18S and ITS2 rRNA gene sequence-structure phylogeny of the Phaeophyceae (SAR, Stramenopiles) with special reference to Laminariales.

The phylogeny of brown algae (Phaeophyceae) has undergone extensive changes in the recent past due to regular new scientific insights. We used nuclear 18S rDNA with an extensive dataset, aiming to increase the accuracy and robustness of the reconstructed phylogenetic trees using a simultaneous sequence-structure approach. Individual secondary structures were generated for all 18S rDNA sequences. The sequence-structure information was encoded and used for an automated simultaneous sequence-structure alignment. Neighbor-joining and profile neighbor-joining trees were calculated based on 186 phaeophycean sequence-structure pairs. Additionally, sequence-structure neighbor-joining, maximum parsimony and maximum likelihood trees were reconstructed on a representative subset. Using a similar approach, ITS2 rDNA sequence-structure information was used to reconstruct a neighbor-joining tree including 604 sequence-structure pairs of the Laminariales. Our study results are in significant agreement with previous single marker 18S and ITS2 rDNA analyses. Moreover, the 18S results are in wide agreement with recent multi-marker analyses. The bootstrap support was significantly higher for our sequence-structure analysis in comparison to sequence-only analyses in this study and the available literature. This study supports the simultaneous inclusion of sequence-structure data at least for 18S to obtain more accurate and robust phylogenetic trees compared to sequence-only analyses.

Ordovician origin and subsequent diversification of the brown algae.

Brown algae are the only group of heterokont protists exhibiting complex multicellularity. Since their origin, brown algae have adapted to various marine habitats, evolving diverse thallus morphologies and gamete types. However, the evolutionary processes behind these transitions remain unclear due to a lack of a robust phylogenetic framework and problems with time estimation. To address these issues, we employed plastid genome data from 138 species, including heterokont algae, red algae, and other red-derived algae. Based on a robust phylogeny and new interpretations of algal fossils, we estimated the geological times for brown algal origin and diversification. The results reveal that brown algae first evolved true multicellularity, with plasmodesmata and reproductive cell differentiation, during the late Ordovician Period (ca. 450 Ma), coinciding with a major diversification of marine fauna (the Great Ordovician Biodiversification Event) and a proliferation of multicellular green algae. Despite its early Paleozoic origin, the diversification of major orders within this brown algal clade accelerated only during the Mesozoic Era, coincident with both Pangea rifting and the diversification of other heterokont algae (e.g., diatoms), coccolithophores, and dinoflagellates, with their red algal-derived plastids. The transition from ancestral isogamy to oogamy was followed by three simultaneous reappearances of isogamy during the Cretaceous Period. These are concordant with a positive character correlation between parthenogenesis and isogamy. Our new brown algal timeline, combined with a knowledge of past environmental conditions, shed new light on brown algal diversification and the intertwined evolution of multicellularity and sexual reproduction.

Honeycomb lung is a major risk factor for preoperative radiological tumor size underestimation in patients with primary lung cancer.

Background: Lung cancer frequently occurs in lungs with background idiopathic interstitial pneumonias (IIPs). Limited resection is often selected to treat lung cancer in patients with IIPs in whom respiratory function is already compromised. However, accurate surgical margins are essential for curative resection; underestimating these margins is a risk for residual lung cancer after surgery. We aimed to investigate the findings of lung fields adjacent to cancer segments affect the estimation of tumor size on computed tomography compared with the pathological specimen. Methods: This analytical observational study retrospectively investigated 896 patients with lung cancer operated on at Fujita Health University from January 2015 to June 2020. The definition of underestimation was a ≥10 mm difference between the radiological and pathological maximum sizes of the tumor. Results: The lung tumors were in 15 honeycomb, 30 reticulated, 207 emphysematous, and 628 normal lungs. The ratio of underestimation in honeycomb lungs was 33.3% compared to 7.4% without honeycombing (P=0.004). Multivariate analysis showed that honeycombing was a significant risk factor for tumor size underestimation. A Bland-Altman plot represented wide 95% limits of agreement, -40.8 to 70.2 mm, between the pathological and radiological maximum tumor sizes in honeycomb lungs.

The phase angle as a predictor of postoperative complications in patients undergoing lung cancer surgery.

PURPOSE: The phase angle (PhA), calculated by bioelectrical impedance analysis, is used as a nutritional risk indicator. A low preoperative PhA has been reported as a marker of postoperative complications in patients with cancer; however, the relationship between the PhA and postoperative complications in patients with lung cancer remains unknown. We conducted this study to assess the predictive ability of the preoperative PhA for postoperative complications in patients undergoing surgery for primary lung cancer. METHODS: We reviewed the data on 240 patients who underwent surgery for primary lung cancer at our institution between August, 2019 and August, 2021. RESULTS: The PhA value in this study was 4.7 ± 0.7°. According to the Clavien-Dindo classification, grade ≥ II postoperative complications occurred in 53 patients (22.0%). Based on the multivariate logistic analysis, only the PhA (odds ratio, 0.51, 95% confidence interval, 0.29-0.90, p = 0.018) was an independent predictor of Clavien-Dindo grade ≥ II postoperative complications. CONCLUSIONS: The PhA may be a valuable marker for predicting the risk of postoperative complications following lung cancer surgery.

[Paclitaxel plus Bevacizumab Combination Therapy for Esophageal Metastasis of Breast Cancer-A Case Report].

An 80-year-old woman with a history of left breast cancer complained of dysphagia. At the age of 67 years, she had undergone a left modified radical mastectomy, chemotherapy, and endocrine therapy for left breast cancer. Six years after adjuvant therapy completion, she developed dysphagia. Chest CT showed only midesophageal stenosis. Endoscopic examination revealed whole circumferential stenosis without mucosal abnormality located 25 cm from the incisors, and a biopsy showed histologically normal mucosa. Endoscopic balloon dilatation was performed 5 times in 1 year and 3 months. Subsequently, a biopsy specimen revealed adenocarcinoma, which suggested metastasis from the previous breast cancer. One month after the initiation of tamoxifen administration, dyspnea due to pleural effusion was encountered. We treated this via pleural adhesion therapy and changed the treatment to paclitaxel plus bevacizumab combination therapy. She continued paclitaxel plus bevacizumab therapy for 1 year and 4 months without any signs of recurrence.

Whole genome population structure of North Atlantic kelp confirms high-latitude glacial refugia.

Coastal refugia during the Last Glacial Maximum (~21,000 years ago) have been hypothesized at high latitudes in the North Atlantic, suggesting marine populations persisted through cycles of glaciation and are potentially adapted to local environments. Here, whole-genome sequencing was used to test whether North Atlantic marine coastal populations of the kelp Alaria esculenta survived in the area of southwestern Greenland during the Last Glacial Maximum. We present the first annotated genome for A. esculenta and call variant positions in 54 individuals from populations in Atlantic Canada, Greenland, Faroe Islands, Norway and Ireland. Differentiation across populations was reflected in ~1.9 million single nucleotide polymorphisms, which further revealed mixed ancestry in the Faroe Islands individuals between putative Greenlandic and European lineages. Time-calibrated organellar phylogenies suggested Greenlandic populations were established during the last interglacial period more than 100,000 years ago, and that the Faroe Islands population was probably established following the Last Glacial Maximum. Patterns in population statistics, including nucleotide diversity, minor allele frequencies, heterozygosity and linkage disequilibrium decay, nonetheless suggested glaciation reduced Canadian Atlantic and Greenlandic populations to small effective sizes during the most recent glaciation. Functional differentiation was further reflected in exon read coverage, which revealed expansions unique to Greenland in 337 exons representing 162 genes, and a modest degree of exon loss (103 exons from 56 genes). Altogether, our genomic results provide strong evidence that A. esculenta populations were resilient to past climatic fluctuations related to glaciations and that high-latitude populations are potentially already adapted to local conditions as a result.

A case of inflammatory mass resulting from calcium crystal deposition disease around the thoracic spine.

Calcium crystal deposition diseases are transient benign diseases that can cause intense pain. They can sometimes cause masses and soft tissue edema around the calcification, which should be differentiated from tumors and abscesses. We report a case of calcium crystal deposition disease with an enhanced mass on the ventral side of the vertebral bodies resembling tumors and abscesses. A female patient in her 50s visited our hospital complaining of chest pain. Computed tomography revealed a soft tissue mass with polygonal high-density lesions on the ventral side of the thoracic spine. Initially, we suspected it to be a perivertebral tumor and considered a biopsy. However, the pain rapidly improved with the administration of oral acetaminophen (Caronal, Chuo-ku/Tokyo/Japan). Hence, the patient was followed up for the time being. The mass disappeared after 3 months. In addition, polygonal high-density lesions inside the mass disappeared over time. Therefore, it was diagnosed as an inflammatory mass due to calcium crystal deposition disease. Calcium crystal deposition diseases can cause soft tissue edema and inflammatory mass around the calcium crystal deposit that can be confused with a perivertebral tumor. This report elucidates the importance of identifying calcifications within and near the masses to diagnose an inflammatory mass resulting from calcium crystal deposition.

Tracheobronchial reconstruction by inverted Barclay's method for tracheobronchial injury in an 8-year-old girl: a case report.

BACKGROUND: Tracheobronchial injury in children is rare but can be highly fatal in severe cases. Therefore, prompt diagnosis and treatment are required. The appropriate treatment method depends on the extent and severity of the injury. CASE PRESENTATION: An 8-year-old girl fell from the fifth floor and was transported to a local hospital. She had a tracheobronchial injury, went into cardiopulmonary arrest during transportation to our hospital. She was revived with cardiopulmonary resuscitation, and veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was commenced. Subsequently, we performed tracheobronchial reconstruction by inverted Barclay's method for tracheobronchial injury. She was switched from VA-ECMO to venovenous (VV)-ECMO 4 days postoperatively, and VV-ECMO was eventually discontinued 27 days after the surgery. The patient was awake and weaned off the ventilator on postoperative day 58. She was discharged 97 days after the surgery. CONCLUSIONS: Tracheobronchial reconstruction by inverted Barclay's method is the preferred surgical technique when other reconstruction techniques are expected to cause excessive tension on the anastomosis of the right main bronchus.

[Case of Unresectable Gastric Mixed Neuroendocrine Neoplasm(MiNEN)Treated with Chemotherapy].

A 68-year-old man diagnosed with gastric mixed neuroendocrine-non-neuroendocrine neoplasia(MiNEN)concomitant with liver metastasis received chemotherapy using ramucirumab and paclitaxel. A decrease in tumor marker levels and size of the metastatic liver lesions was observed after 3 courses of treatment. However, the patient developed progressive disease after 9 courses of chemotherapy; hence, nivolumab chemotherapy was initiated. Although liver metastases were reduced after 2 courses of nivolumab, the patient developed new liver lesions after 18 courses of treatment; irinotecan, S-1 and oxaliplatin, and trifluridine/tipiracil were then administered. Liver metastases progressed despite changing the regimen, and the patient died 25 months after the initiation of chemotherapy. Gastric MiNEN usually shows poor prognosis, and there is lack of consensus regarding optimal treatment. Ramucirumab and nivolumab are relatively well-tolerated and may be effective for chemotherapy.

Providing a phylogenetic framework for trait-based analyses in brown algae: Phylogenomic tree inferred from 32 nuclear protein-coding sequences.

In the study of the evolution of biological complexity, a reliable phylogenetic framework is needed. Many attempts have been made to resolve phylogenetic relationships between higher groups (i.e., interordinal) of brown algae (Phaeophyceae) based on molecular evidence, but most of these relationships remain unclear. Analyses based on small multi-gene data (including chloroplast, mitochondrial and nuclear sequences) have yielded inconclusive and sometimes contradictory results. To address this problem, we have analyzed 32 nuclear protein-coding sequences in 39 Phaeophycean species belonging to eight orders. The resulting nuclear-based phylogenomic trees provide virtually full support for the phylogenetic relationships within the studied taxa, with few exceptions. The relationships largely confirm phylogenetic trees based on nuclear, chloroplast and mitochondrial sequences, except for the placement of the Sphacelariales with weak bootstrap support. Our study indicates that nuclear protein-coding sequences provide significant support to conclusively resolve phylogenetic relationships among Phaeophyceae, and may be a powerful approach to fully resolve interordinal relationships with increased taxon sampling.

Whole-genome sequencing reveals forgotten lineages and recurrent hybridizations within the kelp genus Alaria (Phaeophyceae).

The genomic era continues to revolutionize our understanding of the evolution of biodiversity. In phycology, emphasis remains on assembling nuclear and organellar genomes, leaving the full potential of genomic datasets to answer long-standing questions about the evolution of biodiversity largely unexplored. Here, we used whole-genome sequencing (WGS) datasets to survey species diversity in the kelp genus Alaria, compare phylogenetic signals across organellar and nuclear genomes, and specifically test whether phylogenies behave like trees or networks. Genomes were sequenced from across the global distribution of Alaria (including Alaria crassifolia, A. praelonga, A. crispa, A. marginata, and A. esculenta), representing over 550 GB of data and over 2.2 billion paired reads. Genomic datasets retrieved 3,814 and 4,536 single-nucleotide polymorphisms (SNPs) for mitochondrial and chloroplast genomes, respectively, and upwards of 148,542 high-quality nuclear SNPs. WGS revealed an Arctic lineage of Alaria, which we hypothesize represents the synonymized taxon A. grandifolia. The SNP datasets also revealed inconsistent topologies across genomic compartments, and hybridization (i.e., phylogenetic networks) between Pacific A. praelonga, A. crispa, and putative A. grandifolia, and between some lineages of the A. marginata complex. Our analysis demonstrates the potential for WGS data to advance our understanding of evolution and biodiversity beyond amplicon sequencing, and that hybridization is potentially an important mechanism contributing to novel lineages within Alaria. We also emphasize the importance of surveying phylogenetic signals across organellar and nuclear genomes, such that models of mixed ancestry become integrated into our evolutionary and taxonomic understanding.

Discovery of a novel brown algal genus and species Setoutiphycus delamareoides (Phaeophyceae, Ectocarpales) from the Seto Inland Sea, Japan.

We describe a new genus and species of brown algae from the Seto Inland Sea, Japan. This species is similar to Delamarea in gross morphology and anatomy, but distinctive in having longer thalli with rare branching and shorter cortical cells. In culture, pluri-zoids derived from plurilocular zoidangia on the erect thalli developed into filamentous gametophytes bearing ectocarpoid plurilocular zoidangia, but also formed parenchymatous erect thalli of sub-sympodial growth similar to Trachynema often having branches, and formed lateral and terminal plurilocular zoidangia. Molecular phylogenies using concatenated chloroplast and mitochondrial gene sequences showed the new alga nested in the clade composed of ectocarpalean genera with diffuse growth, parenchymatous thalli, and multiple chloroplasts, but this species is distinctive. Therefore, we propose Setoutiphycus delamareoides gen. & sp. nov. for this new alga, and provisionally place it in Chordariaceae, Ectocarpales. The Seto Inland Sea repeatedly dried during sea level regressions during glacial periods, and the present sea level recovered after the last glacial maximums (LGM), ca. 10,000 years ago. Therefore, it is unlikely that the species evolved within this area. Its distribution in the area may be explained as a remnant population that survived in refugia in southern Japan during the LGM.

[Change in Therapy for Malignant Pleural Mesothelioma at Our Hospital].

When molecular target drug began to be used for chemotherapy to treat malignant pleural mesothelioma in 2014, we introduced this treatment strategy for 61 patients who were diagnosed and were being treated in our hospital. Chemotherapy was performed on 37 patients, while 12 patients underwent surgical remedy and best supportive care was provided to another 12 patients. Molecular target drug was used as the primary chemotherapy treatment in 14 cases, while it was the secondary treatment in 22 others. Pleural decortication was performed as the operative method for all the 12 cases requiring surgical remedy, and 2 of these cases were shifted to extrapleural pneumonectomy. By the chemotherapy, there were many cases of PS≥2, non‒epithelial type, advanced stage, LMR<2.74 of the biomarker. When we compared surgical remedy with the chemotherapy clinicopathologically. In the prognostic examination, in median survival time of all cases, as for 23 months, the chemotherapy, 31 months, the surgical remedy was not reached. Prognostic improvement of stage ⅢA was determined according to the stage of the chemotherapy. A multivariate variable analysis revealed that only a non‒sarcomatous type was a good prognostic factor, and surgery remedy was not.

Clofibric acid increases molecular species of phosphatidylethanolamine containing arachidonic acid for biogenesis of peroxisomal membranes in peroxisome proliferation in the liver.

The biogenesis of peroxisomes in relation to the trafficking of proteins to peroxisomes has been extensively examined. However, the supply of phospholipids, which is needed to generate peroxisomal membranes in mammals, remains unclear. Therefore, we herein investigated metabolic alterations induced by clofibric acid, a peroxisome proliferator, in the synthesis of phospholipids, particularly phosphatidylethanolamine (PE) molecular species, and their relationship with the biogenesis of peroxisomal membranes. The subcutaneous administration of clofibric acid to rats at a relatively low dose (130 mg/kg) once a day time-dependently and gradually increased the integrated perimeter of peroxisomes per 100 µm2 hepatocyte cytoplasm (PA). A strong correlation was observed between the content (µmol/mg DNA) of PE containing arachidonic acid (20:4) and PA (r2 = 0.9168). Moreover, the content of PE containing octadecenoic acid (18:1) positively correlated with PA (r2 = 0.8094). The treatment with clofibric acid markedly accelerated the formation of 16:0-20:4 PE by increasing the production of 20:4 and the activity of acyl chain remodeling of pre-existing PE molecular species. Increases in the acyl chain remodeling of PE by clofibric acid were mainly linked to the up-regulated expression of the Lpcat3 gene. On the other hand, clofibric acid markedly increased the formation of palmitic acid (16:0)-18:1 PE through de novo synthesis. These results suggest that the enhanced formation of particular PE molecular species is related to increases in the mass of peroxisomal membranes in peroxisome proliferation in the liver.

Evaluation of prognosis after thoracoscopic lobectomy for primary lung cancer.

INTRODUCTION: Thoracoscopic lobectomy for primary lung cancer is performed at many institutions. However, few reports are available on postoperative prognosis for progressive stages. In 2004, we adopted lobectomy by video-assisted thoracoscopic surgery (VATS), which would be applicable to the clinical stages up to stage IIIA. This study reports long-term outcomes of surgery for primary lung cancer at several stages, including IIIA. METHODS: We compared the long-term outcomes of 315 VATS cases with those of 159 open thoracotomy cases. RESULTS: The overall 5-year survival rate was 78.1% for the VATS group and 61.9% for the open thoracotomy group. A statistically significant difference between the survival curves of the two groups was observed (P = .001). When analyzing the survival curves for both groups by pathological (p) stage, significant differences were observed for p-stages IB and IIIA, with the VATS group producing better results than the open thoracotomy group. CONCLUSION: The long-term outcomes of patients with primary lung cancer at our institution were more favorable in the group undergoing VATS lobectomy than in the group undergoing open thoracotomy.

[A Case of Intraductal Apocrine Carcinoma of the Breast].

A female in her 60s who complained of nipple discharge in her left breast for 1 year. A soft mass ill-defined margin in the border of AB area was observed. Mammography showed a focal asymmetric density. Ultrasonography disclosed an irregular heterogenous low echoic lesion in the AB area of her left breast. MRI image showed an enhanced lesion in the inner area. The pathological diagnosis by core needle biopsy was non-invasive ductal carcinoma with apocrine metaplasia. Mastectomy with sentinel lymph node biopsy of the left breast was performed. Post operative histopathological examination revealed intraductal apocrine carcinoma without lymph node metastasis. Estrogen and progesterone receptors were negative. Three years after operation without any adjuvant treatment, she has no recurrence of lesion.

[A Case of Metastatic Pancreatic Ductal Adenocarcinoma Successfully Treated with Modified FOLFIRINOX and Concurrent Radiotherapy].

A 70-year-old man with metastatic pancreatic ductal adenocarcinoma(cT4N1bM1, cStage Ⅳ)underwent chemotherapy with modified FOLFIRINOX without any severe adverse event to 20 cycles. In the middle of that, concurrent irradiation toward primary lesion(total dose, 43.2 Gy)was administered. Grade 1 adverse events include anemia, thrombocytopenia, hypoalbuminemia, hypokalemia, alkaline phosphatase increased, hypertension, peripheral sensory neuropathy, fatigue, anorexia and nausea. The relative dose intensities of oxaliplatin, irinotecan and fluorouracil at 6 months after beginning of treatment were 77.6, 84.0 and 88.3 percent, respectively. The total dose of administered oxaliplatin was 825 mg to the square meter. The primary lesion had been stable for the 20 cycles, although peritoneal dissemination had progressively increased in size. For 17 months, opioid was not necessary for the control of abdominal or back pain to the end of third-line treatment. Though safety or clinical benefits of modified FOLFIRINOX plus concurrent radiotherapy for metastatic pancreatic ductal adenocarcinoma have not been reported, in this case, such treatment might contribute to prolong prognosis or prevent developing abdominal or back pain.

[A Case of Malignant Thyroid Lymphoma That Was Difficult to Differentiate from Methotrexate-Associated Lymphoproliferative Disorders(MTX-LPD)].

A female patient in her 60s was going to get treatment for rheumatoid arthritis(RA). Considering the possibility of using biologics, CT examination was performed for screening of malignant diseases. A mass shadow in the left lobe of the thyroid gland was detected. The patient was followed up, and ultrasonography did not reveal any malignant findings. She was treated with methotrexate(MTX), and 1 year later, the thyroid mass was enlarged on CT. Ultrasonography revealed an enlarged hypoechoic region. Fine needle aspiration cytology revealed malignant lymphoma. Excisional biopsy was performed to determine the treatment plan. The pathological diagnosis was follicular lymphoma, and the possibility of methotrexate- associated lymphoproliferative disorders(MTX-LPD)persisted. It was difficult to discontinue MTX because of the high activity of RA. She was treated with rituximab for malignant lymphoma and concurrently with MTX for RA. The thyroid tumor disappeared for 3 months. Four years later, there is no sign of tumor recurrence.

Global Diversity and Geographic Distributions of Padina Species (Dictyotales, Phaeophyceae): New Insights Based on Molecular and Morphological Analyses.

The taxonomic status and species diversity of the brown algal genus Padina (Dictyotales, Phaeophyceae) was assessed based on DNA sequences and the morpho-anatomy of specimens collected worldwide, especially from tropical and subtropical western Pacific regions. Phylogenetic analyses using chloroplast rbcL and mitochondrial cox3 gene sequences demonstrated four distinct clades for newly collected samples with high bootstrap support. Each species clade possesses a suite of morphological features that are not shared by any known species of Padina. These are P. imbricata sp. nov., Padina lutea sp. nov., P. moffittianoides sp. nov., and P. nitida sp. nov. The occurrence of these and other species of Padina clearly points to an elevated diversity of the genus in tropical/subtropical waters of the western Pacific. Phylogenetic analyses provided new insights into biogeographic characteristics of the genus, with many species in the Pacific Ocean showing shared/overlapping distributions, whereas species from the Mediterranean/Atlantic and/or the Indian Ocean tend to be confined to particular regions. Consideration has also been given to the evolutionary time frame of the genus Padina based on molecular time trees: a time tree of the concatenated data set (rbcL + cox3) revealed the estimated divergence time in the mid-Cretaceous, whereas those of cox3 and rbcL showed older estimates pointing to the periods of mid-Jurassic and Early Cretaceous, respectively.