The 2021 plan for hospital care centralization in Poland - When politics overwhelms the policy process.

The health system in Poland is characterized by oversized hospital infrastructure, with simultaneous deficits in the ambulatory and long-term care sectors. The main challenges of the hospital sector involve i.a. weak stewardship and fragmented governance with a concurrent problem of persistent hospital debts as well as huge workforce deficits. The objective of this paper is to present the government's 2021 plan for hospital care centralization. The reform project aimed i.a. at improving hospital service coordination by implementing a professional and centralized system for hospital sector supervision and effective restructuration processes. The proposed regulation project focused on three major issues: (1) adjusting the existing hospital network towards better concentration of specialized services; (2) launching an independent central agency responsible for monitoring public hospital financial standing as well as initiating and/or managing hospitals restructuration processes; and (3) introducing a formal certification of hospital managers competencies. The reform plans were developed in a relatively short time frame, with a top-down approach and strongly pushed towards the adoption in 2022. Many of the health system stakeholders were strongly opposed to the project which, in connection with new challenges faced by the health system in 2022 (the economic crisis) led the reform suspension. At the same time, a new restructuration and debt relief programme for public hospitals was announced.

A Social Network Analysis of Tweets Related to Mandatory COVID-19 Vaccination in Poland.

Poland's efforts to combat COVID-19 were hindered by endemic vaccination hesitancy and the prevalence of opponents to pandemic restrictions. In this environment, the policy of a COVID-19 vaccination mandate faces strong resistance in the public debate. Exploring the discourse around this resistance could help uncover the motives and develop an understanding of vaccination hesitancy in Poland. This paper aims to conduct a social network analysis and content analysis of Twitter discussions around the intention of the Polish Ministry of Health to introduce mandatory vaccinations for COVID-19. Twitter was chosen as a platform to study because of the critical role it played during the global health crisis. Twitter data were retrieved from 26 July to 9 December 2021 through the API v2 for Academic Research, and analysed using NodeXL and Gephi. When conducting social network analysis, nodes were ranked by their betweenness centrality. Clustering analysis with the Clauset-Newman-Moore algorithm revealed two important groups of users: advocates and opponents of mandatory vaccination. The temporal trends of tweets, the most used hashtags, the sentiment expressed in the most popular tweets, and correlations with epidemiological data were also studied. The results reveal a substantial degree of polarisation, a high intensity of the discussion, and a high degree of involvement of Twitter users. Vaccination mandate advocates were consistently more numerous, but less engaged and less mobilised to "preach" their own stances. Vaccination mandate opponents were vocal and more mobilised to participate: either as original authors or as information diffusers. Our research leads to the conclusion that systematic monitoring of the public debate on vaccines is essential not only in counteracting misinformation, but also in crafting evidence-based as well as emotionally motivating narratives.

Poland: Health System Review.

This analysis of the Polish health system reviews recent developments in organization and governance, health financing, health care provision, health reforms and health system performance. In late 2017, the Polish government committed to increase the share of public expenditures on health to 6% of GDP by 2024. If the GDP continues to grow in the years to come, this will present an opportunity to tackle mounting health challenges such as socioeconomic inequalities in health, high rates of obesity, rising burden of mental disorders and population ageing that put strain on health care resources. It is also an opportunity to tackle certain longstanding imbalances in the health sector, including overreliance on acute hospital care compared with other types of care, including ambulatory care and long-term care; shortages of human resources; the negligible role of health promotion and disease prevention vis-a-vis curative care; and poor financial situation in the hospital sector. Finally, the additional resources are much needed to implement important ongoing reforms, including the reform of primary care. The resources have to be spent wisely and waste should be minimized. The introduction, in 2016, of a special system (IOWISZ) of assessing investments in the health sector that require public financing (including from the EU funds) as well as the work undertaken by the Polish health technology assessment (HTA) agency (AOTMiT), which evaluates health technologies and publicly-financed health policy programmes as well as sets prices of goods and services, should help ensure that these goals are achieved. Recent reforms, such as the ongoing reform of primary care that seeks to improve coordination of care and the introduction of the hospital network, go in the right direction; however, a number of longstanding unresolved problems, such as hospital indebtedness, need to be tackled.

Poland: health system review

This analysis of the Polish health system reviews recent developments in organization and governance, health financing, health care provision, health reforms and health system performance. In late 2017, the Polish governmentcommitted to increase the share of public expenditures on health to 6% of GDP by 2024. If the GDP continues to grow in the years to come, this will present an opportunity to tackle mounting health challenges such as socioeconomicinequalities in health, high rates of obesity, rising burden of mental disorders and population ageing that put strain on health care resources. It is also an opportunity to tackle certain longstanding imbalances in the health sector, including overreliance on acute hospital care compared with other types of care, including ambulatory care and long-term care; shortages of human resources; the negligible role of health promotion and disease prevention vis-à-vis curative care; and poor financial situation in the hospital sector.Finally, the additional resources are much needed to implement important ongoing reforms, including the reform of primary care. The resources have to be spent wisely and waste should be minimized.The introduction, in 2016, of a special system (IOWISZ) of assessing investments in the health sector that require public financing (including from the EU funds) as well as the work undertaken by the Polish health technology assessment (HTA) agency (AOTMiT), which evaluates health technologies and publicly financed health policy programmes as well as sets prices of goods and services, should help ensure that these goals are achieved. Recent reforms, such as the ongoing reform of primary care that seeks to improvecoordination of care and the introduction of the hospital network, go in the right direction; however, a number of longstanding unresolved problems, such as hospital indebtedness, need to be tackled.

Combining Structural Aggregation Propensity and Stability Predictions To Redesign Protein Solubility.

The aggregation propensity of each particular protein seems to be shaped by evolution according to its natural abundance in the cell. The production and downstream processing of recombinant polypeptides implies attaining concentrations that are orders of magnitude above their natural levels, often resulting in their aggregation; a phenomenon that precludes the marketing of many globular proteins for biomedical or biotechnological applications. Therefore, there is a huge interest in methods aimed to increase the proteins solubility above their natural limits. Here, we demonstrate that an updated version of our AGGRESCAN 3D structural aggregation predictor, that now takes into account protein stability, allows for designing mutations at specific positions in the structure that improve the solubility of proteins without compromising their conformation. Using this approach, we have designed a highly soluble variant of the green fluorescent protein and a human single-domain VH antibody displaying significantly reduced aggregation propensity. Overall, our data indicate that the solubility of unrelated proteins can be easily tuned by in silico-designed nondestabilizing amino acid changes at their surfaces.

Predicting Real-Valued Protein Residue Fluctuation Using FlexPred.

The conventional view of a protein structure as static provides only a limited picture. There is increasing evidence that protein dynamics are often vital to protein function including interaction with partners such as other proteins, nucleic acids, and small molecules. Considering flexibility is also important in applications such as computational protein docking and protein design. While residue flexibility is partially indicated by experimental measures such as the B-factor from X-ray crystallography and ensemble fluctuation from nuclear magnetic resonance (NMR) spectroscopy as well as computational molecular dynamics (MD) simulation, these techniques are resource-intensive. In this chapter, we describe the web server and stand-alone version of FlexPred, which rapidly predicts absolute per-residue fluctuation from a three-dimensional protein structure. On a set of 592 nonredundant structures, comparing the fluctuations predicted by FlexPred to the observed fluctuations in MD simulations showed an average correlation coefficient of 0.669 and an average root mean square error of 1.07 Å. FlexPred is available at http://kiharalab.org/flexPred/ .

Coarse-Grained Simulations of Membrane Insertion and Folding of Small Helical Proteins Using the CABS Model.

The CABS coarse-grained model is a well-established tool for modeling globular proteins (predicting their structure, dynamics, and interactions). Here we introduce an extension of the CABS representation and force field (CABS-membrane) to the modeling of the effect of the biological membrane environment on the structure of membrane proteins. We validate the CABS-membrane model in folding simulations of 10 short helical membrane proteins not using any knowledge about their structure. The simulations start from random protein conformations placed outside the membrane environment and allow for full flexibility of the modeled proteins during their spontaneous insertion into the membrane. In the resulting trajectories, we have found models close to the experimental membrane structures. We also attempted to select the correctly folded models using simple filtering followed by structural clustering combined with reconstruction to the all-atom representation and all-atom scoring. The CABS-membrane model is a promising approach for further development toward modeling of large protein-membrane systems.

Institutional analysis of health promotion for older people in Europe - concept and research tool.

BACKGROUND: European societies are ageing rapidly and thus health promotion for older people (HP4OP) is becoming an increasingly relevant issue. Crucial here is not only the clinical aspect of health promotion but also its organisational and institutional dimension. The latter has been relatively neglected in research on HP4OP. This issue is addressed in this study, constituting a part of the EU project ProHealth65+, engaging ten member countries. This paper is based on two intertwining research goals: (1) exploring which institutions/organisations are performing HP4OP activities in selected European countries (including sectors involved, performed roles of these institutions, organisation of those activities); (2) developing an institutional approach to HP4OP. Thus, the paper provides a description of the analytical tools for further research in this area. METHODS: The mentioned aims were addressed through the mutual use of two complementary methods: (a) a literature review of scientific and grey literature; and (b) questionnaire survey with selected expert respondents from 10 European countries. The expert respondents, selected by the project's collaborating partners, were asked to fill in a custom designed questionnaire concerning HP4OP institutional aspects. RESULTS: The literature review provided an overview of the organisational arrangements in different HP4OP initiatives. It also enabled the development of functional institutional definitions of health promotion, health promotion activities and interventions, as well as an institutional definition adequate to the health promotion context. The distinctions between sectors were also clarified. The elaborated questionnaires provided in-depth information on countries specifically indicating the key sectors involved in HP4OP in those selected countries. These are: health care, regional/local authorities, NGO's/voluntary institutions. The questionnaire and literature review both resulted in the indication of a significant level of cross-sectorial cooperation in HP4OP. CONCLUSIONS: The inclusion of the institutional analysis within the study of HP4OP provides a valuable opportunity to analyse, in a systematic way, good practices in this respect, also in terms of institutional arrangements. A failure to address this aspect in policymaking might potentially cause organisational failure even in evidence-based programmes. This paper frames the perception of this problem.

Implementation of the cross-border healthcare directive in Poland: How not to encourage patients to seek care abroad?

In October 2014, after over 12 months of delay, Poland finally implemented directive 2011/24/EU on the application of patients' rights in cross-border healthcare. The implementing legislation in the area of cost reimbursement and prior authorization is very restrictive. The goal is to either defer the public payer's expenses into the future or to discourage patients from seeking care abroad or from seeking care altogether. The Polish government and the Ministry of Health, the key stakeholders in the implementation process, seemed to overlook the potential monetary benefits that the implementation of the directive could bring, for example, by promoting Poland as a destination for health tourism. Other stakeholders, such as patients and healthcare providers, had no real influence on the policy process. So far, the number of applications for planned treatment abroad has been very low and the majority of them were actually turned down as they did not meet the formal requirements. This number is likely to remain low in the future as accessing such care is cumbersome and not affordable for many patients. Overall, while the directive does not aim to encourage patients to seek cross-border healthcare, the current national regulations in Poland do not seem to facilitate access to cross-border healthcare, which is the main goal of the directive.

Ensemble-based evaluation for protein structure models.

MOTIVATION: Comparing protein tertiary structures is a fundamental procedure in structural biology and protein bioinformatics. Structure comparison is important particularly for evaluating computational protein structure models. Most of the model structure evaluation methods perform rigid body superimposition of a structure model to its crystal structure and measure the difference of the corresponding residue or atom positions between them. However, these methods neglect intrinsic flexibility of proteins by treating the native structure as a rigid molecule. Because different parts of proteins have different levels of flexibility, for example, exposed loop regions are usually more flexible than the core region of a protein structure, disagreement of a model to the native needs to be evaluated differently depending on the flexibility of residues in a protein. RESULTS: We propose a score named FlexScore for comparing protein structures that consider flexibility of each residue in the native state of proteins. Flexibility information may be extracted from experiments such as NMR or molecular dynamics simulation. FlexScore considers an ensemble of conformations of a protein described as a multivariate Gaussian distribution of atomic displacements and compares a query computational model with the ensemble. We compare FlexScore with other commonly used structure similarity scores over various examples. FlexScore agrees with experts' intuitive assessment of computational models and provides information of practical usefulness of models. AVAILABILITY AND IMPLEMENTATION: https://bitbucket.org/mjamroz/flexscore CONTACT: dkihara@purdue.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

CABS-dock web server for the flexible docking of peptides to proteins without prior knowledge of the binding site.

Protein-peptide interactions play a key role in cell functions. Their structural characterization, though challenging, is important for the discovery of new drugs. The CABS-dock web server provides an interface for modeling protein-peptide interactions using a highly efficient protocol for the flexible docking of peptides to proteins. While other docking algorithms require pre-defined localization of the binding site, CABS-dock does not require such knowledge. Given a protein receptor structure and a peptide sequence (and starting from random conformations and positions of the peptide), CABS-dock performs simulation search for the binding site allowing for full flexibility of the peptide and small fluctuations of the receptor backbone. This protocol was extensively tested over the largest dataset of non-redundant protein-peptide interactions available to date (including bound and unbound docking cases). For over 80% of bound and unbound dataset cases, we obtained models with high or medium accuracy (sufficient for practical applications). Additionally, as optional features, CABS-dock can exclude user-selected binding modes from docking search or to increase the level of flexibility for chosen receptor fragments. CABS-dock is freely available as a web server at http://biocomp.chem.uw.edu.pl/CABSdock.

Facilitation of the PED analysis of large molecules by using global coordinates.

Global coordinates have been found to be useful in the potential energy distribution (PED) analyses of the following large molecules: [13]-acene and [33]-helicene. The global coordinate is defined based on much distanced fragments of the analysed molecule, whereas so far, the coordinates used in the analysis were based on stretchings, bendings, or torsions of the adjacent atoms. It has been shown that the PED analyses performed using the global coordinate and the classical ones can lead to exactly the same PED contributions. The global coordinates may significantly improve the facility of the analysis of the vibrational spectra of large molecules.

AGGRESCAN3D (A3D): server for prediction of aggregation properties of protein structures.

Protein aggregation underlies an increasing number of disorders and constitutes a major bottleneck in the development of therapeutic proteins. Our present understanding on the molecular determinants of protein aggregation has crystalized in a series of predictive algorithms to identify aggregation-prone sites. A majority of these methods rely only on sequence. Therefore, they find difficulties to predict the aggregation properties of folded globular proteins, where aggregation-prone sites are often not contiguous in sequence or buried inside the native structure. The AGGRESCAN3D (A3D) server overcomes these limitations by taking into account the protein structure and the experimental aggregation propensity scale from the well-established AGGRESCAN method. Using the A3D server, the identified aggregation-prone residues can be virtually mutated to design variants with increased solubility, or to test the impact of pathogenic mutations. Additionally, A3D server enables to take into account the dynamic fluctuations of protein structure in solution, which may influence aggregation propensity. This is possible in A3D Dynamic Mode that exploits the CABS-flex approach for the fast simulations of flexibility of globular proteins. The A3D server can be accessed at http://biocomp.chem.uw.edu.pl/A3D/.

The first attempt to create a national strategy for reducing waiting times in Poland: will it succeed?

The waiting lists package, proposed in March 2014, is the first attempt to create a national strategy to reduce waiting times for specialist care in Poland. The policy proposes a number of measures directed at primary, specialist ambulatory and hospital care with the goal of shifting patients to the lowest possible level of care. Initially, it has been welcomed by the patients and there has been, so far, no strong opposition against the reform from other stakeholders. However, this may be because there is some disbelief that the policy would actually be implemented (due to limited funding available for its implementation) and because some of the proposed changes are vague and have yet to be clarified. One stakeholder group that may obstruct the implementation of the reform, if they are not satisfied with the final shape of the proposed measures, is the primary care doctors. They are directly affected by the reform and enjoy a relatively strong bargaining position compared to other groups of medical professionals. Thus, the future of the reform remains uncertain.

KnotProt: a database of proteins with knots and slipknots.

The protein topology database KnotProt, http://knotprot.cent.uw.edu.pl/, collects information about protein structures with open polypeptide chains forming knots or slipknots. The knotting complexity of the cataloged proteins is presented in the form of a matrix diagram that shows users the knot type of the entire polypeptide chain and of each of its subchains. The pattern visible in the matrix gives the knotting fingerprint of a given protein and permits users to determine, for example, the minimal length of the knotted regions (knot's core size) or the depth of a knot, i.e. how many amino acids can be removed from either end of the cataloged protein structure before converting it from a knot to a different type of knot. In addition, the database presents extensive information about the biological functions, families and fold types of proteins with non-trivial knotting. As an additional feature, the KnotProt database enables users to submit protein or polymer chains and generate their knotting fingerprints.

Structure prediction of the second extracellular loop in G-protein-coupled receptors.

G-protein-coupled receptors (GPCRs) play key roles in living organisms. Therefore, it is important to determine their functional structures. The second extracellular loop (ECL2) is a functionally important region of GPCRs, which poses significant challenge for computational structure prediction methods. In this work, we evaluated CABS, a well-established protein modeling tool for predicting ECL2 structure in 13 GPCRs. The ECL2s (with between 13 and 34 residues) are predicted in an environment of other extracellular loops being fully flexible and the transmembrane domain fixed in its x-ray conformation. The modeling procedure used theoretical predictions of ECL2 secondary structure and experimental constraints on disulfide bridges. Our approach yielded ensembles of low-energy conformers and the most populated conformers that contained models close to the available x-ray structures. The level of similarity between the predicted models and x-ray structures is comparable to that of other state-of-the-art computational methods. Our results extend other studies by including newly crystallized GPCRs.

CABS-flex predictions of protein flexibility compared with NMR ensembles.

MOTIVATION: Identification of flexible regions of protein structures is important for understanding of their biological functions. Recently, we have developed a fast approach for predicting protein structure fluctuations from a single protein model: the CABS-flex. CABS-flex was shown to be an efficient alternative to conventional all-atom molecular dynamics (MD). In this work, we evaluate CABS-flex and MD predictions by comparison with protein structural variations within NMR ensembles. RESULTS: Based on a benchmark set of 140 proteins, we show that the relative fluctuations of protein residues obtained from CABS-flex are well correlated to those of NMR ensembles. On average, this correlation is stronger than that between MD and NMR ensembles. In conclusion, CABS-flex is useful and complementary to MD in predicting protein regions that undergo conformational changes as well as the extent of such changes. AVAILABILITY AND IMPLEMENTATION: The CABS-flex is freely available to all users at http://biocomp.chem.uw.edu.pl/CABSflex. CONTACT: sekmi@chem.uw.edu.pl SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Protocols for efficient simulations of long-time protein dynamics using coarse-grained CABS model.

Coarse-grained (CG) modeling is a well-acknowledged simulation approach for getting insight into long-time scale protein folding events at reasonable computational cost. Depending on the design of a CG model, the simulation protocols vary from highly case-specific-requiring user-defined assumptions about the folding scenario-to more sophisticated blind prediction methods for which only a protein sequence is required. Here we describe the framework protocol for the simulations of long-term dynamics of globular proteins, with the use of the CABS CG protein model and sequence data. The simulations can start from a random or a selected (e.g., native) structure. The described protocol has been validated using experimental data for protein folding model systems-the prediction results agreed well with the experimental results.