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Opinion statementPharmacogenomics is increasingly important to guide objective, safe, and effective individualised prescribing. Personalised prescribing has revolutionised treatments in the past decade, allowing clinicians to maximise drug efficacy and minimise adverse effects based on a person’s genetic profile. Opioids, the gold standard for cancer pain relief, are among the commonest medications prescribed in palliative care practice. This narrative review examines the literature surrounding opioid pharmacogenomics and its applicability to the palliative care cancer population. There is currently limited intersection between the fields of palliative care and pharmacogenomics, but growing evidence presents a need to build linkages between the two disciplines. Pharmacogenomic evidence guiding opioid prescribing is currently available for codeine and tramadol, which relates to CYP2D6 gene variants. However, these medications are prescribed less commonly for pain in palliative care. Research is accelerating with other opioids, where oxycodone (CYP2D6) and methadone (CYP2B6, ABCB1) already have moderate evidence of an association in terms of drug metabolism and downstream analgesic response and side effects. OPRM1 and COMT are receiving increasing attention and have implications for all opioids, with changes in opioid dosage requirements observed but they have not yet been studied widely enough to be considered clinically actionable. Current evidence indicates that incorporation of pharmacogenomic testing into opioid prescribing practice should focus on the CYP2D6 gene and its actionable variants. Although opioid pharmacogenomic tests are not widely used in clinical practice, the progressively reducing costs and rapid turnover means greater accessibility and affordability to patients, and thus, clinicians will be increasingly asked to provide guidance in this area. The upsurge in pharmacogenomic research will likely discover more actionable gene variants to expand international guidelines to impact opioid prescribing. This rapidly expanding area requires consideration and monitoring by clinicians in order for key findings with clinical implications to be accessible, meaningfully interpretable and communicated.

Background Recent reports suggested a different predictive value for TyG index compared to HOMA-IR in coronary artery calcification (CAC) and other atherosclerotic outcomes, despite that both indices are proposed as surrogate markers of insulin resistance. We hypothesized a key role for liver pathology as an explanation and therefore assessed the relationship among the two indices and the intrahepatic lipid content stratified by PNPLA3 rs738409 genotypes as a known non-alcoholic fatty liver disease (NAFLD) genetic risk. Methods Thirty-nine women from a prior GDM-genetic study were recalled with PNPLA3 rs738409 CC and GG genotypes for metabolic phenotyping and to assess hepatic triglyceride content (HTGC). 75 g OGTT was performed, fasting lipid, glucose, insulin levels and calculated insulin resistance indices (TyG and HOMA2-IR) were used. HTGC was measured by MR based methods. Mann–Whitney-U, χ2 and for the correlation analysis Spearman rank order tests were applied. Results The PNPLA3 rs738409 genotype had a significant effect on the direct correlation between the HOMA2-IR and TyG index: the correlation (R = 0.52, p = 0.0054) found in the CC group was completely abolished in those with the GG (NAFLD) risk genotype. In addition, the HOMA2-IR correlated with HTGC in the entire study population (R = 0.69, p CC R = 0.62, p = 0.0006, GG: R = 0.74, p = 0.0058). In contrast, the correlation between TyG index and HTGC was only significant in rs738409 CC genotype group (R = 0.42, p = 0.0284) but not in GG group. A similar pattern was observed in the correlation between TG and HTGC (CC: R = 0.41, p = 0.0335), when the components of the TyG index were separately assessed. Conclusions PNPLA3 rs738409 risk genotype completely decoupled the direct correlation between two surrogate markers of insulin resistance: TyG and HOMA2-IR confirming our hypothesis. The liver lipid content increased in parallel with the HOMA2-IR independent of genotype, in contrast to the TyG index where the risk genotype abolished the correlation. This phenomenon seems to be related to the nature of hepatic fat accumulation and to the different concepts establishing the two insulin resistance markers.

In this paper, we report on the utilization of micro-technology based tools to fight viral infections. Inspired by various hemoperfusion and immune-affinity capture systems, a blood virus depletion device has been developed that offers highly efficient capture and removal of the targeted virus from the circulation, thus decreasing virus load. Single-domain antibodies against the Wuhan (VHH-72) virus strain produced by recombinant DNA technology were immobilized on the surface of glass micro-beads, which were then utilized as stationary phase. For feasibility testing, the virus suspension was flown through the prototype immune-affinity device that captured the viruses and the filtered media left the column. The feasibility test of the proposed technology was performed in a Biosafety Level 4 classified laboratory using the Wuhan SARS-CoV-2 strain. The laboratory scale device actually captured 120,000 virus particles from the culture media circulation proving the feasibility of the suggested technology. This performance has an estimated capture ability of 15 million virus particles by using the therapeutic size column design, representing three times over-engineering with the assumption of 5 million genomic virus copies in an average viremic patient. Our results suggested that this new therapeutic virus capture device could significantly lower virus load thus preventing the development of more severe COVID-19 cases and consequently reducing mortality rate. Graphical Abstract

In recent years, multi-level modeling has become more and more popular. It is mainly due to the fact that multi-level modeling aims to reduce or even totally eliminate any accidental complexity inadvertently created as by-product in traditional model design. Moreover, besides reducing model complexity, multi-level modeling also improves on general comprehension of models. The key enablers of multi-level modeling are the concepts of clabjects and deep instantiation. The latter is often governed by the potency notion, of which many different interpretations and variations emerged over the years. However, there exist also some approaches that disregard the potency notion. Thus, multi-level modeling approaches tend to take advantage of different theoretical and practical backgrounds. In this paper, we propose a unifying framework, the Multi-Level Modeling Playground (MLMP), which is a validating modeling environment for multi-level modeling research. The MLMP environment is based on our multi-layer modeling framework (the Dynamic Multi-Layer Algebra), which provides useful mechanisms to validate different multi-level modeling constructs. Since beyond the structure also the well-formedness rules of the modeling constructs can be specified, our proposed MLMP environment delivers several practical benefits: i) well-formedness is always verified, ii) multi-level constructs can be experimented with independently of any concrete tool chains, and iii) relationships (i.e., correlations or exclusions) between different multi-level constructs can be easily investigated in practice. Also, the capability of the environment is demonstrated via complete examples inspired by state-of-the-art research literature.

In the endeavour to understand the causes and consequences of the variation in animal personality, a wide range of studies were carried out, utilising various aspects to make sense of this biological phenomenon. One such aspect integrated the study of physiological traits, investigating hypothesised physiological correlates of personality. Although many of such studies were carried out on vertebrates (predominantly on birds and mammals), studies using arthropods (mainly insects) as model organisms were also at the forefront of this area of research. In order to review the current state of knowledge on the relationship between personality and the most frequently studied physiological parameters in arthropods, we searched for scientific articles that investigated this relationship. In our review, we only included papers utilising a repeated-measures methodology to be conceptually and formally concordant with the study of animal personality. Based on our literature survey, metabolic rate, thermal physiology, immunophysiology, and endocrine regulation, as well as exogenous agents (such as toxins) were often identified as significant affectors shaping animal personality in arthropods. We found only weak support for state-dependence of personality when the state is approximated by singular elements (or effectors) of condition. We conclude that a more comprehensive integration of physiological parameters with condition may be required for a better understanding of state’s importance in animal personality. Also, a notable knowledge gap persists in arthropods regarding the association between metabolic rate and hormonal regulation, and their combined effects on personality. We discuss the findings published on the physiological correlates of animal personality in arthropods with the aim to summarise current knowledge, putting it into the context of current theory on the origin of animal personality.

Magnetic Resonance Imaging (MRI) provides a unique opportunity to investigate neural changes in healthy and clinical conditions. Its large inherent susceptibility to motion, however, often confounds the measurement. Approaches assessing, correcting, or preventing motion corruption of MRI measurements are under active development, and such efforts can greatly benefit from carefully controlled datasets. We present a unique dataset of structural brain MRI images collected from 148 healthy adults which includes both motion-free and motion-affected data acquired from the same participants. This matched dataset allows direct evaluation of motion artefacts, their impact on derived data, and testing approaches to correct for them. Our dataset further stands out by containing images with different levels of motion artefacts from the same participants, is enriched with expert scoring characterizing the image quality from a clinical point of view and is also complemented with standard image quality metrics obtained from MRIQC. The goal of the dataset is to raise awareness of the issue and provide a useful resource to assess and improve current motion correction approaches.

Background TCF7L2 rs7903146 and PNPLA3 rs738409 gene variants confer the strongest risk for type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD), respectively. Pancreatic triacylglycerol content (PTGC) was reported to have a role in T2DM development. We aimed to assess the correlation between PTGC and hepatic triacylglycerol content (HTGC) stratified by PNPLA3 rs738409 genotype and subsequently interactions between PTGC and gene variants associated with β-cell dysfunction (TCF7L2, WFS1) and visceral adiposity (11ΒHSD1) on β-cell function were also tested. Methods PTGC and HTGC were assessed using MR in a post-hoc analysis of a genotype-based (PNPLA3 rs738409) recall study of 39 (lipid- and glucose lowering) drug-naïve women. Oral glucose tolerance test, HbA1c, insulin indices, anthropometric data were evaluated. The effect of minor allele carrying of TCF7L2 (rs7903146); WFS1 (rs1801214) and 11ΒHSD1 (rs4844880) variants in combination with PTGC was studied on surrogate markers of β-cell function. We used Spearman’s rank-order, Mann-Whitney-U tests, and linear regression models. Results PTGC and HTGC values were correlated after stratification by the rs738409 variant (only in CC genotype group R = 0.67, p = 10− 4). PTGC and HbA1c values correlated in the entire study population (R = 0.58, p = 10− 4). Insulin resistance, sensitivity and disposition indices were correlated with PTGC (HOMA2-IR: R = 0.42, p = 0.008; TyG: R = 0.38, p = 0.018; Matsuda: R= − 0.48, p = 0.002; DIbasal: R=−0.33, p = 0.039; ISSI-2: R=−0.35, p = 0.028). Surrogate markers of β-cell function (HOMA2-B, AUCinsulin/AUCglucose) correlated significantly with PTGC in subjects with the following genotypes rs7903146: CC R = 0.51, p = 0.022; rs18001214: CT + CC R = 0.55, p = 0.013; rs4844880: TA + AA R = 0.56, p = 0.016. The strongest interactions were found between PTGC and TCF7L2 rs7903146 effect on HOMA2-B (p = 0.001) and AUCinsulin/AUCglucose (p = 0.013). Conclusions The PNPLA3 rs738409 genotype has a major effect on the correlation between PTGC and HTGC. Furthermore we first report the combined effect of PTGC and individual risk gene variants of TCF7L2, WFS1 and 11ΒHSD1 on β-cell dysfunction. The correlation between pancreatic lipid accumulation and HbA1c also indicates an important role for the latter pathology.

Some filoviruses can be transmitted to humans by zoonotic spillover events from their natural host and filovirus outbreaks have occured with increasing frequency in the last years. The filovirus Lloviu virus (LLOV), was identified in 2002 in Schreiber’s bats (Miniopterus schreibersii) in Spain and was subsequently detected in bats in Hungary. Here we isolate infectious LLOV from the blood of a live sampled Schreiber’s bat in Hungary. The isolate is subsequently sequenced and cultured in the Miniopterus sp. kidney cell line SuBK12-08. It is furthermore able to infect monkey and human cells, suggesting that LLOV might have spillover potential. A multi-year surveillance of LLOV in bats in Hungary detects LLOV RNA in both deceased and live animals as well as in coupled ectoparasites from the families Nycteribiidae and Ixodidae. This correlates with LLOV seropositivity in sampled Schreiber’s bats. Our data support the role of bats, specifically Miniopterus schreibersii as hosts for LLOV in Europe. We suggest that bat-associated parasites might play a role in the natural ecology of filoviruses in temperate climate regions compared to filoviruses in the tropics.

The Scoliosis Research Society Outcomes Questionnaire (SRS-22) is a health-related quality-of-life (HRQL) tool for scoliosis patients. Since no equivalent questionnaire exists for spondylolysis patients, we characterized patient-reported scores in pediatric spondylolysis patients using the SRS-22, and compared these scores to previously published values for age-matched controls and patients with pre-operative adolescent idiopathic scoliosis (AIS). A single-institution cross-sectional observational study was performed using SRS-22 data from spondylolysis patients aged 12–18 years. Mean SRS-22 domain scores were compared to the existing literature values for adolescent control and AIS cohorts via unpaired Student t tests (α = 0.05) and against minimal clinically important differences (MCIDs). Thirty-five patients met inclusion criteria. Mean (± SD) spondylolysis patients’ scores met the MCID across all domains except Mental Health ( $$\alpha$$ = 0.05). Spondylolysis patient scores for Pain, Function, and Self-Image were significantly lower (p

In an effort to characterize differently aged bourbons and to determine whether bourbons could be “fingerprinted” by their chemical compositions, we used Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) to characterize 2 distinct sets of bourbon samples. The first set of bourbons were prepared using the same mash bill but were aged differently (unaged (0 years), 2 years, 4 years, and 6 years) in oak barrels. The results showed an increase in the number of chemical compounds present as the bourbon ages. Most of the large changes in chemical composition occur in the first 2 years of aging. We also analyzed single barrel bourbons, which were produced identically but maturated in different, adjacent barrels, and the results suggested that significant differences exist among these samples. These results suggest that “fingerprinting” of different bourbons for authentication purposes may be complicated and that careful analyses, coupled with more comprehensive identification of chemical compounds in bourbons, are needed.

Lake Balaton, the largest lake in Central Europe, underwent severe eutrophication from the 1960s to the 1990s, due to phosphorus loadings from external anthropogenic sources. The subsequent and complex eutrophication control and lake restoration program resulted in a significant decrease in the external phosphorus loading to the lake. Consequently, Lake Balaton has been returning to its former meso-eutrophic character. In this paper, we explore the long-term dynamics of chlorophyll a (Chl a) concentration, a proxy for phytoplankton biomass, and zooplankton biomass in Lake Balaton during its re-oligotrophication period from 2001 to 2017, and attempt to draw some conclusions on the subsequent changes in the fish stock. We found a proportional decrease in zooplankton and phytoplankton biomasses at moderate phytoplankton levels. However, below a certain phytoplankton concentration (−1 Chl a), the decrease in phytoplankton biomass was not coupled with a further decline in zooplankton biomass because the fraction of small phytoplankton, edible for zooplankton, showed a much smaller decrease in biomass compared with large non-edible phytoplankton. Thus, improvements in water quality (i.e., reduced nutrient loading), partly via concomitant changes in the phytoplankton size distribution, did not cause a large difference in the fish stock in this shallow lake.

Occurrence of the smallest phototrophic microorganisms (photoautotrophic picoplankton, APP) in Lake Balaton was discovered in the early 1980s. This triggered a series of systematic studies on APP and resulted in the setting of a unique long-term picoplankton dataset. In this review, we intend to summarize the obtained results and to give a new insight on APP ecology and diversity in Lake Balaton. According to the results, APP dynamics depends on trophic state, temperature, nutrient, and light availability, as well as grazing pressure. APP abundance in Lake Balaton decreased to a low level (1–2 × 105 cells mL−1) as a consequence of decreasing nutrient supply (oligotrophication) during the past more than two decades, and followed a characteristic seasonal dynamics with higher abundance values from spring to autumn than in winter. Concomitantly, however, the APP contribution to both phytoplankton biomass and primary production increased (up to 70% and 40–50%, respectively) during oligotrophication. Regarding annual pattern, picocyanobacteria are dominant from spring to autumn, while in winter, picoeukaryotes are the most abundant, most likely due to the different light and temperature optima of these groups. Within picocyanobacteria, single cells and microcolonies were both observed with mid-summer dominance of the latter which correlated well with the density of cladocerans. Community-level chromatic adaptation (i.e., dominance of phycoerythrin- or phycocyanin-rich forms) of planktonic picocyanobacteria was also found as a function of underwater light quality. Sequence analysis studies of APP in Lake Balaton revealed that both picocyanobacteria and picoeukaryotes represent a diverse and dynamic community consisting several freshwater genotypes (picocyanobacteria: Synechococcus, Cyanobium; picoeukaryotes: Choricystis, Stichococcus, Mychonastes, Nannochloris, and Nannochloropsis).

The global impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is significant in terms of public health effects and its long-term socio-economic implications. Among all social groups, the elderly is by far the most affected age group regarding morbidity and mortality. In multiple countries spanning several continents, there are an increasing number of reports referencing the novel coronavirus disease-2019 (COVID-19) spread among nursing homes. These areas are now recognized as potent hotspots regarding the pandemic, which one considers with special regard. Herein, we present currently available data of fatal COVID-19 cases throughout Hungary, along with the analysis of the co-morbidity network. We also report on viral genomic data originating from a nursing home resident. The genomic data was used for viral haplotype network analysis. We emphasize the urgent need for public health authorities to focus on nursing homes and residential service units worldwide, especially in the care of the elderly and infirmed. Our results further emphasize the recent statement released by the World Health Organization (WHO) regarding the vulnerability among seniors and especially the high risk of COVID-19 emergence throughout nursing and social homes.

Systemic administration of cholinergic antagonist scopolamine (SCO) is a widely used model to induce experimental cognitive impairment during preclinical drug testing of putative procognitive compounds. This model, however, has limited predictive validity partly due to its peripheral side-effects, therefore objective neuroimaging measures would greatly enhance its translational value. To this end, we administered SCO and peripherally acting butylscopolamine (BSCO) in preclinical functional MRI (fMRI, 9.4T) studies and measured their effects on whisker stimulation induced fMRI activation in Wistar rats. Beside the commonly used gradient echo echo-planar imaging (GE EPI) an arterial spin labeling method was also used to elucidate the vasculature-related properties of the BOLD-response. To account for anesthesia-effects, in two separate experiments we used isoflurane and combined (isoflurane + i.p. dexmedetomidine) anesthesia. In the second experiment with GE EPI and spin echo (SE) EPI sequences the effect of donepezil (DON) was also examined. In isoflurane anesthesia with GE EPI, SCO decreased the evoked BOLD response in the barrel cortex (BC), while BSCO increased it in the anterior cingulate cortex. In the combined anesthesia SCO decreased the activation in the BC as well as in the inferior colliculus (IC) while BSCO reduced the response merely in the IC. Our results revealed that SCO attenuated the evoked BOLD activation in the BC as a probable central effect in both experiments while its other detected actions depended on the type of anesthesia or dose and the given fMRI sequences.

Background Inflammatory bowel diseases (IBD) are a group of chronic and recurrent gastrointestinal disorders that are difficult to control. Recently, a new IBD therapy based on the targeting of the endogenous opioid system has been proposed. Consequently, due to the fact that endogenous enkephalins have an anti-inflammatory effect, we aimed at investigating the degradation of serum enkephalin (Met- and Leu-enkephalin) in patients with IBD. Methods Enkephalin degradation in serum of patients with IBD was characterized using mass spectrometry methods. Calculated half-life (T 1/2 ) of enkephalins were compared and correlated with the disease type and gender of the patients. Additionally, statistical analysis was used to examine the dynamics of changes in terms of inhibition of enkephalins degradation within research groups. Results Our research indicates that the degree of enkephalins degradation depends on the gender of the patients. The difference is most evident for the rate of Met-enkephalin degradation between men (mean T 1/2 = 13.61 min) and women (mean T 1/2 = 21.84 min) with Crohn’s disease (CD). Conclusions The most significant alternation of enkephalins degradation in serum samples of IBD patients, compared to control group, were observed in both Crohn’s disease and ulcerative colitis (UC) female patients. We suggest that the differences observed between the genders in IBD patients may be explained by regulation of enkephalinases activity by estradiol.

In this study the temporal trends of common vole’s active burrow index in alfalfa fields were evaluated. The investigation was conducted in southern Hungary after an outbreak of common vole in 2014, during the growing population phase within two consecutive years. The average number of active burrows in 2017 was about 5 times higher than in 2016. In all sampling sites the temporal trends of active burrow index showed exponential increasing with 24% (2016) and 100% (2017) growing rate.

Type 2 diabetes mellitus (T2DM) is one of the most common multifactorial diseases and several membrane transporters are involved in its development, complications and treatment. We have recently developed a flow-cytometry assay panel for the quantitative determination of red cell membrane protein levels with potential relevance in diseases. Here we report a detailed phenotypic analysis of a medium scale, clinically based study on the expression of T2DM-related membrane proteins, the GLUT1, GLUT3, MCT1, URAT1, ABCA1, ABCG2 and the PMCA4 transporters in erythrocytes. By comparing age-matched control subjects and three groups of T2DM patients (recently diagnosed, successfully managed, and patients with disease-related complications), we found significant differences in the membrane expression levels of the transporters in these groups. This is a first detailed analysis of T2DM related alterations in erythrocyte membrane transporter protein levels, and the results suggest significant changes in some of the transporter expression levels in various patient groups. By performing a further, more detailed analysis of the clinical and molecular biology parameters, these data may serve as a basis of establishing new, personalized diagnostic markers helping the prevention and treatment of type 2 diabetes.