120-GBaud 16-QAM silicon photonics IQ modulator for data center interconnection.

We demonstrated all-silicon IQ modulators (IQMs) operating at 120-GBaud 16-QAM with suitable bandwidth, and output power. We required optical signal-to-noise-ratio (rOSNR) that have promising potential to be used in 800-Gbps small-form-factor pluggable transceivers for data center interconnection. First, we tested an IQM chip using discrete drivers and achieved a per-polarization TX output power of -18.74 dBm and an rOSNR of 23.51 dB over a 100-km standard SMF. Notably, a low BER of 1.4e-3 was obtained using our SiP IQM chip without employing nonlinear compensation, optical equalization, or an ultra-wide-bandwidth, high-ENOB OMA. Furthermore, we investigated the performance of a 3D packaged transmitter by emulating its frequency response using an IQM chip, discrete drivers, and a programmable optical filter. With a laser power of 17 dBm, we achieved a per-polarization output power of -15.64 dBm and an rOSNR of 23.35 dB.

Post-traumatic Non-haemophilic Haemosiderotic Synovitis of the Elbow: A Case Report.

Haemosiderotic synovitis (HS) is a rare synovial proliferative disease secondary to haemarthrosis, often with articular cartilage destruction. It is most frequently reported in patients with haemophiliacs, and the knee joint is most frequently affected. However, there are no reports on the elbow joint without haemophiliacs. A 60-year-old woman who had undergone osteosynthesis for a left radial head fracture 8 years earlier came to our clinic with left elbow pain. X-rays and CT scans showed osteopenia and osteoarthritic changes throughout the elbow joint. MRI revealed joint effusion and synovial membrane hyperplasia. Surgical synovectomy and screw removal were performed. The pathological diagnosis of the synovial membrane was HS. Postoperatively, the pain was relieved, osteopenia improved and there was no recurrence of symptoms. This is the first report of non-haemophilic HS of the elbow; post-traumatic HS caused elbow arthropathy, which was improved by screw removal and synovectomy. Level of Evidence: Level V (Therapeutic).

Localized-diffusive and ballistic-diffusive transitions in kicked incommensurate lattices.

By using the kicked Harper model, the effect of dynamical perturbations to the localized and ballistic phases in quasiperiodic lattice systems is investigated. The transition from the localized phase to diffusive phase via a critical subdiffusion t^{α} (t is time) with 0<α<1 is observed. In addition, we confirm the existence of the transition from the ballistic phase to the diffusive phase via a critical superdiffusion with 1<α<2.

In vitro Effects of Cellulose Acetate on Fermentation Profiles, the Microbiome, and Gamma-aminobutyric Acid Production in Human Stool Cultures.

Gamma-aminobutyric acid (GABA) is considered as a potential candidate substance that mediates the effects of intestinal bacteria on human mental health. In the present study, we evaluated the effect of water-soluble cellulose acetate (WSCA), a type of cellulose ester, on fermentation and microbial profiles, and GABA production in human stool cultures prepared from fresh feces from volunteers. In addition, the GABA-producing ability of Bacteroides uniformis, which can utilize WSCA, was evaluated in a pure-culture study. All incubations were conducted anaerobically. WSCA supplementation increased (P < 0.05) acetate and propionate production and decreased (P < 0.05) the pH in human fecal cultures. WSCA significantly altered the microbiota, selectively increasing the relative abundance of B. uniformis (P < 0.05). Pure-culture study results revealed that B. uniformis produces GABA, possibly via a glutamate-dependent acid resistance system under low pH conditions. In conclusion, WSCA could be a potential prebiotic material that is fermented by intestinal bacteria and increases short-chain fatty acid and GABA production in the human gut. Bacteroides uniformis might play an important role in both WSCA degradation and GABA production in the intestine.

Oral Ingestion of AP Collagen Peptide Leads to Systemic Absorption of Gly-Pro-Hyp, Alleviating H2O2-Induced Dermal Fibroblast Aging.

Collagen-derived dipeptides and tripeptides have various physiological activities. In this study, we compared the plasma kinetics of free Hyp, peptide-derived Hyp, Pro-Hyp, cyclo(Pro-Hyp), Hyp-Gly, Gly-Pro-Hyp, and Gly-Pro-Ala after ingestion of four different collagen samples: AP collagen peptide (APCP), general collagen peptide, collagen, and APCP and γ-aminobutyric acid (GABA) combination. Each peptide was measured by high-performance liquid chromatography and triple quadrupole mass spectrometer. We found that, among all the peptides that were analyzed, only Gly-Pro-Hyp was significantly increased after ingestion of APCP compared with that of general collagen peptides and collagen. In addition, ingestion of the APCP and GABA combination improved the absorption efficiency of Gly-Pro-Ala. Finally, we reveal that Gly-Pro-Hyp was effective for preventing H2O2-induced reduction in extracellular matrix (ECM)-related genes, COL1A, elastin, and fibronectin, in dermal fibroblasts. Taken together, APCP significantly enhances the absorption of Gly-Pro-Hyp, which might act as an ECM-associated signaling factor in dermal fibroblasts, and the APCP and GABA combination promotes Gly-Pro-Ala absorption. Clinical Trial Registration number: UMIN000047972.

Effects of Free Linoleic Acid and Oleic Acid in Sesame Meal Extract as Pancreatic Lipase Inhibitors on Postprandial Triglyceridemia: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Volunteers.

A great number of chemically diverse pancreatic lipase (PL) inhibitors have been identified to tackle obesity; however, very few of them have entered clinical studies. The ethanolic extract of sesame meal is a potent PL inhibitor, and its activity hinges exclusively on two free fatty acids: linoleic acid and oleic acid, which were proven to reduce postprandial triglyceride excursion in rats. Herein, to investigate the clinical efficacy of the sesame meal extract, in a crossover trial, 30 healthy volunteers were randomized to receive the sesame meal extract containing experimental food or placebo along with a high-fat meal. Treatment with the sesame meal extract significantly lowered the incremental postprandial serum triglyceride concentration and reduced the incremental area under the curve (iAUC) by 16.8% (p-value = 0.03) compared to placebo. Significant decreases in postprandial remnant-like lipoprotein particle cholesterol and low-density lipoprotein particles were also observed, whereas high-density lipoprotein cholesterol was increased. These results suggest that treatment with the sesame meal extract significantly reduced the postprandial excursion of triglycerides and improved the lipidemic profile after high dietary fat intake in healthy individuals, indicating the substantial potential of free linoleic acid and oleic acid and natural products rich in these compounds for the management of obesity and related conditions.

Free Linoleic Acid and Oleic Acid Reduce Fat Digestion and Absorption In Vivo as Potent Pancreatic Lipase Inhibitors Derived from Sesame Meal.

Pancreatic lipase catalyzes the cleavage of triacylglycerols at the oil-water interface, and is known as the dominant determiner of dietary fat digestion. Reducing dietary fat digestion and absorption by modulating the activity of pancreatic lipase has become a favorable strategy to tackle obesity. Orlistat is, at present, the only pancreatic lipase inhibitor approved for the treatment of obesity; however, an array of gastrointestinal adverse effects associated with orlistat limits its tolerability. As a safe alternative to orlistat, a number of natural product-derived compounds with varying degrees of pancreatic lipase inhibitory activity have been reported. We herein reported that bioactivity-guided fractionation of sesame meal led to the identification of free linoleic acid and oleic acid as potent inhibitors of porcine pancreatic lipase in vitro with an IC50 of 23.1 µg/mL (82.4 µM) and 11.7 µg/mL (41.4 µM), respectively. In rats, a single oral dose of the mixture of these fatty acids significantly suppressed the elevation of blood triacylglycerol level following fat intake. These results substantiate the role of free linoleic acid and oleic acid as a novel class of natural product-derived functional molecules that act as pancreatic lipase inhibitors, and their potential for healthy, routine-based weight management.

Localization and delocalization properties in quasi-periodically-driven one-dimensional disordered systems.

Localization and delocalization of quantum diffusion in a time-continuous one-dimensional Anderson model perturbed by the quasiperiodic harmonic oscillations of M colors is investigated systematically, which has been partly reported by a preliminary Letter [H. S. Yamada and K. S. Ikeda, Phys. Rev. E 103, L040202 (2021)2470-004510.1103/PhysRevE.103.L040202]. We investigate in detail the localization-delocalization characteristics of the model with respect to three parameters: the disorder strength W, the perturbation strength ε, and the number of colors, M, which plays the similar role of spatial dimension. In particular, attention is focused on the presence of localization-delocalization transition (LDT) and its critical properties. For M≥3 the LDT exists and a normal diffusion is recovered above a critical strength ε, and the characteristics of diffusion dynamics mimic the diffusion process predicted for the stochastically perturbed Anderson model even though M is not large. These results are compared with the results of discrete-time quantum maps, i.e., the Anderson map and the standard map. Further, the features of delocalized dynamics are discussed in comparison with a limit model which has no static disordered part.

Analysis of drug adverse events in elderly patients based on the Japanese Adverse Drug Event Report Database.

WHAT IS KNOWN AND OBJECTIVE: Compared with the general adult population, pharmacokinetics and changes in drug responsiveness occur to a greater extent in the elderly. Interactions may occur between drugs used in combination to treat various diseases and may cause adverse events (AEs). We conducted a cross-sectional risk assessment of AEs in elderly patients based on information gathered from Japanese medical practices with the goal of obtaining information that will contribute to optimizing pharmacotherapy. METHODS: The Japanese Adverse Drug Event Report database was used to determine the incidence of AEs in elderly patients (aged 80 years or older) compared with patients aged less than 80 years old by evaluating the reporting odds ratio using the data obtained from reports. RESULTS AND DISCUSSION: Hypnotics and anxiolytics, as well as anticoagulants and theophylline, were identified as groups of drugs that warrant special attention in the elderly. Hypnotics and anxiolytics, especially those that are short-acting, tend to cause delirium and geriatric syndromes including falls and fractures. With respect to anticoagulants, no increase in the risk of bleeding was evident and the dose was believed to be properly adjusted; however, there was an increased risk of anemia. Theophylline toxicity tended to occur more frequently in the elderly, suggesting the need for drug monitoring. WHAT IS NEW AND CONCLUSION: Based on these cross-sectional studies, the evaluation of the risk of AEs for drugs commonly used in the elderly based on near real-world information was achieved.

The Origin of Epithelium with Low-Grade Atypia in Early Gastric Cancer.

INTRODUCTION: Helicobacter pylori (HP) infection causes chronic inflammation and atrophy of the gastric mucosa and thus a high risk of gastric cancer (GC). With the increasing success of HP infection treatment, a larger number of GCs that develop after eradication can be assessed. Several studies have shown that epithelium with low-grade atypia (ELA) is a frequent characteristic of these GCs, but the origin of this condition is unknown. In this study, we compared the mucin phenotype, cellular proliferation, and p53 staining in ELA and cancerous tissues obtained from patients with GC with and without HP eradication. METHODS: The study population consisted of 23 patients with GC that developed after successful HP eradication therapy (eradicated group) and 24 patients with GC and HP infection (infected group). The prevalence of ELA was determined by hematoxylin and eosin staining. Tumor tissue and ELA samples were further analyzed by immunohistochemical staining for Muc5AC, Muc2, p53, and Ki-67. RESULTS: The ELA coverage rate was significantly higher in the eradicated group than in the infected group. Gastric-type mucin was frequently expressed by the ELA, and the mucin phenotypes of ELA and cancerous areas differed in 75% of cases. The Ki-67 labeling index was consistently lower in ELA than in the cancerous mucosa. Fourteen of 21 (66.7%) cancerous lesions, but only 3 ELA samples, were p53-positive. CONCLUSION: In most cases, ELA on the surfaces of GCs seems to have originated from normal gastric cells, not from cancer cells.

NMR and EPR-DEER Structure of a Dimeric Guanylate Cyclase Activator Protein-5 from Zebrafish Photoreceptors.

Retinal guanylate cyclases (RetGCs) are regulated by a family of guanylate cyclase-activating proteins (called GCAP1-7). GCAPs form dimers that bind to Ca2+ and confer Ca2+ sensitive activation of RetGC during visual phototransduction. The GCAP5 homologue from zebrafish contains two nonconserved cysteine residues (Cys15 and Cys17) that bind to ferrous ion, which stabilizes GCAP5 dimerization and diminishes its ability to activate RetGC. Here, we present NMR and EPR-DEER structural analysis of a GCAP5 dimer in the Mg2+-bound, Ca2+-free, Fe2+-free activator state. The NMR-derived structure of GCAP5 is similar to the crystal structure of Ca2+-bound GCAP1 (root-mean-square deviation of 2.4 Å), except that the N-terminal helix of GCAP5 is extended by two residues, which allows the sulfhydryl groups of Cys15 and Cys17 to become more solvent exposed in GCAP5 to facilitate Fe2+ binding. Nitroxide spin-label probes were covalently attached to particular cysteine residues engineered in GCAP5: C15, C17, T26C, C28, N56C, C69, C105, N139C, E152C, and S159C. The intermolecular distance of each spin-label probe in dimeric GCAP5 (measured by EPR-DEER) defined restraints for calculating the dimer structure by molecular docking. The GCAP5 dimer possesses intermolecular hydrophobic contacts involving the side chain atoms of H18, Y21, M25, F72, V76, and W93, as well as an intermolecular salt bridge between R22 and D71. The structural model of the GCAP5 dimer was validated by mutations (H18E/Y21E, H18A/Y21A, R22D, R22A, M25E, D71R, F72E, and V76E) at the dimer interface that disrupt dimerization of GCAP5 and affect the activation of RetGC. We propose that GCAP5 dimerization may play a role in the Fe2+-dependent regulation of cyclase activity in zebrafish photoreceptors.

Presence and absence of delocalization-localization transition in coherently perturbed disordered lattices.

A new type of delocalization induced by coherent harmonic perturbations in one-dimensional Anderson-localized disordered systems is investigated. With only a few M frequencies a normal diffusion is realized, but the transition to a localized state always occurs as the perturbation strength is weakened below a critical value. The nature of the transition qualitatively follows the Anderson transition (AT) if the number of degrees of freedom M+1 is regarded as the spatial dimension d. However, the critical dimension is found to be d=M+1=3 and is not d=M+1=2, which should naturally be expected by the one-parameter scaling hypothesis.

Chemical and microbial characterization for fermentation of water-soluble cellulose acetate in human stool cultures.

BACKGROUND: Water-soluble cellulose acetate (WSCA), a synthetic fiber source, was applied to human stool cultures and to pure cultures of representative Bacteroides species to characterize the fermentation properties of WSCA in the human gut, and to assess the potential availability of WSCA as a food or additive candidate. RESULTS: All nine of the different types of WSCA tested here provided increased acetate levels in human stool cultures. Greater levels of deacetylation were observed as the degree of substitution of hydroxyl groups by acetyl groups decreased. Among the nine tested types of WSCA, CA-0.78-128 caused the largest shifts of the microbial community, including an increased abundance of members of the genus Bacteroides, especially Bacteroides uniformis. Of four representative human gut Bacteroides species, only B. uniformis grew in pure culture on WSCA to produce acetate actively. CONCLUSION: Water-soluble cellulose acetate has the potential for dietary application in human and other monogastric animals, based on the enhanced production of short-chain fatty acids (SCFAs), in particular acetate, in the hindgut. Short-chain fatty acid production is caused by selective proliferation of specific gut bacteria belonging to the genus Bacteroides. © 2020 Society of Chemical Industry.

Critical phenomena of dynamical delocalization in quantum maps: Standard map and Anderson map.

Following the paper exploring the Anderson localization of monochromatically perturbed kicked quantum maps [Phys. Rev. E 97, 012210 (2018)2470-004510.1103/PhysRevE.97.012210], the delocalization-localization transition phenomena in polychromatically perturbed quantum maps (QM) is investigated focusing particularly on the dependency of critical phenomena on the number M of the harmonic perturbations, where M+1=d corresponds to the spatial dimension of the ordinary disordered lattice. The standard map and the Anderson map are treated and compared. As the basis of analysis, we apply the self-consistent theory (SCT) of the localization for our systems, taking a plausible hypothesis on the mean-free-path parameter which worked successfully in the analyses of the monochromatically perturbed QMs. We compare in detail the numerical results with the predictions of the SCT by largely increasing M. The numerically obtained index of critical subdiffusion t^{α} (t:time) agrees well with the prediction of one-parameter scaling theory α=2/(M+1), but the numerically obtained critical exponent of localization length significantly deviates from the SCT prediction. Deviation from the SCT prediction is drastic for the critical perturbation strength of the transition: If M is fixed, then the SCT presents plausible prediction for the parameter dependence of the critical value, but its value is 1/(M-1) times smaller than the SCT prediction, which implies existence of a strong cooperativity of the harmonic perturbations with the main mode.

Study of the cartilage matrix production-promoting effect of chicken leg extract and identification of the active ingredient.

BACKGROUND/OBJECTIVES: Osteoarthritis (OA) is a major public health issue in Japan and other countries, and foods that prevent or treat OA are in strong demand. Proteins and peptides in chicken meat and bones are known for being rich in functional and nutritional ingredients for the improvement of osteoporosis. We speculated that chicken legs, a food consumed in many regions of the world, may also contain such ingredients. In this study, we aim to (i) evaluate the effect of chicken leg extract (CLE) on the promotion of cartilage matrix production and (ii) identify the active ingredient in CLE that contributes to this function. MATERIALS/METHODS: Artificial CLE digest was prepared, and the acid mucopolysaccharide production-promoting activity of the CLE digest was evaluated by alcian blue staining of ATDC5 cells. CLE was orally administered to rabbits with burr holes in the knee joint of the femur, and the degree of regeneration of cartilage matrix was evaluated. Furthermore, we investigated orally administered CLE-derived peptides in human plasma using LC-MS. From measuring the acid mucopolysaccharide production-promotion activity of these peptides, a molecule considered to be an active ingredient in the CLE digest was identified. RESULTS: CLE digest promoted acid mucopolysaccharide production and facilitated regeneration of cartilage matrix in in vitro and in vivo experiments. Four peptides including phenylalanyl-hydroxyproline (Phe-Hyp) were detected as CLE-derived peptides in human plasma. The effect of CLE was inferred to be due to Phe-Hyp, which was confirmed to be present in the CLE digest. CONCLUSIONS: It was shown that CLE stimulated the production of articular cartilage matrix both in vitro and in vivo, and that CLE could be an effective food for preventing or treating OA. Furthermore, only Phe-Hyp was confirmed as the active compound in the CLE digest, suggesting that the activity of CLE was due to Phe-Hyp.

Nodal-line semimetal superlattices.

Spatial modulations, such as superlattices, to realize topological materials have recently been studied in theoretical and experimental works. In this paper, we investigate properties of the superlattices of the nodal-line semimetal and the normal insulator. We consider two types of superlattices, with the stacking direction being perpendicular or parallel to the plane where the nodal line lies. In particular, we show that when the stacking direction is parallel to the plane, the nodal lines remain but they change their shapes because of the folding of the Brillouin zone. We also study the superlattices with magnetization. One can expect that the quantum anomalous Hall (QAH) phase emerges in some cases, depending on the direction of the magnetization. If the magnetization is along the C 2-invariant axis, the superlattice becomes the Weyl semimetal phase if the C 2-invariant axis intersects the nodal lines, and otherwise it becomes the QAH phase.

Relationship Between the Review Time and Various PMDA Consultations in Recent New Drug Approval Cases in Japan.

BACKGROUND: It is considered important that the applicants and reviewers communicate well from the development stage and that both mutually understand the development strategy and application contents in conducting the review efficiently after the application is submitted. Therefore, we focus on Pharmaceuticals and Medical Devices Agency (PMDA) consultations from the viewpoint of communication before the application and clarify the issues to consider in the challenge to reduce the review time in terms of the relationship between the review time and various PMDA consultations. METHODS: We investigated the relationship between the review time and various PMDA consultations for the drugs with new active ingredients approved in Japan using public information from the PMDA. RESULTS: Review times tended to be shorter as more PMDA consultations were conducted. In standard review products, statistically significant differences were noted in the review times (median). When looking at the results of the cases of each category of PMDA consultations, variations in the review times were greater as the consultations were conducted in the later stages of clinical development. Review times tended to be shorter when prior assessment consultations were conducted. In standard review products, significant reductions were noted with the review time (median). CONCLUSIONS: It was suggested that conducting more PMDA consultations might lead to shorter review times. Regarding the review times, variations from the standard review time could possibly be smaller by conducting PMDA consultations from the early stage of clinical development in Japan. It was suggested that review times could possibly be further reduced by conducting prior assessment consultations.

Effects of Vonoprazan Compared with Esomeprazole on the Healing of Artificial Postendoscopic Submucosal Dissection Ulcers: A Prospective, Multicenter, Two-Arm, Randomized Controlled Trial.

BACKGROUND: Vonoprazan affords more clinical benefits than proton pump inhibitors (PPIs) during the healing of gastroduodenal ulcers. However, it remains controversial whether vonoprazan is more effective than PPIs when used to heal artificial ulcers arising after endoscopic submucosal dissection (ESD). AIM: This study investigated the effects of vonoprazan compared with esomeprazole on the healing of post-ESD artificial ulcers. METHODS: Sixty patients who underwent gastric ESD between May 2015 and May 2017 were randomized to treatment with vonoprazan (V group) or esomeprazole (E group) for 8 weeks. Upper endoscopy was performed at 4 and 8 weeks after ESD, and drug effects were estimated based on the ulcer healing rates and shrinkage rates. RESULTS: Fifty-three patients were analyzed. The respective 4- and 8-week ulcer healing rates did not differ significantly between V and E groups (8.0 versus 11.5%, P = 0.669; 88.9 versus 84.6%, P = 0.420). Similarly, the respective 4- and 8-week ulcer shrinkage rates did not differ significantly between V and E groups (96.8 versus 97.5%, P = 0.656; 100 versus 100%, P = 0.257). CONCLUSION: The healing of artificial ulcers after ESD did not differ using vonoprazan or esomeprazole. Both vonoprazan and esomeprazole were effective when used to promote artificial ulcer healing after ESD.

Gastrocnemius Myalgia as a Rare Initial Manifestation of Crohn's Disease.

The initial symptoms of Crohn's disease (CD) sometimes present as extraintestinal lesions, which can be a diagnostic challenge for physicians. Painful legs, known as "gastrocnemius myalgia syndrome", are rare complications that often precede abdominal manifestations. We herein report the case of a 38-year-old man who presented with bilateral leg myalgia lasting for 4 months. Magnetic resonance imaging showed abnormal intensity, and a muscle biopsy revealed inflammatory cell infiltration. Abdominal symptoms appeared three months after the myalgia onset, and the diagnosis of CD was confirmed later by endoscopic and radiological findings. To our knowledge, this is the first description of gastrocnemius myalgia syndrome in Japan.