Zanubrutinib in relapsed/refractory mantle cell lymphoma: long-term efficacy and safety results from a phase 2 study.

Bruton tyrosine kinase (BTK) inhibitor is an established treatment for relapsed/refractory (R/R) mantle cell lymphoma (MCL). Zanubrutinib, a highly selective BTK inhibitor, is approved for patients with MCL who have received ≥1 prior therapy. We report the long-term safety and efficacy results from the multicenter, open-label, phase 2 registration trial of zanubrutinib. Patients (n = 86) received oral zanubrutinib 160 mg twice daily. The primary endpoint was the overall response rate (ORR), assessed per Lugano 2014. After a median follow-up of 35.3 months, the ORR was 83.7%, with 77.9% achieving complete response (CR); the median duration of response was not reached. Median progression-free survival (PFS) was 33.0 months (95% confidence interval [CI], 19.4-NE). The 36-month PFS and overall survival (OS) rates were 47.6% (95% CI, 36.2-58.1) and 74.8% (95% CI, 63.7-83.0), respectively. The safety profile was largely unchanged with extended follow-up. Most common (≥20%) all-grade adverse events (AEs) were neutrophil count decreased (46.5%), upper respiratory tract infection (38.4%), rash (36.0%), white blood cell count decreased (33.7%), and platelet count decreased (32.6%); most were grade 1/2 events. Most common (≥10%) grade ≥3 AEs were neutrophil count decreased (18.6%) and pneumonia (12.8%). Rates of infection, neutropenia, and bleeding were highest in the first 6 months of therapy and decreased thereafter. No cases of atrial fibrillation/flutter, grade ≥3 cardiac AEs, second primary malignancies, or tumor lysis syndrome were reported. After extended follow-up, zanubrutinib demonstrated durable responses and a favorable safety profile in R/R MCL. The trial is registered at ClinicalTrials.gov as NCT03206970.

Development strategy of non-GMO organism for increased hemoproteins in Corynebacterium glutamicum: a growth-acceleration-targeted evolution.

Heme, found in hemoproteins, is a valuable source of iron, an essential mineral. The need for an alternative hemoprotein source has emerged due to the inherent risks of large-scale livestock farming and animal proteins. Corynebacterium glutamicum, regarded for Qualified Presumption of Safety or Generally Recognized as Safe, can biosynthesize hemoproteins. C. glutamicum single-cell protein (SCP) can be a valuable alternative hemoprotein for supplying heme iron without adversely affecting blood fat levels. We constructed the chemostat culture system to increase hemoprotein content in C. glutamicum SCP. Through adaptive evolution, hemoprotein levels could be naturally increased to address oxidative stress resulting from enhanced growth rate. In addition, we used several specific plasmids containing growth-accelerating genes and the hemA promoter to expedite the evolutionary process. Following chemostat culture for 15 days, the plasmid in selected descendants was cured. The evolved strains showed improved specific growth rates from 0.59 h-1 to 0.62 h-1, 20% enhanced resistance to oxidative stress, and increased heme concentration from 12.95 µg/g-DCW to 14.22-15.24 µg/g-DCW. Notably, the putative peptidyl-tRNA hydrolase-based evolved strain manifested the most significant increase (30%) of hemoproteins. This is the first report presenting the potential of a growth-acceleration-targeted evolution (GATE) strategy for developing non-GMO industrial strains with increased bio-product productivity.

Development of a Normal Porcine Cell Line Growing in a Heme-Supplemented, Serum-Free Condition for Cultured Meat.

A key element for the cost-effective development of cultured meat is a cell line culturable in serum-free conditions to reduce production costs. Heme supplementation in cultured meat mimics the original meat flavor and color. This study introduced a bacterial extract generated from Corynebacterium that was selected for high-heme expression by directed evolution. A normal porcine cell line, PK15, was used to apply the bacterial heme extract as a supplement. Consistent with prior research, we observed the cytotoxicity of PK15 to the heme extract at 10 mM or higher. However, after long-term exposure, PK15 adapted to tolerate up to 40 mM of heme. An RNA-seq analysis of these heme-adapted PK15 cells (PK15H) revealed a set of altered genes, mainly involved in cell proliferation, metabolism, and inflammation. We found that cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1), lactoperoxidase (LPO), and glutathione peroxidase 5 (GPX5) were upregulated in the PK15H heme dose dependently. When we reduced serum serially from 2% to serum free, we derived the PK15H subpopulation that was transiently maintained with 5-10 mM heme extract. Altogether, our study reports a porcine cell culturable in high-heme media that can be maintained in serum-free conditions and proposes a marker gene that plays a critical role in this adaptation process.

Changes in agricultural nitrogen (N) balance of OECD countries and its causes and impacts.

The Organization for Economic Co-operation and Development (OECD) developed soil surface nutrient balance and made it mandatory for member countries to report annual nutrient budgets since 1990. This study aimed to evaluate the status of nitrogen (N) management in member countries and to figure out why N surplus levels differ across countries and how they relate to other agri-environmental indicators, by analyzing the N budgets from 35 OECD countries over the last 30 years. Of the three factors determining N balance (agricultural land area, N input, and N output), agricultural land area decreased in most OECD countries, negatively affecting N balance reduction. However, OECD's average N balance highly decreased from 91 to 46 kg ha-1 over the last 30 years due to the decrease in N input through inorganic fertilizers and manure, especially in EU countries with high N input levels, while N output did not meaningfully change. In comparison, in Japan and Korea, the N balance slightly increased and they became the highest N balance country recently. A higher N balance led to lower N use efficiency and higher ammonia (NH3) and nitrous oxide (N2O) emission intensities. More densely populated countries with smaller agricultural land per capita (ranging from 0.03 to 0.47 ha capita-1) showed a higher N balance (228-80 kg ha-1), presumably due to higher N input for more agricultural production on limited land. The most densely populated countries among OECD members (Belgium, the Netherlands, Korea, and Japan) had similar N input levels. However, two EU countries had much higher N output than two Asian countries due to higher pasture production, which led to a lower N balance and higher N use efficiency. Therefore, highly populated countries with small arable land areas per capita might need multilateral efforts to alleviate agricultural N balance.

Male castration increases adiposity via small intestinal microbial alterations.

Castration of young males is widely used in the cattle industry to improve meat quality, but the mechanism linking hypogonadism and host metabolism is not clear. Here, we use metataxonomic and metabolomic approaches to evaluate the intestinal microbiota and host metabolism in male, castrated male (CtM), and female cattle. After pubescence, the CtM cattle harbor distinct ileal microbiota dominated by the family Peptostreptococcaceae and exhibit distinct serum and muscle amino acid profiles (i.e., highly abundant branched-chain amino acids), with increased extra- and intramuscular fat storage. We also evaluate the causative factor(s) that underpin the alteration of the intestinal microbiota and host metabolic phenotype in response to hypogonadism. Castration of male mice phenocopies both the intestinal microbial alterations and obese-prone metabolism observed in cattle. Antibiotic treatment and fecal microbiota transplantation experiments in a mouse model confirm that the intestinal microbial alterations associated with hypogonadism are a key contributor to the obese phenotype in the CtM animals. Collectively, targeting the gut microbiota is a potential therapeutic strategy for the treatment of both hypogonadism and obesity.

The passive sampler assisted human exposure risk characterization for tetrachloroethene soil vapor intrusion scenario.

The potential human health risks associated with soil vapor intrusion and volatile organic compounds (VOCs) exposure were characterized at an industrialized site by the quantification of gaseous VOCs in soil pores using a passive sampling technique. The gaseous tetrachloroethene (PCE) in soil pores varied between 12 and 5,400 µg m-3 showing 3 orders of magnitude variation with dependence on groundwater PCE concentrations. Though the PCE concentration in the air only varied between 0.45 and 1.5 µg m-3 showing negligible variations compared to the variation observed in soil pores. The PCE concentration in the air varied between 0.45 and 1.5 µg m-3. The calculation of fugacity suggested that the PCE in the test site originated from groundwater. Measured PCE in groundwater ranged from 14 to 2,400 times higher than PCE in soil gas. This indicates that conducting a vapor intrusion risk assessment using passive soil gas sampling is critical for accurate risk characterization and assessment. Estimated PCE inhalation cancer risks for street cleaners and indoor residents varied between 10-6 and 10-4 with a low plausible hazard, and between 10-3 and 10-2 with a high risk, respectively. The results of this study demonstrate that passive sampling offers a significantly lower cost and labor-intensive approach compared to traditional methods for assessing pollution distribution in contaminated sites and characterizing risks. This highlights the potential for wider application of passive sampling techniques in environmental studies.

Foci-Xpress: Automated and Fast Nuclear Foci Counting Tool.

In the nucleus, distinct, discrete spots or regions called "foci" have been identified, each harboring a specific molecular function. Accurate and efficient quantification of these foci is essential for understanding cellular dynamics and signaling pathways. In this study, we present an innovative automated image analysis method designed to precisely quantify subcellular foci within the cell nucleus. Manual foci counting methods can be tedious and time-consuming. To address these challenges, we developed an open-source software that automatically counts the number of foci from the indicated image files. We compared the foci counting efficiency, velocity, accuracy, and convenience of Foci-Xpress with those of other conventional methods in foci-induced models. We can adjust the brightness of foci to establish a threshold. The Foci-Xpress method was significantly faster than other conventional methods. Its accuracy was similar to that of conventional methods. The most significant strength of Foci-Xpress is automation, which eliminates the need for analyzing equipment while counting. This enhanced throughput facilitates comprehensive statistical analyses and supports robust conclusions from experiments. Furthermore, automation completely rules out biases caused by researchers, such as manual errors or daily variations. Thus, Foci-Xpress is a convincing, convenient, and easily accessible focus-counting tool for cell biologists.

A novel approach to predicting the synergy of anti-cancer drug combinations using document-based feature extraction.

BACKGROUND: To reduce drug side effects and enhance their therapeutic effect compared with single drugs, drug combination research, combining two or more drugs, is highly important. Conducting in-vivo and in-vitro experiments on a vast number of drug combinations incurs astronomical time and cost. To reduce the number of combinations, researchers classify whether drug combinations are synergistic through in-silico methods. Since unstructured data, such as biomedical documents, include experimental types, methods, and results, it can be beneficial extracting features from documents to predict anti-cancer drug combination synergy. However, few studies predict anti-cancer drug combination synergy using document-extracted features. RESULTS: We present a novel approach for anti-cancer drug combination synergy prediction using document-based feature extraction. Our approach is divided into two steps. First, we extracted documents containing validated anti-cancer drug combinations and cell lines. Drug and cell line synonyms in the extracted documents were converted into representative words, and the documents were preprocessed by tokenization, lemmatization, and stopword removal. Second, the drug and cell line features were extracted from the preprocessed documents, and training data were constructed by feature concatenation. A prediction model based on deep and machine learning was created using the training data. The use of our features yielded higher results compared to the majority of published studies. CONCLUSIONS: Using our prediction model, researchers can save time and cost on new anti-cancer drug combination discoveries. Additionally, since our feature extraction method does not require structuring of unstructured data, new data can be immediately applied without any data scalability issues.

Nocardioides palaemonis sp. nov. and Tessaracoccus palaemonis sp. nov., isolated from the gastrointestinal tract of lake prawn.

Two novel Gram-stain-positive, non-motile and non-spore-forming bacterial strains, designated J2M5T and J1M15T, were isolated from the gastrointestinal tract of a lake prawn Palaemon paucidens. Strain J2M5T was an obligately aerobic bacterium that formed milky-coloured colonies and showed a rod-coccus cell cycle, while strain J1M15T was a facultatively aerobic bacterium that formed orangish-yellow-coloured colonies and showed rod-shaped cells. Strains J2M5T and J1M15T showed the highest 16S rRNA gene sequence similarity to Nocardioides ganghwensis JC2055T (98.63 %) and Tessaracoccus flavescens SST-39T (98.08 %), respectively. The whole-genome sequence of strain J2M5T was 4.52 Mbp in size and the genomic G+C content directly calculated from the genome sequence of strain J2M5T was 72.5 mol%. The whole-genome sequence of strain J1M15T was 3.20 Mbp in size and the genomic G+C content directly calculated from the genome sequence of strain J1M15T was 69.6mol %. Strains J2M5T and J1M15T showed high OrthoANI similarity to N. ganghwensis JC2055T (83.6 %) and T. flavescens (77.2 %), respectively. We analysed the genome sequences of strains J2M5T and J1M15T in terms of carbohydrate-active enzymes, antibiotic resistance genes and virulence factor genes. Strains J2M5T and J1M15T contained MK-8 (H4) and MK-9 (H4) as the predominant respiratory quinones, respectively. The major polar lipids of both strains were phosphatidylglycerol and diphosphatidylglycerol. Additionally, strain J2M5T possessed phosphatidylcholine, phosphatidylserine and phosphatidylethanolamine. The cellular sugar components of strain J2M5T were ribose, mannose, glucose and galactose, and its cellular amino acid components were l-alanine and l-lysine. The cellular sugar components of strain J1M15T were rhamnose, ribose, mannose and glucose, and its cellular amino acid component was l-alanine. The major cellular fatty acids of strains J2M5T and J1M15T were iso-C16 : 0 and anteiso-C15 : 0, respectively. The multiple taxonomic analyses indicated that strains J2M5T and J1M15T represent novel species of the genus Nocardioides and Tessaracoccus, respectively. We propose the names Nocardioides palaemonis sp. nov. and Tessaracoccus palaemonis sp. nov. for strain J2M5T (=KCTC 49461T=CCUG 74767T) and strain J1M15T (=KCTC 49462T=CCUG 74766T), respectively.

Parasphingorhabdus cellanae sp. nov., isolated from the gut of a Korean limpet, Cellana toreuma.

A novel bacterium, designated strain JHSY0214T, was isolated from the gut of a Korean limpet, Cellana toreuma. Cells of strain JHSY0214T were Gram-stain-negative, strictly aerobic, yellow-pigmented, non-spore-forming, non-motile and showed a rod-coccus growth cycle. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the strain belonged to the genus Parasphingorhabdus, and was most closely related to Parasphingorhabdus litoris KCTC 12764T (98.71 %). Strain JHSY0214T had two fluoroquinolone-resistance genes and seven multidrug-resistance efflux pump genes, but did not have beta-lactamase genes and zinc resistance genes compared with P. litoris KCTC 12764T. Strain JHSY0214T grew optimally at 30 °C, pH 7.0 and in the presence of 2 % (w/v) NaCl. The predominant cellular fatty acids of strain JHSY0214T were summed feature 8 (C18 : 1 ω6c and/or C18 : 1 ω7c; 41.2 %), summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c; 21 %) and C16 : 0 (18.9 %). The major isoprenoid quinone was ubiquinone-10. The major polar lipids were sphingoglycolipid and phosphatidylethanolamine. The genomic DNA G+C content was 52.8 mol%. Based on phylogenetic, genotypic and phenotypic data, strain JHSY0214T represents a novel species of the genus Parasphingorhabdus, for which the name Parasphingorhabdus cellanae is proposed. The type strain is JHSY0214T (=KCTC 82387T=DSM 112279T).

Aerobic Methanotrophy and Co-occurrence Networks of a Tropical Rainforest and Oil Palm Plantations in Malaysia.

Oil palm (OP) plantations are gradually replacing tropical rainforest in Malaysia, one of the largest palm oil producers globally. Conversion of lands to OP plantations has been associated with compositional shifts of the microbial community, with consequences on the greenhouse gas (GHG) emissions. While the impact of the change in land use has recently been investigated for microorganisms involved in N2O emission, the response of the aerobic methanotrophs to OP agriculture remains to be determined. Here, we monitored the bacterial community composition, focusing on the aerobic methanotrophs, in OP agricultural soils since 2012, 2006, and 1993, as well as in a tropical rainforest, in 2019 and 2020. High-affinity methane uptake was confirmed, showing significantly lower rates in the OP plantations than in the tropical rainforest, but values increased with continuous OP agriculture. The bacterial, including the methanotrophic community composition, was modified with ongoing OP agriculture. The methanotrophic community composition was predominantly composed of unclassified methanotrophs, with the canonical (Methylocystis) and putative methanotrophs thought to catalyze high-affinity methane oxidation present at higher relative abundance in the oldest OP plantation. Results suggest that the methanotrophic community was relatively more stable within each site, exhibiting less temporal variations than the total bacterial community. Uncharacteristically, a 16S rRNA gene-based co-occurrence network analysis revealed a more complex and connected community in the OP agricultural soil, which may influence the resilience of the bacterial community to disturbances. Overall, we provide a first insight into the ecology and role of the aerobic methanotrophs as a methane sink in OP agricultural soils.

Resolution-enhanced optical inspection system to examine metallic nanostructures using structured illumination.

We developed a structured illumination-based optical inspection system to inspect metallic nanostructures in real time. To address this, we used post-image-processing techniques to enhance the image resolution. To examine the fabricated metallic nanostructures in real time, a compact and highly resolved optical inspection system was designed for practical industrial use. Structured illumination microscopy yields multiple images with various linear illumination patterns, which can be used to reconstruct resolution-enhanced images. Images of nanosized posts and complex structures reflected in the structured illumination were reconstructed into images with improved resolution. A comparison with wide-field images demonstrates that the optical inspection system exhibits high performance and is available as a real-time nanostructure inspection platform. Because it does not require special environmental conditions and enables multiple systems to be covered in arrays, the developed system is expected to provide real-time and noninvasive inspections during the production of large-area nanostructured components.

Variations in the anterior thoracic wall with sternalis muscle and accessory pectoralis major muscle.

PURPOSE: The new type of the sternalis muscle needs to be recognized, and the accessory pectoralis major muscle (AcPM) was found between the pectoralis major and minor muscle. It needs to be acknowledged those two different variations can exist in one case. METHODS: The muscle was found on a 73-year-old male cadaver during the dissection class for the anterior thoracic wall. It was proceeded to identify the adjacent structures with precise dissection. RESULTS: The cadaver had sternalis muscle bilaterally. Both side sternalis muscles had a medial and lateral belly and attached to pectoral fascia and rectus abdominis sheath. The pectoralis major muscle (PMaj) had a more profound slip attached to the costal cartilage of rib 4 and 5, which is AcPM. The pectoral nerve traveled through the clavipectoral fascia to the AcPM and through PMaj to the sternalis muscle. CONCLUSIONS: This study presented a new type of sternalis muscle. Two different variations were developed along with the pectoral nerve. It needs to be recognized in the diagnostic images, the muscle rehab outcome, and the surgical complication.

Anaerostipes hominis sp. nov., a novel butyrate-producing bacteria isolated from faeces of a patient with Crohn's disease.

Cultivation and isolation of gut bacteria are necessary for understanding their role in the intestinal ecosystem. We isolated a novel bacterium, designated strain BG01T, from the faeces of a patient with Crohn's disease. Strain BG01T was a strictly anaerobic, rod-shaped, Gram-variable and endospore-forming bacterium. Strain BG01T possessed C12 : 0, C18 : 0 dimethyl aldehyde (DMA) and C18 : 1 ω9c DMA as predominant cellular fatty acids and meso-diaminopimelic acid as a diagnostic diamino acid. Strain BG01T grew at 15-45 °C (optimum, 37 °C), with 0-4 % (w/v) NaCl (optimum, 0-1 %), at pH 6-10 (optimum, pH 7) and was resistant to bile salt, but not to ampicillin, metronidazole, vancomycin and cefoperazone. Butyrate, propionate, oxalacetate and fumarate were produced as fermentation end products from Gifu anaerobic medium broth. Strain BG01T showed 97.7 % 16S rRNA gene sequence similarity, and 92.0 and 48.5 % of average nucleotide identity and digital DNA-DNA hybridization values, respectively, with Anaerostipes caccae KCTC 15019T. Genomic analysis indicated that strain BG01T had a butyrate-producing pathway. The genomic G+C content of the strain was 43.5 mol%. Results of the phenotypic, phylogenetic and genotypic analyses indicated that strain BG01T represents a novel butyrate-producing species of the genus Anaerostipes, for which the name Anaerostipes hominis sp. nov. is proposed. The type strain is BG01T (=KCTC 15617T=JCM 32275T).

Chitinibacter bivalviorum sp. nov., isolated from the gut of the freshwater mussel Anodonta arcaeformis.

A novel Gram-stain-negative, aerobic, rod-shaped bacterium with a single polar flagellum, designated strain 2T18T, was isolated from the gut of the freshwater mussel Anodonta arcaeformis collected in the Republic of Korea. Phylogenetic analyses based on 16S rRNA gene sequences showed that the strain belonged to the genus Chitinibacter. Strain 2T18T formed a monophyletic clade with Chitinibacter fontanus KCTC 42982T, C. tainanensis KACC 11706T and C. alvei KCTC 23839T, with sequence similarities of 98.5, 98.4 and 95.9 %, respectively. Strain 2T18T exhibited optimal growth at 30 °C, at pH 8 and with 0.5 % (w/v) NaCl. The major isoprenoid quinone was ubiquinone-8 (Q-8). The predominant fatty acids were summed feature 3 (C16 : 1 ω6c and/or C16 : 1 ω7c) and C16 : 0. The polar lipids comprised phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, one unidentified lipid, three unidentified phospholipids and two unidentified aminophospholipids. The G+C content of the genomic DNA was 50.6 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between strains 2T18T and C. fontanus KCTC 42982T were below the thresholds used for the delineation of a novel species. Based on the phylogenetic, phenotypic, chemotaxonomic and genotypic characteristics, strain 2T18T represents a novel species of the genus Chitinibacter, for which the name Chitinibacter bivalviorum sp. nov. is proposed. The type strain is 2T18T (=KCTC 72821T=CCUG 74764T).

Brevilactibacter coleopterorum sp. nov., isolated from the intestine of the dark diving beetle Hydrophilus acuminatus, and Weissella coleopterorum sp. nov., isolated from the intestine of the diving beetle Cybister lewisianus.

A polyphasic taxonomic approach was used to characterize two novel bacterial strains, designated as HDW11T and HDW19T, isolated from intestine samples of the dark diving beetle Hydrophilus acuminatus and the diving beetle Cybister lewisianus, respectively. Both isolates were Gram-stain-positive, facultatively anaerobic and non-motile. Strain HDW11T grew optimally at 30 °C, pH 8 and in the presence of 1% (w/v) NaCl. Strain HDW19T grew optimally at 25 °C, pH 7 and in the presence of 0.3% (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences and genome sequences revealed that strain HDW11T is a member of the genus Brevilactibacter and is closely related to Brevilactibacter flavus VG341T [with 97.9% 16S rRNA sequence identity and 79.1% average nucleotide identity (ANI)], and that strain HDW19T belongs to the genus Weissella and is closely related to W. koreensis KCTC 3621T (with 98.9% 16S rRNA sequence identity and 79.5% ANI). The major cellular fatty acids of strains HDW11T and HDW19T were C18:1 ω9c and anteiso-C15:0, respectively. The sole respiratory quinone of strain HDW11T was MK-9 (H4). The major polar lipid components of strain HDW11T were diphosphatidylglycerol and phosphatidylglycerol, and the major polar lipid component of strain HDW19T was diphosphatidylglycerol. The genomic DNA G+C content of strains HDW11T and HDW19T were 72.1 and 37.2 mol%, respectively. The results of phylogenetic, phenotypic, chemotaxonomic and genotypic analyses suggest that strain HDW11T represents a novel species within the genus Brevilactibacter, and that strain HDW19T represents a novel species within the genus Weissella. We propose the name Brevilactibacter coleopterorum sp. nov. for strain HDW11T (=KACC 21335T=KCTC 49320T=JCM 33680T) and the name Weissella coleopterorum for strain HDW19T (=KACC 21347T=KCTC 43114T=JCM 33684T).

Tessaracoccus coleopterorum sp. nov., isolated from the intestine of the dark diving beetle, Hydrophilus acuminatus.

A polyphasic taxonomic approach was used to characterize a novel bacterium, designated as strain HDW20T, isolated from the intestine of the dark diving beetle Hydrophilus acuminatus. The isolate was Gram-stain-positive, facultatively anaerobic, non-motile, coccus-shaped, and formed pale orange colonies. Phylogenetic analysis based on 16S rRNA gene sequences and genome sequences showed that the isolate belonged to the genus Tessaracoccus in the phylum Actinobacteria and was closely related to T. flavescens SST-39T, T. defluvii JCM 17540T, and T. aquimaris NSG39T, with the highest 16S rRNA gene sequence similarity of 98.5 % and a highest average nucleotide identity (ANI) value of 80.6 %. The major cellular fatty acids were C18 : 1 ω9c and anteiso-C15 : 0. The main respiratory quinone was MK-9 (H4). The major polar lipid components were phosphatidylglycerol and diphosphatidylglycerol. The genomic DNA G+C content was 69.0 %. The isolate contains ʟʟ-diaminopimelic acid, ʟ-alanine, and ʟ-lysine as amino acid components, and ribose, glucose, and galactose as sugar components of the cell wall peptidoglycan. The results of phylogenetic, phenotypic, chemotaxonomic, and genotypic analyses suggested that strain HDW20T represents a novel species within the genus Tessaracoccus. We propose the name Tessaracoccus coleopterorum sp. nov. The type strain is HDW20T (=KACC 21348T=KCTC 49324T=JCM 33674T).

Early Prediction of the Need for Orthognathic Surgery in Patients With Repaired Unilateral Cleft Lip and Palate Using Machine Learning and Longitudinal Lateral Cephalometric Analysis Data.

ABSTRACT: The purpose of this study was to determine the cephalometric predictors of the future need for orthognathic surgery in patients with repaired unilateral cleft lip and palate (UCLP) using machine learning. This study included 56 Korean patients with UCLP, who were treated by a single surgeon and a single orthodontist with the same treatment protocol. Lateral cephalograms were obtained before the commencement of orthodontic/orthopedic treatment (T0; mean age, 6.3 years) and at at least of 15 years of age (T1; mean age, 16.7 years). 38 cephalometric variables were measured. At T1 stage, 3 cephalometric criteria (ANB ≤ -3°; Wits appraisal ≤ -5 mm; Harvold unit difference ≥34 mm for surgery group) were used to classify the subjects into the surgery group (n = 10, 17.9%) and non-surgery group (n = 46, 82.1%). Independent t-test was used for statistical analyses. The Boruta method and XGBoost algorithm were used to determine the cephalometric variables for the prediction model. At T0 stage, 2 variables exhibited a significant intergroup difference (ANB and facial convexity angle [FCA], all P < 0.05). However, 18 cephalometric variables at the T1 stage and 14 variables in the amount of change (ΔT1-T0) exhibited significant intergroup differences (all, more significant than P < 0.05). At T0 stage, the ANB, PP-FH, combination factor, and FCA were selected as predictive parameters with a cross-validation accuracy of 87.4%. It was possible to predict the future need for surgery to correct sagittal skeletal discrepancy in UCLP patients at the age of 6 years.

Variations of the musculofascial axillary arch with the adjacent lymph nodes.

PURPOSE: This unique case gives the extent of knowledge in the axilla area with axillary arch (AA) and a discussion of its clinical importance. MATERIALS AND METHOD: The anatomical anomaly was found during the dissection class for the brachial plexus. It was identified through the precise dissection of the structures bilaterally. RESULTS: The cadaver had fascial and muscular AA bilaterally. The fascial AA was separated into the superficial and deep arch group. The superficial arch group connected to the clavipectoral fascia and the axillary fascia. The deep arch group attached to the subscapular fascia. The muscular AA had superficial and deep variations. The superficial muscular AA attached between accessory slip of latissimus dorsi muscle (LDa) and pectoralis quartus muscle (PQ). The deep muscular AA attached to the crest of lesser tubercle of the humerus from LDa. The adipose tissue with the level one central lymph node was located lateral to the pectoralis minor muscle expand from pectoral lymph node through between LDa and PQ. CONCLUSION: This case showed the fascial and muscular AA together. The muscular AA had both complete and incomplete attachment types. It could give functional and neurological problems in the axilla, such as thoracic outlet syndrome. Additionally, the structures presented with the axillary lymph node. It helps to understand the patient's condition with the AA in the axilla and could provide.

FGFR1 is associated with c-MYC and proangiogenic molecules in metastatic renal cell carcinoma under anti-angiogenic therapy.

AIMS: This study aimed to investigate the clinicopathological significance of FGFR1 and c-MYC expression, particularly in relation to angiogenesis in clear cell renal cell carcinoma (CCRCC). METHODS AND RESULTS: Immunohistochemistry and fluorescence in-situ hybridisation were conducted with tissue microarrays from 91 metastatic CCRCC patients who received VEGF receptor tyrosine kinase inhibitors (VEGFR-TKIs). The expression of angiogenic molecules, FGFR1 and c-MYC, and tumoral vascular density (TVD) and mRNA expression and TVD of 533 CCRCCs in The Cancer Genome Atlas (TCGA) were analysed. FGFR1, pFGFR1 and c-MYC expression was observed in 29.1, 74.4 and 30.8% of tumours, respectively. FGFR1high was an independent worse prognostic factor for overall (HR = 1.871, P = 0.032) and progression-free (HR = 1.976, P = 0.016) survival. FGFR1high was significantly related to VEGFR-TKI responsiveness (P = 0.011). The presence of FGFR1high /c-MYChigh showed a positive correlation with proangiogenic markers, including VEGF (P = 0.018) and HIF-1α (P < 0.0001). FGFR1high /c-MYChigh tumours showed higher TVDs together with higher VEGFR2 and PDGFR-ß expression (both P < 0.0001). FGFR1 and c-MYC expression was also positively correlated with the expression of hypoxia-related and proangiogenic-related genes in the TCGA data. CONCLUSIONS: FGFR1 and c-MYC may be involved in tumour angiogenesis and FGFR1 may represent a promising therapeutic target in metastatic CCRCC.