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Focuses on a study on the control of the activities of biological communities over the seepage flow chemistry and the rare earth element (REE) distribution of white clam in the Off Hatsushima cold seepage at Sagami Bay, Japan. Effect of biological and biogeochemical processes on oceanic chemistry; Analytical method and sampling; Results and discussion; Summary.

Despite recent advances in the knowledge of interindividual taste differences, the underlying genetic backgrounds have remained to be fully elucidated. Much of the taste variation among different mammalian species can be explained by pseudogenization of taste receptors. Here I investigated whether the most recent disruptions of taste receptor genes segregate with their intact forms in modern humans by analyzing 14 ethnically diverse populations. The results revealed an unprecedented prevalence of 25 segregating loss-of-function (LoF) taste receptor variants, identifying one of the most pronounced cases of functional population diversity in the human genome. LoF variant frequency in taste receptors (2.10%) was considerably higher than the overall LoF frequency in human genome (0.16%). In particular, molecular evolutionary rates of candidate sour (14.7%) and bitter (1.8%) receptors were far higher in humans than those of sweet (0.02%), salty (0.05%), and umami (0.17%) receptors compared with other carnivorous mammals, although not all of the taste receptors were identified. Many LoF variants are population-specific, some of which arose even after population differentiation, not before divergence of the modern and archaic human. I conclude that modern humans might have been losing some sour and bitter receptor genes because of high-frequency LoF variants. [ABSTRACT FROM AUTHOR]

This study introduces a new imaging, spatial transcriptomics (ST), and single-cell RNA-sequencing integration pipeline to characterize neoplastic cell state transitions during tumorigenesis. We applied a semi-supervised analysis pipeline to examine premalignant pancreatic intraepithelial neoplasias (PanINs) that can develop into pancreatic ductal adenocarcinoma (PDAC). Their strict diagnosis on formalin-fixed and paraffin-embedded (FFPE) samples limited the single-cell characterization of human PanINs within their microenvironment. We leverage whole transcriptome FFPE ST to enable the study of a rare cohort of matched low-grade (LG) and high-grade (HG) PanIN lesions to track progression and map cellular phenotypes relative to single-cell PDAC datasets. We demonstrate that cancer-associated fibroblasts (CAFs), including antigen-presenting CAFs, are located close to PanINs. We further observed a transition from CAF-related inflammatory signaling to cellular proliferation during PanIN progression. We validate these findings with single-cell high-dimensional imaging proteomics and transcriptomics technologies. Altogether, our semi-supervised learning framework for spatial multi-omics has broad applicability across cancer types to decipher the spatiotemporal dynamics of carcinogenesis., Competing Interests: Declaration of interests E.M.J. reports other support from Abmeta; personal fees from Genocea; personal fees from Achilles; personal fees from DragonFly; personal fees from Candel Therapeutics; other support from the Parker Institute; grants and other support from Lustgarten; personal fees from Carta; grants and other support from Genentech; grants and other support from AstraZeneca; personal fees from NextCure; and grants and other support from Break Through Cancer outside of the submitted work. E.J.F. is on the Scientific Advisory Board of Viosera Therapeutics/Resistance Bio and is a consultant to Mestag Therapeutics. W.J.H. reports patent royalties from Rodeo/Amgen and speaking/travel honoraria from Exelixis and Standard BioTools., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Although prevalent in 50%-90% of pancreatic ductal adenocarcinomas, the clinical relevance of "cancerization of ducts" (COD) remains unknown., Methods: Pathologists retrospectively reviewed slides classifying prevalence of COD. Histopathological parameters, location of first recurrence, recurrence-free survival (RFS), and overall survival (OS) were collected from the institutional pancreatectomy registry., Results: Among 311 pancreatic ductal adenocarcinomas, COD was present in 216 (69.5%) and more prevalent in the cohort that underwent upfront surgery (75.3% vs 63.1%, P = 0.019). Furthermore, COD was associated with female gender (P = 0.040), advanced T stage (P = 0.007), perineural invasion (P = 0.014), lymphovascular invasion (P = 0.025), and R1 margin (P = 0.009), but not N stage (P = 0.401) or tumor differentiation (P = 0.717). In multivariable regression, COD was associated with less liver recurrence (odds ratio, 0.44; P < 0.005). This association was driven by the cohort of patients who had received preoperative treatment (odds ratio, 0.18; P < 0.001). COD was not predictive for RFS or OS., Conclusions: Cancerization of ducts was not associated with RFS or OS. Currently underrecognized, standardized implementation into histopathological reports may have merit, and further mechanistic scientific experiments need to illuminate its clinical and biologic impact., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Contrast enhanced pulmonary vein magnetic resonance angiography (PV CE-MRA) has value in atrial ablation pre-procedural planning. We aimed to provide high fidelity, ECG gated PV CE-MRA accelerated by variable density Cartesian sampling (VD-CASPR) with image navigator (iNAV) respiratory motion correction acquired in under 4 min. We describe its use in part during the global iodinated contrast shortage. VD-CASPR/iNAV framework was applied to ECG-gated inversion and saturation recovery gradient recalled echo PV CE-MRA in 65 patients (66 exams) using .15 mmol/kg Gadobutrol. Image quality was assessed by three physicians, and anatomical segmentation quality by two technologists. Left atrial SNR and left atrial/myocardial CNR were measured. 12 patients had CTA within 6 months of MRA. Two readers assessed PV ostial measurements versus CTA for intermodality/interobserver agreement. Inter-rater/intermodality reliability, reproducibility of ostial measurements, SNR/CNR, image, and anatomical segmentation quality was compared. The mean acquisition time was 3.58 ± 0.60 min. Of 35 PV pre-ablation datasets (34 patients), mean anatomical segmentation quality score was 3.66 ± 0.54 and 3.63 ± 0.55 as rated by technologists 1 and 2, respectively (p = 0.7113). Good/excellent anatomical segmentation quality (grade 3/4) was seen in 97% of exams. Each rated one exam as moderate quality (grade 2). 95% received a majority image quality score of good/excellent by three physicians. Ostial PV measurements correlated moderate to excellently with CTA (ICCs range 0.52-0.86). No difference in SNR was observed between IR and SR. High quality PV CE-MRA is possible in under 4 min using iNAV bolus timing/motion correction and VD-CASPR., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Clinical application of cardiac magnetic resonance (CMR) is expanding but CMR assessment of LV diastolic function is still being validated. The purpose of this study was to validate assessments of left ventricular (LV) diastolic dysfunction (DD) using CMR by comparing with transthoracic echocardiography (TTE) performed on the same day. Patients with suspected or diagnosed cardiomyopathy (n = 63) and healthy volunteers (n = 24) were prospectively recruited and included in the study. CMR diastolic parameters were measured on cine images and velocity-encoded phase contrast cine images and compared with corresponding parameters measured on TTE. A contextual correlation feature tracking method was developed to calculate the mitral annular velocity curve. LV DD was classified by CMR and TTE following 2016 guidelines. Overall DD classification was 78.1% concordant between CMR and TTE (p < 0.0001). The trans-mitral inflow parameters correlated well between the two modalities (E, r = 0.78; A, r = 0.90; E/A, r = 0.82; all p < 0.0001) while the remaining diastolic parameters showed moderate correlation (e', r = 0.64; E/e', r = 0.54; left atrial volume index (LAVi), r = 0.61; all p < 0.0001). Classification of LV diastolic function by CMR showed good concordance with standardized grades established for TTE. CMR-based LV diastolic function may be integrated in routine clinical practice.Name of the registry: Technical Development of Cardiovascular Magnetic Resonance Imaging. Trial registration number: NCT00027170. Date of registration: November 26, 2001. URL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT00027170., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Understanding microplastic (MP) behavior in oceans is crucial for reducing marine plastic pollution. However, the complex process underlying MP transportation to the deep seafloor remains unknown despite the deep sea being considered its major sink. We focused on MP distribution in Sagami Bay (adjacent to highly populated areas of Japan), the plate triple junction connected through the Sagami Trough, and the abyssal plain immediately below the Kuroshio Extension. We observed the highest number of MPs in the abyssal stations, more than previously reported. The polymer types and aspect ratio of MPs in the abyssal stations significantly differed from those in the bathyal/hadal stations. The study suggests that MPs accumulated in the open ocean surface layer sink to the abyssal plains immediately below it, while MPs from land sources accumulate in the bathyal depth and are transported to the hadal depth near the coast through turbidity currents along the submarine canyon., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Global activities involving the collection of marine biodiversity information have provided a large amount of biological observation records that cover various spatiotemporal areas. To predict biological responses or distribution changes in response to environmental changes by using these observation records, it is essential to analyze not only the current marine physicochemical environmental conditions but also the past conditions when the organisms were observed. We developed a new function to estimate the past marine environmental conditions for the observation records in our marine biodiversity database (Biological Information System for Marine Life: BISMaL) and examine whether the database can reliably estimate thermal habitats for both benthic and planktonic marine organisms. For the benthic squat lobster Shinkaia crosnieri, the estimated and observed in situ temperatures were similar to each other. For the planktonic chaetognaths Krohnitta pacifica and K. subtilis, the estimated temperatures showed clear seasonal changes specific to their distribution areas. These results indicated that BISMaL can reliably provide past habitat conditions regardless of planktonic or benthic lifestyles. BISMaL, which provides both biological observations and estimated past environmental conditions through web services, could lower the barrier to data access and use and make data-driven science available not only for data scientists but also for various marine scientists, such as taxonomists, ecologists and field scientists. Database URL:  https://www.godac.jamstec.go.jp/bismal/e/., (© The Author(s) 2023. Published by Oxford University Press.)

Phagocytosis is one of the methods used to acquire symbiotic bacteria to establish intracellular symbiosis. A deep-sea mussel, Bathymodiolus japonicus , acquires its symbiont from the environment by phagocytosis of gill epithelial cells and receives nutrients from them. However, the manner by which mussels retain the symbiont without phagosome digestion remains unknown. Here, we show that controlling the mechanistic target of rapamycin complex 1 (mTORC1) in mussels leads to retaining symbionts in gill cells. The symbiont is essential for the host mussel nutrition; however, depleting the symbiont's energy source triggers the phagosome digestion of symbionts. Meanwhile, the inhibition of mTORC1 by rapamycin prevented the digestion of the resident symbionts and of the engulfed exogenous dead symbionts in gill cells. This indicates that mTORC1 promotes phagosome digestion of symbionts under reduced nutrient supply from the symbiont. The regulation mechanism of phagosome digestion by mTORC1 through nutrient signaling with symbionts is key for maintaining animal-microbe intracellular nutritional symbiosis.

Understanding the timing and spectrum of genetic alterations that contribute to the development of pancreatic cancer is essential for effective interventions and treatments. The aim of this study was to characterize somatic ATM alterations in noninvasive pancreatic precursor lesions and invasive pancreatic adenocarcinomas from patients with and without pathogenic germline ATM variants. DNA was isolated and sequenced from the invasive pancreatic ductal adenocarcinomas and precursor lesions of patients with a pathogenic germline ATM variant. Tumor and precursor lesions from these patients as well as colloid carcinoma from patients without a germline ATM variant were immunolabeled to assess ATM expression. Among patients with a pathogenic germline ATM variant, somatic ATM alterations, either mutations and/or loss of protein expression, were identified in 75.0% of invasive pancreatic adenocarcinomas but only 7.1% of pancreatic precursor lesions. Loss of ATM expression was also detected in 31.0% of colloid carcinomas from patients unselected for germline ATM status, significantly higher than in pancreatic precursor lesions [pancreatic intraepithelial neoplasms (p = 0.0013); intraductal papillary mucinous neoplasms, p = 0.0040] and pancreatic ductal adenocarcinoma (p = 0.0076) unselected for germline ATM status. These data are consistent with the second hit to ATM being a late event in pancreatic tumorigenesis. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)

Purpose of developing the guidelines: Newborn screening (NBS) for congenital hypothyroidism (CH) was started in 1979 in Japan, and early diagnosis and treatment improved the intelligence prognosis of CH patients. The incidence of CH was once about one in 5,000-8,000 births, but has been increased with diagnosis of subclinical CH. The disease requires continuous treatment and specialized medical facilities should conduct differential diagnosis and treatment in patients who are positive by NBS to avoid unnecessary treatment. The Guidelines for Mass Screening of Congenital Hypothyroidism (1998 version) were developed by the Mass Screening Committee of the Japanese Society for Pediatric Endocrinology in 1998. Subsequently, the guidelines were revised in 2014. Here, we have added minor revisions to the 2014 version to include the most recent findings. Target disease/conditions: Primary congenital hypothyroidism . Users of the Guidelines: Physician specialists in pediatric endocrinology, pediatric specialists, physicians referring pediatric practitioners, general physicians, laboratory technicians in charge of mass screening, and patients., Competing Interests: None of the committee members have a conflict of interest regarding development of the guidelines, based on the criteria for conflict of interest of the Japan Pediatric Society and in accordance with the rules of the Japanese Society for Pediatric Endocrinology., (2023©The Japanese Society for Pediatric Endocrinology.)

Background: Restrictive cardiomyopathy (RCM) places patients at high risk for adverse events. In this study, we aim to evaluate the association between left atrial function and time to adverse events such as all-cause mortality and cardiovascular hospitalizations related to RCM. Material and Methods: In this single-center study, ninety-eight patients with a clinical diagnosis of RCM were recruited from our registry: 30 women (31%); age (mean ± standard deviation) 61 ± 13 years. These patients underwent cardiac magnetic resonance (CMR) imaging from May 2007 to September 2015. Left atrial (LA) function (reservoir, contractile, and conduit strain), LA diameter and area, and left ventricular function (global longitudinal strain, ejection fraction), and volume were quantified, and the presence of late gadolinium enhancement was visually assessed. The cutoff value of the LA reservoir strain was selected based on tertile. An adjusted Cox proportional regression analysis was used to assess time to adverse outcomes with a median follow up of 49 months. Results: In our cohort, all-cause mortality was 36% (35/98). Composite events (all-cause mortality and cardiovascular hospitalizations) occurred in 56% of patients (55/98). All-cause mortality and composite events were significantly associated with a decreased LA reservoir strain (adjusted hazard ratio (aHR) = 0.957, p = 0.002 and aHR = 0.969, p = 0.008) using a stepwise elimination of imaging variables, demographics, and comorbidities. All-cause mortality and composite events were six and almost four times higher, respectively, in patients with the LA reservoir strain <15% (aHR = 5.971, p = 0.005, and HR = 4.252, p = 0.001) compared to patients with the LA reservoir strain >34%. Survival was significantly reduced in patients with an LA reservoir strain <15% (p = 0.008). Conclusions: The decreased LA reservoir strain is independently associated with time to adverse events in patients with RCM.

The Society for Cardiovascular Magnetic Resonance (SCMR) is an international society focused on the research, education, and clinical application of cardiovascular magnetic resonance (CMR). "Cases of SCMR" is a case series hosted on the SCMR website ( https://www.scmr.org ) that demonstrates the utility and importance of CMR in the clinical diagnosis and management of cardiovascular disease. The COVID-19 Case Collection highlights the impact of coronavirus disease 2019 (COVID-19) on the heart as demonstrated on CMR. Each case in series consists of the clinical presentation and the role of CMR in diagnosis and guiding clinical management. The cases are all instructive and helpful in the approach to patient management. We present a digital archive of the 2021 Cases of SCMR and the 2020 and 2021 COVID-19 Case Collection series of nine cases as a means of further enhancing the education of those interested in CMR and as a means of more readily identifying these cases using a PubMed or similar literature search engine., (© 2022. The Author(s).)

Oncogenic mutations in the small GTPase RAS contribute to ~30% of human cancers. In a Drosophila genetic screen, we identified novel and evolutionary conserved cancer genes that affect Ras-driven tumorigenesis and metastasis in Drosophila including confirmation of the tetraspanin Tsp29Fb. However, it was not known whether the mammalian Tsp29Fb orthologue, TSPAN6, has any role in RAS-driven human epithelial tumors. Here we show that TSPAN6 suppressed tumor growth and metastatic dissemination of human RAS activating mutant pancreatic cancer xenografts. Whole-body knockout as well as tumor cell autonomous inactivation using floxed alleles of Tspan6 in mice enhanced Kras G12D -driven lung tumor initiation and malignant progression. Mechanistically, TSPAN6 binds to the EGFR and blocks EGFR-induced RAS activation. Moreover, we show that inactivation of TSPAN6 induces an epithelial-to-mesenchymal transition and inhibits cell migration in vitro and in vivo. Finally, low TSPAN6 expression correlates with poor prognosis of patients with lung and pancreatic cancers with mesenchymal morphology. Our results uncover TSPAN6 as a novel tumor suppressor receptor that controls epithelial cell identify and restrains RAS-driven epithelial cancer., (© 2022. Crown.)

Few studies have investigated the prevalence of polybrominated diphenyl ethers (PBDEs) in deep-sea sharks. In this study, the levels and profiles of PBDEs were determined in liver samples of eight different species of deep-sea sharks collected in Suruga Bay, Japan. Widespread contamination of PBDEs in the deep-sea environment was reconfirmed in this study as these persistent organic pollutants (POPs) were detected in all specimens analyzed. Mean ΣPBDE levels in the deep-sea sharks ranged from 7 to 517 ng/g of lipid weight. The distribution patterns of BDE homologues were similar in all species where tetra-BDEs provided the dominant contribution to total PBDEs (46%). PBDEs levels were similar to, or higher than, those seen in other deep-sea sharks from different regions. The levels of PBDEs were likely to reflect their feeding preferences as higher PBDE levels were seen in species with higher trophic positions., (Copyright © 2022. Published by Elsevier Ltd.)

Autosomal dominant polycystic kidney disease (ADPKD) has been associated with cardiac abnormalities including mitral valve prolapse and aneurysmal dilatation of the aortic root. Herein, we investigated the potential association of pericardial effusion with ADPKD. Subjects with ADPKD ( n = 117) and control subjects without ADPKD matched for age, gender and renal function ( n = 117) undergoing MRI including ECG-gated cine MRI of the aorta and heart were evaluated for pericardial effusion independently by three observers measuring the maximum pericardial effusion thickness in diastole using electronic calipers. Pericardial effusion thickness was larger in ADPKD subjects compared to matched controls (Mann-Whitney p = 0.001) with pericardial effusion thickness >5 mm observed in 24 of 117 (21%) ADPKD subjects compared to 4 of 117 (3%) controls ( p = 0.00006). Pericardial effusion thickness in ADPKD was associated with female gender patients (1.2 mm greater than in males, p = 0.03) and pleural effusion thickness ( p < 0.001) in multivariate analyses. No subjects exhibited symptoms related to pericardial effusion or required pericardiocentesis. In conclusion, pericardial effusion appears to be more prevalent in ADPKD compared to controls. Although in this retrospective cross-sectional study we did not identify clinical significance, future investigations of pericardial effusion in ADPKD subjects may help to more fully understand its role in this disease.

Background: Although intracardiac injection or intracoronary delivery of mesenchymal stem cells (MSCs) has been reported, there have been few studies on the intravenous injection of MSCs, particularly in Japan. Methods and Results: Five patients with left ventricular ejection fraction (LVEF) ≤45% received 1.0×10 8 MSCs intravenously. The procedure did not induce significant changes in vital signs. One patient had an elevated body temperature after 1 day, but recovered spontaneously. Laboratory tests remained normal for 1 month after cell delivery. Computed tomography was performed after 1-2 years, and there was no evidence of malignancy. Conclusions: In this pilot study of patients with reduced LVEF, intravenous MSC delivery had no adverse effects., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021, THE JAPANESE CIRCULATION SOCIETY.)

Epigenetic alterations are increasingly recognized as important contributors to the development and progression of pancreatic ductal adenocarcinoma. 5-hydroxymethylcytosine (5hmC) is an epigenetic DNA mark generated through the ten-eleven translocation (TET) enzyme-mediated pathway and is closely linked to gene activation. However, the timing of alterations in epigenetic regulation in the progression of pancreatic neoplasia is not well understood. In this study, we hypothesized that aberrant expression of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) and subsequent global 5hmC alteration are linked to early tumorigenesis in the pancreas. Therefore, we evaluated alterations of 5hmC and TET1 levels using immunohistochemistry in pancreatic neoplasms (n = 380) and normal ducts (n = 118). The study cohort included representation of the full spectrum of precancerous lesions from low- and high-grade pancreatic intraepithelial neoplasia (n = 95), intraductal papillary mucinous neoplasms (all subtypes, n = 129), intraductal oncocytic papillary neoplasms (n = 12), and mucinous cystic neoplasms (n = 144). 5hmC and TET1 were significantly downregulated in all types of precancerous lesion and associated invasive pancreatic ductal adenocarcinomas compared with normal ductal epithelium (all p < 0.001), and expression of 5hmC positively correlated with expression of TET1. Importantly, downregulation of both 5hmC and TET1 was observed in most low-grade precancerous lesions. There were no clear associations between 5hmC levels and clinicopathological factors, thereby suggesting a common epigenetic abnormality across precancerous lesions. We conclude that downregulation of 5hmC and TET1 is an early event in pancreatic tumorigenesis. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (© 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Hyperspectral data in the near infrared range were examined for nine common types of plastic particles of 1 mm and 100-500 μm sizes on dry and wet glass fiber filters. Weaker peak intensities were detected for small particles compared to large particles, and the reflectances were weaker at longer wavelengths when the particles were measured on a wet filter. These phenomena are explainable due to the effect of the correlation between the particle size and the absorption of infrared light by water. We constructed robust classification models that are capable of classifying polymer types, regardless of particle size or filter conditions (wet vs. dry), based on hyperspectral data for small particles measured on wet filters. Using the models, we also successfully classified the polymer type of polystyrene beads covered with microalgae, which simulates the natural conditions of microplastics in the ocean. This study suggests that hyperspectral imaging techniques with appropriate classification models allow the identification of microplastics without the time- and labor-consuming procedures of drying samples and removing biofilms, thus enabling more rapid analyses.

Background: The prevalence of abdominal aortic aneurysm is high in chronic obstructive pulmonary disease (COPD) population. Emphysema involves proteolytic destruction of elastic fibers. Therefore, emphysema may also contribute to thoracic aorta dilatation. This study assessed aorta dilation in smokers stratified by presence of COPD, emphysema and airway thickening., Methods: Aorta diameters were measured on 3D magnetic resonance angiography in smokers recruited from the Multi-Ethnic Study of Atherosclerosis (MESA), the Emphysema and Cancer Action Project (EMCAP), and the local community. COPD was defined by standard spirometric criteria; emphysema was measured quantitatively on computed tomography and bronchitis was determined from medical history., Results: Participants (n = 315, age 58-79) included 150 with COPD and 165 without COPD, of whom 56% and 19%, respectively, had emphysema. Subjects in the most severe quartile of emphysematous change showed the largest diameter at all four aorta locations compared to those in the least severe quartiles (all p < 0.001). Comparing subjects with and without COPD, aorta diameters were larger in participants with severe COPD in ascending and arch (both p < 0.001), and abdominal aorta (p = 0.001). Chronic bronchitis and bronchial wall thickness did not correlate with aorta diameter. In subjects with emphysema, subjects with coexistence of COPD showed larger aorta than those without COPD in ascending (p = 0.003), arch (p = 0.002), and abdominal aorta (p = 0.04)., Conclusions: This study showed larger aorta diameter in subjects with COPD and severe emphysema compared to COPD related to chronic bronchitis or bronchial wall thickening., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The accuracy of speckle-tracking echocardiography (STE) depends on temporal resolution. The goal of this study was to demonstrate the feasibility of relatively high frame rate (rHi-FR) (~200 fps) for STE. Methods: In this prospective study, echocardiographic images were acquired using clinical scanners on patients with normal left ventricular systolic function using rHi-FR and conventional frame rate (Reg-FR) (~50 FPS). GLS values were evaluated on apical 4-, 2- and 3-chamber images acquired in both rHi-FR and Reg-FR. Inter-observer and intra-observer variabilities were assessed in rHi-FR and Reg-FR. Results: There were 143 echocardiograms evaluated in this study. The frame rate of rHi-FR was 190 ± 25 and Reg-FR was 50 ± 3, and the heart rate was 71 ± 13. Absolute strain values measured in rHi-FR were significantly higher than those measured in Reg-FR (all p < 0.001). Inter-observer and intra-observer correlations were strong in both rHi-FR and Reg-FR. Conclusions: We demonstrated that absolute strain values were significantly higher using rHi-FR when compared with Reg-FR. It is plausible that higher temporal resolution enabled the measurement of myocardial strain at desired time point. Further investigations are necessary to evaluate the value of rHi-FR to assess myocardial strain in the setting of tachycardia.

Aims: The recent emergence of novel, pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a global health emergency. The coronaviral entry requires the spike (S)-protein for attachment to the host cell surface, and employs human angiotensin-converting enzyme 2 (hACE2) for entry and transmembrane protease serine 2 (TMPRSS2) for S-protein priming. Although coronaviruses undergo evolution by mutating themselves, it is also essential to know the host genetic factors. Here, we describe the single nucleotide variations (SNVs) in human ACE2 and TMPRSS2 ., Methods: The genetic variants derived from five population-sequencing projects were classified by variant type, allele frequency (AF), ethnic group and estimated pathogenicity. The SNVs in SARS-CoV-2/hACE2 contact residues were investigated. The genetic variability was normalised using non-linear regression and the total number of SNVs was estimated by the derived formulas., Results: We detected 349 and 551 SNVs in ACE2 and TMPRSS2 , respectively, in a total of 156 513 individuals. The vast majority (>97%) of the SNVs were very rare (AF <0.1%) and population-specific, and were computationally estimated to be more frequently deleterious than the SNVs with high AF. These SNVs were distributed throughout the coding regions; some ACE 2 variants were located in the SARS-CoV-2/hACE2 contact residues, with a hemizygous state occurring in males. Using regression analysis, the total numbers of genetic variations in ACE2 and TMPRSS2 were 1.1×10 3 and 1.5×10 3 , respectively, for a population of one million people., Conclusion: The majority of SNVs in ACE2 and TMPRSS2 are rare, population-specific and deleterious, and a multitude of very rare SNVs may explain different susceptibility to SARS-CoV-2., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

The abyss (3500-6500 m) covers the bulk of the deep ocean floor yet little is known about the extent of plastic debris on the abyssal seafloor. Using video imagery we undertook a quantitative assessment of the debris present on the abyssal seafloor (5700-5800 m depth) beneath the Kuroshio Extension current system in the Northwest Pacific. This body of water is one of the major transit pathways for the massive amounts of debris that are entering the North Pacific Ocean from Asia. Shallower sites (1400-1500 m depth) were also investigated for comparison. The dominant type of debris was single-use plastics - mainly bags and food packaging. The density of the plastic debris (mean 4561 items/km 2 ) in the abyssal zone was the highest recorded for an abyssal plain suggesting that the deep-sea basin in the Northwest Pacific is a significant reservoir of plastic debris., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Intraductal papillary mucinous neoplasms (IPMNs) are non-invasive precursor lesions that can progress to invasive pancreatic cancer and are classified as low-grade or high-grade based on the morphology of the neoplastic epithelium. We aimed to compare genetic alterations in low-grade and high-grade regions of the same IPMN in order to identify molecular alterations underlying neoplastic progression., Design: We performed multiregion whole exome sequencing on tissue samples from 17 IPMNs with both low-grade and high-grade dysplasia (76 IPMN regions, including 49 from low-grade dysplasia and 27 from high-grade dysplasia). We reconstructed the phylogeny for each case, and we assessed mutations in a novel driver gene in an independent cohort of 63 IPMN cyst fluid samples., Results: Our multiregion whole exome sequencing identified KLF4 , a previously unreported genetic driver of IPMN tumorigenesis, with hotspot mutations in one of two codons identified in >50% of the analyzed IPMNs. Mutations in KLF4 were significantly more prevalent in low-grade regions in our sequenced cases. Phylogenetic analyses of whole exome sequencing data demonstrated diverse patterns of IPMN initiation and progression. Hotspot mutations in KLF4 were also identified in an independent cohort of IPMN cyst fluid samples, again with a significantly higher prevalence in low-grade IPMNs., Conclusion: Hotspot mutations in KLF4 occur at high prevalence in IPMNs. Unique among pancreatic driver genes, KLF4 mutations are enriched in low-grade IPMNs. These data highlight distinct molecular features of low-grade and high-grade dysplasia and suggest diverse pathways to high-grade dysplasia via the IPMN pathway., Competing Interests: Competing interests: LDW receives research support from Applied Materials. VBG is an employee of Personal Genome Diagnostics. The other authors declare no conflict of interest., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Symbiotic associations with beneficial microorganisms endow a variety of host animals with adaptability to the environment. Stable transmission of symbionts across host generations is a key event in the maintenance of symbiotic associations through evolutionary time. However, our understanding of the mechanisms of symbiont transmission remains fragmentary. The deep-sea clam Phreagena okutanii harbors chemoautotrophic intracellular symbiotic bacteria in gill epithelial cells, and depends on these symbionts for nutrition. In this study, we focused on the association of these maternally transmitted symbionts with ovarian germ cells in juvenile female clams. First, we established a sex identification method for small P. okutanii individuals, and morphologically classified female germ cells observed in the ovary. Then, we investigated the association of the endosymbiotic bacteria with germ cells. We found that the symbionts were localized on the outer surface of the cell membrane of primary oocytes and not within the cluster of oogonia. Based on our findings, we discuss the processes and mechanisms of symbiont vertical transmission in P. okutanii .

The gene mutation profiles of gastric neuroendocrine neoplasms are incompletely understood. The purpose of this study was to characterize the molecular pathology of poorly differentiated neuroendocrine carcinoma (NEC) and mixed neuroendocrine‒non-neuroendocrine neoplasm (MiNEN) of the stomach. Surgical cases of gastric NEC (n = 7) and MiNEN (n = 6) were examined by clinical review, immunohistochemistry, microsatellite instability (MSI) analysis and whole-exome sequencing. NEC cases consisted of small- (n = 2) and large-cell types (n = 4). All cases of MiNEN were histologically composed of large-cell type NEC and tubular adenocarcinoma. Whole-exome sequencing analysis detected recurrent mutations in TP53 in 8 cases (62%), and they were more frequently observed in MiNEN than in NEC (100% vs. 29%). Frameshift mutations of APC were observed in two cases of MiNEN. One case of large-cell type NEC had a frameshift mutation with loss of heterozygosity in RB1. The other mutated genes (e.g., ARID1 and KRAS) were detected in a single case each. A high level of MSI was confirmed in one case of MiNEN, which harbored mutations in two well-differentiated neuroendocrine tumor (NET)-related genes (MEN1 and ATRX1). In cases of MiNEN, two histological components shared mutations in TP53, APC and ZNF521, whereas alterations in CTNNB1, KMT2C, PTEN and SPEN were observed in neuroendocrine components only. In conclusion, TP53 is a single, frequently mutated gene in gastric NEC and MiNEN, and alterations in other genes are less common, resembling the mutation profiles of gastric adenocarcinomas. Gene mutations frequently observed in well-differentiated NET were uncommon but not entirely exclusive., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aims: To characterise the karyotypic abnormalities and heterogeneities in intravascular lymphoma (IVL)., Methods: G-banded karyotyping was performed on biopsy specimens from a single-centre IVL cohort comprising intravascular large B-cell lymphoma (IVLBCL, n=12) and NK/T-cell lymphoma (IVNKTCL, n=1)., Results: Five IVLBCL cases and one IVNKTCL case (total 46%) were found to have normal karyotypes, and the cytogenetic abnormalities observed in the other seven IVLBCL cases (54%) were investigated further. These seven karyotypes were uniformly complex with an average of 13 aberrations. The seven cases all had abnormalities involving chromosome 6, with 57% involving structural abnormalities at 6q13, and chromosome 8, with 43% involving abnormalities at 8p11.2. In addition, 71% had aberrations at 19q13. On average, 4.4 chromosomal gains and losses were detected per case. Cytogenetic heterogeneities were observed in six cases (86%) and tetraploidy in three cases (43%). There was no significant difference in progression-free survival (p=0.92) and overall survival (p=0.61) between the IVLBCL cases with complex and normal karyotypes., Conclusion: Approximately half of IVLBCL cases had a highly heterogeneous pattern of karyotypes with different clonal numerical and structural chromosome aberrations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Analyses of environmental DNA (eDNA) from macroorganisms in aquatic environments have greatly advanced in recent years. In particular, eDNA metabarcoding of fish using universal PCR primers has been reported in various waters. Although pumped deep-sea water was used for eDNA metabarcoding of deep-sea fish, conventional methods only resulted in small amounts of extracted eDNA and subsequent few or no PCR amplicons. To optimize eDNA metabarcoding of deep-sea fish from pumped deep-sea water, we modified conventional procedures of eDNA extraction and PCR amplification. Here, we propose a modified eDNA extraction method, in which a filter used for eDNA sampling was shredded and incubated in microtubes for efficient lysis of eDNA sources. Total eDNA yield extracted using the modified protocol was approximately six-fold higher than that extracted by the conventional protocol. The PCR enzyme Platinum SuperFi II DNA Polymerase successfully amplified a target region of fish universal primers (MiFish) from trace amounts of eDNA extracted from pumped deep-sea water and suppressed nonspecific amplifications more effectively than the enzyme used in conventional methods. Approximately 93% of the sequence reads acquired by next generation sequencing of these amplicons were derived from fish. The improved procedure presented here provided effective eDNA metabarcoding of deep-sea fish.•A modified eDNA extraction protocol, in which a filter was shredded and incubated in microtubes, increased eDNA yields extracted from pumped deep-sea water over the conventional method.•The PCR enzyme Platinum SuperFi II DNA polymerase improved the amplification efficiency of trace amounts of MiFish objectives in eDNA extracted from pumped deep-sea water with suppressing nonspecific amplifications.•The use of Platinum SuperFi II DNA polymerase for eDNA metabarcoding using MiFish primers resulted in the acquisition of abundant sequence reads of deep-sea fish through next generation sequencing., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors. Published by Elsevier B.V.)

Plastic pollution has become one of the most emergent issues threating aquatic and terrestrial ecosystems. However, it is still challenging to rapidly detect small microplastics. Here, we present a method to rapidly detect microplastics using hyperspectral imaging in which we optimized a commercially available hyperspectral imaging system (Pika NIR-640, Resonon Inc., USA). The optimizations included: (1) changing the four-lamp assembly to a symmetrical set of converged-light near-infrared lamps that are placed sideways instead of above the sample stage; (2) adopting a macro-photography technique by applying an extension tube between the camera and the lens, and moving the lens of the hyperspectral camera to the imaging target (working distance of ~3 cm); (3) adjusting the exposure and aspect ratio by tuning the frame rate and scan speed of the imaging system. After optimization, the detection resolution of each pixel improved from 250 µm to 14.8 µm. With the optimized system, microplastics down to 100 µm in size were rapidly detected. This result is promising for the application of our new method in the accelerated detection of microplastics and will contribute to a better understanding of the microplastic pollution situation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s). Published by Elsevier B.V.)

(1) Background: This study sought to explore how the novel coronavirus (COVID-19) pandemic affected the echocardiography (TTE) laboratory operations at a high volume medical center in New York City. Changes in cardiac imaging study volume, turn-around time, and abnormal findings were analyzed and compared to a pre-pandemic period. (2) Methods: Volume of all cardiac imaging studies and TTE reports between 11 March 2020 to 5 May 2020 and the same calendar period in 2019 were retrospectively identified and compared. (3) Results: During the pandemic, our center experienced a 46.72% reduction in TTEs, 82.47% reduction in transesophageal echocardiograms, 83.16% reduction in stress echo, 70.32% reduction in nuclear tests, 46.25% reduction in calcium score, 73.91% reduction in coronary computed tomography angiography, and 87.23% reduction in cardiac magnetic resonance imaging. TTE findings were overall similar between 2020 and 2019 (all p ≥ 0.05), except for a significantly higher right ventricular systolic pressure in 2020 (39.8 ± 14.2 vs. 34.6 ± 11.2 mmHg, p = 0.012). (4) Conclusions: Despite encountering an influx of critically ill patients, our hospital center experienced a reduction in the number of cardiac imaging studies, which likely represents a change in both patient mindset and physician management approach.

Intraductal papillary mucinous neoplasms (IPMNs) are commonly identified non-invasive cyst-forming pancreatic neoplasms with the potential to progress into invasive pancreatic adenocarcinoma. There are few in vitro models with which to study the biology of IPMNs and their progression to invasive carcinoma. Therefore, we generated a living biobank of organoids from seven normal pancreatic ducts and ten IPMNs. We characterized eight IPMN organoid samples using whole genome sequencing and characterized five IPMN organoids and seven normal pancreatic duct organoids using transcriptome sequencing. We identified an average of 11,344 somatic mutations in the genomes of organoids derived from IPMNs, with one sample harboring 61,537 somatic mutations enriched for T→C transitions and T→A transversions. Recurrent coding somatic mutations were identified in 15 genes, including KRAS, GNAS, RNF43, PHF3, and RBM10. The most frequently mutated genes were KRAS, GNAS, and RNF43, with somatic mutations identified in six (75%), four (50%), and three (37.5%) IPMN organoid samples, respectively. On average, we identified 36 structural variants in IPMN derived organoids, and none had an unstable phenotype (> 200 structural variants). Transcriptome sequencing identified 28 genes differentially expressed between normal pancreatic duct organoid and IPMN organoid samples. The most significantly upregulated and downregulated genes were CLDN18 and FOXA1. Immunohistochemical analysis of FOXA1 expression in 112 IPMNs, 113 mucinous cystic neoplasms, and 145 pancreatic ductal adenocarcinomas demonstrated statistically significant loss of expression in low-grade IPMNs (p < 0.0016), mucinous cystic neoplasms (p < 0.0001), and pancreatic ductal adenocarcinoma of any histologic grade (p < 0.0001) compared to normal pancreatic ducts. These data indicate that FOXA1 loss of expression occurs early in pancreatic tumorigenesis. Our study highlights the utility of organoid culture to study the genetics and biology of normal pancreatic duct and IPMNs. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (© 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Aims: Intravascular NK/T-cell lymphoma (IVNKTCL) is a rare disease, which is characterised by exclusive growth of large cells within the lumen of small vessels, Epstein-Barr virus infection and somatic mutations in epigenetic regulator genes. Here, we elucidate the transcriptomic complexity of IVNKTCL., Methods: IVNKTCL cases were retrieved from a single-centre cohort of 25 intravascular lymphomas. RNA-seq and whole exome sequencing (WES) were performed to analyse transcriptomic abnormalities and mutations in splicing factors., Results: Approximately 88% of the total reads from the RNA-seq were considered exonic, while the remaining reads (12%) were mapped to intronic or intergenic regions. We detected 28,941 alternative splicing events, some of which would produce abnormal proteins rarely found in normal cells. The detected events also included tumour-specific splicing alterations in oncogenes and tumour suppressors (e.g., HRAS , MDM2 and VEGFA ). WES identified premature termination mutations or copy number losses in a total of 15 splicing regulator genes, including SF3B5 , SRSF12 and TNPO3 ., Conclusions: This study raises the possibility that IVNKTCL may be driven by multiple complex regulatory loops, including non-exonic expression and aberrant splicing, in addition to defects in epigenetic regulation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Organochlorine pesticides (OCPs) are environmental contaminants with potentially adverse effects on neurodevelopment. Previous findings on the association between prenatal exposure to OCPs and the maternal or infant thyroid hormone system are inconsistent. Moreover, the influence of exposure to multiple OCPs and other chemical compounds is not clearly understood. Our study therefore aimed to examine the association between OCP exposure and both maternal and infant thyroid hormone systems. We also explored multiple exposure effects of OCPs and the influence of each compound using weighted quantile sum (WQS) methods. The study population included 514 participants in the Hokkaido study, recruited from 2002 to 2005 at one hospital in Sapporo, Japan. To quantify 29 OCPs, maternal blood samples were analyzed using gas chromatography/mass spectrometry. Blood samples for measuring thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels were obtained from mothers during the early gestational stage (mean 11.4 weeks), and from infants between 7 and 43 days of age. The data of 333 mother child pairs with OCP and thyroid hormone measurements were included in the final analyses. Multivariate regression models showed a negative association between maternal FT4 and levels of o,p'-dichlorodiphenyldichloroethylene (DDE), o,p'-dichlorodiphenyltrichloroethane (DDT), and dieldrin. The WQS analysis showed that o,p'-DDT (48.6%), cis-heptachlorepoxide (22.8%), dieldrin (15.4%) were the primary contributors to the significant multiple exposure effect of OCPs on maternal FT4. For infants, we found a positive association between FT4 and cis-nonachlor and mirex. The most contributory compounds in the multiple exposure effect were trans-nonachlor (27.1%) and cis-nonachlor (13.8%), while several compounds contributed to the WQS via small weights (0.4-9.1%). These results indicate that OCPs, even at very low levels, may influence maternal and child thyroid hormone levels, which could modulate child development., (Copyright © 2020 Elsevier Inc. All rights reserved.)