Biomechanical Integrity Score of the Female Pelvic Floor for Stress Urinary Incontinence.

INTRODUCTION AND HYPOTHESIS: This study is aimed at developing and validating a new integral parameter, the Biomechanical Integrity score (BI-score) of the female pelvic floor for stress urinary incontinence conditions. METHODS: A total of 130 subjects were included in the observational cohort study; 70 subjects had normal pelvic floor conditions, and 60 subjects had stress urinary incontinence (SUI). A Vaginal Tactile Imager (VTI) was used to acquire and automatically calculate 52 biomechanical parameters for eight VTI test procedures (probe insertion, elevation, rotation, Valsalva maneuver, voluntary muscle contractions in two planes, relaxation, and reflex contraction). Statistical methods were applied (t test, correlation) to identify the VTI parameters sensitive to the pelvic SUI conditions. RESULTS: Twenty-seven parameters were identified as statistically sensitive to SUI development. They were subdivided into five groups to characterize tissue elasticity (group 1), pelvic support (group 2), pelvic muscle contraction (group 3), involuntary muscle relaxation (group 4), and pelvic muscle mobility (group 5). Every parameter was transformed to its standard deviation units using the dataset for normal pelvic conditions, similar to the T-score for bone density. Linear combinations with specified weights led to the composition of five component parameters for groups 1-5 and to the BI-score in standard deviation units. The p value for the BI-score has p = 4.0 × 10-28 for SUI versus normal conditions. CONCLUSIONS: Quantitative transformations of the pelvic tissues, support structures, and functions under diseased conditions may be studied with the SUI BI-score in future research and clinical applications.

Comparative Health Behaviour of Young People with Disabilities in Hungary: A Cross-Sectional Study.

The health status of Hungary's population is unfavorable, with significant differences in health indicators not only compared to the EU15 but also to the Visegrad countries. Unfavorable health indicators can be disproportionate and particularly affect vulnerable groups, such as people with disabilities. In this study, we set out to compare the health behavior of disabled youth and youth with typical development in Hungary. We also aimed to compare the health behavior of adolescents in the Visegrad countries. The eating habits of both groups of young people we examined are unfavorable. Adolescents with disabilities experience a significantly higher rate of school stress than children with typical development in Hungary. The prevalence of somatic complaints and parameters of poor mental well-being are significantly higher in Hungary than in the other Visegrad countries. The results indicate that additional interventions are needed in Hungary and that differentiated, professional health promotion is needed for young people with disabilities. The researchers recommend extending the study to disabled adolescents living in Visegrad countries, on the basis of which an injury-specific health promotion methodology could be developed with international interprofessional cooperation.

Freshwater fish scale database.

Scales of the ray finned fishes can be used for multiple purposes. Beside others by their specific structure and elemental composition they are usable for age determination and food-web researches. Additionally, just their presence, absence, shape, location, or numbers could provide a reliable taxonomic information. The fish scales show remarkable size variation also, which characteristics provide reliable information about the environmental needs of freshwater fish. But till now this information was not interpretable and comparable in the absence of a sufficiently large and detailed database. In this study we provide a database which can facilitate the further complex comparative studies. Our dataset consists of 2954 scale photos characterising 193 freshwater fish species. All photos have a uniquely identification code showing exactly which species the scale belongs to. In addition to the photos, our database includes a table showing the exact taxonomic classification of the studied species, the average body profile-index, and the relative scale size, as well as the ecological (flow and feeding habitat preferences) and life strategic characteristics (feeding and breeding guild memberships) of each species. The sampled species have diverse origin, covering five biogeographical regions. An average of five adults from each species were selected for sampling. Three-to-four scales were collected from the anterior part of the body between the dorsal fin and the lateral line. The removed scales were cleaned and prepared to microscope slides, and after this process they were photographed or scanned. Our database can be used for both research and educational purposes. A large number of scale photos assigned of species can be an opportunity to create an automatic species identification system. Moreover, the subjectivity in morphometric measurements can be eliminated by analysing the database with artificial intelligence.

Multiplexed serum biomarkers to discriminate nonviable and ectopic pregnancy.

OBJECTIVE: To evaluate combinations of candidate biomarkers to develop a multiplexed prediction model for identifying the viability and location of an early pregnancy. In this study, we assessed 24 biomarkers with multiple machine learning-based methodologies to assess if multiplexed biomarkers may improve the diagnosis of normal and abnormal early pregnancies. DESIGN: A nested case-control design evaluated the predictive ability and discrimination of biomarkers in patients at risk of early pregnancy failure in the first trimester to classify viability and location. SETTING: Three university hospitals. PATIENTS: A total of 218 individuals with pain and/or bleeding in early pregnancy: 75 had an ongoing intrauterine gestation; 68 had ectopic pregnancies (EPs); and 75 had miscarriages. INTERVENTIONS: Serum levels of 24 biomarkers were assessed in the same patients. Multiple machine learning-based methodologies to evaluate combinations of these top candidates to develop a multiplexed prediction model for the identification of a nonviable pregnancy (ongoing intrauterine pregnancy vs. miscarriage or EP) and an EP (EP vs. ongoing intrauterine pregnancy or miscarriage). MAIN OUTCOME MEASURES: The predicted classification using each model was compared with the actual diagnosis, and sensitivity, specificity, positive predictive value, negative predictive value, conclusive classification, and accuracy were calculated. RESULTS: Models using classification regression tree analysis using 3 (pregnancy-specific beta-1-glycoprotein 3 [PSG3], chorionic gonadotropin-alpha subunit, and pregnancy-associated plasma protein-A) biomarkers were able to predict a maximum sensitivity of 93.3% and a maximum specificity of 98.6%. The model with the highest accuracy was 97.4% (with 70.2% receiving classification). Models using an overlapping group of 3 (soluble fms-like tyrosine kinase-1, PSG3, and tissue factor pathway inhibitor 2) biomarkers achieved a maximum sensitivity of 98.5% and a maximum specificity of 95.3%. The model with the highest accuracy was 94.4% (with 65.6% receiving classification). When the models were used simultaneously, the conclusive classification increased to 72.7% with an accuracy of 95.9%. The predictive ability of the biomarkers in the random forest produced similar test characteristics when using 11 predictive biomarkers. CONCLUSION: We have demonstrated a pool of biomarkers from divergent biological pathways that can be used to classify individuals with potential early pregnancy loss. The biomarkers choriogonadotropin alpha, pregnancy-associated plasma protein-A, and PSG3 can be used to predict viability, and soluble fms-like tyrosine kinase-1, tissue factor pathway inhibitor 2, and PSG3 can be used to predict pregnancy location.

An overlooked phenomenon: complex interactions of potential error sources on the quality of bacterial de novo genome assemblies.

BACKGROUND: Parameters adversely affecting the contiguity and accuracy of the assemblies from Illumina next-generation sequencing (NGS) are well described. However, past studies generally focused on their additive effects, overlooking their potential interactions possibly exacerbating one another's effects in a multiplicative manner. To investigate whether or not they act interactively on de novo genome assembly quality, we simulated sequencing data for 13 bacterial reference genomes, with varying levels of error rate, sequencing depth, PCR and optical duplicate ratios. RESULTS: We assessed the quality of assemblies from the simulated sequencing data with a number of contiguity and accuracy metrics, which we used to quantify both additive and multiplicative effects of the four parameters. We found that the tested parameters are engaged in complex interactions, exerting multiplicative, rather than additive, effects on assembly quality. Also, the ratio of non-repeated regions and GC% of the original genomes can shape how the four parameters affect assembly quality. CONCLUSIONS: We provide a framework for consideration in future studies using de novo genome assembly of bacterial genomes, e.g. in choosing the optimal sequencing depth, balancing between its positive effect on contiguity and negative effect on accuracy due to its interaction with error rate. Furthermore, the properties of the genomes to be sequenced also should be taken into account, as they might influence the effects of error sources themselves.

Evaluation of novel biomarkers for early pregnancy outcome prediction†.

OBJECTIVE: To assess performance and discriminatory capacity of commercially available enzyme-linked immunosorbent assays of biomarkers for predicting first trimester pregnancy outcome in a multi-center cohort. DESIGN: In a case-control study at three academic centers of women with pain and bleeding in early pregnancy, enzyme-linked immunosorbent assays of biomarkers were screened for assay performance. Performance was assessed via functional sensitivity, assay reportable range, recovery/linearity, and intra-assay precision (%Coefficient of Variation). Top candidates were analyzed for discriminatory capacity for viability and location among 210 women with tubal ectopic pregnancy, viable intrauterine pregnancy, or miscarriage. Assay discrimination was assessed by visual plots, area under the curve with 95% confidence intervals, and measures of central tendency with two-sample t-tests. RESULTS: Of 25 biomarkers evaluated, 22 demonstrated good or acceptable assay performance. Transgelin-2, oviductal glycoprotein, and integrin-linked kinase were rejected due to poor performance. The best biomarkers for discrimination of pregnancy location were pregnancy-specific beta-1-glycoprotein 9, pregnancy-specific beta-1-glycoprotein 1, insulin-like growth factor binding protein 1, kisspeptin (KISS1), pregnancy-specific beta-1-glycoprotein 3, and beta parvin (PARVB). The best biomarkers for discrimination of pregnancy viability were pregnancy-specific beta-1-glycoprotein 9, pregnancy-specific beta-1-glycoprotein 3, EH domain-containing protein 3, KISS1, WAP four-disulfide core domain protein 2 (HE4), quiescin sulfhydryl oxidase 2, and pregnancy-specific beta-1-glycoprotein 1. CONCLUSION: Performance of commercially available enzyme-linked immunosorbent assays was acceptable for a panel of novel biomarkers to predict early pregnancy outcome. Of these, six and seven candidates demonstrated good discriminatory capacity of pregnancy location and viability, respectively, when validated in a distinct external population. Four markers demonstrated good discrimination for both location and viability.

Zinc prevents vaginal candidiasis by inhibiting expression of an inflammatory fungal protein.

Candida causes an estimated half-billion cases of vulvovaginal candidiasis (VVC) every year. VVC is most commonly caused by Candida albicans, which, in this setting, triggers nonprotective neutrophil infiltration, aggressive local inflammation, and symptomatic disease. Despite its prevalence, little is known about the molecular mechanisms underpinning the immunopathology of this fungal infection. In this study, we describe the molecular determinant of VVC immunopathology and a potentially straightforward way to prevent disease. In response to zinc limitation, C. albicans releases a trace mineral binding molecule called Pra1 (pH-regulated antigen). Here, we show that the PRA1 gene is strongly up-regulated during vaginal infections and that its expression positively correlated with proinflammatory cytokine concentrations in women. Genetic deletion of PRA1 prevented vaginal inflammation in mice, and application of a zinc solution down-regulated expression of the gene and also blocked immunopathology. We also show that treatment of women suffering from recurrent VVC with a zinc gel prevented reinfections. We have therefore identified a key mediator of symptomatic VVC, giving us an opportunity to develop a range of preventative measures for combatting this disease.

Correlation between the female pelvic floor biomechanical parameters and the severity of stress urinary incontinence.

BACKGROUND: Stress urinary incontinence (SUI) is a common condition that requires proper evaluation to select a personalized therapy. Vaginal Tactile Imaging (VTI) is a novel method to assess the biomechanical parameters of the pelvic floor. METHODS: Women with SUI were enrolled in this cross-sectional study. Participants completed the Medical, Epidemiologic, and Social Aspects of Aging (MESA) questionnaire and the Patient Global Impression of Severity Question (PGI-S) and underwent a VTI examination. Based on the MESA and PGI-S questionnaires, participants were divided into mild, moderate, and severe SUI groups. Fifty-two biomechanical parameters of the pelvic floor were measured by VTI and compared between the groups (mild vs. moderate and severe). SUI Score and Index were calculated from the MESA questionnaire. Pearson correlation was used to determine the strength of association between selected VTI parameters and the MESA SUI Index and MESA SUI Score. RESULTS: Thirty-one women were enrolled into the study. Significant differences were observed in the VTI parameters 16, 22-24, 38, 39 when the difference between mild and severe subgroups of SUI based on the PGI-S score was examined. Parameter 16 refers to the maximum gradient at the perineal body, parameter 22-24 refers to the pressure response of the tissues behind the vaginal walls, and parameter 38, 39 refers the maximum pressure change and value on the right side at voluntary muscle contraction. VTI parameter 49, describing the displacement of the maximum pressure peak in the anterior compartment, showed a significant difference between the mild SUI and the moderate-severe SUI according to the MESA SUI score (mean ± SD 14.06 ± 5.16 vs. 7.54 ± 7.46, P = 0.04). The MESA SUI Index and SUI Score displayed a positive correlation concerning VTI parameters 4 (the maximum value of the posterior gradient) and 27 (the displacement of the maximum pressure peak in the anterior compartment) (VTI4 vs. MESA SUI Index r = 0.373, P = 0.039; VTI4 vs. MESA SUI Score r = 0.376, P = 0.037; VTI27 vs. MESA SUI Index r = 0.366, P = 0.043; VTI27 vs. MESA SUI Score r = 0.363, P = 0.044). CONCLUSIONS: Female pelvic floor biomechanical parameters, as measured by VTI, correlate significantly with the severity of SUI and may help guide therapeutic decisions.

Depletion of muscularis macrophages ameliorates inflammation-driven dysmotility in murine colitis model.

Previously, the presence of a blood-myenteric plexus barrier and its disruption was reported in experimentally induced colitis via a macrophage-dependent process. The aim of this study is to reveal how myenteric barrier disruption and subsequent neuronal injury affects gut motility in vivo in a murine colitis model. We induced colitis with dextran sulfate sodium (DSS), with the co-administration of liposome-encapsulated clodronate (L-clodronate) to simultaneously deplete blood monocytes contributing to macrophage infiltration in the inflamed muscularis of experimental mice. DSS-treated animals receiving concurrent L-clodronate injection showed significantly decreased blood monocyte numbers and colon muscularis macrophage (MM) density compared to DSS-treated control (DSS-vehicle). DSS-clodronate-treated mice exhibited significantly slower whole gut transit time than DSS-vehicle-treated animals and comparable to that of controls. Experiments with oral gavage-fed Evans-blue dye showed similar whole gut transit times in DSS-clodronate-treated mice as in control animals. Furthermore, qPCR-analysis and immunofluorescence on colon muscularis samples revealed that factors associated with neuroinflammation and neurodegeneration, including Bax1, Hdac4, IL-18, Casp8 and Hif1a are overexpressed after DSS-treatment, but not in the case of concurrent L-clodronate administration. Our findings highlight that MM-infiltration in the muscularis layer is responsible for colitis-associated dysmotility and enteric neuronal dysfunction along with the release of mediators associated with neurodegeneration in a murine experimental model.

Speedy bearings to slacked steering: Mapping the navigation patterns and motions of Viking voyages.

Viking sailors ruled the North Atlantic Ocean for about three hundred years. Their main sailing route was the 60° 21' 55'' latitude between Norway and Greenland. Although they did not have a magnetic compass, in sunshine they used a sun-compass to determine the geographical north (solar Viking navigation: SVN). It has been hypothesized that when the Sun was invisible, Viking navigators determined the direction of polarization of skylight with sunstones (dichroic/birefringent crystals), and then estimated the geographical north using the sun-compass (sky-polarimetric Viking navigation: SPVN). Many details of the hypothetical SPVN have been thoroughly revealed in psychophysical laboratory and planetarium experiments. Combining these results with measured celestial polarization patterns, the success of SPVN was obtained as functions of sailing, meteorological and navigation parameters (sunstone type, sailing date, navigation periodicity, night sailing, cloudiness conditions). What was so far lacking in this experimental and computational archeological approach is the study of the success of SVN and a combined navigation using solar cues in sunshine (SVN) and sky polarization at invisible Sun (SPVN), the latter being the most realistic method. In this work we determine the success of the sole SVN and the combined SVN-SPVN relative to the mere SPVN for three navigator types (determining the intended sailing direction with large, medium or small frequencies) at spring equinox and summer solstice, with and without night sailing. We found that to maximize the sailing success, navigators had to choose different navigation methods depending on the navigation frequency. Using sky polarization with very frequent navigation, resulted in the highest chance to survive a three-week voyage from Norway to Greenland.

Application of a Multiplex Platform to Identify Novel Biomarkers for Pregnancy Location and Viability.

Determining early pregnancy location and viability can be cumbersome, often requiring serial evaluations. This study aimed to identify novel biomarker candidates for pregnancy location and viability using a pseudodiscovery high-throughput technique. This was a case-control study among patients presenting for early pregnancy assessment, including ectopic pregnancies, early pregnancy losses, and viable intrauterine pregnancies. For pregnancy location, ectopic pregnancy was considered "case" and non-ectopic considered "control." For pregnancy viability, viable intrauterine pregnancy was considered "case" and early pregnancy loss + ectopic pregnancy were considered "control." Using Proximity Extension Assay technology from Olink Proteomics, serum levels of 1012 proteins were compared separately for pregnancy location and viability. Receiver operator characteristic curves were generated to determine a biomarker's discriminative abilities. Analysis included 13 ectopic pregnancies, 76 early pregnancy losses, and 27 viable intrauterine pregnancies. For pregnancy location, 18 markers had an area under the curve (AUC) ≥0.80, with three being expressed more in ectopic compared to non-ectopic pregnancies: thyrotropin subunit beta, carbonic anhydrase 3, and DEAD (Asp-Glu-Ala-Asp) box polypeptide 58. For pregnancy viability, two markers had an AUC ≥0.80: lutropin subunit beta and serpin B8. While some of the markers had previously been implicated in early pregnancy physiology, others were from pathways not previously explored. Using a high-throughput platform, a large number of proteins were screened as potential biomarkers for pregnancy location and viability, and twenty candidate biomarkers were identified. Further exploration of these proteins may facilitate validation as diagnostic tools for establishing early pregnancy diagnoses.

A randomized controlled pilot trial to assess the effectiveness of a specially formulated food supplement and pelvic floor muscle training in women with stress-predominant urinary incontinence.

BACKGROUND: Pelvic floor muscle training (PFMT) is the first-line treatment approach for stress urinary incontinence. Creatine and leucine have been shown to improve muscle function. Our aim was to assess the effectiveness of a food supplement and PFMT in women with stress-predominant urinary incontinence. METHODS: Women with stress-predominant urinary incontinence were randomized in 1:1 ratio to receive daily oral supplementation for six weeks with either a food supplement (treatment group) or placebo (control group). Both groups were instructed to perform standardized daily PFMT. The primary outcome was the Urogenital Distress Inventory Short Form (UDI-6) score. Secondary outcomes were the Incontinence Impact Questionnaire (IIQ-7) score, Patient's Global Impression of Severity (PGI-S), and Biomechanical Integrity score (BI-score) measured by Vaginal Tactile Imager. To have a power of 80% and a significance level of 5% to detect a decrease of 16 points in the UDI-6 score, a sample size of 32 was needed, with 16 patients in each arm of our trial. RESULTS: Sixteen women in the control group and sixteen in the treatment group completed the trial. Between-group analysis revealed no significant differences between the control and treatment group except for mean change (delta) in vaginal squeeze pressure [(cmH2O, mean ± SD), 5 ± 12 vs. 15 ± 15, P = 0.04] and mean change (delta) in PGI-S score [(mean ± SD), -0.2 ± 0.9 vs. -0.8 ± 0.8, P = 0.04]. Within-group analysis showed that UDI-6 and IIQ-7 scores improved significantly from baseline to six weeks in the treatment group but not in the control group [UDI-6 score (mean ± SD) 45 ± 21 vs. 29 ± 21, P = 0.02; 43 ± 18 vs. 33 ± 26, P = 0.22] [IIQ-7 score (mean ± SD) 50 ± 30 vs. 30 ± 21, P = 0.01; 48 ± 23 vs.40 ± 28, P = 0.36]. PGI-S scores only improved in the treatment group from baseline to six weeks after treatment [PGI-S score (mean ± SD) 3.1 ± 0.8 vs. 2.3 ± 0.8, P = 0.0001]. BI-score, on average, improved significantly in the treatment and control group as well [SD unit, mean, from - 1.06 to -0.58, P = 0.001; from - 0.66 to -0.42, P = 0.04]. CONCLUSIONS: Women with stress-predominant urinary incontinence receiving a specially formulated supplement in addition to daily PFMT for six weeks had significantly improved urinary symptoms (decrease in UDI-6 score and IIQ-7) and BI-score compared to their baseline. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05358769. 27/04/2022.

Application of a Multiplex Platform to Identify Novel Biomarkers for Pregnancy Location and Viability.

Determining early pregnancy location and viability can be cumbersome, often requiring serial evaluations. This study aimed to identify novel biomarker candidates for pregnancy location and viability using a pseudodiscovery high through-put technique. This was a case-control study among patients presenting for early pregnancy assessment, including ectopic pregnancies, early pregnancy losses, and viable intrauterine pregnancies. For pregnancy location, ectopic pregnancy was considered "case" and non-ectopic considered "control." For pregnancy viability, viable intrauterine pregnancy was considered "case" and early pregnancy loss + ectopic pregnancy were considered "control." Using Proximity Extension Assay technology from Olink Proteomics, serum levels of 1012 proteins were compared separately for pregnancy location and viability. Receiver operator characteristic curves were generated to determine a biomarker's discriminative abilities. Analysis included 13 ectopic pregnancies, 76 early pregnancy losses, and 27 viable intrauterine pregnancies. For pregnancy location, 18 markers had an area under the curve (AUC) ≥ 0.80, with three being expressed more in ectopic compared to non-ectopic pregnancies: thyrotropin subunit beta, carbonic anhydrase 3, and DEAD (Asp-Glu-Ala-Asp) box polypeptide 58. For pregnancy viability, two markers had an AUC ≥ 0.80: lutropin subunit beta and serpin B8. While some of the markers were previously identified as implicated in early pregnancy physiology, others were from pathways not previously explored. Using a high through-put platform, a large number of proteins were screened as potential biomarkers for pregnancy location and viability, and twenty candidate biomarkers were identified. Further exploration of these proteins may facilitate validation as diagnostic tools for establishing early pregnancy diagnoses.

BRAF RNA is prognostic and widely expressed in lung adenocarcinoma.

Background: BRAF is a critical member of proliferation pathways in cancer, and a mutation is present in only 2-4% of lung adenocarcinomas (LADC). There is no data available on the expression pattern of BRAF RNA that might result in enhanced signalling and drug resistance. Methods: LADC tissue samples (n=64) were fixed and processed into paraffin blocks. Tissue microarrays (TMA) were constructed, and RNAScope® in situ hybridization (ISH) assay was performed for wild-type (WT) BRAF RNA. Apart from pathological assessment of tumor samples (grade, necrosis, vascular involvement and peritumoral infiltration), anti-programmed death ligand 1 (PD-L1) and anti-programmed death 1 (PD-1) immunohistochemistry and validation in public databases [The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA)] were carried out. Results: WT BRAF RNA is expressed in LADC, with no significant expressional difference between early-stage (I-II) and advanced-stage (III-IV) patients (P=0.317). Never smokers exhibited significantly increased BRAF expression (compared to current and ex-smokers, P<0.01) and tumor necrosis correlated significantly with BRAF expression (P=0.014). PD-L1 expression was assessed on tumor cells and immune cells, PD-1 expression was evaluated on immune cells. There was no significant difference in BRAF RNA expression between tumor cell PD-L1-high vs. low patients (P=0.124), but it was decreased in immune cell PD-L1-high patients (P=0.03). Kaplan-Meier survival analysis showed that high BRAF expression was associated with significantly decreased OS (P<0.01) and was an independent negative prognostic factor according to multivariate Cox hazard regression (P=0.024). TCGA validation cohort confirmed our findings regarding OS in early-stage patients (P=0.034). Conclusions: We found an increased expression of BRAF RNA in all stages in LADC. High BRAF expression was associated with tumor necrosis, distinct immune checkpoint biology and outcomes. We recommend further evaluating the potential of targeting overexpressed BRAF pathways in LADC.

Implication of the Gut Microbiome and Microbial-Derived Metabolites in Immune-Related Adverse Events: Emergence of Novel Biomarkers for Cancer Immunotherapy.

Immune checkpoint inhibitors (ICIs) have changed how we think about tumor management. Combinations of anti-programmed death ligand-1 (PD-L1) immunotherapy have become the standard of care in many advanced-stage cancers, including as a first-line therapy. Aside from improved anti-tumor immunity, the mechanism of action of immune checkpoint inhibitors (ICIs) exposes a new toxicity profile known as immune-related adverse effects (irAEs). This novel toxicity can damage any organ, but the skin, digestive and endocrine systems are the most frequently afflicted. Most ICI-attributed toxicity symptoms are mild, but some are severe and necessitate multidisciplinary side effect management. Obtaining knowledge on the various forms of immune-related toxicities and swiftly changing treatment techniques to lower the probability of experiencing severe irAEs has become a priority in oncological care. In recent years, there has been a growing understanding of an intriguing link between the gut microbiome and ICI outcomes. Multiple studies have demonstrated a connection between microbial metagenomic and metatranscriptomic patterns and ICI efficacy in malignant melanoma, lung and colorectal cancer. The immunomodulatory effect of the gut microbiome can have a real effect on the biological background of irAEs as well. Furthermore, specific microbial signatures and metabolites might be associated with the onset and severity of toxicity symptoms. By identifying these biological factors, novel biomarkers can be used in clinical practice to predict and manage potential irAEs. This comprehensive review aims to summarize the clinical aspects and biological background of ICI-related irAEs and their potential association with the gut microbiome and metabolome. We aim to explore the current state of knowledge on the most important and reliable irAE-related biomarkers of microbial origin and discuss the intriguing connection between ICI efficacy and toxicity.

Validation of a multiple marker test for early pregnancy outcome prediction.

PURPOSE: To validate the use of a multiple biomarker test panel for predicting first trimester pregnancy outcome in a multi-center cohort. METHODS: A case-control study of women presenting with pain and bleeding in early pregnancy at 5-10 weeks gestational age was performed at three academic centers. Sera from women with ectopic pregnancy (EP), viable intrauterine pregnancy (IUP), and miscarriage (SAB) were analyzed via immunoassay for Activin A (AA), Progesterone (P4), A Disintegrin And Metalloprotease-12 (ADAM12), pregnancy-associated plasma protein A (PAPP-A), glycodelin (Glyc), and human chorionic gonadotropin (hCG). Biomarkers were assessed for reproducibility using medians, ranges, standard deviations, and area under receiver-operating characteristic curve (AUC) and accuracy in early pregnancy outcome classification compared to a previous derivation population. RESULTS: In 192 pregnancies, the biomarkers demonstrated good reproducibility with similar medians, ranges, and AUCs when compared to the derivation population except glycodelin. Pregnancy location was conclusively classified in 53% (n = 94) of the whole study sample with 78% accuracy. Pregnancy viability was conclusively classified in 58% (n = 112) of the new sample with 89% accuracy. Results were similar with subsequent model revisions where glycodelin was excluded and in the subgroups of subjects with a hCG below 2000 mIU/mL and a gestational age less than 6 weeks. CONCLUSION: The use of a panel of biomarkers to maximize test accuracy of a prediction of pregnancy location and prediction of pregnancy viability was reproducible and validated in an external population from which it was derived, but clinical utility is limited based on the test characteristics obtained.

Blood-seeking horseflies prefer vessel-imitating temperature gradients on host-mimicking targets: Experimental corroboration of a new explanation of the visual unattractiveness of zebras to tabanids.

Several hypotheses tried to explain the advantages of zebra stripes. According to the most recent explanation, since the borderlines of sunlit white and black stripes can hamper thermal vessel detection by blood-seeking female horseflies, striped host animals are unattractive to these parasites which prefer hosts with a homogeneous coat, on which the temperature gradients above blood vessels can be detected more easily. This hypothesis has been tested in a field experiment with horseflies walking on a grey barrel with thin black stripes which were slightly warmer than their grey surroundings in sunshine, while in shade both areas had practically the same temperature. To eliminate the multiple (optical and thermal) cues of this test target, we repeated this experiment with improved test surfaces: we attracted horseflies by water- or host-imitating homogeneous black test surfaces, beneath which a heatable wire ran. When heated, this invisible and mechanically impalpable wire imitated thermally the slightly warmer subsurface blood vessels, otherwise it was thermally imperceptible. We measured the times spent by landed and walking horseflies on the test surface parts with and without underlying heated or unheated wire. We found that walking female and male horseflies had no preference for any (wired or wireless) area of the water-imitating horizontal plane test surface on the ground, independent of the temperature (heated or unheated) of the underlying wire. These horseflies looked for water, rather than a host. On the other hand, in the case of host-imitating test surfaces, female horseflies preferred the thin surface regions above the wire only if it was heated and thus warmer than its surroundings. This behaviour can be explained exclusively with the higher temperature of the wire given the lack of other sensorial cues. Our results prove the thermal vessel recognition of female horseflies and support the idea that sunlit zebra stripes impede the thermal detection of a host's vessels by blood-seeking horseflies, the consequence of which is the visual (non-thermal) unattractiveness of zebras to horseflies.

Self-rated health status and hygienic behaviour of pregnant women in Hungary during the pandemic.

OBJECTIVES: The aim of our research was to investigate the self-rated health status, health behaviour and hygiene habits of pregnant women, and to explore the influencing factors during the pandemic. METHODS: The sample included 1,200 pregnant women who gave birth in the most progressive institutions of the three examined counties in Hungary; 839 questionnaires were returned, based on which the willingness to answer can be said to be 69.9%. After data cleaning, 640 questionnaires were added to the database. Descriptive statistical analyses and correlation tests were performed, during which we used the Pearson's chi-square test and Fisher's exact test. RESULTS: Socio-demographic factors show a significant correlation with the perceived state of health and the degree of responsibility for health, however, the existence of a chronic disease does not affect either the self-assessed state of health or hygienic behaviour. Factors influencing hygienic behaviour include residence, education, assessed income, and gestational age. We found no correlation between health status and hygienic attitude. CONCLUSIONS: Our results draw attention to the fact that among pregnant women - especially pregnant women with low socioeconomic status - education about hygiene habits is of particular importance. Teamwork is needed in this area, which should start during the period of preparation for pregnancy, but at the latest in the early stages of pregnancy.

Sunlit zebra stripes may confuse the thermal perception of blood vessels causing the visual unattractiveness of zebras to horseflies.

Multiple hypotheses have been proposed for possible functions of zebra stripes. The most thoroughly experimentally supported advantage of zebra stripes is their visual unattractiveness to horseflies (tabanids) and tsetse flies. We propose here a plausible hypothesis why biting horseflies avoid host animals with striped pelages: in sunshine the temperature gradients of the skin above the slightly warmer blood vessels are difficult to distinguish from the temperature gradients induced by the hairs at the borderlines of warmer black and cooler white stripes. To test this hypothesis, we performed a field experiment with tabanids walking on a host-imitating grey test target with vessel-mimicking thin black stripes which were slightly warmer than their grey surroundings in sunshine, while under shady conditions both areas had practically the same temperature as demonstrated by thermography. We found that horseflies spend more time walking on thin black stripes than surrounding grey areas as expected by chance, but only when the substrate is sunlit. This is because the black stripes are warmer than the surrounding grey areas in the sun, but not in the shade. This is consistent with the flies' well-documented attraction to warmer temperatures and provides indirect support for the proposed hypothesis. The frequent false vessel locations at the numerous black-white borderlines, the subsequent painful bitings with unsuccessful blood-sucking attempts and the host's fly-repellent reactions enhance considerably the chance that horseflies cannot evade host responses and are swatted by them. To eliminate this risk, a good evolutionary strategy was the avoidance of striped (and spotted) host animals.

Patients' Assessment of Chronic Illness Care (PACIC): Validation and Evaluation of PACIC Scale among Patients with Type 2 Diabetes in Hungary.

Introduction: The aims of this study were to evaluate the psychometric properties of the Hungarian translation of the PACIC in a sample of patients with type 2 diabetes and to reveal the associations between the mean PACIC scores and the number of chronic diseases, or visits to GPs, and specialist. An exploratory factor analysis (EFA) has also been performed to test the structural validity of the PACIC scale. Methods: The Hungarian version of PACIC was validated using randomly selected patients with type 2 diabetes (N = 684) from licensed GP practices. Results: Floor (1.6%-30.2%) and ceiling effects (11.3-33.6%) were similar of the PACIC scale. The internal consistency of the total scale (Cronbach's alpha 0.93) was excellent and subscales were good (between 0.73-0.9). The mean scores of each PACIC subscale group were between 2.99-3.53. There was a weak significant correlation between the mean PACIC scores of subscales and the number of GP visits (p < 0.001), and specialist visits (p < 0.001). The EFA identified four factors on the sample (KMO = 0.931). Gender and education showed correlation with some new factors. Conclusion: The psychometric properties of the Hungarian version of PACIC questionnaire showed a reasonable level of validity among patients with type 2 diabetes. Now, this instrument is ready to assess the chronic care of diabetic patients in Hungary.