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Neurons in central nervous systems receive multiple synaptic inputs and transform them into a largely standardized output to their target cells-the action potential. A simplified model posits that synaptic signals are integrated by linear summation and passive propagation towards the axon initial segment, where the threshold for spike generation is either crossed or not. However, multiple lines of research during past decades have shown that signal integration in individual neurons is much more complex, with important functional consequences at the cellular, network, and behavioral-cognitive level. The interplay between concomitant excitatory and inhibitory postsynaptic potentials depends strongly on the relative timing and localization of the respective synapses. In addition, dendrites contain multiple voltage-dependent conductances, which allow scaling of postsynaptic potentials, non-linear input processing, and compartmentalization of signals. Together, these features enable a rich variety of single-neuron computations, including non-linear operations and synaptic plasticity. Hence, we have to revise over-simplified messages from textbooks and use simplified computational models like integrate-and-fire neurons with some caution. This concept article summarizes the most important mechanisms of dendritic integration and highlights some recent developments in the field., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Dealing with chronic inflammatory skin conditions like atopic dermatitis and psoriasis can be extremely difficult. Current treatments, such as topical corticosteroids, often have limitations and side effects. However, researchers have discovered that the placenta's remarkable properties may provide a breakthrough in effectively addressing these skin conditions. The placenta comprises three essential tissues: decidua, placental membrane, and umbilical cord. Placental derivatives have shown significant potential in treating psoriasis by reducing inflammatory cytokines and inhibiting keratinocyte proliferation. In the case of atopic dermatitis, umbilical cord stem cells have demonstrated anti-inflammatory effects by targeting critical factors and promoting anti-inflammatory cytokines. The scope of benefits associated with placental derivatives transcends these specific applications. They also potentially address other inflammatory skin diseases, such as vitiligo, by stimulating melanin production. Moreover, these derivatives have been leveraged in the treatment of pemphigus and epidermolysis bullosa (EB), showcasing potential as a wound dressing that could eliminate the necessity for painful dressing changes in EB patients. In summary, the integration of placental derivatives stands to revolutionize our approach to inflammatory skin conditions owing to their distinct properties and the prospective benefits they offer. This comprehensive review delves into the current applications of placental derivatives in addressing inflammatory skin diseases, presenting a novel treatment approach., Competing Interests: Declarations Competing Interests The authors have no conflict of interest to declare. Ethical Approval not applicable., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Microplastics (MPs) and heavy metal pollution pose significant environmental threat, potentially leading to agroecosystem toxicity and jeopardizing food security. Therefore, this study aims to evaluate the abundance and risk assessment of these pollutants in five different farmlands of Ernakulam district, India. Results showed that MPs content in agricultural fields near commercialized areas such as Kakkanad Nedungapuzha, Nedumbassery, and Kadamakuddy was dominant compared to Nechoor, a rural area. The average microplastic abundance was found to be 45.6 ± 26.4 items kg⁻ 1 dw. Polypropylene (PP) and polyethylene (PE) were the dominant polymers found in the soil samples, constituting 45% and 25% of the microplastic content, respectively. The pollution load index of MPs indicates that the sampling sites are considered to be polluted as PLI > 1 with hazard level I. The heavy metal pollution status follows the order: Cu (80.3 to 724 mg/kg) > Zn (77 to 543.5 mg/kg) > Cr (171.65 to 334.65 mg/kg) > As (10.25 to 79.5 mg/kg) > Pb (2.05 to 30.3 mg/kg) > Cd (0.3 to 14.35 mg/kg). Calculated pollution load index (PLI) geo-accumulation index (Igeo), ecological risk assessment values indicate that commercialized regions exhibit high levels of trace metals, namely Cu, Zn, As, Cd, and Cr, posing a significant concern for the agricultural ecosystem. Our results indicate heightened microplastics and heavy metals prevalence in farmlands adjacent to commercial zones, necessitating immediate preventive action to mitigate increasing concentrations., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Soil and wastewater samples contaminated by petroleum-related industries were collected from various locations in Saudi Arabia, a country known for its vast oil reserves. The samples were analyzed for their physicochemical properties, including the presence of metals, petroleum hydrocarbons, and aromatic compounds. A total of 264 fungal isolates were analyzed and categorized into eight groups of Aspergillus (194 isolates) and four groups of Penicillium (70 isolates). The potential of these fungal groups to grow in oil or its derivatives was investigated. Two isolates, Aspergillus tubingensis FA-KSU5 and A. niger FU-KSU69, were utilized in two remediation experiments-one targeting wastewater and the other focusing on polluted soil. The FA-KSU5 strain demonstrated complete removal of Fe 3+ , As 3+ , Cr 6+ , Zn 2+ , Mn 2+ , Cu 2+ and Cd 2+ , with bioremediation efficiency for petroleum hydrocarbons in the wastewater from these sites ranging between 90.80 and 98.58%. Additionally, the FU-KSU69 strain achieved up to 100% reduction of Co 2+ , Ba 2+ , B 3+ , V + , Ni 2+ , Pb 2+ and Hg 2+ , with removal efficiency ranging from 93.17 to 96.02% for aromatic hydrocarbons after 180 min of wastewater treatment. After 21 days of soil incubation with Aspergillus tubingensis FA-KSU5, there was a 93.15% to 98.48% reduction in total petroleum hydrocarbons (TPHs) and an 88.11% to 97.31% decrease in polycyclic aromatic hydrocarbons (PAHs). This strain exhibited the highest removal rates for Cd 2+ and As 3+ followed by Fe 3+ , Zn 2+ , Cr 6+ , Se 4+ and Cu 2+ . Aspergillus niger FU-KSU69 achieved a 90.37% to 94.90% reduction in TPHs and a 95.13% to 98.15% decrease in PAHs, with significant removal of Ni 2+ , Pb 2+ and Hg 2+ , followed by Co 2+ , V + , Ba 2+ and B 3+ . The enzymatic activity in the treated soils increased by 1.54- to 3.57-fold compared to the polluted soil. Although the mixture of wastewater and polluted soil exhibited high cytotoxicity against normal human cell lines, following mycoremediation, all treated soils and effluents with the dead fungal biomass showed no toxicity against normal human cell lines at concentrations up to 500 µL/mL, with IC 50 values ≥ 1000 µL/mL. SEM and IR analysis revealed morphological and biochemical alterations in the biomass of A. tubingensis FA-KSU5 and A. niger FA-KSU69 when exposed to petroleum effluents. This study successfully introduces non-toxigenic and environmentally friendly fungal strains play a crucial role in the bioremediation of contaminated environments. Both strains serve as low-cost and effective adsorbents for bio-remediating petroleum wastewater and oil-contaminated soil. Heavy metals and hydrocarbons, the primary pollutants, were either completely removed or reduced to permissible levels according to international guidelines using the dead biomass of FA-KSU5 and FA-KSU69 fungi. Consequently, the environments associated with this globally significant industry are rendered biologically safe, particularly for humans, as evidenced by the absence of cytotoxicity in samples treated with A. tubingensis FA-KSU5 and A. niger FA-KSU69 on various human cell types., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

We aimed to determine the effect of the access sheath diameter used in percutaneous nephrolithotomy (PNL) on renal function. We also investigated the predictors of impaired renal function. Data were prospectively collected from patients who underwent PNL from December 2020 to December 2021. The patients were randomized into two groups according to access sheath diameter: Group 1 (22 Fr, n = 44) and Group 2 (28 Fr, n = 44). Relative renal function (RRF) was calculated by technetium-99 m dimercaptosuccinic acid scintigraphy, and glomerular filtration rate (GFR) was calculated by diethylenetriamine pentaacetic acid scintigraphy. A difference of 5% or more in RRF was considered a significant functional change. Preoperative and postoperative Kidney Injury Molecule-1 (KIM-1) levels were measured. Preoperative demographic data and stone characteristics were similar between the groups. There were also no statistically significant differences between the groups in terms of scar development, changes in RRF, GFR, or KIM-1/creatinine (Cr) (p > 0.05). Significant deterioration in RRF was detected in a total of six (6.8%) patients, three in each group. The factors predicting loss of function were analyzed by regrouping the patients without loss of function as Group A (n = 82) and those with loss as Group B (n = 6). Only stone volume was statistically significant in multivariate analysis (p = 0.002). Access sheath diameter had no significant effect on renal function after PNL. However, the stone volume was found to independently correlate to a loss of renal function after PNL., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Recent research shows exercise is good for heart health, emphasizing the importance of physical activity. Sedentary behavior increases the risk of cardiovascular disease, while exercise can help prevent and treat it. Additionally, physical exercise can modulate the expression of lncRNAs, influencing cardiovascular disease progression. Therefore, understanding this relationship could help identify prospective biomarkers and therapeutic targets pertaining to cardiovascular ailments. This review has underscored recent advancements concerning the potential biomarkers of lncRNAs in cardiovascular diseases, while also summarizing existing knowledge regarding dysregulated lncRNAs and their plausible molecular mechanisms. Additionally, we have contributed novel perspectives on the underlying mechanisms of lncRNAs, which hold promise as potential biomarkers and therapeutic targets for cardiovascular conditions. The knowledge imparted in this review may prove valuable in guiding the design of future investigations and furthering the understanding of lncRNAs as diagnostic, prognostic, and therapeutic biomarkers for cardiovascular diseases., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Research has shown that relying only on self-reports for diagnosing psychiatric disorders does not yield accurate results at all times. The advances of technology as well as artificial intelligence and other machine learning algorithms have allowed the introduction of point of care testing (POCT) including EEG characterization and correlations with possible psychopathology. Nonlinear methods of EEG analysis have significant advantages over linear methods. Empirical mode decomposition (EMD) is a reliable nonlinear method of EEG pre-processing. In this chapter, we compare two existing EEG complexity measures - Higuchi fractal dimension (HFD) and sample entropy (SE), with our newly proposed method using Higuchi fractal dimension from the Hilbert Huang transform (HFD-HHT). We present an example using the three complexity measures on a 2-minute EEG recorded from a healthy 20-year-old male after signal pre-processing. Furthermore, we showed the usefulness of these complexity measures in the classification of major depressive disorder (MDD) with healthy controls. Our study is in line with previous research and has shown an increase in HFD and SE values in the full, alpha and beta frequency bands suggestive of an increase in EEG irregularity. Moreover, the HFD-HHT values decreased in those three bands for majority of electrodes which is suggestive of a decrease in irregularity in the frequency-time domain. We conclude that all three complexity measures can be vital features useful for EEG analysis which could be incorporated in POCT systems., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Intracerebral hemorrhage is a highly prevalent and prognostically poor disease, imposing immeasurable harm on human life and health. However, the treatment options for intracerebral hemorrhage are severely limited, particularly in terms of improving the microenvironment of the lesion, promoting neuronal cell survival, and enhancing neural function. This review comprehensively discussed the application of stem cell therapy for intracerebral hemorrhage, providing a systematic summary of its developmental history, types of transplants, transplantation routes, and transplantation timing. Moreover, this review presented the latest research progress in enhancing the efficacy of stem cell transplantation, including pretransplantation preconditioning, genetic modification, combined therapy, and other diverse strategies. Furthermore, this review pioneeringly elaborated on the barriers to clinical translation for stem cell therapy. These discussions were of significant importance for promoting stem cell therapy for intracerebral hemorrhage, facilitating its clinical translation, and improving patient prognosis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Controlled mRNA storage and stability is essential for oocyte meiosis and early embryonic development. However, how to regulate mRNA storage and stability in mammalian oogenesis remains elusive. Here we showed that LSM14B, a component of membraneless compartments including P-body-like granules and mitochondria-associated ribonucleoprotein domain (MARDO) in germ cell, is indispensable for female fertility. To reveal loss of LSM14B disrupted primordial follicle assembly and caused mRNA reduction in non-growing oocytes, which was concomitant with the impaired assembly of P-body-like granules. 10× Genomics single-cell RNA-sequencing and immunostaining were performed. Meanwhile, we conducted RNA-seq analysis of GV-stage oocytes and found that Lsm14b deficiency not only impaired the maternal mRNA accumulation but also disrupted the translation in fully grown oocytes, which was closely associated with dissolution of MARDO components. Moreover, Lsm14b-deficient oocytes reassembled a pronucleus containing decondensed chromatin after extrusion of the first polar body, through compromising the activation of maturation promoting factor, while the defects were restored via WEE1/2 inhibitor. Together, our findings reveal that Lsm14b plays a pivotal role in mammalian oogenesis by specifically controlling of oocyte mRNA storage and stability., (© 2023. The Author(s).)

Anthropogenic eutrophication is a global environmental problem threatening the ecological functions of many inland freshwaters and diminishing their abilities to meet their designated uses. Water authorities worldwide are being pressed to improve their abilities to monitor, predict, and manage the incidence of harmful algal blooms (HABs). While most water quality management decisions are still based on conventional monitoring programs that lack the needed spatio-temporal resolution for effective lake/reservoir management, recent advances in remote sensing are providing new opportunities towards better understanding water quality variability in these important freshwater systems. This study assessed the potential of using the Sentinel 2 Multispectral Instrument to predict and assess the spatio-temporal variability in the water quality of the Qaraoun Reservoir, a poorly monitored Mediterranean hypereutrophic monomictic reservoir that is subject to extensive periods of HABs. The work first evaluated the ability to transfer and recalibrate previously developed reservoir-specific Landsat 7 and 8 water quality models when used with Sentinel 2 data. The results showed poor transferability between Landsat and Sentinel 2, with most models experiencing a significant drop in their predictive skill even after recalibration. Sentinel 2 models were then developed for the reservoir based on 153 water quality samples collected over 2 years. The models explored different functional forms, including multiple linear regressions (MLR), multivariate adaptive regression splines (MARS), random forests (RF), and support vector regressions (SVR). The results showed that the RF models outperformed their MLR, MARS, and SVR counterparts with regard to predicting chlorophyll-a, total suspended solids, Secchi disk depth, and phycocyanin. The coefficient of determination (R 2 ) for the RF models varied between 85% for TSS up to 95% for SDD. Moreover, the study explored the potential of quantifying cyanotoxin concentrations indirectly from the Sentinel 2 MSI imagery by benefiting from the strong relationship between cyanotoxin levels and chlorophyll-a concentrations., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Cyanobacterial harmful algal blooms (CHABs) are a global environmental concern that encompasses public health issues, water availability, and water quality owing to the production of various secondary metabolites (SMs), including cyanotoxins in freshwater, brackish water, and marine ecosystems. The frequency, extent, magnitude, and duration of CHABs are increasing globally. Cyanobacterial species traits and changing environmental conditions, including anthropogenic pressure, eutrophication, and global climate change, together allow cyanobacteria to thrive. The cyanotoxins include a diverse range of low molecular weight compounds with varying biochemical properties and modes of action. With the application of modern molecular biology techniques, many important aspects of cyanobacteria are being elucidated, including aspects of their diversity, gene-environment interactions, and genes that express cyanotoxins. The toxicological, environmental, and economic impacts of CHABs strongly advocate the need for continuing, extensive efforts to monitor cyanobacterial growth and to understand the mechanisms regulating species composition and cyanotoxin biosynthesis. In this review, we critically examined the genomic organization of some cyanobacterial species that lead to the production of cyanotoxins and their characteristic properties discovered to date., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

The progression of disease for an individual can be described mathematically as a stochastic process. The individual experiences a failure event when the disease path first reaches or crosses a critical disease level. This happening defines a failure event and a first hitting time or time-to-event, both of which are important in medical contexts. When the context involves explanatory variables then there is usually an interest in incorporating regression structures into the analysis and the methodology known as threshold regression comes into play. To date, most applications of threshold regression have been based on parametric families of stochastic processes. This paper presents a semiparametric form of threshold regression that requires the stochastic process to have only one key property, namely, stationary independent increments. As this property is frequently encountered in real applications, this model has potential for use in many fields. The mathematical underpinnings of this semiparametric approach for estimation and prediction are described. The basic data element required by the model is a pair of readings representing the observed change in time and the observed change in disease level, arising from either a failure event or survival of the individual to the end of the data record. An extension is presented for applications where the underlying disease process is unobservable but component covariate processes are available to construct a surrogate disease process. Threshold regression, used in combination with a data technique called Markov decomposition, allows the methods to handle longitudinal time-to-event data by uncoupling a longitudinal record into a sequence of single records. Computational aspects of the methods are straightforward. An array of simulation experiments that verify computational feasibility and statistical inference are reported in an online supplement. Case applications based on longitudinal observational data from The Osteoarthritis Initiative (OAI) study are presented to demonstrate the methodology and its practical use., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Arcobacter spp. has gained clinical significance as an emerging diarrheagenic pathogen associated with water reservoirs in recent years. The complete clinical significance of Arcobacter remains rather speculative due to the virulence and antibiotic susceptibility of individual strains. This study aimed to assess the prevalence of Arcobacter spp. in fish, water, and shellfish. A total of 150 samples were collected from the Adana, Kayseri and Kahramanmaras provinces in Turkey. Arcobacter spp. was isolated from 32 (21%) of the 150 samples. The most prevalent species was A. cryaerophilus, 17 (56%), A. butzleri 13 (37%) and A. lacus 2 (6%). As a result, the ratios of the mviN, irgA, pldA, tlyA and hecA target genes were found as 17 (51%), 1 (3%), 7 (23%), 7 (23%), 1 (3%), respectively. While bla OXA-61, tetO and tetW were positive in all isolates, were found as mcr1/2/6, mcr3/7, and mcr5, genes %37.5, %25, and %34.3, respectively. Although in A. butzleri was found 10 (58%), 1 (3%), 3 (43%), 2 (28%) (mviN, irgA, pldA, and tlyA, respectively) virulence genes 7 (42%), 4 (57%), 5 (72%), 1 (3%) was found (mviN, irgA, tlyA, and hecA, respectively) virulence genes in A. cryoaerophilus. Moreover, was found for the mcr 1/2/6 7 (58%) genes, for the mcr 3/7 genes 3 (38%) in A. butzleri. In A. cryoaerophilus was found for the mcr 1/2/6 genes 5 (42%), for the mcr 3/7 genes 5 (62%), and for the mcr 5 gene 10 (100%). Thus, the current study indicated that the existence of Arcobacter spp. isolated from fish and mussel samples may pose a potential risk to public health., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Key Message: Positive selection genes are related to metabolism, while differentially expressed genes are related to photosynthesis, suggesting that genetic adaptation and expression regulation may play independent roles in different gene classes. Genome-wide investigation of the molecular mechanisms for high-altitude adaptation is an intriguing topic in evolutionary biology. The Qinghai-Tibet Plateau (QTP) with its extremely variable environments is an ideal site for studying high-altitude adaptation. Here, we used transcriptome data of 100 individuals from 20 populations collected from various altitudes on the QTP to investigate the adaptive mechanisms of the aquatic plant Batrachium bungei at both the genetic and transcriptional level. To explore genes and biological pathways that may contribute to QTP adaptation, we employed a two-step approach, in which we identified positively selected genes and differentially expressed genes using the landscape genomic and differential expression approaches. The positive selection analysis showed that genes involved in metabolic regulation played a crucial role in B. bungei adaptation to the extreme environments of the QTP, especially intense ultraviolet radiation. Altitude-based differential expression analysis suggested that B. bungei could increase the rate of energy dissipation or reduce the efficiency of light energy absorption by down regulating the expression of photosynthesis-related genes to adapt to the strong ultraviolet radiation. Weighted gene co-expression network analysis identified ribosomal genes as hubs of altitude adaptation in B. bungei. Only a small part of genes (about 10%) overlapped between positively selected genes and differentially expressed genes in B. bungei, suggesting that genetic adaptation and gene expression regulation might play relatively independent roles in different categories of functional genes. Taken together, this study enriches our understanding of the high-altitude adaptation mechanism of B. bungei on the QTP., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The aim was to investigate the association between plasma levels of cellular adhesion molecules (CAMs) and risk factors, subtypes, severity and short-term mortality of acute ischemic stroke (IS), and to identify a panel of biomarkers to predict short-term mortality after IS. The prospective study evaluated 132 IS patients within 24 h of their hospital admission. The baseline IS severity was assessed using the National Institutes Health Stroke Scale (NIHSS) and categorized as mild (NIHSS < 5), moderate (NIHSS 5-14) and severe (NIHSS ≥ 15). After three-month follow-up, the disability was assessed using the modified Rankin Scale (mRS); moreover, the patients were classified as survivors and non-survivors. Baseline inflammatory and anti-inflammatory cytokines and soluble CAMs were evaluated. Twenty-nine (21.9%) IS patients were non-survivors and showed higher NIHSS and soluble vascular cellular adhesion molecule 1 (sVCAM-1) than the survivors. The sVCAM-1 levels positively correlated with age, homocysteine, severity, and disability. The model #3 combining sVCAM-1 and NIHSS showed better results to predict short-term mortality with an area under the curve receiving operating characteristics (AUC/ROC) of 0.8841 [95% confidence interval (CI): 0.795-0.941] than the models with sVCAM-1 and NIHSS alone, with positive predictive value of 68.0%, negative predictive value of 91.3%, and accuracy of 86.5%. In conclusion, the combined model with baseline severity of IS and sVCAM-1 levels can early predict the prognosis of IS patients who may benefit with therapeutic measures of personalized therapy that taken into account these biomarkers. Moreover, this result suggests that VCAM-1 might be a potential target for the therapeutic strategies in IS., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The level P-glycoprotein (Pgp) in organs of pregnant rabbits and its content and activity in the placental barrier at different stages of pregnancy were studied. An increase in Pgp content in the jejunum on days 7, 14, 21, and 28 of pregnancy in comparison with this parameter non-pregnant females was revealed by ELISA; in the liver, Pgp content was higher on day 7 and tended to increase on day 14; in the kidney and cerebral cortex, Pgp content was higher on day 28 of pregnancy in parallel with an increase in serum progesterone concentration. We also observed a decrease in Pgp content in the placenta on days 21 and 28 of pregnancy in comparison with day 14 and a decrease in Pgp activity in the placental barrier, which was confirmed by enhanced penetration of fexofenadine (Pgp substrate) through the barrier., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

Microorganisms in hot deserts face heat and other environmental conditions, such as desiccation, UV radiation, or low nutrient availability. Therefore, this hostile environment harbour microorganisms with acquired characteristics related to survival in their habitat, which can be exploited in biotechnology. In this work, the genome of Paenibacillus sp. MDMC362 isolated from the Merzouga desert in Morocco was sequenced to understand its survival strategy's genetic basis; and to evaluate the thermostability of a catalase extracted from genomic annotation files using molecular dynamics. Paenibacillus sp. MDMC362 genome was rich in genetic elements involved in the fight against different stresses, notably temperature stress, UV radiations, osmotic stress, carbon starvation, and oxidative stress. Indeed, we could identify genes of the operons groES-groEL and hrcA-grpE-dnaK and those involved in the different stages of sporulation, which can help the bacteria to survive the high temperatures imposed by a desertic environment. We also observed the genetic components of the UvrABC system and additional mechanisms involved in DNA repair, which help overcome UV radiation damage. Other genes have been identified in the genome, like those coding for ectoine and proline, that aids fight osmotic stress and desiccation. Catalase thermostability investigation using molecular dynamics showed that the protein reached stability and conserved its compactness at temperatures up to 373.15 K. These results suggest a potential thermostability of the enzyme. Since the studied protein is a core protein, thermostability could be conserved among Paenibacillus sp. MDMC362 closely related strains; however, bacteria from harsh environments may have a slight advantage regarding protein stability., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Impaired reproductive health is a worldwide problem that affects the psychological well-being of a society. Despite the technological developments to treat infertility, the global infertility rate is increasing significantly. Many infertility conditions are currently treated using various advanced clinical approaches such as intrauterine semination (IUI), in vitro fertilization (IVF), and intracytoplasmic injection (ICSI). Nonetheless, clinical management of some conditions such as dysfunctional endometrium, premature ovarian failure, and ovarian physiological aging still pose significant challenges. Stem cells based therapeutic strategies have a long-standing history to treat many infertility conditions, but ethical restrictions do not allow the broad-scale utilization of adult mesenchymal stromal/stem cells (MSCs). Easily accessible, placental derived or amniotic stem cells present an invaluable alternative source of non-immunogenic and non-tumorigenic stem cells that possess multilineage potential. Given these characteristics, placental or amniotic stem cells (ASCs) have been investigated for therapeutic purposes to address infertility in the last decade. This study aims to summarize the current standing and progress of human amniotic epithelial stem cells (hAECs), amniotic mesenchymal stem cells (hAMSCs), and amniotic fluid stem cells (hAFSCs) in the field of reproductive medicine. The therapeutic potential of these cells to restore or enhance normal ovarian function and pregnancy outcomes are highlighted in this study., (© 2022. The Author(s).)

Pollution with emerging microscopic contaminants such as microplastics (MPs) and nanoplastics (NPs) including polystyrene (PS) in aquatic and terrestrial environments is increasingly recognized. PS is largely used in packaging materials and is dumped directly into the ecosystem. PS micro-nano-plastics (MNPs) can be potentially bioaccumulated in the food chain and can cause human health concerns through food consumption. Earlier MP research has focused on the aquatic environments, but recent researches show significant MP and NP contamination in the terrestrial environments especially agricultural fields. Though PS is the hotspot of MPs research, however, to our knowledge, this systematic review represents the first of its kind that specifically focused on PS contamination in agricultural soils, covering sources, effects, and ways of PS mitigation. The paper also provides updated information on the effects of PS on soil organisms, its uptake by plants, and effects on higher animals as well as human beings. Directions for future research are also proposed to increase our understanding of the environmental contamination of PS in terrestrial environments., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Human amniotic epithelial cells (hAECs), which are a type of placental stem cell, express stem cell marker genes and are capable of differentiating into all three germ layers under appropriate culture conditions. hAECs are known to undergo TGF-β-dependent epithelial-mesenchymal transition (EMT); however, the impact of EMT on the stemness or differentiation of hAECs has not yet been determined. Here, we first confirmed that hAECs undergo EMT immediately after starting primary culture. Comprehensive transcriptome analysis using RNA-seq revealed that inhibition of TGF-β-dependent EMT maintained the expression of stemness-related genes, including NANOG and POU5F1, in hAECs. Moreover, the maintenance of stemness did not affect the nontumorigenic characteristics of hAECs. We showed for the first time that TGF-β-dependent EMT negatively affected the stemness of hAECs, providing novel insight into cellular processes of placental stem cells., (© 2022. The Author(s).)

The performance of a fast and simple analytical procedure for rare earth elements (REEs) quantification from secondary sources was investigated in the present work. Seven silicate-rich certified reference materials (CRMs) in the form of Andesite (JA-1), Basalt (JB-3), Rhyolite (JR-1, JR-2), Granite (JG-2), Granodiorite (JG-3), and Till (TILL-1), were used for the optimization and characterization of the analysis method. The optimized method was used in the analysis of nine mining wastes selected within the ENVIREE project, under the ERA-MIN Program of the 7th Framework, having as the main aim to ensure a policy securing long-term access of REEs secondary sources at reasonable costs. For silicate-rich samples efficient solid dissolution involves sintering with Na 2 O 2 at 460 °C and a sample to oxidizing reagent ratio of 1:6.5. Inductively coupled plasma-mass spectrometry (ICP-MS) was used in the quantification of the REEs with aerosol dilution of samples applied to minimize the salt effect on the plasma and interface regions. The work performed in the present study clearly shows that accurate reports on the REE concentrations from geological matrices also involves as mandatory the estimation of the overall uncertainty from various sources (sample preparation or analyte measurements). In the analysis of geological samples, the proposed analysis method has on average 23% of the overall uncertainty explained by the sample preparation and 77% accounted by the analysis steps. Moreover, the method described by effective, cheap, robust and safe attributes, can be recommended as an accessible alternative to the HF wet digestion method. Although from all the investigated tailings samples, only those from Sweden and Czech Republic can be regarded as potential secondary sources for REEs, investigation of other resources with interest at European level might bring a great benefit in the general attempt to develop an economically viable method for the production of rare earth elements., (© 2022. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

Background: Pressure ulcers (PUs), a result of ischemic reperfusion (IR) injuries, are prevalent skin problems which show refractoriness against standard therapeutic approaches. Besides, scar formation is a critical complication of ulcers that affects functionality and the skin's cosmetic aspect. The current study aimed to investigate the effects of placenta-derived human amniotic epithelial cells (hAECs), as important agents of regenerative medicine and stem cell therapy, on accelerating the healing of IR ulcers in mice. We also evaluated the effects of these cells on reducing the TGFβ-induced scar formation., Methods: Male Balb/c mice at the age of 6-8 weeks were subjected to three IR cycles. Afterward, the mice were divided into three experimental groups (n = 6 per group), including the control group, vehicle group, and hAECs treatment group. Mice of the treatment group received 100 μL of fresh hAECs 1 × 10 6 cell/ml suspension in PBS. Afterward, mice were assessed by histological, stereological, molecular, and western blotting techniques at 3, 7, 14, and 21 days after wounding., Results: The histological and stereological results showed the most diminutive scar formation and better healing in the hAECs treated group compared to control group. Furthermore, our results demonstrated that the expression level of Col1A1 on days 3, 14, and 21 in the hAECs treated group was significantly lower than control. Additionally, injection of hAECs significantly reduced the expression level of Col3A1 on days 3, 7, and 21 while increased Col3A1 on the day 14. Otherwise, in the hAECs treated group, the expression levels of VEGFA on days 7 and 14 were higher, which showed that hAECs could promote angiogenesis and wound healing. Also, cell therapy significantly lowered the protein levels of TGF-β1 on day 14, while the protein level of TGF-β3 on day 14 was significantly higher. This data could demonstrate the role of hAECs in scar reduction in IR wounds., Conclusion: These results suggest that hAECs can promote re-epithelialization and wound closure in an animal model of PU. They also reduced scar formation during wound healing by reducing the expression of TGF-β1/ TGF-β3 ratio., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Lupus erythematosus is an autoimmune disease that causes damage to multiple organs ranging from skin lesions to systemic manifestations. Cutaneous lupus erythematosus (CLE) is a common type of lupus erythematosus (LE), but its molecular mechanisms are currently unknown. The study aimed to explore changes in the gene expression profiles and identify key genes involved in CLE, hoping to uncover its molecular mechanism and identify new targets for CLE., Method: We analyzed the microarray dataset (GSE109248) derived from the Gene Expression Omnibus (GEO) database, which was a transcriptome profiling of CLE cutaneous lesions. The differentially expressed genes (DEGs) were identified, and the functional annotation of DEGs was performed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Protein-protein interaction (PPI) network was also constructed to identify hub genes involved in CLE., Result: A total of 755 up-regulated DEGs and 405 down-regulated DEGs were identified. GO enrichment analysis showed that defense response to virus, immune response, and type I interferon signaling pathway were the most significant enrichment items in DEGs. The KEGG pathway analysis identified 51 significant enrichment pathways, which mainly included systemic lupus erythematosus, osteoclast differentiation, cytokine-cytokine receptor interaction, and primary immunodeficiency. Based on the PPI network, the study identified the top 10 hub genes involved in CLE, which were CXCL10, CCR7, FPR3, PPARGC1A, MMP9, IRF7, IL2RG, SOCS1, ISG15, and GSTM3. By comparison between subtypes, the results showed that ACLE had the least DEGs, while CCLE showed the most gene and functional changes., Conclusion: The identified hub genes and functional pathways found in this study may expand our understanding on the underlying pathogenesis of CLE and provide new insights into potential biomarkers or targets for the diagnosis and treatment of CLE. Key Points • The bioinformatics analysis based on CLE patients and healthy controls was performed and 1160 DEGs were identified • The 1160 DEGs were mainly enriched in biological processes related to immune responses, including innate immune response, type I interferon signaling pathway, interferon-γ-mediated signaling pathway, positive regulation of T cell proliferation, regulation of immune response, antigen processing, and presentation via MHC class Ib and so on • KEGG pathway enrichment analysis indicated that DEGs were mainly enriched in several immune-related diseases and virus infection, including systemic lupus erythematosus, primary immunodeficiency, herpes simplex infection, measles, influenza A, and so on • The hub genes such as CXCL10, IRF7, MMP9, CCR7, and SOCS1 may become new markers or targets for the diagnosis and treatment of CLE., (© 2021. International League of Associations for Rheumatology (ILAR).)

Proper evaluation of water quality is pertinent to estuarine habitat restoration. Identifying the degrading factors of the water environment and predicting the trend of eutrophication are key to restore the habitat. Through trophic level index (TLI), water quality index (WQI), modified Nemerow pollution index (NPI), and the Random Forest (RF) model, water samples collected from various estuaries of Taihu Lake from 2017 to 2019 were evaluated. To predict the water quality development, four scenarios were set viz. S1: add or remove an ecological buffer, S2: increase or reduce the external nutrients, S3: open or close the dam/gate, and S4: increase or decrease the internal release. In Wuli Lake, the nutrient concentrations in the river regions were higher than in the lake regions, while a contrary trend was observed in Gonghu Bay. The estuarine water quality in the dry season (WQI = 40.91, NPI = 1.73) was merely worse than that in the wet season (WQI = 47.27, NPI = 1.67). On the other hand, the eutrophic status in the wet season (TLI Wet  = 57.93) was worse than that in the dry season (TLI Dry  = 57.23). The estuarine water quality of Taihu Lake has improved from 2017 to 2019 but still belongs to medium level. The principal component analysis (PCA) revealed that dam construction, land use types, unstable hydrodynamic conditions, and trumpet-shaped estuary were the main factors that aggravated the water quality degradation. The RF model has strong forecasting capabilities for estuarine water quality. When the estuaries are close to residential and industrial districts, controlling the surface runoff and improving sewage treatment efficiency are the most effective measures to improve the water quality. In the estuaries, the sediments are usually disturbed by the wind-waves. Conclusively, reducing sediment disturbance and internal contamination accumulation via biological and engineering measures is the key to estuarine restoration., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Phytoestrogens are naturally plant-derived compounds that could bind to estrogen receptors and mimic estrogenic effects. Previous studies showed a positive association between phytoestrogens and hypothyroidism; however, little is known on phytoestrogens and thyroid hormones. This study was designed to investigate the associations between urinary phytoestrogens and thyroid hormone levels. Based on the US National Health and Nutrition Examination Survey (NHANES) 2007-2010, 4103 participants were recruited in this cross-sectional study. Linear regression models and multiple linear regressions models were applied to examine the relationships between urinary phytoestrogens and thyroid hormone levels. Urinary O-desmethylangolensin (O-DMA) was found to be correlated with serum FT 4 levels in the female 20-60-year-of-age group (β=0.018, 95% CI: 0.006, 0.031). Higher enterolactone (ENT) levels were significantly positively associated with TSH levels in the 12-19-year-of-age female group (β=0.196, 95% CI: 0.081, 0.311). In the male group, enterodiol (END) was significantly positively correlated with TSH and TT 3 in the 12-19-year-of-age group, respectively (TT 3 : β=3.444, 95% CI: 0.150, 6.737; TSH: β=0.104, 95% CI: 0.005, 0.203). However, equol (EQU) levels were negatively associated with TT 4 (12-19-year-of-age: β=- 0.166, 95% CI: - 0.279, - 0.034; 20-60-year-of-age: β=- 0.132, 95% CI: - 0.230, - 0.034). Our study provided epidemiological evidence that urinary phytoestrogens were powerfully associated with thyroid hormone levels. The results also supported that phytoestrogens acted as endocrine disruptors. It is imperative and important to pay attention to the intake of phytoestrogens., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Fuchs endothelial corneal dystrophy (FECD) is one of the main causes for corneal endothelial blindness, which is characterized by the progressive decline of corneal endothelial cells. Poly (ADP-ribose) polymerase (PARP) was reported to be involved in cell death and apoptosis of several diseases. However, the role of PARP1 in the progression of FECD remains elusive. In the present study, we reported that UVA irradiation caused the corneal endothelial damage and corneal edema in mice, which was accompanied with the elevated activity of PARP1 and PAR. The PARP1 inhibitor PJ34 resolved the corneal edema and protected corneal endothelium from UVA-induced oxidative damage, mitochondrial dysfunction, and cell apoptosis. Mechanistically, PARP1 inhibition exerted its anti-apoptotic effects through downregulation of the phosphorylation levels of JNK1/2 and p38 MAPK and subsequently the increase of MKP-1. Our results suggest that PARP1 inhibition protects corneal endothelium from UVA-induced oxidative damage, which provides a potential alternative strategy for the therapy of FECD., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Emerging medical imaging applications in healthcare, the number and volume of medical images is growing dramatically. Information needs of users in such circumstances, either for clinical or research activities, make the role of powerful medical image search engines more significant. In this paper, a text-based multi-dimensional medical image indexing technique is proposed in which correlation of the features-usages (according to the user's queries) is considered to provide an off-the content indexing while taking users' interestingness into account. Assuming that each medical image has some extracted features (e.g., based on the DICOM standard), correlations of the features are discovered by performing data mining techniques (i.e., quantitative association pattern discovery), on the history of users' queries as a data set. Then, based on the pairwise correlation of the features of medical images (a.k.a. Affinity), set of the all features is fragmented into subsets (using method like the vertical fragmentation of the tables in distribution of relational DBs). After that, each of these subsets of the features turn into a hierarchy of the features (by applying a hierarchical clustering algorithm on that subset), subsequently all of these distinct hierarchies together make a multi-dimensional structure of the features of medical images, which is in fact the proposed text-based (feature-based) multi-dimensional index structure. Constructing and using such text-based multi-dimensional index structure via its specific required operations, medical image retrieval process would be improved in the underlying medical image search engine. Generally, an indexing technique is to provide a logical representation of documents in order to optimize the retrieval process. The proposed indexing technique is designed such that can improve retrieval of medical images in a medical image search engine in terms of its effectiveness and efficiency. Considering correlation of the features of the image would semantically improve precision (effectiveness) of the retrieval process, while traversing them through the hierarchy in one dimension would try to optimize (i.e., minimize) the resources to have a better efficiency. The proposed text-based multi-dimensional indexing technique is implemented using the open source search engine Lucene, and compared with the built-in indexing technique available in the Lucene search engine, and also with the Terrier platform (available for the benchmarking of information retrieval systems) and other the most related indexing techniques. Evaluation results of memory usage and time complexity analysis, beside the experimental evaluations efficiency and effectiveness measures show that the proposed multi-dimensional indexing technique significantly improves both efficiency and effectiveness for a medical image search engine., (© 2021. International Federation for Medical and Biological Engineering.)

This article revisits the properties of BaBiO 3 examined extensively in the last two decades because of its electronic properties as a superconductor and as a semiconductor photocatalyst. Solid-state syntheses of this bismuthate have often involved BaCO 3 as the barium source, which may lead to the formation of BaBiO 3 /BaCO 3 heterostructures that could have an impact on the electronic properties and, more importantly, on the photocatalytic activity of this bismuthate. Accordingly, we synthesized BaBiO 3 by a solid-state route to avoid the use of a carbonate; it was characterized by XRD, SEM, and EDX, while elemental mapping characterized the composition and the morphology of the crystalline BaBiO 3 and its thin films with respect to structure, optoelectronic, and photocatalytic properties. XPS, periodic DFT calculations, and electrochemical impedance spectroscopy ascertained the electronic and electrical properties, while Raman and DRS spectroscopies assessed the relevant optical properties. The photocatalytic activity was determined via the degradation of phenol in aqueous media. Although some results accorded with earlier studies, the newer electronic structural data on this bismuthate, together with the photocatalytic experiments carried out in the presence of selective radical trapping agents, led to elucidating some of the mechanistic details of the photocatalytic processes that previous views of the BaBiO 3 band structure failed to address or clarify. Analytical refinement of the XRD data inferred the as-synthesized BaBiO 3 adopted the C 2/m symmetry rather than the I 2/m structure reported earlier, while Tauc plots from DRS spectra yielded a bandgap of 2.05 eV versus the range of 1.1-2.25 eV reported by others; the corresponding flatband potentials were 1.61 eV (E VB ) and - 0.44 eV (E CB ). The photocatalytic activity of BaBiO 3 was somewhat greater than that of the well-known Evonik P25 TiO 2 photocatalyst under comparable experimental conditions., (© 2021. The Author(s), under exclusive licence to European Photochemistry Association, European Society for Photobiology.)

Although migraine is a neurological disorder known for its long, physiopathology remains unclear. The aim of this study was to investigate the levels of hematological parameters and neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR) and neutrophil/monocyte ratio (NMR) used as inflammatory markers in patients diagnosed with migraine. This retrospective study was performed with 250 patients and 215 healthy volunteers who were followed up in the neurology outpatient clinic with the diagnosis of migraine. Hematological parameters, C-reactive protein (CRP), NLR, PLR, LMR, NMR ratios were compared in the patient and control groups. Patients with migraine were grouped according to loss of function, the severity of pain and aura. 20.8% of patients in the mean age of 36.37 ± 8.683 had migraine with aura. We found that NMR values in migraine with aura (MWA) were significantly higher than in the control group. CRP, PLR and NMR values in migraine without aura (MWOA) were significantly higher than in the control group. Mean platelet volume (MPV) and platelet values were higher in patients with MWA and MWOA compared to the control group but did not show a statistically significant difference. We believe that these results support systemic inflammation in patients with migraine and the presence of a continuous inflammatory process even in periods without attacks. More comprehensive studies are needed to clarify the underlying pathophysiology that may guide the follow-up and treatment of the disease., (© 2020. Belgian Neurological Society.)

Purpose: Adaptive servo-ventilation (ASV) is a therapy designed for patients with central sleep apnea (CSA) and Cheyne Stokes respiration. The aim of this study was to find predictors of ASV usage in patients with CSA in a routine sleep clinic cohort., Methods: In this retrospective study, consecutive patients in whom ASV therapy was initiated at the University Hospital Regensburg between 2011 and 2015, were analyzed. Analysis included polysomnographies of diagnostic and ASV initiation nights, a phone questionnaire on ASV usage, readout of the ASV device 1 month after initiation ("early ASV usage," 1 month after ASV initiation), and the readout of the last month before a reappointment date set in 2015 ("late ASV usage," median 17 months after ASV initiation)., Results: In 69 consecutive patients, the mean early and late ASV usage per night was 4.8 ± 2.5 h and 4.1 ± 3.0 h, respectively. Seventeen months after initiation, 57% of patients used the device ≥ 4 h per night, and of those 91% reported a subjective benefit from ASV therapy. Early ASV usage was significantly associated with late ASV usage (univariable regression: Beta 0.8, 95%CI [0.6; 1.0] p < 0.001). In multivariable regression analysis, short duration of slow wave sleep (N3) during diagnostic polysomnography (Beta - 6.2, 95%CI [- 11.0; - 1.5]; p = 0.011) and subjective benefit from ASV (Beta 174.0, 95%CI [68.6; 279.5]; p = 0.002) were significantly associated with longer late ASV usage., Conclusion: Early ASV usage predicts late ASV usage. In addition, low slow wave sleep before ASV initiation and subjective benefit from ASV may contribute to higher late ASV usage.

This study investigates the effect of environmental risk factors among North Indian children aged between 6 and 16 years associated with body mass index by comparing fasting and non-fasting urine Bisphenol-A, urine creatinine, and serum thyroid levels with other potential confounding factors. A total of 301 children were enrolled, and term fasting and non-fasting were used based on the sample collection, either first morning or random. Children were grouped into obese, non-obese, and underweight categories based on age- and gender-specific Centre for Disease Control (CDC) 2000 growth chart and grouped according to their body mass index. The overall mean ± SD (standard deviation) of age (years) was 10.45±2.39 (boys age 10.38±2.38 and girls age 10.45±2.40). Urinary Bisphenol-A concentration (ng/mL ± SD) was higher among obese (2.40±4.70) than non-obese (1.30±1.67) and underweight (1.84±3.46) category children. Higher levels of fasting urinary Bisphenol-A (≥2 ng/mL) and thyroid-stimulating hormone (TSH) (≥12.7 μg/dL) were associated with obesity than those of non-fasting children. Being non-fasting among girls at quartile 4 (obese, >2.1800 ng/mL; underweight, >2.1325 ng/mL) had higher odds (obese adjusted odds ratio (aOR) 7.72 (95% CI 0.08-1368.52), underweight adjusted odds ratio (aOR) 12.45 (95% CI 1.55-171.24)] than fasting children. We recommend awareness programs and policy guidelines by engaging teachers and parents for the physical assessment of the presence of Bisphenol-A in food packaging materials to reduce the potential exposure to other chemical migrations sources. Graphical abstract.

Lanthanum-modified bentonite (LMB) is widely used for eutrophication control and has demonstrated good efficiency in some eutrophic lakes. However, the efficiency of LMB on eutrophication control in some eutrophic lakes, where the structure of food webs is mainly dominated by omni-benthivorous fish, remains ambiguous. Omni-benthivorous fish usually disturbs sediment and promotes the release of internal nutrients, the effect of which on the efficacy of LMB remains to be studied. Thus, a 30-day mesocosm experiment was conducted to determine whether omni-benthivorous fish disturbance and LMB would cause antagonistic responses. LMB significantly reduced dissolved P concentration in overlying water, converting mobile P to bound P in the surface layer of sediment in the absence of crucian carp (Carassius carassius). However, there were significantly negative interaction effects between LMB and crucian carp. Although LMB still effectively reduced the total dissolved phosphorus (TDP) and soluble reactive phosphorus (SRP) concentrations of overlying water in the presence of crucian carp, it had limited efficacy on inhibiting the increased concentrations of suspended solids, particulate nutrients, and chlorophyll a (Chl a) due to crucian carp disturbance. Furthermore, the crucian carp disturbance also increased the risk of mobile P releasing from surface sediment, whether with or without LMB application. The results indicated that the efficacy of LMB was insufficient to offset the negative effect of omni-benthivorous fish disturbance on eutrophication control. Hence, the omni-benthivorous fish also need to be considered for eutrophication control in shallow eutrophic lakes. Some measures need to be taken to control the biomass of omni-benthivorous fish.

Hepatic ischemia and reperfusion injury (IRI) is an acute inflammatory process that results from surgical interventions, such as liver resection surgery or transplantation, or hemorrhagic shock. This pathology has become a severe clinical issue, due to the increasing incidence of hepatic cancer and the high number of liver transplants. So far, an effective treatment has not been implemented in the clinic. Despite its importance, hepatic IRI has not attracted much interest as an inflammatory disease, and only a few reviews addressed it from a therapeutic perspective with drug delivery nanosystems. In the last decades, drug delivery nanosystems have proved to be a major asset in therapy because of their ability to optimize drug delivery, either by passive or active targeting. Passive targeting is achieved through the enhanced permeability and retention (EPR) effect, a main feature in inflammation that allows the accumulation of the nanocarriers in inflammation sites, enabling a higher efficacy of treatment than conventional therapies. These systems also can be actively targeted to specific compounds, such as inflammatory markers and overexpressed receptors in immune system intermediaries, allowing an even more specialized therapy that have already showed encouraging results. In this manuscript, we review drug delivery nanosystems designed for hepatic IRI treatment, addressing their current state in clinical trials, discussing the main hurdles that hinder their successful translation to the market and providing some suggestions that could potentially advance their clinical translation.

Refugee children are defined as an at-risk population as they have a high risk of physical and mental health conditions. While data exist regarding the mental health of refugee children, there are limited data about their medical health issues and mortality. Therefore, this study aimed to analyze the demographic data, clinical results, treatment/management data, and mortality data of hospitalized refugee children. This is a descriptive study that analyzed the demographic data, clinical findings, treatment/management data, and mortality data of 728 refugee children aged between 1 month and 18 years who were hospitalized in a tertiary pediatric hospital between 2013 and 2018. During the 5 year duration of this study (2013-2018), there were 12,031 patients hospitalized in the department of general pediatrics. Of these patients, 728 (6%) were refugee children [median age 1.2 (IQR 4.4) years]. The most frequent ethnic origin was Syrian, followed by Iraqi and Afghan [465 (63.87%); 174 (23.9%), and 39 (5.3%), respectively]. The median duration of hospitalization was 6 (IQR 6) days. Those refugee patients who were hospitalized in the pediatric intensive care unit were significantly younger [median age 3.7 (IQR 9.4) years]. The mortality rate in the department of general pediatrics was 16.4% for refugee patients and 8.6% for non-refugee patients (p = 0.001). A logistic regression model revealed that factors associated with mortality included younger age (OR 1.6; CI 1.2-2.1) and being a refugee (OR 2.1; CI 1.3-3.2). Our study revealed detailed knowledge about demographic, clinical, and mortality data, with the largest known series about refugee children in the literature. The results show that mortality rates are significantly higher in refugee pediatric patients who are hospitalized in Turkey than in non-refugee patients.

Most of the commercially available pharmaceutical products for oral administration route are marketed in the tablet dosage forms. However, compression of multiparticulate systems is a challenge for the pharmaceutical research and industry, especially if the individual unit is a coated particle, as the release of the active ingredient depends on the integrity of the coating. In the present study, polymer-coated pellets tableted with different types of excipients (powder, granules, pellets) then were investigated by various tablet-destructive (microscopic) and tablet non-destructive (microfocus X-ray; microCT) imaging methods. The information obtained from the independent evaluation of the in vitro drug release profiles model is confirmed by the results obtained by image analysis, regardless of whether X-ray or stereomicroscopic images of the coated, tableted pellets were used for image analysis. The results of this study show that the novel easy-to-use, fast, and non-destructive MFX method is a good alternative to the already used microscopic image analysis methods regarding the characterization of particulates, compressed into tablets.

Immune-inflammatory, metabolic, oxidative, and nitrosative stress (IMO&NS) pathways and, consequently, neurotoxicity are involved in acute ischemic stroke (IS). The simultaneous assessment of multiple IMO&NS biomarkers may be useful to predict IS and its prognosis. The aim of this study was to identify the IMO&NS biomarkers, which predict short-term IS outcome. The study included 176 IS patients and 176 healthy controls. Modified Rankin scale (mRS) was applied within 8 h after IS (baseline) and 3 months later (endpoint). Blood samples were obtained within 24 h after hospital admission. IS was associated with increased white blood cell (WBC) counts, high sensitivity C-reactive protein (hsCRP), interleukin (IL-6), lipid hydroperoxides (LOOHs), nitric oxide metabolites (NOx), homocysteine, ferritin, erythrocyte sedimentation rate (ESR), glucose, insulin, and lowered iron, 25-hydroxyvitamin D [25(OH)D], total cholesterol, and high-density lipoprotein (HDL) cholesterol. We found that 89.4% of the IS patients may be correctly classified using the cumulative effects of male sex, systolic blood pressure (SBP), glucose, NOx, LOOH, 25(OH)D, IL-6, and WBC with sensitivity of 86.2% and specificity of 93.0%. Moreover, increased baseline disability (mRS ≥ 3) was associated with increased ferritin, IL-6, hsCRP, WBC, ESR, and glucose. We found that 25.0% of the variance in the 3-month endpoint (mRS) was explained by the regression on glucose, ESR, age (all positively), and HDL-cholesterol, and 25(OH)D (both negatively). These results show that the cumulative effects of IMO&NS biomarkers are associated with IS and predict a poor outcome at 3-month follow-up.