Publications by authors named "Yutaka Suzuki"

815 Publications

TSS-seq of Toxoplasma gondii sporozoites revealed a novel motif in stage-specific promoters.

Infect Genet Evol 2022 Jan 15:105213. Epub 2022 Jan 15.

Division of Collaboration and Education, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Hokkaido 001-0020, Japan; International Collaboration Unit, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Hokkaido 001-0020, Japan. Electronic address:

Toxoplasma gondii is one of the most common zoonotic protozoan parasites. It has three major infectious stages: rapidly multiplying tachyzoites (Tz), slowly replicating bradyzoites (Bz) and a resting/free-living stage, sporozoites (Sz). The regulatory mechanisms governing stage-specific gene expression are not fully understood. Few transcriptional start sites (TSS) are known for Sz. In this study, we obtained TSS of Sz using an oligo-capping method and RNA-seq analysis. We identified 1,043,503 TSS in the Sz transcriptome. These defined 38,973 TSS clusters, of which, 11,925 were expressed in Sz and 1535 TSS differentially expressed in Sz. Based on these data, we defined promoter regions and novel sporozoite stage-specific motifs using MEME. TGTANNTACA was distributed around -55 to -75 regions from each TSS. Interestingly, the same motif was reported in another apicomplexan, Plasmodium berghei, as a cis-element of female-specific gametocyte genes, implying the presence of common regulatory machinery. Further comparative analysis should better define the distribution and function of these elements in other members of this important parasitic phylum.
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http://dx.doi.org/10.1016/j.meegid.2022.105213DOI Listing
January 2022

Localizing spontaneously hemostatic colonic diverticular bleeding using VISCOCLEAR gel: A case report.

Ann Med Surg (Lond) 2022 Jan 4;73:103141. Epub 2021 Dec 4.

Department of Surgery, International University of Health and Welfare Hospital, 537-3, Iguchi, Nasushiobara, Tochigi, 329-2763, Japan.

Colonic diverticular bleeding is the most common type of gastrointestinal bleeding. We report a case of an 82-year-old man with a chief complaint of melena. Enhanced computed tomography showed multiple diverticula, and water-assisted colonoscopy could not help identify the diverticulum responsible for bleeding. We injected VISCOCLEAR, a novel gel formulation, into the digestive tract endoscopically and successfully localized the bleeding point. Moreover, the use of VISCOCLEAR secured a clear visual field with reduced glare, as seen in the digital endoscopic image. Subsequently, we performed hemostatic clipping. The course after the endoscopic treatment was unremarkable. In this case, we could identify the exposed bleeding vessels in the diverticulum using VISCOCLEAR and perform hemostatic clipping. We intend to evaluate the effectiveness of VISCOCLEAR further by analyzing a series of cases.
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http://dx.doi.org/10.1016/j.amsu.2021.103141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8683678PMC
January 2022

Indocyanine green fluorescent lymphography during open inguinal hernia repair in a patient who developed postoperative ultrasonic hydrocele: A case report.

Int J Surg Case Rep 2022 Jan 18;90:106691. Epub 2021 Dec 18.

Department of Surgery, International University of Health and Welfare Hospital, Japan. Electronic address:

Background: To our knowledge, no reports of indocyanine green (ICG) fluorescent lymphography during inguinal hernia repair currently exist. We report the case of a patient who underwent ICG fluorescent lymphography during open inguinal hernia repair.

Case Presentation: A 63-year-old man was referred to our department for treatment of a right inguinal hernia, during which an ICG lymphography was performed. The patient had a history of robot-assisted radical prostatectomy for prostate cancer. Following induction of general anesthesia, 0.25 mg of ICG was injected into the right testicle and the scrotum was gently massaged, after which an open inguinal hernia repair was performed. During the operation, fluorescence from the ICG was observed in two lymphatic vessels in the spermatic cord. The ICG fluorescent vessels were resected due to the strong adhesion between the lymphatic vessels and the hernia sac. ICG leakage was observed in the resected vessels. An open tension-free technique was performed using an open mesh plug. The patient was discharged one day postoperatively. The histological diagnosis of the resected vessel was a lymphatic vessel. He had a slight postoperative hydrocele that was detected at the follow-up clinic 10 days postoperatively during ultrasonic examination (ultrasonic hydrocele).

Conclusion: We report the use of ICG fluorescent lymphography during open inguinal hernia repair in a patient who developed postoperative ultrasonic hydrocele. This case may indicate a relationship between lymphatic vessel injury and hydrocele.
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http://dx.doi.org/10.1016/j.ijscr.2021.106691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8717256PMC
January 2022

Preoperative Masseter Muscle Sarcopenia Predicts Mortality in Patients With Oesophageal Cancer.

Anticancer Res 2022 Jan;42(1):301-310

Department of Surgery, International University of Health and Welfare Hospital, Tochigi, Japan.

Background/aim: The impact of masseter muscle sarcopenia on the prognosis of patients with oesophageal cancer after oesophagectomy remains unclear.

Patients And Methods: We retrospectively analysed data from 70 patients with oesophageal cancer who underwent oesophagectomy between 2013 and 2019. Overall survival and disease-free survival rates were analysed using Cox proportional hazards models and Kaplan-Meier curves with the log-rank test.

Results: Masseter muscle sarcopenia was diagnosed in 36 patients. Multivariate analysis identified cytokeratin 19 fragment >1.1 (p=0.04); stage II, III, and IV cancer (p=0.01); and masseter muscle sarcopenia (p<0.01) as significant independent predictors of disease-free survival. Stage II, III, and IV cancer (p<0.01); masseter muscle sarcopenia (p<0.01); and postoperative pneumonia (p<0.01) were significant independent predictors of overall survival.

Conclusion: Preoperative masseter muscle sarcopenia could be a strong predictor of long-term outcomes in patients who undergo oesophagectomy for oesophageal cancer.
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http://dx.doi.org/10.21873/anticanres.15486DOI Listing
January 2022

HTLV-1 infection promotes excessive T cell activation and transformation into adult T cell leukemia/lymphoma.

J Clin Invest 2021 12;131(24)

Division of Genomics and Transcriptomics, Joint Research Center for Human Retrovirus Infection.

Human T cell leukemia virus type 1 (HTLV-1) mainly infects CD4+ T cells and induces chronic, persistent infection in infected individuals, with some developing adult T cell leukemia/lymphoma (ATL). HTLV-1 alters cellular differentiation, activation, and survival; however, it is unknown whether and how these changes contribute to the malignant transformation of infected cells. In this study, we used single-cell RNA-sequencing and T cell receptor-sequencing to investigate the differentiation and HTLV-1-mediated transformation of T cells. We analyzed 87,742 PBMCs from 12 infected and 3 uninfected individuals. Using multiple independent bioinformatics methods, we demonstrated the seamless transition of naive T cells into activated T cells, whereby HTLV-1-infected cells in an activated state further transformed into ATL cells, which are characterized as clonally expanded, highly activated T cells. Notably, the greater the activation state of ATL cells, the more they acquire Treg signatures. Intriguingly, the expression of HLA class II genes in HTLV-1-infected cells was uniquely induced by the viral protein Tax and further upregulated in ATL cells. Functional assays revealed that HTLV-1-infected cells upregulated HLA class II molecules and acted as tolerogenic antigen-presenting cells to induce anergy of antigen-specific T cells. In conclusion, our study revealed the in vivo mechanisms of HTLV-1-mediated transformation and immune escape at the single-cell level.
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http://dx.doi.org/10.1172/JCI150472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8670839PMC
December 2021

The proteome, not the transcriptome, predicts that oocyte superovulation affects embryonic phenotypes in mice.

Sci Rep 2021 12 9;11(1):23731. Epub 2021 Dec 9.

Max Planck Institute for Molecular Biomedicine, Roentgenstrasse 20, 48149, Muenster, Germany.

Superovulation is the epitome for generating oocytes for molecular embryology in mice, and it is used to model medically assisted reproduction in humans. However, whether a superovulated oocyte is normal, is an open question. This study establishes for the first time that superovulation is associated with proteome changes that affect phenotypic traits in mice, whereas the transcriptome is far less predictive. The proteins that were differentially expressed in superovulated mouse oocytes and embryos compared to their naturally ovulated counterparts were enriched in ontology terms describing abnormal mammalian phenotypes: a thinner zona pellucida, a smaller oocyte diameter, increased frequency of cleavage arrest, and defective blastocyst formation, which could all be verified functionally. Moreover, our findings indicate that embryos with such abnormalities are negatively selected during preimplantation, and ascribe these abnormalities to incomplete ovarian maturation during the time of the conventional superovulation, since they could be corrected upon postponement of the ovulatory stimulus by 24 h. Our data place constraints on the common view that superovulated oocytes are suitable for drawing general conclusions about developmental processes, and underscore the importance of including the proteins in a modern molecular definition of oocyte quality.
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http://dx.doi.org/10.1038/s41598-021-03054-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8660899PMC
December 2021

IκBα is required for full transcriptional induction of some NFκB-regulated genes in response to TNF in MCF-7 cells.

NPJ Syst Biol Appl 2021 Dec 1;7(1):42. Epub 2021 Dec 1.

Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Inflammatory stimuli triggers the degradation of three inhibitory κB (IκB) proteins, allowing for nuclear translocation of nuclear factor-κB (NFκB) for transcriptional induction of its target genes. Of these three, IκBα is a well-known negative feedback regulator that limits the duration of NFκB activity. We sought to determine whether IκBα's role in enabling or limiting NFκB activation is important for tumor necrosis factor (TNF)-induced gene expression in human breast cancer cells (MCF-7). Contrary to our expectations, many more TNF-response genes showed reduced induction than enhanced induction in IκBα knockdown cells. Mathematical modeling was used to investigate the underlying mechanism. We found that the reduced activation of some NFκB target genes in IκBα-deficient cells could be explained by the incoherent feedforward loop (IFFL) model. In addition, for a subset of genes, prolonged NFκB activity due to loss of negative feedback control did not prolong their transient activation; this implied a multi-state transcription cycle control of gene induction. Genes encoding key inflammation-related transcription factors, such as JUNB and KLF10, were found to be best represented by a model that contained both the IFFL and the transcription cycle motif. Our analysis sheds light on the regulatory strategies that safeguard inflammatory gene expression from overproduction and repositions the function of IκBα not only as a negative feedback regulator of NFκB but also as an enabler of NFκB-regulated stimulus-responsive inflammatory gene expression. This study indicates the complex involvement of IκBα in the inflammatory response to TNF that is induced by radiation therapy in breast cancer.
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http://dx.doi.org/10.1038/s41540-021-00204-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8636565PMC
December 2021

Gene expression signatures as candidate biomarkers of response to PD-1 blockade in non-small cell lung cancers.

PLoS One 2021 29;16(11):e0260500. Epub 2021 Nov 29.

Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan.

Although anti-PD-1/PD-L1 monotherapy has achieved clinical success in non-small cell lung cancer (NSCLC), definitive predictive biomarkers remain to be elucidated. In this study, we performed whole-transcriptome sequencing of pretreatment tumor tissue samples and pretreatment and on-treatment whole blood samples (WB) samples obtained from a clinically annotated cohort of NSCLC patients (n = 40) treated with nivolumab (anti-PD-1) monotherapy. Using a single-sample gene set enrichment scoring method, we found that the tumors of responders with lung adenocarcinoma (LUAD, n = 20) are inherently immunogenic to promote antitumor immunity, whereas those with lung squamous cell carcinoma (LUSC, n = 18) have a less immunosuppressive tumor microenvironment. These findings suggested that nivolumab may function as a molecular targeted agent in LUAD and as an immunomodulating agent in LUSC. In addition, our study explains why the reliability of PD-L1 expression on tumor cells as a predictive biomarker for the response to nivolumab monotherapy is quite different between LUAD and LUSC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0260500PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8629226PMC
January 2022

Transcriptomic Analysis of the Effects of Chemokine Receptor CXCR3 Deficiency on Immune Responses in the Mouse Brain during Infection.

Microorganisms 2021 Nov 12;9(11). Epub 2021 Nov 12.

National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Hokkaido, Japan.

The obligate intracellular parasite infects warm-blooded animals, including humans. We previously revealed through a whole-brain transcriptome analysis that infection with in mice causes immune response-associated genes to be upregulated, for instance, chemokines and chemokine receptors such as CXC chemokine receptor 3 (CXCR3) and its ligand CXC chemokine ligand 10 (CXCL10). Here, we describe the effect of CXCR3 on responses against infection in the mouse brain. In vivo assays using CXCR3-deficient mice showed that the absence of CXCR3 delayed the normal recovery of body weight and increased the brain parasite burden, suggesting that CXCR3 plays a role in the control of pathology in the brain, the site where chronic infection occurs. Therefore, to further analyze the function of CXCR3 in the brain, we profiled the gene expression patterns of primary astrocytes and microglia by RNA sequencing and subsequent analyses. CXCR3 deficiency impaired the normal upregulation of immune-related genes during infection, in astrocytes and microglia alike. Collectively, our results suggest that the immune-related genes upregulated by CXCR3 perform a particular role in controlling pathology when the host is chronically infected with in the brain.
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http://dx.doi.org/10.3390/microorganisms9112340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8620038PMC
November 2021

Chemerin Regulates Epithelial Barrier Function of Mammary Glands in Dairy Cows.

Animals (Basel) 2021 Nov 9;11(11). Epub 2021 Nov 9.

Graduate School of Agricultural Science, Tohoku University, 468-1 Aramaki Aza Aoba, Aoba-ku, Sendai 980-0842, Japan.

Epithelial barrier function in the mammary gland acts as a forefront of the defense mechanism against mastitis, which is widespread and a major disorder in dairy production. Chemerin is a chemoattractant protein with potent antimicrobial ability, but its role in the mammary gland remains unelucidated. The aim of this study was to determine the function of chemerin in mammary epithelial tissue of dairy cows in lactation or dry-off periods. Mammary epithelial cells produced chemerin protein, and secreted chemerin was detected in milk samples. Chemerin treatment promoted the proliferation of cultured bovine mammary epithelial cells and protected the integrity of the epithelial cell layer from hydrogen peroxide (HO)-induced damage. Meanwhile, chemerin levels were higher in mammary tissue with mastitis. Tumor necrosis factor alpha (TNF-α) strongly upregulated the expression of the chemerin-coding gene () in mammary epithelial cells. Therefore, chemerin was suggested to support mammary epithelial cell growth and epithelial barrier function and to be regulated by inflammatory stimuli. Our results may indicate chemerin as a novel therapeutic target for diseases in the bovine mammary gland.
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http://dx.doi.org/10.3390/ani11113194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8614423PMC
November 2021

Accelerated discovery of novel glycoside hydrolases using targeted functional profiling and selective pressure on the rumen microbiome.

Microbiome 2021 Nov 23;9(1):229. Epub 2021 Nov 23.

Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, T6G2P5, Canada.

Background: Carbohydrate-active enzymes (CAZymes) form the most widespread and structurally diverse set of enzymes involved in the breakdown, biosynthesis, or modification of lignocellulose that can be found in living organisms. However, the structural diversity of CAZymes has rendered the targeted discovery of novel enzymes extremely challenging, as these proteins catalyze many different chemical reactions and are sourced by a vast array of microbes. Consequently, many uncharacterized members of CAZyme families of interest have been overlooked by current methodologies (e.g., metagenomic screening) used to discover lignocellulolytic enzymes.

Results: In the present study, we combined phenotype-based selective pressure on the rumen microbiota with targeted functional profiling to guide the discovery of unknown CAZymes. In this study, we found 61 families of glycoside hydrolases (GH) (out of 182 CAZymes) from protein sequences deposited in the CAZy database-currently associated with more than 20,324 microbial genomes. Phenotype-based selective pressure on the rumen microbiome showed that lignocellulolytic bacteria (e.g., Fibrobacter succinogenes, Butyrivibrio proteoclasticus) and three GH families (e.g., GH11, GH13, GH45) exhibited an increased relative abundance in the rumen of feed efficient cattle when compared to their inefficient counterparts. These results paved the way for the application of targeted functional profiling to screen members of the GH11 and GH45 families against a de novo protein reference database comprised of 1184 uncharacterized enzymes, which led to the identification of 18 putative xylanases (GH11) and three putative endoglucanases (GH45). The biochemical proof of the xylanolytic activity of the newly discovered enzyme validated the computational simulations and demonstrated the stability of the most abundant xylanase.

Conclusions: These findings contribute to the discovery of novel enzymes for the breakdown, biosynthesis, or modification of lignocellulose and demonstrate that the rumen microbiome is a source of promising enzyme candidates for the biotechnology industry. The combined approaches conceptualized in this study can be adapted to any microbial environment, provided that the targeted microbiome is easy to manipulate and facilitates enrichment for the microbes of interest. Video Abstract.
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http://dx.doi.org/10.1186/s40168-021-01147-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8609826PMC
November 2021

TIGIT/CD155 axis mediates resistance to immunotherapy in patients with melanoma with the inflamed tumor microenvironment.

J Immunother Cancer 2021 11;9(11)

Research Institute, Chiba Cancer Center, Chiba, Japan

Background: Patients with cancer benefit from treatment with immune checkpoint inhibitors (ICIs), and those with an inflamed tumor microenvironment (TME) and/or high tumor mutation burden (TMB), particularly, tend to respond to ICIs; however, some patients fail, whereas others acquire resistance after initial response despite the inflamed TME and/or high TMB. We assessed the detailed biological mechanisms of resistance to ICIs such as programmed death 1 and/or cytotoxic T-lymphocyte-associated protein 4 blockade therapies using clinical samples.

Methods: We established four pairs of autologous tumor cell lines and tumor-infiltrating lymphocytes (TILs) from patients with melanoma treated with ICIs. These tumor cell lines and TILs were subjected to comprehensive analyses and in vitro functional assays. We assessed tumor volume and TILs in vivo mouse models to validate identified mechanism. Furthermore, we analyzed additional clinical samples from another large melanoma cohort.

Results: Two patients were super-responders, and the others acquired resistance: the first patient had a non-inflamed TME and acquired resistance due to the loss of the beta-2 microglobulin gene, and the other acquired resistance despite having inflamed TME and extremely high TMB which are reportedly predictive biomarkers. Tumor cell line and paired TIL analyses showed high CD155, TIGIT ligand, and TIGIT expression in the tumor cell line and tumor-infiltrating T cells, respectively. TIGIT blockade or CD155-deletion activated T cells in a functional assay using an autologous cell line and paired TILs from this patient. CD155 expression increased in surviving tumor cells after coculturing with TILs from a responder, which suppressed TIGIT T-cell activation. Consistently, TIGIT blockade or CD155-deletion could aid in overcoming resistance to ICIs in vivo mouse models. In clinical samples, CD155 was related to resistance to ICIs in patients with melanoma with an inflamed TME, including both primary and acquired resistance.

Conclusions: The TIGIT/CD155 axis mediates resistance to ICIs in patients with melanoma with an inflamed TME, promoting the development of TIGIT blockade therapies in such patients with cancer.
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http://dx.doi.org/10.1136/jitc-2021-003134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8603290PMC
November 2021

Cell cycle arrest determines adult neural stem cell ontogeny by an embryonic Notch-nonoscillatory Hey1 module.

Nat Commun 2021 11 12;12(1):6562. Epub 2021 Nov 12.

Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 113-0033, Japan.

Quiescent neural stem cells (NSCs) in the adult mouse brain are the source of neurogenesis that regulates innate and adaptive behaviors. Adult NSCs in the subventricular zone are derived from a subpopulation of embryonic neural stem-progenitor cells (NPCs) that is characterized by a slower cell cycle relative to the more abundant rapid cycling NPCs that build the brain. Yet, how slow cell cycle can cause the establishment of adult NSCs remains largely unknown. Here, we demonstrate that Notch and an effector Hey1 form a module that is upregulated by cell cycle arrest in slowly dividing NPCs. In contrast to the oscillatory expression of the Notch effectors Hes1 and Hes5 in fast cycling progenitors, Hey1 displays a non-oscillatory stationary expression pattern and contributes to the long-term maintenance of NSCs. These findings reveal a novel division of labor in Notch effectors where cell cycle rate biases effector selection and cell fate.
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http://dx.doi.org/10.1038/s41467-021-26605-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8589987PMC
November 2021

Prognostic significance of osteopenia in patients with colorectal cancer: A retrospective cohort study.

Ann Gastroenterol Surg 2021 Nov 26;5(6):832-843. Epub 2021 Jul 26.

Department of Surgery International University of Health and Welfare Hospital Nasushiobara Japan.

Aim: We examined the prognostic impact of osteopenia on the long-term outcomes of patients with colorectal cancer after laparoscopic colectomy along with other nutritional factors, including sarcopenia or the Glasgow Prognostic Score.

Methods: This retrospective cohort study analyzed the data of 230 patients with stage Ⅰ-Ⅲ colorectal cancers who underwent surgical resection between November 2010 and December 2015. Osteopenia and sarcopenia were evaluated by measuring the average pixel density in the mid-vertebral core of the 11th thoracic vertebra on enhanced computed tomography and the psoas muscle mass area at the third lumbar vertebra, respectively. The overall survival and disease-free survival rates were analyzed using Cox proportional hazards model and Kaplan-Meier curves with the log-rank test.

Results: Osteopenia was identified in 43 patients (18.7%). Univariate analysis showed that the disease-free survival rate was significantly worse in patients with stage II-III cancers, vascular invasion, carcinoembryonic antigen (CA) >5.0 ng/mL, CA19-9 > 37.0 U/mL, sarcopenia, and osteopenia (all  < .01). Multivariate analysis revealed that stage II-III cancers ( = .01), vascular invasion ( = .01), carcinoembryonic antigen >5.0 ( < .01), and osteopenia ( < .01) were significant independent disease-free survival predictors. In univariate analysis, the overall survival rate significantly decreased in patients with stage II-III cancers ( = .03), carcinoembryonic antigen >5.0 ( < .01), CA19-9 > 37.0 ( < .01), sarcopenia ( < .01), and osteopenia ( < .01). Multivariate analysis indicated that carcinoembryonic antigen >5.0 ( = .04), CA19-9 > 37.0 ( = .05), and osteopenia ( < .01) were significant independent predictors of overall survival.

Conclusion: Preoperative osteopenia could be a strong predictor of long-term outcomes in patients undergoing resection for colorectal cancer.
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http://dx.doi.org/10.1002/ags3.12491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560618PMC
November 2021

Rescue Partial ALPPS for Left Hemihepatectomy with Reconstruction of the Middle Hepatic Vein.

Dig Surg 2021 9;38(5-6):325-329. Epub 2021 Nov 9.

Department of Hepato-Biliary-Pancreatic Surgery, Kyorin University Hospital, Mitaka-City, Japan.

Major hepatectomy in patients with insufficient future liver remnant (FLR) volume and impaired liver functional reserve has considerable risks for posthepatectomy liver failure (PHLF). The patient was a male in his 70s with an intrahepatic cholangiocarcinoma in left hemiliver, involving the middle hepatic vein (MHV). Although FLR volume after left hemihepatectomy was estimated to be 64.4% of the total liver volume, an indocyanine green retention rate at 15 min (ICG-R15) value was 24.2%, thus the patient underwent left portal vein embolization. The FLR volume increased to 71.3%; however, the noncongestive FLR volume was re-estimated as 45.8% after resection of the MHV, the ICG-R15 value was 29.0%, and ICG-Krem was calculated as 0.037. We performed partial rescue Associating Liver Partition and Portal vein occlusion for Staged hepatectomy (ALPPS) for left hemihepatectomy with the MHV reconstruction. On the first stage, partial liver partition was done along Rex-Cantlie's line, preserving the MHV and sacrificing the remaining branches to segment 8. The FLR volume increased to 77.4% on day 14. The ICG-R15 value was 29.6%, but ICG-Krem after MHV reconstruction was estimated to be 0.059. The second-stage operation on day 21 was left hemihepatectomy with the MHV reconstruction using the left superficial femoral vein graft. The usage of rescue partial ALPPS may contribute to preventing PHLF by introducing occlusion of the portal and/or venous branches in the left hemiliver before curative hepatectomy.
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http://dx.doi.org/10.1159/000520695DOI Listing
January 2022

Laparoscopic cholecystectomy completely guided by indocyanine green fluorescence in a patient with gallstone: A case report.

Int J Surg Case Rep 2021 Nov 19;88:106533. Epub 2021 Oct 19.

Department of Surgery, International University of Health and Welfare, Tochigi, Japan.

Introduction: We report the execution of a cholecystectomy under complete fluorescence guidance using near-infrared camera images without switching to the white light mode, a method that has not been reported previously.

Presentation Of Case: An Asian woman in her fifties with no history of abdominal surgery was administered indocyanine green (ICG, 25 mg) intravenously 16 h before the surgery. Laparoscopic surgery was performed using VISION SENSE® with the four-trocar technique. The entire laparoscopic procedure was performed under fluorescence guidance. The orientation of the gallbladder neck can be recognized from the beginning of the procedure, and the serosal first incision could be positioned appropriately. All procedures were performed while the common bile duct was visualized. Peeling around the cystic duct and gallbladder bed was appropriately guided by ICG fluorescence.

Discussion: This method may be a safer form of surgery because the fluorescence did not disturb the surgical procedures.

Conclusion: Since this method was successful in this case, a case series is warranted.
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http://dx.doi.org/10.1016/j.ijscr.2021.106533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577460PMC
November 2021

Ethylene Induced by Sound Stimulation Enhances Anthocyanin Accumulation in Grape Berry Skin through Direct Upregulation of UDP-Glucose: Flavonoid 3--Glucosyltransferase.

Cells 2021 10 19;10(10). Epub 2021 Oct 19.

The Institute of Enology and Viticulture, University of Yamanashi, 1-13-1 Kitashin, Kofu 400-0005, Yamanashi, Japan.

Global warming has resulted in the loss of anthocyanin accumulation in berry skin. Sound stimulation can be used as a potential method for enhancing fruit color development since many plants recognize sound vibration as an external stimulus and alter their physiological status in response to it. Sound stimulation (sine wave sound at 1000 Hz) enhanced anthocyanin accumulation in grape cultured cells and berry skins in field-grown grapevines at the early stage of ripening. The transcription of and , which encode the key enzymes in anthocyanin and ethylene biosynthesis, respectively, was upregulated in grape cultured cells exposed to sound stimulation. In contrast, the transcription of and , which encode a transcription factor for and a key enzyme in abscisic acid biosynthesis, respectively, was not affected by the sound stimulation. A treatment with an ethylene biosynthesis inhibitor, aminoethoxyvinyl glycine hydrochloride, revered the enhancement of anthocyanin accumulation by sound stimulation. As the promoter assay using a GUS reporter gene demonstrated that promoter was directly activated by the ethylene-releasing compound ethephon, which enhanced anthocyanin accumulation in grape cultured cells, we conclude that sound stimulation enhanced anthocyanin accumulation through the direct upregulation of by ethylene biosynthesis. Our findings suggest that sound stimulation contributes to alleviating poor coloration in berry skin as a novel and innovative practical technique in viticulture.
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http://dx.doi.org/10.3390/cells10102799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534375PMC
October 2021

Nivolumab in combination with radiotherapy for metastatic esophageal neuroendocrine carcinoma after esophagectomy: a case report.

Surg Case Rep 2021 Oct 1;7(1):221. Epub 2021 Oct 1.

Department of Surgery, International University of Health and Welfare Hospital, 537-3, Iguchi, Nasushiobara City, Tochigi, 329-2763, Japan.

Background: Metastatic neuroendocrine carcinoma has an extremely poor prognosis, and no effective second-line treatment is available. Herein, we describe a case of multiple metastases after primary resection of esophageal neuroendocrine carcinoma successfully treated with nivolumab plus radiotherapy in a short time.

Case Presentation: A man in his 70s presented to our hospital after an abnormality was detected on an upper gastrointestinal series. Upper gastrointestinal endoscopy revealed a type 2 tumor spanning the endothelial cell junction to the abdominal esophagus. Histopathological examination of the biopsy confirmed a diagnosis of esophageal neuroendocrine carcinoma. The patient had no distant metastases. Thoracoscopic esophagectomy with three-field lymph node dissection was performed. Histopathological examination confirmed a diagnosis of esophageal neuroendocrine carcinoma with features of adenoid cystic-like carcinoma and squamoid pattern (pT2 [MP], INF a, ly1, v1 [EVG], pIM0, pDM0, pRM0, pN1 [1/28], M0; Stage II), which was positive for synaptophysin. The postoperative course was good, with no complications. The patient was treated with 100 mg of irinotecan and 100 mg of cisplatin, administered every 4 weeks, as postoperative adjuvant chemotherapy. Grade 3 loss of appetite was observed, and adjuvant chemotherapy was discontinued after four cycles of first-line treatment. A positron emission tomography-computed tomography scan 3 years after surgery showed abnormal uptake in the subaortic, left hilar, and left axillary lymph nodes, and in a mass in the right lung apex. The patient was diagnosed with metastatic esophageal neuroendocrine carcinoma postoperatively. First-line treatment could not be repeated due to toxicity from the initial treatment. Nivolumab (240 mg every 2 weeks) was administered as second-line treatment, and radiotherapy was started (56 Gy delivered in 28 fractions to the local [subaortic and hilar] lymph nodes). After 10 cycles of nivolumab in combination with radiotherapy (56 Gy), a positron emission tomography-computed tomography scan showed disappearance of all lesions. A complete response was achieved. Maintenance therapy (240 mg of nivolumab) was continued. No recurrence has been observed for 42 months.

Conclusions: We experienced a case in which nivolumab in combination with radiotherapy was effective for metastatic esophageal neuroendocrine carcinoma after primary resection.
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http://dx.doi.org/10.1186/s40792-021-01307-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486903PMC
October 2021

Clinical impact of perioperative atrial fibrillation on long-term recurrence of malignancy.

Heart Vessels 2021 Sep 30. Epub 2021 Sep 30.

Department of Cardiology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan.

Perioperative complications have been reported to be associated with a lower incidence of cancer-free survival. Perioperative atrial fibrillation (POAF) is one of occasionally observed complications in patients with malignancies who undergo noncardiac surgeries. However, the long-term clinical impact of POAF on those with malignancies have remained unknown. This was a prospective, single-center, observational study. Patients who underwent noncardiac surgeries for definitive malignancies between 2014 and 2017 were included. The primary and secondary endpoints were 3-year recurrence of malignancies and cancer death, respectively. The present study included consecutive 752 patients (mean age, 68 ± 11 years; males, 62%), and POAF was observed in 77 patients. The follow-up duration was 1037 (interquartile range, 699-1408) days. The 3-year recurrence of malignancies was observed in 239 (32%) patients (POAF, 32 [42%]; non-POAF, 207 [31%]) and 3-year mortality was 130 patients (17%). Cardiac, noncardiac, and cancer deaths were observed in 4 (0.5%), 126 (17%), and 111 (15%) patients, respectively. Multivariate Cox regression analysis demonstrated that POAF was associated with 3-year recurrence of malignancies (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.15-2.52). Landmark analysis demonstrated that POAF tended to be correlated with the incidence of 3-year cancer death (HR, 1.79; 95% CI, 0.96-3.31). In conclusion, POAF is associated with the subsequent recurrence of malignancies. The association of arrhythmia with cancer death may be revealed under longer follow-up durations.Clinical Trial Registration: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018270 . UMIN ID: UMIN000016146.
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http://dx.doi.org/10.1007/s00380-021-01954-4DOI Listing
September 2021

Effect of Vitamin D Supplements on Relapse of Digestive Tract Cancer with Tumor Stromal Immune Response: A Secondary Analysis of the AMATERASU Randomized Clinical Trial.

Cancers (Basel) 2021 Sep 20;13(18). Epub 2021 Sep 20.

Division of Molecular Epidemiology, The Jikei University School of Medicine, Tokyo 105-8461, Japan.

The aim was to examine whether vitamin D supplementation (2000 IU/day) reduces the risk of relapse in a subgroup of patients with digestive tract cancer, showing a sufficient immune response in tumor stroma by conducting secondary subgroup analyses of the AMATERASU randomized, double-blind, placebo-controlled trial (UMIN000001977). A total of 372 patients were divided into two subgroups stratified by the median density of immune cells infiltrating in tumor stroma into higher and lower halves. In the higher-half subgroup of CD56+ cells, the relapse ratio was significantly lower in the vitamin D group (7.4%) than in the placebo group (20.5%) (subdistribution hazard ratio (SHR), 0.35; 95% confidence interval (CI), 0.15-0.82), but it was equivalent (25.2% vs. 22.7%) in the lower-half subgroup of CD56+ cells (SHR, 1.21; 95% CI, 0.68-2.19) with a significant interaction ( = 0.02). Although there were no significant differences, the risk of relapse was lower in the vitamin D group than in the placebo group in the higher half of CD45RO+ memory T cells (8.9% vs. 19.2%), and of CD8+ cytotoxic T cells (11.3% vs. 22.5%). In patients with digestive tract cancer, vitamin D supplementation was hypothesized to reduce the risk of relapse in the subgroup of patients who already have an adequate infiltration of immune cells in their tumor stroma.
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http://dx.doi.org/10.3390/cancers13184708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470811PMC
September 2021

A combination approach of pseudotime analysis and mathematical modeling for understanding drug-resistant mechanisms.

Sci Rep 2021 09 16;11(1):18511. Epub 2021 Sep 16.

Laboratory of Cell Systems, Institute for Protein Research, Osaka University, Osaka, 565-0871, Japan.

Cancer cells acquire drug resistance through the following stages: nonresistant, pre-resistant, and resistant. Although the molecular mechanism of drug resistance is well investigated, the process of drug resistance acquisition remains largely unknown. Here we elucidate the molecular mechanisms underlying the process of drug resistance acquisition by sequential analysis of gene expression patterns in tamoxifen-treated breast cancer cells. Single-cell RNA-sequencing indicates that tamoxifen-resistant cells can be subgrouped into two, one showing altered gene expression related to metabolic regulation and another showing high expression levels of adhesion-related molecules and histone-modifying enzymes. Pseudotime analysis showed a cell transition trajectory to the two resistant subgroups that stem from a shared pre-resistant state. An ordinary differential equation model based on the trajectory fitted well with the experimental results of cell growth. Based on the established model, it was predicted and experimentally validated that inhibition of transition to both resistant subtypes would prevent the appearance of tamoxifen resistance.
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http://dx.doi.org/10.1038/s41598-021-97887-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445918PMC
September 2021

Application of long-read sequencing to the detection of structural variants in human cancer genomes.

Comput Struct Biotechnol J 2021 28;19:4207-4216. Epub 2021 Jul 28.

Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8561, Japan.

In recent years, the so-called long-read sequencing technology has had a substantial impact on various aspects of genome sciences. Here, we introduce recent studies of cancerous structural variants (SVs) using long-read sequencing technologies, namely Pacific Biosciences (PacBio) sequencers, Oxford Nanopore Technologies (ONT) sequencers, and linked-read methods. By taking advantage of long-read lengths, these technologies have enabled the precise detection of SVs, including long insertions by transposable elements, such as LINE-1. In addition to SV detection, the epigenome status (including DNA methylation and haplotype information) surrounding SV loci has also been unveiled by long-read sequencing technologies, to identify the effects of SVs. Among the various research fields in which long-read sequencing has been applied, cancer genomics has shown the most remarkable advances. In fact, many studies are beginning to shed light on the detection of SVs and the elucidation of their complex structures in various types of cancer. In the particular case of cancers, we summarize the technical limitations of the application of this technology to the analysis of clinical samples. We will introduce recent achievements from this viewpoint. However, a similar approach will be started for other applications in the near future. Therefore, by complementing the current short-read sequencing analysis, long-read sequencing should reveal the complex nature of human genomes in their healthy and disease states, which will open a new opportunity for a better understanding of disease development and for a novel strategy for drug development.
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http://dx.doi.org/10.1016/j.csbj.2021.07.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350331PMC
July 2021

Perineal stapled prolapse resection in combination with Thiersch operation for relapsed rectal prolapse: a case report.

Surg Case Rep 2021 Sep 3;7(1):200. Epub 2021 Sep 3.

Department of Surgery, International University of Health and Welfare Hospital, 537-3, Iguchi, Nasushiobara, Tochigi, 329-2763, Japan.

Background: Treatment options for complete rectal prolapse include over 100 procedures. In previous reports, operative rectal prolapse repair, regardless of the technique by perineal approach, was associated with high recurrence rates. However, there is no consensus on the optimal surgical procedure for relapsed rectal prolapse.

Case Presentation: A 97-year-old woman was admitted to our hospital with a chief complaint of complete rectal prolapse measuring > 5 cm. The patient had a history of laparoscopic anterior suture rectopexy without sigmoid resection under general anesthesia for complete rectal prolapse one year prior. The patient's postoperative course was uneventful. However, her dementia worsened (Hasegawa's dementia scale: 5/30 points) after the first operation. Further, moderate-to-severe aortic valve stenosis was first diagnosed with heart failure 6 months after the operation. Nine months after the initial surgery, she experienced a recurrence of complete rectal prolapse measuring approximately 5 cm. Considering the coexistence of advanced age, severe dementia, and aortic valve stenosis, surgery under general anesthesia was not indicated. Perineal stapled prolapse resection in combination with the t operation was planned because of its minimal invasiveness and shortened hospital stay. The procedure was performed by a team of two surgeons in the jack knife position, under spinal anesthesia. The prolapse was cut along the long-axis direction with three linear staplers and resected along the short-axis direction with four linear staplers. The cross-section of the linear stapler was reinforced with 3-0 Vicryl sutures. After rectal resection, the Thiersch operation using 1-0 nylon thread 1 cm away from the anal verge was additionally performed. The operative time was 24 min, and intraoperative blood loss was 1 mL. The postoperative course was uneventful. Three months after the operation, no recurrence was observed, and defecation function was good with improvements of Wexner score.

Conclusions: Perineal stapled prolapse resection in combination with the Thiersch operation could be a useful option for patients with relapsed rectal prolapse and with poor general condition, who are not indicated for other surgical procedures.
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http://dx.doi.org/10.1186/s40792-021-01287-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417194PMC
September 2021

TUBB3 E410K Syndrome With Childhood-Onset Nonalcoholic Steatohepatitis.

J Clin Endocrinol Metab 2022 Jan;107(1):e38-e43

Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.

Context: Nonalcoholic fatty liver disease (NAFLD) is becoming a major issue worldwide, even in children. Multiple parallel hits hypothesis has been suggested as progress of NAFLD, but the mechanism of NAFLD is not completely understood. β-Tubulin is essential in mitoses, neuronal migration, and axon guidance during neuronal development. Pathogenic variants in the TUBB3 gene were shown to be associated with a wide spectrum of neurological abnormalities, but not accompanied by hepatic complications, such as NAFLD.

Objective: This work aims to examine the association between TUBB3 mutation and nonalcoholic steatohepatitis (NASH).

Methods: An 11-year-old girl has been followed up as having atypical Möbius syndrome since infancy, as she was born with bilateral ptosis, paralytic strabismus, and facial weakness. At age 7 years, she was diagnosed with TUBB3 E410K syndrome by whole-exome sequencing. At age 10 years, her blood examination revealed elevated liver transaminase levels, which persisted for almost 2 years. She underwent liver biopsy, the results of which were suggestive of NASH.

Results: The expression of TUBB3 was absent, but that of tyrosine hydroxylase (TH) was present in the parenchymal nerve fibers of the liver. On the other hand, in comparison with an autopsy case of NASH and a normal control, these showed coexpression of TUBB3 and TH in the liver.

Conclusion: We report the first case of TUBB3 E410K syndrome accompanied by NASH. This case suggests that the TUBB3 mutation may be associated with the pathogenesis and progression of NASH in humans.
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http://dx.doi.org/10.1210/clinem/dgab628DOI Listing
January 2022

The Evolving Genomic Landscape of Esophageal Squamous Cell Carcinoma Under Chemoradiotherapy.

Cancer Res 2021 10 19;81(19):4926-4938. Epub 2021 Aug 19.

Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Esophageal squamous cell carcinoma (ESCC) often recurs after chemoradiotherapy, and the prognosis of ESCC after chemoradiotherapy has not improved over the past few decades. The mutation process in chemoradiotherapy-resistant clones and the functional relevance of genetic alterations remain unclear. To address these problems, we performed whole-exome sequencing of 52 tumor samples from 33 patients with ESCC who received radiotherapy combined with 5-fluorouracil/platinum. In multiregion analyses of pretreatment and locally recurrent lesions from five cases, most driver gene-altered clones remained under chemoradiotherapy selection pressure, while few driver gene alterations were acquired at recurrence. The mutation signatures of recurrent ESCC, including increased deletion frequency and platinum dose-dependent base substitution signatures, were substantially different from those of primary ESCC and reflected the iatrogenic impacts of chemoradiotherapy. Single-region analysis of 28 pretreatment tumors indicated that focal copy-number gain at the locus was significantly associated with poor progression-free survival and overall survival after chemoradiotherapy. gain remained throughout the chemoradiotherapy course and potentially contributes to intrinsic resistance to chemoradiotherapy. Consistent with these findings, copy number and mRNA and protein levels in ESCC cell lines correlated positively with resistance to radiotherapy, and knockdown improved sensitivity to radiotherapy. Overall, these data characterize the clonal evolution process induced by chemoradiotherapy and clinically relevant associations for genetic alterations in ESCC. These findings increase our understanding of therapeutic resistance and support the rationale for precision chemoradiotherapy. SIGNIFICANCE: Whole-exome sequencing reveals the genetic evolution of ESCC during chemoradiotherapy, highlighting gain in pretreatment tumors as a potential marker of therapy resistance.
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http://dx.doi.org/10.1158/0008-5472.CAN-21-0653DOI Listing
October 2021

Bile acid dysmetabolism in the gut-microbiota-liver axis under hepatitis C virus infection.

Liver Int 2022 Jan 5;42(1):124-134. Epub 2021 Sep 5.

Department of Clinical Laboratory Medicine, Nagoya City University Hospital, Nagoya, Japan.

Background & Aims: We recently analysed and reported the features of the micro biome under hepatitis C virus (HCV) infection, but the effect of HCV infection on bile acid (BA) metabolism in the gut-liver axis remains poorly understood. The aim of this study was to clarify the characteristics of the gut-liver axis in HCV-infected patients.

Methods: The faecal BAs composition and gut microbiota from 100 chronic hepatitis C (CHC) patients were compared with those from 23 healthy individuals. For transcriptional analysis of the liver, 22 mild CHC (fibrosis stages [F] 0-2) and 42 advanced CHC (F3-4) cases were compared with 12 healthy individuals. The findings were confirmed using chimeric mice with human hepatocytes infected with HCV HCR6.

Results: Chronic hepatitis C patients, even at earlier disease stages, showed BA profiles distinct from healthy individuals, in which faecal deoxycholic acid (DCA) was significantly reduced and lithocholic acid or ursodeoxycholic acid became dominant. The decrease in faecal DCA was correlated with reduction in commensal Clostridiales and increase in oral Lactobacillales. Impaired biosynthesis of cholic acid (CA) was observed as a reduction in the transcription level of cytochrome P450 8B1 (CYP8B1), a key enzyme in CA biosynthesis. The reductions in faecal DCA and liver CYP8B1 were also observed in HCV-infected chimeric mice.

Conclusions: Chronic hepatitis C alters the intestinal BA profile, in association with the imbalance of BA biosynthesis, which differs from the pattern in NAFLD. These imbalances appear to drive disease progression through the gut-microbiome-liver axis.
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http://dx.doi.org/10.1111/liv.15041DOI Listing
January 2022

Cashew nut shell liquid potentially mitigates methane emission from the feces of Thai native ruminant livestock by modifying fecal microbiota.

Anim Sci J 2021 Dec;92(1):e13614

Graduate School of Agriculture, Hokkaido University, Sapporo, Japan.

The methane-mitigating potency of cashew nutshell liquid (CNSL) was evaluated by investigating gas production from batch cultures using feces from Thai native ruminants that had been incubated for different periods. Feces was obtained from four Thai native cattle and four swamp buffaloes reared under practical feeding conditions at the Kasetsart University farm, Thailand. Fecal slurry from the same farm was also included in the analysis. CNSL addition successfully suppressed the methane production potential of feces from both ruminants by shifting short chain fatty acid profiles towards propionate production. Methane mitigation continued for almost 150 days, although the degree of mitigation was more apparent from Day 0 to Day 30. Bacterial and archaeal community shifts with CNSL addition were observed in feces from both ruminants; specifically, Bacteroides increased, whereas Lachnospiraceae and Ruminococcaceae decreased in feces to which CNSL was added. Fecal slurry did not show marked changes in gas production with CNSL addition. The findings showed that the addition of CNSL to the feces of ruminants native to the Southeast Asian region can suppress methane emission. Because CNSL can be easily obtained as a byproduct of the local cashew industry in this region, its on-site application might be ideal.
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http://dx.doi.org/10.1111/asj.13614DOI Listing
December 2021

Minimally invasive colostomy with endoscopy as a novel technique for creation of a trephine stoma.

Sci Rep 2021 08 17;11(1):16694. Epub 2021 Aug 17.

Department of Surgery, International University of Health and Welfare Hospital, 537-3, Iguchi, Nasushiobara, Tochigi, 329-2763, Japan.

The conventional approach of trephine stoma creation is associated with various limitations, including poor elevation of the sigmoid colon, misidentification of the target organs, and poor visualization of the operative field, which may require conversion to an open approach. Our study aimed to evaluate the safety, feasibility, and complications of minimally invasive colostomy with endoscopy (MICE), a new technique for trephine stoma creation. This retrospective cohort study included 14 patients. Patients diagnosed with obstructive rectal cancer or bladder and rectal disorders due to spinal cord injury or bone metastasis requiring sigmoid loop colostomy were eligible for the procedure. MICE was performed using a combination of endoscopic and fluoroscopic procedures. The primary endpoint was the technical success of MICE. Technical success using MICE was achieved in all 14 cases. The mean total operative time was 52.6 (range 32-107) min, and mean blood loss was 18.9 (range 1-50) mL. There was no incidence of conversion to open surgery. Postoperative complications included peristomal abscess formation and ischemic colitis in each case. MICE may be useful as a minimally invasive approach for trephine stoma creation that overcomes the problems of a conventional approach in high-risk patients.
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http://dx.doi.org/10.1038/s41598-021-96357-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370984PMC
August 2021

Addition of ginkgo fruit to cattle feces and slurry suppresses methane production by altering the microbial community structure.

Anim Sci J 2021 Dec;92(1):e13620

Graduate School of Agriculture, Hokkaido University, Sapporo, Japan.

The effect of ginkgo fruit addition on methane production potential of cattle feces and slurry was assessed in relation to other fermentation products and the microbial community. Holstein cattle fresh feces and slurry were left at 30°C for 0, 30, 60, 90, and 180 days with/without ginkgo fruit to monitor the effect on fermentation potential. With the addition of ginkgo fruit, methane production potential of feces was reduced on Day 30 and thereafter, and that of slurry was consistently reduced over the experimental period. As a general trend, ginkgo fruit addition resulted in decreased acetate and increased propionate in feces and acetate accumulation in slurry. With ginkgo fruit addition, MiSeq analyses indicated decreases in methanogen (in particular Methanocorpusculum), Ruminococcaceae, and Clostridiaceae populations and increases in Bacteroidaceae and Porphyromonadaceae populations, which essentially agreed with quantitative real-time polymerase chain reaction (qPCR) assay results. These data indicate that direct addition of ginkgo fruit to cattle excreta is useful for reducing methane emissions by altering the microbial community structure. The application of ginkgo fruit to lower methane emissions from cattle excreta is, therefore, useful in cases in which the excreta is left without special management for a long period of time.
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http://dx.doi.org/10.1111/asj.13620DOI Listing
December 2021

Elucidation of the speciation history of three sister species of crown-of-thorns starfish (Acanthaster spp.) based on genomic analysis.

DNA Res 2021 Aug;28(4)

School of Life Science and Technology, Tokyo Institute of Technology, Meguro-ku, Tokyo 152-8550, Japan.

The crown-of-thorns starfish (COTS) is a coral predator that is widely distributed in Indo-Pacific Oceans. A previous phylogenetic study using partial mitochondrial sequences suggested that COTS had diverged into four distinct species, but a nuclear genome-based analysis to confirm this was not conducted. To address this, COTS species nuclear genome sequences were analysed here, sequencing Northern Indian Ocean (NIO) and Red Sea (RS) species genomes for the first time, followed by a comparative analysis with the Pacific Ocean (PO) species. Phylogenetic analysis and ADMIXTURE analysis revealed clear divergences between the three COTS species. Furthermore, within the PO species, the phylogenetic position of the Hawaiian sample was further away from the other Pacific-derived samples than expected based on the mitochondrial data, suggesting that it may be a PO subspecies. The pairwise sequentially Markovian coalescent model showed that the trajectories of the population size diverged by region during the Mid-Pleistocene transition when the sea-level was dramatically decreased, strongly suggesting that the three COTS species experienced allopatric speciation. Analysis of the orthologues indicated that there were remarkable genes with species-specific positive selection in the genomes of the PO and RS species, which suggested that there may be local adaptations in the COTS species.
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http://dx.doi.org/10.1093/dnares/dsab012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386664PMC
August 2021
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