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Abstract Entanglements serve as a resource for any quantum information system and are deterministically generated or swapped by a joint measurement called complete Bell state measurement (BSM). The determinism arises from a quantum nondemolition measurement of two coupled qubits with the help of readout ancilla, which inevitably requires extra physical qubits. We here demonstrate a deterministic and complete BSM with only a nitrogen atom in a nitrogen-vacancy (NV) center in diamond as a quantum memory without relying on any carbon isotopes, which are the extra qubits, by exploiting electron‒nitrogen (14N) double qutrits at a zero magnetic field. The degenerate logical qubits within the subspace of qutrits on the electron and nitrogen spins are holonomically controlled by arbitrarily polarized microwave and radiofrequency pulses via zero-field-split states as the ancilla, thus enabling the complete BSM deterministically. Since the system works under an isotope-free and field-free environment, the demonstration paves the way to realize high-fidelity quantum repeaters for long-haul quantum networks and quantum interfaces for large-scale distributed quantum computers.

Abstract Nasal pressure signal is commonly used to evaluate obstructive sleep apnea. This study aimed to assess its safety for respiratory monitoring during sedation. A total of 45 adult patients undergoing sedation with propofol and fentanyl for invasive endoscopic procedures were enrolled. While both nasal pressure and capnograph signals were continuously recorded, only the nasal pressure signal was displayed. The primary outcome was the incidence of oxygen desaturation below 90%. The secondary outcomes were the ability to predict the desaturation and incidence of harmful events and false alarms, defined as an apnea waveform lasting more than 3 min without desaturation. Of the 45 participants, 43 completed the study. At least one desaturation event occurred in 12 patients (27.9%; 95% confidence interval 15.3–43.7%). In these 12 patients, more than half of the desaturation events were predictable in 9 patients by capnography and 11 patients by nasal pressure monitoring (p = 0.59). In the 43 patients, false alarms were detected in 7 patients with capnography and 11 patients with nasal pressure monitoring (p = 0.427). Harmful events unrelated to nasal pressure monitoring occurred in 2 patients. Nasal pressure monitoring is safe and possibly useful for respiratory monitoring despite false alarms during sedation.

The development of fluorescent Cd2+ sensors requires strict selectivity over Zn2+ because of the high availability of Zn2+ in the natural environment. In this paper, bisquinoline-based fluorescent sensors with a 2-aminoethanol backbone were investigated. The weak coordination ability of quinoline compared to well-studied pyridine is suitable for Cd2+ selectivity rather than Zn2+. In the presence of 3 equiv. of metal ions, TriMeO-N,O-BQMAE (N,O-bis(5,6,7-trimethoxy-2-quinolylmethyl)-2-methylaminoethanol (3)), as well as its N,N-isomer TriMeO-N,N-BQMAE (N,N-bis(5,6,7-trimethoxy-2-quinolylmethyl)-2-methoxyethylamine (6)), exhibits Cd2+-selective fluorescence enhancement over Zn2+ in DMF-HEPES buffer (1:1, 50 mM HEPES, 0.1 M KCl, pH = 7.5) (IZn/ICd = 26–34%), which has similar selectivity in comparison to the corresponding ethylenediamine derivative TriMeOBQDMEN (N,N’-bis(5,6,7-trimethoxy-2-quinolylmethyl)-N,N’-dimethylethylenediamine) under the same experimental condition (IZn/ICd = 24%). The fluorescence mechanisms of N,O- and N,N-isomers of BQMAE are quite different, judging from the fluorescence lifetimes of their metal complexes. The Cd2+ complex with TriMeO-N,O-BQMAE (3) exhibits a long fluorescence lifetime similar to that of TriMeOBQDMEN via intramolecular excimer emission, whereas the Cd2+ complex with TriMeO-N,N-BQMAE (6) exhibits a short lifetime from monomer emission.

Abstract Although the efficacy and safety of salvage techniques for biliary cannulation in endoscopic retrograde cholangiopancreatography (ERCP) have been reported, few reports analyzed the choice of techniques and their clinical outcomes in large cohorts. This study aimed to evaluate the outcomes of biliary cannulation in patients with native papillae. We retrospectively identified 1021 patients who underwent initial ERCP from January 2013 to March 2020. We investigated background factors, treatment details, cannulation success rates, and adverse event rates. Then we analyzed a series of treatment processes, including salvage techniques such as double guidewire technique (DGT), needle knife pre-cutting (NKP), and transpancreatic pre-cut papillotomy (TPPP). The initial ERCP success rate using standard technique alone was 62.8%, which increased to 94.3% including salvage techniques. Salvage techniques were frequently required in patients with long oral protrusions (OR 2.38; 95% CI 1.80–3.15; p

Sequential Knoevenagel condensation/cyclization using cyclic active methylene compounds such as Meldrum's acid have been studied. The reaction of 2-(1-phenylvinyl)benzaldehyde and Meldrum's acid, dimedone, or 1,3-indandione with piperidine/AcOH or L-proline at room temperature for 17–18 h gave cyclized indene derivatives in 63–80% yield. The reaction of 2-(3,5-dimethoxyphenyl)benzaldehyde and Meldrum's acid at room temperature for 17 h gave a fluorene derivative in 98% yield. Furthermore, the reaction of 2-(3,5-dimethoxybenzyl)benzaldehyde and Meldrum's acid with piperidine at room temperature for 18 h gave a dihydroanthracene derivative bearing Meldrum's acid in 83% yield. The reaction of 2-(3,5-dimethoxybenzyl)benzaldehyde and Meldrum's acid with piperidine at 110 °C for 2 h gave Meldrum's acid fragmentated dihydroanthracene derivative in 48% yield. The reaction mechanisms of the cyclization steps and Meldrum's acid fragmentation have been examined by the DFT calculations. [ABSTRACT FROM AUTHOR]

N-Monosubstituted ethylenediamine derivatives with three methylene-tethered aromatic groups ((ArCH2)2NCH2CH2N(R)CH2Ar (R-ArArAr), where Ar = 2-pyridyl, 2-quinolyl, 1- and 3-isoquinolyl and 2-quinoxalyl; R = methyl, benzyl and phenyl) were utilized as pentadentate ligands for copper(II) complexation. Fifteen mononuclear copper(II) complexes were synthesized and exhibit differences in cyclic voltammetry, absorption spectroscopy and solid state geometries, depending on the aromatic group (Ar) and the substituent on the aliphatic nitrogen atom (R) of the ligand. Compared with the pyridine and isoquinoline complexes, the quinoline and quinoxaline derivatives exhibit distinct Cu(II)/Cu(I) redox potentials and d–d transition absorption wavelengths. Similarly, the phenyl derivatives are different from their methyl and benzyl counterparts. These characteristic trends are discussed in relation to the square-pyramidal/trigonal–bipyramidal structure of the complexes which is perturbed by the location of quinoline moieties in the penta- or hexacoordinate complexes with Jahn–Teller distortion. In addition, the results are compared to the copper(II) complexes with pyridine/quinoline mixed ligands, Ph-Ar1Ar2Ar3 ((Ar1CH2)(Ar2CH2)NCH2CH2N(Ph)CH2Ar3). [ABSTRACT FROM AUTHOR]

Abstract Both EZH2 and its homolog EZH1 function as histone H3 Lysine 27 (H3K27) methyltransferases and repress the transcription of target genes. Dysregulation of H3K27 trimethylation (H3K27me3) plays an important role in the development and progression of cancers such as hepatocellular carcinoma (HCC). This study investigated the relationship between the expression of EZH1/2 and the level of H3K27me3 in HCC. Additionally, the role of EZH1/2 in cell growth, tumorigenicity, and resistance to sorafenib were also analyzed. Both the lentiviral knockdown and the pharmacological inhibition of EZH1/2 (UNC1999) diminished the level of H3K27me3 and suppressed cell growth in liver cancer cells, compared with EZH1 or EZH2 single knockdown. Although a significant association was observed between EZH2 expression and H3K27me3 levels in HCC samples, overexpression of EZH1 appeared to contribute to enhanced H3K27me3 levels in some EZH2lowH3K27me3high cases. Akt suppression following sorafenib treatment resulted in an increase of the H3K27me3 levels through a decrease in EZH2 phosphorylation at serine 21. The combined use of sorafenib and UNC1999 exhibited synergistic antitumor effects in vitro and in vivo. Combination treatment canceled the sorafenib-induced enhancement in H3K27me3 levels, indicating that activation of EZH2 function is one of the mechanisms of sorafenib-resistance in HCC. In conclusion, sorafenib plus EZH1/2 inhibitors may comprise a novel therapeutic approach in HCC.

Abstract We previously identified insulin-like growth factor-II messenger ribonucleic acid-binding protein 3 (IMP3) as a valuable marker to distinguish malignant from benign lesions in pancreatic solid masses. The aim of this prospective study was to evaluate the usefulness of IMP3 and p53 immunohistochemical staining in endoscopic ultrasound-guided fine-needle aspiration (EUS–FNA) samples for pancreatic solid masses. The study recruited 90 consecutive patients with pancreatic masses, including 62 pancreatic ductal adenocarcinomas (PDACs), 11 benign tumors, and 17 other tumors, who underwent EUS–FNA, and conducted IMP3 and p53 immunohistochemical staining. The main outcome measurement was improved diagnostic utility using IMP3 and p53 immunohistochemical staining. IMP3 and p53 expressions were detected in 60.8% and 49.4% of malignant lesions, 69.4% and 58.1% of PDACs, and 0% of benign lesions, respectively. In PDAC and benign tumors, the use of IMP3 and/or p53 immunostaining increased the sensitivity of cytohistological analysis from 88.7 to 93.5%, although the difference was not statistically significant. The sensitivity of histological analysis combined with that of IMP3 staining was 91.9%, which was significantly greater than that of histology alone (80.6%). The use of IMP3 and p53 immunohistochemical staining did not significantly improve the sensitivity of cytohistological analysis; however, IMP3 staining may be helpful for the histological analysis of malignant pancreatic tumors.

Introduction and objectives: Acute cholangitis, which is characterized by biliary infection and acute liver injury, may impact cirrhosis prognosis. However, the prognosis itself remains unclear. Materials and methods: This multicenter retrospective cohort study compared the mortality and liver function change between patients with and without cirrhosis who underwent endoscopic treatment for acute cholangitis caused by choledocholithiasis between January 2004 and December 2019. Results: We analyzed 699 patients, 44 of whom had cirrhosis. The cirrhotic group had a significantly higher 30-day mortality rate than the noncirrhotic group (14% vs. 1%; P < 0.001). The cirrhotic group also had significantly lower total bilirubin and albumin recovery. However, all patients with cirrhosis who survived achieved total-bilirubin recovery, and 91% achieved albumin recovery within 90 days. In multivariable Cox regression analysis, the independent risk factors for total-bilirubin recovery included cirrhosis (hazard ratio, 0.37; 95%CI, 0.24‒0.58; P < 0.001) and high total-bilirubin level (0.46; 95%CI, 0.34‒0.60; P < 0.001), whereas those for albumin recovery were cirrhosis (0.51; 95%CI, 0.33‒0.79; P = 0.002), high age (0.62; 95%CI, 0.47‒0.82; P < 0.001), organ dysfunction (0.62; 95%CI, 0.39‒0.96; P = 0.03), low albumin level (0.57; 95%CI, 0.36‒0.91; P = 0.02), and high C-reactive protein level (0.73; 95%CI, 0.56‒0.95; P = 0.02). Conclusions: Patients with cirrhosis complicated with acute cholangitis had poor prognosis. Recovery of liver function after endoscopic treatment was slow; nevertheless, most patients who survived could recover within 90 days.

Abstract Background Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has high accuracy and a low complication rate; therefore, it has been widely used as a useful tool for diagnosis of and to determine treatment strategies for pancreatic tumors. Recently, reports of the recurrence of needle tract seeding after EUS-FNA are emerging. Case presentation An 83-year-old woman was referred to our hospital to undergo further examination of her pancreatic tumor. Multidetector computed tomography (MDCT) revealed a 25-mm-diameter mass in the pancreatic body. She underwent EUS-FNA (transgastric, 22-G needle, 2 passes) and was subsequently diagnosed with adenocarcinoma. Distal pancreatosplenectomy followed by adjuvant chemotherapy with S-1 for 6 months was performed. The level of carbohydrate antigen 19–9 gradually increased 22 months after surgery, and MDCT, which was performed 3 months later, revealed a 23-mm low-density mass in the stomach and paragastric lymph node swelling. Gastroendoscopy revealed a submucosal tumor, and endoscopic ultrasound revealed a hypoechoic mass in the submucosa of the gastric wall. Partial gastrectomy with lymph node resection was performed. The pathological findings showed adenocarcinoma extending from the subserosa to the submucosa and lymph node metastasis, consistent with a tumor recurrence from the resected pancreatic tumor. She received adjuvant chemotherapy with S-1; recurrence was not observed for 5 months, at the time of this writing. Conclusion It is important to pay careful attention to the development of needle tract seeding in patients with pancreatic cancer diagnosed by EUS-FNA. This is the first case of needle tract seeding with lymph node metastasis, highlighting the need for caution and providing novel insight in the postoperative follow-up of patients with pancreatic body/tail cancer.

While amplicon sequencing of 16S rRNA is a common method for studying microbial community, it has been difficult to identify genera and species using next-generation sequencers to examine some regions (e.g., V3-V4 of 16S rRNA) because of the short read lengths. However, the advent of third-generation sequencers has made it possible to analyze the full length of the 16S rRNA gene, which allowed for species level identification at low cost. In this study, we evaluated the accuracy of the identification with a third-generation sequencer, MinION from Oxford Nanopore Technologies, using nine indigenous bacteria that can pose problems with food poisoning and opportunistic infections as an example. We demonstrated that Enterococcus faecalis and Enterococcus hirae could be identified at the species level with an accuracy of 96.4% to 97.5%. We also demonstrated that the absolute counts of various bacteria could be determined by spiking the sample with a bacterium as an internal standard. Then, we tested whether this convenient bacterial identification method could evaluate the antibiotic sensitivities of multiple bacteria simultaneously. In order to evaluate antimicrobial susceptibility, a mock community, an artificial mixture of the nine bacterial strains, was prepared and cultured in the presence of the antibiotics ofloxacin or chloramphenicol, and the 16S rRNAs were analyzed by using Nanopore sequencer. We confirmed that antibiotic-induced cell count reductions could be measured simultaneously by quantifying the abundances of various bacteria in the mock community before and after culture. It was thus shown that the antibiotic sensitivities of multiple bacteria could be evaluated simultaneously, with distinction made between bactericidal action and bacteriostatic action. This methodology would allow rapid evaluation of antibiotic activity spectrum at the species level containing a wide variety of bacteria, such as biofilm bacteria and gut microbiota.

Background: Diagnosing biliary tract cancer is difficult because endoscopic retrograde cholangiopancreatography (ERCP) is performed fluoroscopically, and the sensitivity of bile cytology is low. Liquid biopsy of bile using targeted sequencing is expected to improve diagnosis and treatment, but few studies have been conducted. In this study, we examined whether liquid biopsy of bile improves the diagnostic sensitivity of biliary strictures. Methods: A total of 72 patients with biliary strictures who underwent ERCP at Chiba University Hospital between April 2018 and March 2021 were examined. Of these, 43 and 29 were clinically and pathologically diagnosed as having malignant and benign biliary strictures, respectively. We performed targeted sequencing of bile obtained from these patients, and the sensitivity of this method was compared with that of bile cytology. Detection of at least one oncogenic mutation was defined as having malignancy. Results: The sensitivity of bile cytology was 27.9%, whereas that of genomic analysis was 46.5%. Comparing bile cytology alone with the combination of cytology and genomic analysis, the latter was more sensitive (53.5%, p <.001). Among the 43 patients with malignant biliary strictures, mutations with FDA‐approved drugs were detected in 11 (26%). Conclusions: Liquid biopsy of bile can potentially diagnose malignancy and detect therapeutic targets. [ABSTRACT FROM AUTHOR]