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Ecological networks are more sensitive to plant than to animal extinction under climate change
(2016)
Impacts of climate change on individual species are increasingly well documented, but we lack understanding of how these effects propagate through ecological communities. Here we combine species distribution models with ecological network analyses to test potential impacts of climate change on >700 plant and animal species in pollination and seed-dispersal networks from central Europe. We discover that animal species that interact with a low diversity of plant species have narrow climatic niches and are most vulnerable to climate change. In contrast, biotic specialization of plants is not related to climatic niche breadth and vulnerability. A simulation model incorporating different scenarios of species coextinction and capacities for partner switches shows that projected plant extinctions under climate change are more likely to trigger animal coextinctions than vice versa. This result demonstrates that impacts of climate change on biodiversity can be amplified via extinction cascades from plants to animals in ecological networks.
Background: MicroRNA-21 (miR-21) is up-regulated in tumor tissue of patients with malignant diseases, including hepatocellular carcinoma (HCC). Elevated concentrations of miR-21 have also been found in sera or plasma from patients with malignancies, rendering it an interesting candidate as serum/plasma marker for malignancies. Here we correlated serum miR-21 levels with clinical parameters in patients with different stages of chronic hepatitis C virus infection (CHC) and CHC-associated HCC.
Methodology/Principal Findings: 62 CHC patients, 29 patients with CHC and HCC and 19 healthy controls were prospectively enrolled. RNA was extracted from the sera and miR-21 as well as miR-16 levels were analyzed by quantitative real-time PCR; miR-21 levels (normalized by miR-16) were correlated with standard liver parameters, histological grading and staging of CHC. The data show that serum levels of miR-21 were elevated in patients with CHC compared to healthy controls (P<0.001); there was no difference between serum miR-21 in patients with CHC and CHC-associated HCC. Serum miR-21 levels correlated with histological activity index (HAI) in the liver (r = −0.494, P = 0.00002), alanine aminotransferase (ALT) (r = −0.309, P = 0.007), aspartate aminotransferase (r = −0.495, P = 0.000007), bilirubin (r = −0.362, P = 0.002), international normalized ratio (r = −0.338, P = 0.034) and γ-glutamyltransferase (r = −0.244, P = 0.034). Multivariate analysis revealed that ALT and miR-21 serum levels were independently associated with HAI. At a cut-off dCT of 1.96, miR-21 discriminated between minimal and mild-severe necroinflammation (AUC = 0.758) with a sensitivity of 53.3% and a specificity of 95.2%.
Conclusions/Significance: The serum miR-21 level is a marker for necroinflammatory activity, but does not differ between patients with HCV and HCV-induced HCC.
Background: Photochemical internalization (PCI) is a novel technology for light-induced enhancement of the local therapeutic effect of cancer drugs, utilizing a specially designed photosensitizing molecule (fimaporfin). The photosensitizing molecules are trapped in endosomes along with macromolecules or drugs. Photoactivation of fimaporfin disrupts the endosomal membranes so that drug molecules are released from endosomes inside cells and can reach their therapeutic target in the cell cytosol or nucleus. Compared with photodynamic therapy, the main cytotoxic effect with PCI is disruption of the endosomal membrane resulting in delivery of chemotherapy drug, and not to the photochemical reactions per se. In this study we investigated the effect of PCI with gemcitabine in patients with inoperable perihilar cholangiocarcinoma (CCA).
Methods: The in vitro cytotoxic effect of PCI with gemcitabine was studied on two CCA-derived cell lines. In a fimaporfin dose-escalation phase I clinical study, we administered PCI with gemcitabine in patients with perihilar CCA (n = 16) to establish a safe and tolerable fimaporfin dose and to get early signals of efficacy. The patients enrolled in the study had tumors in which the whole length of the tumor could be illuminated from the inside of the bile duct, using an optical fiber inserted via an endoscope (Fig. 1). Fimaporfin was administered intravenously at day 0; gemcitabine (i.v.) and intraluminal biliary endoscopic laser light application on day 4; followed by standard gemcitabine/cisplatin chemotherapy.
Results: Preclinical experiments showed that PCI enhanced the effect of gemcitabine. In patients with CCA, PCI with gemcitabine was well tolerated with no dose-limiting toxicities, and no unexpected safety signals. Disease control was achieved in 10 of 11 evaluable patients, with a clearly superior effect in the two highest dose groups. The objective response rate (ORR) was 42%, including two complete responses, while ORR at the highest dose was 60%. Progression-free survival at 6 months was 75%, and median overall survival (mOS) was 15.4 months, with 22.8 months at the highest fimaporfin dose.
Conclusion: Photochemical internalization with gemcitabine was found to be safe and resulted in encouraging response and survival rates in patients with unresectable perihilar CCA.
Large carnivores often impact human livelihoods and well‐being. Previous research has mostly focused on the negative impacts of large carnivores on human well‐being but has rarely considered the positive aspects of living with large carnivores. In particular, we know very little on people's direct experiences with large carnivores like personal encounters and on people's awareness and tolerance toward their exposure to large carnivores. Here, we focus on the wolf (Canis lupus), and report on a phone survey in Germany. We examined whether encounters with wolves were positive or negative experiences and quantified people's awareness and tolerance related to their exposure to wolves. We found that the majority of people reported positive experiences when encountering wolves, regardless of whether wolves were encountered in the wild within Germany, in the wild abroad, or in captivity. The frequency of encounters did not affect the probability to report positive, neutral, or negative experiences. Moreover, people in Germany expressed a high tolerance of living in close vicinity to wolves. These findings are novel and important because they highlight the positive aspects of living in proximity with large carnivores in human‐dominated landscapes.
Objectives: An increasing number of treatment-determining biomarkers has been identified in non-small cell lung cancer (NSCLC) and molecular testing is recommended to enable optimal individualized treatment. However, data on implementation of these recommendations in the “real-world” setting are scarce. This study presents comprehensive details on the frequency, methodology and results of biomarker testing of advanced NSCLC in Germany.
Patients and methods: This analysis included 3,717 patients with advanced NSCLC (2,921 non-squamous; 796 squamous), recruited into the CRISP registry at start of systemic therapy by 150 German sites between December 2015 and June 2019. Evaluated were the molecular biomarkers EGFR, ALK, ROS1, BRAF, KRAS, MET, TP53, RET, HER2, as well as expression of PD-L1.
Results: In total, 90.5 % of the patients were tested for biomarkers. Testing rates were 92.2 % (non-squamous), 70.7 % (squamous) and increased from 83.2 % in 2015/16 to 94.2% in 2019. Overall testing rates for EGFR, ALK, ROS1, and BRAF were 72.5 %, 74.5 %, 66.1 %, and 53.0 %, respectively (non-squamous). Testing rates for PD-L1 expression were 64.5 % (non-squamous), and 58.5 % (squamous). The most common testing methods were immunohistochemistry (68.5 % non-squamous, 58.3 % squamous), and next-generation sequencing (38.7 % non-squamous, 14.4 % squamous). Reasons for not testing were insufficient tumor material or lack of guideline recommendations (squamous). No alteration was found in 37.8 % (non-squamous), and 57.9 % (squamous), respectively. Most common alterations in non-squamous tumors (all patients/all patients tested for the respective biomarker): KRAS (17.3 %/39.2 %), TP53 (14.1 %/51.4 %), and EGFR (11.0 %/15.1 %); in squamous tumors: TP53 (7.0 %/69.1 %), MET (1.5 %/11.1 %), and EGFR (1.1 %/4.4 %). Median PFS (non-squamous) was 8.7 months (95 % CI 7.4–10.4) with druggable EGFR mutation, and 8.0 months (95 % CI 3.9–9.2) with druggable ALK alterations.
Conclusion: Testing rates in Germany are high nationwide and acceptable in international comparison, but still leave out a significant portion of patients, who could potentially benefit. Thus, specific measures are needed to increase implementation.
Highly promising preclinical data obtained in cultured cells and in nude mice bearing xenografts contrast with the rather modest clinical efficacy of Polo-like kinase 1 (Plk1) inhibitors. In the present study, we investigated if Plk1 might be a suitable target in hepatocellular carcinoma (HCC) and if a genetically engineered mouse tumor model that well reflects the tumor cell and micro-environmental features of naturally occurring cancers might be suitable to study anti-Plk1 therapy. Analysis of Plk1 expression in human HCC samples confirmed that HCC express much higher Plk1 levels than the adjacent normal liver tissue. Inhibition of Plk1 by an adenovirus encoding for a short hairpin RNA against Plk1 or by the small-molecule inhibitor BI 2536 reduced the viability of HCC cell lines and inhibited HCC xenograft progression in nude mice. Treatment of transforming growth factor (TGF) α/c-myc bitransgenic mice with BI 2536 during hepatocarcinogenesis reduced the number of dysplastic foci and of Ki-67-positive cells within the foci, indicating diminished tumorigenesis. In contrast, BI 2536 had no significant effect on HCC progression in the transgenic mouse HCC model as revealed by magnetic resonance imaging. Measurement of BI 2536 by mass spectrometry revealed considerably lower BI 2536 levels in HCC compared with the adjacent normal liver tissue. In conclusion, low intratumoral levels are a novel mechanism of resistance to the Plk1 inhibitor BI 2536. Plk1 inhibitors achieving sufficient intratumoral levels are highly promising in HCC treatment.
Background: MicroRNAs circulating in the blood, stabilized by complexation with proteins and/or additionally by encapsulation in lipid vesicles, are currently being evaluated as biomarkers. The consequences of their differential association with lipids/vesicles for their stability and use as biomarkers are largely unexplored and are subject of the present study.
Methods: The levels of a set of selected microRNAs were determined by quantitative reverse-transcription PCR after extraction from sera or vesicle- and non-vesicle fractions prepared from sera. The stability of these microRNAs after incubation with RNase A or RNase inhibitor, an inhibitor of RNase A family enzymes was studied.
Results: The levels of microRNA-1 and microRNA-122, but not those of microRNA-16, microRNA-21 and microRNA-142-3p, declined significantly during a 5-h incubation of the sera. RNase inhibitor prevented the loss of microRNAs in serum as well as the degradation of microRNA-122, a microRNA not expressed in blood cells, in whole blood. Stabilization of microRNA-122 was also achieved by hemolysis. Prolonged incubation of the sera led to enrichment of vesicle-associated relative to non-vesicle-associated microRNAs. Vesicle-associated microRNAs were more resistant to RNase A treatment than the respective microRNAs not associated with vesicles.
Conclusions: Serum microRNAs showed differential stability upon prolonged incubation. RNase inhibitor might be useful to robustly preserve the pattern of cell-free circulating microRNAs. In the case of microRNAs not expressed in blood cells this can also be achieved by hemolysis. Vesicle-associated microRNAs appeared to be more stable than those not associated with vesicles, which might be useful to disclose additional biomarker properties of miRNAs.
Species’ functional traits set the blueprint for pair-wise interactions in ecological networks. Yet, it is unknown to what extent the functional diversity of plant and animal communities controls network assembly along environmental gradients in real-world ecosystems. Here we address this question with a unique dataset of mutualistic bird–fruit, bird–flower and insect–flower interaction networks and associated functional traits of 200 plant and 282 animal species sampled along broad climate and land-use gradients on Mt. Kilimanjaro. We show that plant functional diversity is mainly limited by precipitation, while animal functional diversity is primarily limited by temperature. Furthermore, shifts in plant and animal functional diversity along the elevational gradient control the niche breadth and partitioning of the respective other trophic level. These findings reveal that climatic constraints on the functional diversity of either plants or animals determine the relative importance of bottom-up and top-down control in plant–animal interaction networks.
Aim: The identification of the mechanisms determining spatial variation in biological diversity along elevational gradients is a central objective in ecology and biogeography. Here, we disentangle the direct and indirect effects of abiotic drivers (climatic conditions, and land use) and biotic drivers (vegetation structure and food resources) on functional diversity and composition of bird and bat assemblages along a tropical elevational gradient. Location: Southern slopes of Mt. Kilimanjaro, Tanzania, East Africa. Methods: We counted birds and recorded bat sonotypes on 58 plots distributed in near-natural and anthropogenically modified habitats from 700 to 4,600 m above sea level. For the recorded taxa, we compiled functional traits related to movement, foraging and body size from museum specimens and databases. Further, we recorded mean annual temperature, precipitation, vegetation complexity as well as the number of fruits, flowers, and insect biomass as measures of resource availability on each study site. Results: Using path analyses, we found similar responses of bird and bat functional diversity to the variation in abiotic and biotic drivers along the elevational gradient. In contrast, the functional composition of both taxa showed distinct responses to abiotic and biotic drivers. For both groups, direct temperature effects were most important, followed by resource availability, precipitation and vegetation complexity. Main Conclusions: Our findings indicate that physiological and metabolic constraints imposed by temperature and resource availability determine the functional diversity of bird and bat assemblages, whereas the composition of individual functional traits is driven by taxon-specific processes. Our study illustrates that distinct filtering mechanisms can result in similar patterns of functional diversity along broad environmental gradients. Such differences need to be taken into account when it comes to conserving the functional diversity of flying vertebrates on tropical mountains.
Objectives: To analyze the performance of radiological assessment categories and quantitative computational analysis of apparent diffusion coefficient (ADC) maps using variant machine learning algorithms to differentiate clinically significant versus insignificant prostate cancer (PCa). Methods: Retrospectively, 73 patients were included in the study. The patients (mean age, 66.3 ± 7.6 years) were examined with multiparametric MRI (mpMRI) prior to radical prostatectomy (n = 33) or targeted biopsy (n = 40). The index lesion was annotated in MRI ADC and the equivalent histologic slides according to the highest Gleason Grade Group (GrG). Volumes of interest (VOIs) were determined for each lesion and normal-appearing peripheral zone. VOIs were processed by radiomic analysis. For the classification of lesions according to their clinical significance (GrG ≥ 3), principal component (PC) analysis, univariate analysis (UA) with consecutive support vector machines, neural networks, and random forest analysis were performed. Results: PC analysis discriminated between benign and malignant prostate tissue. PC evaluation yielded no stratification of PCa lesions according to their clinical significance, but UA revealed differences in clinical assessment categories and radiomic features. We trained three classification models with fifteen feature subsets. We identified a subset of shape features which improved the diagnostic accuracy of the clinical assessment categories (maximum increase in diagnostic accuracy ΔAUC = + 0.05, p < 0.001) while also identifying combinations of features and models which reduced overall accuracy. Conclusions: The impact of radiomic features to differentiate PCa lesions according to their clinical significance remains controversial. It depends on feature selection and the employed machine learning algorithms. It can result in improvement or reduction of diagnostic performance.
Background and aims: Expression of carbonic anhydrase IX (CA9), an enzyme expressed in response to hypoxia, acidosis and oncogenic alterations, is reported to be a prognostic factor in HCC patients. Here we evaluated serum CA9 levels in HCC and cirrhosis patients.
Methods: HCC and cirrhosis patients were prospectively recruited and CA9 levels were determined. CA9 levels were compared to stages of cirrhosis and HCC stages. The association of the CA9 levels and overall survival (OS) was assessed. Furthermore, immunohistochemical CA9 expression in HCC and cirrhosis was evaluated.
Results: 215 patients with HCC were included. The median serum CA9 concentration in patients with HCC was 370 pg/ml and significantly higher than in a healthy cohort. Patients with advanced cancer stages (BCLC and ALBI score) had hid significant higher levels of CA9 in the serum. HCC patients with high serum CA9 concentrations (>400 pg/ml) had an increased mortality risk (hazard ratio (HR) 1.690, 95% confidence interval (CI) 1.017–2.809, P = 0.043). Serum CA9 concentration in cirrhotic patients did not differ significantly from HCC patients. Higher CA9 levels in cirrhotic patients correlated with portal hypertension and esophageal varices. Patients with ethanol induced cirrhosis had the highest CA9 levels in both cohorts. Levels of CA9 did not correlate with immunohistochemical expression.
Conclusions: We conclude that a high CA9 level is a possible prognostic indicator for a poor outcome in HCC patients. The high CA9 levels are probably mainly associated with portal hypertension. Ductular reactions might be a possible source of serum CA9.
Background: To assess the potential of radiomic features to quantify components of blood in intraaortic vessels to non-invasively predict moderate-to-severe anemia in non-contrast enhanced CT scans. Methods: One hundred patients (median age, 69 years; range, 19–94 years) who received CT scans of the thoracolumbar spine and blood-testing for hemoglobin and hematocrit levels ± 24 h between 08/2018 and 11/2019 were retrospectively included. Intraaortic blood was segmented using a spherical volume of interest of 1 cm diameter with consecutive radiomic analysis applying PyRadiomics software. Feature selection was performed applying analysis of correlation and collinearity. The final feature set was obtained to differentiate moderate-to-severe anemia. Random forest machine learning was applied and predictive performance was assessed. A decision-tree was obtained to propose a cut-off value of CT Hounsfield units (HU). Results: High correlation with hemoglobin and hematocrit levels was shown for first-order radiomic features (p < 0.001 to p = 0.032). The top 3 features showed high correlation to hemoglobin values (p) and minimal collinearity (r) to the top ranked feature Median (p < 0.001), Energy (p = 0.002, r = 0.387), Minimum (p = 0.032, r = 0.437). Median (p < 0.001) and Minimum (p = 0.003) differed in moderate-to-severe anemia compared to non-anemic state. Median yielded superiority to the combination of Median and Minimum (p(AUC) = 0.015, p(precision) = 0.017, p(accuracy) = 0.612) in the predictive performance employing random forest analysis. A Median HU value ≤ 36.5 indicated moderate-to-severe anemia (accuracy = 0.90, precision = 0.80). Conclusions: First-order radiomic features correlate with hemoglobin levels and may be feasible for the prediction of moderate-to-severe anemia. High dimensional radiomic features did not aid augmenting the data in our exemplary use case of intraluminal blood component assessment.
The quantum molecular dynamic method is used to study multifragmentation and fragment flow and their dependence on in-medium cross sections, momentum dependent interactions, and the nuclear equation of state, for collisions of 197Au+197Au and 93Nb+93Nb in the bombarding energy regime from 100 to 800A MeV. Time and impact parameter dependence of the fragment formation and their implications for the conjectured liquid-vapor phase transition are investigated. We find that the inclusive fragment mass distribution is independent of the equation of state and exhibits a power-law behavior Y(A)∼A-τ with an exponent τ≊-2.3. True multifragmentation events are found in central collisions for energies Elab∼30–200 MeV/nucleon. The associated light fragment (d,t,α) to proton ratios increase with the multiplicity of charged particles and decrease with energy, in agreement with recent experiments. The calculated absolute charged particle multiplicities, the multiplicities of intermediate mass (A>4) fragments, and their respective rapidity distributions do compare well with recent 4π data, but are quite insensitive to the equation of state. On the other hand, these quantities depend sensitively on the nucleon-nucleon scattering cross section, and can be used to determine σ experimentally. The transverse momentum flow of the complex fragments increases with the stiffness of the equation of state. Reduced (in-medium) n-n scattering cross sections reduce the fragment flow. Momentum dependent interactions increase the fragment flow. It is shown that the measured fragment flow at 200A MeV can be reproduced in the model. We find that also the increase of the px/A values with the fragment mass is in agreement with experiments. The calculated fragment flow is too small as compared to the plastic ball data, if a soft equation of state with in-medium corrections (momentum dependent interactions plus reduced cross sections) is employed. An alternative, most intriguing resolution of the puzzle about the stiffness of the equation of state could be an increase of the scattering cross sections due to precritical scattering in the vicinity of a phase transition.
Nuclear transport models including density- and momentum-dependent mean-field effects are compared to intranuclear-cascade models and tested on recent data on inclusive p-like cross sections for 800A-MeV La+La. We find a remarkable agreement between most model calculations but a systematic disagreement with the measured yield at 20°, possibly indicating a need for modification of nuclear transport properties at high densities.
Stopping power and thermalization in relativistic heavy ion collisions is investigated employing the quantum molecular dynamics approach. For heavy systems stopping of the incoming nuclei is predicted, independent of the energy. The influence of the quantum effects and their increasing importance at low energies, is demonstrated by inspection of the mean free path of the nucleons and the n-n collision number. Classical models, which neglect these effects, overestimate the stopping and the thermalization as well as the collective flow and squeeze out. The sensitivity of the transverse and longitudinal momentum transfer to the in-medium cross section and to the pressure is investigated.
We demonstrate that momentum-dependent nuclear interactions (MDI) have a large effect on the dynamics and on the observables of high-energy heavy-ion collisions: A soft potential with MDI suppresses pion and kaon yields much more strongly than a local hard potential and results in transverse momenta intermediate between soft and hard local potentials. The collective-flow angles and the deuteron-to-proton ratios are rather insensitive to the MDI. Only simultaneous measurements of these observables can give clues on the nuclear equation of state at densities of interest for supernova collapse and neutron-star stability.
Attitude polarization describes an increasing attitude difference between groups and is increasingly recognized as a multidimensional phenomenon. However, a unified framework to study polarization across multiple dimensions is lacking. We introduce the attitudinal space framework (ASF) to fully quantify attitudinal diversity. We highlight two key measures—attitudinal extremization and attitudinal dispersion—to quantify across- and within-group attitudinal patterns. First, we show that affective polarization in the US electorate is weaker than previously thought based on mean differences alone: in both Democrat and Republican partisans, attitudinal dispersion increased between 1988 and 2008. Second, we examined attitudes toward wolves in Germany. Despite attitude differences between regions with and without wolves, we did not find differences in attitudinal extremization or dispersion, suggesting only weak attitude polarization. These results illustrate how the ASF is applicable to a wide range of social systems and offers an important avenue to understanding societal transformations.
Purpose: To identify transjugular intrahepatic portosystemic shunt (TIPS) thrombosis in abdominal CT scans applying quantitative image analysis.
Materials and methods: We retrospectively screened 184 patients to include 20 patients (male, 8; female, 12; mean age, 60.7 ± 8.87 years) with (case, n = 10) and without (control, n = 10) in-TIPS thrombosis who underwent clinically indicated contrast-enhanced and unenhanced abdominal CT followed by conventional TIPS-angiography between 08/2014 and 06/2020. First, images were scored visually. Second, region of interest (ROI) based quantitative measurements of CT attenuation were performed in the inferior vena cava (IVC), portal vein and in four TIPS locations. Minimum, maximum and average Hounsfield unit (HU) values were used as absolute and relative quantitative features. We analyzed the features with univariate testing.
Results: Subjective scores identified in-TIPS thrombosis in contrast-enhanced scans with an accuracy of 0.667 – 0.833. Patients with in-TIPS thrombosis had significantly lower average (p < 0.001), minimum (p < 0.001) and maximum HU (p = 0.043) in contrast-enhanced images. The in-TIPS / IVC ratio in contrast-enhanced images was significantly lower in patients with in-TIPS thrombosis (p < 0.001). No significant differences were found for unenhanced images. Analyzing the visually most suspicious ROI with consecutive calculation of its ratio to the IVC, all patients with a ratio < 1 suffered from in-TIPS thrombosis (p < 0.001, sensitivity and specificity = 100%).
Conclusion: Quantitative analysis of abdominal CT scans facilitates the stratification of in-TIPS thrombosis. In contrast-enhanced scans, an in-TIPS / IVC ratio < 1 could non-invasively stratify all patients with in-TIPS thrombosis.