Description of Aliirhizobium terrae sp. nov., A Plant Growth-Promoting Bacterium Isolated from a Maize-Rice Rotation Agriculture Field.

A polyphasic taxonomic approach was used to characterize a novel bacterium, designated strain CC-CFT758T, isolated from a maize-rice rotation agriculture field in Taiwan. The cells are aerobic, Gram-stain-negative, rod-shaped, positive for catalase and oxidase, and grow at 20-30 °C (optimal 30 â„ƒ), at pH 6.0-8.0 (optimal 8.0), and with 0-4% (w/v) NaCl (optimum, 2-3%). Phylogenetic analysis based on 16S rRNA gene sequencing, the strain CC-CFT758T belongs to the genus "Aliirhizobium" of the family Rhizobiaceae. The closest known relatives of this strain are "Aliirhizobium wenxiniae" 166T (with 98.7% similarity), "Aliirhizobium cellulosilyticum" SEMIA 448T (with 97.9% similarity), and "Aliirhizobium smilacinae" PTYR-5T (with 97.0% similarity). The genome size was 5.9 Mbp, with a G + C content of 60.6%. Values of digital DNA-DNA hybridization between the strain and closely related species were 29.5% for "Ali. cellulosilyticum", and 23.9% for "Ali. wenxiniae" and "Ali. smilacinae". Strain CC-CFT758T exhibited the highest orthologous average nucleotide identity (OrthoANI) values with members of the genus "Aliirhizobium", ranging from 80.4 to 81.6% (n = 3). Chemotaxonomical analysis indicated that strain CC-CFT758T contained C16:0, C16:0 3OH, C19:0 cyclo ω8c, C14:0 3OH/iso-C16:1 I, and C18:2 ω6,9c/ante C18:0 as dominant fatty acids, and the major polyamines were putrescine and spermidine. The polar lipids comprised diphosphatidylglycerol, phosphatidylcholin, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, seven unidentified aminolipids, three unidentified phospholipids, and two unidentified polar lipids. Strain CC-CFT758T exhibited distinct phylogenetic, phenotypic, and chemotaxonomic characteristics, as well as unique results in comparative analysis of 16S rRNA gene sequence, OrthoANI, AAI, dDDH, and phylogenomic placement. Therefore, this strain represents a new species of the genus "Aliirhizobium", for which the name Aliirhizobium terrae sp. nov. is proposed, with the type strain is CC-CFT758T (= BCRC 81364T = JCM 35482T).

A multicenter phase Ia study of AbGn-107, a novel antibody-drug conjugate, in patients with advanced gastrointestinal cancer.

AbGn-107 is an antibody-drug conjugate directed against AG-7 antigen, a Lewis A-like glycol-epitope expressed in a variety of gastrointestinal (GI) malignancies. Based on promising antitumor activity of AbGn-107 in both in vitro and in vivo preclinical studies, we performed a GI cancer-specific Phase I trial. Standard 3 + 3 dose escalation was used evaluating intravenous doses ranging from 0.1 mg/kg every 4 weeks to 1.0 mg/kg every 2 weeks. Key eligibility included chemo-refractory locally advanced, recurrent, or metastatic gastric, colorectal, pancreatic, or biliary cancer, with ECOG PS 0-1; positive AG-7 expression was not required during dose escalation phase. Patients were treated until disease progression or unacceptable toxicity, with tumor assessments every 8 weeks. Primary objectives included safety and determination of maximum tolerated dose; secondary objectives included efficacy defined by objective response rate. Thirty-nine patients were enrolled across seven dose levels during dose escalation phase. Based on safety profile and pharmacokinetic data, 1.0 mg/kg Q2W was selected as the dose schedule for cohort expansion phase, in which an additional seven patients were enrolled. Median number of lines of prior therapy was 3 (range 1-7). AbGn-107 was generally well-tolerated, with infections, cytopenias, hyponatremia, fatigue, abdominal pain, and diarrhea representing the most common grade 3 or higher treatment-emergent adverse events. One subject achieved a partial response, while 18 (46.2%) achieved a best response of stable disease. Disease control lasting > 6 months was observed in 6 subjects (13.0%), including 4 of 15 (26.7%) treated at the highest dose level. AbGn-107 showed a reasonable safety profile and modest clinical activity in this highly pretreated patient population. Further evaluation is required to assess the clinical validity of AG-7 as a suitable antigen for therapeutic targeting. Clinical Trial information: NCT02908451.

Neopusillimonas aromaticivorans sp. nov. isolated from poultry manure.

A polyphasic taxonomic approach was used to characterize a novel bacterium, designated strain CC-YST667T, isolated from poultry manure sampled in Taiwan. The cells were observed to be aerobic, motile and non-spore-forming rods, displaying positive reactions for oxidase. Optimal growth of CC-YST667T was observed at 25 °C, pH 8.0 and with 1 % (w/v) NaCl. The polar lipid profile consisted of phosphatidylmonomethylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine and multiple unidentified polar lipids. The major polyamine was spermidine. The major cellular fatty acids (>5 %) included C16 : 0, C17 : 0cyclo, C19 : 0cyclo ω8c and C14 : 0 3OH/iso-C16 : 1 I. On the basis of the results of analysis of 16S rRNA gene sequences, this isolate showed the closest phylogenetic relationship with 'Neopusillimonas minor' (with 98.2 % similarity) and Paralcaligenes ureilyticus (with 97.3 % similarity) of the family Alcaligenaceae. The draft genome, (3.3 Mb) with a DNA G+C content of 57.2 mol%, harboured various genes involved in the biodegradation of aromatic hydrocarbons. CC-YST667T shared highest orthologous average nucleotide identity (OrthoANI) with the type strains of species of of the genera Neopusillimonas (72.4‒77.9 %, n=2), Pusillimonas (72.8‒73.0 %, n=2) and Pollutimonas (71.7‒73.0 %, n=5). On the basis of its distinct phylogenetic, phenotypic and chemotaxonomic traits together with the results of comparative 16S rRNA gene sequencing, OrthoANI, digital DNA-DNA hybridization (DDH) and the phylogenomic placement, strain CC-YST667T is considered to represent a novel species of the genus Neopusillimonas, for which the name Neopusillimonas aromaticivorans sp. nov. is proposed. The type strain is CC-YST667T (=BCRC 81321T =JCM 34761T).

Description of Flavobacterium agricola sp. nov., an auxin producing bacterium isolated from paddy field.

An auxin-producing bacterial strain, CC-SYL302T, was isolated from paddy soil in Taiwan and identified using a polyphasic taxonomic approach. The cells were observed to be aerobic, non-motile, non-spore-forming rods, and tested positive for catalase and oxidase. Produced carotenoid but flexirubin-type pigments were absent. Optimal growth of strain CC-SYL302T was observed at 25 °C, pH 7.0, and with 2% (w/v) NaCl present. Based on analysis of 16S rRNA gene sequences, it was determined that strain CC-SYL302T belongs to the genus Flavobacterium of the Flavobacteriaceae family. The closest known relatives of this strain are F. tangerinum YIM 102701-2 T (with 93.3% similarity) and F. cucumis R2A45-3 T (with 93.1% similarity). Digital DNA-DNA hybridization (dDDH) values were calculated to assess the genetic distance between strain CC-SYL302T and its closest relatives, with mean values of 21.3% for F. tangerinum and 20.4% for F. cucumis. Strain CC-SYL302T exhibited the highest orthologous average nucleotide identity (OrthoANI) values with members of the Flavobacterium genus, ranging from 67.2 to 72.1% (n = 22). The dominating cellular fatty acids (> 5%) included iso-C14:0, iso-C15:0, iso-C16:0, iso-C15:0 3-OH, iso-C17:0 3-OH, C16:1 ω6c/C16:1 ω7c and C16:0 10-methyl/iso-C17:1 ω9c. The polar lipid profile consisted of phosphatidylethanolamine, an unidentified aminolipid, an unidentified aminophospholipid, and nine unidentified polar lipids. The genome (2.7 Mb) contained 33.6% GC content, and the major polyamines were putrescine and sym-homospermidine. Strain CC-SYL302T exhibits distinct phylogenetic, phenotypic, and chemotaxonomic characteristics, as well as unique results in comparative analysis of 16S rRNA gene sequence, OrthoANI, dDDH, and phylogenomic placement. Therefore, it is proposed that this strain represents a new species of the Flavobacterium genus, for which the name Flavobacterium agricola sp. nov. is proposed. The type strain is CC-SYL302T (= BCRC 81320 T = JCM 34764 T).

Loss of Major Histocompatibility Complex Class I, CD8 + Tumor-infiltrating Lymphocytes, and PD-L1 Expression in Ovarian Clear Cell Carcinoma.

Ovarian clear cell carcinoma (OCCC), a chemoresistant ovarian cancer, shows a modest response to anti-programmed death-1/programmed death ligand-1 (PD-1/PD-L1) therapies. The effects of anti-PD-1/PD-L1 therapies rely on cytotoxic T-cell response, which is triggered by antigen presentation mediated by major histocompatibility complex (MHC) class I. The loss of MHC class I with simultaneous PD-L1 expression has been noted in several cancer types; however, these findings and their prognostic value have rarely been evaluated in OCCC. We collected data from 76 patients with OCCC for clinicopathologic analysis. Loss of MHC class I expression was seen in 44.7% of the cases including 39.3% to 47.4% of the PD-L1 + cases and was associated with fewer CD8 + tumor-infiltrating lymphocytes (TILs). PD-L1 positivity was associated with a higher number of CD8 + TILs. Cox proportional hazard models showed that high (≥50/mm 2 ) CD8 + TILs was associated with shorter disease-specific survival (hazard ratio [HR]=3.447, 95% confidence interval [CI]: 1.222-9.720, P =0.019) and overall survival (HR=3.053, 95% CI: 1.105-8.43, P =0.031). PD-L1 positivity using Combined Positive Score was associated with shorter progression-free survival (HR=3.246, 95% CI: 1.435-7.339, P =0.005), disease-specific survival (HR=4.124, 95% CI: 1.403-12.116, P =0.010), and overall survival (HR=4.489, 95% CI: 1.553-12.972, P =0.006). Loss of MHC class I may contribute to immune evasion and resistance to anti-PD-1/PD-L1 therapies in OCCC, and CD8 + TILs and PD-L1 positivity using Combined Positive Score may have a negative prognostic value.

Description of Pseudogemmobacter faecipullorum sp. nov., isolated from poultry manure.

A polyphasic taxonomic approach was used to characterize a novel bacterium, designated strain CC-YST710T, isolated from poultry manure sampled in Taiwan. Cells of strain CC-YST710T were aerobic, Gram-stain-negative, nonmotile, nonspore-forming rods, displaying positive reactions for catalase, and oxidase activities. Strain CC-YST710T was found to grow optimally at 30°C, pH 7.0, and in the presence of 2% (w/v) NaCl. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine, two unidentified phospholipids, four unidentified aminolipids, one unidentified aminophospholipid, and five unidentified lipids. The major polyamine was spermidine. The dominating cellular fatty acids (> 5%) included C16:0, C18:0, and C18:1ω7c/C18:1ω6c. Based on 16S rRNA gene analysis, this isolate showed the closest phylogenetic relationship with 'Pseudogemmobacter humicola' (97.6%), followed by Pseudogemmobacter bohemicus (97.2%) and 'Pseudogemmobacter hezensis' (97.5%). The draft genome (4.3 Mb) had 62.9 mol% G + C content. CC-YST710T can be distinguished from other Pseudogemmobacter species due to the exclusive presence of key genes encoding p-hydroxybenzoate hydroxylase, protocatechuate 3, 4-dioxygenase (α and ß chain), and homogentisate 1, 2-dioxygenase involved in the degradation of phenolic compounds such as p-hydroxybenzoic acid, protocatechuate, and homogentisate, respectively. Orthologous average nucleotide identity (OrthoANI) of the isolate with the type strains of the genera Pseudogemmobacter were 77.6%‒78.0% (n = 3), followed by Tabrizicola (72.3%‒73.7%, n = 5), and Gemmobacter(72.3%‒73.5%, n = 7). Based on its distinct phylogenetic, phenotypic, and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, digital DDH, and the phylogenomic placement, strain CC-YST710T is considered to represent a novel Pseudogemmobacter species, for which the name Pseudogemmobacter faecipullorum sp. nov. (type strain CC-YST710T = BCRC 81286T = JCM 34182T).

Niabella agricola sp. nov., isolated from paddy soil.

A polyphasic taxonomic approach was used to characterize a Gram-stain-negative, orange-coloured bacterium (designated strain CC-SYL272T) isolated from paddy soil. Cells were observed to be strictly aerobic, non-motile and non-spore-forming rods, exhibiting positive catalase and oxidase. Strain CC-SYL272T was found to grow optimally at 20-40 °C, pH 6.0-8.0 and NaCl 0-2 % (w/v). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain CC-SYL272T belongs to the genus Niabella, family Chitinophagaceae, and is most closely related to Niabella pedocola (97.8 %) followed by Niabella drilacis (97.2 %) and established a distinct taxonomic lineage associated with these species. The highest orthologous average nucleotide identity (OrthoANI) values were recorded for strain CC-SYL272T versus Niabella species (69.1-83.5 %, n=8). The mean digital DNA-DNA hybridization (dDDH) value obtained for strain CC-SYL272T against N. pedocola was 27.3 %. The polar lipid profile consisted of phosphatidylethanolamine and five unidentified lipids. The major polyamines were putrescine and sym-homospermidine. The dominating cellular fatty acids (>5 %) included iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3OH and C16 : 1 ω6c/C16 : 1 ω7c. The draft genome (6.25 Mb) of strain CC-SYL272T spanned three contigs having 47.1 mol% DNA G+C content, 5087 protein-encoding genes, 10 rRNA genes and 44 tRNA genes. The genome harboured genes involved in the depolymerization of both animal and plant polysaccharides. Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement, strain CC-SYL272T is considered to represent a novel species of the genus Niabella, affiliated to the family Chitinophagaceae, for which the name Niabella agricola sp. nov. is proposed. The type strain is CC-SYL272T (=BCRC 81319T=JCM 34758T).

Targeted Next-generation Sequencing Reveals a Wide Morphologic and Immunophenotypic Spectrum of Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma.

Primary intestinal T-cell lymphoma (PITL) is highly aggressive and includes celiac disease-related enteropathy-associated T-cell lymphoma (EATL), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), and primary intestinal peripheral T-cell lymphoma, not otherwise specified (ITCL-NOS). MEITL is the most common PITL in Asia, comprising of monomorphic medium-sized cells typically expressing CD8, CD56, and cytotoxic granules. Occasional cases with intermediate features between MEITL and ITCL-NOS are difficult to be classified and warrant further investigation. We collected 54 surgically resected PITLs from Taiwan, with 80% presenting with bowel perforation. The overall outcome was poor with a median survival of 7 months. Based on histopathology (monomorphic vs. pleomorphic) and immunophenotype, we classified these cases into 4 groups: MEITL with typical immunophenotype (n=34), MEITL with atypical immunophenotype (n=5), pleomorphic PITL with MEITL-like immunophenotype (n=6), and ITCL-NOS (n=9). There was no EATL in our cohort. Targeted next-generation sequencing of the first 3 groups showed highly prevalent loss-of-function mutations for SETD2 (85%, 80%, and 83%, respectively) and frequent activating mutations for STAT5B (64%, 60%, and 50%, respectively) and JAK3 (38%, 20%, and 50%, respectively). In contrast, ITCL-NOS cases had less frequent mutations of SETD2 (56%) and STAT5B (11%) and rare JAK3 mutations (11%). Our results suggest that there is a wider morphologic and immunophenotypic spectrum of MEITL as currently defined in the 2017 WHO classification. MEITL with atypical immunophenotype and PITL with MEITL-like immunophenotype shared clinicopathologic and molecular features similar to MEITL but distinct from ITCL-NOS, indicating that such cases may be considered as immunophenotypic or histopathologic variants of MEITL.

Pusillimonas faecipullorum sp. nov., isolated from the poultry manure.

A polyphasic taxonomic approach was used to characterize a novel bacterium, designated strain CC-YST705T, isolated from poultry manure sampled in Taiwan. Cells of strain CC-YST705T were aerobic, Gram-stain-negative, non-motile, non-spore-forming rods, displaying positive reactions for catalase, oxidase and ß-glucosidase. Optimal growth occurred at 30 °C and pH 8. Strain CC-YST705T shared the highest (> 96.0%) pair-wise 16S rRNA gene sequence similarity with Pusillimonas noertemannii (96.7%), followed by Pusillimonas caeni (96.6%), Eoetvoesia caeni (96.1%) and Paracandidimonas soli (96.0%), and formed a distinct phyletic lineage associate with the clade that accommodated Pusillimonas species. The draft genome (3.1 Mb) having 57.4 mol % G + C content contained genes involved in the catabolism of aromatic hydrocarbons. The orthologous average nucleotide identity (OrthoANI) values were 62.8-73.1% (n = 8), 72.6 (n = 1), 71.5% (n = 1) compared within the type strains of the genera Pusillimonas, Eoetvoesia and Paracandidimonas, respectively. The polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, one unidentified aminolipid, two unidentified phospholipids and five unidentified lipids. The major polyamine was spermidine. The dominating cellular fatty acids (> 5%) included C12:0, C16:0, C17:0 cyclo, C19:0 cyclo ω8c and 2 C14:0 3OH/iso-C16:1 I. Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, digital DDH, and the phylogenomic placement, strain CC-YST705T is considered to represent a novel species of the genus Pusillimonas, for which the name Pusillimonas faecipullorum sp. nov. is proposed. The type strain is CC-YST705T (= BCRC 81285 T = JCM 34168 T).

Agrilactobacillus fermenti sp. nov. isolated from fermented vegetable residue.

A polyphasic taxonomic approach was used to characterize a Gram-stain-positive fermentative bacterium, designated strain CC-MHH1034T, isolated from a fermented vegetable residue. Cells of strain CC-MHH1034T were facultatively anaerobic, non-motile, and non-spore-forming rods, exhibiting positive catalase, oxidase and protease activities. Optimal growth occurred at 30 °Ð¡ and pH 6.0. Strain CC-MHH1034T shared the highest 16S rRNA gene sequence similarities with Agrilactobacillus composti (95.9 %) followed by Agrilactobacillus yilanensis (95.1 %) and established a distinct taxonomic lineage associated with these species. Highest orthologous average nucleotide identity (OrthoANI) values were recorded for strain CC-MHH1034T versus Agrilactobacillus (71.1-71.6 %, n=2) followed by Ligilactobacillus (66.5-66.8 %, n=2), Lactobacillus (64.1-65.8 %, n=4). The mean digital DNA-DNA hybridization (dDDH) value obtained for strain CC-MHH1034T against Agrilactobacillus was 19.2-19.5 % (n=2). The polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol, two unidentified aminolipids, four unidentified glycolipids, four unidentified phospholipids and one unidentified lipid. The major polyamine was sym-homospermidine and meso-diaminopimelic acid was detected as the cell-wall peptidoglycan. The dominating cellular fatty acids (>5 %) included C16 : 0, iso-C15 : 0, anteiso-C15 : 0 and C18 : 1 ω9c. Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, dDDH, and the phylogenomic placement, strain CC-MHH1034T is considered to represent a novel species of the genus Agrilactobacillus, affiliated to the family Lactobacillaceae, for which the name Agrilactobacillus fermenti sp. nov. is proposed. The type strain is CC-MHH1034T (=BCRC 81220T=JCM 33476T).

Vineibacter terrae gen. nov., sp. nov., an ammonium-assimilating and nitrate-reducing bacterium isolated from vineyard soil.

A polyphasic taxonomic approach was used to characterize a Gram-stain-negative bacterium, designated strain CC-CFT640T, isolated from vineyard soil sampled in Taiwan. Cells of strain CC-CFT640T were aerobic, non-motile, nitrate-reducing rods. Test results were positive for catalase, oxidase and proteinase activities. Optimal growth occurred at 30 °Ð¡ and pH 7. Strain CC-CFT640T showed highest 16S rRNA gene sequence similarity to members of the genus Enhydrobacter (90.0 %, n=1) followed by Hypericibacter (89.4-90.0 %, n=2), Reyranella (88.8-89.8 %, n=5) and Nitrospirillum (89.2-89.4 %, n=2), and formed a distinct phyletic lineage distantly associated with the clade that predominately accommodated Reynerella species. The DNA G+C composition of the genome (2.1 Mb) was 67.9 mol%. Genes involved in the reduction of nitrate to nitrite, nitric oxide and nitrous oxide were found. In addition, genes encoding dissimilatory nitrate reduction to ammonia, ammonium transport and ammonium assimilation were also detected. Average nucleotide identity values were 73.3 % (n=1), 74.0-74.6 % (n=2), 67.5-68.3 % (n=2) when compared within the type strains of the genera Enhydrobacter, Reyranella and Niveispirillum, respectively. The dominant cellular fatty acids (>5 %) included C16 : 0, iso-C17 : 1 ω10c, C19 : 0 cyclo ω8c, C18 : 1 2-OH and C18 : 1 ω7c/C18 : 1 ω6c. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, three unidentified aminolipids, three unidentified phospholipids and an unidentified aminophospholipid. The major respiratory quinone was ubiquinone 10 and the major polyamine was spermidine. Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequencing, digital DNA-DNA hybridization, average nucleotide identity and phylogenomic placement, strain CC-CFT640T is considered to represent a novel genus and species of the family Rhodospirillaceae, for which the name Vineibacter terrae gen. nov., sp. nov. is proposed. The type strain is CC-CFT640T (=BCRC 81219T=JCM 33507T).

Zeimonas arvi gen. nov., sp. nov., of the family Burkholderiaceae, harboring biphenyl- and phenolic acid-metabolizing genes, isolated from a long-term ecological research field.

A polyphasic taxonomic approach was used to characterize a Gram-stain-negative bacterium, designated strain CC-CFT501T, harboring xenobiotic- and allelochemical-metabolizing genes, isolated from a long-term ecological research field in Taiwan. Cells of strain CC-CFT501T were catalase- and oxidase-positive, non-motile and short rods. Optimal growth occurred at 30 °C, pH 8 and 1% NaCl. Strain CC-CFT501T was found to share high 16S rRNA gene sequence similarity with the members of genera Quisquiliibacterium (94.3%, n = 1), Pandoraea (93.4-94.0%, n = 23) and Paraburkholderia (93.3-94.0%, n = 9), affiliated to the family Burkholderiaceae. Strain CC-CFT501T shared 76.4% orthologous average nucleotide identity (OrthoANI) and 20.9% digital DNA-DNA hybridization (dDDH) values with Quisquiliibacterium transsilvanicum DSM 29781T. Draft genome sequence (3.83 Mb) of strain CC-CFT501T revealed several genes encoding the proteins involved in biphenyl and phenolic acid metabolism. Fatty acid profile contained C16:0, C18:0, C10:0 3-OH, C16:1 ω7c/C16:1 ω6c and C18:1 ω7c/C18:1 ω6c in predominant amounts. The polar lipid profile consisted of phosphatidylethanolamine, thirteen unidentified amino lipids, two unidentified phospholipids and two unidentified glycolipids. The major polyamine was spermidine and ubiquinone Q-8 was the sole respiratory quinone. The DNA G + C content was 70.0 mol%. Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, ANI and dDDH analyses, strain CC-CFT501T is considered to represent a novel genus and species of the family Burkholderiaceae, for which the name Zeimonas arvi gen. nov., sp. nov. is proposed. The type strain of the type species is CC-CFT501T (= BCRC 81218T = JCM 33506T).

Description of Devosia faecipullorum sp. nov., harboring antibiotic- and toxic compound-resistace genes, isolated from poultry manure.

A polyphasic taxonomic approach was used to characterize a Gram-stain-negative bacterium, designated strain CC-YST696T, harbouring antibiotic- and toxic compound-resistace genes, isolated from poultry manure in Taiwan. Cells of CC-YST696T were short rods, motile with polar flagella, catalase- and oxidase-positive. Optimal growth occurred at 30 °Ð¡, pH 9 and with 1 % NaCl. The results of phylogenetic analyses based on 16S rRNA genes revealed a distinct taxonomic position attained by CC-YST696T associated with Devosia chinhatensis (97.9 % sequence identity), Devosia riboflavina (97.3 %) and Devosia indica (97.2 %), and with lower sequence similarity values to other species. Average nucleotide identity (ANI) values were 72.8-80.0 % (n=17) compared within the type strains of species of of the genus Devosia. CC-YST696T contained C16:0, C18:0, C18:1ω7c 11-methyl and C18:1ω6c/ C18:1ω7c as the predominant fatty acids. The polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol, two unidentified aminolipids, three unidentified glycolipids, two unidentified phospholipids and three unidentified lipids. The DNA G+C content was 62.2 mol% and the predominant quinone was ubiquinone Q-10. On the basis of its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence and ANI analyses, strain CC-YST696T is proposed to represent a novel species of the genus Devosia, for which the name Devosia faecipullorum sp. nov. (type strain CC-YST696T=BCRC 81284T=JCM 34167T) is proposed.

Flavobacterium difficile sp. nov., isolated from a freshwater waterfall.

A bacterial strain designated KDG-16 T is isolated from a freshwater waterfall in Taiwan and characterized to determine its taxonomic affiliation. Cells of strain KDG-16 T are Gram-stain-negative, strictly aerobic, motile by gliding, rod-shaped and form light yellow colonies. Optimal growth occurs at 20-25 °C, pH 6-7, and with 0% NaCl. Phylogenetic analyses based on 16S rRNA gene sequences and an up-to-date bacterial core gene set reveal that strain KDG-16 T is affiliated with species in the genus Flavobacterium. Analysis of 16S rRNA gene sequences shows that strain KDG-16 T shares the highest similarity with Flavobacterium terrigena DSM 17934 T (97.7%). The average nucleotide identity, average amino acid identity and digital DNA-DNA hybridization values between strain KDG-16 T and the closely related Flavobacterium species are below the cut-off values of 95-96, 90 and 70%, respectively, used for species demarcation. Strain KDG-16 T contains iso-C15:0, iso-C15:1 G and iso-C17:0 3-OH as the predominant fatty acids. The polar lipid profile consists of phosphatidylethanolamine, one uncharacterized aminophospholipid, one uncharacterized phospholipid, two uncharacterized aminolipids and two uncharacterized lipids. The major polyamine is homospermidine. The major isoprenoid quinone is MK-6. Genomic DNA G + C content of strain KDG-16 T is 31.6%. Based on the polyphasic taxonomic data obtained, strain KDG-16 T is considered to represent a novel species in the genus Flavobacterium, for which the name Flavobacterium difficile sp. nov. is proposed. The type strain is KDG-16 T (= BCRC 81194 T = LMG 31332 T).

Analytical validation of human epidermal growth factor receptor 2 immunohistochemistry by the use of the A0485 antibody versus the 4B5 antibody and breast versus gastric scoring guidelines in ovarian clear cell carcinoma.

AIMS: The aim of this study was to evaluate human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) in ovarian clear cell carcinoma (OCCC) by using two antibodies and two scoring guidelines in correlation with HER2 amplification and clinicopathological features. METHODS AND RESULTS: A tissue microarray was constructed by use of a total of 71 OCCC cases for IHC (the A0485 antibody and the 4B5 antibody) and dual-colour silver in-situ hybridisation (DISH). Two pathologists independently scored the IHC according to the 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) breast cancer guidelines (breast guidelines) and the 2016 ASCO/CAP gastro-oesophageal adenocarcinoma guidelines (gastric guidelines). IHC concordances between A0485 and 4B5 were 87.3-93.0%. Three to 16 (4.2-22.5%) cases had an IHC score of 2+/3+ with frequent basolateral/lateral membranous staining. The 4B5 antibody yielded fewer IHC 2+ cases than the A0485 antibody (n = 2-6 versus n = 5-12). Five (7.0%) cases had HER2 amplification as determined with DISH. Cases with papillary-predominant growth patterns were significantly more likely to have HER2 amplification (P = 0.0051). In predicting DISH results, IHC scored according to the gastric guidelines yielded 100%/100% sensitivity and 83.3-95.5%/98.2-100% specificity, and IHC scored according to the breast guidelines yielded 60-80%/33.3-66.7% sensitivity and 95.5-100%/100% specificity (including/excluding IHC 2+ cases). One case had intratumoral heterogeneity, with discordant results between primary and metastatic tumour specimens. CONCLUSION: We demonstrated HER2 amplification in 7% of OCCC cases, and the molecular change is significantly associated with papillary-predominant growth patterns. In predicting HER2 amplification, a combination of 4B5 IHC and gastric guidelines provides the best sensitivity and fewer equivocal (IHC 2+) cases. Given the intratumoral heterogeneity, assessment of HER2 status on whole tissue sections and on both primary and metastatic tumour specimens is recommended.

Aeromicrobium terrae sp. nov., isolated from a maize field.

A polyphasic taxonomic approach was used to characterize a Gram-stain-positive bacterium, designated strain CC-CFT486T, isolated from soil sampled in a maize field in Taiwan. Cells of strain CC-CFT486T were short rods, motile with polar flagella, catalase-positive and oxidase-positive. Optimal growth occurred at 30 °Ð¡, pH 8 and 1 % NaCl. Phylogenetic analyses based on 16S rRNA genes revealed a distinct taxonomic position attained by strain CC-CFT486T associated with Aeromicrobium panacisoli (97.0 % sequence identity), Aeromicrobium lacus (97.0 %), Aeromicrobium erythreum (96.8 %) and Aeromicrobium alkaliterrae (96.8 %), and lower sequence similarity values to other species. Average nucleotide identity (ANI) values were 70.6-77.8 % (n=11) compared within the type strains of the genus Aeromicrobium. Strain CC-CFT486T contained C16 : 0, C17 : 0, C17 : 1 ω8c and C18 : 1 ω9c as the predominant fatty acids. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, two unidentified aminophospholipids and three unknown phospholipids. The cell wall peptidoglycan of strains CC-CFT486T contained ll-diaminopimelic acid (ll-DAP) and the major polyamine was spermidine. The DNA G+C content was 70.6 mol% and the predominant quinone was menaquinone 9 (MK-9). Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence and ANI analyses, strain CC-CFT486T is proposed to represent a novel Aeromicrobium species, for which the name Aeromicrobium terrae sp. nov. (type strain CC-CFT486T=BCRC 81217T=JCM 33499T).

Diffuse Intratumoral Stromal Inflammation in Ovarian Clear Cell Carcinoma is Associated With Loss of Mismatch Repair Protein and High PD-L1 Expression.

Ovarian clear cell carcinoma (OCCC) is an aggressive chemotherapy-resistant cancer with limited treatment options, and some OCCCs have mismatch repair (MMR) deficiency (MMRD). Emerging evidence has revealed that various cancers with MMRD are susceptible to anti-programmed death-1/programmed death ligand-1 (anti-PD-1/PD-L1) immunotherapy, and certain histologic features are associated with MMRD. However, few studies have addressed this in OCCC. We reviewed 76 OCCCs for tumor-associated inflammation (intratumoral stromal inflammation and peritumoral lymphocytes) and performed immunohistochemistry for 4 MMR proteins and PD-L1. MMR-deficient OCCCs were analyzed for microsatellite instability (MSI), and those with MLH1 loss were tested for MLH1 promoter methylation. No patients fulfilled the Amsterdam II criteria for the diagnosis of Lynch syndrome. Four (5.3%) tumors showed diffuse intratumoral stromal inflammation obliterating the tumor-stroma interfaces, and none had peritumoral lymphoid aggregates. MMRD was found in 2 (2.6%) tumors; one had MLH1/PMS2 loss (MSI-high and MLH1 promoter methylation was detected) and the other had MSH2/MSH6 loss (MSI-low). Twenty (26.3%) tumors showed tumoral PD-L1 expression ≥1%. Both MMR-deficient tumors showed diffuse intratumoral stromal inflammation and tumoral PD-L1 expression ≥50%. Three of the 4 (75%) tumors with diffuse intratumoral stromal inflammation also showed tumoral PD-L1 expression ≥50%. None of the tumors without diffuse intratumoral stromal inflammation showed MMRD (P=0.021) or tumoral PD-L1 expression ≥50% (P=0.0001). We identified a strong correlation among diffuse intratumoral stromal inflammation, MMRD, and high tumoral PD-L1 expression in a small but significant subset of OCCCs. Histologic evaluation can facilitate patient selection for subsequent anti-PD-1/PD-L1 immunotherapy.

Cerasibacillus terrae sp. nov., isolated from maize field, and emended description of Cerasibacillus quisquiliarum Nakamura et al. 2004.

A polyphasic taxonomic approach was used to characterize a Gram-stain-positive bacterium, designated strain CC-CFT480T, isolated from soil sampled in a maize field in Taiwan, ROC. Cells of strain CC-CFT480T were rod-shaped, motile with polar flagella, catalase-positive and oxidase-positive. Optimal growth occurred at 30 °Ð¡, pH 8 and 3 % NaCl. Phylogenetic analyses based on 16S rRNA genes revealed a distinct taxonomic position attained by strain CC-CFT480T associated with Cerasibacillus quisquiliarum (97.2 % sequence identity), Virgibacillus soli (95.7 %), Virgibacillus carmonensis (95.4 %) and Virgibacillus byunsanensis (95.2 %), and lower sequence similarity values to other species. Average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain CC-CFT480T and C. quisquiliarum were 74.2 and 20.1 %, respectively. Strain CC-CFT480T contained iso-C15:0, C16:1 ω7c alcohol and iso-C17:1 ω10c as the predominant fatty acids. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, two unknown aminophospholipids, one uncharacterized aminophospholipid and two unknown phospholipids. The major polyamine was spermidine. The DNA G+C content was 34.8 mol% and the predominant quinone was menaquinone 7 (MK-7). Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, ANI and dDDH analyses, strain CC-CFT480T is proposed to represent a novel Cerasibacillus species, for which the name Cerasibacillus terrae sp. nov. (type strain CC-CFT480T=BCRC 81216T=JCM 33498T).

Characterization of Driver Mutations in Anaplastic Thyroid Carcinoma Identifies RAS and PIK3CA Mutations as Negative Survival Predictors.

Anaplastic thyroid carcinoma (ATC) is rare but highly aggressive. We investigated the association of selected driver mutations, including BRAF, RAS, PIK3CA, TERT promoter, TP53, POLE, and mismatch repair deficiency (MMR-D) with the clinicopathological features of ATC to identify prognostic and predictive biomarkers. Thirty-nine retrospective cases from pathology archives were enrolled for clinicopathology analysis and immunohistochemistry, and 27 cases had sufficient specimens for further molecular testing using targeted next-generation sequencing and mass spectrometry. BRAFV600E and RAS mutations were identified in 25.9% and 40.7% of ATC, respectively. BRAFV600E mutation was significantly associated with coexisting papillary thyroid carcinoma (p = 0.009) and RAS mutations with female gender (p = 0.012). In univariant analysis, the non-BRAF/RAS tumors were significantly associated with the presence of a sarcomatoid pattern (p = 0.045). PIK3CA, TERT promoter, and TP53 mutations were identified in 14.8%, 81.5%, and 70.4% of cases, respectively. No MMR-D or POLE mutations were detected. In survival analyses, RAS and PIK3CA mutations were significantly associated with inferior outcomes (p = 0.03 and p = 0.006, respectively). In conclusion, driver mutations in ATC are associated with distinct clinicopathological features. RAS and PIK3CA mutations were negative predictors for patient survival. Emerging therapeutic agents targeting BRAF, RAS, and PI3 kinase may benefit a substantial proportion of ATC patients.

Description of Azoarcus nasutitermitis sp. nov. and Azoarcus rhizosphaerae sp. nov., two nitrogen-fixing species isolated from termite nest and rhizosphere of Ficus religiosa.

A polyphasic taxonomic approach was used to characterise two presumably novel bacteria, designated strains CC-YHH838T and CC-YHH848T isolated from termite nest and rhizosphere of Ficus religiosa, respectively. These two nitrogen-fixing strains were observed to be Gram-staining-negative, aerobic rod, and colonies were yellowish in color. Growth of strains was observed at 20-37 °C, pH 7-8, and in the presence of 1-2% NaCl. Phylogenetic analyses based on 16S rRNA genes revealed a distinct taxonomic position attained by strain CC-YHH838T and CC-YHH848T associated with Thauera hydrothermalis (97.1% sequence identity), and formed a separate branch with Azoarcus indigens (95.4%), Aromatoleum aromaticum (96.2%), and lower sequence similarity to other species. The calculation of OrthoANI values pointed out strains CC-YHH838T and CC-YHH848T gave 78.9% and 79.8% compared to Thauera hydrothermalis, respectively. The major fatty acids (> 5%) were C16:0, C17:0 cyclo, C10:0 3-OH, C16:1ω7c/C16:1ω6c and C18:1ω7c/C18:1ω6c. The polar lipid profile comprised phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and unidentified aminophospholipid and phospholipids; the predominant polyamines were putrescine and spermidine. The predominant respiratory system was ubiquinone (Q-8) and the DNA G + C contents were 61.4 ± 0.1 mol% and 60.2 ± 1.3 mol%, respectively. Based on the phylogenetic and polyphasic comparisons, strains CC-YHH838T and CC-YHH848T are proposed to represent two novel species within the genus Azoarcus in the family Rhodocyclaceae, for which the name Azoarcus nasutitermitis sp. nov. (type strain CC-YHH838T = BCRC 81059T = JCM 32001T) and Azoarcus rhizosphaerae sp. nov. (type strain CC-YHH848T = BCRC 81060T = JCM 32002T) were proposed.