Introduction: Drug interactions (DDIs) represent an important clinical problem particularly in elderly patients due to polytherapy, comorbidity and physiological change in pharmacodynamic and pharmacokinetic pathways. In this study we investigated the association between drugs prescribed during hospital or clinical room discharge and the development of DDIs with drugs daily used from each patient. Methods: we performed an observational, retrospective, multicenter study on medical records of outpatients referred to general practitioners. Drug interactions (DDIs) were measured using the drug interactions probability scale. Collected data were analyzed using the Statistical Package for the Social Sciences. Results: During the study we evaluated 1,622 medical records. We recorded the development of DDIs in 10.3% of patients, of those 11.6% induced the hospitalization. Logistic regression showed an association between DDIs and sex and number of drugs used (P = 0.023). Conclusion: this real-life study shows that DDIs are common in elderly patients and physicians must take more attention after hospital discharge revaluating the treatment in order to reduce the risk of DDIs and hospitalization.

Smartphone Addiction is a social issue caused by excessive smartphone use, affecting decision-making processes. Current research on the risky decision-making abilities of smartphone addicts is limited. This study used the fNIRS brain imaging technique and a Sequential Risk-Taking Task experimental paradigm to investigate the decision-making behavior and brain activity of smartphone addicts under varying risk levels. Using a mixed experimental design, the research assessed decision-making ability and brain activation levels as dependent variables across two groups (addiction and control), two risk amounts (high and low), and two outcomes (gain and loss). The study included 42 participants, with 25 in the addiction group and 17 in the control group. Results indicated that risk level significantly impacted the decision-making ability of smartphone addicts, with high-risk levels leading to weaker decision-making ability and increased risk-taking. However, at low risk levels, decision-making abilities between addicts and healthy individuals showed no significant difference. Furthermore, brain imaging results using fNIRS revealed stronger brain activation in the dlPFC region for smartphone addicts under loss outcome conditions, with no significant differences between the two groups in terms of brain activation at varying risk volumes. These findings are critical in promoting healthy smartphone use, guiding clinical treatment, and advancing brain mechanism research.

Background Very few cases of Pneumocystis jirovecii pneumonia (PCP) have been reported in COVID-19 so far, mostly in patients with concomitant HIV infection or in solid organ transplant recipients. Despite COVID-19 is associated with lymphopenia and use of steroids, there are no studies specifically aimed to investigate risk factors for PCP in COVID-19 Methods retrospective case-control study in a cohort of patients with confirmed COVID-19. Direct immunofluorescence assay on respiratory samples was used to diagnose PCP. Results We enrolled 54 patients. Patients with PCP had significant lower median lymphocyte values (p=0.033), longer COVID-19 disease duration (p=0.014), higher cumulative dose of steroid received (p=0.026), higher CRP values (p=0.005) and lower SARS-CoV-2 vaccination rate than controls (p=0.029). Cumulative steroid dose (p=0.042) and the highest CRP value during the stay (p=0.012) were identified as risk factor for PCP, while SARS-CoV-2 vaccination with one (p=0.029) and two doses (p=0.049) as a protective factor for PCP, although not independently associated. Conclusions PCP develops in COVID-19 patients regardless of immunosuppressive conditions. However, a higher rate of PCP is significantly associated with the cumulative steroidal dose, high CRP values and lack of vaccination.

The report [1] shows that in many European cities the sewer system is older than 40 years, potentially reducing their ability to cope with more intense pluvial flooding [2] addition to climate change, urbanization is an important factor increasing the flooding risk, as it increases of impervious surfaces. Flash floods are particularly troublesome, causing not only the overloading of drainage systems [3], but also urban transport disruption, affecting human health, and contributing to pollution due to untreated sewage discharges [4]. Pluvial floods in urban areas are caused by short-duration precipitation, high intensity and on small scale. Such rainfall is difficult to predict and does not always apply to catchment areas. In Poland, heavy rainfall lasts relatively short, from a few minutes to a few, at most, several hours [5]. The method of the Analytic Hierarchy Process (AHP) was used to rank the importance of criteria characterizing exposure in urban areas. The ranking is based on expert judgements. The article focuses on exposure which is one of the components of risk. Geographical Information System (GIS) is integrated with Multicriteria Decision Analysis (MCDA) to evaluate exposure of urban area on pluvial floods.

The risk of the emergence and reemergence of zoonoses is high in regions that are under anthropogenic actions, as they contribute to the risk of vector disease transmission. Yellow fever (YF) is among the main pathogenic arboviral disease in the world, and the Culicidae Aedes albopictus has been proposed to have the potential to transmit yellow fever virus (YFV). This mosquito inhabits both urban and wild environments, and under experimental conditions, it has been shown to be susceptible to infection by YFV. In this study, the vector competence of the mosquito Ae. albopictus for the YFV was investigated. Female Ae. albopictus were exposed to non-human primates (NHP) of the genus Callithrix infected with YFV for blood meal. Subsequently, on the 14th and 21st days post infection, the legs, heads, thorax/abdomen and saliva of the arthropods were collected and analyzed by viral isolation and molecular analysis techniques to verify the infection, dissemination and transmission. The presence of YFV was detected in saliva samples through viral isolation and in the head, thorax/abdomen and legs both by viral isolation and by molecular detection. The susceptibility of Ae. Albopictus to YFV confers a potential risk of reemergence of urban YF in Brazil.

Substantial evidence indicates that bisphenol A (BPA), a ubiquitous environmental chemical used in the synthesis of polycarbonate plastics and epoxy resins, can impair brain development. Clinical and epidemiological studies exploring potential connections between BPA and neurodevelopmental disorders in humans have repeatedly identified correlations between early BPA exposure and developmental disorders, like attention deficit/hyperactivity disorder and autism spectrum disorder. Investigations using invertebrate and vertebrate animal models have revealed that developmental exposure to BPA can impair multiple aspects of neuronal development, including neural stem cell proliferation and differentiation, synapse formation, and synaptic plasticity—neuronal phenotypes that are thought to underpin the fundamental changes in behavior associated neurodevelopmental disorders. Consistent with BPA-associated neuronal phenotypes, behavioral analyses of BPA-treated animals have shown significant impacts on behavioral endophenotypes related to neurodevelopmental disorders, including altered locomotor activity, learning and memory deficits, and anxiety-like behavior. To contextualize the correlations between BPA and neurodevelopmental disorders in humans, this review summarizes current literature reporting on the developmental neurotoxicity of BPA in laboratory animals, with an emphasis on neuronal phenotypes, molecular mechanisms, and behavioral outcomes. The collective works described here predominantly support the notion that gestational exposure to BPA should be regarded as a risk factor for neurodevelopmental disorders.

Preeclampsia (PE) is associated with an increased risk of cardiovascular disease (CVD) in later life. Postpartum cardiovascular risk screening could identify patients who would benefit most from lifestyle interventions. However, there are no readily available methods to identify these high-risk women. We propose that placental lesions may be useful in this regard. Here, we sought to determine the association between placental lesions and lifetime CVD risk. Placentas from 85 PE women were evaluated for histopathological lesions. At 6 months postpartum, a lifetime cardiovascular risk score was calculated. Placental lesions were compared between CVD risk groups and the association was assessed using odds ratios. Multivariable logistic regression was used to develop prediction models for CVD risk with placental pathology. Placentas from high-risk women had more severe lesions of maternal vascular malperfusion (MVM) and resulted in a 3-fold increased risk of screening high-risk for CVD (OR 3.10[1.20-7.92]) compared to women without these lesions. MVM lesion severity was moderately predictive of high-risk screening (AUC 0.63[0.51,0.75]; sensitivity 71.8%[54.6,84.4]; specificity 54.7%[41.5,67.3]. When clinical parameters were added, the model’s predictive performance improved (AUC 0.73[0.62,0.84]; sensitivity 78.4%[65.4,87.5]; specificity 51.6%[34.8,68.0]. The results suggest that placenta pathology may provide a unique modality to identify women for cardiovascular screening.

Epigenetics, specifically DNA methylation, allows for estimation of animal age from blood or remotely sampled skin. This multi tissue epigenetic aging clock uses 110 longitudinal samples from 34 Navy bottlenose dolphins (Tursiops truncatus), identifying 195 cytosine-phosphate-guanine sites associated with chronological aging via leave-one-individual-out-cross-validation (R2=0.95). With a median absolute error of 2.5 years this clock improves age estimation capacity in wild dolphins, expanding conservation efforts, enabling better understanding of population demographics.

Background and objectives: Induction of labor (IOL) is an event that occurs in up to one-quarter of pregnancies; less is known about the outcomes and safety of IOL in obese pregnant woman; no data is available on misoprostol vaginal insert (MVI) IOL in high-risk pregnancy obese women. Objectives: (1) to evaluate the rate of successful IOL with 200 μg MVI in obese (Body Mass Index - BMI over 30 kg/m2) high-risk pregnant women: late-term pregnancy, hypertension or diabetes, compared to obese non-high-risk ones; (2) to evaluate the safety profile of MVI in high-risk pregnancy obese patients. Study design: We conducted a cross-sectional study in "Filantropia" Clinical Hospital, Bucharest, Romania, from June 2017 to September 2019 (28 months). From a total of 11,096 registered live births, IOL was performed in 206 obese patients; 74 obese high-risk pregnant patients matched the inclusion criteria; of these, 33.8% pregnancies (n=25) were late-term (41 – 41+6 weeks), 43.2% (n=32) had associated pathologies (hypertension and diabetes); labor induction was guided using a standardized protocol. We evaluated the maternal and gestational age, parity, fetal tachysystole, hyper-stimulation, initial cervical status, time from induction to delivery, drug side effects, mode of delivery, and neonatal outcomes. Results: (a) The overall successful labor induction rate, evaluated by the vaginal delivery rate, was 71.6% (n=53), spontaneously or instrumentally assisted; 28.4% (n=21) births were unsuccessful MVI IOL, converted into caesareans. (b) No significant differences were found regarding the maternal outcomes; in terms of perinatal outcomes of safety, four cases of high-risk pregnancies vaginally delivered were associated with neonatal intensive care unit (NICU) admissions and a one-minute Apgar score under seven (5.4%). Most cases with adverse effects of misoprostol have been managed conservatively, except for three emergency C-section cases. Conclusions: Misoprostol vaginal insert is a safe choice in IOL in obese high-risk pregnancies with good maternal and perinatal outcomes.

In order to establish a new discipline specializing in accident science from the perspective of safety science. Under the guidance of the current research theories and methods of safety science, combined with the research paradigm of humanities and social medicine, this paper puts forward new viewpoints, new theories and new models about accident research. First of all, through literature retrieval, this paper analyzes the relevant research results of accidents at home and abroad, and expounds the existing problems and the basic trend of accident science research. Secondly, it puts forward eight kinds of attribute relations of the accident, and makes clear the characteristics and connotation of the accident. In the study of accident types, a hierarchical classification model based on accident cognition is created for the first time. It also points out the logical relevance of five levels of accident science research and the realistic relevance of three levels. At the same time, according to the thought of science of science, this paper puts forward a new definition of safety under the thinking of accident science and other basic concepts related to safety science, and explains the connotation. In addition, it creates and constructs the basic concept of accident science, establishes the conceptual model of accident science, and points out the “3-4-5” model of accident science research and its connotation. Thirdly, draw lessons from the interdisciplinary paradigm to study the relevant theoretical basis and discipline classification relationship of accident science, and construct the tree of accident science. Finally, the research contents of three main aspects of accident science are summarized. The results show that the research results in this paper not only play a fundamental role in the basic construction of accident science, but also further enrich and perfect the discipline system of safety science, which has a certain theoretical significance.

The current spreading novel coronavirus SARS-CoV-2 is highly infectious and pathogenic and has attracted global attention. Recent studies have found that SARS-CoV-2 and SARS-CoV share around 80% of homology and use the same cell entry receptor, ACE2. These inspired us to study other receptors of SARS-CoV, which may be used for SARS-CoV-2 binding as well. In this study, we screened the gene expression of three receptors (ACE2, DC-SIGN and L-SIGN) in four datasets of normal lung tissue from lung adenocarcinoma patients and two single-cell RNA sequencing datasets from normal lung and bronchial epithelial cells separately. No significant difference in gene expression of these three receptors were found between gender groups (male vs female). We found higher gene expression of DC-SIGN in elder with age>60 and higher gene expression of L-SIGN in Caucasian than Asian. Similar to ACE2, we observed significantly higher DC-SIGN gene expression in the lungs of smokers, especially former smokers. However, smokers upregulate ACE2 and DC-SIGN gene expression in different cell types. In the whole lung, ACE2 is actively expressed in remodeled Alveolar Type II cells of former smokers, while DC-SIGN is largely expressed in monocytes of former smokers and dendritic cells of current smokers. In bronchial epithelium, no obvious gene expression of DC-SIGN and L-SIGN was observed while ACE2 was found to be actively expressed in goblet cells of current smokers and club cells of non-smokers. In conclusion, our findings may indicate that smokers, especially former smokers, and people over 60 have higher risk and are more susceptible to SARS-CoV-2 infection. Also, this study provides hints on possible SARS-CoV-2 pathogenicity mechanisms in lung infection.

In last decades, growing migration flows have modified the obstetric clinical care, requiring specific attention by health care systems. The aim was to describe the phenomenon focusing on miscarriage (pregnancy loss at <20 weeks). Patients admitted for care at miscarriage in a six-year period (2012-17) were revised. Miscarriage rates in all ethnic groups, dichotomized in early (within the first 12 weeks of gestation) and late (at <20 weeks) pregnancy loss. Associations between women's characteristics (age, parity, inter-pregnancy interval (IPI)) were explored to elucidate any differences. A total of 1,940 patients were included, segregated in early (n = 1769, 91.2%) and late (n = 171, 8.8%) pregnancy losses. Caucasian ethnicity was the most common (87.9%), leaving the minority groups to 12.1%. Maternal age was higher among Caucasians women than other subgroups, in contrast to Asiatic patients. Nulliparity was observed in 1045 (53.9%) patient, more widespread among Caucasian and Maghrebins. A positive obstetric history counting at least one miscarriage was frequent, ranging from 22.2% to 75%, in particular among Asiatic women, while the recurrence in Caucasians. In Afro-Carribeans the most relevant rate of late miscarriage was found. By multiple regression modelling, maternal age, nulliparity and Afro-Carribean were identified as determinants. Maternal ethnicity should be considered in the management of pregnancy losses in combination with already well-defined risk factors, including age at miscarriare and nulliparity.

Background: The aim of this study was to investigate the risk of obstructive sleep apnea (OSA) among ankylosing spondylitis (AS) patients in a nationwide population. Methods: We conducted a nationwide cohort study between 2003 and 2013 using the Taiwan National Health Insurance Research Database. The AS cohort included 2210 patients who were newly diagnosed between 2003 and 2013. Randomly selected non-AS controls were matched at a 1:4 ratio based on age, sex and index date. The endpoint of OSA was occurrence or the end of 2013. Cumulative incidences, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated after adjusting for age, gender, comorbidities and co-medications. Multivariate analyses were performed using Cox proportional hazards model. Due to violation of the proportionality assumption, landmark analysis was conducted to explore the risk of OSA during specific follow-up periods. Results: The adjusted HR (aHR) of OSA for the AS group was 2.826 (95% C.I. = 1.727–4.625) compared to the control group. On landmark analysis, aHR was 7.919 (95% C.I. = 3.169–19.792) for AS group 0–24 months from index date, and decreased to 1.816 (95% C.I. = 0.944–3.494) at ≥ 24 months from index date. On subgroup analyses increased risks of OSA in AS group compared to the control group were found for both males and females (aHRs were 4.533 (95% C.I. = 1.441–14.262) and 2.672 (95% C.I. = 1.522–4.692) for females and males, respectively). On age stratified analysis, there was significant risk only for the 40–59 age group with aHR of 3.913 (95% C.I. = 1.890–8.102). Conclusions: A higher risk of developing OSA was found among newly diagnosed AS cohort during the 12-year follow-up period, especially within 2 years after AS index date and in the 40–59 age group.

Previous research suggests that the economic crisis can affect mental health. The purpose of this study was to analyse the association of risk of poor mental health with various socioeconomic, demographic, health, quality of life and social support variables; and to evaluate the contribution of socioeconomic variables most affected by the beginning of the economic crisis (employment situation and income) on the changes in the prevalence of the risk of poor mental health between 2005 and 2010. A study of prevalence evolution in adult population residents of the Valencian Community in the Spanish Mediterranean was conducted. We studied 5781 subjects in 2005 and 3479 in 2010. Logistic regression models have been adjusted to analyse the association between variables. A standardization procedure was carried out to evaluate which part of the changes in overall prevalence could be attributed to variations in the population structure by age, sex, employment status and income between the years under study. The prevalence of GHQ + increased from 2005 to 2010, in both men and women. Several variables were closely associated with the risk of poor mental health (sex, age, country of birth, number of non-mental chronic diseases, social support, disability, cohabitation in couple, employment status, and income). The changes produced as a result of the onset of the economic crisis in income and unemployment (increase in low income and in unemployment rates) contributed to the increase of poor mental health risk. This could confirm the sensitivity of mental health to the economic deterioration caused by the crisis.

In order to summarized the polygenic background of psychiatric diseases, polygenic risk scores (PRS) have been developed. Recently, PRS have been use to predict patients with higher comorbidities in psychiatric diseases, like dual diagnosis. PRS are principally derived in analysis of Caucasian and Asian populations, we are not aware of how this PRS could be applied in populations with high admixture. In order to explored this, the present work has the aim to analyzed if previous calculated PRS for psychiatric diseases could predict dual diagnosis in Mexican population, and also, if PRS calculation could be influenced by Mexican Amerindian (MA) global ancestry. We performed PRS calculation, using PRSice, with summary genome-wide association statistics previously published for psychiatric diseases, and also, performed Nagelkerke correlation test in order to established if PRS are correlated with dual diagnosis. We found that dual diagnosis could be predicted by major depressive disorder polygenic risk score. Nevertheless, schizophrenia polygenic risk score is highly correlated with global MA ancestry, independently of the schizophrenia diagnosis. Our results reinforced the notion that PRS calculation could be deviated by the MA global ancestry, nevertheless analysis on larger sample sizes are required in order to clarified this issue.

Persistent cervical infection with high-risk Human papillomaviruses (hrHPVs) is a necessary, but not sufficient, condition for the development of cervical cancer. Therefore, there are other co-factors facilitating the hrHPV carcinogenic process, one of which is smoking. In order to assess the effect of smoking on high-risk (hr) HPV DNA positivity and on the expression of HPV E7 oncoprotein, as a surrogate of persistent hrHPV infection, we used data from women recruited for the PIPAVIR project, which examined the role of E7 protein detection in cervical cancer screening. Women were tested for hrHPV DNA, using Multiplex Genotyping and E7 protein, using a novel sandwich ELISA method, and gave information on their smoking habits. Among 1473 women, hrHPV prevalence was 19.1%. The odds ratio (OR) for hrHPV positivity of smokers compared to non-smokers was 1.785 (95%CI: 1.365-2.332, p<0.001). The ORs for E7 positivity, concerning hrHPV positive women, ranged from 0.720 to 1.360 depending on the E7 detection assay used, but this was not statistically significant. Smoking increases the probability of hrHPV infection, and smoking intensity is positively associated to this increase. Smoking is not related to an increased probability of E7 protein positivity for hrHPV positive women.

Whereas waste management research has focused on mostly urban municipalities in South Africa, not much is known about the current performance of waste management services from the perspective of community residents in rural municipalities. This study reports on the status and effectiveness of waste management practices from the perspective of community residents in the Umkhanyakude and Zululand Districts in the rural areas of the KwaZulu-Natal province of South Africa. Making use of structured questionnaires, primary data was obtained by interviewing 333 respondents representing households in the study area. Results have revealed several shortfalls in the provision of municipal waste management services, except for solid waste removal from households (66%), and management of landfill sites (41%). The degree of dissatisfaction for waste management services rendered was very high (97.3%). Furthermore, the majority (61.4%) of respondents were not willing to participate in waste segregation due to lack of appropriate knowledge and infrastructure. The study also pinpointed some benefits associated with waste minimization, as well as barriers constraining effective waste recycling. Based on these findings, there is a dire need for transforming current waste management practices toward increased recycling rates by creating more environmental awareness and a supporting infrastructure.

'Cv 'Doña María' table grape is a high-quality table grape variety included in the Protected Designation of Origin (PDO) of the European Union "The bagged grape of the Vinalopó." The PDO stipulates that grape clusters must be protected with paper bags from inclement weather and insects, which helps enhance the final grape quality. However, 'Doña María' is a variety prone to high shattering in the late stages of ripening on the vine and during postharvest. Inorganic calcium treatments are one of the most commonly used tools to reduce this disorder, but the translocation of this mineral from veraison onward has been questioned. In this study, five applications were performed, from veraison to harvest, using sorbitol-chelated calcium (0.7 % + 1.0 %), Ca(NO3)2 (Ca) at 0.7% and sorbitol at 1%. It was observed that bagged grapes (not wetted with the solutions) only increased the concentration of total and bound calcium when treated with Sorbitol-Ca. This resulted in reduced berry drop during cultivation and postharvest and improved fruit firmness. Additionally, it reduced grape metabolism indicators such as respiration rate, weight loss, malic acid degradation, prevented abscisic acid (ABA) and malondialdehyde (MDA) accumulation, and favored the accumulation of secondary metabolites such as total polyphenols, increased antioxidant activity, and sugar content. The application of sorbitol-chelated calcium is an effective and safe tool that enhances fruit quality and prevents losses due to shattering during postharvest.

Listeria monocytogenes is an emerging pathogen responsible for serious foodborne disease, listeriosis. Commensal gut microbiota is the first line of defense against pathogen internalization. Gut microbiome can be modified by prebiotic substrates, which are among others frequently added to food products and dietary supplement. Prebiotics should selectively support the growth of beneficial microbes and thus improve host health. Nevertheless, little is known about their effect on growth of L. monocytogenes. The aim of this study was to evaluate the growth ability of four L. monocytogenes strains, representing the most common serotypes, on prebiotic oligosaccharides: beta(1,3)-D-glucan, inulin, fructooligosaccharides, galactooligosaccharides, lactulose, raffinose, stachyose, 2´-fucosyllactose and mixture of human milk oligosaccharides as a sole carbon source. The results showed that only beta(1,3)-D-glucan was metabolized by L. monocytogenes. Therefore, the health-safety of beta(1,3)-D-glucan in respect to listeriosis development should be furthermore studied.

The serendipitous discovery of antiparasitic drugs, such as quinine and artemisinin from plant origin reveals that the search for new chemical pharmacophores from medicinal plants is valuable. The present study sought to explore the antiplasmodial, antileishmanial, and antitrypanosomal activities of extracts from Lippia adoensis. Crude extracts of L. adoensis leaves and twigs, which were obtained by extraction using 70% ethanol in water, were assayed for antiplasmodial activity against P. falciparum 3D7 and Dd2 through the SYBR green I-based fluorescence assay; and for antileishmanial, antitrypanosomal, and cytotoxic effects on Leishmania donovani, Trypanosoma brucei brucei, and Vero cells, respectively, using the resazurin colorimetric assays. The phytochemical analysis of the extracts was performed using a liquid chromatography-mass spectrometry (LC-MS) feature-based detection and molecular networking flow on Global Natural Product Social (GNPS). As a result, the crude extracts from L. adoensis inhibited growth of P. falciparum (3D7 and Dd2) (IC50s; (3D7): 10.008 and 97.467 μg/mL; (Dd2): 29.48 and 26.96 μg/mL), L. Donovani (IC50s: 22.879-10.522 μg/mL), and T. brucei brucei (IC50s: 2.3085-55.06 μg/mL). The extracts were found to be non-cytotoxic to Vero cells, thus yielding median cytotoxic concentrations (CC50s) above 100 μg/mL. The LC-MS tandem molecular networking flow predicted that the extracts contain valsafungin A and bacillamidin on the first cluster, and fatty acids, ketone and aldehyde derivatives on the second cluster. Overall, the present study demonstrated the antiparasitic effects of L. adoensis extracts, thus justifying the use of this plant in the traditional treatment of fever and malaria conditions. Nevertheless, detailed metabolomic studies and antiparasitic mechanisms of action of the extracts are expected to unveil the potential antiparasitic hit compounds.

Compared to the general population, patients with inflammatory bowel disease (IBD) are less likely to be vaccinated, putting them at an increased risk of vaccine-preventable illnesses. This risk is further compounded by the immunosuppressive therapies commonly used in IBD management. Therefore, developing new treatments for IBD that maintain immune function is crucial, as successful management can lead to better vaccination outcomes and overall health for these patients. Here, we investigate the potential of recombinant banana lectin (rBanLec) as a supporting therapeutic measure to improve IBD control and possibly increase vaccination rates among IBD patients. By examining the therapeutic efficacy of rBanLec in a murine model of experimental colitis, we aim to lay the foundation for its application in improving vaccination outcomes. After inducing experimental colitis in C57BL/6 and BALB/c mice with 2,4,6-trinitrobenzene sulfonic acid, we treated animals orally with varying doses of rBanLec 0.1-10 µg/ml (0.01 – 1 µg/dose) during the course of the disease. We assessed the severity of colitis and rBanLec’s modulation of the immune response compared to control groups. rBanLec administration resulted in a dose-dependent reduction in colitis severity (less pronounced weight loss, less shortening of the colon) and an improved recovery profile, highlighting its therapeutic potential. Notably, rBanLec-treated mice exhibited significant modulation of the immune response, favoring anti-inflammatory pathways (primarily reduction in a local [TNFα]/[IL-10]) crucial for effective vaccination. Our findings suggest that rBanLec could mitigate the adverse effects of immunosuppressive therapy on vaccine responsiveness in IBD patients. By improving the underlying immune response, rBanLec may increase the efficacy of vaccinations, offering a dual benefit of disease management and prevention of vaccine-preventable illnesses. Further studies are required to translate these findings into clinical practice.

This review aims to explore the intricate relationship between epigenetic mechanisms, stress, and affective disorders, focusing on how early life experiences and coping mechanisms contribute to susceptibility to mood disorders. Epigenetic factors play a crucial role in regulating gene expression without altering the DNA (deoxyribonucleic acid) sequence, and recent research has revealed associations between epigenetic changes and maladaptive responses to stress or psychiatric disorders. A scoping review of 33 studies employing the PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta-Analyses – Statement) guidelines investigates the role of stress-induced epigenetic mechanisms and coping strategies in affective disorders' occurrence, development, and progression. The analysis encompasses various stress factors, including childhood trauma, work-related stress, and dietary deficiencies, alongside epigenetic changes such as DNA methylation and altered gene expression. Findings indicate that specific stress-related genes frequently exhibit epigenetic changes associated with affective disorders. Moreover, the review examines coping mechanisms in patients with bipolar disorder and major depressive disorder, revealing mixed associations between coping strategies and symptom severity. While active coping is correlated with better outcomes, emotion-focused coping may exacerbate depressive or manic episodes. Overall, this review underscores the complex interplay between genetic predisposition, environmental stressors, coping mechanisms, and affective disorders. Understanding these interactions is essential for developing targeted interventions and personalized treatment strategies for individuals with mood disorders. However, further research is needed to elucidate specific genomic loci involved in affective disorders and the clinical implications of coping strategies in therapeutic settings.

Pipeline conflicts arising from data dependencies are a common issue encountered in the hardware implementation of layered QC-LDPC decoders. This paper proposes an efficient layered decoding architecture to reduce pipeline conflicts without introducing stall cycles, by reordering the processing order offline and using the patch method based on variable-to-check message. The experimental results on the LDPC code of the IEEE802.16 standard in the OFDM-PON system demonstrate that the proposed architecture has a sensitivity improvement of 0.125 dBm and 0.375 dBm, respectively, compared with our previous work and the method described in the other work.

Abstract: Field studies with large-stemmed plants Artemisia dubia (wormwood) have been carried out at Vėžaičiai Branch LAMMC since 2018. According to three years of experimental results, annual dry matter (DM) yield varied from 7.94 to 10.14 t ha-1. Growing conditions, nitrogen ap-plication level and harvesting time had significant impacts on Artemisia dubia productivity. This article presents the results of research on preparation and use of Artemisia dubia biomass for en-ergy conversion and evaluation of technological-technical and environmental parameters of these plants utilization for solid biofuel. For experiments were used 6 variants of Artemisia dubia samples, which were grown in 2021: plants were cut three times and two fertilization options were used: (1) no fertilization and (2) fertilization with 180 kg ha-1 of nitrogen fertilizer. These harvested plants were chopped, milled and were pressed into the pellets. The physi-cal-mechanical characteristics (mоisture content, density and strength) of Artemisia dubia pellets were investigated. During this study, it was found that the density in dry mass (DM) of pellets ranged from 1119.86 to 1192.44 kg m-3. The pellet moisture content ranged from 8.80 to 10.49%. After testing of pellet strength, it was found that the pellets which were made from plant bio-mass PK-1-1, were the most resistant to compression, they withstood 560.36 N of pressure. Dry fuel lower heating value (LHV) of pellets was sufficiently high and was very close to pine saw-dust pellets, it varied from 17.46±0.25 MJ kg-1 to 18.14±0.28 MJ kg-1. The ash content of burned pellets ranged from 3.62±0.02% to 6.47±0.09%. Emissions of harmful pollutants – CO2, CO, NOx and unburnt hydrocarbons (CxHy) did not exceed the maximum permissible levels. Summariz-ing the results of investigated properties, cоmbustion and emissiоns of Artemisia dubia pellets, it can be concluded that this biofuel can be used for production of pressed biofuel and it is charac-terized by sufficient high quality, efficient combustion and permissible emissions to the envi-ronment.

This paper aims to demonstrate that, beyond the small world of Riemann-Liouville and Caputo derivatives, there is a vast and rich world with many derivatives suitable for specific problems and various theoretical frameworks to develop, corresponding to the different paths taken. Notions of time and scale sequences are introduced and general associated basic derivatives, namely right/stretching and left/shrinking, are defined. A general framework for fractional derivative definitions is reviewed and applied to get both known and new fractional order derivatives. Several fractional derivatives are considered, mainly: Liouville, Hadamard, Euler, bilinear, tempered, q-derivative, and Hahn.

Background: Across the world, antibiotic resistance is a critical challenge. To address such a problem, it has to be done to investigate new antibiotic sources. Aim of the study: Study of the antibacterial activity of Corallopyronin A in preclinical animal testing and randomized human clinical trials stages 1/2, as well as investigating the purification of Corallopyronin A from different soil conditions in Egypt. Type of the study: Screening experimental study. Methodology: Egypt's various soil conditions were tested to develop bacterial isolates that produced the antibiotic compound Corallopyronin A. Reversed phase HPLC was used to purify Myxopyronin A. The broth microdilution method and the paper disc diffusion assay determined the test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity. Moreover, in vivo antibacterial spectrum, adverse medication responses, and pharmacokinetics were found in phases 1/2 of randomized clinical studies involving humans and animal models. Results: Corallopyronin A was generated from the culture supernatant of the soil bacterial isolate Corallococcus coralloides M2, cultivated on a Casein yeast peptone( CYP) plate. The test antibiotic prevented the growth of several Gram-ve bacteria, including Escherichia coli, at MICs higher than 100 mcg/ ml; while blocking the development of many Gram +ve bacteria, with MICs ranging from 3 to 15 mcg/ ml. However, eukaryotic cells—such as those found in fungi and humans—were unaffected. A bactericidal consequence of the test antibiotic was detected in the inhibition of prokaryotic DNA-dependent RNA polymerase( RNLP). Conclusion: The synthesis of the bactericidal antibiotic Corallopyronin A from Corallococcus coralloides M2 isolated from different soil settings in Egypt intrigued the current investigation.

Objective: Mechanical bowel preparation is essential for the visualisation of the colon during colonoscopy, and previous studies have identified changes in gut microbiota composition after bowel preparation and colonoscopy. Considering the gut microbiota is increasingly implicated in mood, we aimed to explore the potential impact of this intervention on mood and the microbiota-gut-brain axis. Methods: We conducted a pre-post intervention study, with timepoints of one week before and one month after bowel preparation and colonoscopy, in community-dwelling adults referred for colonoscopy. Our primary outcome was change in average Hospital Anxiety and Depression Scale depression sub-scores using generalised estimating equations. We also examined changes in average anxiety, stress, and quality of life scores, and faecal microbiota composition and potential function using 16S rRNA sequencing. We further explored associations between changes in depressive symptoms and the gut microbiota and conducted post-hoc analyses to explore potential effect modifiers. Key Results: 59 participants were included in the analyses. Depressive symptoms decreased one-month post-procedure compared to baseline (adjusted β=−0.64; 95%CI: −1.18, −0.11). Irritable bowel syndrome (IBS) appeared to moderate this relationship (1.78; 0.292, 3.26); depressive symptoms increased in those with, and decreased in those without, IBS. Changes in gut microbiome composition included reduced alpha diversity, modest effects on beta-diversity, and increases in genera associated with potential health benefits, one-month post-procedure compared to baseline. Increases in the CLR-transformed abundance of Ruminococcaceae UCG-009 were associated with improvements in depressive symptoms. Conclusions: There is preliminary evidence of a potential mental health effect of bowel preparation and colonoscopy, which may be associated with changes to the gut microbiota. There may also be a differential mental health impact of this procedure for those with and without IBS. Considering the limitations of our study, further research is required to confirm these findings and their clinical relevance.

Ever since Varela and Maturana proposed the concept of autopoiesis as the minimal requirement for life, there has been a focus on cellular systems that erect topological boundaries to separate themselves from their surrounding environment. Here we reconsider whether the existence of such a spatial boundary is strictly necessary for self-producing entities. This work presents a novel computational model of a minimal autopoietic system inspired by dendrites and molecular dynamics simulations in three-dimensional space. A series of simulation experiments where the metabolic pathways of a particular autocatalytic set are successively inhibited until autocatalytic entities that could be considered autopoietic are produced. These entities maintain their distinctness in an environment containing multiple identical instances of the entities without the existence of a topological boundary. This gives rise to the concept of a metabolic boundary which manifests as emergent self-selection criteria for the processes of self-production without any need for unique identifiers. However, the adoption of such a boundary comes at a cost, as these autopoietic entities are less suited to their simulated environment than their autocatalytic counterparts. Finally, this work showcases a generalized metabolism-centered approach to the study of autopoiesis that can be applied to both physical and abstract systems alike.

Silicon carbide single crystal (SiC) has been widely used in the field of power devices, while it is difficult to fabricate ultra-flat surface by traditional manufacturing technologies due to its difficult-to-machine property. This paper investigates the interaction process during femtosecond laser ablation of crystalline silicon carbide based on the two-temperature model simulation and experimental study. The findings reveal that parameters such as laser pulse energy, scanning interval, and defocus amount exert significant influence on ablation depth, roughness, and surface morphology. The femtosecond laser proves effective in removing surface defects from cut SiC substrates, albeit resulting in increased surface roughness. However, subsequent polishing treatment of the laser-ablated silicon carbide surface can mitigate this roughness, underscoring the feasibility of laser surface ablation for silicon carbide single crystals.

Phyllanthus emblica (P. emblica) has been described in many studies to have multiple therapeutic activities and is considered an important part of Ayurvedic and Unani medicinal systems. This study successfully synthesized P. emblica loaded polyvinylalcohol/gelatin based cryogels (PVA/Gel/P.emblica) to examine their potential in wound dressing applications. Swelling tests, Brunauer-Emmett-Teller (BET) and morphology analysis were conducted within the scope of characterization studies. In vitro cell culture studies were performed using HaCaT cells to illustrate the suitability of the synthesized cryogels as wound dressing material. The swelling tests and BET analysis results showed that swelling and surface area properties of cryogels increased with increasing P. emblica amounts. Morphological results displayed that the cryogels had a dense, interconnected pore morphology and a macroporous structure. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), trypan blue exclusion and live-dead assay results revealed that adding of P. emblica into cryogels led to enhanced cell proliferation, increased cell number, and improved cell viability. Based on the phase contrast microscope, scanning electron microscope (SEM), immunofluorescence and giemsa staining images, it was observed that P. emblica promoted cell attachment, proliferation and penetration. In conclusion, it has been shown that PVA/Gel/P.emblica cryogels are suitable for use as wound dressing materials and can be developed with further studies.

Severe Acute Respiratory Disease Syndrome Coronavirus 2 has caused a global pandemic. Monoclonal antibodies, antiviral therapy (Remdesivir) and immunomodulatory agents represent one of the most promising therapies to prevent disease progression and reduce the relative risk of severe COVID-19. The aim of this study was to evaluate the impact on the disease progression of the main pharmacological options approved for the patients admitted in hospital with acute COVID-19 infection, according to their vaccination status.. We conducted a study including adult patients with confirmed COVID-19 admitted to the Infectious Diseases Unit of Alessandria’s Hospital in Italy, from October 2021 to March 2022. 102 patients were included in the analysis. The mean age was 69.2 ±15.4 years, 66.7% were males. According to the internal hospital’s guidelines, 47.06% patients with mild to moderate disease were treated with mAbs, 45.10% were treated with Remdesivir, of which 10.78% received combination therapy with mAbs. The most frequently complications were pneumonia (18.63%), respiratory failure (15.68%) and acute respiratory distress syndrome (13.72%). The mean length of hospitalization was 13.42 (±10.90) days and the mortality rate was 11.76%. The treatment with mAbs and immunomodulatory therapy for mild to moderate COVID-19 infection seem to be effective to improve the outcome reducing disease progression and mortality. C-reactive protein (CRP) and ferritin could be considered a good inflammatory marker of disease progression.

Abstract. Babies born to severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) infected mothers are at greater risk for perinatal morbidity and more likely to receive a neurodevelopmental diagnosis in the first year of life. However, the effect of maternal infection on placental function and neonatal outcomes varies depending upon the patient population. We set out to test our hypothesis that maternal SARS-CoV-2 infection in our underserved, socioeconomically disadvantaged, predominantly African American and Latina population in the Bronx, NY would have effects evident at birth. Fifty-five SARS-CoV-2 positive and 61 negative third trimester patients were randomly selected from Montefiore Medical Center (MMC), Bronx, NY. In addition, two positive cases from Yale New Haven Hospital, CT were included as controls. All 55 placentas delivered by SARS-CoV-2 positive mothers were uninfected by the virus, based on immunohistochemistry, in-situ hybridization, and qPCR analysis. However, placental villous infarcts, mild preeclampsia, shortened gestational periods and lower Apgar scores were observed in the infected cases. These findings suggest that even without entering the placenta, SARS-CoV-2 can affect various systemic pathways culminating in altered placental development and function, which may adversely affect the fetus, especially in a high-risk patient population such as ours. These results underline the importance of vaccination among pregnant women, particularly in low resource areas.

A 1-year prospective study was carried out on patients in the ICU unit at a tertiary care hospital, Hail, Kingdom of Saudi Arabia. A total of 163 bacterial isolates were obtained from different clinical specimens with a high proportion of bacteria found associated with ventilator-associated pneumoniae (70, 43%), followed by catheter-associated urinary tract infection (39, 24%), central line-associated bloodstream infection (25, 15%), and surgical site infection (14, 8.6%). Klebsiella pneumoniae was the most common isolate (39, 24%), followed by Acinetobacter baumannii (35, 21.47%), Pseudomonas aeruginosa (25, 15%), and Proteus spp (23, 14%). Among the highly prevalent bacterial isolates, extended-spectrum beta-lactamase was predominant (42, 42.4%). Proper use of antibiotics, continuous monitoring of drug sensitivity patterns, and taking all precautionary measures to prevent beta-lactamases-producing organisms in the clinical settings are crucial and significant factors to fend off life-threatening infections and for a better outcome.

Abstract Background Single nucleotide polymorphism (SNP) are the most common type of genetic polymorphism. SNP can significantly affect the expression activity of genes and the level of protein production. Researching the role of SNP in the occurrence of diseases is an important and urgent task, as it allows to predict the risk of pathology, its severity and outcome. Purpose of the study: study of the frequency of I148M polymorphism of the PNPLA3 gene in residents of the Republic of Sakha (Yakutia), associated with a high risk of steatosis and liver fibrosis. Methods A total of 3132 peripheral venous blood samples were used for population studies, studies patients with chronic hepatitis B and C, studies patients with NAFLD. Genotyping of DNA samples was carried out by real time-PCR. Reagent kits were used for genotyping I148M polymorphism of the PNPLA3 gene. Results In the present study, it was found that in the Yakut population the carriage of the GG genotype (49%) of the PNPLA3 gene I148M polymorphism predominates. When conducting a comparative frequency analysis, there were no statistically significant differences between the control group and the group with NAFLD patients(p=0,82). A comparative frequency analysis of the distribution of genotypes and alleles of I148M polymorphism of the PNPLA3 gene in the control group and the group of patients with chronic hepatitis B and C showed that we did not reveal significantly significant differences (p = 0.45). Conclusions The frequency of homozygotes for the mutant G allele of the I148M polymorphism of the PNPLA3 gene in the Yakut population significantly exceeds the frequency indicator of the G allele in other world populations.

Social distancing, washing hands and good hygiene are essential and currently the most potent methods available to curb down the unprecedented speed by which the new coronavirus is spreading across the globe. Even under lockdown, which is necessary to significantly reduce the number of people that get infected by an ill person, are there additional measures that each of us can embrace to even further reduce the risk of infection and the severity of the COVID-19 disease? Given the lack of licensed drugs that target SARS-CoV-2 specifically, we have to look into additional non-specific defense mechanisms that animals and humans evolved to protect themselves from pathogen invasions. The goal of this article is to describe how various of our non-specific defense mechanisms work, which actually precede the inflammatory response, and to discuss whether we can exploit the unique features of the coronavirus envelope and the self-cleaning machinery of the human respiratory tract to strengthen our self-defense. The challenge is to actively interfere with supportive measures during the short time window between getting exposed and before an inflammatory response gets initiated.

Variable flow emitters are a new type of emitter for underground drip irrigation that are used in locations where soil moisture is difficult to transport to the surface, which leads to crop emer-gence difficulties. The flow channel structure parameters of emitters affect the hydraulic per-formance of the emitter and its anticlogging ability. In this study, the variable flow emitter at the conventional low–flow water supply stage is taken as the research object. A combination of CFD numerical simulation of a two–phase flow of water and sand and clear water testing of test samples is applied to study the influence laws of 10 groups of variable flow emitter structural combinations on the effluent flow rate (q), flow index (x), particle passage rate and flow field inside the flow channel. The results show that the Realizable k–ε turbulence model can be used to simulate the flow field inside the variable flow emitter flow channel. The nRMSE between the measured and simulated values of q is 11.23%, and the relative error between the measured and simulated values of x is 4.66%, which gives a high simulation accuracy. The polar analysis shows that the tooth angle A has the smallest effect on the effluent flow rate q0.1 under 0.1 MPa, x, and particle passage rate of the variable flow emitter. The depth of the flow channel D, the spacing of the teeth B, and the height of the teeth E have a different order of precedence in the influence of the three indices, which are D > B > E > A, B > E > D > A, and E > B > D > A, respectively. The value of particle passage rate is positively correlated with the mean flow velocity (v) and the mean turbulent kinetic energy (k) in the flow channel, and particle passage rate tends to increase and then decrease with the increase of x. The retention time (t) of the particles in the flow channel is closely related to the magnitude of v and k. Three multivariate linear regression equations (R2 = 0.883 ~ 0.995) were constructed for q0.1, x, and particle passage rate versus the flow channel structural parameters. Using the scipy.optimize.minimize function in Python, we de-termined the three optimal combinations of flow channel structural parameters corresponding to better hydraulic performance: q0.1 is 1.5 or 2 L/h (objective function y = min x), better clogging resistance (y = max particle passage rate), and both (y = min (0.5 x - 0.5 particle passage rate)). The research results can provide a ref-erence for the optimal design of variable flow emitters.

A major problem of the technological production process of the metallurgical-grade silicon is formation of a large amount of microsilica. However, this material can be a significant source of raw materials for its own production. Hence, this study is aimed to solve the problem of micro-silica utilization, i.e. the technogenic dust-like waste generated during the melting of the technical-grade silicon. Within this study, the technology of the joint briquetting of microsilica was investigated with the carbonaceous reducing agents, i.e. by obtaining of mono-charge and by melting of the technical-grade silicon from the obtained mono-charge in the 200kVA ore-thermal furnace. Results of the study show that the briquettes in the melting process of the technical-grade silicon can be used in the range from 0 to 50%. The using of briquettes may significantly improve the technological parameters. When briquetted charge is applied only, the technological parameters will deteriorate significantly. The material balance of silicon melting showed the recovery rates of the main elements (Si, Al, Ca and Fe). It recorded a decrease in content of aluminum from 1.9-2.1% to 0.5-0.7%, calcium from 0.2-0.3% to 0.07-0.1% and titanium from 0.2-0.23% to 0.11-0.13% during the transition to briquetted monocharge. Phosphorus content increased from 0.004-0.005 to 0.011-0.013%.

Evans' Syndrome (ES) is a rare autoimmune disorder characterized by the simultaneous occurrence of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Thrombotic complications in ES patients are uncommon, particularly involving Buerger's Disease (BD). We report a case of a 49-year-old male with ES and a history of diabetes and heavy smoking, presenting with a necrotic wound on his right great toe. Diagnostic evaluations revealed severe stenosis and thrombosis in the lower limb arteries, diagnosed as BD. The patient underwent successful popliteal-tibioperoneal artery bypass surgery and subsequent disarticulation and revision of the distal phalanx, followed by the application of an acellular dermal matrix (ADM) to promote healing. Post-surgery, the patient showed significant improvement in blood flow and complete epithelialization without complications. This case highlights the importance of a multidisciplinary approach in managing complex wounds in ES patients, suggesting potential treatment pathways for future cases involving BD

This paper, from the perspective of Mode 3 of knowledge production, takes the important carrier of knowledge, scientific research papers, as the research object. The mainstream databases (SCIE and SSCI) are chosen as the data sources. Firstly, bibliometric methods are applied to analyze the cooperation status among the main bodies of paper production, including authors and their affiliated institutions, countries, and disciplines; secondly, the Analytic Hierarchy Process (AHP) is used to construct a comprehensive evaluation model for the state of research cooperation in carbon neutrality. Based on the evaluation model, the cooperation characteristics of different disciplinary fields and the relationship between paper cooperation status and high-impact research papers are comparatively analyzed. At the same time, an analysis is conducted on the support from the government, the sponsorship from enterprises, and the participation of the public in the process of paper production. Finally, some suggestions are put forward on how to build an innovative ecosystem for carbon neutrality research from the perspective of Mode 3 of knowledge production.

Vitamin A, or retinol, is one of the most effective anti-ageing molecules, but it presents issues with photo-sensitivity and irritation. Retinol-like alternatives are emerging, but have so far been less effective. Here, we present a Silibum marianum extract (SME) as a retinol-like ingredient providing both safety and efficacy. SME was compared to the reference compound, retinol, and to the main alternative, bakuchiol. In ex vivo tests, skin explants from a 58-year-old donor were treated with pure retinol (0.1%), bakuchiol (0.2%) or SME (0.8%). After 5 days, collagen and hyaluronic acid levels were analysed. A placebo-controlled study involving 57 volunteers (ages 45-73 years) was also conducted, with products applied twice-daily for 56 days. Results were measured by AEVA-HE and VISA. Levels of collagen III were significantly increased by SME, by 23% and 16% compared to bakuchiol and retinol, respectively. Compared to bakuchiol, SME treatment increased hyaluronic acid production by 36%. In clinical tests, SME had a significantly stronger anti-wrinkle effect than bakuchiol – reducing the number of wrinkles on the forehead by 21%, and their circumference by 17% – producing effects similar to retinol, and better than bakuchiol. In the self-assessment, 43% of volunteers reported discomfort while using retinol, as compared to 0% for the SME formulation. By enhancing levels of collagen III – the youth collagen – and hyaluronic acid in the skin, SME paves the way for the maturation of collagen I fibrils and skin plumping. With its stronger efficacy compared to bakuchiol and enhanced safety profile compared to retinol, SME may be the next-generation of natural alternatives to retinoids.

To make wind power more competitive, it is necessary to reduce turbine downtime and reduce costs associated with wind turbine Operation and Maintenance (O&amp;M). Incorporating machine learning in developing condition-based predictive maintenance methodologies for wind turbines can enhance their efficiency and reliability. This paper presents a monitoring method that utilizes Base Density for the Support Vector Machine (BDSVM) and the evolutionary Fourier spectra of vibrations. This method allows smart monitoring of the function evolution of the turbine. A complex optimal function (FO) for 5-degree order has been developed that will be the boundary function of the BDSVM to timely determine the magnitude, frequency, and place of the failure occurring in wind turbine drive.

Aim: To evaluate the panmacular subthreshold micropulse laser treatment results among patients with central serous chorioretinopathy (CSC) and their correlation with functional and morphological parameters. Material and methods: The examined group included 10 non-treated and 41 treated patients with acute, recurrent, and chronic CSC (13 F, 38 M, mean age 44.11±6.5) and 14 healthy controls (6 F, 8 M, mean age 45±9.3). The BCVA examination, ophthalmoscopy, microp-erimetry, angio-OCT and OCT were performed. The medical history regarding chronic general disorders and known risk factors were recorded. Results: Complete resorption of SRF was obtained in 100% aCSC, 86.66% cCSC, and 63.63% r CSC. BCVA and RetSens significantly improved most of the patients treated in aCSC. The lowest BCVA and RetSens, but the largest pachyvessel and disease duration, were found in rCSC. A strong negative correlation between final BCVA and disease duration was found. No patient demonstrated laser lesions following treatment. Conclusions: The panmacular MPLT therapy leads to long-term enhancement of functional and morphological parameters in all CSC patients. The acute CSC patients showed the most significant improvement. The procedure is safe and could be considered a preferred treatment option for all active CSC cases. Timely treatment is crucial for beneficial outcomes.

A great deal of studies have assessed the expression of noncoding RNAs (ncRNAs) as well as their relevant molecular functions and biological mechanisms in the individuals of alcohol dependence. Alcohol dependence is one of the most prevalent neuropsychological disorders worldwide, and its pathogenesis is intricate and inadequately understood. There is considerable evidence demonstrating substantial links between multiple genetic factors and the development of alcohol dependence. Critical roles of ncRNAs have been emphasized in the pathophysiology of mental diseases including alcohol dependence. In the comprehension of ncRNAs action and their mechanisms of modification, they have emerged as therapeutic targets for a variety of psychiatric illness including alcohol dependence. Worth mentioning, dysregulated expression of ncRNAs has been regularly detected in individuals of alcohol dependence. An in-depth knowledge of roles of ncRNAs and m6A modification may be valuable for the development of a novel treatment against alcohol dependence. In general, a deeper comprehension of functional roles ncRNAs may make significant contributions to the precise diagnosis and/or actual treatment of alcohol dependence. Here in this review, we mostly focused on the up-to-date knowledge regarding alterations and/or modifications in the expression of ncRNAs in alcohol dependence, and then, presented their prospects for future research and therapeutic application with a novel concept of engram-system.

To address the insufficient mechanical properties of calcined phosphogypsum, this research aims to investigate the utilization of basalt fiber and calcium carbonate whiskers as reinforcing agents. The study examines their impact on the flexural and compressive strength, toughness, water resistance, and tensile strength of calcined phosphogypsum. In the individual tests, basalt fibers with different lengths (3 mm, 6 mm, 9 mm, and 18 mm) were added at dosages of 0%, 0.5%, 1.0%, and 1.5% respectively. The findings demonstrate that basalt fiber effectively enhances the flexural and compressive strength, toughness, and tensile strength of calcined phosphogypsum, albeit potentially compromising water resistance. Among the various fiber lengths, the 6 mm fibers exhibit the most advantageous influence on the performance of calcined phosphogypsum. A subsequent test was conducted to investigate the impact of cross-scale fibers on the properties of calcined phosphogypsum by mixing 6 mm basalt fibers and calcium carbonate whiskers. The results illustrate that calcium carbonate whisker refines the pores, thereby improving the flexural strength and toughness of calcined phosphogypsum. Furthermore, it compensates for the water resistance limitations associated with the sole utilization of basalt fiber while further augmenting the tensile strength and strain capacity. However, it should be noted that increasing the dosage of both calcium carbonate whiskers and basalt fibers concurrently leads to increased porosity of phosphogypsum and reduced compressive strength.

In the conservation of monumental heritage, the collection and utilization of information are of primary importance. The Heritage Building Information Modeling (HBIM) procedure harnesses the potential of three-dimensional models, offering significant advantages in accessing documentation, interoperability, multidimensionality of intervention design, cost evaluation and maintenance management. Attention here is focused on the Certosa di Pisa, a large historical complex built in the 14th century as a monastery of the Carthusian order, currently in a state of deterioration and in need of restoration and re-functionalization. The multifaceted nature of this monumental complex, with its intricate interplay of architectural elements spanning different historical periods and featuring diverse techniques, poses a significant challenge for structural safety assessment. This case study presents an opportunity to explore an HBIM approach to streamline the diagnostic process and facilitate the intervention design phase. The goal is achieved by utilizing an accurate 3D model enriched with data from multiple sources and automating certain operations for structural assessment. The usefulness of the HBIM methodology is highlighted as a valuable tool in the realm of Cultural Heritage structures for both technicians and scholars alike.

This paper illustrates an experimental activity for the closed-loop position control of an actuator made using shape memory alloy (SMA) wire. A solution with the self-sensing effect was implemented to miniaturize the systems, i.e., without external sensors. A proportional control algorithm was initially used, demonstrating the idea's feasibility: the wire can behave simultaneously as an actuator and sensor. An experimental investigation was subsequently conducted for the optimization of the developed actuator. As for the material, a Flexinol wire, Ni-Ti alloy, with a diameter of 0.150 mm and a length of 200 mm, was used. Preliminarily, a characterization of the SMA wire at constant and variable loads was carried out: the characteristics detected are elongation vs. electric current and elongation vs. electrical resistance. The control system is PC-based with a data acquisition card (DAQ). A drive board has been designed and built to read the wire's electrical resistance and power it by pulse width modulation (PWM). A notable result is that the actuator works with good precision and in dynamic conditions, even when it is called to support a load up to 65% different from that for which the electrical resistance-length correlation has previously been experimentally obtained, on which the control is based. This opens up the possibility of using the actuator in a counteracting configuration with a spring, which makes hardware implementation and control management simple.

The Songpan-Ganze Orogenic Belt (SGOB) is bounded by the South China, North China, and Qiang-tang blocks and forms the eastern margin of the Tibetan Plateau. The Tiechanghe granite is located at the junction of the southeast margin of the SGOB and the western margin of the Yangtze Block. To elucidate the genetic relationship between the Tiechanghe granite and the surrounding molybdenum deposits in Western Sichuan, in this study, we conducted U-Pb zircon and molybdenite Re-Os isotopic dating. The results indicate that the Tiechanghe granite predominantly consists of monzogranite, with minor occur-rences of syenogranite, while the molybdenum deposits are mainly found in skarn and quartz veins. The laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) U-Pb zircon ages of the Tiechanghe granite range from 162.9±0.7 Ma to 163.4±0.6 Ma, and the zircon LA-ICP-MS U-Pb age of the pegmatite veins is 164.1±0.9 Ma. These ages are consistent with the weighted average Re-Os age of the Ziershi molybdenite (160.3±1.6 Ma) within the error margins. These findings and previously ob-tained magmatic and metallogenic ages for the region suggest that a magmatic and mineralization event involving granite, molybdenum, tungsten, and copper occurred at around 162–164 Ma in the study area. This discovery broadens the exploration perspective for mineral resources in the Jiulong area of Western Sichuan and the entirety of Western Sichuan.

This study investigates cloud cavitation suppression around a model scale NACA66 hydrofoil using active water injection and explores the effect of multiple injection parameters. Numerical simulations and a mixed-level orthogonal test method are employed to systematically analyze the impact of jet angle αjet, jet location Ljet, and jet velocity Ujet on cavitation suppression efficiency and hydrofoil energy performance. The study reveals that jet location has the greatest influence on cavitation suppression, while jet angle has the greatest influence on hydrofoil energy performance. The optimal parameter combination (Ljet = 0.30C, αjet = +60 degrees, Ujet = 3.25 m/s) effectively balances energy performance and cavitation suppression, reducing cavitation volume by 49.34% and improving lift-drag ratio by 8.55%. The study found that the jet's introduction not only enhances vapor condensation and reduces the intensity of the vapor-liquid exchange process but also disrupts the internal structure of cavitation clouds and elevates pressure on the hydrofoil suction surface, thereby effectively suppressing cavitation. Further analysis shows that positive-going horizontal jet components enhance the lift-drag ratio, while negative-going components have a detrimental effect. Jet arrangements near the trailing edge negatively impact both cavitation suppression and energy performance. These findings provide valuable reference for selecting optimal injection parameters to achieve a balance between cavitation suppression and energy performance in hydrodynamic systems.

Drowsiness is a main factor for various costly defects, even fatal accidents in areas such as construction, transportation, industry and medicine, due to the lack of monitoring vigilance in the mentioned areas. The implementation of a drowsiness detection system can greatly help to reduce the defects and accident rates by alerting individuals when they enter a drowsy state. This research proposes an Electroencephalography (EEG) based approach for detecting drowsiness. EEG signals are passed through a preprocessing chain composed of artifact removal and segmentation to ensure accurate detection followed by different feature extraction methods to extract the different features related to drowsiness. This work explores the use of various machine learning algorithms such as Support Vector Machine (SVM) the K Nearest Neighbor (KNN) the Naive Bayes (NB) the Decision Tree (DT) and the Multilayer Perceptron (MLP) to analyze EEG signals sourced from the DROZY database, carefully labeled into two distinct states of alertness (awake, and drowsy). Segmentation into 10-second intervals ensures precise detection, while a relevant feature selection layer enhances accuracy and generalizability. The proposed approach achieves high accuracy rates of 99.84% and 96.4% for intra (subject by subject) and inter (cross-subject) modes, respectively. SVM emerges as the most effective model for drowsiness detection in the intra mode, while MLP demonstrates superior accuracy in the inter mode. This research offers a promising avenue for implementing proactive drowsiness detection systems to enhance occupational safety across various industries.

Introduction: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection may cause acute respiratory failure but also remains responsible for many other pathologies, including electrolyte disorders. SARS-CoV-2 infection can cause dysfunction of the renin-angiotensin-aldosterone system and disrupt water hemostasis with thirst and appetite abnormalities. Dysnatremia affects prognosis and may be associated with mortality in patients admitted to SARS-CoV2 intensive care. Patients and Methods: The study included 209 patients admitted to the Intensive Care Unit between April 12, 2021, and March 1, 2022 who were over 18 years old and diagnosed with SARS-CoV-2 infection by clinical and thoracic tomography findings or with a positive reverse transcription polymerase chain reaction (RT-PCR) test result. The laboratory markers, treatment modalities, nutritional, and respiratory support also for outcome evaluation, length of stay in the ICU, total hospitalization duration, and mortality in ICU were recorded.The laboratory marker comparison was made admission with the final assessment performed before the time of mortality in ICU or discharge. Results: Inotropic requirements among patients were high which was reflected in the first-month mortality. Hypernatremia presence was associated with an increase in enteral support and inotropic support requirement and mortality. Hypernatremia was correlated with diabetes mellitus, chronic renal failure, and a longer duration under mechanical ventilation. Discussion: Hypernatremia was an important risk factor in ICU patients hospitalized for SARS-CoV-2 infection, which was also affected by the treatment regimens given itself. This complex relationship underlies the importance of proper electrolyte management, especially in patients who were under severe stress and organ failure.

The high flammability and lack of charrability of polystyrene (PS) pose significant limitations on its broader applications. Therefore, there is an urgent need for a straightforward and efficient method for the synthesis of flame-retardant PS, which still poses a considerable challenge. In this study, we present an efficient approach to enhance the flame-retardant properties of PS through direct phosphorylating aromatic C(sp2)-H bonds using commercially available and inexpensive manganese catalyst. A range of phosphonates served as reactive substrates to enable a tunable degree of polymer functionalization. The corresponding phosphorylated PS specimens were determined by means of 1H NMR, 31P NMR, FTIR spectroscopy and GPC. Microscale combustion calorimetry (MCC) tests indicate that this protocol indeed enhances the flame-retardant performance of PS. Moreover, other advantages associated with the incorporation of the phosphonate group have been observed, including improved thermal resistance and wettability. This cost-effective strategy of Mn-catalyzed C-H can also be utilized to directly obtain phosphonate modification of waste foamed PS and styrene acrylonitrile copolymer, providing a new method for the purpose of recycling and upgrading PS plastics.

A new quinazolinone alkaloid, named peniquinazolinone A (1), as well as eleven known com-pounds, 2-(2-hydroxy-3-phenylpropionamido)-N-methylbenzamide (2), viridicatin (3), viridicatol (4), (±)-cyclopeptin (5a/5b), dehydrocyclopeptin (6), cyclopenin (7), cyclopenol (8), methyl-indole-3-carboxylate (9), 2,5-dihydroxyphenyl acetate (10), methyl m-hydroxyphenylacetate (11), conidiogenone B (12), was isolated from the endophytic Penicillium sp. HJT-A-6. The chemical structures of all compounds were elucidated by comprehensive spectroscopic analysis, including 1D, 2D NMR, and HRESIMS. The absolute configuration at C-13 of peniquinazolinone A (1) was established by applying the modified Mosher’s method. Compounds 2, 3, and 7 exhibited an op-timal promoting effect on the seed germination of Rhodiola tibetica at a concentration of 0.01 mg/mL, while the optimal concentration for compounds 4 and 9 to promote Rhodiola tibetica seed germination was 0.001 mg/mL. Compound 12 showed optimal seed-germination-promoting activity at a concentration of 0.1 mg/mL. Compared with the positive drug 6-benzyladenine (6-BA), compounds 2, 3, 4, 7, 9, and 12 could extend the seed-germination period of Rhodiola tibetica up to the 11th day.

The branch prediction units (BPUs) generally have security vulnerabilities, which can be used by attackers to obtain the execution status, jump directions, and jump address of conditional branches, and the existing protection methods cannot defend against these attacks. Therefore, this article proposes a hardware security protection method for conditional branches of embedded systems. This method calculates the number of updates to the branch target buffer (BTB). When it exceeds the threshold, BTB is locked to prevent attackers from analyzing the execution status of branches based on the time difference of whether BTB is updated. Moreover, the hybrid physical unclonable function (PUF) circuit is designed to provide confidentiality protection for the jump directions, jump addresses, and their indexes, preventing attackers from stealing these critical data. If these mechanism fails and attackers successfully tamper with conditional branches, this paper proposes a control flow integrity (CFI) protection mechanism based on branch labels to timely detect tampering with instruction codes, jump addresses, and jump directions. The proposed method is implemented and tested on FPGA. The experimental results show that this method can achieve fine-grained security protection for conditional branches, with about 5.4% resource overhead and less than 5.5% performance overhead.

Mannosylerythritol lipids (MELs), one of the most promising biosurfactants (BS), are glycolipids produced by yeasts or fungi, with great environmental performance and a high compatibility with the human body. MELs besides working as typical surfactants, can form diverse structures when in the critical aggregation concentration (CAC), reducing the surface tension of water and other solutions, and being stable over a wide range of conditions. Among others, MELs present anti-microbial, antitumor, antioxidant and anti-inflammatory activity, skin and hair repair capacity, which opens possibilities for their use in applications from cosmetics and pharmaceutics to bio-remediation and agriculture. However, their market share is still low when compared to other glycolipids, due to their less developed production process and higher production cost. This re-view gathers information on the potential applications of MELs mentioned on the literature since 1993. Furthermore, it is also explored the current strategies being developed to enhance the market presence of MELs, in parallel with the ones developed for rhamnolipids and sophorolipids.

This study aimed to evaluate the impact of Candida albicans on subgingival biofilm formation on dental implant surfaces. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were used to compare biofilm structure and microbial biomass in the presence and absence of the fungus after periods of 24, 48, and 72 h. Quantitative polymerase chain reaction (qPCR) was used to quantify the number of viable and total micro-organisms for each of the biofilm-forming strains. A general linear model was applied to compare CLSM and qPCR results between control and test conditions. The biofilm developed with C. albicans at 72 h had a higher bacterial biomass, with a significantly higher cell viability (p &lt; 0.05). After both 48 and 72 h of incubation, in the presence of C. albicans, there was a significant increase in counts of Fusobacterium nucleatum and Porphyromonas gingivalis and in the cell viability of Streptococcus oralis, Aggregatibacter actinomycetemcomitans, F. nucleatum, and P. gingivalis. Using a dynamic in vitro multispecies biofilm model, C. albicans exacerbated the development of the biofilm grown on dental implant surfaces, significantly increasing the number and cell viability of periodontal bacteria.

Lignin fibers typically influence the mixture performance of stone matrix asphalt (SMA), such as strength, stability, durability, noise level, rutting resistance, fatigue life, and water sensitivity. However, limited studies were conducted to analyze the influence of fibers on the percent voids in mineral aggregate in bituminous mixture (VMA) during the mixture design. This study analyzed the effect of different fibers and fiber contents on the VMA in SMA mixture design. A surface-dry condition method test and Marshall Stability test were applied on the SMA mixture with four different fibers (i.e., flocculent lignin fiber, mineral fiber, polyester fiber, blended fiber). The test results indicated that the bulk specific gravity of SMA mixtures and asphalt saturation decreased with the increasing fiber content, whilst the percent air voids in bituminous mixtures (VV), Marshall Stability and VMA increased. Mineral fiber had the most obvious impact on the bulk specific gravity of bituminous mixtures, while flocculent lignin fiber had a minimal impact. The mixture with mineral fiber and polyester fiber had significant effects on the volumetric properties, and, consequently, exhibited better VMA over the conventional SMA mixture with lignin fiber. Modified fiber content range was also provided, which will widen the utilization of mineral fiber and polyester fiber in the applications of SMA mixtures. The mixture evaluation suggested no statistically significant difference between lignin fiber and polyester fiber on the stability. The mineral fiber required a much larger fiber content to improve the mixture performance than other fibers. Overall, the results can be a reference to guide SMA mixture design.

In this paper, a semi-empirical model of air waves induced by falling rock is described. The model is composed of a uniform motion phase (velocity close to 0 m·s^-1) and an acceleration movement phase. The uniform motion phase was determined based on experimentally and the acceleration movement phase was derived by theoretical analysis. A series of experiments were performed to verify the semi-empirical model and elucidated the law of the uniform motion phase. The acceleration movement phase accounted for a larger portion with a greater height of the falling rock. Experimental results of different falling heights of the goaf showed close agreement with theoretical analysis values. The semi-empirical model could accurately and conveniently estimate the velocity of air wave induced by falling rock. Thus, the semi-empirical model can provide a reference and basis for estimating the speed of air waves and designing protective measures in mines.

Exosomes are produced by all cell types, their biogenesis is of endosomal origin, originating as a result of cell membrane invagination. Furthermore, physiochemical characteristics are important prerequisites for their commercial application. The representative size range of exosomes is 50-200 nm. Whereas, comparative to animal cell, exosomes from plant cell sources have a relatively larger size range, moreover, exhibit broader therapeutic potential. In this review study, we have briefly discussed the research potential of plant-derived exosomes. Including their earlier studies on biogenesis, characterization, isolation methods, and possible therapeutic applications. Additionally, we have quoted targeted drug delivery for targeted therapies and have provided insights of methods for customizing exosomes produced from plants with various drugs. Most-importantly, here we have embodied exosomes from plant sources are natural nano-inducers possessing the ability for inter-kingdom communication, resulting in cross-kingdom regulations.

The mutation in NF2 is the most common alteration associated with meningioma oncogenesis, and it is related to the loss of a suppressing protein called merlin. At the same time, alterations in energy production are visible in cancer cells where increased demand for energy is observed. Fatty acid oxidation could be one of the ways cancer cells obtain energy. This metabolic pathway uses the acylcarnitine shuttle system, which is responsible for the acylation of fatty acids and their transport through mitochondria. Therefore, this study aimed to profile acylcarnitines with short-, medium- and long-acyl chain length in meningiomas to assess their changes in tumors with different NF2 mutation statuses. For the analysis, solid-phase microextraction (SPME) coupled with liquid chromatography high resolution mass spectrometry (LC-HRMS) was used. The presented sampling method enables low invasive and easy collection of the analytes from the studied lesions, which can be crucial for future analysis of potential biomarkers in the surgery room. It was observed that higher levels of these analytes characterized meningiomas with NF2 mutation. Moreover, increased energy consumption and elevated levels of acylcarnitines show that these analytes can be considered as a marker of increased fatty acid oxidation in NF2 mutated cells.

Elizabethkingia anophelis is an opportunistic pathogen causing lifethreatening infections in humans, particularly in immunocompromised patients, neonates and elderly. Infections caused by this species are exceptionally challenging to treat due to its multiresistance to antimicrobials. We report a case of central line-associated bloodstream infection by E. anophelis in a 2.5-year-old girl with acute lymphoblastic leukemia successfully treated with a combination of piperacillin/tazobactam and amikacin. The literature was also reviewed on paediatric infections caused by E. anophelis. Accurate identification with MALDI-TOF, or using molecular techniques, is crucial because of varying susceptibilities among species. Early, accurate diagnosis and prompt effective treatment optimize outcomes.

SOC stock (SOCS) changes caused by land use changes are still unclear, and understanding this response is essential for many environmental policies and land management practices. In this study, we investigated the temporal-spatial and vertical distribution characteristics of SOCS on the Western Sichuan Plateau (WSP) using the sparrow search algorithm-random forest regression (SSA-RFR) models with excellent model applicability and accuracy. The temporal-spatial varia-tions in the SOCS were modeled using 1080 soil samples and a set of nine environmental covariates. We analyzed the effect of land use changes on the SOCS on the WSP. The total SOCS increased by 18.03 Tg C from 1990 to 2020. The results of this study confirmed that the SOCS in the study area has increased significantly since 2010, with an increase of 27.88 Tg C compared to the total SOCS in 2010. We found that the spatial distribution of the SOCS increased from southeast to northwest, and the vertical distribution of the SOCS in the study area decreased with increasing soil depth. Forest and grassland are the main sources of SOCS, the total SOCS in the forest and grassland accounted for 37.53 and 59.39% of the total SOC pool in 2020, respectively. Expansion of the wetlands, forest, and grassland areas could increase SOCS in the study area.

Introduction: Cleft lip with or without cleft palate (CL/P) is the most common congenital face anomaly in the world of multifactorial etiology. Objective: To determine the prevalence and characteristics of cleft palate. To identify associated risk factors to guide prevention and/or prenatal detection for early intervention and better health outcomes. To assess the rehabilitation protocols after operations in cleft palate. Design: Retrospective descriptive and clinical study. Patients: One hundred and three children with cleft palate treated in the Department of Head and Neck Surgery Clinic for Children and Young Adults, Department of Clinical Pediatrics, University of Warmia and Mazury, were included in the study. Methods: Records evaluation was conducted regarding sex, cleft type, mother occupation, parents education, histories of cleft in any of parents. The data were analyzed using R (R core team 2021) and the ordinal logistic regression analyses. Results: Children of stressed mothers during pregnancy had 9.4 times higher odds of having bilateral cleft. While there was no evidence that children sex, order of birth, and body mass as well as risk of maternal toxicity at work or reporting infections or drugs toxicity had a significant effect on the dependent variable. Conclusions: Children of parents with cleft history and having low educated mothers had higher probability of bilateral cleft palate. Children of stressed mothers during pregnancy had higher odds of having bilateral cleft. In literature, there is a lack of reports about rehabilitation in different operations methods in children with cleft palates.

BRCA1 and 2 pathogenic variants increase lifetime risks of breast (50-75%) and ovarian cancer (15-20%). Guidelines recommend breast screening (MRI and mammogram) or risk-reducing mastectomy with salpingo-oophorectomy for ovarian cancer prevention. We sought to 1) characterize the population of BRCA1/2 carriers in Newfoundland and Labrador (NL) 2) evaluate risk-reducing interventions 3) identify factors influencing screening and prevention adherence. Methods: This is a retrospective study from a population-based provincial cohort of BRCA1/2 carriers. Eligibility criteria for risk-reducing interventions were defined for each case and patients were categorized based on their level of adherence with recommended screening or prevention. Chi-squared and regression analyses were used to determine which factors influenced uptake and level of adherence. Results: 276 BRCA1/2 carriers were identified; 156 living NL females composed the study population. Unaffected females were younger at testing than those with a cancer diagnosis (44.4 y versus 51.7 y; p=0.002). Categorized by eligibility, 61.0%, 61.6%, 39.0% and 75.7% of patients underwent MRI, mammogram, risk-reducing mastectomy, and risk-reducing salpingo-oophorectomy, respectively. Individuals with breast cancer were more likely to have risk-reducing mastectomy (64.7% versus 35.3%; p<0.001), and those who attended specialty hereditary cancer clinic were more likely to be adherent with breast/ovarian cancer recommendations (73.2% versus 13.4%; p<0.001) and to undergo risk-reducing salpingo-oophorectomy(84.1% versus 15.9%; p<0.001). Conclusions: Nearly 40% of female BRCA1/2 carriers were not receiving breast surveillance according to evidence-based recommendations. Cancer risk reduction and uptake of breast imaging and prophylactic breast and pelvic surgeries are significantly higher in patients who receive dedicated specialty care. Organized hereditary cancer prevention programs will be a valuable component of Canadian health care systems and have the potential to reduce the burden of disease country-wide.

The efficient preparation of single-stranded DNA (ssDNA) rings, as a macromolecular construction approach with topological features, has aroused much interest due to their numerous applications in biotechnology and DNA nanotechnology. However, an extra splint is essential for enzymatic circularization, and by-products of multimers are usually present at high concentrations. Here, we proposed a simple and robust strategy of using permuted precursor (linear ssDNA) for circularization by forming an intramolecular dynamic nick using a part of the linear ssDNA substrate itself as the template. After the simulation of the secondary structure for desired circular ssDNA, the linear ssDNA substrate is designed to have its ends on the duplex part (≥5 bp). By using this permuted substrate with 5'-phosphate, the splint-free circularization is simply carried out by T4 DNA ligase. Very interestingly, formation of only several base pairs (2–4) flanking the nick is enough for ligation, although they form only instantaneously under ligation conditions. More significantly, the 5 bp intramolecular duplex part commonly exists in genomes or functional DNA, demonstrating the high generality of our approach. Our findings are helpful for understanding the mechanism of enzymatic DNA ligation from the viewpoint of substrate binding.

For monitoring of chimeric antigen receptor (CAR) T-cell therapies antigen-based CAR detection methods are usually applied. However, for each target-antigen a separate detection system is required. Furthermore, when monitoring CAR T-cells in the blood of patients treated with bispecific antibodies or T-cell engagers (bsAbs/BiTEs) recognize the same antigen, these methods producing false-positive results in clinical diagnostics. Anti-CAR-linker monoclonal antibodies (mAbs) targeting the linker sequence between the variable domains of the antigen binding CAR fragment, promise an universal and unbiased CAR detection. To test this, we analyzed clinical specimens of all BCMA- and CD19 targeting CAR T-cell products currently approved for clinical use. We found a highly specific and sensitive CAR detection by using anti-CAR-linker mAb in blood cells from patients treated with Ide-cel, Tisa-cel, Axi-cel, Brexu-cel, and Liso-cel. For Ide-cel and Tisa-cel the sensitivity was significant lower compared to antigen-based CAR detection assays. Strikingly, the specificity of anti-CAR linker mAb was not affected by the simultaneous presence of bispecific blinatumomab or teclistamab for Axi-cel, Brexu-cel, Liso-cel or Ide-cel, respectively. Cilta-cel (containing an monomeric G4S-CAR linker) could not be detected by anti-CAR linker mAb. In conclusion, anti-CAR-linker mAbs are highly specific and useful for CAR T-cell monitoring but not universal applicable.

Bacteriophages (phages) are potential alternatives to chemical antimicrobials against pathogens of public health significance. Understanding the diversity and host specificity of phages is important for developing effective phage biocontrol approaches. Here, we assessed the host range, morphology, and genetic diversity of eight Salmonella enterica phages isolated from a wastewater treatment plant. The host range analysis revealed that six out of eight phages lysed more than 81% of the 43 Salmonella enterica isolates tested. The genomic sequences of all phages were determined. Whole genome sequencing data (WGS) data revealed that phage genome sizes ranged from 41 to 114 kb with GC contents be-tween 39.9 and 50.0 %. Two of the phages SB13 and SB28 represent new species Epsep-timavirus SB13 and genera Macdonaldcampvirus, respectively as designated by the In-ternational Committee for the Taxonomy of Viruses (ICTV) as per genome based taxonomic classification. One phage (SB18) belonged to the Myoviridae morphotype while the re-maining phages belonged to the Siphoviridae morphotype. The gene content analyses showed that none of the phages possessed virulence, toxin, antibiotic resistance, type I-VI toxin-antitoxin modules or lysogeny genes. Three (SB3, SB15 and SB18) out of the eight phages possessed tailspike proteins. Whole genome-based phylogeny of the eight phages with their 113 homologs revealed three clusters A, B, C and seven subclusters (A1, A2, A3, B1, B2, C1 and C2). While cluster C1 phages were predominantly isolated from animal sources, cluster B contained phages from both wastewater and animal sources. The broad host range of these phages highlights their potential use to control the presence of S. enterica in foods.

A low-cost bio-mass-derived carbon substrate has been employed to synthesize MoS₂@carbon composites through a hydrothermal method. Carbon fibers derived from natural cotton provide a three-dimensional and open framework for the uniform growth of MoS₂ nanosheets, thus constructing hierarchically coaxial architecture. The unique structure could synergistically benefit fast Li-ion and electron transport from the conductive carbon scaffold and porous MoS₂ nanostructures. As a result, the MoS₂@carbon composites, when served as anodes for Li-ion batteries, exhibit a high reversible specific capacity of 820 mAh g^-1, high-rate capability (457 mAh g^-1 at 2 A g^-1), and excellent cycling stability. The superior electrochemical performance makes the MoS₂@carbon composites to be low-cost and promising anode materials for Li-ion batteries.

Air quality is a topic of growing relevance on the global agenda. Two key indicators of air quali-ty, nitrogen dioxide (NO2) and carbon monoxide (CO), represent significant hazards to human health and the environment putting the sustainability of natural resources at risk. Therefore, it is imperative to regularly monitor and reduce atmospheric pollutant concentrations to mitigate their harmful consequences. This study presents an analysis of NO2 total and CO emissions in Argentina, utilizing remote sensing data. The research aims to determine the spatiotemporal distribution of NO2 and CO emissions in Argentina from 2019 to 2021. Subsequently, it seeks to establish the influence of land uses and land cover on the emission of NO2 and CO through dif-ferent climatic, anthropic, and natural indicators. The study was carried out in Argentina during the period 2019-2021, where random points were placed for the different land covers with a total of 800 points surveyed. The year with the highest CO concentration (mol/m-2) was 2020. The values were highest for tree covers and herbaceous wetland coverage in the northern part of the country. For total NO2, the highest concentrations were reached during the years 2020 and 2021. Regarding its distribution, throughout the evaluated period, the highest concentrations of total NO2 were found in the built-up and cropland coverages, with the capital of the country and the northern region of the Buenos Aires province being the most affected areas. In addition, the concentration of CO was influenced by climatic variables (atmospheric pressure, wind speed, maximum environment temperature, Palmer index), natural (height, humidity, NDVI), and ur-ban variables (distances to mining extraction, airports, power plants, urban index) for the differ-ent uses and land covers. Finally, the concentrations of total NO2 were influenced by climatic variables (Palmer index and wind speed), natural (height and NDVI), and urban variables (dis-tance to airports, power plants, industries, service stations, and open dumpsites) for the differ-ent uses and land cover. This study contributes to sustainable environmental management, ena-bling the formulation of effective strategies for mitigating emissions and promoting the long-term health and well-being of communities.

Background: A comparison of the amino acid (AA) plasma profile and markers of intestinal absorption-inflammation between healthy subjects aged 65-70 years and age-matched patients affected by stage 3b-4 chronic kidney disease (CKD3b-4) was performed. Methods: eleven healthy volunteers were compared with 12 CKD3b-4 patients at their first outpatient control (T0) and after 12-months (T12). Adherence to a low protein diet (LPD, 0.6±0.1 g/kg/day) was assessed by Urea Nitrogen Appearance. The following parameters were assessed: renal function, nutritional parameters, bioelectrical impedance analysis, plasma levels of 20 total aminoacids (TAAs), both essential (EAAs) including branched-chain amino acids (BCAAs) and non-essential (NEAAs). Zonulin and faecal Calprotectin markers were used to evaluate intestinal permeability/inflammation. Results: Four patients dropped out of the study; in the remaining 8 residual kidney function (RKF) remained stable, their LPD adherence had risen to 0.89g/kg/day, anaemia had worsened and extracellular body fluid had increased. In comparison to healthy subjects, TAA levels of histidine, arginine, asparagine, threonine, glycine, and glutamine had all increased. No variation in BCAAs was observed. A significant increase was detected in faecal calprotectin and zonulin levels in CKD patients as the disease progressed. Conclusions: This study confirms the finding in aged patients of an alteration in levels of several AAs secondary to uraemia. Intestinal markers provide confirmation of a relevant alteration to the intestinal function in CKD patients.

Earth’s extinction crisis is escalating, and threat classification schemes are increasingly important for assessing which human activities are the most prominent drivers of species declines. However, a quantitative understanding of the conservation responses needed to abate threatening processes, and avoid species extinctions, is often lacking. Here, we provide a threat abatement framework which groups threats based on the shared conservation goal of the actions needed to abate their impact. We apply this framework to Australia’s threatened species to quantify the relative importance of achieving different conservation response goals. Our analysis shows the most important conservation responses across Australia are habitat retention and restoration, due to the combined impact of threatening processes causing habitat destruction and degradation (e.g. logging, mining, urbanisation and agriculture), which affects the majority (86%) of Australia’s threatened species and the effective control of invasive species (82%). Most species also require conservation responses focussed on improved fire management (66%). We show that implementing responses in isolation will be inadequate for abating species extinctions as almost all species (89%) require multiple, integrated management responses to redress their threats. We also acknowledge that already small and potentially genetically compromised taxa may require more direct interventions (e.g. captive insurance populations or genetic rescue). Our analysis highlights the necessity of addressing multiple threats at appropriate geographic scales across Australia. Our threat abatement framework ensures that core conservation actions can be identified and aid recovery of threatened species, and can be applied to other geographic regions and conservation contexts.

During the last few years, the world witnessed one of the worst calamities to humankind- the COVID-19 pandemic. We also witnessed the development of vaccines at an unprecedented pace against the SARS-CoV-2- the causative agent. India was among the hard-hit countries by COVID-19, developed its indigenous vaccine and implemented vaccines developed in other countries as well. Initially, the antibody level and the neutralizing antibody titer against the pathogen were considered as the correlates of immune protection from the disease. However, the long-term protection from the pathogen was provided by the immune memory cells viz. T and B memory cells and their ability to efficiently make recall responses. In this regard, globally the research studies focused mainly on the mRNA-based vaccines. The studies on immune memory response, particularly- the B cell memory response bestowed by the vaccines given to Indians is relatively obscure. We studied the level of RBD specific memory B cells in the peripheral circulation of the study participants and the ability of B cells to secrete antigen-specific antibodies among Indians vaccinated with Covaxin (BBV152), Covishield (AZD1222), Corbevax (BECOV2D) and Sputnik Light (Gam-COVID-Vac) as well as unvaccinated individuals. Our study revealed that Corbevax and Sputnik Light conferred better antibody-secreting cell (ASC) responses.

Source water quality is a key determinant of drinking water quality. The recast European Union 2020/2184 drinking water directive (DWD) introduced the obligation for comprehensive risk assessment in drinking water supplies, including the water source and incorporated new elements of natural origin in the list of parameters to be monitored. The current study is the first comprehensive assessment of 15 natural elements (B, Ba, Be, Ca, Co, K, Li, Mg, Mo, Na, Se, Sr, Ti, U and V) in 1155 (82%) Hungarian drinking water sources, including surface water, bank filtered and groundwater sources. Parameters posing a risk to health (Se, V and U) were typically below the lower limit of quantification (LOQ), but higher concentrations (max. 7.0, 17 and 41 µg/L, respectively) may occur in confined locations, the latter exceeding the DWD parametric value in one water supply. Li in a small geographical area, Mg and Ca in the majority of the water supplies reached the concentration range assumed to be protective to health. Water sources were grouped in 6 clusters based on their element distribution, some of them also showing clear geographical patterns. Water types were not differentiated, with the exception of karstic waters (dominated by Ca and Mg). None of the investigated parameters are expected to be a source of public health concern.

The intranasal route of drug administration is characterized by high bioavailability and is considered promising for rapid delivery of drugs with systemic action to the central nervous system, bypassing the blood-brain barrier. This is particularly important for the use of neuroprotective drugs in the treatment of brain tissue damage in infants caused by the effects of intrauterine hypoxia. Creation of new dosage forms for neonatology with the use of software and mathematical technologies in pharmaceutical development allows to create cerebroprotective drugs with controlled pharmaco-technological properties, thus reducing time and resources for necessary research. We developed a formulation of a new nasal gel formulation with Angiolin using Box-Benken experiment design for the therapy of prenatal CNS damage. It was found that the consistency properties of the nasal gel were significantly influenced by the gelling agent and mucoadhesive component - sodium salt of carboxymethylcellulose. We have optimized the composition of nasal gel formulation with Angiolin using the formed models and relationships between the factors. The optimized composition of the obtained nasal gel has satisfactory parameters of thixotropic properties. The developed 1% gel for neuroprotection with Angiolin meets all the requirements for harmlessness and safety to drug forms of this group - low toxicity, absence of local irritant and allergic effect.

In this paper, based on our previous expertise on ceramic artifacts, several archaeometric methods applied to some samples collected from the Dudești archaeological site (Oltenia region, Romania) are reported for the first time in the literature. The chemical composition and microstructural and morphological characterization of these samples offer important conclusions about the processing conditions. Some specific techniques such as X-ray diffraction (XRD), wave-length-dispersive X-ray fluorescence (WDXRF), Optical microscopy (OM), stereomicroscopy, scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy and Raman spectroscopy, provide composition information about pigments and their decay processes. Additionally, the Brunauer-Emmett-Teller (BET) method helps to estimate pore sizes and specific surface areas. Thermal analysis (TGA) was used to establish details regarding the production technology and the raw materials source used to make the ceramics, too. The obtained results indicated that the ceramics are based on a paste of muscovite, feldspar, with high plasticity, quartz, melanterite, and calcite, the latter in very low concentrations. According to the obtained results, we could assume that non-calcareous clays are present in the investigated samples because calcium exists in low concentrations. Gypsum is present, too, in very low concentration, identified by the presence of sulfate group in WDXRF. In the same context, iron oxides significantly impact the firing atmosphere of iron-rich clay, resulting in blackening under reducing conditions and reddish coloration under oxidative conditions. Using hematite and gypsum as pigments further contributes to the color variations in the pottery. The consistent firing temperature range of 200-600 °C in Dudești pottery implies a standardized production process, the variation in color being dependent on the specific reducing/oxidative regime conditions. This relationship between clay composition and local sources suggests a connection to Neolithic pottery production in the region and their color depending on the reducing/oxidative regime conditions.

Abstract: Short-chain fatty acids (SCFAs) are the major microbial metabolites produced in the gut through the fermentation of non-digestible fibers. SCFAs act through free fatty acid receptor 2 and 3 (FFAR2 and 3), which are known to be expressed on glucagon-like peptide-1 (GLP-1)-secreting L-cells. This pathway is suggested to protect the intestinal mucosa. We aimed to investigate how lack of fiber affects the production of SCFAs and the vulnerability of the co-lon. Additionally, the involvement of FFAR2 and 3 in GLP-1 secretion and intestinal protection. SCFA concentrations in luminal contents from chow- or fiber-free diet-fed mice were analysed by LC‒MS. SCFAs were applied to isolated perfused colons from FFAR2/3 double KO and WT mice, and the secretion of GLP-1 was measured. Dextran sulfate sodium (DSS) colitis was induced in chow- or fiber-free diet-fed mice as well as in FFAR2/3 KO and WT mice. The removal of die-tary fiber significantly decreased total colonic SCFA concentrations, with specific decreases in acetate, propionate, and butyrate. SCFAs significantly increased colonic GLP-1 secretion but not in FFAR2/3 KO mice. In the DSS model, the removal of dietary fiber increased the severity and delayed recovery. Colitis severity was independent of FFAR2 and FFAR3 signaling.

Background/Aim: Stool gluten immunogenic peptides (GIP) determination is now considered a valuable tool for detecting dietary lapses in treated celiac disease (CeD) patients. Our study aims to explore the diagnostic performance of a qualitative lateral flow immunoassay point-of-care test (LFIA/PoCT) compared with a qualitative enzyme-linked immunosorbent assay (ELISA) for detection of stool GIP. Methods: The study is a post hoc analysis of stool samples collected in the real-life conditions from a cohort of gluten-free diet-treated CeD patients. Stool GIP was measured in µg/g of stool using an ELISA kit (iVYLISA GIP S®, Biomedal SL). For the qualitative evaluation of stool GIP, a LFIA/PoCT test (GlutenDetect®; Biomedal S.L) was employed, which reported results as positive or negative. The LFIA/PoCT performance was evaluated against ELISA, considered as the gold standard. GIP concentrations

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by renal tubular cystic dilatations. The cysts can develop anywhere along the nephron and over time the cystic dilatation lead to kidney enlargement. On the other hand, the cysts begin to reduce the number of functional nephrons as a consequence of cystic expansion that further contributes to the decline in renal function over the years. The pressure exerted by the dilated cysts lead to compensatory mechanisms that further contribute to the decline in renal function. These structural changes are responsible of glomerular hyperfiltration states, albuminuria, proteinuria, and haematuria. However, the presentation of ADPKD varies in children from a completely asymptomatic child with incidental ultrasound detection of cysts to a rapidly progressive disease. There have been reports of early onset of ADPKD in children younger than 2 years that showed a more rapid decline in renal function. ADPKD is caused by mutation in PKD1 and PKD2 genes. Today, the PKD1 gene mutation seems to account for up to 85% of the cases worldwide, and it is associated with worse renal outcomes. Individuals with PKD2 gene mutation seem to present a milder form of the disease, with a more delayed onset of end stage kidney disease. The cardinal sign of ADPKD is the presence of renal cysts during renal ultrasound. The current guidelines provide the clinicians the recommendations for genetic testing in children with a positive family history. Given that the vast majority of children with ADPKD present with normal or supra normal kidney function we explored the glomerular filtration rates dynamics and the renal ultrasound adjusted percentiles. 14 out of 16 patients had kidney percentile over 90%. The gene mutations were equally distributed among our cohort. In addition, we compared the modified Schwartz formula to the quadratic equation after adjusting the serum creatinine measurements. It seems that even though children with ADPKD have enlarged kidneys, the renal function is more likely normal or near normal when the quadratic estimation of glomerular filtration rate is used (qGFR tended to be lower, 111.95 ± 12.43 ml/min/1.73m2 compared to Schwartz eGFR 126.28 ± 33.07ml/min/1.73m2, p=0.14). Also, when the quadratic equation was employed, not even a patient reached the glomerular hyperfiltration thresholds. The quadratic formula showed that glomerular filtration rates are linear or slightly decreasing after 1-year of follow-up (Quadratic ΔeGFR=0.32±5.78ml/min/1.73m2) as opposed to Schwartz formula that can falsely classify children in a hyperfiltration state ΔeGFR=7.51±19.46ml/min/1.73m2), p=0.019.

A large diversity of epigenetic factors, such as microRNAs and histones modifications, are known to be capable of regulating gene expression without altering DNA sequence itself. In particular, miR-1 is considered the first essential microRNA in cardiac development. In this study, miR-1 potential role in early cardiac chamber differentiation is analyzed through specific signaling pathways. For this, we performed in chick embryos functional experiments by means of miR-1 microinjections into the posterior cardiac precursors -of both primitive endocardial tubes- committed to sinoatrial region fates. Subsequently, embryos were subjected to whole mount in situ hybridization, immunohistochemistry and RT-qPCR analysis. As a relevant nov-elty, our results revealed that miR-1 increases Tbx5, Gata4 and AMHC1, while this microRNA diminishes Mef2c expression, during early differentiation of cardiac sinoatrial region. Further-more, we observed in this developmental context that miR-1 upregulates CRABPII and RARß, and downregulates CRABPI, which are three crucial factors in retinoic acid signaling pathway. Interestingly, we also noticed that miR-1 directly interacts with HDAC4 and Calmodulin, as well as with Erk2/MAPK1, which are three key factors actively involved in Mef2c regulation. Our study shows, for the first time, a key role of miR-1 as an epigenetic regulator in early differenti-ation of cardiac sinoatrial region through orchestrating opposite actions between retinoic acid and Mef2c, fundamental to properly assign cardiac cells to their respective heart chambers. A better understanding of those molecular mechanisms modulated by miR-1 will definitely help in fields applied to therapy and cardiac regeneration and repair.

Hybrid reinforcement in a composite material (CM), in many situations, allows better govern material mechanical properties. Polymer matrix CM plate is reinforced with small particles and macro-fibers. Particles are oil shale ash (OSA) powder, macro-fibers – basalt fiber threads im-pregnated by matrix material. With the goal to find out elastic properties of the matrix- polymer with OSA, samples with its different concentrations were experimentally fabricated and their elastic properties were experimentally measured. Obtained data were used in numerical model-ling. Was observed polymer matrix composite slab, reinforced with OSA and three-dimensional (3D) basalt fiber fabric. Fabric are forming threads impregnated by matrix (polymer resin mixed with OSA particles). Damage accumulation in the stretched slab was modelled. Impregnated thread, in the modelling, is observed as a macro-fiber (MF) with averaged elastic properties. With the load increase MF in the material began to break. At first, appeared isolated single breaks. A probabilistic sequential MF rupture accumulation model was accepted and numerical-ly realized. The geometry of the reinforcing knitted fabric was modeled using the Leaf and Glaskin approach. In the knitted fabric highly, stressed MF cross-sections are observed as po-tential location where thread breakage can occur. If one thread breaks, the cross-sections of the adjacent threads experience the overload caused by this rupture. More overloaded crossection in the adjacent overloaded thread breaks and we obtain two adjacent broken MF designated as a defect with the size j=2. The probabilities of obtaining defect consisting of at least 2, 3, … j adjacent broken MF in the plate were calculated. The calculations continued until the rupture process becomes unstable (j→∞). The overstresses on adjacent threads in the CM were calculat-ed using the FEM three-dimensional numerical approach. Analytical and stochastic methods were used for the load-carrying capacity determination and different size defects accumulation in the hybrid composite material (HCM) plate. Also, was calculated the probability of the plate rupture.

Introduction: maxillary hypoplasia and mandibular asymmetry may be corrected with orthognathic surgery at the completion of growth. Many patients require segmental Le Fort I osteotomies to obtain the most stable results. Unfortunately, if Invisalign is chosen for pre-surgical preparation, ClinCheck © software does not allow for prediction when these complex surgeries are planned. The objective of this paper was to show the potential of aligners beyond its software in most complex cases like multiple-piece maxillary osteotomies in cleft and non-cleft patients. Method: Thirteen patients who underwent pre-surgical treatment with clear aligners-Invisalign (study group) were matched in terms of diagnosis, surgical procedure, and orthodontic complexity with thirteen patients treated using fixed appliances (control group). A technique based on simple superimposition was devised to enhance the software for creating a suitable occlusion for segmental pre-surgical treatments. Virtual curves following the lower arch were employed to guide the correct pre-surgical positions of the upper teeth. The amount of impressions required in both groups to achieve satisfactory pre-surgical alignment of the segmented arches was compared. Results: one or no refinement phase were needed in the Invisalign group to reach an acceptable pre-surgical occlusion while the amount of pre-surgical impressions taken in order to reach adequate coordination with fixed appliance treatment was slightly higher. The average overall treatment duration did not show a statistically significant variation between the groups. Conclusions: it appears that clear aligner could serve as an effective treatment for individuals with skeletal discrepancies, including cleft and craniofacial anomalies, necessitating segmental Le Fort I osteotomies when aided by the suggested superimposition approach during digital pre-surgical movement simulations. More sophisticated softwares will certainly be implemented in the future.

Background:Caregiving for individuals with neurological disease involves providing physical, emotional, and social support, which can be a challenging and stressful experience. This study aims to compare the caregivers' burden, including the impact on mental and physical health, social support, and quality of life, in different neurodegenerative disorders. Methods:Fifty-five primary caregivers (F=41;mean age=53.07±12.29) of patients with Parkinson's Disease (PD=26), Multiple System Atrophy (MSA=16), and Amyotrophic Lateral Sclerosis (ALS=13), took part in the study. Standardized screening scales for the quality of life (EQ-5D/EQ-VAS and PQoL), levels of the caregiving burden (CBI and FSQ), and the assessment of the anxiety-depressive axis (HADS) were administered. Results: The mean CBI score was higher for caregivers of MSA patients (28.81±21.90) and ALS (25.15±16.23) than for caregivers of PD patients (16.08±10.34; p=0.036). Critical burden (cut-off>36) was present in the caregivers of MSA (31.3%), ALS (23.1%), and PD (19.2%) patients. Caregivers of patients with ALS had a worse perception of quality of life (EQ-5D total score) than caregivers of patients with MSA and PD (p

Two new dimacrolide sesquiterpene pyridine alkaloids (DMSPAs), dimacroregelines A (1) and B (2), were isolated from the stems of Tripterygium regelii. The structures of both compounds were characterized by extensive 1D and 2D NMR spectroscopic analyses, as well as HRESIMS data. Compounds 1 and 2 are two rare DMSPAs possessing unique 2-(3′-carboxybutyl)-3-furanoic acid units forming the second macrocyclic ring, representing the first example of DMSPAs bearing an extra furan ring in their second macrocyclic ring system. Compound 2 showed inhibitory effects on the proliferation of human rheumatoid arthritis synovial fibroblast cell (MH7A) at a concentration of 20 μM.

This study examined local communities' perceptions of mangroves in coastal southeastern Cuba. A variety of methods were employed, including mixed and structured questionnaire surveys, interviews with key informants, and document reviews. Data were gathered from 334 respondents living in communities adjacent to four mangrove social-ecological systems (SESs). The analysis focused on five variables: community use of mangrove resources, ecosystem services, threats to the ecosystem, management activities, and social-ecological relationships. To qualitatively assess the influence of social-ecological relationships and governance, a matrix was created based on anthropogenic activities identified by respondents and their perceptions of ecosystem services. The results indicated that while local people recognize the uses and ecosystem services of mangroves, they do not rely on them for their livelihoods. They also showed moderate to full awareness of management responsibilities and activities at each site. The most commonly identified threats were climate change, drought, and deforestation. Three types of social-ecological relationships were identified based on the characteristics of the communities, their economic activities, and their impacts on the mangroves: urban-industrial, rural-agricultural, and rural-agricultural/tourism. Finally, the research proposed a set of five recommendations and eight associated indicators to ensure that mangrove management framework become more inclusive and participatory, thereby contributing to the articulation of mangrove SES governance in the southeastern region of Cuba.

The application of OpenAI's advanced artificial intelligence language model, ChatGPT, in education has garnered widespread attention from the academic community. The openness and intelligence features of ChatGPT demonstrate great potential and value in supporting students' learning, daily life, and communication. This study, grounded in the theoretical frameworks of Innovation Diffusion Theory (IDT) and the Technology Acceptance Model (TAM), conducted a systematic empirical analysis through a questionnaire survey of 677 university students who had used or were currently using ChatGPT. The results indicate that the six perceived attributes of innovation significantly influence university students' behavioral intention to use ChatGPT, while attitudes towards ChatGPT, perceived usefulness, and perceived ease of use indirectly influence students' behavioral intention to continue using ChatGPT. Based on the findings of this study, we propose an extended Technology Acceptance Model (TAM) that incorporates key elements of Innovation Diffusion Theory (IDT) to optimize the application of advanced technologies, such as ChatGPT, in education, thereby improving students' learning efficiency and behavioral performance. These findings not only provide important insights into the complex relationships between college students’ perceptions of ChatdGPT technology and predictors of behavioral intentions, but can also help relevant education departments, higher education institutions, and university teachers to effectively plan and evaluate the use of ChatGPT as a learning tool.

Background: Hurricanes and other wind events are significant disturbances that affect coastal urban forests around the world. Past research has led to the creation of wind resistance ratings for different tree species which can be used in urban forest management efforts to mitigate the effects of these storms. While useful, these ratings have been limited to species common to one global region (Florida, USA).Methods: Drawing on past ratings and data from a global literature review on tropical storm research, we created a machine learning model to broaden both the geographic coverage and the variety of species currently assessed for their resistance to wind.Results: We were able to assign wind resistance ratings to 281 new species based on the available data and our modelling efforts. The model accuracy and agreement with the original ratings when applied to the testing data set was high with 91% accuracy.Conclusions: The resulting list of wind resistance ratings has been adapted into a spreadsheet-based decision aid for managers, allowing them to assess the overall susceptibility of their urban forest to wind events like hurricanes.

Autoimmune blistering diseases represent a group of chronic severe, disabling, potentially fatal disorders of the skin and/or mucous membranes primarily mediated by pathogenic auto-antibodies. Despite their rarity, these diseases are associated with significant morbidity and mortality, a profound negative impact on the patient’s quality of life and impose a considerable economic burden. Rituximab, an anti CD-20 monoclonal antibody represents the first line of therapy for pemphigus, regardless of its severity as it ensures high rates of rapid, long-lasting complete remission. Nevertheless, disease recurrence is the rule, all patients requiring maintenance therapy with rituximab sooner or later. While innate resistance to rituximab in pemphigus patients is exceptional, acquired resistance is frequent and may develop even in patients with initial complete response to rituximab, representing a real challenge for physicians. We discuss the various resistance mechanisms and their complex interplay, as well as the numerous therapeutic alternatives that may be used to circumvent rituximab resistance. As no therapeutic measure is universally efficient, individualization of rituximab treatment regimen and tailored adjuvant therapies in refractory pemphigus cases are mandatory.

Drought affects human and natural systems, human and animal life and health, and socioeconomic activities. Drought consequences depend on its type and class, but also on the preparedness and resistance of communities to this climate disturbance. In the last decades, droughts accounted for about 16% of the total number of disasters but were responsible for 95% of the number of deaths and 26% of economic losses in Africa. This study aims to assess the drought regime in Southern Africa based on drought and vegetation indices. The SPI and SPEI were calculated at different timescales, using ERA5 data for the 1971 – 2020 period. The spatiotemporal distribution of drought descriptors was analyzed and compared with the patterns of the NDVI, EVI and VCI vegetation indices. The results reveal (i) the occurrence of droughts of various classes and at different timescales throughout the study period and region, (ii) high spatial variability in the number, duration, severity and intensity of drought, which tends to decrease with increasing timescale, (iii) high spatial-temporal agreement between drought and vegetation indices that confirm the dryness of vegetation during drought. These results aim to support policymakers in defining legislation to manage drought and water resources.

Ferritin is an indirect marker for total body iron stores. Comparison of the ferritin concentrations in the meconium with the concentrations of proteins regulating iron metabolism could aid better understanding of principles behind the adjustment between the fetal iron pool and newborn body size. Ferritin, transferrin, haptoglobin, ceruloplasmin, lactoferrin, myeloperoxidase, neutrophil gelatinase-associated lipocalin (NGAL) and calprotectin concentrations were measured by ELISA in meconium samples from 122 neonates. The neonates were classified according to the meconium ferritin tertiles and the values were collated with the meconium concentrations of other proteins and newborn body weight and length measurements. Increasing ferritin concentrations in meconium in consecutive tertiles (p < 0.05) were parallel to increased NGAL concentrations (p < 0.05). The interrelationships between the meconium concentrations of transferrin, haptoglobin and NGAL as well as between myeloperoxidase, calprotectin and lactoferrin are maintained in all subsequent tertiles of ferritin concentrations, (p < 0.05). In contrast to ferritin, increasing meconium NGAL concentrations in consecutive tertiles were linked to increased concentrations of transferrin, haptoglobin, lactoferrin and myeloperoxidase (p < 0.05) and of calprotectin, ferritin and ceruloplasmin (p < 0.1). Meconium ceruloplasmin concentrations correlate exclusively with neutrophil granule proteins, i.e. myeloperoxidase, NGAL, lactoferrin and calprotectin (p < 0.05). Meconium ferritin concentrations negatively correlates with birth weight (r= -0.20) and length (r= -0.31) of neonates, whereas NGAL concentrations just with birth length (r= -0.26). The remaining proteins did not show such relationships with the size of the newborn. High meconium concentrations of both ferritin and NGAL may specifically characterize neonates of smaller size. High meconium concentrations of both ferritin and NGAL may specifically characterize neonates with lower body measurements. Correlations between meconium transferrin, haptoglobin and NGAL may confirm the interrelationships of these proteins for proper iron control and transport in the intrauterine environment. Meconium ceruloplasmin concentrations may reflect the control of neutrophil activity in utero.

Systematic reviews represent a powerful instrument to summarize the existing evidence in medical literature. However, articles for a systematic review are hard to identify, and mostly require a structured search of the literature through a number of databases, using keyword-based search strategies, followed by the painstaking manual selection of pieces of evidence that are pertinent to the query. A.I. algorithms may offer solutions to reduce the workload on investigators. We applied BERTopic, a newer and much-recognized transformer-based topic-modeling algorithm, to two datasets of 6137 and 5309 articles of newly published systematic reviews in the area of peri-implantitis and bone regeneration in implant dentistry. In the two datasets, BERTopic identified 14 and 22 clusters, respectively, and it automatically created labels describing the nature of the topics for each individual cluster based on semantic interpretation of their titles. Most themes regarded the query theme, but in both conditions, BERTopic also uncovered articles related to off-themes, which composed around 30% of the dataset—with sensitivity up to 0.79 and specificities of at least 0.99. Our results suggest that adding a topic-modeling step to the screening process could potentially save working hours for researchers involved in systematic reviews of the literature.

Soft magnetic composites cores were produced by Spark Plasma Sintering (SPS) from Ni3Fe@ZnFe2O4 and NiFeMo@ZnFe2O4 pseudo-core-shell powders. In the Fe-Ni alloys@ZnFe2O4 pseudo-core-shell composite powders, the core is a large nanocrystalline Permalloy or Supermalloy particle obtained by mechanical alloying, and the shell is a pseudo continuously layer of Zn ferrite particles. The pseudo-core-shell powders have been compacted by SPS at temperatures between 500-700 ºC, with a holding time of 0 minutes. Several techniques were used for the characterisation of the powders and sintered compacts: X-ray diffraction, scanning electron microscopy, energy dispersive X-ray spectroscopy, magnetic hysteresis measurements (DC and AC) and electrical resistivity. The electrical resistivity is stabilised at values of about 7·10-3 Ω·m for sintering temperatures between 600-700 °C and this value is 3 orders of magnitude higher than the electrical resistivity of sintered Fe compacts. The best relative initial permeability was obtained for the Supermalloy/ZnFe2O4 composite compacts sintered at 600 ºC, which decreases linearly for the entire frequency range studied, from around 95 to 50. Up a frequency of 2,000 Hz the power losses are lower than 1.5 W/kg. At the frequency of 10 kHz, the power losses are larger, but they remain at a low level. In the case of Supermalloy/ZnFe2O4 composite compact SPS-ed at 700 °C, the specific power losses are even lower than 5 W/kg. The power losses decomposition proved that intra-particles losses give the main part of the losses.

Geothermal energy, being a clean energy source, has immense potential, and accurate wellbore modeling is crucial for optimizing the drilling process and ensuring safety. This paper presents a novel geothermal wellbore model based on the drift-flux approach, tested under three different temperature and pressure well conditions. The proposed model integrates the conservation equations of mass, momentum, and energy, incorporating the gas-liquid two-phase flow drift-flux model and heat transfer model. Key features include handling heat transfer between the for-mation and the wellbore, addressing the slip relationship between gas and liquid phases, and accounting for wellbore friction. The nonlinear equations are discretized using the finite differ-ence method, and the highly nonlinear system is solved using the Newton-Raphson method. Numerical simulation, validation, and comparison with existing models demonstrate the en-hanced accuracy of this model. In our tests, the model achieved high accuracy in calculating bottom hole pressure and temperature, with Mean Relative Errors (MRE) significantly lower than those of other models. These results offer valuable insights for optimizing drilling parameters and ensuring drilling safety. Comparisons indicate that this approach significantly outperforms others in capturing the complex dynamics of geothermal wellbores, making it a superior tool for geo-thermal energy development.

Nanocellulose (CNC) seems to be a promising surfactant, which, together with expandable graphite (EG), forms the essence of an effective natural-based fire retardant wood coating. In our research, the most suitable composition of the mixture was tested concerning good solubility, dispersion, and consistency. Favorable results were achieved with the formulation composed of a 4% CNC alkaline solution with 80 wt.% of selected EG. Subsequently, six different EG were used to prepare these wood fire retardant coatings. The effectiveness of treatments was verified using a test with a radiant heat source, where the test samples' relative weight loss, relative burning rate, and surface temperature during 600 sec were evaluated. All prepared formulations can be characterized as more or less equally effective. However, the best results were obtained with EG of GG 200 – 100 N, where the mass loss of the sample was 8.10 ± 1.24%. Very good results were also achieved by graphite 25 E + 180 HPH (8.70 ± 0.89%), which is similar to the previous one, even according to the microscopic assessment of the coating as well as the expanded layer. Graphite type 25 K + 180 (8.86 ± 0.65 %) shows the expanded layer's best cohesion, coating uniformity, and ease of application. The results of this work confirmed that the CNC coating itself has significant retardation effects.

The article presents the results of studies aimed to identify the effect of foliar treatments of winter wheat, sugar beets and soybeans with mineral and bioorganic fertilizers. Their positive effect on increasing the concentration of mineral forms of nitrogen in soil was revealed. The crop types have a greater influence on the size of nitrous oxide emissions: in winter wheat crops - 679 µg/m3, soybeans - 637.2 µg/m3, sugar beets - 576.8 µg/m3. The amounts of nitrous oxide emissions were lower in the variants without the use of phosphorus-potassium fertilizers. The Ruter AA fertilizer showed the greatest efficiency on winter wheat crops - 42.7 c/ha. Soybean grain yield of 44.2 c/ha was also achieved by using Ruter AA, as well as Geo-humate together with phosphorus-potassium fertilizers. On the background of the actual supply of phosphorus and potassium, maximum yield was obtained when using N30 on the leaf - 39.3 c/ha. Foliar feeding ensured a yield of sugar beet root crops of up to 67.1-77.4 c/ha on the backdrop of the application of phosphorus-potassium fertilizers with the advantage of using Amino turbo. The largest yield of sugar beet roots without use of mineral phosphorus and potassium was ensured by N30 treatment of the leaf in the phases of 4-6 and 8 leaves - 63.2 t/ha. Of the organo-mineral fertilizers and biostimulants, the best result was shown by the use of Ruter A - 62.6 t/ha. We believe that foliar feeding of crops can be a sustainable farming method that can increase crop yields and reduce N2O emissions.

MicroRNAs (miRNA) exert regulatory actions via base-pairing with their binding sites on target mRNAs. Cooperative-binding, i.e., synergism, among binding sites on a mRNA is biochemically well-characterized. We studied whether this synergism is reflected in global relationship between miRNA-mediated regulatory activity and miRNA-binding-site count on the target mRNAs, i.e., leading to a non-linear relationship between the two. Recently, using our own and public datasets, we have enquired into miRNA regulatory actions: first, we analyzed the power-law distribution pattern of miRNA binding sites; second, strikingly, mRNAs for core miRNA regulatory apparatus proteins have extra-ordinarily high binding site counts, forming self-feedback-control loops; third, we revealed that tumor suppressor mRNAs generally have more sites than oncogene mRNAs; and fourth, we characterized enrichment of miRNA target mRNAs in translationally less-active polysomes relative to more-active polysomes. In these four studies, obvious correlation was observed qualitatively between the extent to which a mRNA is miRNA-regulated and its binding sites count. This paper summarizes the used datasets. We also re-analyzed the correlation by comparative linear and non-linear regression analyses. The results support a non-linear, instead of linear, relationship between the two parameters, conceivably a transcriptome-level reflection of cooperative-binding/synergism among miRNA binding sites on a target mRNA.

Background: In response to inflammation, the absorption of nutritional iron is restricted. Multiple inflammation-related signaling pathways can lead to ferroptosis, an iron-dependent mechanism of programmed cell death. Since the pathophysiological significance of the presence and uptake of iron in chronic inflammation is still unknown, we tested the effect of a low iron diet on the clinical course of arthritis in the mouse model of collagen-induced arthritis (CIA). Methods: Six- to eight-week-old male DBA/1 mice were fed either a normal or a low iron diet starting three weeks before arthritis induction. From day four after the collagen-booster made on day 25, the development of arthritis was regularly monitored until the end of the experiment (day 34), using a standard clinical arthritis score. The complete blood count was determined as well as Fe2+, Fe3+, oxidized and reduced glutathione (GSH and GSSG) and malondialdehyde (MDA) in whole paw tissue by ELISA. Quantitative PCR was performed from whole paw tissue for glutathione peroxidase 4 and other key regulator genes of iron metabolism and ferroptosis. We used nonparametric tests to com-pare markers of iron metabolism and ferroptosis as well as nonlinear regression models for longitu-dinal data for signs of arthritis. Results: Mice fed a low iron diet showed a significantly less severe course of arthritis compared to mice fed a normal iron diet (p

The kinase pathway plays a crucial role in blood vessel function. Particular attention is paid to VEGFR-type 2 angiogenesis and vascular morphogenesis as the tyrosin kinase pathway is preferentially activated. In silico studies were performed on several peptides that affect VEGFR2 in both stimulating and inhibitory ways. This investigation aims to examine the molecular properties of VEGFR2, a molecule primarily involved in the processes of vasculogenesis and angiogenesis. These relationships were defined by the interactions between vascular endothelial growth factor receptor 2 (VEGFR2) and the structural features of the systems. The chemical space of the inhibitory peptides and stimulators was described using topological and energetic properties. Furthermore, chimeric models of stimulating and inhibitory proteins (for VEGFR2) were computed using the protein system structures. The interaction between the chimeric proteins and VEGFR was computed. The chemical space was further characterized using complex manifolds and high-dimensional data visualization. The results show that a slightly similar chemical area is shared by VEGFR2 and is shared by stimulating and inhibitory proteins. On the other hand, the stimulator peptides and the inhibitors have distinct chemical spaces.

Commercially cultivated Prunus species are commonly grown in adjacent or mixed orchards, and can be infected with unique or commonly shared viruses. Apple (Malus domestica), another member of the Rosacea and distantly related to Prunus, can share the same growing regions and common pathogens. Pollen can be a major route for virus transmission, and analysis of the pollen virome in tree fruit orchards can provide insights into these virus pathogen complexes from mixed production sites. Commercial honey bee (Apis mellifera) pollination is essential for improved fruit set and yield in tree fruit production systems. Here we describe the metagenomics-based detection of plant viruses through bee and pollen samples collected during the spring bloom period from a mixed Prunus and Malus orchard. Twenty-one unique viruses were detected in samples collected during apricot (Prunus armeniaca), sweet cherry (Prunus avium), peach (Prunus persica), and apple blooms. Ilarviruses prune dwarf virus (PDV) and prunus necrotic ringspot virus (PNRSV), Secoviridae family members tomato necrotic ringspot virus, tobacco necrotic ringspot virus, and prunus virus F, and Capillovirus cherry virus A (CVA) were detected in all time points, while other viruses were detected with restricted ranges. These results demonstrate the benefits of area-wide monitoring through bee pollination activities, and provide new insights into the diversity of viruses in tree fruit pollination ecosystems.

We assessed depression, anxiety, and stress in healthcare workers (HCWs) in 2023 and the evo-lution of depression in 2023 compared with 2022. In September-November 2023, 181 HCWs from the Infectious Diseases Hospital, Cluj-Napoca, Romania, completed the Depression, Anxiety, and Stress 21 Scale (DASS-21 R), the Patient Health Questionnaire-9 (PHQ-9), and the Hamilton Anxiety Rating Scale (HAM-A). The prevalence of moderate-to-severe levels was 13.81% for DASS-Depression, 18.79% for DASS-Anxiety, 16.02% for DASS-Stress, 19.89% for PHQ-9, and 12.16% for HAM-A. Moderate-to-severe PHQ-9 clinical depression was found in 19.89% of respondents, and moderate-to-severe HAM-A clinical anxiety in 12.16%. Moderate-to-severe PHQ-9 depres-sion was significantly lower in the 2023 study group (19.89%, N=181) compared with 2022 (30.60%, N=114) (p=0.036), also within the 2022-2023 follow-up study group (N=88) (p=0.026). We did not find significant statistical differences between those infected vs. non-infected, vaccinated vs. non-vaccinated, working with vs. non-working with SARS-CoV-2 infected patients. Males were significantly more stressed (p=0.018) and anxious (p=0.034), and physicians in training had the highest prevalence of moderate-to-severe depression (31.60%), followed by physicians (25.64%). In 2023, depression, anxiety, and stress symptoms decreased but remained within a concerning range. By addressing these psychological issues, we can prevent professional crises in the healthcare system.

We report the case of a 61-year-old woman who was referred to the Oral Surgery and Implantology Unit of the University Hospitals of Geneva to take care edentulous sites after dental avulsions of teeth 11 and 21 following traumatic shock due to endotracheal intubation under general anaesthesia. The dental history revealed that the patient had a history of generalized chronic periodontitis that had been treated several years earlier. Treatment consisted, for the first time to our knowledge, of immediate insertion of implants at sites 11 and 21 with simultaneous bone augmentation in a single surgical procedure and immediate restorations.

Existing research indicates that mineralization of Carlin-type gold deposit is related to geological structures, but current studies mostly focus on the qualitative association, and lack quantitative analysis of the relationship between mineralization and structural features, which limits the potential for predictive mineral exploration. In this study, the Nibao Carlin-type gold deposit was selected as the research area to conduct three-dimensional geological modeling, spatial analysis, and three-dimensional prospectivity modeling. Spatial analysis revealed that the majority of gold ore bodies are situated near the main fault, with gold mineralization primarily occurring within a spatial range of approximately -80 meters to 20 meters from the main fault plane. This spatial distribution predominantly aligns in a SW-NE direction. Spatial characteristic extraction of fault slope indicators suggests that the slope angles are conducive to the migration and accumulation of ore-forming hydrothermal fluids, with ore body metal content rapidly increasing within an angle range of approximately 20° to 60°. The shape analysis of the mainfault indicates that the principal spaces of mineralization enrichment are within -10m to 20m of the fault plane undulations, where gold resources are concentrated in a relatively flat area. However, the degree of mineralization is more pronounced in the protruding sections than in the depressed areas. The areas with significant dip changes in faults display higher variations in orebody attitudes, with mineralization noticeably weaker in areas where the fault steepness changes markedly. Ore-bearing units exhibit significantly higher grades within the -17° to 3° interval of fault steepness transition. This interval also sees a rapid accumulation of gold resources. The Nibao gold mine's mineralization is derived from deep, ore-bearing hydrothermal fluids ascending along major fractures, precipitating, and accumulating in favorable ore-hosting spaces (faults, anticline cores) and lithological combinations (sedimentary tuffs, tuffs). Three deep potential gold targets were identified, highlighting the deep western edge of the F1 fault and the deep southeast-trending lower plate as prospective areas for future exploration. This study underscores the effectiveness of 3D prospective modeling as an indispensable tool for elucidating the spatial distribution of fault-controlled Carlin-type gold deposits and their tectonic determinants.