mechanisms can guide the development of pore minimisation strategies.

A 19-year-old man with a history of Peutz-Jeghers syndrome (PJS) and two previous partial small bowel resections because of intussusception presented with lower abdominal pain. Computed tomography (CT) showed concentric multilayer and cord-like structures in the transverse colon. Colo-colonic intussusception was suspected and he was hospitalized. After two therapeutic enemas were unsuccessful, a colonoscopy was performed. The intussusception was reduced and a 40-mm transverse colon polyp with a thick stalk was resected. After the procedure, his abdominal pain was relieved and he was discharged on the sixth hospital day. This case and several previous reports suggest that PJS polyps with tumor diameter exceeding 30 mm and location in the transverse or sigmoid colon can cause intussusception. Endoscopic treatment should be considered for these lesions.

Abstract Background Pulmonary inflammatory leiomyosarcoma (PILMS) is a rare type of myogenic tumor with prominent lymphohistiocytic infiltration. Despite their histological similarities, PILMS is immunohistochemically and genetically distinct from soft tissue inflammatory leiomyosarcoma, and its clinicopathological picture including DNA methylome data remains still unknown. Case presentation Here we present a case of PILMS in an 18-year-old male who underwent lobectomy. As reported previously, the current case demonstrated spindle myoid cell proliferation with smooth muscle differentiation within a prominent lymphohistiocytic infiltration and a diploid genome with a MUC3A gene alteration. DNA methylation analysis predicted this case to be an “inflammatory myofibroblastic tumor” (IMT) according to the Deutsches Krebsforschungszentrum (DKFZ) classifier. The data was analyzed by t-distributed stochastic neighbor embedding, which plotted the case tumor in the vicinity of IMT, however, there were no IMT histological features. These discordant results could be due to background non-neoplastic inflammatory cells. Conclusions As the DNA methylation classification of PILMS might be a potential diagnostic pitfall, an integrative histological and genetic approach is required for its accurate diagnosis.

IntroductionSepsis is a life-threatening inflammatory condition caused by dysregulated host responses to infection. Extracellular cold-inducible RNA-binding protein (eCIRP) is a recently discovered damage-associated molecular pattern that causes inflammation and organ injury in sepsis. Kupffer cells can be activated and polarized to the inflammatory M1 phenotype, contributing to tissue damage by producing proinflammatory mediators. We hypothesized that eCIRP promotes Kupffer cell M1 polarization in sepsis.MethodsWe stimulated Kupffer cells isolated from wild-type (WT) and TLR4-/- mice with recombinant mouse (rm) CIRP (i.e., eCIRP) and assessed supernatant IL-6 and TNFα levels by ELISA. The mRNA expression of iNOS and CD206 for M1 and M2 markers, respectively, was assessed by qPCR. We induced sepsis in WT and CIRP-/- mice by cecal ligation and puncture (CLP) and assessed iNOS and CD206 expression in Kupffer cells by flow cytometry.ResultseCIRP dose- and time-dependently increased IL-6 and TNFα release from WT Kupffer cells. In TLR4-/- Kupffer cells, their increase after eCIRP stimulation was prevented. eCIRP significantly increased iNOS gene expression, while it did not alter CD206 expression in WT Kupffer cells. In TLR4-/- Kupffer cells, however, iNOS expression was significantly decreased compared with WT Kupffer cells after eCIRP stimulation. iNOS expression in Kupffer cells was significantly increased at 20 h after CLP in WT mice. In contrast, Kupffer cell iNOS expression in CIRP-/- mice was significantly decreased compared with WT mice after CLP. CD206 expression in Kupffer cells was not different across all groups. Kupffer cell M1/M2 ratio was significantly increased in WT septic mice, while it was significantly decreased in CIRP-/- mice compared to WT mice after CLP.ConclusionOur data have clearly shown that eCIRP induces Kupffer cell M1 polarization via TLR4 pathway in sepsis, resulting in overproduction of inflammatory cytokines. eCIRP could be a promising therapeutic target to attenuate inflammation by preventing Kupffer cell M1 polarization in sepsis.

Abstract Pseudoinvasion is a phenomenon in which adenomatous tissue deviates into the submucosa with the mucosal lamina propria in colorectal epithelial tumors. A relatively large, stalked, neoplastic lesion of the sigmoid colon is considered at high risk of pseudoinvasion. A few reports have described endoscopic mucosal resection or polypectomy for colorectal tumors with pseudoinvasion, but the vertical margins were not sufficiently assessed. Because a positive margin can be a risk factor for recurrence, endoscopic treatment for pseudoinvasion should be carefully considered. We herein report a case in which even endoscopic submucosal dissection (ESD) was not adequate for curative resection of pseudoinvasion in early colorectal cancer. The endoscopic findings of a 25‐mm Type 0‐Is lesion in the sigmoid colon suggested a low possibility of carcinoma invasion into the deep submucosa. Although ESD was considered to be indicated in this case, laparoscopic sigmoid colon resection was eventually performed because we observed a broadly pulled muscle layer and an almost undetectable submucosal layer during ESD. The surgical specimen showed that the tumor glands of pseudoinvasion existed beyond the planned ESD dissection line, indicating that the vertical margin would have been positive if we had continued ESD. Whether pseudoinvasion was associated with the infeasibility of ESD remains unclear. This case indicates that diagnosing the presence and depth of pseudoinvasion by magnified endoscopy with narrow‐band imaging is challenging and that preoperative examinations, such as endoscopic ultrasound, may be needed for a tumor with a high risk of pseudoinvasion.

In this case, a 66-year-old female patient presented with the chief complaint of abdominal distention. Computed tomography and magnetic resonance imaging revealed no enlarged ovaries or obvious primary lesions; however, massive ascites and peritoneal disseminated nodules were observed. Ascites cytology revealed adenocarcinoma and immunohistochemical findings suggested serous carcinoma. The patient then underwent tumor reduction surgery after preoperative chemotherapy for suspected Stage IIIC primary peritoneal carcinoma. Postoperative histopathology revealed carcinoma consisting mainly of high-grade serous carcinoma (HGSC) and sarcoma. In addition, serous intraepithelial carcinoma (STIC) of the fallopian tube was observed in the fimbriae of the left fallopian tube. Recently, it has been noted in the literature that most cases of peritoneal carcinoma are metastases or dissemination of carcinoma originating from the fimbriae of the fallopian tube. This is a rare case of peritoneal carcinosarcoma with STIC, and its report leads to a better understanding of the disease’s features and possible therapeutic approaches.

Bulk metallic glasses (BMGs) are non-crystalline class of advanced materials and have found potential applications in the biomedical field. Although there are numerous conventional manufacturing approaches for processing BMGs, the most commonly used like copper-mould casting have some limitations. It is not easy to manage and control the critical cooling rate, especially when the fabrication of complex BMG geometries is involved. Other limitations of these techniques include the size constraints, non-flexibility, and the tooling and accessories are costly. The emergence of additive manufacturing (AM) has opened another promising manufacturing route for processing BMGs. AM processes, particularly laser powder-bed fusion (PBF-LB/M) builds parts layer-by-layer and successively fused the powder-melted feedstocks using prescribed computer-controlled laser scanner system, thereby forming a BMGs part upon sufficiently rapid cooling to ensure the glass forming-ability. PBF-LB/M overcomes the limitations of the pre-existing BMGs processing techniques by not only improving the part size, but also produces exceptionally complex structures and patient-specific implants. This review article aims to summarise and discuss the mechanism of BMGs formation through PBF-LB/M for biomedical applications and to highlight the current scientific and technological challenges as well as the future research perspectives towards overcoming the pore-mediated microcracks, partial crystallisation, brittleness and BMG size constraint.

We consider a basic system to securely and remotely control many IoT devices. Specifically, we require that: 1) a system manager broadcasts information to IoT devices, e.g., wireless environment, only the designated devices can identify operations sent from the manager; 2) each IoT device can detect (malicious) manipulation of the broadcast information and hence prevents maliciously generated operations from being executed. In this paper, we introduce anonymous broadcast authentication (ABA) as a core cryptographic primitive of the basic remote-control system. Specifically, we formally define the syntax and security notions for ABA so that it achieves the above requirements. We then show provably-secure ABA constructions and their implementations to provide their practical performance. Our promising results show that the ABA constructions can remotely control devices over a typical wireless network within a second.

Several types of mucinous lesions of the fallopian tube have been reported, including metaplastic and neoplastic lesions, most of which exhibit gastric phenotypes. Here, we report a unique case of a mucinous tumor arising in the right fallopian tube of a 36-year-old female who presented with refractory abdominal pain for approximately one year. Abdominal CT and MRI found a cystic lesion leading to the diagnosis of hematosalpinx, thus right salpingo-oophorectomy and appendectomy were performed. Macroscopic findings included cystic dilatation of the distal portion of the right fallopian tube, filled with gelatinous mucin. Histologically, mucinous columnar cells proliferated in papillary configurations in the cystic region without invasion, resembling low-grade appendiceal mucinous neoplasms. Immunohistochemical analysis revealed that the neoplastic cells expressed CDX-2 and SATB2, but not WT-1, PAX8, ER, PgR, or claudin 18. Sanger sequencing of the mucinous lesion identified a KRAS exon 2 mutation (p.G12A), confirming similar pathologic and genetic characteristics to ovarian mucinous borderline tumors. This rare low grade intestinal-type mucinous tumor indicates the fallopian tube epithelium can give rise to tumors resembling low-grade appendiceal mucinous neoplasms and cause pseudomyxoma peritonei without appendiceal lesions.

The advent of the Internet of Things brought a new age of interconnected device functionality, ranging from personal devices and smart houses to industrial control systems. However, increased security risks have emerged in its wake, in particular self-replicating malware that exploits weak device security. Studies modeling malware epidemics aim to predict malware behavior in essential ways, usually assuming a number of simplifications, but they invariably simplify the single most important subdynamics of malware: random propagation. In our previous work, we derived and presented the first exact mathematical model of random propagation, defined as the subdynamics of propagation of a malware model. The propagation dynamics were derived for the SIS model in discrete form. In this work, we generalize the methodology of derivation and extend it to any Markov chain model of malware based on random propagation. We also propose a second method of derivation based on modifying the simplest form of the model and adjusting it for more complex models. We validated the two methodologies on three malware models, using simulations to confirm the exactness of the propagation dynamics. Stochastic errors of less than 0.2% were found in all simulations. In comparison, the standard nonlinear model of propagation (present in ∼95% of studies) has an average error of 5% and a maximum of 9.88% against simulations. Moreover, our model has a low mathematical trade-off of only two additional operations, being a proper substitute to the standard literature model whenever the dynamical equations are solved numerically.

Although current guidelines recommend the use of prostanoid infusion that includes epoprostenol for high-risk pulmonary arterial hypertension patients, epoprostenol has many adverse effects. We report a case of a heritable pulmonary arterial hypertension patient who had transient biventricular hypertrophy during high-dose administration of epoprostenol. In this case, biventricular hypertrophy with worsening of dyspnea was observed during the uptitration of epoprostenol. Inflammatory diseases and endocrine disorders were ruled out as causes of the ventricular hypertrophy. After epoprostenol was changed to intravenous treprostinil, the biventricular hypertrophy normalized, in connection with dyspnea improvement. The use of high-dose epoprostenol may contribute to cardiac hypertrophy. Résumé: Bien que les lignes directrices en vigueur recommandent les perfusions de prostanoïdes comprenant de l’époprosténol chez les patients à risque élevé atteints d’hypertension artérielle pulmonaire, les effets indésirables de l’époprosténol sont nombreux. Nous décrivons ici le cas d’un patient atteint d’hypertension artérielle pulmonaire héréditaire ayant présenté une hypertrophie biventriculaire transitoire pendant le traitement par de l’époprosténol à dose élevée. Pour ce patient, une hypertrophie biventriculaire accompagnée d’une aggravation des symptômes de dyspnée ont été observées lors de l’ajustement à la hausse de la dose d’époprosténol. Les maladies inflammatoires et les troubles endocriniens ont été écartés comme facteurs étiologiques de l’hypertrophie ventriculaire. Après le remplacement de l’époprosténol par du tréprostinil intraveineux, l’hypertrophie biventriculaire s’est résorbée, et les symptômes de dyspnée se sont atténués. Il semble donc que l’utilisation de l’époprosténol à dose élevée puisse contribuer à l’hypertrophie cardiaque.

ABSTRACT: Growth in chickens, especially meat-type chickens (broilers), is extremely rapid, but studies on the regulatory mechanism of intestinal glucose absorption with growth are few, contradictory, and unclear. Here, we investigated the regulation of intestinal glucose absorption with growth in broiler chickens using oral glucose gavage, intestinal Evans blue transit, intestinal glucose absorption, scanning electron microscopy, and glucose absorption- and cell junction-related gene expression analyses. Peak blood glucose levels after oral glucose gavage occurred at 10 and 50 min in chickens at 1 wk (C1W) and 5 wk (C5W) of age, respectively. The area under the curve for glucose levels was greater for the C5W than the C1W (P = 0.035). The stain ratio in the small intestine in the C5W was lower than that in the C1W (P = 0.01), but there were no differences in the tissue regions stained with Evans blue and the migration distance of Evans blue from Meckel's diverticulum. In everted sac and Ussing chamber experiments, we observed reduced intestinal glucose uptake and electrogenic glucose absorption in the jejunum of the C5W. Phloridzin, an inhibitor of sodium/glucose cotransporter 1 (SGLT1), suppressed the glucose-induced short-circuit current in the C1W (P = 0.016) but not the C5W. Although the addition of NaCl solution stimulated the glucose-induced short-circuit current in the C1W, no differences between the treatments were observed (P = 0.056), which was also the case in the C5W. Additionally, tissue conductance was diminished in the C5W compared with that in the C1W. Moreover, in the C5W, the intestinal tract was more developed and the jejunal villi were enlarged. In conclusion, glucose absorption throughout the intestine could be greater in C5W than in C1W; however, reduced SGLT1 sensitivity, decreased ion permeability, and intestinal overdevelopment lead to decreased local glucose absorption in the jejunum with growth in broiler chickens. These data provide a detailed analysis of intestinal glucose absorption in growing broiler chickens, and can contribute to the development of novel feeds.

# Background/Purpose This study aimed to evaluate how a two-week program using the in-phase mode of a balance adjustment system (the BASYS) affected postural control in participants with chronic ankle instability (CAI). It was hypothesized that the in-phase mode on the BASYS would lead to improved postural control compared with training on a balance disc. # Study Design Randomized control trial. # Methods Twenty participants with CAI were recruited. The participants were divided into two intervention groups: the BASYS (n = 10) and Balance Disc (BD; cushion type, n = 10). All participants underwent six supervised training sessions over a two-week period. Static postural control during single leg standing with closed eyes was assessed for the CAI limb. We collected COP data while participants balanced on the BASYS. The test was performed for 30 sec, and the total trajectory length and 95% ellipse area were calculated. In the assessment of dynamic postural stability, Y-Balance tests-anterior, posteromedial, and posterolateral directions were measured on the CAI limb for all participants and normalized to the individual's leg length. Participants were recorded at three instances: pretraining (Pre), post-training 1 (Post1: after the first training), and post-training 2 (Post2: after the last training). # Results There was an effect on time in the COP total trajectory length of the BASYS group, which was significantly decreased for Post 1 and Post 2 than for the Pre (p = 0.001, 0.0001). Group differences and time-by-group interactions were not observed for either of the Y-balance test reach distances. # Conclusions The study's primary finding was that two weeks of intervention in the in-phase mode on the BASYS improved static postural control in participants with CAI. # Level of Evidence Level Ⅰ, randomized control trial

Abstract Background Sodium-glucose cotransporter 2 inhibitors are a novel class of anti-hyperglycemic agents. Although several cases of perioperative euglycemic diabetic ketoacidosis have been linked to these medications, the association remains unclear. This study aimed to examine the association between sodium-glucose cotransporter 2 inhibitor use and the incidence of perioperative metabolic acidosis with euglycemia, the surrogating outcome of perioperative euglycemic diabetic ketoacidosis. Method This was a retrospective, matched cohort study, which was conducted in the intensive care unit of a tertiary care facility in Japan. We identified patients aged 20 years or older with diabetes mellitus who received pharmacologic therapy and were admitted to the intensive care unit after elective surgery between April 2014 and March 2019. We extracted the following data from the electronic medical record for matching: age, sex, surgery year, surgical site, hemoglobin A1c level, and prescription for sodium-glucose cotransporter 2 inhibitors. Eligible patients were divided into two groups, those who were prescribed sodium-glucose cotransporter 2 inhibitors (SGLT2-i group) and those who were not (control group). For each patient in the SGLT2-i group, we randomly selected four patients from the control group matched for the extracted characteristics. The primary outcome was the incidence of metabolic acidosis with an elevated anion gap and euglycemia. The secondary outcome was the lowest pH value of each patient during their ICU stay. Results A total of 155 patients were included in this study. Patients receiving sodium-glucose cotransporter 2 inhibitors had comparable characteristics to control participants; however, the proportions of patients undergoing dialysis were not similar. Metabolic acidosis with euglycemia was seen in 7/31 (22.6%) patients receiving sodium-glucose cotransporter 2 inhibitors and in 10/124 (8.1%) control patients (p = 0.047). Conclusions This study shows that the use of sodium-glucose cotransporter 2 inhibitors is associated with a significantly higher incidence of metabolic acidosis with euglycemia. Patients receiving sodium-glucose cotransporter 2 inhibitors who are scheduled to undergo invasive surgical procedures should be closely monitored for the development of euglycemic diabetic ketoacidosis.

G47Δ is a third-generation, triple-mutated oncolytic HSV-1 that has demonstrated anti-tumor efficacy in preclinical studies. Here the authors report the results of a phase I/II study of G47Δ in patients with recurrent or progressive glioblastoma.

Abstract An 81‐year‐old man with chronic pancreatitis was being treated with a protease inhibitor. He developed an acute exacerbation of chronic pancreatitis and dyspnea. Contrast‐enhanced computed tomography showed disruption of the main pancreatic duct, a cystic lesion connecting the mediastinum to the main pancreatic duct, and left pleural effusion. We diagnosed a pancreatic pseudocyst, mediastinal pancreatic pseudocyst, and pancreatic pleural effusion. Endoscopic retrograde pancreatography showed leakage of contrast medium from the pancreatic body; furthermore, a cystic cavity extending to the mediastinum through a pancreatic duct fistula was visualized. An endoscopic transpapillary nasopancreatic drainage tube was placed in the cystic cavity. Computed tomography showed that the mediastinal pseudocyst and pleural effusion had disappeared. Endoscopic transpapillary pancreatic duct drainage may be useful when a connection between the main pancreatic duct and a mediastinal pseudocyst is confirmed by imaging.

In this paper, we investigate the impact of a bit-labeling scheme on security performance of bit-interleaved coded modulation (BICM) systems for the Gaussian wiretap channel, where the concept of security gap plays an important role. To exemplify this, we present optimization algorithms of bit-labeling, where a difference of the achievable information rates (AIRs) for the legitimate receiver and the eavesdropper is maximized. Our results demonstrate that the conventional Gray labeling may not be necessarily optimal in terms of security gap, and the proposed bit-labeling can significantly improve its performance at the cost of degradation in the achievable bit-error rate (BER) performance by the legitimate receiver. We also demonstrate that, for high order quadrature amplitude modulation (QAM), such as 64QAM, the dimension-wise optimization of bit-labeling may be sufficient to achieve similar security gap performance to the direct two-dimensional optimization. The proposed bit-labeling optimization approach can be combined with the state-of-the-art coding schemes to further reduce a security gap.

Small bowel capsule endoscopy (SBCE) is a convenient and minimally invasive method widely used to evaluate the small intestine. However, especially in the distal ileum, visualization of the intestinal mucosa is frequently hampered by the remaining intestinal contents, making it difficult to detect critical lesions. Although several studies have reported on the efficacy of bowel preparation before SBCE, no standardized protocol has been established. Herein, we determined the optimal preparation method for better visualization of the distal ileum using SBCE. We retrospectively analyzed 259 consecutive patients who had undergone SBCE between July 2009 and December 2019, divided into three groups: Group A (no preparation except overnight fasting), Group B (ingestion of 1–2 L polyethylene glycol 4 h before colonoscopy after overnight fasting and performing SBCE immediately after colonoscopy), and Group C (ingestion of 0.9 L magnesium citrate [MC] before SBCE after overnight fasting). The visibility of the intestinal mucosa in the first 10 min and at the last 10 min during the period of observation of the distal ileum was examined using a scoring system and compared. The visibility of the images captured by SBCE was assessed based on the scoring of the degree of bile/chyme staining, residual fluid and debris, brightness, bubble reduction, and visualized mucosa. The status of intestinal collapse was also assessed. In the first 10 min of observation of the distal ileum, no significant differences were detected among the groups. In the last 10 min, significantly better images were acquired in Group C in terms of bile/chyme staining, brightness, bubble reduction, and visualized mucosa. Bowel preparation using a low-dose MC solution 2 h before SBCE provided significantly higher-quality images of the distal ileum. Further optimization, such as the timing of initiating the preparation, is necessary to determine the optimal regimen for bowel preparation prior to SBCE.

Abstract Background Adenosquamous carcinoma of the prostate (ASCP) is an extremely rare and aggressive prostate cancer variant, whose genomic characteristics have not been elucidated. Although liquid biopsy of circulating tumor cells (CTCs) is an emerging topic in oncology, no study has assessed CTCs in patients with ASCP. Case presentation. A 76-year-old man presented with discomfort in his urethra. His prostate-specific antigen (PSA) level was 13.37 ng/mL. A computed tomography (CT) scan indicated a prostate mass with multiple lymph node and lung metastases. The patient underwent transurethral resection of the prostate and prostatic needle biopsy; both specimens demonstrated Gleason grade group 5 acinar adenocarcinoma of the prostate. Bone scintigraphy indicated bone metastasis in the ischium. Combined androgen blockade was implemented, and his serum PSA level rapidly decreased to 0.01 ng/mL. However, a CT scan 6 months after the initial diagnosis revealed worsening of the disease. The patient therefore underwent repeated prostatic needle biopsy; its specimen demonstrated prostatic adenocarcinoma together with squamous carcinoma components. As immunohistochemical analyses showed the tumor cells to be negative for CD56, chromogranin A, synaptophysin, and PSA, the definitive diagnosis was ASCP. Although the patient underwent chemotherapy (docetaxel and cabazitaxel), he died of the disease 3 months after the diagnosis of ASCP, or 13 months after the initial diagnosis of prostatic adenocarcinoma. His PSA values remained ≤ 0.2 ng/mL. CTCs from the patient’s blood (collected before starting docetaxel) were analyzed and genomically assessed. It showed 5 cytokeratin (CK)+ CTCs, 14 CK− CTCs, and 8 CTC clusters, per 10 mL. Next-generation sequencing identified a total of 14 mutations in 8 oncogenes or tumor suppressor genes: PIK3CB, APC, CDKN2A, PTEN, BRCA2, RB1, TP53, and CDK12. Of 14 mutations, 9 (64%) were detected on CK− CTCs and 5 (36%) were detected on CK+ CTCs. Conclusions This is the first report of CTC analysis and genomic assessment in ASCP. Although the prognosis of ASCP is dismal due to lack of effective treatment, genomic analysis of CTCs might lead to effective treatment options and improved survival.

Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare a rare subtype of hepatocellular carcinoma. The IMbrave150 trial demonstrated that atezolizumab and bevacizumab therapy (ABT) has better treatment outcomes than sorafenib for advanced HCC. However, since patients with known FLHCC were excluded from this trial, the effects of ABT on FLHCC remain unknown. We report the first case of ABT for advanced FLHCC followed by hepatectomy presenting pseudoprogression of lymph node (LN) metastases which was pathologically proven after surgery. The patient was a 30-year-old man with advanced FLHCC and multiple LN metastases behind the pancreatic head, and ABT was introduced. After four courses of treatment, CT indicated a minor decrease in the intratumor vascularity of the liver tumor. However, the size of metastatic LNs increased. Subsequently, the patient presented with bloody stool, and colonoscopy revealed immune-related colitis caused by atezolizumab. Therefore, the fifth course was canceled. A right hemihepatectomy following percutaneous transhepatic portal vein embolization (PTPE) was performed to increase the future liver remnant volume. After PTPE, dynamic CT revealed an objective response to ABT; SD in RECIST 1.1 (7% increase in the LN size and no change of liver tumor), and PR in modified RECIST (47% decrease in the intratumor vascularity of the liver tumor and LNs). Three weeks after PTPE, right hemihepatectomy plus nodal dissection was successfully performed. Pathological findings revealed that approximately 60%–70% of the liver tumor and 70%–80% of the metastatic LNs were necrotic, indicating a good response to ABT. The increasing size of metastatic LNs that occurred during the treatment course was deemed pseudoprogression. Pseudoprogression can be found in patients with solid malignancies treated with immune checkpoint inhibitors, however, rarely occurs in HCC. The first response to metastatic LNs was observed 20 weeks after ABT initiation combined with an increase in nodal volume and a decrease in vascularity. In the updated data of the IMbrave150 trial, 19% of the first responses occurred after week 24. Physicians should consider that ABT may also be effective in FLHCC and may cause pseudoprogression before determining a treatment strategy.

Pheochromocytoma/paraganglioma (PPGL)-related hypercatecholaminemic crisis is a rare lethal condition caused by uncontrolled catecholamine secretion, occasionally leading to critical fluctuation in blood pressure (BP). Emergent transcatheter arterial embolization (TAE) has been employed for spontaneous PPGL rupture, but never, to our knowledge, for critical fluctuation in BP associated with PPGL-related hypercatecholaminemic crisis. We describe here our experience utilizing this method to control critical fluctuation in BP associated with this crisis in a 44-year-old man with an unruptured retroperitoneal paraganglioma. The patient experienced sudden severe left abdominal pain and came to our emergency department, where he exhibited severe fluctuation in BP and underwent laboratory testing that showed hypercatecholaminuria and computed tomography (CT) that revealed a left retroperitoneal tumor with no apparent intra- or retroperitoneal hematoma. We performed emergent TAE from the left inferior phrenic artery using gelatin sponge, which stabilized his BP and relieved his abdominal pain. Histologic examination following elective surgical resection of the tumor confirmed our diagnosis of unruptured retroperitoneal paraganglioma. We believe that TAE represents an important option for the emergent treatment of the critical BP fluctuation associated with PPGL-related hypercatecholaminemic crisis.

Abstract Oligodendrogliomas are defined by mutation in isocitrate dehydrogenase (NADP(+)) (IDH)1/2 genes and chromosome 1p/19q codeletion. World Health Organisation diagnosis endorses testing for 1p/19q codeletion to distinguish IDH mutant (Mut) oligodendrogliomas from astrocytomas because these gliomas require different treatments and they have different outcomes. Several methods have been used to identify 1p/19q status; however, these techniques are not routinely available and require substantial infrastructure investment. Two recent studies reported reduced immunostaining for trimethylation at lysine 27 on histone H3 (H3K27me3) in IDH Mut 1p/19q codeleted oligodendroglioma. However, the specificity of H3K27me3 immunostaining in this setting is controversial. Therefore, we developed an easy-to-implement immunohistochemical surrogate for IDH Mut glioma subclassification and evaluated a validated adult glioma cohort. We screened 145 adult glioma cases, consisting of 45 IDH Mut and 1p/19q codeleted oligodendrogliomas, 30 IDH Mut astrocytomas, 16 IDH wild-type (Wt) astrocytomas, and 54 IDH Wt glioblastomas (GBMs). We compared immunostaining with DNA sequencing and fluorescent in situ hybridization analysis and assessed differences in H3K27me3 staining between oligodendroglial and astrocytic lineages and between IDH1-R132H and non-canonical (non-R132H) IDH1/2 Mut oligodendroglioma. A loss of H3K27me3 was observed in 36/40 (90%) of IDH1-R132H Mut oligodendroglioma. In contrast, loss of H3K27me3 was never seen in IDH1-R132L or IDH2-mutated 1p/19q codeleted oligodendrogliomas. IDH Mut astrocytoma, IDH Wt astrocytoma and GBM showed preserved nuclear staining in 87%, 94%, and 91% of cases, respectively. A high recursive partitioning model predicted probability score (0.9835) indicated that the loss of H3K27me3 is frequent to IDH1-R132H Mut oligodendroglioma. Our results demonstrate H3K27me3 immunohistochemical evaluation to be a cost-effective and reliable method for defining 1p/19q codeletion along with IDH1-R132H and ATRX immunostaining, even in the absence of 1p/19q testing.

Introduction Median raphe cysts are rare benign lesions of the male genitalia that can develop anywhere along the midline from meatus to anus. They are believed to be caused by a defect in closure of median raphe during embryonic development. These cysts commonly appear in childhood or adolescence, although some are diagnosed after middle age, typically triggered by infection or trauma. Pigmented median raphe cysts, or those containing melanin pigment and/or melanocytes, are extremely rare. Case presentation A 78‐year‐old man visited our hospital with a complaint of a penile mass that he first noticed in his 50s which slowly grew, eventually causing voiding difficulty. He had no history of infection or trauma. The lesion was excised, and the pathological diagnosis was pigmented median raphe cyst. Conclusion We successfully treated a rare case of pigmented median raphe cyst of the penis that developed after middle age without infection or trauma history.

Sepsis is characterized by life-threatening organ dysfunction caused by a dysregulated host response to infection. Extracellular cold-inducible RNA-binding protein (eCIRP) is a damage-associated molecular pattern (DAMP) that promotes inflammation and induces cell death via apoptosis, NETosis, and/or pyroptosis. Ferroptosis is a form of regulated cell death characterized by the accumulation of lipid peroxide on cellular membranes. We hypothesize that eCIRP induces ferroptosis in macrophages and lung tissue during sepsis. RAW 264.7 cells stimulated with recombinant murine (rm) CIRP significantly decreased the expression of glutathione peroxidase 4 (GPX4), a negative regulator of ferroptosis, and increased lipid reactive oxygen species (ROS) in a TLR4 dependent manner. In TLR4-/- peritoneal macrophages, depression of GPX4 expression and increase in lipid ROS levels were attenuated after rmCIRP-treatment compared to WT macrophages. rmCIRP also induced cell death in RAW 264.7 cells which was corrected by the ferroptosis inhibitor, ferrostatin-1 (Fer-1). Intraperitoneal injection of rmCIRP decreased GPX4 expression and increased lipid ROS in lung tissue, whereas the increase of lipid ROS was reduced by Fer-1 treatment. GPX4 expression was significantly decreased, while malondialdehyde (MDA), iron levels, and injury scores were significantly increased in lungs of WT mice after cecal ligation and puncture (CLP)-induced sepsis compared to CIRP-/- mice. Treatment with C23, a specific eCIRP inhibitor, in CLP mice alleviated the decrease in GPX4 and increase in MDA levels of lung tissue. These findings suggest that eCIRP induces ferroptosis in septic lungs by decreasing GPX4 and increasing lipid ROS. Therefore, regulation of ferroptosis by targeting eCIRP may provide a new therapeutic approach in sepsis and other inflammatory diseases.

Abstract Background Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B) is a standard method for pathological diagnosis of pancreatic solid lesions. The EchoTip ProCore 20G® (PC20), a 20-gauge biopsy needle with a forward-bevel core trap, has been available in Japan since 2015. Methods We compared the efficacy of the PC20 with that of the EchoTip ProCore 22G® (PC22) and Acquire 22G® (AC22) in EUS-FNA/B for diagnosing pancreatic cancer. This retrospective study included 191 patients with pancreatic cancer who underwent EUS-FNA/B using the PC20, PC22, or AC22 at our facility from April 2013 to October 2019. We investigated the patients’ clinical characteristics and the diagnostic accuracy and safety of each needle. Results A sufficient stroke length of puncture was secured in all patients. The maximum length under EUS was shorter with the AC22 (22.1 ± 2.2 mm) than PC20 (30.6 ± 0.7 mm, p 0.99). One patient (0.9%) in the PC20 group developed mild pancreatitis, but no adverse events occurred with the other needles. Conclusions The PC20 showed better diagnostic capability than the PC22. The diagnostic efficacy was similar between the PC20 and AC22. The high histological accuracy of the PC20 could be advantageous for lesions in which histological assessment is critical.

Abstract Background With the recent increased use of lanthanum carbonate, several cases of lanthanum phosphate deposition to gastric mucosa in dialysis patients have been reported. However, the endoscopic appearance of the early-stage lesion and the over-time alterations of endoscopic findings due to the progression of lanthanum phosphate deposition remain unclear. Case presentation An 80-year-old man receiving dialysis and taking lanthanum carbonate as a phosphate binder over a 4-year period underwent upper gastrointestinal endoscopy four times beginning 1 year after initiation of treatment. The first endoscopic examination (after 1 year of exposure to lanthanum carbonate) revealed rough mucosa with a few areas of white granular mucosa. Over the 3 years of endoscopic follow-up, the white granular mucosa spread and multiple erosions appeared. Histopathological findings of biopsy specimens from an erosion showed extensive infiltration by histiocytes containing deposits. Scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX) revealed that the presence of the deposits containing phosphorus and lanthanum in the gastric mucosa. On the basis of these results, the patient was diagnosed with gastropathy associated with lanthanum phosphate deposition. Conclusions Over a 3-year period, endoscopic findings associated with lanthanum deposition gradually changed and expanded from the early stage.

Background Studies assessing the effect of suvorexant on delirium prevention included patients treated before development of delirium, which can introduce immortal time bias. The objective of the present study was to evaluate the effect of suvorexant on delirium, comparing patients treated before the onset of delirium with patients treated within 72h of admission using the same dataset. Methods Data from adult patients admitted to the ICU from August 2018 to July 2021 were retrospectively analyzed. In “any time before” analysis, the incidence of delirium was compared for patients who received suvorexant at any time during their ICU stay (suvorexant) (unless delirium developed before treatment) with patients who either did not receive suvorexant or received suvorexant after development of delirium (control). This design was used in previously published studies. In “within 72h” analysis, the incidence of delirium was compared for patients who received suvorexant within 72 hours of admission (suvorexant) and patients who did not receive suvorexant or received it more than 72 hours after admission (control). Patients who developed delirium during the initial 72 hours were excluded from “within 72h” analysis (N = 799). Results “Within 72h” analysis included 1,255 patients, and “any time before” analysis included 2,054 patients (of 6599 admissions). The unadjusted hazard ratio of “any time before” analysis was 0.16 and the 95% confidence interval was 0.13–0.21 (pConclusion Reducing the effect of immortal time bias led to a significantly reduced effect of suvorexant for the prevention of delirium.

Abstract Recent developments in systemic chemotherapy for advanced hepatocellular carcinoma have been outstanding. However, reports on conversion surgery after lenvatinib therapy are scarce. We present the first case of advanced hepatocellular carcinoma with tumor thrombus in the suprahepatic vena cava close to the right atrium, which shrank after 12 weeks’ administration of lenvatinib, thereby leading to successful conversion surgery without using total vascular exclusion or extracorporeal circulation. The treatment strategy for hepatocellular carcinoma with macroscopic hepatic vein tumor thrombus is controversial, however, from a Japanese nationwide survey, surgical resection has been accepted as one of the treatment options for advanced hepatocellular carcinoma with hepatic vein tumor thrombus in Japan. However, the survival rate after resection of hepatocellular carcinoma having inferior vena cava tumor thrombus with extracorporeal circulation was reported to be worse than without extracorporeal circulation, and some preoperative down-sizing therapy for inferior vena cava tumor thrombus was advocated. Preoperative lenvatinib therapy might be a promising option among the multidisciplinary treatments for hepatocellular carcinoma with macroscopic tumor thrombus in the hepatic veins.

Abstract Background Considering the adverse effects of sleep disturbance in critical care settings, accurate assessment could aid therapy; however, methodological inadequacies mean that no viable option is currently available. Research in healthy population has recently shown that a non-wearable sleep measurement device placed under the mattress of the bed could be beneficial in intensive care settings. Therefore, we aimed to validate this device compared with polysomnography (PSG) and to assess how it related to subjective sleep evaluations. Methods This observational study measured the sleep of critically ill adult patients. The primary goal was to validate the Nemuri SCAN (NSCAN; Paramount Bed Co., Ltd., Tokyo, Japan) against the reference standard PSG for 24 h. The secondary goal was to evaluate the association between the objective parameters obtained from NSCAN and PSG and the subjective report data obtained using the Richards–Campbell Sleep Questionnaire (RCSQ) for the nighttime. Results Eleven participants were evaluated. The median of the total sleep time scored by PSG was 456.0 (353.0–517.5) min during the nighttime and 305.0 (186.2–542.5) min during the daytime. PSG over 24 h revealed significant decreases in restorative sleep, with excessive daytime sleep, but with a normal quantity of nighttime sleep. The agreement, sensitivity, and specificity rates (with 95% confidence intervals) for the NSCAN compared with PSG were 68.4% (67.9–69.0%), 90.1% (89.7–90.6%), and 38.7% (37.9–39.7%), respectively. The median RCSQ value when subjectively evaluating nighttime sleep was 68.0 (26.3–83.5); this showed no correlation with the NSCAN sleep parameters, despite a positive correlation with the ratio of the stage N2 isolated or combined with restorative sleep in the PSG assessment. Conclusions NSCAN had moderate agreement, high sensitivity, and poor specificity in intensive care settings, which is most likely due to its inability to identify immobile wakefulness often observed in critically ill patients or sleep depth. This remains a barrier to its use in the assessment of subjective sleep quality. Trial registration This investigation was part of an interventional trial registered with the University Hospital Medical Information Network Individual Clinical Trials Registry ( UMIN000026350 , http://www.umin.ac.jp/icdr/index-j.html ) on March 1, 2017.

We introduce group-testing aggregate message authentication code (GTA MAC) and provide its formal study. We first specify its syntax and security requirements. Then, we present a scheme of generic construction which applies non-adaptive group-testing to aggregate MAC. We also confirm the security of the generic construction based on that of underlying aggregate MAC and a useful property of matrices representing non-adaptive group-testing. In addition, we instantiate the generic construction using the aggregate MAC scheme proposed by Katz and Lindell or a scheme using a cryptographic hash function for aggregating tags. Finally, we present some implementation results to show the effectiveness of our proposed GTA MAC.

Aim The complement system is important for defending against pathogens, however, excessive complement activation is associated with a poor prognosis and organ dysfunction in sepsis. Complement factor H (CFH) acts to prevent excessive complement activation and damage to the self through the regulation of the complement alternative pathway. We investigated the association between plasma CFH levels on admission to the intensive care unit (ICU) and 90‐day mortality, severity scores, and organ dysfunction in patients with sepsis. Methods We assessed the relationship between the plasma CFH on admission to the ICU and 90‐day mortality, severity scores such as the Acute Physiology and Chronic Health Evaluation II score, Sequential Organ Failure Assessment score, and Simplified Acute Physiology Score 2, and organ dysfunction. Results This analysis included 62 patients. The plasma CFH levels were significantly lower in 90‐day non‐survivors than in survivors (70.0 μg/mL [interquartile range, 51.2–97.6] versus 104.8 μg/mL [interquartile range, 66.8–124.2]; P = 0.006) . The plasma CFH levels were associated with 90‐day mortality (odds ratio 0.977; 95% confidence interval, 0.957–0.994; P = 0.01). The plasma CFH levels were negatively correlated with severity scores. The Sequential Organ Failure Assessment scores for the coagulation and neurological components were negatively correlated with the CFH concentration. Conclusion Lower plasma levels of CFH were associated with increased severity and mortality in patients with sepsis on admission to the ICU and were correlated with central nervous system dysfunction and coagulopathy.

Metastatic uterine tumors originating from extragenital cancers are a rare clinical occurrence. We report a case of metastatic uterine cancer derived from small-cell lung cancer (SCLC) that necessitated surgical treatment. The patient was a 59 y/o female who had undergone chemotherapy for stage IIIB SCLC. A 15 cm uterine tumor lesion was initially detected on CT scans. The patient had previously been diagnosed with uterine fibroids, but compared to the most recent CT scans taken one and a half months earlier, imaging diagnosis revealed a sudden increase in the size of the tumor when compared to the 8 cm myoma fibroid noted previously. Additional work-up with MRI scans revealed T2-enhanced images of a tumor that had almost completely invaded the myometrium; the tumor presented with marked diffusion-weighted enhancement, and a flow void was noted within the tumor. A differential diagnosis of uterine sarcoma was considered, but due to the lack of focal hemorrhage or necrosis findings on MRI imaging, the possibility of differential diagnosis of metastatic SCLC was also noted. As the patient was experiencing abdominal symptoms including abdominal distension and tenderness due the tumor, a simple hysterectomy and bilateral salpingo-oophorectomy were performed to palliate the symptoms. During the surgical procedures, intra-abdominal findings noted peritoneal dissemination while intraoperative cell cytology diagnosis of ascites revealed small-cell cancer. The final histopathological diagnosis likewise revealed metastatic small-cell cancer from the primary lung cancer. The clinical status of the lung cancer was evaluated as progressive disease (PD), and a change in chemotherapy regimen was necessitated. Further disease progression was noted on CT scans at 2 and a half months after surgery, and with gradual systemic disease progression, the patient died of disease at 3 months postsurgery. Initial evaluation of rapidly enlarging uterine tumors should include a differential diagnosis of uterine sarcoma; additionally, it is necessary to also consider the rare possibility of metastatic disease as in the present case with a clinical history of extragenital malignancy.

Endoplasmic reticulum (ER) stress has been proposed to play a role in metabolic diseases. Here, Sasako and colleagues identify stromal cell-derived factor 2 like 1 (Sdf2l1) as a regulator of the ER stress response to feeding in the liver, and suggest that its downregulation may promote diabetes and hepatic steatosis in humans.

Abstract Background Recent studies have suggested that quick Sequential Organ Failure Assessment (qSOFA) scores have limited utility in early prognostication in high-mortality populations. The purpose of this study was to investigate the association between pre-ICU qSOFA scores and in-hospital mortality among patients admitted to the ICU with suspected sepsis. This study also aimed to describe detailed clinical characteristics of qSOFA-negative (

Abstract Background Long-term survival after resection of metastases from pancreatic ductal adenocarcinoma is rare. Case presentation A 54-year-old man underwent pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) with UICC staging pT3N1M0 followed by adjuvant chemotherapy with gemcitabine (GEM). Three years after radical resection of the primary tumor, a tiny nodule was found in the lower lobe of the left lung. Despite treatment with GEM, it increased gradually, but no other metastases were found. Eighteen months after the first indication of the nodule, wedge resection was performed. Pathological examination of the nodule indicated a metastatic tumor from PDAC. Pulmonary metastasectomy was again performed for lung oligometastases at 77 and 101 months after PD. The patient has been asymptomatic without tumor recurrence for 4 years since the last pulmonary resection. Conclusions In PDAC, the treatment strategy for oligometastasis is controversial. However, a few cases of long-term survival after pulmonary metastasectomy for oligometastasis of PDAC have been reported. More such cases need to be studied to address this issue effectively.

Introduction Since pheochromocytomas present with various complications due to catecholamine hypersecretion, their perioperative management needs special attention. Case presentation A 45‐year‐old man visited our hospital with a complaint of abdominal swelling. Radiological and endocrinological assessments determined the tumor as a giant (>20 cm) cystic pheochromocytoma. After administration of doxazosin, the patient underwent radical surgery. Since the tumor was extremely large and fixed to surrounding structures, we punctured it and aspirated cystic fluid to improve the tumor's mobility. However, during the aspiration, the patient developed acute hypotension, which could be reversed by suction withdrawal and vasopressor administration. A similar event occurred during a second aspiration. Eventually, the tumor was successfully excised with negative surgical margin. The cystic fluid proved to contain extremely high concentrations of catecholamines, which might result in the hypotension. Conclusion We report the first case who developed acute hypotension due to aspiration of cystic fluid from giant pheochromocytoma.

Abstract Background The Japanese Society of Respiratory Care Medicine and the Japanese Society of Intensive Care Medicine provide here a clinical practice guideline for the management of adult patients with ARDS in the ICU. Method The guideline was developed applying the GRADE system for performing robust systematic reviews with plausible recommendations. The guideline consists of 13 clinical questions mainly regarding ventilator settings and drug therapies (the last question includes 11 medications that are not approved for clinical use in Japan). Results The recommendations for adult patients with ARDS include: we suggest against early tracheostomy (GRADE 2C), we suggest using NPPV for early respiratory management (GRADE 2C), we recommend the use of low tidal volumes at 6-8 mL/kg (GRADE 1B), we suggest setting the plateau pressure at 30cmH20 or less (GRADE2B), we suggest using PEEP within the range of plateau pressures less than or equal to 30cmH2O, without compromising hemodynamics (Grade 2B), and using higher PEEP levels in patients with moderate to severe ARDS (Grade 2B), we suggest using protocolized methods for liberation from mechanical ventilation (Grade 2D), we suggest prone positioning especially in patients with moderate to severe respiratory dysfunction (GRADE 2C), we suggest against the use of high frequency oscillation (GRADE 2C), we suggest the use of neuromuscular blocking agents in patients requiring mechanical ventilation under certain circumstances (GRADE 2B), we suggest fluid restriction in the management of ARDS (GRADE 2A), we do not suggest the use of neutrophil elastase inhibitors (GRADE 2D), we suggest the administration of steroids, equivalent to methylprednisolone 1-2mg/kg/ day (GRADE 2A), and we do not recommend other medications for the treatment of adult patients with ARDS (GRADE1B; inhaled/intravenous β2 stimulants, prostaglandin E1, activated protein C, ketoconazole, and lisofylline, GRADE 1C; inhaled nitric oxide, GRADE 1D; surfactant, GRADE 2B; granulocyte macrophage colony-stimulating factor, N-acetylcysteine, GRADE 2C; Statin.) Conclusions This article was translated from the Japanese version originally published as the ARDS clinical practice guidelines 2016 by the committee of ARDS clinical practice guideline (Tokyo, 2016, 293p, available from http://www.jsicm.org/ARDSGL/ARDSGL2016.pdf ). The original article, written for Japanese healthcare providers, provides points of view that are different from those in other countries.

Abstract γ-Glutamyltranspeptidase (GGT) is upregulated in a variety of human cancers including primary and secondary hepatic tumors. This motivated us to use γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), a novel fluorophore emitting light at around 520 nm following enzymatic reaction with GGT, as a tool for the intraoperative identification of hepatic tumors. gGlu-HMRG was topically applied to 103 freshly resected hepatic specimens. Fluorescence imaging using gGlu-HMRG identified hepatic tumors with the sensitivity/specificity of 48%/96% for hepatocellular carcinoma, 100%/100% for intrahepatic cholangiocarcinoma, and 87%/100% for colorectal liver metastasis. High gGlu-HMRG fluorescence intensity was positively associated with the incidence of microscopic vascular invasion in HCC and the risk of early postoperative recurrence in CRLM. These results suggest that gGlu-HMRG imaging could not only be a useful intraoperative navigation tool but also provide information related to postoperative disease recurrence.

Abstract We have developed and characterized a bacterial consortium that reductively dechlorinates trichloroethene to ethene. Quantitative PCR analysis for the 16S rRNA and reductive dehalogenase genes showed that the consortium is highly enriched with Dehalococcoides spp. that have two vinyl chloride reductive dehalogenase genes, bvcA and vcrA, and a trichloroethene reductive dehalogenase gene, tceA. The metagenome analysis of the consortium by the next generation sequencer SOLiD 3 Plus suggests that a Dehalococcoides sp. that is highly homologous to D. mccartyi 195 and equipped with vcrA and tceA exists in the consortium. We isolated this Dehalococcoides sp. and designated it as D. mccartyi UCH-ATV1. As the growth of D. mccartyi UCH-ATV1 is too slow under isolated conditions, we constructed a consortium by mixing D. mccartyi UCH-ATV1 with several other bacteria and performed metagenomic sequencing using the single molecule DNA sequencer PacBio RS II. We successfully determined the complete genome sequence of D. mccartyi UCH-ATV1. The strain is equipped with vcrA and tceA, but lacks bvcA. Comparison with tag sequences of SOLiD 3 Plus from the original consortium shows a few differences between the sequences. This suggests that a genome rearrangement of Dehalococcoides sp. occurred during culture.

Temsirolimus is an inhibitor of mammalian target of rapamycin and interstitial lung disease (ILD) is known to be one of the adverse events associated with temsirolimus, which usually improves rapidly after discontinuation of the drug and rarely worsens thereafter. Herein, we report a case of delayed exacerbation of ILD after discontinuation of temsirolimus for metastatic renal cell carcinoma in an 86-year-old male with chronic ILD. The patient developed gradually worsening dyspnea five weeks after an initiation of temsirolimus and was admitted to our facility. On his admission, although a pulmonary function test revealed a decreased diffusion capacity, there was no obvious progression of ILD on HRCT scan. His dyspnea once improved after discontinuation of temsirolimus, but it recurred and acute exacerbation of ILD was diagnosed 40 days after his last administration of temsirolimus. He received high-dose steroid therapy, however, he deteriorated and died. Histopathological examination of the lungs at autopsy revealed overlapping diffuse alveolar damage with chronic interstitial changes. In the present case, since there were no specific factors that could have caused acute exacerbation of ILD except for temsirolimus, it was considered to contribute to the exacerbation of underlying ILD. In conclusion, physicians should be aware of the possibility of temsirolimus-induced ILD not only while the medication is administered, but also even after it is discontinued. It is important to carefully interview the patient and to recognize the value of physiological tests, such as respiratory function tests and blood gas analysis, as well as imaging findings on HRCT.