A Pleistocene legacy structures variation in modern seagrass ecosystems.

Distribution of Earth's biomes is structured by the match between climate and plant traits, which in turn shape associated communities and ecosystem processes and services. However, that climate-trait match can be disrupted by historical events, with lasting ecosystem impacts. As Earth's environment changes faster than at any time in human history, critical questions are whether and how organismal traits and ecosystems can adjust to altered conditions. We quantified the relative importance of current environmental forcing versus evolutionary history in shaping the growth form (stature and biomass) and associated community of eelgrass (Zostera marina), a widespread foundation plant of marine ecosystems along Northern Hemisphere coastlines, which experienced major shifts in distribution and genetic composition during the Pleistocene. We found that eelgrass stature and biomass retain a legacy of the Pleistocene colonization of the Atlantic from the ancestral Pacific range and of more recent within-basin bottlenecks and genetic differentiation. This evolutionary legacy in turn influences the biomass of associated algae and invertebrates that fuel coastal food webs, with effects comparable to or stronger than effects of current environmental forcing. Such historical lags in phenotypic acclimatization may constrain ecosystem adjustments to rapid anthropogenic climate change, thus altering predictions about the future functioning of ecosystems.

Estimation of Small Dense LDL-Cholesterol Levels in Patients with Acute Coronary Syndrome.

Small dense LDL-cholesterol is an established risk factor for atherosclerosis, but it is not routinely measured in clinical practice, and its measurement has not yet been reimbursed. The Sampson equation that uses triglyceride and LDL-cholesterol levels has very recently been proposed to estimate small dense LDL-cholesterol levels. We validated its accuracy in patients with acute coronary syndrome.Serum samples were obtained on admission from hospitalized patients with acute coronary syndrome before heparinization. Small dense LDL-cholesterol levels were measured directly and were also estimated from triglyceride and LDL-cholesterol levels using the Sampson equation. The correlation between the Sampson's equation and direct measurement was investigated.A total of 55 patients were enrolled. The median age was 75 (65, 84) years old, and 35 (64%) were men. There was a moderate correlation between the two methods (r = 0.76, P < 0.001). A lower level of small dense LDL-cholesterol was independently associated with a greater overestimation of the Sampson equation.The Sampson equation is useful for estimating small dense LDL-cholesterol levels in patients with acute coronary syndrome. However, the estimated value may be overestimated in patients with low lipid profiles.

Prognostic Implication of Small Dense LDL-Cholesterol Levels following Acute Coronary Syndrome.

Background and Objectives: Small dense LDL cholesterol is a strong risk factor for atherosclerosis. However, few studies have investigated the impacts of this specific lipid profile on the incident risk of adverse cardiovascular events in patients with acute coronary syndrome. Materials and Methods: Patients with acute coronary syndrome, who underwent revascularization, were included and followed for 2 years. The levels of small dense LDL cholesterol were measured at index discharge (day 0) in the setting of newly administered therapies for secondary prevention, including aspirin and statins, during the index hospitalization. The prognostic impact of small dense LDL-cholesterol levels on the risk of a primary composite endpoint, including cardiac death, non-fatal myocardial infarction, unstable angina pectoris, stroke, and heart failure, was investigated. Results: In total, 46 patients (median 75 (59, 83) years old, 63% men) were included. Median small dense LDL cholesterol was 19.4 (13.5, 23.8) mg/dL at index discharge. All patients initiated statin treatment before the index discharge, with a median LDL-cholesterol level of 77 (64, 109) mg/dL. Small dense LDL-cholesterol level was independently associated with an incremental risk for the primary endpoint (p < 0.05 by adjusting for several potential risk factors, including LDL cholesterol) with a cutoff of 32.6 mg/dL. Conclusions: Small dense LDL-cholesterol level was a significant risk factor for cardiovascular events following presentations of acute coronary syndrome.

The biogeography of community assembly: latitude and predation drive variation in community trait distribution in a guild of epifaunal crustaceans.

While considerable evidence exists of biogeographic patterns in the intensity of species interactions, the influence of these patterns on variation in community structure is less clear. Studying how the distributions of traits in communities vary along global gradients can inform how variation in interactions and other factors contribute to the process of community assembly. Using a model selection approach on measures of trait dispersion in crustaceans associated with eelgrass (Zostera marina) spanning 30° of latitude in two oceans, we found that dispersion strongly increased with increasing predation and decreasing latitude. Ocean and epiphyte load appeared as secondary predictors; Pacific communities were more overdispersed while Atlantic communities were more clustered, and increasing epiphytes were associated with increased clustering. By examining how species interactions and environmental filters influence community structure across biogeographic regions, we demonstrate how both latitudinal variation in species interactions and historical contingency shape these responses. Community trait distributions have implications for ecosystem stability and functioning, and integrating large-scale observations of environmental filters, species interactions and traits can help us predict how communities may respond to environmental change.

Impact of the whole activated clotting time during Impella support on short-term prognosis.

Impella (Abiomed, Danvers, MA, USA) is a percutaneous trans-catheter left ventricular assist device. Anticoagulant therapy targeting whole activated clotting time (ACT) between 160 and 180 s is recommended to prevent pump thrombosis during support. However, we sometimes experience fatal bleeding despite achieving the target ACT range. Consecutive patients who received Impella support in our institute between March 2018 and October 2020 were included in this retrospective study. The association between the averaged ACT levels during the Impella support and 30-day mortality was investigated. A total of 36 patients (71 years old, 61% males) were included. Most of the patients were managed within the recommended therapeutic range of ACT, and the average ACT level was 162 s. The higher ACT group (> 168 s) had older age, smaller body mass index, and higher serum creatinine compared with the lower ACT group (p < 0.05 for all). A higher ACT level was an independent risk factor of 30-day mortality with an adjusted hazard ratio of 1.085 (95% confidence interval 1.037-1.154) with a cut-off level of 168 s. There were only two thromboembolic events. Patients managed with higher ACT levels had a higher risk of 30-day mortality during Impella support. A low-dose heparin purge solution might be recommended in patients with high-risk for bleeding events.

Correlation Between Plasma B-Type Natriuretic Peptide Levels and Remote Dielectric Sensing in Patients with Heart Failure.

Plasma B-type natriuretic peptide (BNP) is a practical tool with which to estimate hemodynamic status including intra-cardiac pressure in patients with heart failure (HF). However, plasma BNP levels cannot be measured immediately in an outpatient private clinic. We investigated the value of remote dielectric sensing (ReDS), a novel non-invasive electromagnetic energy-based tool to quantify lung fluid amount immediately, to predict plasma BNP levels.Successive measurements of ReDS values and plasma BNP levels were performed in patients hospitalized to treat HF in a prospective manner. Correlations between ReDS values and plasma BNP levels were assessed.A total of 117 datasets for HF patients were obtained in this prospective study. The median ReDS value was 28% (interquartile range: 25%, 34%) and the median plasma BNP level was 205 (86, 469) pg/mL, both of which had a slight correlation (r = 0.234, P = 0.011). Their correlation improved when those with a body mass index less than 18.5 (n = 23) were excluded (r = 0.278, P = 0.007).ReDS might be a practical tool for estimating plasma BNP levels, particularly in outpatient private clinics where the immediate measurement of plasma BNP levels is not available.

Prognostic Implications of Mitral Valve Inflow Pattern Overlap during Ivabradine Therapy.

The prognostic impact of mitral inflow wave overlap during ivabradine therapy in patients with heart failure with reduced ejection fraction (HFrEF) remains to be unknown. Thus, in this study, we have retrospectively examined consecutive inpatients with HFrEF admitted with decompensated heart failure who continued ivabradine following the index discharge. Ideal heart rate (HR), at which echocardiographic mitral inflow wave overlap is theoretically 0, was retrospectively calculated as follows: 96 - 0.13 × (deceleration time [msec]). HR difference was then calculated as follows: actual HR - ideal HR. The association between the HR difference at index discharge and a composite outcome of cardiovascular death and heart failure readmissions was investigated. In total, 16 patients (68 [47, 75] years old, 11 men, median left ventricular ejection fraction 28% [22%, 35%]) were included in this study for analysis. Baseline actual HR was determined to be 88 (81, 93) bpm, whereas the ideal HR was calculated as 75 (73, 76) bpm. Following the initiation of ivabradine, actual HR at index discharge was 75 (64, 84) bpm. Patients with optimal HR (actual HR - ideal HR < ± 10 bpm; n = 9) were found to have experienced a lower incidence of the composite endpoint (40% versus 100%, P = 0.013) compared with those with sub-optimal HR (n = 7) with a hazard ratio of 0.10 (95% confidence interval 0.01-0.91) adjusted for actual HR at index discharge. In conclusion, HR modulation therapy using ivabradine may improve outcomes in patients with HFrEF if individualized ideal HR was achieved.

Validation of Inter-Rater and Intra-Rater Reliability of Remote Dielectric Sensing Measurement.

Remote dielectric sensing (ReDS) is a recently introduced non-invasive electromagnetic-based device used to quantify lung fluid levels. Nevertheless, its inter-rater and intra-rater reliability remain uncertain. In 10 healthy volunteers, ReDS values were measured three times successively by the officially trained expert examiner to validate intra-rater reliability. Similar measures were performed by a total of three examiners to validate inter-rater reliability. Intra-class correlation (ICC) was applied to validate each reliability. Ten healthy volunteers [median 34 (32, 40) years old, 10 men, body mass index 23.0 (21.2, 23.9) ] were included. Median ReDS value was 28% (25%, 31%). For the intra-rater reliability, ICC (1, 1) and ICC (1, 3) were 0.966 and 0.988, respectively (P < 0.001). For the inter-rater reliability, ICC (2, 1) and ICC (2, 3) were 0.683 and 0.866, respectively (P < 0.001). Given almost perfect intra-rater reliability, an examiner does not need to repeat ReDS measurement. Given substantial inter-rater reliability, ReDS measurements had better be measured by multiple examiners if possible.

Lung Fluid Volume during Cardiopulmonary Exercise Testing.

Background and Objectives: Cardiopulmonary exercise testing can be used to quantify exercise capacity in patients with heart failure with reduced ejection fraction (HfrEF). Lung fluid levels as measured non-invasively by remote dielectric sensing (ReDSTM), often correlate with intracardiac filling pressures. The change in lung fluid levels in patients with HfrEF during cardiopulmonary exercise testing is unknown. Materials and Methods: Patients with chronic HfrEF who underwent cardiopulmonary exercise testing between October 2021 and March 2022 were prospectively included in this proof-of-concept study, with ReDS values measured before and after testing. Results: Thirteen patients (median age 41 (37, 52) years, 69% men, plasma B-type natriuretic peptide 141 (57, 368) pg/mL) were included. Median peak oxygen consumption was 11.4 (10.7, 14.0) mL/kg/min. During the test, ReDS values increased from 25% to 32% only in one patient on inotropic support, whereas ReDS values remained unchanged in the other 12 patients. The former patient remained hospitalized, whereas the other patients were dischargeable without any new incidence of clinical events during the observational period (median duration 69 (33, 112] days). Conclusions: The ReDS system may be a feasible complementary tool to noninvasively assess the changes in lung fluid levels during cardiopulmonary exercise testing. The clinical implications of ReDS values during exercise needs further investigation.

Change in Lung Fluid Volume during Exercise in Patients with Exercise-Induced Mitral Regurgitation.

Exercise-induced mitral regurgitation (MR) can be diagnosed during stress echocardiography testing. Remote dielectric sensing (ReDSTM) is a noninvasive electromagnetic-based modality to measure lung fluid levels. The change in lung fluid levels in patients with MR during stress echocardiography remains unknown. Patients with symptomatic MR at baseline and suspected worsening exercise-induced MR underwent stress echocardiography. ReDS values were measured before and after the tests. A total of four patients (ages ranging between 74 and 84 years old, three women) underwent stress echocardiography testing using a bicycle ergometer. In patient A, MR effective regurgitant orifice area (EROA) remained unchanged and ReDS values decreased. EROA increased significantly with a small incremental change in ReDS values in patient B and patient C, who underwent valve repair with MitraClip later. Patient D had a mild increase in MR EROA but a considerable increase in ReDS values (from 22% to 32%), and eventually received valve repair with MitraClip. The ReDS system may be a complementary tool to conventional stress echocardiography in the evaluation of clinically significant MR and considering mitral valve intervention.

Prognostic implication of risk scoring systems in patients with cardiogenic shock supported by ECMO and Impella.

We experienced two refractory cardiogenic shock patients receiving veno-arterial extracorporeal membrane oxygenation and Impella percutaneous left ventricular assist device (ECPELLA). TVAD score, which was originally proposed to predict one-year mortality following left ventricular assist device implantation using four objective parameters, was retrospectively calculated using data of day 3 following ECPELLA initiations. One patient with estimated intermediate risk could achieve successful explantation of ECPELLA, whereas another patient with estimated high risk was expired despite explantation of extracorporeal membrane oxygenation. TVAD score might be a useful tool to risk stratify and construct next strategy (i.e., bridge to recovery or bridge to more intensive therapy) for those with ECPELLA, although further studies are warranted to validate this hypothesis.

Impact of Sacubitril/Valsartan on Right Heart Failure.

Sacubitril/valsartan improves mortality and morbidity in patients with heart failure with reduced ejection fraction. However, its impact on right heart failure remains unknown. We experienced a 70-year-old man who was started on sacubitril/valsartan to treat his right heart failure with moderate tricuspid regurgitation. Following the 3-month sacubitril/valsartan treatment, a functional and geological improvement was observed in the right heart as well as amelioration of his congestive symptoms. Sacubitril/valsartan might improve right heart failure in addition to conventionally-proven left heart failure. Further large-scale studies are warranted to validate our findings.

Association Between Adaptive Servo-Ventilation Therapy and Renal Function.

Cardio-renal syndrome is a challenging clinical entity to manage, and is often associated with increased morbidity and mortality. We hypothesized that adaptive servo-ventilation (ASV), non-invasive positive pressure ventilation that ameliorates systemic/pulmonary congestion, may improve renal function in patients with symptomatic heart failure complicated by the cardio-renal syndrome. Patients with symptomatic congestive heart failure who underwent ASV therapy for over 1 month were included in this retrospective study. The trajectory of the estimated glomerular filtration ratio (eGFR) between the pre-1 month period and the post-one-month period (on ASV) were compared. A total of 81 patients (median 65 years old, 65 men) were included. eGFR decreased during the pre-1 month period from 52.7 (41.7, 64.6) down to 49.9 (37.3, 63.5) mL/minute/1.73 m2 (P < 0.001) whereas we observed an increase following one-month of ASV therapy up to 53.4 (38.6, 68.6) mL/minute/1.73 m2 (P = 0.022). A reduction in furosemide equivalent dose following the initiation of ASV therapy was independently associated with increases in eGFR with an adjusted odds ratio of 13.72 (95% confidence interval 3.40-55.3, P < 0.001). In conclusion, short-term ASV therapy was associated with the preservation of renal function, particularly when the dose of loop diuretics was concomitantly reduced.

Therapeutic Strategy for a Patient with Advanced Heart Failure and Schizophrenia Without Cardiac Replacement Therapies.

We had a 58-year-old man with advanced heart failure and progressive end-organ dysfunction refractory to inotropes. Following detailed discussions, he decided not to receive ventricular assist device therapy considering his comorbidity of schizophrenia. A palliative care team initiated 2.5 mg of morphine together with low-dose anti-heart failure medications, which improved not only his heart failure symptoms but also the congestive heart failure itself. Aggressive commitments of the palliative care team might improve not only patients' quality of life but also advanced heart failure itself.

How to Estimate the Optimal Heart Rate in Patients with Heart Failure with Preserved Ejection Fraction.

Ideal heart rate (HR), particularly for those with heart failure with preserved ejection fraction (HFpEF), remains unknown. We hypothesized that cardiac output would be maximum when the overlap between E-wave and A-wave at the trans-mitral flow is "zero" in the Doppler echocardiography. We retrospectively investigated the association among the overlap length between two waves, actual HR, and other echocardiographic parameters to construct a formula for estimating theoretically ideal HR among those with HFpEF. In total, 48 HFpEF patients were included (70-year-olds, 18 males). Given the results of multivariate linear regression analyses, the overlap length was estimated as follows: -1,050 + 8.4 × (HR [bpm]) + 0.6 × (deceleration time [millisecond]) + 1.7 × (A-width [millisecond]), which had a strong agreement with the actually measured overlap length (r = 0.86, P < 0.001). Theoretically ideal HR was calculated by substituting zero into the estimated overlap length as follows: 125 - 0.07 × (deceleration time [millisecond]) - 0.20 × (A-width [millisecond]). In the validation cohort including another 143 HFpEF patients, the estimated overlap using the formula again had a strong agreement with the actually measured overlap (r = 0.72, P < 0.001). In this study, we proposed a novel formula for calculating theoretically ideal HR, consisting of deceleration time and A-width, in the HFpEF cohort. Clinical implication to optimize the HR targeting the theoretically ideal HR should be investigated in prospective studies.

Prediction of treatment response from the microenvironment of tumor immunity in cervical cancer patients treated with chemoradiotherapy.

To supplement clinical decision-making in the management of cervical cancer, various prognostic factors, including tumor immune microenvironments, were examined in patients with cervical cancer treated with definitive chemoradiotherapy. We retrospectively analyzed the expression of CD8, FoxP3, HLA-1, PD-L1, and XRCC4 in 100 cases of cervical cancer. The observed tumor immune microenvironments were also classified into three types: inflamed, excluded, and cold type. Less FoxP3+ T cells and cold-type tumor were found to be poor prognostic factors in addition to non-SCC, large pre-treatment tumor volume, and three or less cycles of concurrent chemotherapy based on multivariate analysis. Cold-type tumors had significantly worse prognoses than the other two types, whereas inflamed- and excluded-type tumors showed similar 5-year disease-specific survival (P < 0.001; 0% vs. 60.3% vs. 72.3%). Radiotherapy could overcome the inhibitory immune microenvironment that occurs in excluded type. Individualized combination therapy adapted to pre-treatment tumor immunity may be necessary to improve radiotherapy outcomes in cervical cancer.

Impact of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor on Heart Failure with Preserved Ejection Fraction.

Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor is a recently introduced oral medication to treat renal anemia, but its clinical implication in patients with heart failure, particularly heart failure with preserved ejection fraction (HFpEF), remains unknown. We had a 91-year-old woman with HFpEF who was admitted to our institute to treat her worsening heart failure. She initiated HIF-PH inhibitor daprodustat to treat her renal anemia (hemoglobin 8.8 g/dL and estimated glomerular filtration ratio 15.6 mL/min/1.73 m2). Following a 6-month treatment with daprodustat, hemoglobin increased up to 10.4 g/dL, left ventricular mass index decreased from 107 g/m2 to 88 g/m2, and plasma B-type natriuretic peptide decreased from 276 pg/mL to 122 pg/mL, despite doses of other medications remaining unchanged. HIF-PH inhibitors might be a promising tool to ameliorate renal anemia and facilitate cardiac reverse remodeling in patients with HFpEF.

Association between radiotherapy-induced alteration of programmed death ligand 1 and survival in patients with uterine cervical cancer undergoing preoperative radiotherapy.

PURPOSE: To evaluate radiotherapy-induced changes in the expression of programmed death ligand 1 (PD-L1), programmed death 1 (PD-1), and human leukocyte antigen class I (HLA-1) in patients with uterine cervical cancer, as well as infiltration of CD8+ and Forkhead box P3+ (FoxP3+) T lymphocytes into tumor tissue and the prognostic value of these parameters. MATERIALS AND METHODS: We performed immunohistochemical analysis of pre-radiotherapy biopsies and corresponding post-radiotherapy resected tissues in 104 uterine cervical cancer patients undergoing preoperative chemoradiotherapy or radiotherapy alone. We scored the expression of various proteins to distinguish positive from negative samples. RESULTS: PD-L1-expressing tumor cells (PD-L1 TC) increased significantly after chemoradiotherapy (p = 0.043). CD8+ T cell infiltration (p = 0.002) and FoxP3+ T cell infiltration (p = 0.003) decreased significantly after chemoradiotherapy. Expression of PD­1, PD-L1-expressing immune cells (PD-L1 IC), and HLA­1 did not change after chemoradiotherapy. In biopsy specimens obtained before chemoradiotherapy or radiotherapy, greater infiltration of CD8+ T cells (p = 0.001) and FoxP3+ T cells (p = 0.003) were significant predictors of better overall survival (OS). In surgical specimens obtained after chemoradiotherapy or radiotherapy, greater infiltration of PD-L1 TC was the only significant predictor of better OS (p < 0.001) and was related to a significantly lower probability of out-of-field recurrence (p = 0.005). CONCLUSION: Chemoradiotherapy induced an immunologic shift that increased PD-L1 TC. Chemoradiotherapy has immunological effects that can influence the results of treatment for uterine cervical cancer.

Spatially explicit modeling of metapopulation dynamics of broadcast spawners and stabilizing/destabilizing effects of heterogeneity of quality across local habitats.

Many coastal invertebrate species are broadcast spawners. These species have a highly sedentary adult stage and disperse by oceanic transport of planktonic larvae. One commercially important group of broadcast spawners is abalones, which live in suitable habitat patches of rock reefs that are discretely distributed. Because of these life-history and habitat characteristics, abalones tend to exhibit a metapopulation structure. Despite fisheries management and the release of juveniles, wild populations of broadcast spawners have undergone dramatic reductions in density due to overexploitation, which has been partly attributed to a failure to account for spatial structure. To clarify the relationship between the persistence of a metapopulation and the bottleneck that occurs during reproduction and dispersal processes caused by spatial structure, we developed a spatially explicit metapopulation model accounting for the effects of both life history and fishery pressure. By analyzing the model, we derived a metric to evaluate metapopulation quality as the leading eigenvalue of a non-negative matrix (the landscape matrix). Using this measure, we clarified that the effect of spatial structure on metapopulation stability is explained well by the mean and variance of parameter values across patches under the condition in which the heterogeneity of the metapopulation network is weak. In particular, the presence of both a higher average and higher variance of quality in the landscape could indicate stable fishery stocks under certain conditions. For example, when the decline in the mean longevity of local patch due to the fishery pressures gradually diminishes, the rescue effects by good patches would work more effectively than the negative effect of bad patches and then the stabilizing effect of spatial heterogeneity could be observed in a metapopulation. Furthermore, optimal patch characteristics for the improvement of quality strongly depend on specific parameter values. For example, when adult fertility is improved, a patch with higher "source" ability is more suitable. In contrast, when the settlement success of planktonic larvae is improved or fishery pressure is reduced, a patch with higher "buffer" ability is more suitable for the improvement of fishery management.

Association between cancer immunity and treatment results in uterine cervical cancer patients treated with radiotherapy.

OBJECTIVE: To evaluate proteins related to tumor immune response and treatment outcome from radiotherapy for uterine cervical cancer patients. METHODS: We performed a retrospective immunohistochemical staining of 81 patients with uterine cervical cancer who underwent definitive radiotherapy. We examined the expression of programmed death ligand 1, human leukocyte antigen class I, tumor-infiltrating CD8+, and forkhead box P3+ (FoxP3+) T cells in tumor tissues. RESULTS: In biopsy specimen, patients with a higher number of CD8+ T cells and FoxP3+ T cells had a better disease-specific survival than patients with a lower number of CD8+ T cells and FoxP3+ cells (P = 0.018 and P = 0.009). Multivariate analysis showed that equivalent dose in 2 Gy fractions (EQD2) of the minimum dose to 90% of the high-risk clinical target volume, FoxP3+ T cells and expression of human leukocyte antigen class I were significant prognostic factors. When the EQD2 is 70 Gy or more, a higher local control rate is obtained regardless of the number of CD8- or FoxP3-positive cells. When EQD2 is <70 Gy, the number of CD8-positive cells has a significant impact on treatment outcome: the recurrence rate (local recurrence rate + distant metastasis rate) was 46.2% in the group with a CD8 value of 230 or higher, whereas the recurrence rate was 75.7% in the group with a CD8 value of less than 230. CONCLUSION: The combination of CD8 or FoxP3 with EQD2 can be potentially useful to predict the treatment results of radiotherapy for cervical cancer, leading to individualized optimal selection of treatment for cervical cancer.