Distinguishing Axillary Lymphadenopathy after COVID-19 Vaccination from Malignant Lymphadenopathy.

Objectives: To study the differences between malignant hypermetabolic axillary lymphadenopathy (MHL) and COVID-19 vaccine-associated axillary hypermetabolic lymphadenopathy (VAHL) using clinical imaging. Methods: A total of 1096 patients underwent Positron Emission Tomography-Computed Tomography (PET-CT) between 1 June 2021 and 30 April 2022 at Ehime University Hospital. In total, 188 patients with axillary lymphadenopathy after the COVID-19 vaccination were evaluated. The patients were classified into three groups such as VAHL (n = 27), MHL (n = 21), and equivocal hypermetabolic axillary lymphadenopathy (EqHL; n = 140). Differences in lymph node (LN) swellings were statistically analyzed using clinical imaging (echography, CT, and 18F-FDG PET). Results: MHL included a higher female population (90.5%) owing to a higher frequency of breast cancer (80.9%). Axillary LNs of MHL did not show any LN fatty hilums (0%); however, those of VAHL and EqHL did (15.8 and 36%, respectively). After the logistic regression analysis of the patients who had axillary lymphadenopathy without any LN fatty hilums, the minor axis length and ellipticity (minor axis/major axis) in the largest axillary LN, SUVmax, and Tissue-to-Background Ratio (TBR) were useful in distinguishing malignant lymphadenopathies. A receiver-operating characteristic (ROC) analysis indicated that a cut-off value of ≥7.3 mm for the axillary LN minor axis (sensitivity: 0.714, specificity: 0.684) and of ≥0.671 for ellipticity (0.667 and 0.773, respectively) in the largest LN with the highest SUVmax and TBR were predictive of MHL. Conclusions: Axillary lymphadenopathy of the minor axis and ellipticity in LN without fatty hilums may be useful to be suspicious for malignancy, even in patients who have received COVID-19 vaccination. Further examinations, such as 18F-FDG PET, are recommended for such patients.

A phase II study (WJOG12819L) to assess the efficacy of osimertinib in patients with EGFR mutation-positive NSCLC in whom systemic disease (T790M-negative) progressed after treatment with first- or second-generation EGFR TKIs and platinum-based chemotherapy.

BACKGROUND: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that is an established standard treatment option for chemotherapy-naive patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). However, of such patients who have received prior treatment with a first- or second-generation EGFR TKI, only approximately half are eligible for osimertinib therapy because its indication as second-line treatment and beyond is limited to metastatic NSCLC that is positive for the T790M resistance mutation of the EGFR gene. This study was initiated at the request of a dedicated network for patients with lung cancer in Japan. METHODS: We conducted a phase II study to assess the efficacy of osimertinib in patients with EGFR mutation-positive NSCLC in whom systemic disease (T790M-negative) progressed after treatment with first- or second-generation EGFR TKIs and platinum-based chemotherapy. The primary end point was response rate (assessed by a central imaging reviewer). RESULTS: From August 2020 to February 2021, 55 patients from 15 institutions were enrolled in the study. The overall response for primary analysis was achieved in 16 patients (29.1 %; 95 % CI, 17.6-42.9), which exceeded the threshold response rate necessary for analysis. Stable disease was found in 16 patients (29.1 %), and progressive disease, in 18 (32.7 %). The median length of progression-free survival (PFS) was 4.07 months (95 % CI 2.10-4.30), and the rate of 12-month PFS was 17.3 %. CONCLUSIONS: Osimertinib demonstrated modest antitumor activity against progressive EGFR T790M-negative disease.

Comparison of 137Cs uptake, depuration and continuous uptake, originating from feed, in five salmonid fish species.

The origin of 137Cs contamination, contamination levels, and its effective ecological half-life can differ among fish species, but until recently it was unknown whether interspecific differences in radiocaesium metabolism existed. We compare the trophic transfer of 137Cs in five salmonid species under controlled conditions. Fish were fed a diet containing 200 Bq kg-1 wet wt concentration of 137Cs for a fixed period of time. While there were almost no differences in contamination levels among individual fish within a species during fixed periods, the rate of 137Cs uptake was statistically different among the species examined, for which the effective half-life of 137Cs ranged 49-84 days. No significant difference in rate of decline in the quantity of 137Cs was apparent among species in two experiments after correcting for differences in growth. The effective half-life was shortest in Oncorhynchus mykiss and O. masou-two species exhibiting the best growth rate in both experiments-indicating an influence of the dilution effect associated with growth. When continuously fed 200 Bq kg-1 wet wt concentration of 137Cs for a period of 209-294 days, contamination levels in the five species ranged 216-240 Bq kg-1 wet wt, and reached a steady state value. Our results indicate metabolic rate, although accompanying a change of body size, did not affect 137Cs contamination levels in fish, which implies that contamination levels in the diet strongly determined contamination levels in fish.

Genetic population structure of Japanese river sculpin Cottus pollux (Cottidae) large-egg type, inferred from mitochondrial DNA sequences.

The geographic distribution of mitochondrial DNA haplotypes from Japanese river sculpin Cottus pollux large-egg type (LE), collected from 55 locations in 22 rivers over most of the species' range in Japan, was examined to assess for patterns of population genetic structure. The 87 haplotypes observed from C. pollux LE were distinguishable from C. pollux middle-egg type and small-egg type haplotypes from previously published research. Cottus pollux LE from each river were largely represented by diagnostic mtDNA haplotypes, with limited geographical associations of haplotypes, suggesting that each river must be treated as a separate management unit.

Use of the forced-oscillation technique to estimate spirometry values.

PURPOSE: Spirometry is sometimes difficult to perform in elderly patients and in those with severe respiratory distress. The forced-oscillation technique (FOT) is a simple and noninvasive method of measuring respiratory impedance. The aim of this study was to determine if FOT data reflect spirometric indices. PATIENTS AND METHODS: Patients underwent both FOT and spirometry procedures prior to inclusion in development (n=1,089) and validation (n=552) studies. Multivariate linear regression analysis was performed to identify FOT parameters predictive of vital capacity (VC), forced VC (FVC), and forced expiratory volume in 1 second (FEV1). A regression equation was used to calculate estimated VC, FVC, and FEV1. We then determined whether the estimated data reflected spirometric indices. Agreement between actual and estimated spirometry data was assessed by Bland-Altman analysis. RESULTS: Significant correlations were observed between actual and estimated VC, FVC, and FEV1 values (all r>0.8 and P<0.001). These results were deemed robust by a separate validation study (all r>0.8 and P<0.001). Bias between the actual data and estimated data for VC, FVC, and FEV1 in the development study was 0.007 L (95% limits of agreement [LOA] 0.907 and -0.893 L), -0.064 L (95% LOA 0.843 and -0.971 L), and -0.039 L (95% LOA 0.735 and -0.814 L), respectively. On the other hand, bias between the actual data and estimated data for VC, FVC, and FEV1 in the validation study was -0.201 L (95% LOA 0.62 and -1.022 L), -0.262 L (95% LOA 0.582 and -1.106 L), and -0.174 L (95% LOA 0.576 and -0.923 L), respectively, suggesting that the estimated data in the validation study did not have high accuracy. CONCLUSION: Further studies are needed to generate more accurate regression equations for spirometric indices based on FOT measurements.

Exposure of a herbivorous fish to ¹³4Cs and ¹³7Cs from the riverbed following the Fukushima disaster.

Ayu Plecoglossus altivelis, a herbivorous fish, is an important fishery resource and key component of the foodweb in many Japanese streams. Radionuclide contamination of this species is likely transferred to higher trophic levels, include humans, in the food chain. After the Fukushima accident in March 2011, ayu were exposed to highly contaminated silt while feeding on algae attached to the riverbed stones. To understand the route by which herbivorous fish are exposed to radionuclides, the activity concentrations of sum of (134)Cs and (137)Cs (radiocesium) were analyzed in riverbed samples (algae and silt) and in the internal organs and the muscle of ayu in five river systems in the Fukushima Prefecture between summer 2011 and autumn 2013. Although there was a positive correlation between the radiocesium activity concentrations in the muscle and the internal organs of ayu, the median activity concentration in the muscle was much lower than those in the internal organs. The activity concentrations of radiocesium in the riverbed samples and the internal organs and the muscle of ayu were correlated with contamination levels in soil samples taken from the watershed upstream of the sample sites. The results of the generalized linear mixed models suggest that the activity concentrations in both the internal organs and the muscle of ayu declined over time. Additionally, the activity concentrations in the internal organs were correlated with those in the riverbed samples that were collected around the same time as the ayu. The activity concentrations in the muscle were correlated with ayu body size. Our results suggest that ayu ingest (134)Cs and (137)Cs while grazing silt and algae from the riverbed, and a part of the (134)Cs and (137)Cs is assimilated into the muscle of the fish.

Phylogeography of the salmonid fish, Dolly Varden Salvelinus malma: multiple glacial refugia in the North Pacific Rim.

The geographic distribution pattern of mitochondrial DNA (control region) sequence polymorphisms from 73 populations of a salmonid fish, Dolly Varden Salvelinus malma, over most of its range in the North Pacific rim, was examined to assess how its spatial population genetic structure has been molded. The observed 68 haplotypes were grouped into three main lineages, which correspond to western, central, and eastern regions in the North Pacific. The two outlier-haplotype groups gave close agreement with DNA types from two congeneric species, white-spotted charr S. leucomaenis and Arctic charr S. alpinus, respectively. These results suggest that the present-day genetic structure of S. malma reflects historical patterns of isolation and re-colonization, and also historical hybridization with co-distributed species. We also placed the haplotypes of S. malma within our study areas into a pre-existing evolutionary relationship of S. alpinus and S. malma throughout the Northern Hemisphere. Phylogenetic analysis revealed that the Western Lineage S. malma was basal to all other lineages of S. malma and S. alpinus. Our data serve as a biogeographic hypothesis for salmonid fishes that the Sea of Japan and/or Sea of Okhotsk regions represents a place of origin for S. malma and S. alpinus groups currently distributed in circumpolar regions.

[Pulmonary non-tuberculous mycobacteriosis complicated with lung cancer].

A 54-year-old man with pulmonary non-tuberculous mycobacteriosis( pulmonary NTM) who had been treated by antituberculous chemotherapy, developed a new nodule of 1.3 cm in size in the segment 1/2 of the right upper lobe. The cavity of 3.5 cm in size in the segment 6 of the right lower lobe from which Mycobacterium intracellulare was bronchoscopically detected, was suspected to be pulmonary NTM lesion. Since lung cancer was highly suspected by radiological examinations, right upper lobectomy and S6 segmentectomy were performed. Pathological diagnosis for the right upper lobe nodule was adenocarcinoma.

Prolactin and upstream migration of the amphidromous teleost, ayu Plecoglossus altivelis.

Changes in mRNA levels of prolactin (PRL) during the upstream migration were examined in fry of the amphidromous fish, ayu Plecoglossus altivelis. Quantification of mRNA has been done with real-time PCR and expressed as whole body or pituitary contents depending the body size of fry. PRL mRNA levels of ayu caught in seawater of the coastal area remained low during early spring. Prior to the start of the upstream migration, the fish caught in the coastal area in mid spring showed increased levels of PRL mRNA. There were further increases in PRL levels in the fish caught in the river. Analysis of proportions revealed that there were significant differences among PRL mRNA in the fish caught in different environmental salinities. Body weight showed a positive relation with PRL mRNA in ayu caught in seawater. A landlocked population of ayu, which migrates from lake to river, showed no significant change in PRL mRNA levels before and after upstream migration. Results in this study indicate the importance of up-regulation of PRL gene expression of ayu during the upstream migration from seawater to fresh water. There is a possible relationship between body size and PRL in the early developmental stage of ayu in seawater, but not in the fish in fresh water.

Tetra-repeat microsatellite markers for the masu salmon (Oncorhynchus masou masou) and its application in cross-subspecies amplification.

We developed tetranucleotide-repeat microsatellite markers for the masu salmon (Oncorhynchus masou) complex. 454 pyrosequencing was used to discover repeat motifs, and seven polymorphic microsatellite-primer sets were identified. The number of alleles detected at each locus ranged from four to 24 and the expected heterozygosity varied from 0.57 to 0.92. Cross-subspecies amplification for O. m. masou, O. m. ishikawae and O. m. subsp. was successful. These microsatellites can be utilized in studies of genetic structure, genetic diversity, and intra- and inter-subspecific hybridization, making a contribution to conservation and management of the Oncorhynchus masou complex.

Changes in prolactin mRNA levels during downstream migration of the amphidromous teleost, ayu Plecoglossus altivelis.

Changes in mRNA levels of prolactin (PRL) during seaward migration and after experimental transfer from fresh water (FW) to seawater (SW) were examined in larvae of the amphidromous fish, ayu Plecoglossus altivelis. In the field study, ayu larvae caught in the surf zone showed lower levels of PRL mRNA than those in the river, while growth hormone (GH) levels showed no significant change. Decrease in PRL gene transcription was also observed 24h after direct transfer from FW to SW, whereas there was no significant influence of water temperature. On the other hand, there was no significant change in GH mRNA levels in relation to SW transfer or environmental temperature. In a raceway with a vertical salinity gradient, PRL mRNA levels of ayu larvae showed a significant reduction during spontaneous migration from FW to SW, which mimicked the results from the field observation and the transfer experiment, and then a gradual increase during the course of development. Whole body water and sodium contents of larvae in a salinity gradient were stable during migration to SW. Results in this study indicated the importance of regulation of PRL gene expression in the downstream migration and acclimation to SW during the early development of ayu.

Mitochondrial DNA population structure of the white-spotted Charr (Salvelinus leucomaenis) in the Lake Biwa water system.

A phylogeographic analysis of mitochondrial DNA sequences was performed in order to elucidate the origin, dispersal process, and genetic structure of white-spotted charr in the Lake Biwa water system. Two haplotypes were most common in the Lake Biwa water system, and were also common in the adjacent inlet rivers of the Sea of Japan. These results suggest that in the glacial periods of the Pleistocene, white-spotted charr dispersed into the northern inlet rivers of Lake Biwa from adjacent inlet rivers of the Sea of Japan by watershed exchanges, colonizing the whole of the Lake Biwa water system. Mitochondrial DNA diversity contrasted sharply between the western and eastern parts of the system, suggesting that the populations in the western part might be more reduced than those in the eastern part in relation to the smaller habitat size. The high overall FST estimate (0.50), together with pairwise comparisons of FST, indicated significant genetic divergence between populations due to isolation and small population size. Hierarchical analysis (AMOVA) also showed that genetic variation was more pronounced among regions (28.39%) and among populations within regions (47.24%) than within populations (24.37%). This suggests that each population in and around the Lake Biwa water system should be treated as a significant unit for conservation and management.

Decomposed pairwise regression analysis of genetic and geographic distances reveals a metapopulation structure of stream-dwelling Dolly Varden charr.

Isolation by distance is usually tested by the correlation of genetic and geographic distances separating all pairwise populations' combinations. However, this method can be significantly biased by only a few highly diverged populations and lose the information of individual population. To detect outlier populations and investigate the relative strengths of gene flow and genetic drift for each population, we propose a decomposed pairwise regression analysis. This analysis was applied to the well-described one-dimensional stepping-stone system of stream-dwelling Dolly Varden charr (Salvelinus malma). When genetic and geographic distances were plotted for all pairs of 17 tributary populations, the correlation was significant but weak (r(2) = 0.184). Seven outlier populations were determined based on the systematic bias of the regression residuals, followed by Akaike's information criteria. The best model, 10 populations included, showed a strong pattern of isolation by distance (r(2) = 0.758), suggesting equilibrium between gene flow and genetic drift in these populations. Each outlier population was also analysed by plotting pairwise genetic and geographic distances against the 10 nonoutlier populations, and categorized into one of the three patterns: strong genetic drift, genetic drift with a limited gene flow and a high level of gene flow. These classifications were generally consistent with a priori predictions for each population (physical barrier, population size, anthropogenic impacts). Combined the genetic analysis with field observations, Dolly Varden in this river appeared to form a mainland-island or source-sink metapopulation structure. The generality of the method will merit many types of spatial genetic analyses.

Intraguild indirect effects through trophic cascades between stream-dwelling fishes.

1. To examine the strength and role of indirect effects through trophic cascades by omnivorous fish on algal biomass in streams, we introduced one of four fish species (ayu Plecoglossus altivelis altivelis, pike gudgeon Pseudogobio esocinus esocinus, Japanese dace Tribolodon hakonensis and pale chub Zacco platypus) in experimental pools. We also investigated the indirect effects of gudgeon, dace and chub on the growth of ayu. 2. We chose the four fish species across a continuum of omnivory. Ayu fed mainly on benthic algae, and gudgeon predominantly on invertebrates. Dace and chub fed on both algae and invertebrates, but dace preyed on invertebrates more than chub. 3. The presence of gudgeon, dace and chub reduced the number of algal-feeding invertebrates and increased the algal biomass through trophic cascades. Consequently, ayu growth rate over the experimental period in pools with one of the three fish species was 25.9-44.1 times greater than the growth rate in pools with only ayu. 4. The positive indirect effect on ayu growth was large for gudgeon and dace and small for chub, whereas the addition of ayu reduced ayu growth considerably due to intraspecific competition. 5. The relative intensity of indirect effects on ayu growth through trophic cascades was predictable from the food overlap between ayu and the other fishes. However, the similar strength of indirect effects by gudgeon and dace that fed differently on algae and invertebrates suggests that feeding behaviour, prey preference and trait-mediated indirect interactions were also important in the prediction.

Phylogeography of white-spotted Charr (Salvelinus leucomaenis) inferred from mitochondrial DNA sequences.

The white-spotted charr (Salvelinus leucomaenis) is a coldwater-adapted fish distributed in far-eastern Asia. To assess phylogeographic patterns of this species over most of its range in the Japanese archipelago and Sakhalin Island, Russia, we examined nucleotide sequences of the mitochondrial DNA (mtDNA) cytochrome b region (557 bp) in 141 individuals from 50 populations. A total of 33 (5.5%) nucleotide positions were polymorphic and defined 29 haplotypes. Phylogenetic analysis assigned the observed haplotypes to four main clades, which were characterized by the idiosyncrasies and discontinuity of geographic distributions. The nested clade analyses revealed that the geographical distribution patterns of some haplotypes and clades were explained by historical event such as past fragmentation. Although substantial genetic differentiation was found among the four main clades, their geographic distributions overlapped extensively in several regions. Since white-spotted charr can potentially use both freshwater and marine environments, coexistence among different lineages can be attributed to secondary contact through range expansion by migratory individuals during multiple glacial periods after interglacial isolation. Finally, our data demonstrate that the current subspecies designation does not reflect the phylogeography of this species based on mtDNA analysis. Hierarchical analysis (AMOVA) also showed that genetic variation was far more pronounced within subspecies than among subspecies (i.e., among discrete regions). These results suggest that each population, rather than each subspecies, must be treated as an evolutionarily significant unit.