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Background/purpose: In cases of missing posterior teeth, treatment modalities based on the shortened dental arch (SDA) concept may be a viable alternative. However, the association between oral health-related quality of life (OHRQoL) and patients’ treatment decisions remains unclear. This study aimed to investigate the association between OHRQoL and the decision to be treated with implant-supported fixed partial dentures (IFPDs) or take a wait-and-see approach in patients with an SDA missing a single second molar and to clarify the impact of IFPD treatment on the OHRQoL. Materials and methods: The Oral Health Impact Profile (OHIP) questionnaire was administered twice (pre- and post-treatment) and once to 41 patients with a unilateral SDA missing a single second molar who chose IFPD treatment (IFPD group, n = 22) and the wait-and-see approach (no treatment group, n = 19), respectively. Logistic regression analysis was performed with IFPD treatment choice as the objective variable and the four OHIP dimension scores, age, and sex as covariates. The pre- and post-treatment values of the OHIP summary and four-dimension scores were compared using a paired t-test. Results: The IFPD treatment choice was significantly associated with sex (male), higher Oral Function dimension scores, and lower Psychosocial Impact dimension scores (all P

With many non-human primates (NHPs) showing continued population decline, there is an ongoing need to better understand their ecology and conservation threats. One such threat is the risk of disease, with various bacterial, viral and parasitic infections previously reported to have damaging consequences for NHP hosts. Strongylid nematodes are one of the most commonly reported parasitic infections in NHPs. Current knowledge of NHP strongylid infections is restricted by their typical occurrence as mixed infections of multiple genera, which are indistinguishable through traditional microscopic approaches. Here, modern metagenomics approaches were applied for insight into the genetic diversity of strongylid infections in South-East and East Asian NHPs. We hypothesized that strongylid nematodes occur in mixed communities of multiple taxa, dominated by Oesophagostomum, matching previous findings using single-specimen genetics. Utilizing the Illumina MiSeq platform, ITS-2 strongylid metabarcoding was applied to 90 samples from various wild NHPs occurring in Malaysian Borneo and Japan. A clear dominance of Oesophagostomum aculeatum was found, with almost all sequences assigned to this species. This study suggests that strongylid communities of Asian NHPs may be less species-rich than those in African NHPs, where multi-genera communities are reported. Such knowledge contributes baseline data, assisting with ongoing monitoring of health threats to NHPs.

ABSTRACT The growing resistance to amoxicillin (AMX)—one of the main antibiotics used in Helicobacter pylori eradication therapy—is an increasing health concern. Several mutations of penicillin-binding protein 1A (PBP1A) are suspected of causing AMX resistance; however, only a limited set of these mutations have been experimentally explored. This study aimed to investigate four PBP1A mutations (i.e., T558S, N562H, T593A, and G595S) carried by strain KIN76, a high-level AMX-resistant clinical H. pylori isolate with an AMX minimal inhibition concentration (MIC) of 2 µg/mL. We transformed a recipient strain 26695 with the DNA containing one to four mutation allele combinations of the pbp1 gene from strain KIN76. Transformants were subjected to genomic exploration and antimicrobial susceptibility testing. The resistance was transformable, and the presence of two to four PBP1A mutations (T558S and N562H, or T593A and G595S), rather than separate single mutations, was necessary to synergistically increase the AMX MIC up to 16-fold compared with the wild-type (WT) strain 26695. An AMX binding assay of PBP1A was performed using these strains, and binding was visualized by chasing Bocillin, a fluorescent penicillin analog. This revealed that all four-mutation allele-transformed strains exhibited decreased affinity to AMX on PBP1A than the WT. Protein structure modeling indicated that functional modifications occur as a result of these amino acid substitutions. This study highlights a new synergistic AMX resistance mechanism and establishes new markers of AMX resistance in H. pylori.IMPORTANCEThe development of resistance to antibiotics, including amoxicillin, is hampering the eradication of Helicobacter pylori infection. The identification of mechanisms driving this resistance is crucial for the development of new therapeutic strategies. We have demonstrated in vitro the synergistic role of novel mutations in the pbp1 gene of H. pylori that is suspected to drive amoxicillin resistance. Also deepening our understanding of amoxicillin resistance mechanisms, this study establishes new molecular markers of amoxicillin resistance that may be useful in molecular-based antibiotic susceptibility testing approaches for clinical practice or epidemiologic investigations.

Background/Aims: A latex agglutination turbidity (LA) assay to test for serum antibodies has been approved in Japan and Korea for mass screening of Helicobacter pylori infection. In this study, we evaluated the LA assay for diagnosing H. pylori infection and predicting gastric mucosal changes in a Mongolian population. Methods: In total, 484 individuals were classified into H. pylori-positive (n=356) and H. pylori-negative (n=128) groups, as determined by histology and H. pylori culture. Results: The best cutoff, sensitivity, and specificity values for the LA assay were 18.35 U/mL, 74.2%, and 65.6%, respectively. The LA values in the atrophic gastritis group were statistically higher than those in the other groups (healthy, chronic gastritis, intestinal metaplasia, and gastric cancer, p

Introduction: Around 50% of patients with heart failure (HF) have an existing iron deficiency (ID), with or without anemia. With such a high prevalence, more research is underway to determine whether addressing ID can improve HF. Aims: This study aimed to critically evaluate the beneficial effects of intravenous iron administration for chronic HF. Methods: Studies were searched in Medline, Embase, and Cochrane for trials investigating the effect of iron supplementation on chronic HF patients. Outcomes of HF and all-cause hospitalizations, as well as cardiovascular-related and all-cause mortalities, were observed. We calculated the odds ratios (ORs) using fixed and random-effect models. The bias was evaluated by funnel plots and Egger's regression tests. Statistical analysis was conducted using RevMan (version 5.4.1). Results: Five studies with a total sample size of 1646 subjects were included in this meta-analysis and systematic review. Four studies reported the all-cause mortality of intravenous iron supplementation for HF. None of them provided evidence for the association between intravenous iron supplementation and all-cause mortality (OR = 0.75, 95% confidence interval [CI] 0.38–1.50, P = 0.42, I2= 0%, fixed effect). Four studies established that intravenous iron therapy significantly decreased hospitalization due to HF (OR = 0.56, 95% CI: 0.34–0.94, P = 0.03, I2= 53%, random effect). Conclusion: Iron supplementation does confer the benefit of iron supplementation in patients with chronic, stable HF with regard to HF hospitalization despite not showing significant associations in all-cause hospitalization, cardiovascular death, or all-cause mortality.

Abstract Background Moso bamboo (Phyllostachys edulis) is a typical East Asian bamboo that does not flower for > 60 years and propagates without seed reproduction. Thus, Moso bamboo can be propagated vegetatively, possibly resulting in highly heterozygous genetic inheritance. Recently, a draft genome of Moso bamboo was reported, followed by whole genome single nucleotide polymorphisms (SNP) analysis, which showed that the genome of Moso bamboo in China has regional characteristics. Moso bamboo in Japan is thought to have been introduced from China over the sea in 1736. However, it is unclear where and how Moso bamboo was introduced in Japan from China. Here, based on detailed analysis of heterozygosity in genome diversity, we estimate the spread of genome diversity and its pedigree of Moso bamboo. Results We sequenced the whole genome of Moso bamboo in Japan and compared them with data reported previously from 15 regions of China. Only 4.1 million loci (0.37% of the analyzed genomic region) were identified as polymorphic loci. We next narrowed down the number of polymorphic loci using several filters and extracted more reliable SNPs. Among the 414,952 high-quality SNPs, 319,431 (77%) loci were identified as heterozygous common to all tested samples. The result suggested that all tested samples were clones via vegetative reproduction. Somatic mutations may accumulate in a heterozygous manner within a single clone. We examined common heterozygous loci between samples from Japan and elsewhere, from which we inferred that an individual closely related to the sample from Fujian, China, was introduced to Japan across the sea without seed reproduction. In addition, we collected 16 samples from four nearby bamboo forests in Japan and performed SNP and insertion/deletion analyses using a genotyping by sequencing (GBS) method. The results suggested that a small number of somatic mutations would spread within and between bamboo groves. Conclusions High heterozygosity in the genome-wide diversity of Moso bamboo implies the vegetative propagation of Moso bamboo from China to Japan, the pedigree of Moso bamboo in Japan, and becomes a useful marker to approach the spread of genome diversity in clonal plants.

Abstract Background Infection with Helicobacter pylori as the cause of gastric cancer is a global public health concern. In addition to protecting germs from antibiotics, biofilms reduce the efficacy of H. pylori eradication therapy. The nucleotide polymorphisms (SNPs) related with the biofilm forming phenotype of Helicobacter pylori were studied. Results Fifty-six H. pylori isolate from Bangladeshi patients were included in this cross-sectional study. Crystal violet assay was used to quantify biofilm amount, and the strains were classified into high- and low-biofilm formers As a result, strains were classified as 19.6% high- and 81.4% low-biofilm formers. These phenotypes were not related to specific clades in the phylogenetic analysis. The accessories genes associated with biofilm from whole-genome sequences were extracted and analysed, and SNPs among the previously reported biofilm-related genes were analysed. Biofilm formation was significantly associated with SNPs of alpA, alpB, cagE, cgt, csd4, csd5, futB, gluP, homD, and murF (P

Abstract Helicobacter pylori is involved in the etiology and severity of several gastroduodenal diseases; however, plasticity of the H. pylori genome makes complete genome assembly difficult. We report here the full genomes of H. pylori strains CHC155 and VN1291 isolated from a non-cardia gastric cancer patient and a duodenal ulcer patient, respectively, and their virulence demonstrated by in vitro infection. Whole-genome sequences were obtained by combining long- and short-reads with a hybrid-assembly approach. Both CHC155 and VN1291 genome possessed four kinds of genomic island: a cag pathogenicity island (cagPAI), two type 4 secretion system islands within an integrative and conjugative element (tfs ICE), and prophage. CHC155 and VN1291 carried East Asian-type cagA and vacA s1m1, and outer membrane protein genes, including two copies of oipA. Corresponded to genetic determinants of antibiotic resistance, chromosomal mutations were identified in CHC155 (rdxA, gyrA, and 23S rRNA) and VN1291 (rdxA, 23S rRNA, and pbp1A). In vitro infection of AGS cells by both strains induced the cell scattering phenotype, tyrosine phosphorylation of CagA, and promoted high levels of IL8 secretion, indicating fully intact phenotypes of the cagPAI. Virulence genes in CHC155 and VN1291 genomes are crucial for H. pylori pathogenesis and are risk factors in the development of gastric cancer and duodenal ulcer. Our in vitro studies indicate that the strains CHC155 and VN1291 carry the pathogenic potential.

Organoboron and organosilicon compounds have potential applications in various fields including materials science and medicinal chemistry. Here the authors report a protocol that enables the dearomative carbo-sila-boration of quinolines.

Objective: There are many models to predict extracapsular extension (ECE) in patients with prostate cancer. We aimed to externally validate several models in a Japanese cohort. Methods: We included patients treated with robotic-assisted radical prostatectomy for prostate cancer. The risk of ECE was calculated for each patient in several models (prostate side-specific and non-side-specific). Model performance was assessed by calculating the receiver operating curve and the area under the curve (AUC), calibration plots, and decision curve analyses. Results: We identified ECE in 117 (32.9%) of the 356 prostate lobes included. Patients with ECE had a statistically significant higher prostate-specific antigen level, percentage of positive digital rectal examination, percentage of hypoechoic nodes, percentage of magnetic resonance imaging nodes or ECE suggestion, percentage of biopsy positive cores, International Society of Urological Pathology grade group, and percentage of core involvement. Among the side-specific models, the Soeterik, Patel, Sayyid, Martini, and Steuber models presented AUC of 0.81, 0.78, 0.77, 0.75, and 0.73, respectively. Among the non-side-specific models, the memorial Sloan Kettering Cancer Center web calculator, the Roach formula, the Partin tables of 2016, 2013, and 2007 presented AUC of 0.74, 0.72, 0.64, 0.61, and 0.60, respectively. However, the 95% confidence interval for most of these models overlapped. The side-specific models presented adequate calibration. In the decision curve analyses, most models showed net benefit, but it overlapped among them. Conclusion: Models predicting ECE were externally validated in Japanese men. The side-specific models predicted better than the non-side-specific models. The Soeterik and Patel models were the most accurate performing models.

Abstract Background We evaluated the microbiota in the stomach of Gastroesophageal Reflux Disease (GERD) patients. We compared Erosive Reflux Disease (ERD) to gastritis and Non-erosive Reflux Disease (NERD) subjects by 16S rRNA approach on gastric biopsy specimens. A total of 197 subjects were included consisting of gastritis (68; 34.52%), ERD (55; 27.92%), and NERD (74; 37.56%). After quality filtering, 187 samples were included for OTU analysis using Qiime2. Results We observed a significant difference in alpha diversity (Shannon and Simpson indexes were P = 0.0016 and P = 0.017, respectively). A significant decrease in alpha diversity index was observed in NERD with Helicobacter pylori (H. pylori)-positive subjects than in gastritis (Simpson index P = 0.022; Shannon index P = 0.029), indicating a significant influence of H. pylori on the diversity in the stomach despite the diseases. In H. pylori-negative samples, alpha diversity measurement by the abundance coverage estimates (ACE) and Fisher Test revealed that ERD had significantly lower richness than gastritis and NERD groups (P = 0.00012 and P = 0.00043, respectively). Anaerobacillus sp. could only be found in ERD patients by LEFse analysis. Conclusions The presence of ERD could alter microbiome diversity. A negative correlation between H. pylori and ERD is shown in this microbiome study but not in NERD.

ABSTRACT Nontuberculous mycobacterial infections are generally believed to be independently acquired from the environment. Although person-to-person transmission of nontuberculous mycobacteria, especially Mycobacterium abscessus subsp. massiliense, is a serious concern among individuals with cystic fibrosis (CF), evidence of its spread among patients without CF has never been established. We unexpectedly found a number of M. abscessus subsp. massiliense cases among patients without CF in a hospital. This study aimed to define the mechanism of M. abscessus subsp. massiliense infection among patients who were ventilator dependent and without CF who had progressive neurodegenerative diseases in our long-term care wards from 2014 to 2018 during suspected nosocomial outbreaks. We conducted whole-genome sequencing of M. abscessus subsp. massiliense isolates from 52 patients and environmental samples. Potential opportunities for in-hospital transmission were analyzed using epidemiological data. M. abscessus subsp. massiliense was isolated from one air sample obtained near a patient without CF who was colonized with M. abscessus subsp. massiliense but not from other potential sources. Phylogenetic analysis of the strains from these patients and the environmental isolate revealed clonal expansion of near-identical M. abscessus subsp. massiliense isolates, with the isolates generally differing by fewer than 22 single nucleotide polymorphisms (SNPs). Approximately half of the isolates differed by fewer than nine SNPs, indicating interpatient transmission. Whole-genome sequencing revealed a potential nosocomial outbreak among patients who were ventilator dependent and without CF. IMPORTANCE The isolation of M. abscessus subsp. massiliense from the air, but not from environmental fluid samples, may suggest airborne transmission. This was the first report to demonstrate person-to-person transmission of M. abscessus subsp. massiliense, even among patients without CF. M. abscessus subsp. massiliense may spread among patients who are ventilator dependent without CF through direct or indirect in-hospital transmission. The current infection control measures should address potential transmission among patients without CF, particularly in facilities that treat patients who are ventilator dependent and patients with preexisting chronic pulmonary diseases, such as CF.

Objectives To examine the national, 6-year trends in in-hospital clinical outcomes of patients with subarachnoid haemorrhage (SAH) who underwent clipping or coiling and the prognostic influence of temporal trends in the Comprehensive Stroke Center (CSC) capabilities on patient outcomes in Japan.Design Retrospective study.Setting Six hundred and thirty-one primary care institutions in Japan.Participants Forty-five thousand and eleven patients with SAH who were urgently hospitalised, identified using the J-ASPECT Diagnosis Procedure Combination database.Primary and secondary outcome measures Annual number of patients with SAH who remained untreated, or who received clipping or coiling, in-hospital mortality and poor functional outcomes (modified Rankin Scale: 3–6) at discharge. Each CSC was assessed using a validated scoring system (CSC score: 1–25 points).Results In the overall cohort, in-hospital mortality decreased (year for trend, OR (95% CI): 0.97 (0.96 to 0.99)), while the proportion of poor functional outcomes remained unchanged (1.00 (0.98 to 1.02)). The proportion of patients who underwent clipping gradually decreased from 46.6% to 38.5%, while that of those who received coiling and those left untreated gradually increased from 16.9% to 22.6% and 35.4% to 38%, respectively. In-hospital mortality of coiled (0.94 (0.89 to 0.98)) and untreated (0.93 (0.90 to 0.96)) patients decreased, whereas that of clipped patients remained stable. CSC score improvement was associated with increased use of coiling (per 1-point increase, 1.14 (1.08 to 1.20)) but not with short-term patient outcomes regardless of treatment modality.Conclusions The 6-year trends indicated lower in-hospital mortality for patients with SAH (attributable to better outcomes), increased use of coiling and multidisciplinary care for untreated patients. Further increasing CSC capabilities may improve overall outcomes, mainly by increasing the use of coiling. Additional studies are necessary to determine the effect of confounders such as aneurysm complexity on outcomes of clipped patients in the modern endovascular era.

Abstract Chemotherapy is a standard therapy for muscle-invasive bladder cancer (MIBC). However, genomic alterations associated with chemotherapy sensitivity in MIBC have not been fully explored. This study aimed to investigate the genomic landscape of MIBC in association with the response to chemotherapy and to explore the biological role of genomic alterations. Genomic alterations in MIBC were sequenced by targeted exome sequencing of 409 genes. Gene expression in MIBC tissues was analyzed by western blotting, immunohistochemistry, and RNA microarray. Cellular sensitivity to gemcitabine and gemcitabine metabolite was examined in bladder cancer cells after modulation of candidate gene. Targeted exome sequencing in 20 cases with MIBC revealed various genomic alterations including pathogenic missense mutation of DPYD gene encoding dihydropyrimidine dehydrogenase (DPD). Conversely, high DPYD and DPD expression were associated with poor response to gemcitabine-containing chemotherapy among patients with MIBC, as well as gemcitabine resistance in bladder cancer cells. DPD suppression rendered cells sensitive to gemcitabine, while DPD overexpression made cells gemcitabine-resistant through reduced activity of the cytotoxic gemcitabine metabolite difluorodeoxycytidine diphosphate. This study revealed the novel role of DPD in gemcitabine metabolism. It has been suggested that DPYD genomic alterations and DPD expression are potential predictive biomarkers in gemcitabine treatment.

Background: Androgen receptor pathway inhibitors (ARPIs) such as abiraterone and enzalutamide have been shown to prolong survival in patients with advanced prostate cancer. However, there is limited evidence on the anticancer effect of a reduced dose of ARPIs. This study compared the prognosis in patients with chemotherapy-naïve castration-resistant prostate cancer (CRPC) between ARPI treatment with standard dose and treatment with reduced dose. Methods: Japanese patients who were treated with ARPI as first-line treatment for CRPC between 2014 and 2018 were included. The associations between dose reduction and clinicopathological factors, progression-free survival, and overall survival were investigated. Results: Of the 162 patients included, 33 (20.4%) patients had their dose reduced during ARPI treatment. In the multivariate analysis, higher PSA, abiraterone treatment, and dose reduction were significant prognostic factors for progression-free survival (PFS); however, dose reduction was not associated with overall survival. In the enzalutamide-treated group, the median PFS was 12.1 months (95% CI, 8.5–21.4 months) in the standard-dose group and 7.2 months (95% CI, 5.0–11.5 months) in the reduced-dose group (P = 0.038). Conclusion: This study suggests inferior oncological outcome when treated with reduced-dose ARPI for CRPC. Full-dose administration of ARPI for CRPC may be appropriate if feasible.

Background: The CHAARTED and LATITUDE trials demonstrated a survival benefit of docetaxel and abiraterone for hormone-sensitive prostate cancer. In this study, we examined the impact of the risk stratification criteria used in the CHAARTED and LATITUDE trials on the prognosis of castration-resistant prostate cancer (CRPC). We also tested whether these risk stratification criteria could help in selecting effective initial treatment for CRPC. Method: Japanese patients with CRPC who were treated with docetaxel or androgen receptor pathway inhibitors such as abiraterone acetate or enzalutamide between 2014 and 2018 were included in this study. Clinicopathological factors, progression-free survival, and overall survival were investigated. Results: Of 215 patients, 110 men (51.2%) and 93 men (43.3%) were grouped as high volume by CHAARTED criteria and high risk by LATITUDE criteria, respectively. Median progression-free survival was 10.3/4.5 months (P

Helicobacter pylori is a pathogen related to severe diseases such as gastric cancer; because of rising antimicrobial-resistant strains, failure to eradicate H. pylori with antibiotics has increased worldwide. Multidrug-resistant H. pylori and gastric cancer is common in Mongolia; therefore, we aimed to explore alternative antimicrobial treatments and the genomes of resistant strains in this country. A total of 361 H. pylori strains isolated from patients in Mongolia were considered. Minimal inhibitory concentrations for two fluoroquinolones (ciprofloxacin and moxifloxacin), rifabutin, and furazolidone were determined via two-fold agar dilution. Genomic mutations in antibiotic-resistant strains were identified by next-generation sequencing using the Illumina Miseq platform and compared with genes from a reference H. pylori strain (26695). The resistance rate of H. pylori strains to quinolones was high (44% to ciprofloxacin and 42% to moxifloxacin), and resistance to rifabutin was low (0.5%); none were resistant to furazolidone. Most quinolone-resistant strains possessed gyrA gene mutations causing amino acid changes (e.g., N87K, A88P, and D91G/Y/N). While one rifabutin-resistant strain had amino acid-substituting mutations in rpoB (D530N and R701C), the other had three novel rpoB mutations; both rifabutin-resistant strains were sensitive to furazolidone. Overall, our findings suggest that rifabutin and/or furazolidone may be an alternative, effective H. pylori treatment in patients who have failed to respond to other treatment regimens.

Although various therapeutic agents have been tried for coronavirus disease-2019 (COVID-19) and evidence has accumulated, the risk of secondary infection is increased by underlying disease and immunosuppressive drugs. We report a case of pneumococcal meningitis in a patient with severe COVID-19 who was receiving dexamethasone and tocilizumab. The patient's symptoms improved with appropriate diagnosis and antimicrobial therapy, and she fortunately returned to society without any neurological sequelae of meningitis.

Accumulating evidence suggests that high levels of Fusobacterium nucleatum in colorectal tumor tissues can be associated with poor prognosis in patients with colorectal cancer (CRC); however, data regarding distinct prognostic subgroups in F. nucleatum–positive CRC remain limited. Herein, we demonstrate that high-iron status was associated with a worse prognosis in patients with CRC with F. nucleatum. Patients with CRC presenting elevated serum transferrin saturation exhibited preferential iron deposition in macrophages in the tumor microenvironment. In addition, F. nucleatum induced CCL8 expression in macrophages via the TLR4/NF-κB signaling pathway, which was inhibited by iron deficiency. Mechanistically, iron attenuated the inhibitory phosphorylation of NF-κB p65 by activating serine/threonine phosphatases, augmenting tumor-promoting chemokine production in macrophages. Our observations indicate a key role for iron in modulating the NF-κB signaling pathway and suggest its prognostic potential as a determining factor for interpatient heterogeneity in F. nucleatum–positive CRC.

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) is a powerful tool widely used for genome editing in various organisms, including plants. It introduces and facilitates the study of rare genetic mutations in a short time and is a potent tool to assist in plant molecular breeding. Radish (Raphanus sativus L.) is an important Brassicaceae vegetable cultivated and consumed worldwide. However, the application of the CRISPR/Cas9 system is limited by the absence of an efficient transformation system in radish. This study aimed to establish a CRISPR/Cas9 system in radish employing the Agrobacterium-mediated genetic transformation system reported recently. For this purpose, we performed genome editing using the CRISPR/Cas9 system targeting the GLABRA1 (GL1) orthologs, RsGL1a and RsGL1b, that induces leaf trichome formation in radish. A Cas9/single guide RNA (sgRNA) vector with a common sgRNA corresponding to RsGL1a and RsGL1b was transferred. A total of eight T0 plants were analyzed, of which six (editing efficiency 75%) had a mutated RsGL1a, five (62.5%) had a mutated RsGL1b, and five showed mutations in both RsGL1a and RsGL1b. Most mutations in T0 plants were short (

We conducted a global-scale study to identify H. pylori antimicrobial-resistant genes (ARG), address their global distribution, and understand their effect on the antimicrobial resistance (AMR) phenotypes of the clinical isolates. We identified ARG using several well-known tools against extensive bacterial ARG databases, then analyzed their correlation with clinical antibiogram data from dozens of patients across countries. This revealed that combining multiple tools and databases, followed by manual selection of ARG from the annotation results, produces more conclusive results than using a single tool or database alone. After curation, the results showed that H. pylori has 42 ARG against 11 different antibiotic classes (16 genes related to single antibiotic class resistance and 26 genes related to multidrug resistance). Further analysis revealed that H. pylori naturally harbors ARG in the core genome, called the ‘Set of ARG commonly found in the Core Genome of H. pylori (ARG-CORE)’, while ARG-ACC—the ARG in the accessory genome—are exclusive to particular strains. In addition, we detected 29 genes of potential efflux pump-related AMR that were mostly categorized as ARG-CORE. The ARG distribution appears to be almost similar either by geographical or H. pylori populations perspective; however, some ARG had a unique distribution since they tend to be found only in a particular region or population. Finally, we demonstrated that the presence of ARG may not directly correlate with the sensitive/resistance phenotype of clinical patient isolates but may influence the minimum inhibitory concentration phenotype.

Abstract Background Myeloid sarcoma (MS) is a rare disease, mostly found in conjunction with acute myelogenous leukemia or other diseases, and primary nonleukemic MS of the spleen is particularly rare. Case presentation We report a 57-year-old male who presented with a spleen mass that was found incidentally, and was enlarged. As a result of various examinations, he was diagnosed with primary MS of the spleen with suspected involvement of the transverse colon, left kidney, pancreatic tail, and left diaphragm. He underwent a total splenectomy, partial pancreatectomy, partial colectomy, left nephrectomy, and left diaphragm partial resection. Histological examination revealed splenic primary MS. Bone marrow biopsy and immunophenotypic flow cytometry revealed no evidence of myeloid leukemia. He underwent umbilical cord blood transplantation, and he is currently living without a sign of recurrence at 10 months after surgery. Conclusions We experienced a very rare case of primary spleen MS that was discovered without a hematologic malignancy. Two cases of surgically resected primary splenic MS have been reported, including the present case.

Background: There is little data on the outcome of cabazitaxel (CBZ) treatment of elderly patients with castration-resistant prostate cancer (CRPC). This study assessed the efficacy and safety of CBZ chemotherapy in patients with CRPC aged 75 years or older in a multiinstitutional study. Methods: We retrospectively reviewed the 74 patients with CRPC treated with CBZ enrolled in 10 institutions. Clinicopathological backgrounds, prognosis including prostate-specific antigen decline, time to treatment failure, progression-free survival, overall survival, and safety profiles were compared between younger (

Summary: A virulence bacterium, Helicobacter pylori, evolved parallel to its host human, therefore, can work as a marker for tracing the human migration. We found H. pylori strains indigenous in the southernmost islands of Japanese Archipelago, Okinawa, and defined them as hspOkinawa and hpRyukyu. Genome data of the strains revealed that hspOkinawa diverged from other East Asian strains about 20,000 years ago, and that hpRyukyu diverged about 45,000 years ago. The closest strains of hpRyukyu were found from Afghanistan, Punjab, and Nepal, which suggest this strain originated in the central Asia and traveled across the Eurasian continent during Paleolithic era. The divergence date of hpRyukyu corresponds with human fossil records in Okinawa. Although it is controversial from human DNA analyses whether descendants of the Paleolithic migrants remain in the modern Japanese population, this study reveals that the bacterium of Paleolithic origin remains in the stomachs of current Japanese.

A voltammetric method has been developed for the determination of the acid dissociation constant (pKa) of (RfSO2)2CHR (Rf = perfluoroalkyl), which is a strongly acidic molecule that serves as an acid catalyst. In acetonitrile solution containing small quantity of the acid, the reduction peak potential of quinone caused by the acid shifted to a more positive side accompanied by an increase in the acidity of the acid. This relationship was in good agreement with an equation derived from the Nernst equation. The present finding has been successfully applied to the determination of the pKa of the acids in acetonitrile with values ranging from 7 to 17.

Abstract Aim With population aging, the number of frail patients with colorectal cancer has increased. The Clinical Frailty Scale (CFS) is a validated tool for assessing frailty, and higher scores indicate worse clinical outcomes following cardiovascular procedures. This retrospective study aimed to examine preoperative frailty in relation to recurrence and mortality following curative resection of colorectal cancer. Methods We retrospectively analyzed data for 729 consecutive patients undergoing curative resection of stage I–stage III colon and rectal adenocarcinoma between January 2009 and December 2016. Frailty was assessed using the CFS: 1 (very fit) to 9 (terminally ill), and frailty was defined as CFS ≥ 4. Recurrence‐free survival (RFS) and overall survival (OS) were compared between frail and nonfrail patients. Cox proportional hazards model was used to calculate hazard ratios (HRs), controlling for potential confounders. Results CFS score was negatively correlated with the Barthel index of activities of daily living (Spearman's ρ = −0.83). Of the 729 patients, 253 (35%) were frail. In multivariable analyses adjusting for potential confounders including age and disease stage, frailty was independently associated with shorter RFS (multivariable HR: 1.70, 95% confidence interval: 1.25‐2.31, P .72). Conclusion Preoperative frailty was independently associated with shorter RFS and OS following resection of nonmetastatic colorectal cancer, regardless of age and disease stage. Further trials are needed to establish treatment strategies for frail patients with colorectal cancer.

Current management of gastric inflammation involves the eradication of Helicobacter pylori. However, the effectiveness of commonly used antibiotics against H. pylori infection has decreased due to antibiotic resistance. Phenotypic-based diagnostics are laborious and finding the cause of resistance can be difficult. Therefore, early detection and understanding of the underlying mechanism of this resistance are necessary. This study evaluated the mutations in the genes related to the Antimicrobial Resistance (AMR) of the clinical isolates from Bangladeshi subjects. Whole-genome sequencing was performed on 56 isolates and the genes (such as pbp1a, rdxA, ribF, fur, gyrA, gyrB, 23S rRNA, and infB) were extracted. The reads were assembled, and the SNPs were extracted by the latest pipeline for antibiotic mutation analysis, ARIBA. The mutations and the association with the antibiotic phenotypes were evaluated using Fisher’s exact test. In this study, the clarithromycin resistance rate was high, 39.3% (22/56), with the median MIC 24 mg/L ranging from 2 to 128 mg/L. The mutation of A2147G was significantly associated with resistance (p = 0.000018) but not in locus A2146G (p = 0.056). Levofloxacin also posed a high resistance. We observed that the mutation of D91N (but not D91Y) (p = 0.002) and N87K (p = 0.002) of gyrA was associated with levofloxacin resistance. Mutations in locus A343V (p = 0.041) of gyrB also showed a significant association. Meanwhile, in the pbp1a gene, several mutations might explain the resistance; they were G594fs (p = 0.036), K306R (p = 0.036), N562Y (p = 0.0006), and V45I (p = 0.018). The prevalence of metronidazole was exceptionally high (96.4%), and numerous mutations occurred in rdxA genes, including the truncation of genes. These results imply that the mutation in genes encoding the target protein of antibiotics remains the critical resistance mechanism in H. pylori.

Perioperative management of pregnant women with heart failure is difficult. Management of anesthesia in pregnant women is especially difficult because all of the currently available choices present challenges. We report a patient with peripartum cardiomyopathy (PPCM) who required an emergent cesarean section and discuss the possible tactics for managing anesthesia. A 40-year-old primipara with severe cardiac and respiratory failure required an emergent cesarean section at 39 +1 gestational weeks. Her left ventricular ejection fraction was between 10% and 15%, and she had orthopnea. General anesthesia was planned after inserting sheaths for percutaneous cardiopulmonary support from the femoral artery and vein. However, when the patient was asked to lie down on the operation bed, she panicked and resisted because of labor pain and dyspnea. Therefore, anesthesia was induced instead of the initial plan. Finally, we successfully managed the anesthesia and delivered the newborn. There are no alternatives to general anesthesia in patients with PPCM presenting with orthopnea. Anesthesia induction in the supine position is impossible in such patients owing to dyspnea. Anesthesia should be started with light sedation in the sitting position, and ketamine or low-dose remifentanil may be an option to maintain maternal hemodynamics and prevent neonatal asphyxia.

Beside diagnostic uncertainties due to the lack of a perfect gold standard test for Helicobacter pylori infection, the diagnosis and the prevalence estimation for this infection encounter particular challenges in Africa including limited diagnostic tools and specific genetic background. We developed and evaluated the accuracy of an enzyme-linked immunosorbent assay (ELISA) system tailored for H. pylori genetics in Africa (HpAfr-ELISA). Strains belonging to main genetic populations infecting Africans were exploited as sources for whole-cell antigens to establish in-house the ELISA system. A phase II unmatched case-control study explored the diagnostic accuracy of the HpAfr-ELISA using a training set of samples collected from dyspeptic patients from Kinshasa, the Democratic Republic of Congo (DRC) who had been tested with invasive standard tests (i.e., histology, culture, and rapid urease test) in 2017. Then the assay was cross-validated through a community-based survey assessing the prevalence of H. pylori and associated factors in 425 adults from Mbujimayi, DRC in 2018. Bayesian inferences were used to deal with statistical uncertainties of estimates (true prevalence, sensitivity, and specificity) in the study population. At its optimal cut-off-value 20.2 U/mL, the assay achieved an estimated sensitivity of 97.6% (95% credible interval [95%CrI]: 89.2; 99.9%) and specificity of 90.5% (95%CrI: 78.6; 98.5). Consistent outcomes obtained at repeated tests attested the robustness of the assay (negative and positive agreements always > 70%). The true prevalence of H. pylori was estimated 53.8% [95%CrI: 42.8; 62.7%]. Increasing age (adjusted odds ratio [aOR] > 1.0 [95% confidence interval (CI): > 1.0; 1.1]; p

Uncaria Hook (UH) is a dry stem with hook of Ucaria plant and is contained in Traditional Japanese and Chinese medicine such as yokukansan, yokukansankachimpihange, chotosan, Gouteng-Baitouweng, and Tianma-Gouteng Yin. UH contains active indole and oxindole alkaloids and has the therapeutic effects on ailments of the cardiovascular and central nervous systems. The recent advances of analytical technology led to reports of detailed pharmacokinetics of UH alkaloids. These observations of pharmacokinetics are extremely important for understanding the treatment’s pharmacological activity, efficacy, and safety. This review describes properties, pharmacology, and the recently accumulated pharmacokinetic findings of UH alkaloids, and discusses challenges and future prospects. UH contains major indole and oxindole alkaloids such as corynoxeine, isocorynoxeine, rhynchophylline, isorhynchophylline, hirsuteine, hirsutine, and geissoschizine methyl ether (GM). These alkaloids exert neuroprotective effects against Alzheimer’s disease, Parkinson’s disease, and depression, and the mechanisms of these effects include anti-oxidant, anti-inflammatory, and neuromodulatory activities. Among the UH alkaloids, GM exhibits comparatively potent pharmacological activity (e.g., agonist activity at 5-HT1A receptors). UH alkaloids are absorbed into the blood circulation and rapidly eliminated when orally administered. UH alkaloids are predominantly metabolized by Cytochrome P450 (CYP) and converted into various metabolites, including oxidized and demethylated forms. Regarding GM metabolism by CYPs, a gender-dependent difference is observed in rats but not in humans. Several alkaloids are detected in the brain after passing through the blood–brain barrier in rats upon orally administered. GM is uniformly distributed in the brain and binds to various channels and receptors such as the 5-HT receptor. By reviewing the pharmacokinetics of UH alkaloids, challenges were found, such as differences in pharmacokinetics between pure drug and crude drug products administration, food-influenced absorption, metabolite excretion profile, and intestinal tissue metabolism of UH alkaloids. This review will provide readers with a better understanding of the pharmacokinetics of UH alkaloids and their future challenges, and will be helpful for further research on UH alkaloids and crude drug products containing UH.

Transcatheter mitral valve repair with the MitraClip, a catheter-based percutaneous edge-to-edge repair technique to correct mitral regurgitation (MR), has been demonstrated in Western studies to be an effective and safe MR treatment strategy. However, randomised clinical trial data on its use in Asian-Pacific patients is limited. Hence, the Asian Pacific Society of Cardiology convened an expert panel to review the available literature on MitraClip and to develop consensus recommendations to guide clinicians in the region. The panel developed statements on the use of MitraClip for the management of degenerative MR, functional MR, and other less common indications, such as acute MR, dynamic MR, hypertrophic obstructive cardiomyopathy, and MR after failed surgical repair. Each statement was voted on by each panel member and consensus was reached when 80% of experts voted ‘agree’ or ‘neutral’. This consensus-building process resulted in 10 consensus recommendations to guide general cardiologists in the evaluation and management of patients in whom MitraClip treatment is being contemplated.

Abstract Background Helicobacter pylori is a pathogenic bacterium that causes various gastrointestinal diseases in the human stomach. H. pylori is well adapted to the human stomach but does not easily infect other animals. As a model animal, Mongolian gerbils are often used, however, the genome of the inoculated H. pylori may accumulate mutations to adapt to the new host. To investigate mutations occurring in H. pylori after infection in Mongolian gerbils, we compared the whole genome sequence of TN2 wild type strain (TN2wt) and next generation sequencing data of retrieved strains from the animals after different lengths of infection. Results We identified mutations in 21 loci of 17 genes of the post-inoculation strains. Of the 17 genes, five were outer membrane proteins that potentially influence on the colonization and inflammation. Missense and nonsense mutations were observed in 15 and 6 loci, respectively. Multiple mutations were observed in three genes. Mutated genes included babA, tlpB, and gltS, which are known to be associated with adaptation to murine. Other mutations were involved with chemoreceptor, pH regulator, and outer membrane proteins, which also have potential to influence on the adaptation to the new host. Conclusions We confirmed mutations in genes previously reported to be associated with adaptation to Mongolian gerbils. We also listed up genes that mutated during the infection to the gerbils, though it needs experiments to prove the influence on adaptation.

This data article contains the data on metabolic profiling of healthy human subjects’ plasma before and after administration of the Japanese Kampo medicine maoto. Four healthy human subjects were recruited. Plasma samples were collected before and 0.25, 0.5, 1, 2, 4 and 8 h after maoto treatment. Endogenous and exogenous compounds in plasma were analyzed using MS. Endogenous compounds including saccharides, amino acids, organic acids and other hydrophilic metabolites were semi-quantitatively measured using GC-MS/MS. Lipid mediators such as arachidonic acid, docosahexaenoic acid and eicosapentaenoic acid were semi-quantitatively measured using LC-MS/MS. Maoto constituents in plasma were quantitatively measured using LC-MS/MS. The data files contain the area ratio values, which were normalized to the intensity of the internal standard, and plasma concentration of maoto compounds. The data article is related to the research article titled “Phenotyping analysis of the Japanese Kampo medicine maoto in healthy human subjects using wide-targeted plasma metabolomics” (Kitagawa et al., 2018).

Structures are reported for six closely related salts of tris(bipyridyl)iron(II) cations, namely tris(2,2′-bipyridine)iron(II) bis(1,1,3,3-tetracyano-2-methoxypropenide) 0.776-hydrate, [Fe(C10H8N2)3](C8H3N4O)2.0.776H2O, (I), tris(2,2′-bipyridine)iron(II) 1,1,3,3-tetracyano-2-(propylsulfanyl)propenide perchlorate, [Fe(C10H8N2)3](C10H7N4S)(ClO4), (II), tris(5,5′-dimethyl-2,2′-bipyridine)iron(II) 1,1,3,3-tetracyano-2-methoxypropenide tetrafluoridoborate ethanol 0.926-solvate, [Fe(C12H12N2)3](C8H3N4O)(BF4).0.926C2H2O, (III), tris(5,5′-dimethyl-2,2′-bipyridine)iron(II) 1,1,3,3-tetracyano-2-ethoxypropenide tetrafluoridoborate, [Fe(C12H12N2)3](C9H5N4O)(BF4), (IV), tris(5,5′-dimethyl-2,2′-bipyridine)iron(II) 1,1,3,3-tetracyano-2-(ethylsufanyl)propenide tetrafluoridoborate, [Fe(C12H12N2)3](C9H5N4S)(BF4), (V), and tris(5,5′-dimethyl-2,2′-bipyridine)iron(II) 1,1,3,3-tetracyano-2-propoxypropenide tetrafluoridoborate, [Fe(C12H12N2)3](C10H7N4O)(BF4), (VI). In compound (I), one of the anions is disordered over two sets of atomic sites with equal occupancies while, in the second anion, just one of the C(CN)2 units is disordered, again over two sets of atomic sites with equal occupancies: the anionic components are linked by multiple C—H...N hydrogen bonds to form a three-dimensional framework. In compound (II), the polynitrile anion is disordered over two sets of atomic sites with occupancies in the approximate ratio 3:1, while the perchlorate anion is disordered over three sets of atomic sites: there are C—N...π interactions between the cations and the polynitrile anion. The polynitrile anion in compound (III) is fully ordered, but the tetrafluoridoborate anion is disordered over two sets of atomic sites with occupancies 0.671 (4) and 0.329 (4): the cations and the tetrafluoridoborate anions are linked by C—H...F interactions to form an interrupted chain. Compounds (IV) and (V) are isostructural and all of the ionic components are fully ordered in both of them: the cations and tetrafluoridoborate anions are linked into C22(12) chains. The polynitrile anion in compound (VI) is disordered over two sets of atomic sites with approximately equal occupancies, and here the chains formed by the cations and the tetrafluoridoborate anions are of the C22(13) type.

Transforming growth factor-β1 (TGF-β1) plays a dual role in cancer, acting as a tumor suppressor in the early stage of cancer development and as a tumor promoter in the later stage of cancer progression in various cancers. In this study, we investigated the association between genetic polymorphisms in TGFB1 and clinicopathological characteristics or oncological outcome in prostate cancer cases treated with androgen-deprivation therapy (ADT) according to metastasis status. Japanese male patients with hormone-sensitive prostate cancer treated with ADT from 1993 to 2005 were included in this study. Genomic DNA was obtained from whole blood samples, and genotyping of TGFB1 (rs2241716 and rs4803455) was performed by PCR-based technique. No significant association between genetic polymorphisms in TGFB1 (rs2241716 and rs4803455) and clinicopathological parameters or prognosis was observed in patients with non-metastatic disease. In patients with metastatic disease, Gleason score in CT/TT carriers (rs2241716) and CA/AA carriers (rs4803455) was unfavorable compared with CC carriers. In addition, the CT/TT alleles in rs2241716 (hazard ratio, 1.82; 95% confidence interval, 1.12–2.94; P = 0.015) and the CA/AA alleles in rs4803455 (hazard ratio, 1.75; 95% confidence interval, 1.03–2.98; P = 0.040) were associated with a higher risk of progression during ADT compared with the CC allele in patients with metastatic disease. TGFB1 genetic variations were associated with adverse characteristics and progression risk in ADT among patients with metastatic disease, but not those with non-metastatic disease, supporting a distinct role of TGF-β signaling between non-metastatic and metastatic prostate cancer.

Postzygotic reproductive isolation maintains species integrity and uniformity and contributes to speciation by restricting the free gene flow between divergent species. In this study we identify causal genes of two Mendelian factors S22A and S22B on rice chromosome 2 inducing F1 pollen sterility in hybrids between Oryza sativa japonica-type cultivar Taichung 65 (T65) and a wild relative of rice species Oryza glumaepatula. The causal gene of S22B in T65 encodes a protein containing DUF1668 and gametophytically expressed in the anthers, designated S22B_j. The O. glumaepatula allele S22B-g, allelic to S22B_j, possesses three non-synonymous substitutions and a 2-bp deletion, leading to a frameshifted translation at the S22B C-terminal region. Transcription level of S22B-j and/or S22B_g did not solely determine the fertility of pollen grains by genotypes at S22B. Western blotting of S22B found that one major band with approximately 46 kDa appeared only at the mature stage and was reduced on semi-sterile heterozygotes at S22B, implying that the 46 kDa band may associated in hybrid sterility. In addition, causal genes of S22A in T65 were found to be S22A_j1 and S22A_j3 encoding DUF1668-containing protein. The allele of a wild rice species Oryza meridionalis Ng at S22B, designated S22B_m, is a loss-of-function allele probably due to large deletion of the gene lacking DUF1668 domain and evolved from the different lineage of O. glumaepatula. Phylogenetic analysis of DUF1668 suggested that many gene duplications occurred before the divergence of current crops in Poaceae, and loss-of-function mutations of DUF1668-containing genes represent the candidate causal genetic events contributing to hybrid incompatibilities. The duplicated DUF1668-domain gene may provide genetic potential to induce hybrid incompatibility by consequent mutations after divergence.

Silicon P-i-N diodes with a p+ region in the anode—where boron atoms are implanted and activated with relatively low-temperature furnace annealing (FA) or high-temperature laser annealing (LA)—show a large difference between the leakage currents of the diode samples activated using FA and LA. In this paper, in order to clarify the cause of the difference in leakage current, the generation current and diffusion current are verified. For estimating the generation current, the trap level was analyzed by deep level transient spectroscopy (DLTS) in a wide bias range of +0.3 V to −160 V, which corresponds to a depletion region width of 0 µm–37 µm, and trap density depth profiles are analyzed using DLTS. The DLTS analysis shows that the trap density is relatively uniform in the FA sample; however, the LA sample has a lower trap density near the p+ region of the anode. The leakage current of the diodes is calculated using the trap density profiles based on the leakage current model that includes generation and diffusion currents. The calculated and measured leakage currents are compared, and the relationship between the trap density and the leakage current is investigated. The reverse bias dependence of the calculated leakage current corresponds with the measured value for the LA sample, which implies that the trap density in the n-substrate obtained by DLTS can explain the measured leakage current well. For the FA sample, the measured leakage current is larger than the calculated value in the high reverse bias region. This suggests that there are large amounts of inactivated boron in the p+ region of the anode of the FA sample because of the low activation temperature. Only a few parts of the inactivated boron are believed to form a deep energy level trap that increases the generation leakage current. In order to reduce the leakage current of the P-i-N diode, it is effective to increase the activation rate of boron in the anode p+ region. By applying the LA method to a reverse-blocking insulated gate bipolar transistor with a built-in P-i-N diode on the collector side, the reverse leakage current can be reduced, and the operating temperature can be improved.

Evaluation of Helicobacter pylori resistance to antibiotics is crucial for treatment strategy in Myanmar. Moreover, the genetic mechanisms involved remain unknown. We aimed to investigate the prevalence of H. pylori infection, antibiotic resistance, and genetic mechanisms in Myanmar. One hundred fifty patients from two cities, Mawlamyine (n = 99) and Yangon (n = 51), were recruited. The prevalence of H. pylori infection was 43.3% (65/150). The successfully cultured H. pylori isolates (n = 65) were tested for antibiotic susceptibility to metronidazole, levofloxacin, clarithromycin, amoxicillin, and tetracycline by Etest, and the resistance rates were 80%, 33.8%, 7.7%, 4.6%, and 0%, respectively. In the multidrug resistance pattern, the metronidazole–levofloxacin resistance was highest for double-drug resistance (16/19; 84.2%), and all triple-drug resistance (3/3) was clarithromycin–metronidazole–levofloxacin resistance. Twenty-three strains were subjected to next-generation sequencing to study their genetic mechanisms. Interestingly, none of the strains resistant to clarithromycin had well-known mutations in 23S rRNA (e.g., A2142G, A2142C, and A2143G). New type mutation genotypes such as pbp1-A (e.g., V45I, S/R414R), 23S rRNA (e.g., T248C), gyrA (e.g., D210N, K230Q), gyrB (e.g., A584V, N679H), rdxA (e.g., V175I, S91P), and frxA (e.g., L33M) were also detected. In conclusion, the prevalence of H. pylori infection and its antibiotic resistance to metronidazole was high in Myanmar. The H. pylori eradication regimen with classical triple therapy, including amoxicillin and clarithromycin, can be used as the first-line therapy in Myanmar. In addition, next-generation sequencing is a powerful high-throughput method for identifying mutations within antibiotic resistance genes and monitoring the spread of H. pylori antibiotic-resistant strains.

SNORKEL1 (SK1) and SNORKEL2 (SK2) are ethylene responsive factors that regulate the internode elongation of deepwater rice in response to submergence. We previously reported that normal cultivated rice lacks SK genes because the Chromosome 12 region containing SK genes was deleted from its genome. However, no study has analyzed how the genome defect occurred in that region by comparing normal cultivated rice and deepwater rice. In this study, comparison of the sequence of the end of Chromosome 12, which contains SK genes, between normal and deepwater rice showed that complicated genome changes such as insertions, deletions, inversions, substitutions, and translocation occurred frequently in this region. In addition to SK1 and SK2 of deepwater rice, gene prediction analysis identified four genes containing AP2/ERF domains in normal cultivated rice and six in deepwater rice; we called these genes SK-LIKE (SKL) genes. SKs and SKLs were present in close proximity to each other, and the SKLs in normal cultivated rice were in tandem. These predicted genes belong to the same AP2/ERF subfamily and were separated into four types: SK1, SK2, SKL3, and SKL4. Sequence comparison indicated that normal cultivated rice possesses a gene with high homology to SK2, which we named SKL1. However, none of the predicted SKLs except for SKL3s were expressed during submergence. Although SKL3s were expressed in both normal and deepwater rice, normal rice does not undergo internode elongation, suggesting that its expression does not contribute to internode elongation. Plants overexpressing SKL1, which showed the most homology to SK2, underwent internode elongation similar to plants overexpressing SK1 and SK2 under normal growth conditions. A yeast one-hybrid assay showed that the C-end of SKL1 has transcription activity, as do the C-ends of SK1 and SK2. Our results suggested that SKLs were derived via gene duplication, but were not expressed and pseudogenized in normal cultivated rice during sequence evolution.

Abstract Background Metastatic renal cancers are relatively common. Most are metastases to the renal parenchyma via a hematogenous route and are derived from lung, breast, and gastrointestinal cancer, malignant melanoma, and hematologic malignant cancer. However, little is known about renal capsule metastasis from other cancers. Case presentation We report a 71-year-old woman with breast cancer who was treated with endocrine therapy. She presented with gross hematuria and was diagnosed as having right renal pelvic cancer and renal cell cancer. She underwent right laparoscopic radical nephroureterectomy. Pathological findings revealed right pelvic cancer and renal capsule metastasis. Conclusion Renal capsule metastasis derived from renal pelvic cancer is very rare. When diagnosing renal capsule cancer, we believe that renal capsule metastasis should also be taken into consideration. Clinical and radiological differential diagnosis of renal capsule metastasis from renal cell cancer and primary renal capsule cancer is difficult. Assessment of the histopathological findings of the surgical specimens seems to be the only realistic approach to achieving the correct diagnosis.

The use of serum anti-Helicobacter pylori IgG and pepsinogen (PG) detection as a diagnostic method was evaluated in Sri Lanka. Gastric biopsies were performed (353 patients), and the prevalence of H. pylori infection was 1.7% (culture) and 2.0% (histology). IgG serology testing showed an area under the curve (AUC) of 0.922 (cut-off, 2.95 U/mL; specificity, 91.56%; sensitivity, 88.89%). Histological evaluation showed mild atrophy (34.3%), moderate atrophy (1.7%), metaplasia (1.7%), chronic gastritis (6.2%), and normal tissue (56%). The PGI/PGII ratio was significantly higher in H. pylori-negative patients (p < 0.01). PGII and PGI/PGII levels were lower in patients with metaplasia than in those with normal mucosa (p = 0.049 and p < 0.001, respectively). The PGI/PGII ratio best discriminated metaplasia and moderate atrophy (AUC 0.88 and 0.76, respectively). PGI and PGII alone showed poor discriminative ability, especially in mild atrophy (0.55 and 0.53, respectively) and chronic gastritis (0.55 and 0.53, respectively). The best cut-off to discriminate metaplasia was 3.25 U/mL (95.19% specificity, 83.33% sensitivity). Anti-H. pylori IgG and PG assessment (ABC method) was performed (group B, 2.0%; group A, 92.1%). The new cut-off more accurately identified patients with metaplasia requiring follow-up (group B, 5.4%). Assessment of anti-H. pylori IgG and PG is valuable in countries with a low prevalence of H. pylori infection.

Abstract Background The elucidation of novel transcripts and their expression in response to various stress conditions is necessary to understand the transcriptional network of plants as an adaptation to biotic and abiotic stresses. We performed strand-specific RNA-Seq (ssRNA-Seq) on rice exposed to cadmium (Cd) for 24 h and investigated the expression of cis-natural antisense transcripts (cis-NATs), a class of endogenous coding or non-protein-coding RNAs with sequence complementarity to the opposite strands of RAP transcripts. Results Many RAP transcripts possessed cis-NATs and these cis-NATs were responsive to some extent. Cis-NATs were upregulated from 26, 266 and 409 RAP gene loci, while 2054, 2501 and 2825 RAP transcripts were upregulated from 38,123 RAP loci under high Cd exposure in roots at 1, 12 and 24 h, respectively. In addition, most of the upregulated cis-NATs showed little upregulation under ABA or cold treatment. A number of cis-NATs were upregulated from less than 35 RAP gene loci in different tissue and time-point combinations under low Cd exposure, suggesting that cis-NATs respond to environmental stress. Furthermore, 409 RAP transcripts with upregulated cis-NATs were classified into three groups based on the expression of the RAP transcripts from the opposite DNA strand, including 138 upregulated, 128 invariable, and 143 downregulated transcripts, although the responses of cis-NATs and RAP transcripts were not always correlated. Conclusions We have shown that the cis-NATs identified by ssRNA-Seq analysis are novel genes and that some of them are stress-specific and show different responses depending on the degree of stress and tissue. These results improve our understanding of the complete molecular mechanism of plant adaptation to Cd exposure.

Reproductive barriers are commonly observed in both animals and plants, in which they maintain species integrity and contribute to speciation. This report shows that a combination of loss-of-function alleles at two duplicated loci, DUPLICATED GAMETOPHYTIC STERILITY 1 (DGS1) on chromosome 4 and DGS2 on chromosome 7, causes pollen sterility in hybrid progeny derived from an interspecific cross between cultivated rice, Oryza sativa, and an Asian annual wild rice, O. nivara. Male gametes carrying the DGS1 allele from O. nivara (DGS1-nivaras) and the DGS2 allele from O. sativa (DGS2-T65s) were sterile, but female gametes carrying the same genotype were fertile. We isolated the causal gene, which encodes a protein homologous to DNA-dependent RNA polymerase (RNAP) III subunit C4 (RPC4). RPC4 facilitates the transcription of 5S rRNAs and tRNAs. The loss-of-function alleles at DGS1-nivaras and DGS2-T65s were caused by weak or nonexpression of RPC4 and an absence of RPC4, respectively. Phylogenetic analysis demonstrated that gene duplication of RPC4 at DGS1 and DGS2 was a recent event that occurred after divergence of the ancestral population of Oryza from other Poaceae or during diversification of AA-genome species.

Clostridium botulinum produces the botulinum neurotoxin (BoNT). Previously, we provided evidence for the “building-block” model of botulinum toxin complex (TC). In this model, a single BoNT is associated with a single nontoxic nonhemagglutinin (NTNHA), yielding M-TC; three HA-70 molecules are attached and form M-TC/HA-70, and one to three “arms” of the HA-33/HA-17 trimer (two HA-33 and one HA-17) further bind to M-TC/HA-70 via HA-17 and HA-70 binding, yielding one-, two-, and three-arm L-TC. Of all TCs, only the three-arm L-TC caused hemagglutination. In this study, we determined the solution structures for the botulinum TCs using small-angle X-ray scattering (SAXS). The mature three-arm L-TC exhibited the shape of a “bird spreading its wings”, in contrast to the model having three “arms”, as revealed by transmission electron microscopy. SAXS images indicated that one of the three arms of the HA-33/HA-17 trimer bound to both HA-70 and BoNT. Taken together, these findings regarding the conformational changes in the building-block architecture of TC may explain why only three-arm L-TC exhibited hemagglutination.

Directed Energy Deposition (DED), which is one of the Additive Manufacturing (AM) processes, can deposit metallic production efficiently by irradiating a high-power laser beam on a baseplate and supplying material powder simultaneously. DED has a problem in low mechanical strength due to residual pore inside of the production. However, the residual pore is also available to fabricate low density production as an opponent idea. If the residual pore could be increased intentionally and drastically, DED is applicable to foam metal fabrication. Foam metal could be produced continuously with high degree of freedom in shaping, if melt-pool can be foamed in DED. Therefore, this paper proposes a simple fabrication method for foam stainless alloy with DED by applying titanium hydride (TiH2) as a foaming agent for melt pool. TiH2 releases hydrogen in a high temperature environment as more than 500℃. Considering that high viscosity and low surface tension are required to stabilize pore generation, material powder also should contain a thickening agent (CaO: calcium oxide) and a surface active agent (Te: tellurium). According to the experimental results, an effect of CaO was hardly observed because the liquid stainless may already have high viscosity enough. On the other hand, Te certainly reduced the critical film thickness and prevented the pore collapse in stainless foam fabrication, according to the porosity rate calculation, the observation with a high speed camera, and the elemental distribution analysis. Furthermore, the proposed method successfully produced a foam structure in stainless steel with high porosity rate as 61% at maximum.

SIRT1 is known to have critical functions in the maintenance of homeostasis and cell survival, and it confers anti-ageing effects on cells and tissues. To identify novel foods and food ingredients with potential anti-ageing functions, a novel system for screening substances that activate the SIRT1 promoter in human colorectal cancer cells was established. We screened several lactic acid bacteria (LAB) and identified Lactobacillus brevis T2102 as a SIRT1-activating strain of LAB. T2102 inactivated β-catenin through SIRT1-mediated deacetylation and consequently suppressed the growth of the human colorectal cancer cell line DLD-1. Furthermore, T2102-induced degradation of β-catenin repressed transcription of the human telomerase reverse transcriptase (hTERT) gene, one of the target genes of β-catenin, which led to the induction of cellular senescence and concomitant growth suppression of DLD-1. These results indicate that SIRT1-activating T2102 might be a promising candidate for developing novel functional foods with anti-cancer properties.

Upon wounding or pathogen invasion, leaves of sorghum [Sorghum bicolor (L.) Moench] plants with the P gene turn purple, whereas leaves with the recessive allele turn brown or tan. This purple phenotype is determined by the production of two 3-deoxyanthocyanidins, apigeninidin and luteolinidin, which are not produced by the tan-phenotype plants. Using map-based cloning in progeny from a cross between purple Nakei-MS3B (PP) and tan Greenleaf (pp) cultivars, we isolated this gene, which was located in a 27-kb genomic region around the 58.1 Mb position on chromosome 6. Four candidate genes identified in this region were similar to the maize leucoanthocyanidin reductase gene. None of them was expressed before wounding, and only the Sb06g029550 gene was induced in both cultivars after wounding. The Sb06g029550 protein was detected in Nakei-MS3B, but only slightly in Greenleaf, in which it may be unstable because of a Cys252Tyr substitution. A recombinant Sb06g029550 protein had a specific flavanone 4-reductase activity, and converted flavanones (naringenin or eriodictyol) to flavan-4-ols (apiforol or luteoforol) in vitro. Our data indicate that the Sb06g029550 gene is involved in the 3-deoxyanthocyanidin synthesis pathway.

Seed dormancy allows wild barley grains to survive dry summers in the Near East but has been selected against for industrial applications such as beer and whisky production that require quicker germination. Here Sato et al. show that Qsd1is a major seed dormancy gene in barley and encodes an alanine aminotransferase.

The Japanese traditional medicine maobushisaishinto (MBST) has been prescribed for treating upper respiratory tract infections, such as a common cold. However, its mode of action is poorly understood, especially concerning the MBST constituent Asiasari Radix (AR). In this study, we focused on AR, with an objective of clarifying its bioavailable active ingredients and role within MBST by performing pharmacokinetic and pharmacological studies. Firstly, we performed qualitative non-targeted analysis utilizing high-resolution mass spectrometry to explore the bioavailable ingredients of AR as well as quantitative targeted analysis to reveal plasma concentrations following oral administration of MBST in rats. Secondly, we performed in vitro pharmacological study of bioavailable AR ingredients in addition to other ingredients of MBST to confirm any agonistic activities against transient receptor potential (TRP) channels. As a result, methyl kakuol and other compounds derived from AR were detected in the rat plasma and showed agonistic activity against TRPA1. This study suggests that methyl kakuol as well as other compounds have the potential to be an active ingredient in AR and thus presumably would contribute in part to the effects exerted by MBST.