Introduction: Covert brain infarcts (CBI) are frequent incidental findings on MRI and associated with future stroke risk in patients without a history of clinically evident cerebrovascular events. However, the prognostic value of CBI in first-ever ischemic stroke patients is unclear and previous studies did not report on different etiological stroke subtypes. We aimed to test CBI phenotypes and their association with stroke recurrence in first-ever ischemic stroke patients according to stroke etiology. Patients and methods: This study is a pooled data analysis of two prospectively collected cohorts of consecutive first-ever ischemic stroke patients admitted to the comprehensive stroke centers of Bern (Switzerland) and Graz (Austria). CBI phenotypes were identified on brain MRI within 72 h after admission. All patients underwent a routine follow-up (median: 12 months) to identify stroke recurrence. Results: Of 1577 consecutive ischemic stroke patients (median age: 71 years), 691 patients showed CBI on brain MRI (44%) and 88 patients had a recurrent ischemic stroke (6%). Baseline CBI were associated with stroke recurrence in multivariable analysis (HR 1.9, 95% CI 1.1–3.3). CBI phenotypes with the highest risk for stroke recurrence were cavitatory CBI in small vessel disease (SVD)-related stroke (HR 7.1, 95% CI 1.6–12.6) and cortical CBI in patients with atrial fibrillation (HR 3.0, 95% CI 1.1–8.1). Discussion and conclusion: This study reports a ≈ 2-fold increased risk for stroke recurrence in first-ever ischemic stroke patients with CBI. The risk of recurrent stroke was highest in patients with cavitatory CBI in SVD-related stroke and cortical CBI in patients with atrial fibrillation. Subject terms: Covert brain infarcts, stroke Graphical abstract

In the past years the interest in Solute Carrier Transporters (SLC) has increased due to their potential as drug targets. At the same time, macrocycles demonstrated promising activities as therapeutic agents. However, the overall macrocycle/SLC‐transporter interaction landscape has not been fully revealed yet. In this study, we present a statistical analysis of macrocycles with measured activity against SLC‐transporter. Using a data mining pipeline based on KNIME retrieved in total 825 bioactivity data points of macrocycles interacting with SLC‐transporter. For further analysis of the SLC inhibitor profiles we developed an interactive KNIME workflow as well as an interactive map of the chemical space coverage utilizing parametric t‐SNE models. The parametric t‐SNE models provide a good discrimination ability among several corresponding SLC subfamilies’ targets. The KNIME workflow, the dataset, and the visualization tool are freely available to the community.

We assess proton decay signatures in the simplest viable $SU(5)$ model with regard to constraints on parameters governing the Standard Model fermion mass spectrum. Experimental signals for all eight two-body proton decay processes result from exchange of two gauge bosons, a single scalar leptoquark, or their combination. Consequently, it enables us to delve into an in-depth anatomy of proton decay modes and anticipate future signatures. Our findings dictate that observing a proton decay into $p\to\pi^0e^+$ indicates gauge boson mediation, with the potential for observation of $p\to\eta^0e^+$ mode. Alternatively, if decay is through $p\to K^+\overline\nu$ process, it is mediated by a scalar leptoquark, possibly allowing the observation of $p\to\pi^0\mu^+$. Detection of both $p\to\pi^0 e^+$ and $p\to K^+\overline\nu$ could enhance $p\to\pi^0\mu^+$ through constructive interference. The model predicts inaccessibility of $p\to\pi^+\overline\nu$, $p\to\eta^0\mu^+$, $p\to K^0e^+$, and $p\to K^0\mu^+$, regardless of the dominant mediation type, in the coming decades. In summary, through a comprehensive analysis of proton decay signals, gauge coupling unification, and fermion masses and mixing, we precisely constrain the parameter space of the $SU(5)$ model in question.

Background: Difficult cholecystectomy, often associated with a heightened risk of complications, poses a significant surgical dilemma. Risk factors, such as patient age, increased body weight, the presence of gallstones, acute cholecystitis, and prior abdominal surgeries, can complicate laparoscopic cholecystectomy and necessitate conver- sion to an open procedure for safety. The aim of our study was to assess the applicability of the Nassar scale in predicting the need for conversion from laparoscopic to open cholecystectomy.Material and methods: In our prospective cohort study, we included 85 patients who underwent either emergency or elective laparoscopic cholecystectomy between December 2021 and October 2023. The Nassar scale was used to assess the complexity of laparoscopic cholecystectomy, incorporating parameters such as ‘Gallbladder,’ ‘Cystic pedicle,’and ‘Adhesions’ to determine a final score ranging from 1 to 5. Statistical analysis involved descriptive and analytical methods, with the significance threshold set at p < 0.05.Results: ANOVA analysis revealed a statistically significant difference in the duration of operative procedures with different Nassar grades (p < 0.001). An increase in the Nassar grade by 1 was associated with a statistically significant6.23-fold increase in the odds of conversion to an open procedure (p < 0.001). Receiver Operating Characteristic (ROC) analysis demonstrated a highly significant association (p < 0.001) between the Nassar grade and the conversion event, with an Area Under the Curve (AUC) of 0.881 (95% CI 0.79,0.96). The optimal cutoff value, identified as >2.5, struck a balance between sensitivity (0.86) and 1-specificity (0.23). Conclusion: Our study underscores the utility of the Nassar scale in surgical practice. It provides valuable insights into assessing the severity of operations, facilitating informed decision-making, and optimizing treatment outcomes for patients undergoing laparoscopic cholecystectomy at our institution.

Abstract. Agricultural headwater streams are important pathways for diffuse sediment and nutrient losses, requiring mitigation strategies beyond in-field measures to intercept the transport of pollutants to downstream freshwater resources. As such, floodplains can be constructed along existing agricultural streams and ditches to improve fluvial stability and promote deposition of sediments and particulate phosphorus. In this study, we evaluated 10 remediated agricultural streams in Sweden for their capacity to reduce sediment and particulate phosphorus export and investigated the interplay between fluvial processes and phosphorus dynamics. Remediated streams with different floodplain designs (either on one side or both sides of the channel, with different width and elevation) were paired with upstream trapezoidal channels as controls. We used sedimentation plates to determine seasonal patterns in sediment deposition on channel beds and floodplains and monthly water quality monitoring. This was combined with continuous flow discharge measurements to examine suspended sediment and particulate phosphorus dynamics and reduction along reaches. Remediated streams with floodplains on both sides of the channel reduced particulate phosphorus concentrations and loads (−54 µg L−1, −0.21 kg ha−1 yr−1) along reaches, whereas increases occurred along streams with one-sided floodplains (27 µg L−1, 0.09 kg ha−1 yr−1) and control streams (46.6 µg L−1). Sediment deposition in remediated streams was five times higher on channel beds than on floodplains and there was no evident lateral distribution of sediments from channel to floodplains. There was no effect from sediment deposition on particulate phosphorus reduction, suggesting that bank stabilization was the key determinant for phosphorus mitigation in remediated streams, which can be realized with two-sided but not one-sided floodplains. Further, the overall narrow floodplain widths likely restricted reach-scale sediment deposition and its impact on P reductions. To fully understand remediated streams' potential for reductions in both nitrogen and different phosphorus species and to avoid pollution swapping effects, there is a need to further investigate how floodplain design can be optimized to achieve a holistic solution towards improved stream water quality.

Accurate identification of the QRS complex is critical to analyse heart rate variability (HRV), which is linked to various adverse outcomes in premature infants. Reliable and accurate extraction of HRV characteristics at a large scale in the neonatal context remains a challenge. In this paper, we investigate the capabilities of 15 state-of-the-art QRS complex detection implementations using two real-world preterm neonatal datasets. As an attempt to improve the accuracy and reliability, we introduce a weighted ensemble-based method as an alternative. Obtained results indicate the superiority of the proposed method over the state of the art on both datasets with an F1-score of 0.966 (95% CI 0.962-0.97) and 0.893 (95% CI 0.892-0.894). This motivates the deployment of ensemble-based methods for any HRV-based analysis to ensure robust and accurate QRS complex detection.

Abstract Women were more affected than men during the COVID-19 pandemic. This study aimed to investigate COVID-19-related stress response in adult women and its association with the relevant socioeconomic, lifestyle and COVID-19-related factors. This research was carried out in eight randomly chosen cities from September 2020 to October 2021. To examine stress, we distributed the COVID Stress Scales (CSS) and the Perceived Stress Scale (PSS). Women also fulfilled a general socio-epidemiologic questionnaire. The study included 1,264 women. Most women were healthy, highly educated, employed, married, nonsmokers who consumed alcohol. The average total CSS score suggested a relatively low COVID-19 related stress), while 1.7% of women had CSS ≥ 100. The mean PSS was around the mid-point value of the scale. Older women, who were not in a relationship, didn’t smoke, didn’t drink alcohol, but used immune boosters, had chronic illnesses and reported losing money during the pandemic had higher CSS scores. A higher level of stress was also experienced by women exposed to the intense reporting about COVID-19, had contact with COVID-19 positive people or took care of COVID-19 positive family members. In this sample of predominantly highly educated women few women experienced very high stress level, probably due to the study timing (after the initial wave) when the pandemic saw attenuated stress levels. To relieve women from stress, structural organization and planning in terms of health care delivery, offsetting economic losses, controlled information dissemination and psychological support for women are needed.

ABSTRACT The paper deals with the population decline in Balkan countries in the last three decades, since 1990. It researches the scale of depopulation in the Balkans and analyses the causes and possible consequences of the population decline. It argues that the failure of imposed neoliberal economic policies in the Balkan countries in the 1990s caused deindustrialization, GDP stagnation and high unemployment rates, especially of young people. Together with the shift in values from traditional to neo-liberal ones which promote materialism, hedonism, consumerism and liberal middle-class feminism, it caused dramatic reduction in fertility (live births per woman) as well as a significant brain drain and economic emigration from the Balkan countries in the last 30 years. Depopulation is becoming a limiting factor for sustainability of Balkan societies. It imposes a long-term danger for demographic survival of these societies, and generates an array of other negative economic, social and political consequences.

Glioblastoma multiforme (GBM) is a highly invasive brain malignancy originating from astrocytes, accounting for approximately 30% of central nervous system malignancies. Despite advancements in therapeutic strategies including surgery, chemotherapy, and radiopharmaceutical drugs, the prognosis for GBM patients remains dismal. The aggressive nature of GBM necessitates the identification of molecular targets and the exploration of effective treatments to inhibit its proliferation. The Notch signaling pathway, which plays a critical role in cellular homeostasis, becomes deregulated in GBM, leading to increased expression of pathway target genes such as MYC, Hes1, and Hey1, thereby promoting cellular proliferation and differentiation. Recent research has highlighted the regulatory role of non-coding RNAs (ncRNAs) in modulating Notch signaling by targeting critical mRNA expression at the post-transcriptional or transcriptional levels. Specifically, various types of ncRNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been shown to control multiple target genes and significantly contribute to the carcinogenesis of GBM. Furthermore, these ncRNAs hold promise as prognostic and predictive markers for GBM. This review aims to summarize the latest studies investigating the regulatory effects of ncRNAs on the Notch signaling pathway in GBM.

BACKGROUND: Computational research plays an important role in predicting the chemical and physical properties of biologically active compounds important in future structural modifications to improve or modify biological activity. OBJECTIVE: This research focuses on quantum chemical and spectroscopic investigations properties of synthesized 4-hydroxycoumarin derivatives. METHODS: Quantum chemical calculations were obtained using B3LYP, HF, and M06-2x level methods with the 6-31++G (d,p) basis set. Afterward, IR, 1H, 13C, UV-Visible experimentally parameters were compared with the results obtained using the B3LYP/6-31+G*(d) basis set of the molecules to be able to characterize the structures. RESULTS: Based on the quantum chemical calculations compound with acetamido group on the phenyl ring is the most reactive, and compound with nitro substituent is the least reactive and the the strongest electrophile among tested compounds. With the exception of compounds with dimethylamino group, all other compounds have a pronounced tautomer between OH and C = O group. The calculated and experimental values are in agreement with each other. CONCLUSION: The molecular structure in the ground state of six 3-cinnamoyl 4-hydroxycoumarin derivatives was optimized using density functional theory. The observed and computed values were compared and it can be concluded that the theoretical results were in good linear agreement with the experimental data.

ABSTRACT This article aimed to identify sources and transport pathways of macro- and microelements in large urbanized rivers under significant anthropogenic pressure. To achieve the objective of this study, the geochemical characteristics of the sediments of the Sava and Danube Rivers and the soils flooded by the Kolubara River were determined. The high content of Mg indicates the dominant origin of the material from loess deposits. The significantly higher contents of Cr and Ni in sediment and soil samples from the Obrenovački Zabran (OZ) than in the samples from the Veliko Ratno Ostrvo (VRO) are the result of increased anthropogenic pressure. Sediments from the VRO show increased Sn and Sb contents. The increase in the content of chalcophile elements is the highest in the sediments from the OZ and ranges from 1.8 to 2.7 times, compared to their concentrations in the Earth’s crust. The soils from OZ and the sediments from the VRO show a decrease in the content of chalcophile elements compared to the sediments from the OZ so the increase is 1.2–1.5, and 0.9–2.3 times, respectively compared to the Earth’s crust. The obtained results revealed that the yield of sedimentary material that has higher concentrations of microelements decreases already at a distance of several km.

Sewage sludge, a biosolid product of wastewater processing, is an often-overlooked source of rich organic waste. Hydrothermal processing (HTP), which uses heat and pressure to convert biomass into various solid, liquid, and gaseous products, has shown promise in converting sewage sludge into new materials with potential application in biofuels, asphalt binders, and bioplastics. In this study we focus on hydrochar, the carbonaceous HTP solid phase, and investigate its use as a bio-based filler in additive manufacturing technologies. We explore the impact of HTP and subsequent thermal activation on chemical and structural properties of sewage sludge and discuss the role of atypical metallic and metalloid dopants in organic material processing. In additive manufacturing composites, although the addition of hydrochar generally decreases mechanical performance, we show that toughness and strain can be recovered with hierarchical microstructures, much like biological materials that achieve outstanding properties by architecting relatively weak building blocks.

BACKGROUND: The association between sex and outcome after endovascular thrombectomy of acute ischemic stroke is unclear. The aim of this study was to compare the clinical and safety outcomes between men and women treated with endovascular thrombectomy in the late 6-to-24-hour window period. METHODS: This multicenter, retrospective observational cohort study included consecutive patients who underwent endovascular thrombectomy of anterior circulation stroke in the late window from 66 clinical sites in 10 countries from January 2014 to May 2022. The primary outcome was the 90-day ordinal modified Rankin Scale score. Secondary outcomes included 90-day functional independence (FI), return of Rankin (RoR) to prestroke baseline, FI or RoR, symptomatic intracranial hemorrhage, and mortality. Multivariable and inverse probability of treatment weighting methods were used. We explored the interaction of sex with baseline characteristics on the outcomes ordinal modified Rankin Scale and FI or RoR. RESULTS: Of 1932 patients, 1055 were women and 877 were men. Women were older (77 versus 69 years), had higher rates of atrial fibrillation, hypertension, and greater prestroke disability, but there was no difference in baseline National Institutes of Health Stroke Scale score. Inverse probability of treatment weighting analysis showed no difference between women and men in ordinal modified Rankin Scale (odds ratio, 0.98 [95% CI, 0.79–1.21]), FI or RoR (odds ratio, 0.98 [95% CI, 0.78–1.22]), severe disability or mortality (odds ratio, 0.99 [95% CI, 0.80–1.23]). The multivariable analysis of the above end points was concordant. There were no interactions between baseline characteristics and sex on the outcomes of ordinal modified Rankin Scale and FI or RoR. CONCLUSIONs: In late presenting patients with anterior circulation stroke treated with endovascular thrombectomy in the 6 to 24-hour window, there was no difference in clinical or safety outcomes between men and women.

ABSTRACT The purpose of this article is to analyse the state and the dynamics of developmental and other aspects of investments in research and development (R&D) in the group of countries in Southeast Europe. The analysis is performed for several countries in Southeast Europe together and by individual countries. The period from 1996 to 2020 is observed in the analysis. In most countries of Southeast Europe, the allocation for R&D is relatively small. Applied research is the most represented. Significant differences can be noticed regarding the sources of financing and to the implementation of allocations for R&D. A particularly important part of this work is devoted to the analysis of the impact of the gross expenditures on R&D on economic growth. This analysis was performed on the basis of regression analysis. Several regression models were formed in which the dependent variable was gross domestic product per capita It can be concluded that the parameters of the financial condition of the observed economy have the greatest influence on the economic growth of the observed group of countries. Allocations for research and development still do not have a significant enough impact on economic growth in observed countries in Southeast Europe.

Background Isoprenaline (ISO), a synthetic catecholamine and a β-adrenoceptor agonist, is widely used to develop an experimental model of myocardial injury (MI) in rats. The leading hypothesis for ISO-induced MI in rats is that it results from catecholamine overstimulation, oxidative stress, inflammatory responses, and development of cardiomyopathy during ISO administration. Folic acid (FA) reduces oxidative stress, improves endothelial function and prevents apoptosis, thereby contributing to cardiovascular protection. This study aimed to investigate the potentially protective effect of FA pretreatment on ISO-induced MI in rats. Methods For 7 days, adult male Wistar albino rats were pretreated with 5 mg/kg/day of FA. On the sixth and seventh days, MI in rats was induced by administering 85 mg/kg/day of ISO. Prooxidant markers in plasma samples, antioxidant capacity in erythrocyte lysates, cardiac damage markers, lipid profile, electrocardiography (ECG) and histopathological analysis were evaluated. Results FA pretreatment significantly alleviated changes induced by ISO; it decreased the homocysteine and high-sensitivity troponin I level. FA moderately decreased the reactive oxygen species (ROS) levels (superoxide anion radical, hydrogen peroxide and thiobarbituric acid reactive substances) and improved the antioxidant activities of catalase, superoxide dismutase and reduced glutathione. ISO reduced the nitrite level and FA significantly alleviated this change. Conclusion It can be concluded that FA, as a mild antioxidant, could be an appropriate cardioprotective substance in the rat model of ISO-induced MI.