Elevated arginine vasopressin levels surrogate acute lung injury in acute decompensated heart failure.

Activated arginine vasopressin (AVP) pathway worsens congestion in heart failure (HF), but its potential to relieve pulmonary congestion is also reported. The pathophysiological role and prognostic utility of AVP elevation in acute decompensated HF (ADHF) are poorly understood. We prospectively enrolled 52 hospitalized patients for ADHF to investigate the association between acute lung injury (ALI) in ADHF and AVP levels on admission. ALI was defined as respiratory failure leading to death, or requiring a respirator or a more than 12-h non-invasive intermittent positive pressure ventilation (NIPPV) support. In addition, we investigated the prognostic value of AVP levels on admission for cardiovascular death or recurrence of ADHF after discharge. ALI was documented in 7 patients (13.5%) during a median hospital stay of 14 days. And the patients with ALI demonstrated significantly higher AVP levels than those without (32.5 ± 21.6 vs. 6.4 ± 8.7 pg/ml, p = 0.018). Besides, the patients with ALI demonstrated significantly higher heart rates (HR) and lower E/e' on admission (HR: 127 ± 24 vs. 97 ± 28 bpm; E/e': 10.6 ± 3.7 vs. 17.4 ± 6.2, all p < 0.05, respectively). Of note, significant hemodilution assessed by hemoglobin and hematocrit values were observed in the patients with ALI 48 h after admission. A receiver operating characteristic curve analysis showed that higher than 7.2 pg/ml surrogate ALI in ADHF (AUC: 0.897, p = 0.001, Sensitivity: 85.7%, and Specificity: 77.8%). In contrast, increased AVP levels on admission could not predict cardiovascular events after discharge. Elevated AVP levels on admission are associated with ALI in ADHF but not cardiovascular events after discharge.

Association Between Aortic Stiffness and Exercise Tolerance in Patients at the Risk Stage of Heart Failure.

BACKGROUND: The number of patients with heart failure (HF) has increased, and it is crucial to prevent the development of HF in patients at risk of HF. The present study aimed to risk stratify patients in Stage A and B HF based on associations between exercise-induced changes in aortic stiffness and exercise tolerance.Methods and Results: Patients in Stage A and B HF who performed a cardiopulmonary exercise test were enrolled in the study (n=106; median age 65.0 years [interquartile range 52.8-73.0 years]). Exercise tolerance was examined by the percentage of predicted peak oxygen consumption (%V̇O2peak). The ascending aortic pressure waveform was estimated non-invasively. Aortic stiffness was assessed using the augmentation index (AIx) and reflection magnitude (RM). Multivariable regression analysis showed that AIx measured both before and after exercise was significantly associated with %V̇O2peak (ß=-0.221 [P=0.049] and ß=-0.342 [P=0.003], respectively). When participants were divided into %V̇O2peak subgroups using a cut-off value of 60%, RM decreased immediately after exercise and remained lower 5 min after exercise in the group with preserved exercise tolerance, but recovered to baseline levels 5 min after exercise in the group with reduced exercise tolerance. CONCLUSIONS: Exercise-induced increases in aortic stiffness were associated with exercise tolerance in patients at risk of HF, suggesting that exercise-induced changes in aortic stiffness may be useful to stratify high-risk patients.

Effectiveness of introducing a 20-gauge core biopsy needle with a core trap in EUS-FNA/B for diagnosing pancreatic cancer.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B) is a standard method for pathological diagnosis of pancreatic solid lesions. The EchoTip ProCore 20G® (PC20), a 20-gauge biopsy needle with a forward-bevel core trap, has been available in Japan since 2015. METHODS: We compared the efficacy of the PC20 with that of the EchoTip ProCore 22G® (PC22) and Acquire 22G® (AC22) in EUS-FNA/B for diagnosing pancreatic cancer. This retrospective study included 191 patients with pancreatic cancer who underwent EUS-FNA/B using the PC20, PC22, or AC22 at our facility from April 2013 to October 2019. We investigated the patients' clinical characteristics and the diagnostic accuracy and safety of each needle. RESULTS: A sufficient stroke length of puncture was secured in all patients. The maximum length under EUS was shorter with the AC22 (22.1 ± 2.2 mm) than PC20 (30.6 ± 0.7 mm, p < 0.01) and PC22 (30.3 ± 0.8 mm, p < 0.01). The histological accuracy was 96.4% with the PC20 but only 58.8% with the PC22 (adjusted p (p-adj) < 0.0001) and 75.0% with the AC22 (p-adj = 0.06). The diagnostic accuracy of the combination of histology and cytology was 96.4% with the PC20, while it was 72.1% with the PC22 (p-adj < 0.0001) and 91.7% with the AC22 (p-adj > 0.99). One patient (0.9%) in the PC20 group developed mild pancreatitis, but no adverse events occurred with the other needles. CONCLUSIONS: The PC20 showed better diagnostic capability than the PC22. The diagnostic efficacy was similar between the PC20 and AC22. The high histological accuracy of the PC20 could be advantageous for lesions in which histological assessment is critical.

Left ventricular contractile performance and heart failure in patients with left ventricular ejection fraction more than 40.

Heart failure (HF) with mid-range left ventricular ejection fraction (LVEF) (HFmrEF) is considered a new category of HF and LVEF < 50%, which is the upper threshold of LVEF for HFmrEF, is thought to represent a mild decrease in LV contractile performance. We aimed to consider an LVEF threshold value to be taken as a surrogate for impairment of LV contractile performance, resulting in new-onset HF. We enrolled 398 patients with LVEF ≥ 40% that underwent cardiac catheterization. Using the LV pressure recording with a catheter-tipped micromanometer, we calculated the inertia force of late systolic aortic flow (IFLSAF), which was sensitive to the slight impairment in LV contractile performance. We evaluated the utility of the IFLSAF for predicting future cardiovascular death or hospitalization for HF. We performed a receiver operating characteristic (ROC) curve analysis to determine the best LVEF threshold value for distinguishing whether the LV maintained the IFLSAF. A multivariate Cox proportional-hazards model revealed that the loss of IFLSAF was significantly associated with the future adverse events (HR: 7.798, 95%CI 2.174-27.969, p = 0.002). According to the ROC curve analysis, an LVEF ≥ 58% indicated that the LV could maintain the IFLSAF. We concluded that the loss of IFLSAF, which could reflect even slight impairment in LV contractile performance, was a reliable indicator for new-onset HF in patients with LVEF ≥ 40%. LVEF ≥ 58% could be taken as a surrogate for the IFLSAF maintenance; this threshold could be useful for risk stratification of new-onset HF in patients with preserved LVEF.

The impact of intraday glucose variability on coronary artery spasm in patients with dysglycemia.

Impaired glucose metabolism is associated with an increased risk of cardiovascular complications, and coronary artery spasm is thought to underlie the development of coronary artery disease. Intraday glucose variability (GV) accelerates oxidative stress and inflammatory cytokine release, but its impact on coronary artery spasm remains unclear. This study investigated the relationship between intraday GV and coronary artery spasm. The study included 50 patients with dysglycemia and suspected coronary spastic angina. GV was analyzed by 24-h monitoring of the blood glucose concentration using a flash glucose monitoring system. The mean amplitude of glycemic excursion (MAGE) was calculated as an index of GV. Coronary artery spasm was assessed using the intracoronary acetylcholine provocation test. Coronary spasm was defined as acetylcholine-induced total or subtotal coronary occlusion. Changes in vessel diameter in response to acetylcholine were evaluated with quantitative coronary angiography. Coronary artery spasms were observed in 21 patients (42%). MAGE was significantly higher in patients with spasms compared to those without spasms (127.5 ± 33.5 vs. 91.4 ± 37.6, p < 0.01). Regression analysis showed a positive correlation between MAGE levels and coronary diameter changes induced by acetylcholine (r = 0.47, p < 0.01). In multiple regression analysis, MAGE was independently associated with acetylcholine-induced coronary diameter change (ß = 0.47, p < 0.01). Intraday GV was associated with coronary artery spasm in patients with dysglycemia.

Value of serial echo-guided ramp studies in a patient with suspicion of device thrombosis after left ventricular assist device implantation.

Thrombus formation inside of the pump is a major cause for device malfunction following the left ventricular assist device (LVAD) implantation. We recently established a novel ramp test protocol facilitating continuous bedside echo monitoring to optimize LVAD function and diagnosing device malfunctions. We describe a case of 29-year-old woman undergoing HeartMate II LVAD implantation, in whom serial ramp studies were used to diagnose intra-device thrombus after device implantation. The 1st ramp study at postoperative day (POD) 26 revealed adequate reduction in ventricular size according to the increase in LVAD speed (left ventricular end-diastolic diameter [LVEDD] at minimum and maximum speeds, 68 and 37 mm, respectively). The patient was discharged home and received routine anticoagulation maintenance therapy. However, a 2nd ramp test was performed on POD 56 due to increased lactase dehydrogenase and brain natriuretic peptide levels and showed marked increase in left ventricle (LV) chamber size without adequate response to the LVAD speed changes (LVEDD at minimum and maximum speeds, 88 and 76 mm, respectively). Given the suspicion for partial pump thrombosis, the patient was immediately hospitalized and received intravenous heparin infusion. After the optimization of the intensive anticoagulation therapy, the patient underwent a 3rd ramp study, which showed a remarkable improvement of the adequate response to LVAD speed changes. The patients eventually underwent cardiac transplant successfully, and the partial clot was found inside of the pump. This case demonstrates the usefulness of serial ramp studies in patients who are suspected to have device thrombosis.

Evaluation of renal circulation in heart failure using superb microvascular imaging, a microvascular flow imaging system.

PURPOSE: Renal circulation evaluation is essential in understanding the cardiorenal relationship in heart failure (HF), and there is a growing interest in imaging techniques that visualize renal circulation. This study aimed to assess the effectiveness of superb microvascular imaging (SMI) in evaluating renal circulation in HF patients. METHOD: The study included 71 HF patients undergoing cardiac catheterization. Prior to catheterization, renal ultrasound examinations were performed. A control group of 18 subjects without HF was also included. SMI was used to measure the vascular index (VI), which was calculated as the percentage of blood flow signal area in the region of interest. The intrarenal perfusion index (IRPI) was determined as a fluctuation index of VI, reflecting variations in the number of blood cells moving through renal tissue during the cardiac cycle. RESULTS: Using the upper 95% confidence interval of IRPI (0.6) from the control group, HF patients were classified into two groups. Patients with IRPI > 0.6 showed a more congestive profile. Right atrial pressure and biphasic or monophasic Doppler intrarenal flow pattern were independent determinants of IRPI > 0.6. In addition, IRPI remained a significant predictor of estimated glomerular filtration rate (eGFR). CONCLUSION: The parameter IRPI as variations in SMI signal during the cardiac cycle may be a useful evaluation method for renal perfusion impairment in HF.

Distinctive left ventricular-arterial and right ventricular-pulmonary arterial coupling observed in patients with heart failure and a higher left ventricular ejection fraction range.

AIMS: Higher left ventricular (LV) ejection fraction (EF) is related to unfavourable prognosis in patients with heart failure (HF) with preserved ejection fraction (HFpEF). The cause of this finding needs to be haemodynamically explained. Thus, we investigated this crucial issue from the perspective of LV-arterial (A) and right ventricular (RV)-pulmonary arterial (PA) coupling. METHODS AND RESULTS: Study patients were derived from our prospective cohort study of patients hospitalized due to acute decompensated HF and LVEF > 40%. We divided the 255 patients into three groups: HF with mildly reduced EF (HFmrEF), HFpEF with 50% ≤ LVEF < 60%, and HFpEF with LVEF ≥ 60%. We compared LV end-systolic elastance (Ees), effective arterial elastance (Ea), and Ees/Ea as a representative of LV-A coupling among groups and compared the ratio of tricuspid annular plane excursion to peak pulmonary arterial systolic pressure (TAPSE/PASP) as a representative of RV-PA coupling. All-cause death and readmission due to HF-free survival was worse in the group with a higher LVEF range. Ees/Ea was greater in HFpEF patients with LVEF ≥ 60% (2.12 ± 0.57) than in those with 50% ≤ LVEF < 60% (1.20 ± 0.14) and those with HFmrEF (0.82 ± 0.09) (P < 0.001). PASP was increased in the groups with higher LVEF; however, TAPSE/PASP did not differ among groups (n = 168, P = 0.17). In a multivariate Cox proportional hazard model, TAPSE/PASP but not PASP was significantly related to event-free survival independent of LVEF. CONCLUSION: HFpEF patients with higher LVEF have unfavourable prognosis and distinctive LV-A coupling: Ees/Ea is elevated up to 2.0 or more. Impaired RV-PA coupling also worsens prognosis in such patients. CLINICAL TRIAL REGISTRATION: URL: https://www.umin.ac.jp/ctr/index.htm Unique identifier: UMIN000017725.

A Case of Myocardial Infarction with Non-obstructive Coronary Arteries Complicated by a Ventricular Septal Rupture: The Challenge of Achieving Hemodynamic Stability Using Impella Devices.

The prognosis of myocardial infarction with non-obstructive coronary arteries (MINOCA) is reported to be as worse as myocardial infarction with obstructive coronary arteries. However, its mechanical complications are still poorly understood. A 71-year-old woman developed MINOCA after ascending aortic replacement surgery. During treatment, the patient experienced cardiogenic shock due to a ventricular septal rupture (VSR). The introduction of Impella devices reduced the left-to-right shunt and improved the patient's hemodynamics. Finally, a scheduled surgical repair was performed under stable conditions. In this report, we focused on the pathophysiology of MINOCA-related VSR and discussed the effectiveness of Impella devices as a bridge to surgical repair and circulatory backup during the perioperative period.

Genetic adaptations in the population history of Arabidopsis thaliana.

A population encounters a variety of environmental stresses, so the full source of its resilience can only be captured by collecting all the signatures of adaptation to the selection of the local environment in its population history. Based on the multiomic data of Arabidopsis thaliana, we constructed a database of phenotypic adaptations (p-adaptations) and gene expression (e-adaptations) adaptations in the population. Through the enrichment analysis of the identified adaptations, we inferred a likely scenario of adaptation that is consistent with the biological evidence from experimental work. We analyzed the dynamics of the allele frequencies at the 23,880 QTLs of 174 traits and 8,618 eQTLs of 1,829 genes with respect to the total SNPs in the genomes and identified 650 p-adaptations and 3,925 e-adaptations [false discovery rate (FDR) = 0.05]. The population underwent large-scale p-adaptations and e-adaptations along 4 lineages. Extremely cold winters and short summers prolonged seed dormancy and expanded the root system architecture. Low temperatures prolonged the growing season, and low light intensity required the increased chloroplast activity. The subtropical and humid environment enhanced phytohormone signaling pathways in response to the biotic and abiotic stresses. Exposure to heavy metals selected alleles for lower heavy metal uptake from soil, lower growth rate, lower resistance to bacteria, and higher expression of photosynthetic genes were selected. The p-adaptations are directly interpretable, while the coadapted gene expressions reflect the physiological requirements for the adaptation. The integration of this information characterizes when and where the population has experienced environmental stress and how the population responded at the molecular level.

Unfavourable outcomes in patients with heart failure with higher preserved left ventricular ejection fraction.

AIMS: Newly introduced drugs for heart failure (HF) have been reported to improve the prognosis of HF with preserved ejection fraction (HFpEF) in the lower range of left ventricular ejection fraction (LVEF). We hypothesized that a higher LVEF is related to an unfavourable prognosis in patients with HFpEF. METHODS AND RESULTS: We tested this hypothesis by analysing the data from a prospective multicentre cohort study in 255 patients admitted to the hospital due to decompensated HF (LVEF > 40% at discharge). The primary endpoint of this study was a composite outcome of all-cause death and readmission due to HF, and the secondary endpoint was readmission due to HF. LVEF and the mitral E/e' ratio were measured using echocardiography. In multicovariate parametric survival time analysis, LVEF [hazard ratio (HR) = 1.046 per 1% increase, P = 0.001], concurrent atrial fibrillation (AF) (HR = 3.203, P < 0.001), and E/e' (HR = 1.083 per 1.0 increase, P < 0.001) were significantly correlated with the primary endpoint. In addition to these covariates, angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) use was significantly correlated with the secondary endpoint (HR = 0.451, P = 0.008). Diagnostic performance plot analysis demonstrated that the discrimination threshold value for LVEF that could identify patients prone to reaching the primary endpoint was ≥57.2%. The prevalence of AF or E/e' ratio did not differ significantly between patients with LVEF ≥ 58% and with 40% < LVEF < 58%. CONCLUSION: A higher LVEF is independently related to poor prognosis in patients with HFpEF, in addition to concurrent AF and an elevated E/e' ratio. ACEI/ARB use, in contrast, was associated with improved prognosis, especially with regard to readmission due to HF. CLINICAL TRIAL REGISTRATION: https://www.umin.ac.jp/ctr/index.htm. UNIQUE IDENTIFIER: UMIN000017725.

Influence of left ventricular ejection fraction on the reduction in N-terminal pro-brain natriuretic peptide by canagliflozin in patients with heart failure and type 2 diabetes: A sub analysis of the CANDLE trial.

AIM: To investigate the effect of left ventricular ejection fraction (LVEF) on the behavior of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with heart failure and type 2 diabetes mellitus with the use of canagliflozin compared to glimepiride. METHODS: Patients (n = 233) from the CANDLE trial were randomly assigned to either the add-on canagliflozin (n = 113) or glimepiride treatment groups (n = 120). The patients were followed-up for 24 weeks. The NT-proBNP levels were measured at baseline and after 24 weeks. The LVEF was determined at baseline. RESULTS: There was a significant relationship between the baseline NT-proBNP level (X1) and the change in NT-proBNP levels from baseline to 24 weeks (Y) in the canagliflozin group (Y = -0.533 × X1 + 178; r = -0.860, p < 0.001). However, this relationship was not observed in the glimepiride group (p = 0.428). The baseline LVEF (X2) correlated with Y with a marginal significance in the canagliflozin group (Y = 7.72 × X2-549; r = 0.192, p = 0.054), but no relationship was observed in the glimepiride group. In the canagliflozin group, bivariate regression analysis showed a significant correlation between Y, X1, and X2; Y = -0.567 × X1-6.04 × X2 + 542 (R = 0.871, p < 0.001). The partial regression coefficients of X1 (p < 0.001) and X2 (p = 0.006) significantly explained the variance in Y. The correlation coefficient for X2 was negative. There was a significant relationship between the logarithmically transformed NT-proBNP [ln(NT-proBNP)] at baseline (X1') and the change in ln(NT-proBNP) values from baseline to 24 weeks (Y'), a surrogate of the rate of change in NT-proBNP levels, in the canagliflozin group (Y' = -0.18 × X1' + 0.93; r = 0.450, p = 0.001). CONCLUSIONS: The baseline NT-proBNP level significantly affected the extent and the rate of its decrease by canagliflozin. The reduction in NT-proBNP levels by canagliflozin was prominent in patients with a higher LVEF at baseline. However, its confounding effect of LVEF on canagliflozin treatment was not recognized without adjusting for the NT-proBNP level at baseline.

Successful treatment of mediastinal pancreatic pseudocyst and pancreatic pleural effusion with endoscopic pancreatic duct drainage: A case report.

An 81-year-old man with chronic pancreatitis was being treated with a protease inhibitor. He developed an acute exacerbation of chronic pancreatitis and dyspnea. Contrast-enhanced computed tomography showed disruption of the main pancreatic duct, a cystic lesion connecting the mediastinum to the main pancreatic duct, and left pleural effusion. We diagnosed a pancreatic pseudocyst, mediastinal pancreatic pseudocyst, and pancreatic pleural effusion. Endoscopic retrograde pancreatography showed leakage of contrast medium from the pancreatic body; furthermore, a cystic cavity extending to the mediastinum through a pancreatic duct fistula was visualized. An endoscopic transpapillary nasopancreatic drainage tube was placed in the cystic cavity. Computed tomography showed that the mediastinal pseudocyst and pleural effusion had disappeared. Endoscopic transpapillary pancreatic duct drainage may be useful when a connection between the main pancreatic duct and a mediastinal pseudocyst is confirmed by imaging.

Intraprocedural Thrombotic Events during Percutaneous Coronary Intervention Due to Acquired Antithrombin Deficiency-related Heparin Resistance Successfully Treated with Antithrombin Gamma Supplementation.

A 75-year-old man receiving treatment for necrotizing pancreatitis developed septic disseminated intravascular coagulation and acute coronary syndrome (ACS). During percutaneous coronary intervention (PCI), a large amount of fresh thrombi appeared after balloon dilatation for the ACS-culprit lesion. Given the low plasma antithrombin (AT) activity and poorly prolonged activated clotting time (ACT), we suspected that acquired AT deficiency-related heparin resistance (HR) was responsible for the thrombus formation. Administration of AT gamma markedly improved ACT, and we successfully completed PCI. We suggest that AT gamma be considered a treatment option for AT deficiency-related HR and subsequent intraprocedural thrombotic events.

Malondialdehyde-Modified Low-Density Lipoprotein as a Predictor of Major Adverse Limb Events after Endovascular Therapy in Patients with Lower Extremity Arterial Disease.

AIM: Adverse limb events after endovascular therapy (EVT) are a major concern. This study aimed to investigate the relationship between serum malondialdehyde-modified low-density lipoprotein (MDA-LDL) level, a potentially potent indicator of atherosclerosis, and clinical outcomes after EVT in patients with lower extremity arterial disease (LEAD). METHODS: A total of 208 LEAD patients who underwent EVT and MDA-LDL measurements were retrospectively analyzed. Those with chronic limb-threatening ischemia (CLTI) were included in the CLTI subgroup (n=106). Patients were further categorized into the High or Low MDA-LDL groups according to the cut-off value calculated by receiver operating characteristic analysis. Major adverse limb events (MALE), a composite of cardiovascular death, limb-related death, major amputation, and target-limb revascularization, were evaluated. RESULTS: MALE occurred in 73 (35%) patients. The median follow-up interval was 17.4 months. The MDA-LDL cut-off values were 100.5 U/L (area under the curve [AUC] 0.651) in the overall population and 98.0 U/L (AUC 0.724) in the CLTI subgroup. Overall, the High MDA-LDL group showed significantly higher total cholesterol (189.7±37.5 mg/dL vs. 159.3±32.0 mg/dL, p＜0.01), low-density lipoprotein cholesterol (114.3±29.7 mg/dL vs. 87.3±25.3 mg/dL, p＜0.01), and triglyceride (166.9±91.1 mg/dL vs. 115.8±52.3 mg/dL, p＜0.01) than the Low MDA-LDL group. Multivariate Cox regression analyses revealed that MDA-LDL and C-reactive protein were independent predictors of MALE. In the CLTI subgroup, MDA-LDL was an independent predictor of MALE. The High MDA-LDL group showed worse MALE-free survival rates than the Low MDA-LDL group in overall (p＜0.01) and in the CLTI subgroup (p=0.01). CONCLUSIONS: Serum MDA-LDL level was associated with MALE after EVT.

Hemodialysis-induced Myocardial Stunning with No Obstructive Coronary Artery Disease: Pathophysiological Significance of Coronary Microvascular Dysfunction.

Hemodialysis (HD)-induced myocardial stunning, characterized by transient left ventricular systolic dysfunction during HD, has been reported to be common and associated with a poor prognosis. However, the pathophysiology is not fully understood. We herein report a case of HD-induced myocardial stunning without obstructive coronary artery disease complicated by coronary microvascular dysfunction (CMD), suggesting that CMD plays a crucial role in the pathophysiology of this disease.

Exploratory analysis of multi-trait coadaptations in light of population history.

During the process of range expansion, populations encounter a variety of environments. They respond to the local environments by modifying their mutually interacting traits. Common approaches of landscape analysis include first focusing on the genes that undergo diversifying selection or directional selection in response to environmental variation. To understand the whole history of populations, it is ideal to capture the history of their range expansion with reference to the series of surrounding environments and to infer the multitrait coadaptation. To this end, we propose a complementary approach; it is an exploratory analysis using up-to-date methods that integrate population genetic features and features of selection on multiple traits. First, we conduct correspondence analysis of site frequency spectra, traits, and environments with auxiliary information of population-specific fixation index (F ST). This visualizes the structure and the ages of populations and helps infer the history of range expansion, encountered environmental changes, and selection on multiple traits. Next, we further investigate the inferred history using an admixture graph that describes the population split and admixture. Finally, principal component analysis of the selection on edge-by-trait (SET) matrix identifies multitrait coadaptation and the associated edges of the admixture graph. We introduce a newly defined factor loadings of environmental variables in order to identify the environmental factors that caused the coadaptation. A numerical simulation of one-dimensional stepping-stone population expansion showed that the exploratory analysis reconstructed the pattern of the environmental selection that was missed by analysis of individual traits. Analysis of a public dataset of natural populations of black cottonwood in northwestern America identified the first principal component (PC) coadaptation of photosynthesis- vs growth-related traits responding to the geographical clines of temperature and day length. The second PC coadaptation of volume-related traits suggested that soil condition was a limiting factor for aboveground environmental selection.

Ventricular Sigmoid Septum as a Risk Factor for Anthracycline-Induced Cancer Therapeutics-Related Cardiac Dysfunction in Patients With Malignant Lymphoma.

Background: Identifying risk factors for cancer therapeutics-related cardiac dysfunction (CTRCD) is essential for the early detection and prompt initiation of medial therapy for CTRCD. No study has investigated whether the sigmoid septum is a risk factor for anthracycline-induced CTRCD. Methods and Results: We enrolled 167 patients with malignant lymphoma who received a CHOP-like regimen from January 2008 to December 2017 and underwent both baseline and follow-up echocardiography. Patients with left ventricular ejection fraction (LVEF) ≤50% were excluded. CTRCD was defined as a ≥10% decline in LVEF and LVEF <50% after chemotherapy. The angle between the anterior wall of the aorta and the ventricular septal surface (ASA) was measured to quantify the sigmoid septum. CTRCD was observed in 36 patients (22%). Mean LVEF and global longitudinal strain (GLS) were lower, left ventricular mass index was higher, and ASA was smaller in patients with CTRCD. In a multivariable Cox proportional hazard analysis, GLS (hazard ratio [HR] per 1% decrease 1.20; 95% confidence interval [CI] 1.07-1.35) and ASA (HR per 1° increase 0.97; 95% CI 0.95-0.99) were identified as independent determinants of CTRCD. An integrated discrimination improvement evaluation confirmed the significant incremental value of ASA for developing CTRCD. Conclusions: Smaller ASA was an independent risk factor and had significant incremental value for CTRCD in patients with malignant lymphoma who received the CHOP-like regimen.

Population structure of chum salmon and selection on the markers collected for stock identification.

Genetic stock identification (GSI) is a major management tool of Pacific salmon (Oncorhynchus Spp.) that has provided rich genetic baseline data of allozymes, microsatellites, and single-nucleotide polymorphisms (SNPs) across the Pacific Rim. Here, we analyzed published data sets for adult chum salmon (Oncorhynchus keta), namely 10 microsatellites, 53 SNPs, and a mitochondrial DNA locus (mtDNA3, control region, and NADH-3 combined) in samples from 495 locations in the same distribution range (n = 61,813). TreeMix analysis of the microsatellite loci identified the greatest convergence toward Japanese/Korean populations and suggested two admixture events from Japan/Korea to Russia and the Alaskan Peninsula. The SNPs had been purposively collected from rapidly evolving genes to increase the power of GSI. The largest expected heterozygosity was observed in Japanese/Korean populations for microsatellites, whereas it was largest in Western Alaskan populations for SNPs, reflecting the SNP discovery process. A regression of SNP population structures on those of microsatellites indicated the selection of the SNP loci according to deviations from the predicted structures. Specifically, we matched the sampling locations of the SNPs with those of the microsatellites and performed regression analyses of SNP allele frequencies on a 2-dimensional scaling (MDS) of matched locations obtained from microsatellite pairwise F ST values. The MDS first axis indicated a latitudinal cline in American and Russian populations, whereas the second axis showed differentiation of Japanese/Korean populations. The top five outlier SNPs included mtDNA3, U502241 (unknown), GnRH373, ras1362, and TCP178, which were identified by principal component analysis. We summarized the functions of 53 nuclear genes surrounding SNPs and the mtDNA3 locus by referring to a gene database system and propose how they may influence the fitness of chum salmon.