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Jerzy Soja,1,2 Karolina Górka,1,2 Iwona Gross-Sondej,1,2 Bogdan Jakieła,2 Sławomir Mikrut,3 Krzysztof Okoń,4 Adam Ćmiel,5 Piotr Sadowski,4 Wojciech Szczeklik,6 Anna Andrychiewicz,7 Tomasz Stachura,1,2 Grażyna Bochenek,1,2 Stanisława Bazan-Socha,2 Krzysztof Sładek1,2 1Department of Pulmonology and Allergology, University Hospital, Kraków, Poland; 2 2nd Department of Internal Medicine, Jagiellonian University Medical College, Kraków, Poland; 3Faculty of Mining, Surveying and Environmental Engineering, AGH University of Science and Technology, Kraków, Poland; 4Department of Pathology, Jagiellonian University Medical College, Kraków, Poland; 5Department of Applied Mathematics, AGH University of Science and Technology, Kraków, Poland; 6Centre for Intensive Care and Perioperative Medicine, Jagiellonian University Medical College, Kraków, Poland; 7Department of Endoscopy, University Hospital, Kraków, PolandCorrespondence: Jerzy Soja, Department of Internal Medicine, Faculty of Medicine, Jagiellonian University Medical College, Jakubowskiego 2, Krakow, 30-688, Poland, Email jerzy.soja@uj.edu.plBackground: Bronchial thermoplasty (BT) is an interventional endoscopic treatment for severe asthma leading to the clinical improvement, but morphologic changes of bronchial wall related to the procedure and predictors of a favorable response to BT remain uncertain. The aim of the study was to validate an endobronchial ultrasound (EBUS) in assessing the effectiveness of BT treatment.Methods: Patients with severe asthma who met the clinical criteria for BT were included. In all patients clinical data, ACT and AQLQ questionnaires, laboratory tests, pulmonary function tests and bronchoscopy with radial probe EBUS and bronchial biopsies were collected. BT was performed in patients with the thickest bronchial wall L2 layer representing ASM. These patients were evaluated before and after 12 months of follow-up. The relationship between baseline parameters and clinical response was explored.Results: Forty patients with severe asthma were enrolled to the study. All 11 patients qualified to BT successfully completed the 3 sessions of bronchoscopy. BT improved asthma control (P=0.006), quality of life (P=0.028) and decreased exacerbation rate (P=0.005). Eight of the 11 patients (72.7%) showed a clinically meaningful improvement. BT also led to a significant decrease in the thicknesses of bronchial wall layers in EBUS (L1 decreased from 0.183 to 0.173 mm, P=0.003; L2 from 0.207 to 0.185 mm, P = 0.003; and L3– 5 from 0.969 to 0.886 mm, P=0.003). Median ASM mass decreased by 61.8% (P=0.002). However, there was no association between baseline patient characteristics and the magnitude of clinical improvement after BT.Conclusion: BT was associated with a significant decrease in the thickness of the bronchial wall layers measured by EBUS including L2 layer representing ASM and ASM mass reduction in bronchial biopsy. EBUS can assess bronchial structural changes related to BT; however, it did not predict the favorable clinical response to therapy.Keywords: airway remodeling, airway smooth muscle, bronchial thermoplasty, bronchial wall layers, endobronchial ultrasound

We present a long-term analysis of the results of the Apollo butterfly Parnassius apollo recovery project in the Pieniny National Park, southern Poland, using a classical population ecology model. Six possible theoretical models of changes in population abundance were constructed and their predictions compared with current data. Models that did not take into account supplementation with captive-reared individuals provided the best fit to the population growth pattern during recovery. This was probably because of the introduction of captive-reared specimens to sites while habitat reconstruction was taking place. In addition, we provide data supporting the hypothesis that a significant reduction in the habitat's carrying capacity occurred during the restoration project, probably as a result of the population being over-supplemented with captive-reared individuals. Our analysis shows that for a recovery project to be successful, captive breeding and habitat restoration should be properly coordinated.

The naiads, large freshwater mussels (Unionida), have very long life spans, are large-bodied, and produce thousands to millions of larvae (glochidia) which typically must attach to host fish tissues to metamorphose into a juvenile mussel. Glochidia develop within a female's marsupial gill demibranch, thus their number is restricted by female size. However, larger mussels acquire more energy, which could be invested in either larger-sized glochidia, in a more glochidia, or a combination of both. The high level of host specialization seen in many naiads may constrain glochidial size and shape around a narrow optimum, while naiads that use a wide range of host fishes may be predicted to possess greater plasticity in glochidial morphology. In this paper, we investigated the relationship between maternal body size and progeny body size and shape, aided by modern digital microscopy. We analyzed the between- and within- species variation of glochidia size and shape relative to female size in four widespread species of European naiads: Anodonta anatina, Anodonta cygnea, Unio crassus and Unio tumidus. Whereas the total reproductive output is collinear with female body size, substantial differences between species in glochidia size were found within genus Anodonta, but not genus Unio where glochidial size is remarkably consistent. The glochidial shape, however, differed within both Unio and Anodonta. We interpret this constant within-species glochidial size in Unio as reflecting a constraint imposed by the likelihood of successful transmission onto and off from a narrow range of hosts, whereas their shape seems to be less constrained. The Anodonta species, inhabiting a wide spectrum of habitats and using more than twice the number of fish hosts than Unio spp., have larger glochidia with greater variation in size and shape. Our results suggest that measures of glochidial variability may also serve as an indicator of host specificity in other naiads.

This prospective, single-center study sought to assess to what extent there is interference between the hybrid technique of single-photon emission tomography-computed tomography with technetium99m-hexamethylpropyleneamine oxime-labeled leukocytes (99mTc-HMPAO-SPECT/CT) and antimicrobial therapy in patients with infective endocarditis (IE).During the years 2015-2019, we enrolled 205 consecutive adults with suspected IE, all underwent 99mTc-HMPAO-SPECT/CT. The study population was divided into those who had received antimicrobial therapy up to 30 days prior to 99mTc-HMPAO-SPECT/CT (group 1, n = 96) and those who had not (group 2, n = 109). Patients were prospectively observed for 12 ± 10 months. Group 1 presented higher positive predictive values (91.89% vs. 60.00%, = 0.001), and decreased negative predictive values (77.97% vs. 90.54%, P = 0.04). Patients treated with antimicrobial therapy displayed false-negative 99mTc-HMPAO-SPECT/CT results more often [odds ratio (OR), 4.63; 95% confidence interval (CI), 1.41-15.23, P = .01], particularly when intravenous (OR 5.37; 95% CI 1.73-16.62, P = .004), definite (OR 9.43; 95% CI 2.65-33.51, P = .001), and combination antibiotic regimens (OR 8.1; 95% CI 2.57-25.64, P = .001) had been administered.Prior antibiotic therapy affects 99mTc-HMPAO-SPECT/CT diagnostic properties. Patients treated with antimicrobial therapy display false-negative 99mTc-HMPAO-SPECT/CT results more often, especially if intravenous, definite, or combination regimens are administered.

Intracranial aneurysms (IAs) are persistent, localised dilatations of the arterial wall that are found in approximately 3% of the general population. The most severe complication of IAs is rupture, which results in devastating consequences such as subarachnoid haemorrhage and brain damage with serious neurological sequelae. Numerous studies have characterised the mechanisms underlying IA development and growth and identified a number of environmental modifiable (smoking, hypertension) and nonmodifiable risk factors (related to the histology of cerebral arteries and genetic factors) in its pathogenesis. Haemodynamic stress also likely plays a crucial role in the formation of IAs and is conditioned by the geometry and morphology of the vessel tree, but its role in the natural history of unruptured IAs remains poorly understood; it is believed that changes in blood flow might generate the haemodynamic forces that are responsible for damage to the vascular wall and vessel remodelling that lead to IA formation. This review summarises the most relevant data on the current theories on the formation of IAs, with particular emphasis on the roles of special conditions resulting from the microscopic anatomy of intracranial arteries, haemodynamic factors, bifurcation morphometry, inflammatory pathways, and the genetic factors involved in IA formation.

Terrestrial gastropods are keenly sensitive to changes in vegetation structure owing to their dependence on moisture. For this reason, low survivorship and recolonisation are to be expected after a fire. The fire described in this paper probably started as a result of the deliberate spring burning of vegetation that got out of control. Analysis of the data collected immediately after the fire does not reveal significant differences in the numbers of snails between habitats. This suggests that there are no refugia for this population: no vegetation-related refugium was confirmed. After the fire, snail numbers were found to have crashed, but the slight increase during the season could have been an indication of incipient recovery. Because the population of this species was consistently small, no differences in survivorship between habitats, regardless of their type, were discernible. The effects of the fire on this population in the River Nida Inland Delta were devastating: while it did survive the fire, its numbers fell sharply, by as much as two orders of magnitude.

A simple method is utilised to study and compare COVID-19 infection dynamics between countries based on curve fitting to publicly shared data of confirmed COVID-19 infections. The method was tested using data from 80 countries from 6 continents. We found that Johnson cumulative density functions (CDFs) were extremely well fitted to the data (R2 > 0.99) and that Johnson CDFs were much better fitted to the tails of the data than either the commonly used normal or lognormal CDFs. Fitted Johnson CDFs can be used to obtain basic parameters of the infection wave, such as the percentage of the population infected during an infection wave, the days of the start, peak and end of the infection wave, and the duration of the wave’s increase and decrease. These parameters can be easily interpreted biologically and used both for describing infection wave dynamics and in further statistical analysis. The usefulness of the parameters obtained was analysed with respect to the relation between the gross domestic product (GDP) per capita, the population density, the percentage of the population infected during an infection wave, the starting day and the duration of the infection wave in the 80 countries. We found that all the above parameters were significantly associated with GDP per capita, but only the percentage of the population infected was significantly associated with population density. If used with caution, this method has a limited ability to predict the future trajectory and parameters of an ongoing infection wave.

Recognizing, quantifying and visualizing associations between two variables is increasingly important. This paper investigates how a new function-valued measure of dependence, the quantile dependence function, can be used to construct tests for independence and to provide an easily interpretable diagnostic plot of existing departures from the null model. The dependence function is designed to detect general dependence structure between variables in quantiles of the joint distribution. It gives an insight into how the dependence structures changes in different parts of the joint distribution. We define new estimators of the dependence function, discuss some of their properties, and apply them to construct new tests of independence. Numerical evidence is given on the test's benefits against three recognized independence tests introduced in the previous years. In real-data analysis, we illustrate the use of our tests and the graphical presentation of the underlying dependence structure., Comment: 40 pages, 3 figures, 1 table

Background To date, there has been no reliable in vitro test to either diagnose or differentiate nonsteroidal anti‐inflammatory drug (NSAID)–exacerbated respiratory disease (N‐ERD). The aim of the present study was to develop and validate an artificial neural network (ANN) for the prediction of N‐ERD in patients with asthma. Methods This study used a prospective database of patients with N‐ERD (n = 121) and aspirin‐tolerant (n = 82) who underwent aspirin challenge from May 2014 to May 2018. Eighteen parameters, including clinical characteristics, inflammatory phenotypes based on sputum cells, as well as eicosanoid levels in induced sputum supernatant (ISS) and urine were extracted for the ANN. Results The validation sensitivity of ANN was 94.12% (80.32%‐99.28%), specificity was 73.08% (52.21%‐88.43%), and accuracy was 85.00% (77.43%‐92.90%) for the prediction of N‐ERD. The area under the receiver operating curve was 0.83 (0.71‐0.90). Conclusions The designed ANN model seems to have powerful prediction capabilities to provide diagnosis of N‐ERD. Although it cannot replace the gold‐standard aspirin challenge test, the implementation of the ANN might provide an added value for identification of patients with N‐ERD. External validation in a large cohort is needed to confirm our results., Artificial neural network based on a set of clinical and biochemical parameters is able to stratify N‐ERD patients among asthmatic population. The sensitivity of the present artificial neural network is 94.12% and specificity is 73.08% for the prediction of N‐ERD. Artificial neural network could become a screening tool and allow to quickly identify patients with a high suspicion of N‐ERD

Introduction: Lung cancer patients (LCP) require invasive evaluation of left adrenal glands (LAG) if distant metastases (M1b/1c) are suspected in CT or PET-CT. Only few studies showed utility of endosonography and particularly EUS-b-FNA as minimally invasive endoscopic method of LAG analysis. Material and Methods: A retrospective study of consecutive LCP was conducted in two pulmonology centers between January 2010 and December 2019. Records of complete endosonographic staging with use of single ultrasound bronchoscope or two scopes were overviewed. The analysis included cases of enlarged LAG (body size or limbs > 10 mm) examined and sampled by EUS-b-FNA or EUS-FNA. Results: 142 of 2596 LCP staged by complete endosonography (M: 88, F: 54 mean age 64.7) had enlarged LAG, which were biopsied by conventional EUS-FNA (52) and/or by EUS-b-FNA (90). Strong correlation with gland diameter (p < 0.001) was observed. The incidence of LAG metastases in analyzed group was 52.1% (74/142) and regarding histology: SCLC 76.9% (10/13), adenocarcinoma 66.7% (44/66), NSCLC 56.3% (9/16) and SCC 17.5% (7/40). A specificity and PPV for both methods were 100%. A sensitivity, accuracy and NPV for EUS-FNA were 91.7%, 96.2%, 93.3% and for EUS-b-FNA 88%, 93.3% and 87%, respectively and no significant differences for both methods were noted (p = 0.62, 0.44, 0.35). No severe complications afterall biopsies were observed. A six months clinical follow up included all negative LCP with enlarged LAG. Conclusions: After our study EUS-b-FNA seems to be a reasonable method of choice for LAG assesssment in LCP.

A class of discrete probability distributions contains distributions with limited support. A typical example is some variant of a Likert scale, with response mapped to either the $\{1, 2, \ldots, 5\}$ or $\{-3, -2, \ldots, 2, 3\}$ set. An interesting subclass of discrete distributions with finite support are distributions limited to two parameters and having no more than one change in probability monotonicity. The main contribution of this paper is to propose a family of distributions fitting the above description, which we call the Generalised Score Distribution (GSD) class. The proposed GSD class covers the whole set of possible mean and variances, for any fixed and finite support. Furthermore, the GSD class can be treated as an underdispersed continuation of a reparametrized beta-binomial distribution. The GSD class parameters are intuitive and can be easily estimated by the method of moments. We also offer a Maximum Likelihood Estimation (MLE) algorithm for the GSD class and evidence that the class properly describes response distributions coming from 24 Multimedia Quality Assessment experiments. At last, we show that the GSD class can be represented as a sum of dichotomous zero-one random variables, which points to an interesting interpretation of the class., All authors contributed equally. 21 pages, 15 figures

There is a great need to understand the impact of complex communities on the free-living parasite stages that are part of them. This task becomes more complex as nonnative species emerge, changing existing relationships and shaping new interactions in the community. A relevant question would be: Can the coexistence of nontarget snails with the target hosts contribute to trematodasis control? We used field and experimental approaches to investigate nonnative competitor-induced parasite dilution. During a three-year field study, we investigated digenean infection in Lymnaea stagnalis from eight Polish lakes inhabited or uninhabited by Potamopyrgus antipodarum. Additionally, we verified the presence of digenean infections in the populations of P. antipodarum. Moreover, we conducted an experimental infection of L. stagnalis with miracidia of Trichobilharzia szidati under increasing densities of P. antipodarum and aimed to infect P. antipodarum with them separately. The prevalence of avian schistosomes in lymnaeid snails was significantly higher in uninhabited lakes than in lakes inhabited by P. antipodarum. Our study indicates that waters with a higher density of invaders have a lower prevalence of avian schistosomes in lymnaeid hosts. The results of experimental studies confirmed that the presence of high densities of P. antipodarum reduces the probability of target host infection. Both field and experimental studies rule out the role of P. antipodarum as a source of avian schistosome cercariae. Here, a nonnative species was tested as a diluter, which in practice may be harmful to the local environment. This work is not a call for the introduction of nonnative species; it is intended to be a stimulus for researchers to continue searching for natural enemies of parasites because, as our results show, they exist. Finding natural enemies to the most dangerous species of human and animal parasites that will pose no threat to the local environment could be groundbreaking.

This paper present simple method to study and to compare the infection dynamics between countries based on curve fitting to the publicly shared data of COVID-19 confirmed infections reported by them. Presented method was tested using data from 80 countries from 6 regions. We found that Johnson Cumulative Distribution Functions (CDF) are extremely well fitted to the data (R2>0.99) and that Johnson CDF is much better fitted to the data at its tails than both commonly used Normal and Lognormal CDF. Fitted Johnson CDFs can be used to obtain basic parameters of the infection wave, such as the percentage of the population infected during the infection wave, day of the start, peak and the end of the infection wave, as well as the duration of the infections wave and the duration of the wave increase and decrease. These parameters may be easily biologically interpreted and used both in describing the infection wave dynamics and in further statistical analysis. The usefulness of the obtained parameters was demonstrated on two examples: the analysis of the relation of the Gross Domestic Product (GDP) per capita and the analysis of the population density on the percentage of the population infected during infection wave, the day of the start, and the duration of the infection wave in analyzed countries. We found that all of the abovementioned parameters were significantly dependent on the GDP per capita, while only the percentage of population infected was significantly dependent on the population density in analyzed countries. Also, if used with caution, presented method has some limited ability to predict the future trajectory and parameters of the ongoing infection wave.

Patients with resectable lung cancer require invasive evaluation of the enlarged left adrenal gland (LAG). Few studies showed the utility of endoscopic ultrasound using ultrasound bronchoscope (EUS‑B) in LAG assessment. Moreover, little is known on the combination of computed tomography (CT), positron emission tomography-computed tomography (PET‑CT), and EUS‑B for predicting left adrenal metastasis.In this retrospective cohort study performed from 2012 to 2019, patients with left adrenal enlargement were evaluated by CT, PET‑CT, and EUS‑B, followed by complete endoscopic mediastinal staging. The adrenal glands were sampled by EUS‑B-guided fine‑needle aspiration. Patients were followed for 6 months.During the staging of lung cancer in 2176 patients, 113 enlarged LAGs (5.19%) were biopsied. Malignancy was reported in 51 LAGs (45.13%). Endoscopic ultrasound upstaged 7 patients (6.2%) and downstaged 11 patients (9.37%) after false CT or PET‑CT findings. There were no biopsy‑related complications. Radiologic predictors of left adrenal metastases had the highest yield at the following cutoff points: Hounsfield units23, standardized uptake value4.2, and LAG size25 mm. Hypoechogenic LAGs with loss of sea‑gull shape on EUS‑B were associated with a 28.67‑fold higher likelihood of metastases. The sensitivity, specificity, accuracy, negative predictive value, and positive predictive value for all ultrasound predictors were 86.21%, 85.45%, 85.84%, 85.45%, and 86.21%, respectively. When combined with radiologic features, the respective values were 93.10%, 94.55%, 93.81%, 92.86%, and 94.74%.Hypoechogenicity and loss of sea‑gull shape on EUS‑B are the most reliable predictors of left adrenal metastasis. The combination of CT, PET‑CT, and EUS‑B improves the noninvasive diagnosis of left adrenal metastases in lung cancer patients.

Introduction Patients with resectable lung cancer require invasive evaluation of enlarged left adrenal gland (LAG). There are only few studies showing utility of endosonography with single ultrasound bronchoscope (EUS-b) in LAG assessment. Combination of CT, PET-CT and EUS-b and ultrasonographic predictors of malignancy (M1b/c) in LAG are not well known. Patients and methods A two center cohort retrospective study was performed from 2012 to 2019. Enlarged LAGs were evaluated by CT, PET-CT and EUS-b. Then, a complete endoscopic mediastinal staging was performed, enlarged LAGs were sampled by EUS-b-FNA. Patients were followed up for 6-months. Results During the diagnosis of 2176 staged LCP, 113 (5.19%) enlarged LAGs were biopsied. 51 (45.13%) were positive for malignancy, predominantly adenocarcinoma (46.9%). Endosonography up-staged 7 (6.2%) patients, and down-staged 11 (9.37%) after false CT or PET-CT findings. No complications were noted after any biopsies. Radiological predictors of LAG metastases had the highest yield if cut offs were set as follows: HU>23, SUV>4.2 and LAG size >25mm. Hypoechogenic LAGs with loss of sea-gull shape in EUS-b indicated 28.67 times bigger likelihood of metastases. The sensitivity, specificity, accuracy, NPV and PPV for all measured ultrasound predictors were: 86.21%, 85.45%, 85.84%, 85.45%, 86.21%, combined with radiological measurements: 93.10%, 94.55%, 93.81%, 92.86% and 94.74%, respectively. Conclusions Hypoechogenicity and loss of sea-gull shape in EUS-b are the most reliable predictors of malignancy in enlarged LAG. A combination of radiological assessment based on CT/PET-CT and EUS-b findings improves noninvasive diagnostics for LAG metastases in LCP.

Background Conclusions from studies evaluating vessel dimensions and their deviations from the values resulting from the principle of minimum work (PMW) on the formation of intracranial aneurysms (IAs) are still inconclusive. The aim of our study was the morphometric analysis of cerebral arterial bifurcations harbouring aneurysms. Methods The study comprised 147 patients with basilar artery (BA) and middle cerebral artery (MCA) aneurysms, and 106 patients constituting the control group. The following morphometric parameters were evaluated: the radii of vessels forming the bifurcation, the junction exponent, the values of the bifurcation angles (Φ1 and Φ2 angles between the parent vessel trunk axis and the larger or smaller branches, respectively; α angle, total bifurcation angle) and the difference between the predicted optimal and observed branch angles. Results The analysed parameters for internal carotid artery (ICA) bifurcations were not significantly different among the groups. MCA and BA bifurcation angles and the radii of the parent MCA and BA vessels with aneurysms were significantly higher compared to the control group. The differences between the predicted optimal and observed branch angles were significantly higher for BA and MCA bifurcations with aneurysms compared to the control group. The mean junction exponent for bifurcations in the circle of Willis (i.e., ICA and BA bifurcations, respectively) and MCA bifurcations with aneurysms was significantly lower than the theoretical optimum and not significantly different among the groups. In a multilevel multivariate logistic regression analysis, the branch angles and the radius from the parent vessel were significant independent predictors of the presence of IAs. The ROC analysis indicated that the α angle was the best performer in discriminating between aneurysmal and non-aneurysmal bifurcations. Conclusions The dimensions of the arteries forming the circle of Willis do not follow the PMW. The deviation from optimum bifurcation geometry for bifurcations beyond the circle of Willis (particularly a wider radius of the parent artery and a wider total bifurcation angle) may lead to the formation of IAs. Further studies are warranted to investigate the significance of vessel dimensions and the bifurcation angle on the magnitude of the shear stress in the walls of arterial bifurcations.

In this paper we reproduce experimental results presented in our earlier work titled "Describing Subjective Experiment Consistency by $p$-Value P-P Plot" that was presented in the course of the 28th ACM International Conference on Multimedia. The paper aims at verifying the soundness of our prior results and helping others understand our software framework. We present artifacts that help reproduce tables, figures and all the data derived from raw subjective responses that were included in our earlier work. Using the artifacts we show that our results are reproducible. We invite everyone to use our software framework for subjective responses analyses going beyond reproducibility efforts., Comment: Please refer to the original publication: https://dl.acm.org/doi/10.1145/3474085.3477935 Related paper: https://dl.acm.org/doi/abs/10.1145/3394171.3413749 or arXiv:2009.13372

Background Conclusions from studies evaluating vessel dimensions and their deviations from values resulting from the principle of minimum work (PMW) on the formation of intracranial aneurysms (IAs) are still inconclusive. Our study aimed to perform a morphometric analysis of cerebral arterial bifurcations harbouring aneurysms. Methods The study comprised 147 patients with basilar artery (BA) and middle cerebral artery (MCA) aneurysms and 106 patients constituting the control group. The following morphometric parameters were evaluated: the radii of vessels forming the bifurcation, the junction exponent, the values of the bifurcation angles (Φ1 and Φ2 angles between the parent vessel trunk axis and the larger or smaller branches, respectively; α angle, the total bifurcation angle) and the difference between the predicted optimal and observed branch angles. Results The analysed parameters for internal carotid artery (ICA) bifurcations were not significantly different among the groups. The MCA and BA bifurcation angles and the radii of the parent MCA and BA vessels with aneurysms were significantly higher than those of the control group. The differences between the predicted optimal and observed branch angles were significantly higher for BA and MCA bifurcations with aneurysms compared to the control group. The mean junction exponent for bifurcations in the circle of Willis (i.e., ICA and BA bifurcations, respectively) and MCA bifurcations with aneurysms was significantly lower than the theoretical optimum and did not significantly differ among the groups. In a multilevel multivariate logistic regression analysis, the branch angles and the radius from the parent vessel were significant independent predictors of the presence of an IA. The ROC analysis indicated that the α angle was the best performer in discriminating between aneurysmal and nonaneurysmal bifurcations. Conclusions The dimensions of the arteries forming the circle of Willis do not follow the PMW. Deviation from the energetically optimum geometry for bifurcations beyond the circle of Willis (particularly, a larger radius of the parent artery and a wider total bifurcation angle) may lead to the formation of IAs. Further studies are warranted to investigate the significance of vessel dimensions and the bifurcation angle on the magnitude of shear stress in the walls of arterial bifurcations.

This study analyzed morphometric and hemodynamic parameters of aneurysmal and non-aneurysmal middle cerebral artery (MCA) bifurcations and their relationship with optimal values derived from the principle of minimum work (PMW). The study included 96 patients with MCA aneurysm and 94 controls. Aneurysm patients presented with significantly higher values of the radius and cross-sectional area of the MCA trunk, angle between the post-bifurcation branches (α angle) and volume flow rate (VFR) and had significantly lower values of junction exponent and pulsatility index than the controls. The Φ1 and Φ2 angles (angles between the MCA trunk axis and the larger and smaller branch, respectively) and α angle in all groups were significantly larger than the optimal PMW-derived angles. The most important independent predictors of MCA aneurysm were junction exponent (odds ratio, OR = 0.42), α angle (OR = 1.07) and VFR (OR = 2.36). Development of cerebral aneurysms might be an independent effect of abnormalities in hemodynamic and morphometric factors. The risk of aneurysm increased proportionally to the deviation of morphometric parameters of the bifurcation from their optimal PMW-derived values. The role of bifurcation angle in aneurysm development needs to be explained in future research as the values of this parameter in both aneurysm patients and non-aneurysmal controls in were scattered considerably around the PMW-derived optimum.

This article reports a large‐scale die‐off of approximately one‐third of the unionid mussels inhabiting a shallow, naturally eutrophic, floodplain lake (Zalew Pinczowski), which took place within the space of just a few days. Mortality was the highest in Pseudanodonta complanata (81%), followed by Unio pictorum (58%), Anodonta cygnea (26%), Unio tumidus (15%), and Anodonta anatina (5%). It was significantly related to mussel size (age) only in A. cygnea, with the mortality rate higher in smaller (young) mussels. Pseudanodonta complanata was already the rarest species in the lake, and the number of survivors decreased to such an extent as to trigger a possible Allee effect. The most likely cause of the die‐off was a motor‐boating incident that had directly preceded the die‐off. Analysis of the water samples collected just after the die‐off revealed an extremely high concentration of phosphate (up to 0.5 mg dm⁻³) and nitrite (up to 0.06 mg dm⁻³). We suggest that the boat movements must have disturbed the lake sediments, thereby disrupting the mussels' physiology and causing mass mortality. The high sensitivity of P. complanata to environmental stress suggests that it may be an effective umbrella species for the protection of co‐occurring mussel species in eutrophic lakes.

The life cycle of unionids is characterized by a obligatory period of larval parasitism on a fish host, any disturbance of which might cause a large-scale decline in the mussel population. Because the probability of fish infestation is so important, we modelled what would happen to a population (in terms of population growth and probability of extinction), if the same number of glochidia were released in one or more separate spawning events, by a hypothetical mussel population living in conditions differing in the probability of fish infestation (a “neutral” scenario, a “good” one and three variants of a “bad” one). The single brood strategy was the best in the “good” scenario. However, when the frequency of unfavourable stochastic events increased (“bad” scenarios), all strategies led to population decline, the single brood strategy being the worst. In “good” and moderately “bad” conditions the double brood strategy performed better than the other multiple brood strategies, but as infestation conditions deteriorated, a greater number of spawning events ensured a slower population decline and longer persistence. Our model can facilitate a better understanding of this problem and set up a framework for further tests in other unionid species and their environmental conditions.

Background Aspirin desensitization followed by daily aspirin use is an effective treatment for aspirin-exacerbated respiratory disease (AERD). Objective To assess clinical features as well as genetic, immune, cytological, and biochemical biomarkers that might predict a positive response to high-dose aspirin therapy in AERD. Methods We enrolled 34 AERD patients with severe asthma who underwent aspirin desensitization followed by 52-week aspirin treatment (650 mg/d). At baseline and at 52 weeks, clinical assessment was performed; phenotypes based on induced sputum cells were identified; eicosanoid, cytokine, and chemokine levels in induced sputum supernatant were determined; and induced sputum expression of 94 genes was assessed. Responders to high-dose aspirin were defined as patients with improvement in 5-item Asthma Control Questionnaire score, 22-item Sino-Nasal Outcome Test (SNOT-22) score, and forced expiratory volume in 1 second at 52 weeks. Results There were 28 responders (82%). Positive baseline predictors of response included female sex (P=0.002), higher SNOT-22 score (P=0.03), higher blood eosinophil count (P=0.01), lower neutrophil percentage in induced sputum (P=0.003), higher expression of the hydroxyprostaglandin dehydrogenase gene, HPGD (P=0.004), and lower expression of the proteoglycan 2 gene, PRG2 (P=0.01). The best prediction model included Asthma Control Test and SNOT-22 scores, blood eosinophils, and total serum immunoglobulin E. Responders showed a marked decrease in sputum eosinophils but no changes in eicosanoid levels. Conclusions and clinical relevance Female sex, high blood eosinophil count, low sputum neutrophil percentage, severe nasal symptoms, high HPGD expression, and low PRG2 expression may predict a positive response to long-term high-dose aspirin therapy in patients with AERD.

This study aimed to analyze the effect of bilateral mediastinal lymphadenectomy (BML) on survival of non-small cell lung cancer (NSCLC) patients. The hypothesis was: BML offers survival benefit as compared with SLND.A randomized clinical trial including stage I-IIIA NSCLC patients was performed. All patients underwent anatomical lung resection. BML was performed during the same operation via additional cervical incision (BML group). In the control group, standard lymphadenectomy (systematic lymph node dissection, SLND) was performed.In total, 102 patients were randomized. No significant difference was found in the type of lung resection, blood loss, chest tube output, air leak, pain, and complications (p = 0.188-0.959). In the BML group, the operative time was longer (318 vs 223 min, p 0.001) with higher number of removed N2 nodes (24 vs 14, p 0.001). The 5-year survival rate was 72 % in the BML group vs 53 % in the SLND group (OR 2.33, 95 % CI 0.95-5.69, p = 0.062). Separate comparisons for different lobar locations of the tumor have shown no significant difference in survival for the right lung tumors and left upper lobe tumors. For the left lower lobe tumors, survival time was longer in the BML group (p = 0.021), and the 5-year survival rate was 90.9 % vs 37.5 %, (OR 16.66, 95 % CI 1.36-204.04, p = 0.0277).In patients with NSCLC located in the left lower lobe, bilateral lymph node dissection may be associated with better survival. The invasiveness of BML is comparable to that of SLND.

Despite the high taxonomic diversity, wide distribution and important ecosystem functions of snails, their ecology remains obscure, and this can hamper their conservation. Overwintering in the studied population of Vertigo moulinsiana is effective enough to allow the majority of it to survive. The population dynamics of V. moulinsiana is specific, where the summer boom in a suboptimal habitat covering a small area (wet patches of sweet grass) can determine the snail's range over much larger areas. Our results suggest that humidity could have been the major factor governing population increase. The summer boom is caused by juveniles appearing in very large numbers during this period, thus the peak height is mostly influenced by the considerable susceptibility of juveniles and eggs to desiccation. The limiting influence of humidity is evident in the unequal spatial distribution of individuals: the wetter the substrate, the greater the abundance of snails. As a consequence, the boom may be spatially regulated and only occurs in wet habitats, even though the snail actually occupies a much larger area. Our results indicate that this V. moulinsiana population does not follow typical models constructed for vertebrates or other animals with high dispersal abilities, like the Ideal Free Distribution (IFD) model, and requires a specific approach. Its specific spatiotemporal pattern should be taken into account during monitoring surveys and conservation actions.

There are phenomena that cannot be measured without subjective testing. However, subjective testing is a complex issue with many influencing factors. These interplay to yield either precise or incorrect results. Researchers require a tool to classify results of subjective experiment as either consistent or inconsistent. This is necessary in order to decide whether to treat the gathered scores as quality ground truth data. Knowing if subjective scores can be trusted is key to drawing valid conclusions and building functional tools based on those scores (e.g., algorithms assessing the perceived quality of multimedia materials). We provide a tool to classify subjective experiment (and all its results) as either consistent or inconsistent. Additionally, the tool identifies stimuli having irregular score distribution. The approach is based on treating subjective scores as a random variable coming from the discrete Generalized Score Distribution (GSD). The GSD, in combination with a bootstrapped G-test of goodness-of-fit, allows to construct $p$-value P-P plot that visualizes experiment's consistency. The tool safeguards researchers from using inconsistent subjective data. In this way, it makes sure that conclusions they draw and tools they build are more precise and trustworthy. The proposed approach works in line with expectations drawn solely on experiment design descriptions of 21 real-life multimedia quality subjective experiments., Comment: 11 pages, 3 figures. Accepted to 28th ACM International Conference on Multimedia (MM '20). For associated data sets, source codes and documentation, see https://github.com/Qub3k/subjective-exp-consistency-check

Introduction: Needle biopsy of enlarged lymph nodes is accepted method for the diagnosis of sarcoidosis, but there is still place for investigating the optimal endosonography guided approach. Objectives: The aim of this study was to assess the relative diagnostic yield of the combination (CUS-b-NA) of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound fine-needle aspiration (EUS-b-FNA) but also a role of cell blocks (CB) and lymph node localization for the diagnosis of sarcoidosis. Methods: This was a prospective, multicenter study including consecutive patients with clinical diagnosis of stage I or II sarcoidosis. CUS-b-NA with smears and CB technique was performed within all group. If sarcoidosis was not confirmed invasive diagnostics was scheduled and 6 months follow-up was continued. Results: Since Nov 2017 to Sep 2019 fifty patients were enrolled for the final analysis. The overall sensitivity of EBUS-TBNA, EUS-b-FNA and CUS-b-NA was 76.6%, 70.2% and 91.7%, respectively. There were no significant differences between EBUS-TBNA and EUS-b-FNA (P=0.52) but CUS-b-NA had significantly higher yield (P=0.005 and P=0.001). No serious complications after all biopsies were observed. Adding CB to smear technique (P=0.008) and biopsy of the subcarinal lymph nodes (P=0.001) significantly increases the diagnostic yield. Conclusions: A diagnostic yield of CUS-b-NA is higher than endosonographic techniques alone in stage I and II of sarcoidosis. The preparation of cytological material including CB technique and the biopsy of subcarinal lymph node station increases diagnostic efficacy.

BackgroundANCA associated vasculitides (AAV) are a heterogeneous group of rare diseases with unknown etiology. In the most severe cases AAV can lead to end stage kidney disease or death. Since etiology and detailed pathogenesis of AAV is not known, the prediction of disease outcome at the time of diagnosis is challenging. Thus, there is an unmet need for tools to identify patients with the highest risk of organ dysfunction and death and apply effective personalized therapy.ObjectivesThe aim of this work was to search for tools allowing outcome prediction at the time of AAV diagnosis. Early identification of patients, who are likely to develop severe organ dysfunction and death is crucial for appropriate disease management. Induction therapy in AAV relays on immunosuppressive drugs characterized by a high risk of severe side effects. Thus, their administration in high doses should be limited only to individual patients with an especially high risk of poor outcome.MethodsWe applied here two methods of identification of AAV patients at risk to develop severe organ dysfunction and death. First method (latent class analysis [LCA] followed by logistic regression) was meant to subcategorize patients and identify a subgroup at subjects at risk to develop chronic renal replacement therapy (CRRT) and death [1]. Second, served to assess individual poor outcome risk and was based on two machine learning (ML) classifiers, which by analyzing clinical information allow assigning computed risk for CRRT and death in an individual patient allowing to identify subjects with high risk of chronic replacement therapy (CRRT) and death. We have evaluated a number of different approaches to build the ML models (including logistic regression, support vector machines, random forests), and obtained the best results for the gradient boosting algorithm implementation called LightGBM [2]. It works as a sequential ensemble of so-called weak learners (decision trees) finally combined in a one prediction model. Both analyses were based on retrospective data from Polish national AAV registry (POLVAS) [3] including presently 565 GPA and 135 MPA patients. The parameters used were: demographic data and laboratory parameters, specific organ involvement, ANCA specificity and time between selected stages of the disease.ResultsLCA used on our AAV cohort identified four subphenotypes – three already previously proposed - and revealing a fourth clinically relevant subphenotype. This new subphenotype includes only GPA patients, usually diagnosed at a younger age as compared to other groups, and characterized by multiorgan involvement, high relapse rate, relatively high risk of death, but no end-stage kidney disease. Logistic regression analysis revealed significant differences in the risk of CRRT and death between those subphenotypes – the worst prognosis was found for severe MPO AAV. On the other hand, using ML approach we obtained an individual prediction model with potentially relevant clinical performance (ROC AUC of 0.85 for CRRT and 0.82 for death).ConclusionWe consider results obtained encouraging. They may offer a new insight into AAV course based on data available at diagnosis, and create a solid foundation for potential clinical decision support system.References[1]Wójcik K et al. Subphenotypes of ANCA-associated vasculitis identified by latent class analysis. Clin Exp Rheumatol. 2021 Mar-Apr;39 Suppl 129(2):62-68.[2]Ke G, at al. Light GBM: A Highly Efficient Gradient Boosting Decision Tree. Advances in Neural Information Processing Systems 30 (NIPS 2017), pp. 3149-3157.[3]Wójcik K et al. Clinical characteristics of Polish patients with ANCA-associated vasculitides-retrospective analysis of POLVAS registry. Clin Rheumatol. 2019 Sep;38(9):2553-2563.AcknowledgementsThis work was supported by a grant from Polish National Science Center UMO-2018/31/B/NZ6/03898Disclosure of InterestsNone declared

Pathogens are one of the main forces driving the evolution and maintenance of the highly polymorphic genes of the vertebrate major histocompatibility complex (MHC). Although MHC proteins are crucial in pathogen recognition, it is still poorly understood how pathogen-mediated selection promotes and maintains MHC diversity, and especially so in host species with highly duplicated MHC genes. Sedge warblers (Acrocephalus schoenobaenus) have highly duplicated MHC genes, and using data from high-throughput MHC genotyping, we were able to investigate to what extent avian malaria parasites explain temporal MHC class I supertype fluctuations in a long-term study population. We investigated infection status and infection intensities of two different strains of Haemoproteus, that is avian malaria parasites that are known to have significant fitness consequences in sedge warblers. We found that prevalence of avian malaria in carriers of specific MHC class I supertypes was a significant predictor of their frequency changes between years. This finding suggests that avian malaria infections partly drive the temporal fluctuations of the MHC class I supertypes. Furthermore, we found that individuals with a large number of different supertypes had higher resistance to avian malaria, but there was no evidence for an optimal MHC class I diversity. Thus, the two studied malaria parasite strains appear to select for a high MHC class I supertype diversity. Such selection may explain the maintenance of the extremely high number of MHC class I gene copies in sedge warblers and possibly also in other passerines where avian malaria is a common disease.

Freshwater mussels of the order Unionida provide important ecosystem functions and services. Unfortunately, some previously widespread species are now seriously endangered. To restore the historical range of the population of Unio crassus in the Biala River, southern Poland, the species was reintroduced into a series of ‘stepping stones’ joining two remnant populations. During the first phase of the study, the relationships between the abundance of U. crassus, physical habitat, and water quality were studied to assess reintroduction potential. In general, chemical water quality improved upstream from the existing population, favouring the decision for reintroduction, whereas morphological variables worsened. Mussel abundance was correlated negatively with the elevation and slope of channel, organic matter contents, and pH (exceeding 8.0), but positively with silt presence, water conductivity, and concentrations of HCO3−, Ca2 +, and NO3−. During the second phase, adult individuals were introduced into one type of functional habitat—marginal channel sectors with still water and fine sediment. Despite the initial very high rate of reproduction in some parts of the upper reach of the river, the juveniles were ultimately recruited only in the lower part of the restored range, resulting in a very rapid change in recruitment at a channel slope of 1.8‰. Recruitment was positively related to silt content, conductivity, and Ca2 + and HCO3– ions, negatively to channel elevation and slope, and water pH. The host fish species showed no correlation with abiotic habitat features within the studied reach. These results imply that most of the habitat traits related to U. crassus occurrence depended on the river's longitudinal profile, not on the chemical water quality, and that final success of introduction should be evaluated after several years.

W artykule zaprezentowano zagadnienia związane z problematyką spoleczenstwa informacyjnego. Glownym celem artykulu jest analiza taksonomiczna uzytkowania Internetu w wojewodztwach Polski. Jako narzedzie analizy wykorzystano metody taksonomiczne.

In Poland, the Aesculapian snake, critically endangered at the edge of its European range, inhabits the lower parts of the Bieszczady Mts. in the SE of the country. This research, carried out between 2009 and 2014, included fieldwork in areas selected on the basis of historical literature data and the results of interviews. 51 breeding mounds were deployed at historical and potential sites of this snake’s occurrence on the forested area of 220,886 ha as a supportive tool for detecting these reptiles. The 371 records of the Aesculapian snake obtained are displayed on maps showing its historical distribution in two periods (1958-1989 and 1995-1998) for comparison. Most records were collected in the centre of the species’ range in the Bieszczady Mts. Most of the breeding mounds (17 out of 29) in this area were colonized by the snake, whereas only two sites were colonized in the outside. The results show that the Aesculapian snake’s range in the Bieszczady Mts has been shrinking. However, most current single records outside the species’ centre of occurrence are from localities close to its historical range; this suggests that relict populations may be surviving there. The proportion of records on the breeding mounds grew in consecutive years. This suggests that breeding mounds deployed near the snake’s existing localities may be a useful tool for monitoring endangered oviparous snakes and their active conservation.

Background Recent work suggests that gene duplications may play an important role in the evolution of immunity genes. Passerine birds, and in particular Sylvioidea warblers, have highly duplicated major histocompatibility complex (MHC) genes, which are key in immunity, compared to other vertebrates. However, reasons for this high MHC gene copy number are yet unclear. High-throughput sequencing (HTS) allows MHC genotyping even in individuals with extremely duplicated genes. This HTS data can reveal evidence of selection, which may help to unravel the putative functions of different gene copies, i.e. neofunctionalization. We performed exhaustive genotyping of MHC class I in a Sylvioidea warbler, the sedge warbler, Acrocephalus schoenobaenus, using the Illumina MiSeq technique on individuals from a wild study population. Results The MHC diversity in 863 genotyped individuals by far exceeds that of any other bird species described to date. A single individual could carry up to 65 different alleles, a large proportion of which are expressed (transcribed). The MHC alleles were of three different lengths differing in evidence of selection, diversity and divergence within our study population. Alleles without any deletions and alleles containing a 6 bp deletion showed characteristics of classical MHC genes, with evidence of multiple sites subject to positive selection and high sequence divergence. In contrast, alleles containing a 3 bp deletion had no sites subject to positive selection and had low divergence. Conclusions Our results suggest that sedge warbler MHC alleles that either have no deletion, or contain a 6 bp deletion, encode classical antigen presenting MHC molecules. In contrast, MHC alleles containing a 3 bp deletion may encode molecules with a different function. This study demonstrates that highly duplicated MHC genes can be characterised with HTS and that selection patterns can be useful for revealing neofunctionalization. Importantly, our results highlight the need to consider the putative function of different MHC genes in future studies of MHC in relation to disease resistance and fitness. Electronic supplementary material The online version of this article (doi:10.1186/s12862-017-0997-9) contains supplementary material, which is available to authorized users.

Artykułu jest poświęcony problemowi sposobu tłumaczenia mentalnych ram modalnych z języka rosyjskiego na język polski. Wykorzystane w artykule przykłady pochodzą z powieści rosyjskiej pisarki Ludmiły Pietruszewskiej Номер Один, или В садах других возможностей i jej polskiego tłumaczenia. Przedmiotem szczególnej uwagi była analiza ram modalnych, których przekład na język polski wpłynął na ich semantyczno-strukturalną charakterystykę.

Introduction Needle biopsy of enlarged lymph nodes is an accepted method for the diagnostic workup of sarcoidosis, but the optimal endosonography‑guided approach is yet to be determined. Objectives The aim of our study was to assess the relative diagnostic yield of combined ultrasound‑guided needle aspiration (CUS‑b‑NA), which includes endobronchial ultrasound‑guided transbronchial needle aspiration (EBUS‑TBNA) with endoscopic ultrasound fine‑needle aspiration (EUS‑b‑FNA), as well as the role of the cell block (CB) technique and lymph node localization in the diagnostic workup of sarcoidosis. Patients and methods This was a prospective multicenter study including consecutive patients with clinical suspicion of stage I or II sarcoidosis. CUS‑b‑NA with smears and CB technique were performed in the whole study group. If a biopsy result was not conclusive, an invasive diagnostic workup and a 6-month follow‑up were scheduled. Results Out of 77 screened patients, 54 signed written consent and 50 were enrolled for the final analysis. The overall sensitivity of EBUS‑TBNA, EUS‑b‑FNA, and CUS‑b‑NA was 76.6%, 70.2%, and 91.7%, respectively. There were no differences between EBUS‑TBNA and EUS‑b‑FNA (P = 0.52) but CUS‑b‑NA had a higher diagnostic yield (P = 0.005 and P = 0.001, respectively). Adding the CB method to smear technique (P = 0.008) and biopsy of the subcarinal lymph nodes increased the diagnostic yield (P = 0.001). Conclusions: The diagnostic yield of CUS‑b‑NA is higher than that of endosonographic techniques alone in the diagnostic workup of stage I and II sarcoidosis. The preparation of cytological material including CB and the choice of the subcarinal lymph node station for the biopsy increase the diagnostic efficacy.