Our aim was to evaluate the immune response of healthcare workers included in the RIPOVAC study, after receiving a booster dose (third dose), in terms of intensity and persistence of induced antibodies. In the second phase of RIPOVAC study, between December 2021 and January 2022, eight months after the second dose, 389 voluntary, immunocompetent, non-pregnant healthcare workers received a booster dose of SARS-CoV-2 vaccine, and a serum sample was obtained. Two groups of patients were established: with and without previous SARS-CoV-2 infection. In order to quantify anti-S1 IgG (AU/mL) we used CMIA (Abbott). All the health workers were anti-S IgG positive 8 months after receiving the booster dose of the vaccine, with a mean of 17040 AU/mL. In 53 patients without previous infection, antibody levels had increased by a mean of 10762 AU/mL. This figure is 7 times higher than the one produced after the second dose (1506 AU/mL). The booster dose produces a robust elevation of the antibody level, which persists at 8 months with levels up to values significantly higher than those reached after the second dose, that allow to predict a persistence of more than one year. The study demonstrates the efficacy of the booster dose of anti-SARS-CoV-2 vaccines.

Our recent studies showed that the treatment of human ovarian tumor cells with NCX4040 resulted in significant depletions of cellular glutathione, formation of reactive oxygen/nitrogen species and cell death. NCX4040 is also cytotoxic to several human colorectal cancer cells (CRC) in vitro and in vivo. Here, we have examined ferroptosis-dependent mechanism(s) of cytotoxicity of NCX4040 in HT-29 and K-RAS mutant HCT116 colon cell lines. Ferroptosis is characterized by accumulation of reactive oxygen species (ROS) within the cell, leading to an iron-dependent oxidative stress-mediated cell death. However, its relevance in the mechanism of NCX4040 cytotoxicity in CRC is not known. We found that NCX4040 generated ROS in CRC cells without any depletion of cellular GSH. Combinations of NCX4040 with erastin (ER) or RSL3 (RAS-selective lethal 3), known inducers of ferroptosis, enhanced CRC death. In contrast, ferrostatin-1, an inhibitor of ferroptosis, significantly inhibited NCX404-induced cell death. Treatment of CRC cells with NCX4040 resulted in induction of lipid peroxidation in a dose- and time-dependent manner. NCX4040 treatment induced several genes related to ferroptosis (e.g., CHAC1, GPX4 and NOX4) in both cell lines. Metabolomic studies also indicated significant increases in both lipid and energy metabolism following the drug treatment in HT-29 and HCT116 cells. These observations strongly suggest that NCX4040 causes ferroptosis-mediated cell death of CRC cells. Furthermore, combinations of NCX4040 and ER or RSL3 may contribute significantly for the treatment of CRC, including those that are difficult to treat due to the presence of Ras mutation in the clinic. NCX4040 induced ferroptosis may also be a dynamic form of cell death for the treatment of other cancers.

Inflammation is the response of the innate immune system to any type of injury. Although acute inflammation is critical for survival, dysregulation of innate immune response leads to chronic in-flammation. Many synthetic anti-inflammatory drugs have side effects, and thus, natural an-ti-inflammatory compounds are still needed. Cannabis sativa L. may provide a good source of in-flammation-reducing molecules. Here, we tested the anti-inflammatory properties of cannabis ex-tracts and pure cannabinoids in lipopolysaccharide (LPS)-induced inflammation in human THP-1 macrophages. We found that pre-treatment with cannabidiol (CBD), delta-9-tetrahydrocannabinol (THC), or extracts containing high levels of CBD or THC reduce the level of induction of various cytokines. The CBD was more efficient than THC, and the extracts were more efficient than pure cannabinoids. Finally, IL-6, IL-10 and monocyte chemoattractant protein-1 (MCP-1) were most sensitive to pre-treatments with CBD and THC, while IL-1β, IL-8 and TNF-α were less responsive. Thus, our work demonstrates the potential of use of cannabinoids or/and cannabis extracts for the reduction of inflammation and establishes IL-6 and MCP-1 as the sensitive markers for the analysis of the effect of cannabinoids on inflammation in macrophages.

The majority of EGFR mutations (85–90%) are exon 19 deletions and L858R point mutation of exon 21, characterized by high sensitivity to EGFR-tyrosine kinase inhibitors (TKIs). Less is known about uncommon mutations (10-15% of EGFR mutations). Predominant mutation types in this category include exon 18 point mutations, exon 21 L861X, exon 20 insertions and exon 20 S768I. This group presents a heterogeneous prevalence, partly due to the different testing methods and to the presence of compound mutation, which in some cases leads to shorter overall survival and different sensitivity to different TKIs than simple mutations. EGFR-TKI sensitivity may also vary depending on the specific mutation and the tertiary structure of the protein. The best strategy remains uncertain and the data of TKIs efficacy are founded of few prospective and some retrospective series. Newer investigational agents are still under study and there are no other approved specific treatment targeting uncommon EGFR mutations. Defining the best treatment option for this patient population remain un unmet medical need. The objective of this review is to evaluate existing data on outcomes, epidemiology and clinical characteristics of lung cancer patients with rare EGFR mutations, with a focus on intracranial activity and response to immunotherapy.

Ion channels are integral membrane proteins that facilitate the movement of ions across cell membranes, playing a key role in a range of biological processes. The high cost and time required for wet lab experiments to characterize ion channels has spurred the development of computational methods for this purpose. In our previous work, we demonstrated the effectiveness of protein language models for ion channel prediction, using a logistic regression classifier to distinguish ion channels from non-ion channels (TooT-BERT-C) and transporters from non-transporters (TooT-BERT-T). In this study, we build upon this approach by using a combination of classical machine learning classifiers and a Convolutional Neural Network (CNN) with fine-tuned representations from ProtBERT, ProtBERT-BFD, and MembraneBERT to discriminate ion channels from non-ion channels. The results of our experiments demonstrate that TooT-BERT-CNN-C, a combination of the representations from ProtBERT-BFD and a CNN, outperforms existing state-of-the-art methods for predicting ion channels, with a Matthews Correlation Coefficient (MCC) of 0.86 and an accuracy of 98.35% on an independent test set.

Thalassemia is a common monogenic autosomal disorder prevalent in India. HbE beta thalassemia is a compound heterozygous state of two different beta globin mutations (HBB), predominant in the Eastern India. In HbE-beta thalassemia (β⁺/β°) patients, one HBB mutation does not produce any functional protein (β°); another mutation produces a structural altered haemoglobin, variant E (β⁺). It has been observed that in HbE-beta thalassemia patients with same type of HBB mutations, there exist diverse phenotypic presentation ranging from very severe, with regular transfusion-dependence to clinically non severe requiring very less transfusion or no transfusion. To explore this phenotypic mystery, we performed trio based expanded whole exome sequencing (WES) of two extreme phenotypes of HbE beta thalassemia subjects with similar HBB genotype and their parents. For WES library preparation, Agilent Sure select V6+UTR kit was used and sequencing was done through the Illumina HiSeq 2500 platform. This study aimed to search for de novo or inherited variants associated with the clinical severity. Six significant inherited variants were found in the genes, ATOH8, TTLL4, P2RX7, PRSS54, SLC9C2 and VRK2 in severe subject, however only one significant inherited variant in MTRR gene was found in non-severe subject. Bioinformatic analysis also confirms that each variant significantly changes in respective protein structure. The identified genes were either associated with iron absorption, oxidative stress, hematopoietic stem cell differentiation, structural organization of RBC cytoskeleton or regulating anemia. No significant de novo variant were identified associated with clinical severity. The finding of this study indicates that the combined effect of mutation load in major pathways may responsible for severe phenotype.

For each $t\in(-1,1)$, exact values of the least upper bounds $$ H(t)=\sup_{\E X=t,\,\E X^2=1} \frac{\E\abs{X}^3}{\E \abs{X-t}^3},\quad \sup_{\E X=t,\,\E X^2=1} \frac{L_1(X)}{L_1(X-t)} $$ are obtained, where $L_1(X)=\E|X|^3/(\E X^2)^{3/2}$ is the non-cental Lyapunov ratio. It is demonstrated that these values are attained only at two-point distributions. As a corollary, S.\,Shorgin's conjecture is proved that states that the exact value is $$ \sup\frac{L_1(X)}{L_1(X-\E X)}= \frac{\sqrt{17 + 7\sqrt7}}{4} = 1.4899\ldots, $$ where the supremum is taken over all non-degenerate distributions of the random variable $X$ with the finite third moment. Also, in terms of the central Lyapunov ratio $L_1(X-\E X)$, an analog of the Berry--Esseen inequality is proved for Poisson random sums of independent identically distributed random variables with the constant $$ 0.3031\cdot H\left(\frac{\E X}{\sqrt{\E X^2}}\right) \left(1-\frac{(\E X)^2}{\E X^2}\right)^{3/2} \le 0.3031\cdot \frac{\sqrt{17 + 7\sqrt7}}{4}<0.4517.$$ where $\Law(X)$ is the common distribution of the summands.

Non-timber forest products (NTFP) have contributed in various ways to the living, livelihoods, and trading of households and communities who live in rural and urban areas all over the world. This paper analyses the value chain of Jiaogulan (Gynostemma pentaphyllum) in the Cao Bang Geopark, Vietnam. 106 actors were surveyed using a semi-structured questionnaire: experts (agricultural extension officers, farmers' associations), harvesters, traders, primary processors, processors, distributors, and consumers. The results show that a map of Jiaogulan value chain, value added of households in main market channels, and impact of value added and distribution of Jiaogulan products on household income.

The Greek seas as a part of the Eastern Mediterranean Sea, have been considered as a hotspot for the entrance of non-indigenous species (NIS). Ballast water functions as a major pathway for the spread of NIS in new environments, posing significant threats to both the ecosystems and human health. Nine non-indigenous fish species, originating from the Red Sea, have been introduced to the Greek seas since 1925. Despite the implemented laws for limiting the spread of NIS and the subsequent impacts, current global environmental issues, such as climate change and micro-plastic pollution, could result in a rapid spread and establishment of NIS in hot-spot regions, including the Greek seas. A more systematic use of advanced tools for the systematic monitoring of all NIS in the Mediterranean Sea is necessary.

Several COVID-19 platforms have been licensed across the world thus far, but vaccine platforms research that can lead to effective antigen delivery is still ongoing. Here, we constructed AdCLD-CoV19 that could modulate humoral immunity by harboring SARS-CoV-2 antigens onto a chimeric adenovirus 5/35 platform that was effective in cellular immunity. By replacing the S1/S2 furin cleavage sequence of the SARS-CoV-2 Spike (S) protein mounted on AdCLD-CoV19 with the linker sequence, high antigen expression was confirmed in various cell lines. The high levels of antigen expression contributed to antigen-specific antibody activity in mice and non-human primates (NHPs) with single vaccination of AdCLD-CoV19. Furthermore, the adenovirus-induced Th1 immune response was specifically raised for the S protein, and these immune responses protected the NHP against live viruses. While AdCLD-CoV19 maintained neutralizing antibody activity against various SARS-CoV-2 variants, it was reduced to single vaccination for β and ο variants, and the reduced neutralizing antibody activity was restored with booster shots. Hence, AdCLD-CoV19 can prevent SARS-CoV-2 with single vaccination, and the new vaccine administration strategy that responds to various variants can maintain the efficacy of the vaccine.

This paper studies the performance improvement of the IEEE 802.15.4 nonbeacon-enabled mode originated by the inclusion of the Request-To-Send/Clear-To-Send (RTS/CTS) handshake mechanism resulting in frame concatenation. Under IEEE 802.15.4 employing RTS/CTS, the backoff procedure is not repeated for each data frame sent but only for each RTS/CTS set. The maximum throughput and minimum delay performance are mathematically derived for both the Chirp Spread Spectrum and Direct Sequence Spread Spectrum Physical layers for the 2.4 GHz band. Results show that the utilization of RTS/CTS significantly enhances the performance of IEEE 802.15.4 applied to healthcare in terms of bandwidth efficiency.

The Short-Term Assessment of Risk and Treatability (START) is deemed the most appropriate instrument for assessing violence risks and management because of its balanced approach between dynamic risk and protective factors. Although several facets of reliability and predictive validity of this tool were strong, its inter-rater reliability, construct validity, and implementation in Asian population were under-investigated. The objective of this research was to examine the inter-rater reliability and construct validity of the START: Thai version within forensic psychiatric inpatients. The participants consisted of 118 forensic psychiatric inpatients hospitalized at Galya Rajanagarindra Institute in Thailand. Trained mental health professionals (i.e., psychiatrists, forensic nurses, clinical psychologists, social workers, and occupational therapists) assessed each participant across twenty domains of the Thai START. The inter-rater reliability was examined using the intraclass correlation coefficient and a confirmatory factor analysis for ordinal data was used to test the construct validity of the scale. The main finding showed a good-to-excellent inter-rater reliability and supported two relational constructs (i.e., strength vs vulnerability subscales) of the Thai START. The Thai START is a promising tool for using in Thai forensic psychiatric setting but some items were not significant in contributing to the scale. This study also provides the guideline for implementing the tool in non-Western forensic psychiatric populations.

Kinetic parameters of SO2 adsorption on unburned carbons from lignite fly ash and activated carbons based on hard coal dust were determined. The model studies were performed using the linear and non-linear regression method for the following models: pseudo first and second-order, intraparticle diffusion, and chemisorption on a heterogeneous surface. The quality of the fitting of a given model to empirical data was assessed based on: R2, R, Δq, SSE, ARE, χ2, HYBRID, MPSD, EABS, and SNE. It was clearly shown that it is the linear regression that more accurately reflects the behaviour of the adsorption system, which is consistent with the first-order kinetic reaction – for activated carbons (SO2+Ar) or chemisorption on a heterogeneous surface – for unburned carbons (SO2+Ar and SO2+Ar+H2O(g)+O2) and activated carbons (SO2+Ar+H2O(g)+O2). Importantly, usually, each of the approaches (linear/non-linear) indicated a different mechanism of the studied phenomenon. A certain universality of the χ2 and HYBRID functions has been proved, the minimization of which repeatedly led to the lowest SNE values for the indicated models. Fitting data by any of the non-linear equations based on the R or R2 functions only, cannot be treated as evidence/prerequisite of the existence of a given adsorption mechanism.

Sweet cherry pomace is a by-product that can be a source of bioactive phenolic compounds. Usually, polyphenols have been extracted using conventional extraction methodologies. However, a significant fraction, called non-extractable polyphenols (NEPs), remains retained in the conventional extraction residues. Therefore, this work is aimed, for the first time, to investigate the release of NEPs from cherry pomace combining pressurized liquid extraction (PLE) and enzyme-assisted extraction (EAE) using Promod enzyme. A response surface methodology was employed to study the influence of temperature, time, and pH on the NEPs extraction. The response variables were the total phenolic content (TPC) measured by Folin-Ciocalteu method, total proanthocyanidin (PA) content evaluated by vanillin, DMAC, and butanol/HCl assays, and total antioxidant capacity determined by Trolox equivalent antioxidant capacity and inhibition of hydroxyl radical assays. The results indicated that PLE-EAE was more suitable and selective to obtain NEPs from sweet cherry pomace than PLE alone. In fact, the extracts obtained by PLE-EAE displayed higher TPC, PA content, and bioactivity than the extracts obtained by PLE under the same extraction conditions, and those obtained by conventional methods. Moreover, size-exclusion chromatography profiles showed that the combination of PLE and EAE enabled the recovery of NEPs with higher molecular weight than PLE without EAE treatment.

Background: Adolescence is a developmental stage when there is a high risk of engaging in non-suicidal self-injury (NSSI). There is recent interest in the study of thwarted belongingness and perceived burdensome as variables associated with the frequency of NSSI in adolescents. Meaning in life (MIL) could be negatively associated with thwarted belongingness and perceived burdensome. To date, no studies have analyzed whether thwarted belongingness and perceived burdensomeness could be associated with the frequency of NSSI in adolescents. On the other hand, no studies have analyzed the buffering role of MIL in the association between thwarted belongingness and perceived burdensomeness and the frequency of NSSI. Aims: a) to test whether thwarted belongingness and perceived burdensomeness are associated with NSSI frequency; b) to test whether MIL moderates the association between thwarted belongingness and NSSI frequency; and c) to test whether MIL moderates the association between perceived burdensomeness and NSSI frequency. Method: The sample consisted of N = 1531 participants between 12 and 18 years old from Spain. The participants filled out the Inventory of Statements about Self-Injury, Purpose-In-Life Test-Adolescents Version, and Interpersonal Needs Questionnaire. Moderation analysis were performed. Results: Thwarted belongingness and perceived burdensomeness were positively associated with the frequency of NSSI in Spanish adolescents. MIL was a moderating variable between thwarted belongingness and the frequency of NSSI, and between perceived burdensomeness and the frequency of NSSI. Conclusion: Thwarted belongingness and perceived burdensomeness could be a risk factor for NSSI and MIL could be a protective factor against NSSI, and adding these variables to current descriptive theories of NSSI in adolescents would allow us to improve the assessment and treatment protocols for adolescents with NSSI.

In microwave imaging it is often of interest to inspect electrically large spatial regions. In these cases, data must be collected over a great deal of measurement points which entails long measurement time and/or costly, and often unfeasible, measurement configurations. In order to counteract such drawbacks, we have recently introduced a microwave imaging algorithm which looks for the scattering targets in terms of equivalent surface currents supported over a given reference plane. While this method is suited to detect shallowly buried targets, it allows to independently process each frequency data, hence the source and the receivers do not need to be synchronized. Moreover, spatial data can be reduced at large extent, without incurring in aliasing artefacts, by properly combining single-frequency reconstructions. In this paper, we validate such an approach by experimental measurements. In particular, the experimental test site consists of a sand box in open air where metallic plate targets are shallowly buried (few cm) under the air/soil interface. The investigated region is illuminated by a fixed transmitting horn antenna whereas the scattered field is collected over a planar measurement aperture at a fixed height from the air-sand interface. The transmitter and the receiver share only the working frequency information. Experimental results confirm the feasibility of the method.

This paper deals with a non-standard finite difference scheme defined on a quasi-uniform mesh for approximate solutions of the Magneto-Hydro Dynamics (MHD) boundary layer flow of an incompressible fluid past a flat plate for a wide range of the magnetic parameter. We show how to improve the obtained numerical results via a mesh refinement and a Richardson extrapolation. The obtained numerical results are favourably compared with those available in the literature.

Arboviruses of medical and veterinary significance have been identified on all 7 continents with every human and animal population at risk for exposure. Like arboviruses, chronic neurodegenerative diseases like Alzheimer’s and Parkinson’s disease are found wherever there are humans. Viral parkinsonism has been documented for a variety of human pathogens though there are few studies that evaluate the effects of viral infection on degenerative neurological diseases. Significant differences in baseline gene and protein expression have been determined between Human Induced Pluripotent Stem Cell lines derived from a non-Parkinson’s disease individual and from an individual with reported Parkinson’s disease. While the organoids generated from each cell line were physically indistinguishable, significant differences were observed in gene and protein expression for neurotransmission and immunity. It was hypothesized that these inherent differences would impact cerebral organoid responses to viral infection. In this preliminary observational study, cerebral organoids from a non-Parkinson’s and Parkinson’s patient were infected with Chikungunya virus and observed for 2 weeks. Parkinson’s organoids lost mass and exhibited a dysfunctional antiviral response. Neurotransmission data from both non-Parkinson’s and Parkinson’s organoids had dysregulation of IL-1, IL-10, IL-6. These cytokines are associated with mood and could be contributing to persistent depression seen in patients following CHIKV infection. Both organoid types had increased expression of CCR5 and CXCL10 which are linked to demyelination, highlighting a potential mechanism for virus-associated parkinsonism. The dysfunctional antiviral response of Parkinson’s organoids highlights the need for more research in neurotropic infections in a neurologically compromised host.

Zinc deficiency, a common malnutrition in children and women is a global public health problem.Burden of zinc deficiencyis more in countries with low meat and high cereal food consumption like Nepal. Nationally representative data on zinc status in Nepal is lacking at present. This study analysed the data from the recent Nepal National Micronutrient status survey 2016(NNMSS-2016) to determinethe prevalence of zinc deficiency and associated risk factors among children aged 6-59 months (n=1462) and non-pregnant women aged 15-49 years(n=1923) from three ecological zones, Hill, Terai, and Mountainof the country. Venous blood was collected from the participants to measure micronutrients such as zinc, markers of anaemia, vitamin A, and markers of inflammation. Stool was collected to assessthe soil-transmitted helminths (STHs) and Helicobacterpylori infection. Socio-demographic, household and other relevant information were collected by a structured questionnaire. Logistic regression was used to examine the predictors of zinc deficiency among the participants.The overall zinc deficiency in children was found to be 22.9% while it was higher in non-pregnant women (24.7%). Predictors associated with zinc deficiency among enrolled children in the study were,living in rural areas (AOR=2.25, 95% CI, [1.13, 4.49]),occurrence of diarrhoea during the two weeks preceding the survey (AOR=1.57, 95% CI, [1.07, 2.30]), household wealth quintile (AOR= 0.48, 95% CI,[0.25, 0.92]) and vitamin A status (AOR=0.49, 95% CI,[0.28, 0.85]. Risk factors associated with zinc deficiency among the non-pregnant women were being underweight (AOR=1.60, 95% CI,[1.15, 2.23]), fever occurrence during two weeks preceding the survey (AOR=1.45, 95% CI,[ 1.06, 1.99]), H. pylori in the stool (AOR=1.32, 95% CI, [1.03, 1.70]), being rich (AOR=0.64, 95% CI,[0.42, 0.98]) and being in the risk of folate deficiency (AOR=0.60, 95% CI,[0.37, 0.96]). We conclude that community focused intervention programs including health and nutrition counselling and livelihood opportunities focusing groups at high-risk may improve the zinc status in Nepal.

This article challenges the notion of the randomness of mutations in eukaryotic cells by unveiling stress-induced human non-random genome editing mechanisms. To account for the existence of such mechanisms, I have developed molecular concepts of the cell environment and cell environmental stressors and, making use of a large quantity of published data, hypothesized the origin of some crucial biological leaps along the evolutionary path of life on Earth under the pressure of natural selection, in particular, 1) virus-cell mating as a primordial form of sexual recombination and symbiosis; 2) Lamarckian CRISPR-Cas systems; 3) eukaryotic gene development; 4) antiviral activity of retrotransposon-guided mutagenic enzymes and finally; 5) the exaptation of antiviral mutagenic mechanisms to stress-induced genome editing mechanisms directed at “hypertranscribed” endogenous genes. Genes transcribed at their maximum rate (hypertranscribed), yet still unable to meet new chronic environmental demands generated by “pollution”, are inadequate and generate more and more intronic retrotransposon transcripts. In this scenario, RNA-guided mutagenic enzymes (e.g. AID/APOBECs), which have been shown to bind to retrotransposon RNA-repetitive sequences, would be surgically targeted by intronic retrotransposons on opened chromatin regions of the same “hypertranscribed” genes. RNA-guided mutagenic enzymes may therefore “Lamarkianly” generate single nucleotide polymorphisms (SNP) and copy number variations (CNV), as well as transposon transposition and chromosomal translocations in the restricted areas of hyperfunctional and inadequate genes, leaving intact the rest of the genome. CNV and SNP of hypertranscribed genes may allow cells to surgically explore a new fitness scenario, which increases their adaptability to stressful environmental conditions. Like the mechanisms of immunoglobulin somatic hypermutation, non-random genome editing mechanisms may generate several cell mutants, and those codifying for the most environmentally-adequate proteins would have a survival advantage and would therefore be Darwinianly selected. Non-random genome editing mechanisms represent a link between environmental changes and biological novelty and plasticity, and provide a molecular basis to reconcile gene-centered and “ecological” views of evolution.

Currently, there is no effective antiviral therapy recommended for the new coronavirus disease 2019 pneumonia (COVID-19). The purpose of this pilot study was to evaluate the safety of Ozonized Saline Solution (O₃SS) used as a complementary therapy in adult patients COVID-19. Twenty-five adult patients who were hospitalized with mild to severe COVID-19 symptoms, who met the inclusion criteria and were being treated from April 18^rd to April 26th, 2020, at the Viamed Virgen De La Paloma Hospital, Madrid, Spain were included in this study. Patients were allocated to receive standard care (SC) that included 200-400 mg hydroxychloroquine twice daily for 5-7 days plus Tocilizumab 400 mg twice daily for 5 days, low molecular weight heparin (LMWH) and 40 mg-60 mg metil-prednisone plus O₃SS, 200 mL, 3-5 µg/mL daily for 10 days. No control group was included, data were compared to clinical trials in this subject. Primary outcomes of treatment with O₃SS were an improvement of clinical symptoms and a reduction in mortality. Secondary end points evaluated included participant clinical status, laboratory examinations, and duration of viral shedding. None of the patients treated with SC + O₃SS died. Improvements in symptoms such as dyspnea, weakness, and reduction in body temperature were observed and corresponded with an improvement of laboratory finding including D-dimer, fibrinogen, LDH, and CRP. No side effects from the O₃SS treatment were observed. Conclusions: COVID-19 patients with mild to severe symptoms who received intravenous O₃SS as a complementary therapy demonstrated no side effects. This preliminary data will be served as base for a future study of the efficacy of this therapy.

In the current context of worldwide honey bee colony losses, among which the varroa mite plays a major role, hope to improve honey bee health lies in part in the breeding of varroa resistant colonies. To do so, methods used to evaluate varroa resistance need better understanding. Repeatability and correlations between traits such as Mite Non-Reproduction (MNR), Varroa Sensitive Hygiene (VSH) and hygienic behaviour are poorly known, due to practical limitations and to their underlying complexity. We investigate (i) the variability, (ii) repeatability of the MNR score and (iii) its correlation with other resistance traits. To reduce the inherent variability of MNR scores, we propose to apply an Empirical Bayes correction. On the short-term (ten days) MNR had a modest repeatability of 0.4 whereas on the long- term (a month) it had a low repeatability of 0.2, similar to other resistance traits. Within our dataset there was no correlation between MNR and VSH. Although MNR is amongst the most popular varroa resistance estimates in field studies, its underlying complex mechanism is not fully understood. Its lack of correlation with better described resistance traits and low repeatability suggest that MNR need to be interpreted cautiously, especially when used for selection.

In December 2019, pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection emerged in Wuhan City, Hubei Province, China. Early in 2020, the World Health Organization (WHO) announced a new name for the 2019-nCoV-caused epidemic disease: coronavirus disease 2019 (COVID-19) and declared COVID-19 to be the sixth international public health emergency. Cellular co-infection is a critical determinant of both viral fitness and infection outcome and plays a crucial role in shaping the host immune response to infections. In this study, sixty-eight public next-generation sequencing libraries from SARS-CoV-2 infected patients were retrieved from the NCBI Sequence Read Archive database using SRA-Toolkit. Using an alignment-free method based on K-mer mapping and extension, SARS-CoV-2 was identified in all except three patients. Influenza A H7N9 (3/68), Human immunodeficiency virus 1 (1/68), rhabdovirus isolate (3/68), Human metapneumovirus (1/68), coronaviruses NL63 (1/68), Parvovirus (1/68), Simian virus 40 (1/68), and hepatitis virus (1/68) genome sequences were detected in SARS-CoV-2 infected patients.

In a recent reformulation of the Marrucci-Ianniruberto constitutive equation for the rheology of entangled polymer melts in the context of non-equilibrium thermodynamics, rather large values of the convective constraint release parameter \beta_{ccr} had to be used in order not to violate the second law of thermodynamics. In this work, we present an appropriate modification of the model which avoids the splitting of the evolution equation for the conformation tensor into an orientation and a stretching part. Then, thermodynamic admissibility dictates simply that \beta_{ccr}≥ 0, thus allowing for more realistic values of \beta_{ccr} to be chosen. Moreover, and in view of recent experimental evidence for a transient stress undershoot (following the overshoot) at high shear rates whose origin may be traced back to molecular tumbling, we have incorporated in the model additional terms accounting, at least in an approximate way, for non-affine deformation through a slip parameter \xi. Use of the new model to describe available experimental data for the transient and steady-state shear and elongational rheology of entangled polystyrene melts and solutions shows close agreement. Overall, the modified model proposed here combines simplicity with accuracy, which renders it an excellent choice for managing complex viscoelastic fluid flows in large-scale numerical calculations.

Although metastasis is the primary cause of death on patients with malignant solid tumors, efficient antimetastatic therapies are not clinically available thus far. Sulfated glycosaminoglycans from marine sources have shown promising pharmacological effects, acting in different steps of the metastatic process. Oversulfated dermatan sulfate from ascidians is effective in preventing metastasis by inhibition of P-selectin, a platelet surface protein involved in the platelet-tumor cell emboli formation. We report in this work that the heparan sulfate isolated from the viscera of the ascidian Phallusia nigra drastically attenuates metastasis of colon carcinoma cells in mice. Our in vitro and in vivo assessments demonstrate that the P. nigra glycan has very low anticoagulant and antithrombotic activities and a reduced hypotension potential, although efficiently preventing metastasis. Therefore, it may be a promising candidate for the development of a novel anti-metastatic drug.

The delivery of Cytochrome c (Cyt c) to the cytosol stimulates apoptosis in cells were its release from mitochondria and apoptosis induction is inhibited. We developed a drug delivery system consisting of Cyt c nanoparticles decorated with folate-poly(ethylene glycol)-poly(lactic-co-glycolic acid)-thiol (FA-PEG-PLGA-SH) to deliver Cyt c into cancer cells and test their targeting in the Lewis Lung Carcinoma (LLC) mouse model. Cyt c-PLGA-PEG-FA nanoparticles (NPs) of 253 ± 55 and 354 ± 11 nm were obtained by Cyt c nanoprecipitation, followed by surface decoration with the co-polymer SH-PLGA-PEG-FA, and compared to a nanoparticle-free formulation. Overexpression of FA in LLC cells and internalization of Cyt c-PLGA-PEG-FA nanoparticles (NPs) was confirmed by confocal microscopy. Caspase activation assays show NPs retain 88-96% Cyt c activity. The NP formulations were more efficient in decreasing LLC cell viability than the NP-free formulation, with IC50: 49.2 to 70.1 μg/ml versus 129.5 μg/ml, respectively. Our NP system is thrice as selective towards cancerous than normal cells. In-vivo studies using tagged nanoparticles show accumulation in mouse LLC tumor 5 min post-injection. In conclusion, our NP delivery system for Cyt c shows superiority over the NP-free formulation and reaches a folic acid-overexpressing tumor in an immune-competent animal model.

The Tumor Microenviroment (TME) is a complex milieu that is increasingly recognized as a key factor in multiple stages of disease progression and responses to therapy as well as escape from immune surveillance. However, the precise contribution of specific immune effector and immune suppressor components of the TME in Burkitt lymphoma (BL) remains poorly understood. In this paper, we applied the computational algorithm CIBERSORT to Gene Expression Profile (GEP) datasets of 40 BL samples to draw a map of immune and stromal components of TME. Furthermore, by VECTRA multispectral immunofluorescence (IF) and multiple immunohistochemistry (IHC), we investigated the TME of an additional series of 40 BL cases and evaluated the possible role of the PD-1/PD-L1 immune checkpoint axis. Our results indicated that M2 polarized macrophages are the most prominent TME component in BL. In addition, we investigated the correlation between PD-L1 and latent membrane protein-2A (LMP2A) expression on tumour cells, highlighting a subgroup of BL cases characterized by a non- canonical latency program of EBV with an activated PD-L1 pathway. In conclusion, our study analysed the TME in BL and identified a tolerogenic immune signature highlighting new potential therapeutic targets.

In the framework of 2D circular membrane Micro-Electric-Mechanical-Systems (MEMS), a new non-linear second-order differential model with singularity in the steady-state case is presented in this paper. In particular, starting from the fact that the electric field magnitude is locally proportional to the curvature of the membrane, the problem is formalized in terms of the mean curvature. Then, a result of existence of at least one solution is achieved. Finally, two different approaches prove that the uniqueness of the solutions is not ensured.

Background: To evaluate the effect of systemic erythropoietin, as well as oral steroids, in the management of recent onset non-arteritic anterior ischemic optic neuropathy (NAION). Method: Ninety-nine eyes of 99 patients diagnosed with NAION within 5 days of onset were included in this single masked randomized clinical trial. Thirty-four patients were randomized into group 1 (systemic erythropoietin), group 2 (oral steroids), and group 3 (control). Group A received 10,000 units of erythropoietin twice a day for three days. Group B received oral prednisone 75 mg daily for two weeks followed by a tapering dose (70 mg for 5 days, 60 mg for 5 days, and 5 mg reductions thereafter every 5 days). Functional and structural outcomes were analyzed at 3 and 6 months following treatment. Best corrected visual acuity (BCVA) was the main outcome measure, and mean deviation (MD) of visual field (VF) test and peripapillary retinal nerve fiber layer thickness (PRNFLT) were secondary outcome measures. Results:The mean BCVA (±SD) at the time of presentation was 1 ± 0.56, 1.01 ± 0.6, and 0.94 ± 0.47 logMAR in groups A, B, and C, respectively (P = 0.140); corresponding values were 0.72 ± 0.45, 0.83 ± 0.46, and 0.78 ± 0.4 logMAR (P = 0.417), and at 6-month follow-up, they were 0.70 ± 0.44, 0.73 ± 0.35, and 0.75 ± 0.39 logMAR, respectively (P = 0.597). Fifty-five percent of patients in group A vesus 34.3% in group B, and 31.2% in group C had an improvement of at least 3 lines in the BCVA values at the 6th-month follow-up visit. (P= 0.04) The mean deviation (MD) at the time of presentation was 19.67 ± 6.2, 20.83 ± 4.83, and 18.94 ± 6.92 decibels (db), respectively (P= 0.483).The corresponding values at month 3 were 18.22 ± 7.5, 19.82 ± 7.15, and 17.65 ± 7.22 db, (P = 0.848); and at month 6 they were 16.56 ± 7.08, 18.15 ± 6.57, and 15.9 ± 5.97 db, respectively. (P = 0.699) PRNFLT at presentation was 189 ± 58, 193 ± 64, and 199 ± 62 micrometers, respectively (P = 0.779), which decreased to 110 ± 45, 127 ± 37, and 119 ± 37 at month 3 (P = 0.423). The corresponding values for month 6 were 88 ± 12, 74 ± 25, and 71 ± 18, respectively (P = 0.041). Conclusion: The findings of our study indicate the beneficial effects of systemic erythropoietin in preserving the function and structure of the optic nerve in recent onset NAION.

Background: Recent developments in our understanding of the interactions between long non-coding RNA (lncRNA) and cellular components have improved treatment approaches for various human diseases including cancer, vascular diseases, and neurological diseases. Although investigation of specific lncRNAs revealed their role in the metabolism of cellular RNA, our understanding of their contribution to post-transcriptional regulation is relatively limited. In this study, we explore the role of lncRNAs in modulating alternative splicing and their impact on downstream protein-RNA interaction networks. Results: Analysis of alternative splicing events across 39 lncRNA wildtype and knockout RNA-sequencing datasets from three human cell lines: HeLa (Cervical Cancer), K562 (Myeloid Leukemia), and U87 (Glioblastoma), resulted in high confidence (fdr < 0.01) identification of 4432 skipped exon events and 2474 retained intron events, implicating 759 genes to be impacted at post-transcriptional level due to the loss of lncRNAs. We observed that a majority of the alternatively spliced genes in a lncRNA knockout were specific to the cell type, in agreement with the finding that genes affected by alternative splicing also displayed enriched functions in a cell type specific manner. To understand the mechanism behind this cell-type specific alternative splicing patterns, we analyzed RNA binding protein (RBP)-RNA interaction profiles across the spliced regions. Conclusions: Despite limited RBP binding data across cell lines, alternatively spliced events detected in lncRNA perturbation experiments were associated with RBPs binding in proximal intron-exon junctions, in a cell type specific manner. The cellular functions affected by alternative splicing were also affected in a cell type specific manner. Based on the RBP binding profiles in HeLa and K562 cells, we hypothesize that several lncRNAs are likely to exhibit a sponge effect in disease contexts, resulting in the functional disruption of RBPs due to altered titration of the RBPs from their target loci. We propose that such lncRNA sponges can extensively rewire the post-transcriptional gene regulatory networks by altering the protein-RNA interaction landscape in a cell-type specific manner.

Gastroenteritis cases associated with non-toxigenic strains of Vibrio parahaemolyticus have been reported in many countries, suggesting the contribution of novel virulence factors. One candidate is zonula occludens toxin (Zot), which increases the intestinal permeability by other bacteria. Recently we identified prophages belonging to the Inoviridae family encoding putative Zot-like toxins in Chilean strains. Based on this information we performed sequence-based analyses of these toxins, followed by phylogenetic and structural analyses using computational tools. Our results showed that Zots found in Chilean V. parahaemolyticus strains are grouped into three different phylogenetic clusters, sharing two conserved motifs (Walker A and B) in their N-terminal region. These motifs are also conserved in Zots from the human pathogens Vibrio cholerae, Neisseria meningitidis and Campylobacter concisus. Although Zots of V. parahaemolyticus do not possess the FCIGRL sequence responsible for the effects produced by V. cholerae, they do possess a conserved secondary structure within their C-terminal region with Zots proteins able to disrupt the intestinal barrier, which is interesting since it has been suggested that the structure and not the Zot sequence would be responsible for the biological effects. This preliminary study provides the basis to study the function of Zots found in V. parahaemolyticus on the intestinal barrier and their possible role as a virulence factor.

Activating mutations in the Epidermal Growth Factor Receptor gene occur as early cancer-driving clonal events in a subset of patients with non-small cell lung cancer (NSCLC) and result in increased sensitivity to EGFR-tyrosine-kinase-inhibitors (EGFR-TKIs). Despite very frequent and often prolonged clinical response to EGFR-TKIs, virtually all advanced EGFR-mutated (EGFRM+) NSCLCs inevitably acquire resistance mechanisms and progress at some point during treatment. Additionally, 20-30% of patients do not respond or respond for a very short time (< 3 months) because of intrinsic resistance. While several mechanisms of acquired EGFR-TKI-resistance have been determined analyzing tumor specimens obtained at disease progression, the factors causing intrinsic TKI-resistance are less understood. However, recent comprehensive molecular-pathological profiling of advanced EGFRM+ NSCLC at baseline has illustrated the co-existence of multiple genetic, phenotypic, and functional mechanisms that may contribute to tumor progression and cause intrinsic TKI-resistance. Several of these mechanisms have been further corroborated by preclinical experiments. Intrinsic resistance can be caused by mechanisms inherent EGFR or by EGFR-independent processes, including genetic, phenotypic or functional tumor changes. This comprehensive review describes the identified mechanisms connected with intrinsic EGFR-TKI-resistance and differences and similarities with acquired resistance and among clinically implemented EGFR-TKIs of different generations. Additionally, the review highlights the need for extensive pre-treatment molecular profiling of advanced NSCLC for identifying inherently TKI-resistant cases and designing potential combinatorial targeted strategies to treat them.

This study aimed to compare three different extracts of Saco sweet cherry, namely non-coloured fraction, coloured fraction and total extract concerning phenolic composition, antioxidant and antidiabetic potential, erythrocytes’ protection and effects on Caco-2 cells. A total of 22 phenolic compounds were identified by LC-DAD. Hydroxycinnamic acids were the most predominant in both non-coloured fraction and total extract, while cyanidin-3-O-rutinoside was the main anthocyanin found in the coloured fraction. The total extract was the most effective against DPPH, nitric oxide and superoxide radicals, and in the inhibition of α-glucosidase enzyme. Finally, the protective effect of the extracts to prevent oxidative damage in human erythrocytes was assessed. The coloured fraction revealed the best activity against hemoglobin oxidation and hemolysis. Regarding to Caco-2 cells, the coloured extract exhibited the most cytotoxic effects, while the total extract was the most efficient in protecting these cells against oxidative damage induced by t-BHP.

Inadequate protein intake can impair protein balance and lead to skeletal muscle atrophy, impaired body growth, and functional decline. Foods provide both non-essential (NEAAs) and essential amino acids (EAAs) that may convey different metabolic stimuli to specific organs and tissues. In this study, we sought to evaluate the impact of six diets with various EAA/NEAA blends on body composition and the risk of developing tissue wasting in late middle-aged male mice. Mice consuming NEAA-based diets, although showing increased food and calorie intake, suffered the most severe weight loss. Interestingly, even moderate NEAAs prevalence was able to induce inflammatory catabolic stimuli, generalized body wasting and systemic metabolic alterations. Complete depletion of retroperitoneal white adipose tissue and a severe loss (>75%) of brown adipose tissue were observed together with muscle wasting. Conversely, EAA-based diets induced significant decreases in weight by reducing primarily fat reserves, but improved clinical parameters. Tissue wasting was caused by altered AA quality, independent of reduced nitrogen or caloric intake. Our results indicate that an optimized balance of AA composition is necessary for preserving overall bodily energy status. These findings are particularly relevant in the context of aging and may be exploited for contrasting its negative correlates including body wasting.

A programmable DC power supply with Real-time Digital Simulator (RTDS)-based photovoltaic (PV) Power Hardware-In-the-Loop (PHIL) simulators have been used to improve the control algorithm and reliability of PV Inverter. This paper proposes a supervisory control algorithm for PV PHIL simulator with non-RTDS device that is an alternative solution of high cost PHIL simulator. However, when such a simulator with conventional algorithm which is used in RTDS is connected to a PV inverter, the output is in the transient state and it makes it impossible to evaluate the performance of the PV Inverter. Therefore proposed algorithm controls the voltage and current target values according to the constant voltage (CV) and constant current (CC) modes to overcome the limitation of the Computing Unit, DC power supply and also uses a multi-rate system to account for the characteristics of each component of simulator. A mathematical models of a PV system, programmable DC power supply, isolated DC measurement device and Computing Unit are integrated to form a real-time processing simulator. Performance tests using a PV PHIL simulator which is applied proposed algorithm connected a PV inverter are carried out and proved superiority and utility of this method against conventional methods.

Non-polio enteroviruses (NPEVs), namely coxsackieviruses (CV), echoviruses (E), enteroviruses (EV), and rhinoviruses (RV), are responsible for a wide variety of illnesses. Some infections can progress to life-threatening complications in children or immunocompromised patients. To date, no treatments have been approved. Several molecules have been evaluated through clinical trials without success. To overcome these failures, the multi-target directed ligand (MTDL) strategy can be applied to tackle enterovirus infections. This work analyzes clinical trials to highlight the best candidates and develops filters to apply to a selection for MTDL synthesis. We explicitly stated the methods used to answer the question: Which solution can fight NPEVs effectively? We note the originality and relevance of this proposal in relation to the state of the art in the enterovirus-inhibitors field. Several combinations are possible to broaden the antiviral spectrum and potency. We discuss data related to the virus and data related to each LEAD compound identified. Overall, this study proposes a perspective on different strategies to overcome issues identified in clinical trials and evaluate the “MTDL” potential to improve the efficiency of drugs synergistically, broaden the targeted, and reduce the adverse effects and drug design cost as well as limit the opportunity of drug-resistant viruses.

Cancer develops from abnormal cell growth in the body, causing significant mortalities every year. To date, potent therapeutic approaches have been developed to eradicate tumor cells, but intolerable toxicity and drug resistance can occur in treated patients, limiting the efficiency of existing treatment strategies. Therefore, searching for novel genes critical for cancer progression and therapeutic response is urgently needed for successful cancer therapy. Recent advances in bioinformatic and proteomic techniques have allowed the identification of a novel category of peptides encoded by non-canonical open reading frames (ncORFs) from historically non-coding genomic regions. Surprisingly, many of the ncORFs express functional microproteins that play a vital role in human cancers. In this review, we provide a comprehensive description of different ncORF types with coding capacity and technological methods in discovering ncORFs among human genomes. We also summarize the diagnostic and prognostic value of these ncORF as well as their carcinogenic role in cancer progression and underestimated potential as therapeutic targets.

Aneurysmal wall enhancement (AWE) of non-ruptured sacular intracranial aneurysms (IA) after endovascular treatment (ET) is a frequently observed imaging finding. So far, its value remains unclear. We aimed to investigate the effect of AWE on aneurysm reperfusion rates in a longitudinal cohort. This is a retrospective MRI study over the timespan of up to 5 years, assessing the correlation of increased AWE of non-ruptured IAs and events of aneurysm reperfusion and retreatment, PHASES Score and grade of AWE. T1 SPACE fat saturation (FS) and T1 SE FS blood suppression sequences after contrast administration were used for visual interpretation of increased AWE. The IAs’ sizes were assessed via the biggest diameter. The grade of enhancement was defined in a grading system from grade 1 to grade 3. 127 consecutive non ruptured IA-patients (58.9 ± 9.0 years, 94 female, 33 male) who underwent elective aneurysm occlusion were included. AWE was observed in 40.2% of patients (51/127) after ET, 6 patients already showed AWE before treatment. In large IAs (which were defined as a single maximum diameter of over 7.5mm,) AWE was significantly associated with aneurysm reperfusion in contrast to large aneurysm without AWE (p = 000.1). All grades of AWE were significantly associated with reperfusion. Our data suggests that in patients with initially large IAs, AWE is correlated with aneurysm reperfusion.

NSCLC is a very aggressive solid tumor, with a poor prognosis due to post-surgical recurrence. Analysis of the specific tumor and immune signatures of NSCLC samples is a critical step in prognostic evaluation and management decisions for patients after surgery. Routine histological assay has some limitations. Therefore, new diagnostic tools with the capability to quickly recognize NSCLC subtypes and correctly identify various markers are needed. We developed a technique for ex vivo expansion of cancer and immune cells from surgical tumor and lung tissue samples of patients with NSCLC (adenocarcinomas and squamous cell carcinomas) and their examination on ex vivo cell preparations and, parallelly, on histological sections after Romanovsky–Giemsa and immunofluorescent/immunochemical staining for cancer-specific and immune-related markers. As a result, PD-L1 expression was detected for some patients only by ex vivo analysis. Immune cell profiling in the tumor microenvironment revealed significant differences in the immunological landscapes between the patients’ tumors, with smokers’ macrophages with simultaneous expression of pro- and anti-inflammatory cytokines, neutrophils, and eosinophils being the dominant populations. The proposed ex vivo analysis may be used as an additional diagnostic tool for quick examining cancer and immune cells in whole tumor samples and avoiding false negatives in histological assays.

Lung cancer (LC) is the second most common cancer and the leading cause of cancer deaths in the U.S. Insulin therapy, a key treatment for managing Type 2 Diabetes Mellitus (T2DM), may increase LC risk. The impact of non-insulin antidiabetic drugs, particularly GLP-1 receptor agonists (GLP-1RAs), on LC risk is not well understood. This study evaluated LC risk in T2DM patients comparing seven non-insulin antidiabetic agents to insulin. Using the TriNetX Analytics platform, we analyzed de-identified electronic health records of 1,040,341 T2DM patients treated between 2005-2019, excluding those with prior antidiabetic use or LC diagnoses. We calculated hazard ratios and confidence intervals for LC risk and used propensity score matching to control for confounding factors. All non-insulin antidiabetic drugs, except alpha-glucosidase inhibitors, significantly reduced LC risk compared to insulin, with GLP-1RAs showing the greatest reduction (HR: 0.49, 95% CI: 0.41, 0.59). GLP-1RAs were consistently associated with lowered LC risk across all histological types, races, genders, and smoking statuses. These findings suggest that non-insulin antidiabetic drugs, particularly GLP-1RAs, may be preferable for managing T2DM while reducing LC risk.

Splenic rupture and hematoma are significant complications that can arise in patients with non-Hodgkin lymphoma (NHL). Understanding these associations is essential for optimal patient management and patients' enhancing outcomes. Histopathological and immunohistochemistry analyses are crucial in diagnosing NHL and assessing splenic involvement. A judicial autopsy was requested by the Prosecutor's Office for a malpractice claim due to a fall in the hospital. In the Emergency Department, a 72-year-old man fell from the gurney, reporting a wound to his forehead. No other symptoms were reported. A face and brain CT scan showed no abnormalities. Nine days after discharge, the patient presented with abdominal pain. Abdominal CT revealed splenic rupture and hemoperitoneum. The patient underwent open splenectomy, but the patient showed signs of hemodynamic shock and subsequently died. The evidence emerging from the autopsy allowed us to diagnose a Mantle Cell non-Hodgkin lymphoma with spleen involvement, previously unknown. Histopathological and immunohistochemical analyses were performed to assess splenic rupture's diagnosis and time estimation. The findings strongly suggest that the splenic rupture was associated with the patient's fall and the pre-existing malignancy. This case highlights the importance of considering underlying hematological malignancies when investigating delayed splenic rupture. Immunohistochemical study of spleen samples allowed the assessment of the timing of splenic hematoma and rupture, leading to establishing a causal relationship with trauma.

This study investigates the impact of Government Consumption (GC) on Saudi Arabia’s GDP during major economic crises from 1969 to 2022, with a focus on periods marked by fluctuations in oil and non-oil revenues. By integrating these revenue streams, the research provides a more comprehensive analysis of fiscal policy effectiveness during economic downturns. Using an Autoregressive Distributed Lag (ARDL) model, the study reveals the complex role of Government Consumption (GC) in stabilizing and stimulating the Saudi economy amidst revenue volatility.Key findings indicate that while GC does not significantly influence GDP in the short term, its long-term effectiveness varies across different crises. Specifically, GC has acted as a buffer against immediate economic shocks during certain crises while providing a stimulus for economic recovery in others. For instance, during the 2020 COVID-19 pandemic, timely fiscal measures significantly boosted GDP, underscoring the importance of adaptive and proactive fiscal policies. Conversely, the 2014-2016 oil price collapse demonstrated that GC alone was insufficient to counteract economic downturns, emphasizing the need for diversified revenue strategies.These findings underscore the dual role of GC in economic stabilization and recovery. During the COVID-19 pandemic, GC played a crucial role in both mitigating negative economic impacts and supporting recovery efforts, showcasing its effectiveness in times of global disruptions. This demonstrates GC's capability as an immediate buffer against economic shocks and a stimulus for economic recovery. In contrast, during the 2014-2016 oil price collapse, GC was less effective, indicating the limitations of relying solely on government spending without broader economic diversification. This highlights the necessity of diversified revenue strategies to complement fiscal measures for long-term economic resilience.The robustness of the findings was ensured through various diagnostic tests, including checks for autocorrelation, heteroskedasticity, and stationarity of residuals. The absence of significant autocorrelation and heteroskedasticity, along with the stationarity of differenced variables, confirms the validity of the econometric models used.The study contributes to the discourse on fiscal policy in oil-dependent economies by illustrating the critical role of diversified revenue strategies and adaptive fiscal measures in enhancing economic resilience. Recommendations are offered for policymakers to optimize fiscal strategies, ensuring robust economic recovery and long-term stability in volatile markets. This research highlights the necessity for Saudi Arabia to refine its fiscal policies towards greater economic diversification and stability.

Previous research has already examined the relationship between Future Anxiety, a construct recently introduced in Italy, and mental health in young adults, although possible mediating variables in this relationship have so far never been investigated. The present study attempts to fill this gap by exploring the incidence of Future Anxiety on psychological distress in a group of 302 young Italian adults (18 - 30 years; M = 21.9; SD = 2.6), presenting and evaluating the simultaneous mediating effect of Intolerance of Uncertainty and Non-Pathological Worry.Findings highlighted how Future Anxiety had a positive and significant direct effect on Stress and Depression, but not on Anxiety. In the three serial mediation models proposed, Intolerance of Uncertainty and Non-Pathological Worry mediated the relationship between Future Anxiety and mental health outcomes. The results also confirmed the hypothesized serial mediation effect by highlighting how young adults with greater Future Anxiety experienced more Intolerance of Uncertainty, which positively affected Non-Pathological Worry levels and, in turn, exacerbated psychological distress. Finally, results indicated that female participants experienced more Stress, Anxiety, and Depression in relation to Future Anxiety compared to males. Starting from the review of main references on this subject, the results discussed provide new insights for understanding youth psychological distress. Finally, practical implications for the design of supportive interventions for this study’s target group are proposed.

This comprehensive review delineates the extensive roles of Akkermansia muciniphila in various health domains, spanning from metabolic and inflammatory diseases to neurodegenerative disorders. A. muciniphila, known for its ability to reside in the mucous layer of the intestine, plays a pivotal role in maintaining gut integrity and interacting with host metabolic processes. Its influence extends to modulating immune responses and potentially easing symptoms across several non-communicable diseases, including obesity, diabetes, and inflammatory bowel disease. Recent studies highlight its capacity to interact with the gut-brain axis, suggesting a possible impact on neuropsychiatric conditions. Despite the promising therapeutic potential of A. muciniphila highlighted in animal and preliminary human studies, challenges remain in its practical application due to stability and cultivation issues. However, the development of pasteurized forms and synthetic mediums offers new avenues for its use in clinical settings, as recognized by regulatory bodies like the European Food Safety Authority. This narrative review serves as a crucial resource for understanding the broad implications of A. muciniphila across different health conditions and its potential integration into therapeutic strategies

In order to solve the problem of large eddy current loss and high temperature rise caused by large amount of permanent magnet, a new type of combined magnetic pole permanent magnet motor is proposed in this paper. The sinusoidal distribution subdomain model of non-uniform air gap rotor is established by using Laplace equation, and the analytical expression of eddy current loss of rotor in uniform air-gap and non-uniform air-gap is derived. The effect of rotor eccentricity on eddy current loss is obtained. According to the characteristics of distributed winding of non-uniform air gap combined pole permanent magnet motor, equivalent treatment is performed to obtain the equivalent thermal conductivity, so as to establish equivalent thermal network model of motor, calculate the temperature value of each component of the motor, and verify the correctness of the thermal network model through the method of magnetothermal bidirectional coupling. Finally, an experimental platform is set up to carry out temperature rise experiments on the two prototypes respectively. Experimental results show that the non-uniform air-gap rotor structure can effectively reduce the rotor eddy current loss and motor temperature rise, and also verify the accuracy of the analytical model calculation results.

The authors undertook pilot studies to assess the accuracy of the reverse engineering process of worn nonstandard spur gears (non-standardized modulus value, unusual profile/pressure angle, high or low teeth), using conventional techniques and measuring instruments. Eight gears were tested, the module of which ranges from 1.020 to 4.98 mm and the number of teeth from 13 to 42. The key parameter, the basic pitch, was selected to estimate the accuracy of the process. The goal is to determine the value of the profile angle. Eleven models were proposed to estimate the nominal tolerance field, using various types of random data distribution. The tested gears were made in IT grade: 6, 7, 8 and 9 according to DIN 3961. Vernier disc micrometers with various measurement ranges were used for research. It has been shown that the nominal module does not have to be treated as a random variable in the population. EIG (Equation of Identity) was developed, allowing conversion of any gear with specific values of geometric parameters into an identical gear with alternative values of these parameters. The directions and degrees of shifts of the estimated tolerance fields relative to the nominal field were determined. The most effective estimating model was selected in the context of the percentage filling of the nominal tolerance field, taking into account the symmetric Student-Fisher distribution with a confidence level of 60%. Further directions of the research activities were described.

Day by day, the share of renewable energy-based power plants such as offshore wind farms and photovoltaic power plants, in the present-day power systems is escalating. Nevertheless, most of these power-producing facilities have been located quite far away from the load centers. At this stage, HVDC power systems provide satisfactory options due to qualities such as reduced line losses, substantial controllability, and environmental advantages. Nevertheless, unique converter designs are required to combine asynchronous HVDC networks with each other and with already existing high voltage alternating current (HVAC) networks. In this study, based on the above special cases, a unique DC-DC modular multilevel converter (MMC) architecture is presented that provides an excellent solution for both integrating modern asynchronous HVDC networks and integrating these modern HVDC power systems with existing asynchronous HVAC power systems. The mathematical analysis of the recommended DC-DC MMC design has been examined in detail and the power transfer between two asynchronous power grids has been realized in a simulation environment. Efficient bilateral power transmission has been made achievable by the control system. The recommended DC-DC MMC topology has shown to be a highly successful approach, in the interconnection of HVDC power systems, according to the simulation results.

We conducted a pilot study to analyze the differential methylation status of 20 primary acinar adenocarcinomas of the lungs. These adenocarcinomas had to be wild type in mutation analysis and had either high (TPS&gt;50%; n=10) or low (TPS&lt;1%; n=10) PD-L1 status to be integrated into our study. To examine the methylation of 866,895 specific sites, we utilized the Illumina Infinium EPIC bead chip array. Both hypermethylation and hypomethylation play significant roles in tumor development, progression, and metastasis. They also impact the formation of the tumor microenvironment, which plays a decisive role in tumor differentiation, epigenetics, dissemination, and immune evasion. The gained methylation patterns were correlated with PD-L1 expression. Our analysis has identified distinct methylation patterns in lung adenocarcinomas with high and low PD-L1 expression. After analyzing the correlation between methylation results of genes and promoters with their pathobiology, we found that tumors with high expression of PD-L1 tend to exhibit oncogenic effects through hypermethylation. On the other hand, tumors with low PD-L1 expression show loss of their suppressor functions through hypomethylation. The suppressor functions of hypermethylated genes and promoters are ineffective compared to simultaneously activated dominant oncogenic mechanisms. The tumor microenvironment supports tumor growth in both groups.

Background: Effective identification and management in the early stages of sepsis are critical for achieving positive outcomes. In this context, neutrophil activation status (NEUT-RI) emerges as a promising and easily interpretable parameter. This study aimed to assess the predictive value of NEUT-RI in diagnosing sepsis and to evaluate its prognostic significance in distinguishing 28-day mortality outcomes. Materials: The study is a secondary retrospective observational analysis. Clinical data upon ICU admission were collected. A control group of critically ill patients without sepsis criteria was included. Patients were divided into subgroups based on renal function for biomarker evaluation, with 28-day outcomes reported for septic and non-septic patients. Results: 200 patients were included in the study. A significant difference between the "septic" and "non-septic" groups was detected in the NEUT-RI plasma concentration (53.80 [49.65–59.05] vs. 48.00 [46.00–49.90], p< 0.001, respectively). NEUT-RI and PCT distinguished between not complicated sepsis and septic shock (PCT 1.71 [0.42 - 12.09] vs 32.59 [8.83 - 100.00], < 0.001 and NEUT-RI 51.50 [47.80 - 56.30] vs 56.20 [52.30 - 61.92], p=0.005). NEUT-RI, PCT and CRP values were significantly different in patients with “renal failure”. NEUT-RI and PCT at admission in ICU in septic group were higher in patients who died (58.80 [53.85-73.10] vs 53.05 [48.90-57.22], p=0.005 and 39.56 [17.39-83.72] vs 3.22 [0.59-32.32], p=0.002, respectively). Both NEUT-RI and PCT showed high negative predictive value and low positive predictive value. Conclusions: The inflammatory biomarkers assessed in this study offer valuable support in the early diagnosis of sepsis. NEUT-RI elevation appears particularly promising for early sepsis detection and severity discrimination upon admission

Pharmacy compounding, the art and science of preparing customized medications to meet individual patient needs, is in a verge of transformation. Traditional methods of compounding often involve manual and time-consuming processes, presenting challenges in terms of consistency, dosage accuracy, quality control, contamination and scalability. However, the emergence of cutting-edge technologies has paved a way for a new era for pharmacy compounding, promising to redefine the way medications are prepared and delivered as pharmacy-tailored personalized medicines. In this multi-site study, more than 30 hospitals and community pharmacies from 8 countries in Europe utilized a novel automated dosing approach inspired by 3D printing for compounding of non-sterile propranolol hydrochloride tablets. CuraBlend® excipient base, a GMP manufactured pharma-ink, intended for automated compounding applications was used. A standardized study protocol to test the automated dosing of tablets with variable weights was performed in all participating pharmacies in 4 different iterative phases. Integrated quality control was performed with an in-process scale and NIR spectroscopy supported by HPLC content uniformity measurements. In total, 6088 propranolol tablets were produced at different locations during this study. It was shown that the dosing accuracy of the process increased from about 90% to 100% from phase 1 to phase 4 by making improvements to the formulation and the hardware solutions. The results indicate that through this novel automated and quality-controlled compounding approach extemporaneous pharmacy manufacturing can take a giant leap forward towards automation and digital manufacture of dosage forms in hospital pharmacies and compounding pharmacies.

The method for quantitative analysis is based on the direct measurement of the analyte using differential pulse voltammetry (DPV), exploiting its oxidation peak. Calibration curves are set up to evaluate the figures of merit of the analytical method (LOD, LOQ, linear range). The application of the sensor for the dosing of GA in real matrices is carried out by analyzing non-alcoholic and alcoholic beverages and comparing the results with those reported in the literature and with the content of total polyphenols determined by the Folin-Ciocalteu method. In all cases, concentrations of GA align with those previously found in the literature for the beverages examined. Moreover, the values are always lower than the total polyphenols content; this demonstrates the good selectivity of the sensor that can discriminate the target molecule from other polyphenols present.

In a single-center, retrospective study, 22 cases were enrolled and divided into two groups: those who underwent surgical wide excision (group A) and those who did not (group B). The study included 13 cases in group A and 9 cases in group B. In group A, 6 cases solely underwent surgical wide excision, while 7 cases received additional treatments like radiotherapy or chemotherapy. Conversely, in group B, 4 cases received chemotherapy, 4 cases received radiotherapy, and 1 case was managed through observation alone. The mean follow-up time was 60.15 months in group A and 43.44 months in group B, with no significant difference observed. In group A, 9 cases resulted in mortality, whereas 6 cases died within the follow-up period in group B. Lesion-free intervals post-operation were observed predominantly in group A, while 7 cases in group B never experienced freedom from skin lesions. Kaplan-Meier survival curve analysis demonstrated a significant difference between the survival curves of the two groups (P = 0.046). Among non-HIV Kaposi’s sarcoma patients, surgical wide excision appears to have a role in treatment. Patients in group A exhibit a more favorable outcome in the survival curve analysis.

The pharmaceutical industry usually utilizes either hydrophobic or hydrophilic substances extracted from raw plant materials for preparing a final product, However, the plant material waste still contain substances with an opposite solubility. The aim of this study was to enhance the comprehensive usability of plant materials by developing a new non-wasting extraction method for eucalypt leaves and by investigating the phytochemical and pharmacological properties of eucalypt extracts and their 3D-printed dosage forms. The present extraction method enabled to prepare both hydrophobic soft extracts and hydrophilic (aqueous) dry extracts. We identified total 28 terpenes in the hydrophobic soft extract. In the hydrophilic dry extract, total 57 substances were identified, and 26 of them were successfully isolated. The eucalypt extracts studied showed a significant antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis, Candida albicans, Corynebacterium diphtheriae gravis, and Corynebacterium diphtheriae mitis. The anti-inflammatory activity of the dry extract was studied with a formalin oedema model in mice. The maximum anti-exudative effect of the dry extract was 61.5% at a dose of 20 mg/kg. The composite gels of polyethylene oxide and eucalypt extract were developed, and the key process parameters for semi-solid extrusion (SSE) 3D printing of such gels were verified. The SSE 3D-printed preparations of novel synergistically acting eucalypt extracts could have uses in antimicrobial and anti-inflammatory medicinal applications.

Single-particle inductively coupled plasma mass spectrometry (spICP-MS) has been used for particle size measurement of diverse types of individual nanoparticles and micrometer-sized carbon-based particles, such as microplastics. However, its applicability to the measurement of micrometer-sized non-carbon-based particles such as silica (SiO2) is unclear. In this study, the applicability of spICP-MS to particle size measurement of non-porous/mesoporous SiO2 micro-spheres with a nominal diameter of 5.0 µm or smaller was investigated. Particle sizes of these microspheres were measured using both spICP-MS based on a conventional calibration approach using an ion standard solution and scanning electron microscopy (SEM) as a reference technique and the results were compared. The particle size distributions obtained using both techniques were in agreement within analytical uncertainty. The applicability of this technique to the detection of metal-containing protein-binding mesoporous SiO2 microspheres was also investigated. Bound iron (Fe)-containing proteins (i.e., lactoferrin and transferrin) of mesoporous SiO2 microspheres were detected using Fe as a presence marker for the proteins. Thus, spICP-MS is applicable to the particle size measurement of large-sized and non-porous/mesoporous SiO2 microspheres; it has considerable potential for element-based detection and qualification of bound proteins of mes-oporous SiO2 microspheres in a variety of applications.

Non-pharmaceutical interventions (NPIs), including social distancing, wearing personal protective equipment, and lockdown measures, have been at the forefront of outbreak control in nursing homes. We used a mixed methodology to assess which NPIs nursing homes in the canton of Geneva, Switzerland, followed for their staff and residents during the first wave of the pandemic, between March 1, 2020 and June 1, 2020. For the qualitative component, we interviewed the attending physicians and/or director of each nursing home. Based on in-vivo codes, NPIs for nursing home workers and residents in each nursing home were thematically classified as: maximally restrictive, moderately restrictive, and minimally restrictive. In the quantitative component, we calculated incident rate ratios (IRR) for infection between the three levels of COVID-19-related measures taken in these nursing homes. We found an equal distribution of maximally (n=4), moderately (n=4), and minimally (n=4) restrictive NPIs. The extent of restriction did not show to be significantly associated with the cumulative incidence of COVID-19 cases among residents (maximally restrictive IRR = 3.90, 95%CI 0.82-45.54, p = 0.184; moderately restrictive IRR = 3.55, 95%CI 0.75-41.42, p = 0.212 ; minimally restrictive IRR = reference). Variabilities in NPIs adopted by nursing homes, and the number of COVID-19 cases appear to be randomly affected.

Background and Objectives: Although researchers suggested that non-pharmaceutical intervention (NPI) and vaccination together can provide the best protection from the COVID-19 [1], people’s willingness to adopt personal NPIs seems to decrease through the COVID-19 waves. This study seeks for an explanation for this observation based on the framework of risk perception. Materials and Methods: Two cross-sectional surveys (N = 407 in Survey 1 and N = 505 in Survey 2) were administered before and in the first outbreak of COVID-19 in Taiwan. The survey items were designed to measure people’s recognized severity of COVID-19, worry of COVID-19, intention to adopt personal NPIs, and attitude toward COVID-19 vaccines. We established a structural model according to the framework of risk perception, which was applied to fit the data of the two surveys. Results: The multigroup SEM (Structural Equation Modeling) results showed that worry (i.e., emotional component of risk perception) fully mediates the influence of recognized severity of COVID-19 (cognitive component of risk perception) on the intention to adopt NPIs in each survey. Before the outbreak (i.e., Survey 1), people’s attitude toward COVID-19 vaccines has nothing to do with their worry of COVID-19. However, when people have experienced the real outbreak of COVID-d19 (i.e., Survey 2), their attitude toward COVID-19 vaccines negatively predicts their worry of COVID-19, forming an indirectly negative effect on their intention to adopt personal NPIs, suggesting the occurrence of the Peltzman effect. That is, receiving vaccination makes people feel safer, that the other way around relaxes their alert for COVID-19, thus, declining the intention to adopt personal NPIs.

Sodium glucose cotransporter 2 inhibitors (SGLT2i) are currently available for the management of type 2 diabetes mellitus. SGLT2i act by inhibiting renal SGLT2, thereby increasing glucosuria and lowering serum glucose. Recent trials are emerging supporting a role for SGLT2i irrespective of the diabetic status pointing towards that SGLT2i have other mechanisms of actions beyond blood sugar control. In this review, we will shed light on the role of this group of medications that act as SGLT2i in non-diabetics focusing on pre-clinical and clinical data highlighting the mechanism of renoprotection and effects of SGLT2i in the non-diabetic kidneys.

The ultimate analysis parameters including carbon (C), hydrogen (H), nitrogen (N), and oxygen (O) content in biomass was rarely found to be predicted by nondestructive tests until to date. In this research, we developed partial least squares regression (PLSR) models to predict the ultimate analysis parameters of chip biomass using near infrared (NIR) raw spectra of non-wood and wood samples from fast growing tree and agricultural residue and nine different traditional spectral preprocessing techniques. These techniques include first derivative (sd1), second derivative (sd2), constant offset, standard normal variate (SNV), multiplicative scatter correction (MSC), vector normalization, min-max normalization, mean centering, sd1 + vector normalization, and sd1 + MSC. Additionally, we employed a genetic algorithm (GA), successive projection algorithm (SPA), multi-preprocessing (MP) 5−range, and MP 3−range to develop a PLSR model for rapid prediction. A dataset consisting of 120 chip biomass samples was utilized for model development in which the samples was non-wood samples of 65-67% and wood samples was 33-35%, and the model performance were evaluated and compared. The selection of the optimum performing model was mainly based on criteria such as the coefficient of determination in the prediction set (R2P), root mean square error of the prediction set (RMSEP), and the ratio of prediction to deviation values (RPD). The optimal model for weight percentage (wt.%) of C was obtained using GA−PLSR, yielding R2P, RMSEP, and RPD values of 0.6954, 1.1252 wt.%, and 1.8, respectively. Similarly, for wt.% of O, the most effective model was obtained using the multi-preprocessing PLSR−5 range method with R2P of 0.7150, RMSEP of 1.3088 wt.%, and RPD of 1.9. For wt.% of N, the optimal model was obtained using the MP PLSR−3 range method, resulting in R2P, RMSEP, and RPD values of 0.6073, 0.1008 wt.%, and 1.6, respectively. However, wt.% of H model provided R2P, RMSEP, and RPD values of 0.5162, 0.2322 wt.%, and 1.5, respectively. Notably, the limit of quantification (LOQ) values for C, H, and O were lower than the minimum reference values used during model development, indicating a high level of sensitivity. However, the LOQ for N, exceeded the minimum reference value, implying the samples to be predicted by the model must be in the range of reference range in calibration set. By scatter plot analysis, the effect of combined non-wood and wood spectra of biomass chips on rapid prediction of ultimate analysis parameters using NIR spectroscopy was investigated. To include different species in a model, the species have to be not only in the different values of the constituents to make a wider range for robust model but also they must provide their trend line characteristics in the scatter plot i.e. correlation coefficient (R), slope and intercept (same slope and slope approached to 1 and intercept is same (no gap) and approached zero, high R approached to 1). The effect of the R, slope and intercept to obtain the better optimized model were studied. The results show that the different species affected model performance of each parameter prediction in a different manner and by scatter plot analysis which of these species were affecting the model negatively and how the model could be improved was indicated. This is the first time of the effect is studied by the principle of scatter plot.

Osteopontin (OPN)-CD44 signaling plays an important role in promoting tumor progression and metastasis. In cancer, OPN and CD44 overexpression is a marker of aggressive disease and poor prognosis, and correlates with therapy resistance. In this study, we aimed to evaluate the association of single nucleotide polymorphisms (SNPs) in the OPN and CD44 genes with clinical outcomes in 307 non-small cell lung cancer (NSCLC) patients treated with radiotherapy or chemoradiotherapy. The potential impact of the variants on plasma OPN levels was also inves-tigated. Multivariate analysis showed that OPN rs11730582 CC carriers had a significantly in-creased risk of death (p = 0.029), while the CD44 rs187116 A allele correlated with reduced risk of locoregional recurrence (p = 0.016) in the curative treatment subset. The rs11730582/rs187116 combination was associated with an elevated risk of metastasis in these patients (p = 0.016). Fur-thermore, the OPN rs1126772 G variant alone (p = 0.018) and in combination with rs11730582 CC (p = 7x10-5) was associated with poor OS in the squamous cell carcinoma subgroup. The rs11730582 CC, rs187116 GG and rs1126772 G, as well as their respective combinations, were in-dependent risk factors for unfavorable treatment outcomes. The impact of rs11730582-rs1126772 haplotypes on OS was also observed. These data suggest that OPN and CD44 germline variants may predict treatment effects in NSCLC.

Objectives: Non-adhesive gel-like embolic materials (NAGLEMs) are becoming increasingly dominant in the endovascular treatment of hypervascularised formations in the head and neck due to a combination of their key properties. The main advantages include their lack of adhesion, effective distribution and penetration through pathological vessels, and crucially, their controlla-bility during the process. Our assigned duty was to scrutinise the literature and assess the efficacy and outcomes of administering NAGLEMs, in comparison to other embolizing substances (name-ly, coils, glue, and particles), among patients treated at our clinic. The procedures involved ana-lyzing the technical aspects, efficiency, and safety of endovascular therapy applied to two catego-ries of hypervascular pathological anomalies, surgically managed from 2015 to 2023. Arteriove-nous malformations (AVMs) located in the head, neck, and paragangliomas with jugular/carotid body localization are combined by intense shunting blood flow and shared requirements for em-bolizates used in endovascular treatment (such as penetration, distribution, delayed polymeriza-tion and controllability). An analysis of the literature was also conducted. Results showed 18 pa-tients diagnosed with neck paragangliomas of the carotid body and jugular type. Five patients with arteriovenous malformation (AVM) of the face and neck were included, consisting of 16 fe-males and 7 males with an average age of 55 ± 13 years. Endovascular procedures were conduct-ed using NAGLEMs (ONYX (Medtronic), SQUID (Balt), and PHIL (Microvention)) and dimethyl sulfoxide (DMSO)-compatible balloon catheters. All patients achieved complete or partial embo-lization of hypervascularized formations using one or more stages of endovascular treatment. Additionally, three AVMs of the face and two paragangliomas of the neck were surgically ex-cised following embolization. In other instances, formations were not deemed necessary to be re-moved. The patients' condition upon discharge was assessed by the modified Rankin Scale (mRs) and rated between 0 and 2. Conclusion: Currently, NAGLEMs are predominantly used to treat hypervascularized formations in the neck and head due to their fundamental properties. These properties include a lack of adhesion and a delay in predictable polymerization (after 30-40 minutes). NAGLEMs also exhibit excellent distribution and penetration throughout the vascular bed of the formation. Adequate controllability of the process is largely achieved through the pres-ence of embolism forms of different viscosity, as well as excellent X-ray visualization.

In this study, sodium alginate (SA) was oxidized with potassium periodate to produce an alginate-based tanning agent. Using OSA as a biodegradable tanning agent and a nano-hydroxyapatite (nano-HAp) low concentration suspension to give flame retardancy to leather, eco-design concepts were applied to establish a chrome-, aldehyde-, and phenol-free tanning process. Micro-DSC, 1H NMR, attenuated total reflection mode Fourier transform infrared spectroscopy (FTIR-ATR), and scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDS) were used to investigate the complex matrix collagen-OSA-nano-HAp. Micro-differential scanning calorimetry (micro-DSC) was used to assess OSA's ability to interact with collagen and stabilize the collagen-OSA matrix, while 1H unilateral nuclear magnetic resonance (NMR) was used to investigate the aqueous environment and limitations around collagen molecules caused by their association with OSA and nano-HAp. Industrial standard tests were used to assess mechanical properties and fire resistance of the new leather prototype. The findings reported here indicate that both OSA and nano-HAp are suitable alternatives for cleaner tanning technologies and more sustainable leather.

Mathematical models of non-small cell lung cancer are powerful tools that use clinical and experimental data to describe various aspects of tumorigenesis. The developed algorithms capture phenotypic changes in the tumor and predict changes in tumor behavior, drug resistance, and clinical outcomes of anti-cancer therapy. The aim of this study was to propose a mathematical model that predicts the changes in the cellular composition of patient-derived tumor organoids over time with a perspective of translation of these results to the parental tumor, and therefore to possible clinical course and outcomes for the patient. Using the data on specific biomarkers of cancer cells (PD-L1), tumor-associated macrophages (CD206), natural killer cells (CD8), and fibroblasts (αSMA) as input, we proposed a model that accurately predicts the cellular composition of patient-derived tumor organoids at a desired time point. Combining the obtained results with “omics” approaches will improve our understanding of the nature of NSCLC. Moreover, their implementation into clinical practice will facilitate a decision-making process on treatment strategy and develop a new personalized approach in anti-cancer therapy.

We aimed to develop a non-linear regression model that could predict the fat fraction of the liver (USFF), similar to magnetic resonance imaging proton density fat fraction (MRI-PDFF), based on quantitative ultrasound (QUS) parameters. We measured and retrospectively collected the ultrasound attenuation coefficient (AC), backscatter-distribution coefficient (BSC-D), and liver stiffness (LS) using shear wave elastography (SWE) in 90 patients with clinically suspected non-alcoholic fatty liver disease (NAFLD) and 51 patients with clinically suspected metabolic-associated fatty liver disease (MAFLD). The MRI-PDFF was also measured in all patients within a month of the ultrasound scan. In the linear regression analysis, only AC and BSC-D showed a significant association with MRI-PDFF. Therefore, we developed prediction models using non-linear least-squares analysis to estimate MRI-PDFF based on the AC and BSC-D parameters. We fitted the models on the NAFLD dataset and evaluated their performance in 3-fold cross-validation repeated five times. We decided to use the model based on both parameters to estimate the ultrasound fat fraction (USFF). The correlation between USFF and MRI-PDFF was strong in NAFLD and very strong in MAFLD. According to a receiver operating characteristics (ROC) analysis, USFF could differentiate between <5% vs. ≥ 5% and < 10% vs. ≥ 10% MRI-PDFF steatosis with excellent, 0.97 and 0.91 area under the curve (AUC) accuracy in the NAFLD and with AUCs of 0.99 and 0.96 in the MAFLD groups. In conclusion, USFF calculated from QUS parameters is an accurate method to quantify liver fat fraction and to diagnose ≥ 5% and ≥ 10% steatosis in both NAFLD and MAFLD. Therefore, USFF can be an ideal non-invasive screening tool for patients with NAFLD and MAFLD risk factors.

In estimating the maximum and minimum index void ratios for mixtures of sand and silt, the values of several empirical constants must be determined based on the type of sand and silt involved. These empirical constants are the filling coefficient, a, and embedment coefficient, b, both of which can be determined either through lab testing or correlations. These constants are then used in equations to predict the maximum and minimum index void ratios of the sand-silt mixtures. The study reported here developed simple correlations for estimating the filling and embedment coefficients using readily obtained laboratory data. These models were found to be excellent in developing filling and embedment coefficients that accurately (R2 values typically of 0.94 or greater.) predicted values of the index void ratios for sand and silt mixtures.

The objective of this study was to investigate the effects of body weight gain during the cashmere non-growing period on cashmere production performance and secondary hair follicle activity, to provide a theoretical basis for appropriate supplementary feeding of cashmere goats. Fifty Inner Mongolian cashmere goats aged 2-4 years old were randomly selected and weighed in May and September 2019, respectively. Based on body weight gain between the two weights, the experi-mental ewe goats were divided into two groups: 0-5.0 kg group (n = 30) and 5.0-10.0 kg group (n = 20). Skin samples and cashmere samples were collected. Results of Pearson correlation analysis showed that body weight gain during the cashmere non-growing period had a moderate and strong positive correlation with cashmere yield (P = 0.021) and cashmere staple length (P = 0.002) respectively, but did not correlate with cashmere diameter (P = 0.254). Compared with cashmere goats with a body weight gain of 0-5.0 kg, cashmere goats with a body weight gain of 5.0-10.0 kg had a 17.10% increment in cashmere yield (P = 0.037), 8.09% increase in cashmere staple length (P=0.045) and had no significant difference in cashmere diameter (P = 0.324). Results of Pearson correlation analysis showed that there was a strong positive correlation between body weight gain and the population of active secondary hair follicles in the skin of cashmere goats (P < 0.01). Compared with cashmere goats with a body weight gain of 0-5.0 kg, cashmere goats with a body weight gain of 5.0-10.0 kg had an increase in the population of active secondary hair follicles (P < 0.05). In conclusion, the body weight gain during the cashmere non-growing period had a sig-nificant effect on secondary hair follicle activity and cashmere production performance in cash-mere goats. Since body weight gain reflects nutritional level to a certain extent, this study suggests that nutritional manipulations such as supplementary feeding during cashmere non-growing periods can increase cashmere production performance. However, specific nutritional manipula-tions during the cashmere non-growing period need further research to increase cashmere pro-duction performance.

Acid stress poses a common challenge for bacteria in diverse environments by the presence of inorganic (e.g., mammals’ stomach) or organic acids (e.g., feed additives; acid-based disinfectants). Limited knowledge exists regarding acid-tolerant strains of specific serotypes, clonal lineages, or sources in human/animal pathogens, namely non-typhoidal Salmonella enterica (NTS) and Enterococcus faecium (Efm). This study evaluated acidic pH and peracetic acid (PAA) susceptibility of Efm (n=72) and NTS (n=60) from diverse epidemiological/genetic backgrounds, and with multiple antibiotic resistance profiles. Efm minimum growth/survival-pH was 4,5-5/3-4 and for NTS 4,0-4,5/3,5-4,0. Among Efm, only those of clade-non-A1 (non-hospital associated) or food chain demonstrated greater tolerance to acidic pH compared to clade-A1 (hospital-associated clones) or clinical isolates (P<0.05). MDR (multidrug-resistant) NTS survived better to acidic pH (P<0.05). The MICPAA/MBCPAA was 70-120/80-150mg/L for Efm and 50-70/60-100mg/L for NTS. Efm-clade-A1 or MDR strains exhibited higher PAA tolerance than clade-non-A1 or non-MDR ones (P<0.05). Higher tolerance was found in non-MDR and clinical NTS than in food chain isolates (P<0.05), but not between different serogroups. This unique study identifies specific NTS or Efm populations more tolerant to acidic pH or PAA, emphasizing the need for further research to tailor control measures of public health and food safety within a One Health framework.

Objectives: Studies on the association between non-steroidal anti-inflammatory drugs (NSAIDs) and major adverse cardiovascular events (MACE) in the Arabian Gulf are scarce. The aim of this study was to evaluate the association between NSAIDs use and MACE in acute coronary syndrome (ACS) patients in the Arabian Gulf region. Methods: Data was analyzed from 3,007 consecutive patients diagnosed with ACS admitted to 29 hospitals in four Arabian Gulf countries from January 2012 to January 2013 as well as being on prior NSAIDs use during the index admission. MACE included stroke/transient ischemic attacks (TIAs), myocardial infarction (MI), all-cause mortality and readmissions for cardiac reasons. Results: The overall mean age of the cohort was 62 ± 12 years and 9.6% (n = 290) of the patients were on prior NSAID use during the index admission. At 12-months follow-up, after adjusting for confounding factors, those on NSAIDs were significantly more likely to have had MACE (adjusted OR (aOR), 1.89; 95% confidence interval (CI): 1.44-2.48; p < 0.001). Specifically, the higher event rates observed were stroke/TIA (aOR, 2.50; 95% CI: 1.51-4.14; p < 0.001) and readmissions for cardiac reasons (aOR, 2.09; 95% CI: 1.59-2.74; p < 0.001) but not MI (aOR, 1.26; 95% CI: 0.80-1.99; p = 0.320) and all-cause mortality (aOR, 0.79; 95% CI: 0.46-1.34; p = 0.383). Conclusions: NSAIDs use was associated with significant stroke/TIA events as well as readmissions for cardiac reasons. However, NSAIDs were not associated with increased MI or all-cause mortality rates in ACS patients in the Arabian Gulf.

Diagnosing Normal Pressure Hydrocephalus (NPH) via non-contrast computed tomography (CT) brain scans is presently a formidable task due to the lack of universally agreed-upon standards for radiographic parameter measurement. A variety of radiological parameters, such as Evans' index, narrow sulci at high parietal convexity, Sylvian fissures' dilation, focally enlarged sulci, and more, are currently measured by radiologists. This study aimed to enhance NPH diagnosis by comparing the accuracy, sensitivity, specificity, and predictive values of radiological parameters, as evaluated by radiologists and AI methods utilizing cerebrospinal fluid volumetry. Results revealed a sensitivity of 77.14% for radiologists and 99.05% for AI, with specificities of 98.21% and 57.14%, respectively, in diagnosing NPH. Radiologists demonstrated NPV, PPV, and accuracy of 82.09%, 97.59%, and 88.02%, while AI reported 98.46%, 68.42%, and 77.42%. ROC curves exhibited an area under the curve of 0.954 for radiologists and 0.784 for AI, signifying the diagnostic index for NPH. In conclusion, although radiologists exhibited superior sensitivity, specificity, and accuracy in diagnosing NPH, AI served as an effective initial screening mechanism for potential NPH cases, potentially easing the radiologists' burden. Given ongoing AI advancements, it's plausible that AI could eventually match or exceed radiologists' diagnostic prowess in identifying hydrocephalus.

With the rising prevalence of obesity, Non-Alcoholic Fatty Liver Disease (NAFLD) now affects 20-25% of the global population. NAFLD, a progressive condition associated with oxidative stress, can result in cirrhosis and liver cancer in 10% and 3% of patients suffering NAFLD, re-spectively. Therapeutic options are currently limited, emphasizing the need for novel treatments. In this study, we examined the potential of activating the transcription factor NRF2, a crucial player in combating oxidative stress, as an innovative approach to treating NAFLD. Utilizing a CRISPR-engineered human cell line, we were able to monitor the expression of heme oxygenase-1 (HMOX1), an NRF2 target, using a Nanoluc luciferase tag. Our model was validated using a known NRF2 activator, after which we screened 1200 FDA-approved drugs, unearthing six compounds (Disulfiram, Thiostrepton, Auranofin, Thimerosal, Halofantrine, and Vorinostat) that enhanced NRF2 activity and antioxidant response. These compounds demonstrated protec-tive effects against oxidative stress and lipid accumulation in vitro. Our study underscores the utility of CRISPR tagging with Nanoluc luciferase in identifying potential NRF2 activators, pav-ing the way for potential NAFLD therapeutics.

Background: The prognostic impact of non-cardiac comorbidities can vary in relation to the left ventricular ejection fraction (EF) in patients with ST-elevation myocardial infarction (STEMI). The aim was to analyze prevalence and long-term prognostic impact of non-cardiac co-morbidities in patients with reduced and preserved EF following STEMI. Method: 3115 STEMI patients undergoing primary PCI were divided in two groups: reduced EF <50% and preserved EF≥50%. Follow-up period was 8 years. Results: Preserved EF was present in 1726 (55.4%) patients and reduced EF was present in 1389 (44.5%) patients. Non-cardiac comorbidities were more frequent in patients with reduced EF as compared with patients with preserved EF (38.9% vs 27.4%, respectively, p<0.001). Lethal outcome was registered in 240 (17.2%) patients with reduced EF and in 40 (2.3%) patients with preserved EF, p<0.001. Diabetes and CKD were independent predictors for 8-year mortality in patients with preserved EF while in patients with reduced EF only CKD was independently associated with 8-year mortality. Conclusion: In the present study the prevalence of non-cardiac comorbidities is similar in patients with reduced and preserved EF after STEMI, but only DM and CKD are independently associated with long-term mortality.

This work aims to investigate the expression levels of four preselected miRNAs previously linked to Cancer and/or Obesity, with the purpose of finding potential biomarkers in the clinical management of Colorectal Cancer (CRC) developed by obese and non-obese patients. We analyzed samples from a total of 65 subjects, 43 affected by CRC and 22 without cancer. Serum and both subcutaneous and omental adipose tissues (SAT and OAT) were analyzed, as well as tumor and non-tumor colorectal tissues in the case of the CRC patients. The relative expression (2-∆∆Ct) levels of 4 miRNAs (miR-181a-5p, miR-143-3p, miR-132-3p and miR-23a-3p) were measured by RT-qPCR. Serum, SAT and OAT expression levels of these miRNAs showed significant differences between subjects with and without CRC, especially in the group of overweight/obese subjects. In CRC serum levels of miR-181a-5p, miR-143-3p and miR-23a-3p correlated with their levels in both SAT and OAT. Moreover, in the case of miR-181a-5p, these correlations were significantly influenced by the body mass index (BMI). From these data, we can conclude that both adiposity and CRC induce changes in the expression of the miRNAs investigated, demonstrating the potential utility of this panel of miRNAs in the diagnosis and prognosis of CRC patients.

Limiting harm to organisms via genetic sampling is an important consideration for rare species. Nondestructive sampling techniques have been developed to address this issue in freshwater mussels. Two methods, visceral swabbing and tissue biopsies, have proven to be effective for DNA sampling, though it is unclear as to which method is preferable for genotyping-by-sequencing (GBS). Tissue biopsies may cause undue stress and damage to organisms, while visceral swabbing potentially reduces the chance of such harm. Our study compared the efficacy of these two DNA sampling methods for generating GBS data for the Unionid freshwater mussel, Texas Pigtoe (Fusconaia askewi). Our results find both methods generate quality sequence data, though some considerations are in order. Tissue biopsies produced significantly higher DNA concentrations and larger numbers of reads when compared to swabs, though there was no significant association between starting DNA concentration and number of reads generated. Swabbing produced greater sequence depth (more reads per sequence) while tissue biopsies revealed greater coverage across the genome (at lower sequence depth). Patterns of genomic variation as characterized in principal component analyses were similar regardless of the sampling method, suggesting that the less invasive swabbing is a viable option for producing quality GBS data in these organisms.

Tissue programmed death ligand-1 (PD-L1) protein expression is predictive of immune checkpoint inhibitor (ICI) benefit. However, tissue PD-L1 can be fraught with tissue acquisition and heterogeneity limitations. Plasma testing can overcome these limitations. However, the overall survival (OS) predictive benefit of plasma PD-L1 assays have not been well characterized. Patients with stage IV non-small cell lung cancer (NSCLC) and plasma cfRNA PD-L1 by PCR expression were identified and assessed for OS. 16 patients treated with front-line ICI-based regimens were assessed and represented a real-world patient population with over half with a performance status of 2 or greater. 10 contemporaneous patients at the same institution treated with chemotherapy alone were also identified and assessed. With a median follow-up of 33 months, median OS was 13 months with a 30% 3-year OS for the ICI treated patients compared to a median OS of 3 months and a 10% 3-year OS for those treated with chemotherapy alone. Comparative log-rank test p-value = 0.014 and a hazard ratio 0.376 (95%-CI 0.134-1.057). Plasma cfRNA PD-L1 was associated with a statistically significant survival benefit from ICI-based treatment compared to chemotherapy in the first line treatment of a real-world patient population of advanced NSCLC.

The presence of a non-structural protein 1 (NS1) in tick-borne encephalitis (TBE) vaccines and the possible induction of an NS1-specific immune response in vaccinated individuals remains a somewhat controversial topic. Previously, we detected the presence of NS1 in Encepur TBE vaccine by mass spectrometry and found the induction of NS1-specific IgG antibodies in mice vaccinated with FSME-Immun TBE vaccine. Here, in this follow-up study, we examined the dynamics and extent of the NS1-specific IgG response in mice vaccinated with these two vaccines in more detail and compared it with the IgG response to the whole virus (WV). Mice were vaccinated at two-week intervals with a total of six doses of each vaccine, and levels of IgG antibodies to TBE virus WV and NS1 were measured by ELISA after each dose. Both vaccines elicited a robust anti-WV IgG response after two doses. The Encepur vaccine did not elicit NS1-specific IgG even after all six doses. In contrast, FSME-Immun vaccine triggered production of NS1-specific IgG after four doses. The results indicate that FSME-Immun is the only vaccine that elicits an NS1-specific antibody response in mice. However, compared to WV-specific IgG, the NS1-specific response is weaker, and a higher number of doses is required to induce detectable levels of NS1-specific IgG antibodies.

Numerical calculations of ultraviolet to near-infrared absorption spectra by cadmium selenide quantum dots (CdSe QDs) doped in anodic aluminum oxide pores were performed using a finite-difference time-domain model. The height, diameter, and periodic spacing of the pores were optimized. Light absorption by the dots was enhanced by increasing the height and decreasing the diameter of the pores. When the height was less than 1 μm, visible light absorption was enhanced as the spacing was reduced from 400 nm to 100 nm. No enhancement was observed for heights greater than 6 μm. Finally, the optical mode coupling of the aluminum oxide and the quantum dots was enhanced by decreasing the pore diameter and periodic spacing, and increasing the height. Laser ablation verified light absorption enhancement by the CdSe QDs. The experiment verified the improvement of the laser-induced damage ability with wavelength of 355-nm after aluminum alloy 6061 coated with functional films, which was fabricated based on numerical calculations.

We performed Bayesian network meta-analysis (NMA) to suggest frontline treatments for patients with high PD-L1 expression (at least 50%). A total of 5,237 patients from 22 studies were included in this NMA. In terms of progression-free survival, immune checkpoint inhibitors (ICIs) plus bevacizumab plus chemotherapy had the highest surface under the cumulative ranking curve (SUCRA) value (98.1%), followed by ICI plus chemotherapy (82.9%). In terms of overall survival (OS), dual immunotherapy plus chemotherapy had the highest SUCRA value (79.1%), followed by ICI plus bevacizumab plus chemotherapy (73.4%). However, there was no significant difference of survival outcomes among treatment regimens combined with immunotherapy. Moreover, ICI plus chemotherapy failed to reveal a significant OS superiority to ICI monotherapy (hazard ratio = 0.978, 95% credible internal: 0.771-1.259). In conclusion, this NMA indicates that ICI plus chemotherapy with/without bevacizumab might to be the best options in terms of OS for NSCLC with high PD-L1 expression. Considering there was no significant difference of survival outcomes among treatment regimens incorporating immunotherapy and ICI plus chemotherapy failed to show significant survival benefits over ICI monotherapy, however, ICI monotherapy may be reasonable as first-line treatment for advanced NSCLC with high PD-L1 expression and no targetable aberrations.

Wheat gluten contains epitopes that trigger celiac disease (CD). A life-long strict gluten-free diet is the only treatment accepted for CD. However, very low-gluten wheat may provide an alternative treatment to CD. Conventional plant breeding methods are not sufficient to produce celiac-safe wheat. RNA interference technology, to some extent, succeeded in the development of safer wheat varieties. However, these varieties had multiple challenges in their implementation. Clustered Regularly Interspaced Short Palindromic Repeats-associated nuclease 9 (CRISPR/Cas9) is a versatile gene-editing tool that has the ability to edit the immunogenic gluten genes. So far, only a few studies have applied CRISPR/Cas9 to modify the wheat genome. In this article, we reviewed published literature that applied CRISPR/Cas9 in wheat genome editing to investigate the current status of the CRISPR/Cas9 system to produce a low-immunogenic wheat variety. We found that in recent years, the CRISPR/Cas9 system has been continuously improved to edit the complex hexaploid wheat genome. Although some reduced immunogenic wheat varieties have been reported, CRISPR/Cas9 has still not been fully explored in editing the wheat genome. We conclude that further studies are required to apply the CRISPR/Cas9 gene-editing system efficiently for the development of celiac-safe wheat variety and to establish it as a “tool to celiac safe wheat.”

Lung cancer is the most common malignancy across the world. The new era in lung cancer treatments, especially this past decade, has yielded novel categories of targeted therapy for specific mutations and adjuvant therapy, both of which have led to improved survival rates. In the present study, we review the changes and development of treatments, with a special focus on adjuvant therapy using tyrosine kinase inhibitors (TKIs) administered to non-small-cell lung carcinoma patients who had a complete resection of the tumor harboring a mutated epidermal growth factor receptor. The clinical trials are dating from the past (chemotherapy trials), present (TKIs) and future (ongoing trials).

Reporting on CSR activities has become the essence of reporting for modern business entities. In this regard, particular attention is paid to public interest companies. Therefore, the following paper aims to answer the question of whether there are differences in the linguistic structure of the studied CSR reports in three selected industry indices on the Warsaw Stock Exchange (WSE) in Poland, i.e. WIG-energy index, WIG-fuel index, WIG-mining index and their relationship with the performance of selected companies. The study was conducted on a purposely selected sample of companies between 2013 and 2018. A total of 138 CSR reports and 138 annual separate financial statements prepared in accordance with international balance sheet law were collected. The study was carried out based on a panel regression model. It was found that CSR reports contained similar average percentages of parts of speech such as nouns and adjectives. When linking the economic performance of companies, expressed with selected indices, to the information on the implementation of CSR concepts, it was revealed that the results are more likely to describe business performance when it is satisfactory.

The relativistic quantum dynamics of a spin-0 scalar particle under the effects of the violation of Lorentz symmetry in the presence of a non-electromagnetic potential is analyzed. The central potential induced by the Lorentz symmetry violation is a linear electric and constant magnetic field and, analyze the effects on the eigenvalues and the wave function. We see there is a dependence of the linear charge density on the quantum numbers of the system

In this ‘New Normal' post-COVID-19 modern world, people's health is becoming increasingly important to track. An advanced technology that uses sensory instruments to track and record critical parameters and communicates with others is the need of the time. It's difficult to keep track of all of the medical parameters and post-operative data of people with non-communicable diseases like diabetes and heart disease on a continuous basis. The system discussed here to be designed for patients who are confined to their homes, particularly when going out and being exposed to the outer world is prohibited. This paper proposed a groundbreaking health management system based on the Internet of Things (IoT) for accessing patient medical parameters in both local and remote areas. When a person's wellbeing becomes urgent, this initiative seeks to send an emergency alert to family members or loved ones. A cloud server records data from the patient's temperature sensor and pulse sensor; the data is analyzed using support vector machine algorithms to identify irregular conditions, and an emergency message is sent to the rest of the family via a mobile application, as well as a warning message to the nearest hospital.

The imipramine ONC201 exerts a novel anti-proliferative activity over a wide spectrum of cancer cell types. ONC201 activates integrated stress response pathway that is associated with induction of Damage Inducible Transcript 3 (DDIT3, also known as C/EBP homologous protein or CHOP). We questioned whether the ONC201/CHOP crosstalk is regulated by diverse signaling pathways in non-metastatic versus metastatic cancer cell lines. Therefore, the Dukes' type B colorectal adenocarcinoma non-metastatic (SW480) and metastatic (LS-174T) cell lines were treated with ONC201. Cell proliferation and apoptosis were evaluated by MTT assay, flow cytometry analysis, gene expression was assessed by Affymetrix microarray, and key regulatory proteins were validated by Western blot assays. Unlike LS-174T cells, SW480 cells were resistant to ONC201 treatment. Gene ontology pathway enrichment analysis of differentially expressed genes revealed substantial differences between LS-174T and SW480 responsiveness to ONC201 treatment. In both cell lines, CHOP expression was upregulated in response to ONC201 treatment, however, its upstream regulatory mechanisms were not identical. Although, PERK, ATF6 and IRE1 ER-stress pathways were found to upregulated CHOP in both cell types, the BAK/BAX pathway was a notable regulator of CHOP in the metastatic LS-174T cells alone. In addition, CHOP RNA splicing profiles were varied between the two cell lines, which was further modified in response to ONC201 treatments. In conclusion, we delineated the signaling mechanisms regulating the expression of CHOP in non-metastatic versus metastatic colorectal cells in response to ONC201 treatment. The observed differences were related to cellular plasticity and metabolic reprogramming.

Streptococcal infection is a main infectious diseases for farmed grey mullet (Mugil cephalus). This study were to identify spreptococcal species in diseased farmed grey mullet and to investigate differences in susceptibility to 13 antibiotics and in genotypes between the stains from the grey mullet and non-grey mullet. 170 samples from diseased farmed grey mullet were collected from three county in 2013 -2016. Multiplex PCR identified L. garviea (146) as the main pathogen, S. agalactia (9), S. dysgalactiae (19), and double infection (5), but no S. iniae. The prevalence changed annually and differed among three counties. Pulsed-field gel electrophoresis (PFGE) analysis demonstrated identical genotype with an ApaI-digested DNA pattern. Disc diffusion results demonstrated differences in antibiotic susceptibility between the strains from grey mullet (146) and non-grey mullet (30). Almost all strains resisted to clindamycin and all strains were susceptible to six antibiotic in grey mullet and 4 antibiotics in non-grey mullet. The reduced susceptible strains was more in non-grey mullet than grey mullet group. The reduced susceptible strains were observed the highest in 2014 and in Chiayi county and decreased from 2014 to 2016. However, the strains with reduced susceptibility to ceftriaxone, cirpofoxacin, moxifloxacin, tetracycline for human treatment were observed.

Vaccination against tick-borne encephalitis (TBE) is based on the use of formalin-inactivated, culture-derived whole-virus vaccines. Immune response following vaccination is primarily directed to the viral envelope (E) protein, the major viral surface antigen. In Europe, two TBE vaccines are available in adult and pediatric formulations, FSME-IMMUN® (Pfizer) and Encepur® (GlaxoSmithKline). Herein, we analyzed the content of these vaccines using mass spectrometry (MS). The MS analysis revealed that the Encepur vaccine contains not only proteins of the whole virus particle, but also viral non-structural protein 1 (NS1). MS analysis of the FSME-IMMUN vaccine failed due to the high content of human serum albumin used as a stabilizer in the vaccine. However, the presence of NS1 in FSME-IMMUN was confirmed by immunization of mice with six doses of this vaccine, which led to a robust anti-NS1 antibody response. NS1-specific western blot analysis detected anti-NS1 antibodies also in sera of humans who received multiple doses of either of these two vaccines; however, most vaccinees who received ≤3 doses were negative for NS1-specific antibodies. The contribution of NS1-specific antibodies to protection against TBE was demonstrated by immunization of mice with purified NS1 antigen, which led to a significant (p < 0.01) prolongation of the mean survival time after lethal virus challenge. This indicates that stimulation of anti-NS1 immunity by the TBE vaccines may increase their protective effect.

In the present study, a mathematical model of non-steady partial differential equation from the process of oxygen mass transport in the human pulmonary circulation is proposed. Mathematical modelling of this kind of problems lead to a non-steady partial differential equation and for its numerical simulation, we have used finite differences. The aim of the process is the exact numerical analysis of the study, wherein consistency, stability and convergence is proposed. The necessity of doing the process is that, we would like to increase the order of numerical solution to a higher order scheme. An increment in the order of numerical solution makes the numerical simulation more accurate, also makes the numerical simulation being more complicated. In addition, the process of numerical analysis of the study in this order of solution needs more research work.

The Populus L. genus unites tree species, which are botanically grouped into several sections. The species successfully hybridize both in the same section and between some sections. The poplar hybridization widely occurs in nature and in variety breeding. Therefore, the development of poplar species specific molecular markers is very actual. The effective markers for trees of the Aigeiros Daby section have been recently developed using the polymorphism of the 5S rDNA non-transcribed spacers (NTSs). In this article, the 5S rDNA NTS based markers were designed for several species of the Leuce Daby section. The alb9 marker amplifies one fragment with DNA matrix of P. alba and P. × canescens (natural hybrid P. alba × P. tremula). The alb2 marker works the same way except the case with P. bolleana. In this case, the amplification of three fragments was observed. The tremu1 marker amplification is detected with DNA matrix of P. tremula and P. × canescens. Thus, the developed markers may be applied as useful tool for the P. alba, P. tremula, P. × canescens and P. bolleana identification in such areas of plant science as botany, dendrology, genetics of populations, variety breeding etc.

Paenibacillus sp. tmac-D7 was isolated from coastline growing Trifolium macraei (double-head clover) root nodules from Bodega Bay, California. The draft genome is 5,567,337 bp with a G+C% of 52.4%, an N50 of 114,261 bp, and 5,282 predicted protein-coding genes. Paenibacillus, while found in many other environments, is frequently isolated from root nodules, with many acting as plant pathogen antagonists. Paenibacillus sp. tmac-D7 is the first genome of a non-rhizobial endophyte isolate from wild Trifolium macraei (double-head clover).

The highest efficiency solar cell won in the efficiency race does not always give the most excellent annual energy yield in the real world solar condition that the spectrum is ever-changing. The study of the radiative coupling of the concentrator solar cells implied that the efficiency could increase by the recycle of the radiative recombination generated by the surplus current in upper junction. Such configuration is called by a super-multi-junction cell. We expanded the model in the concentrator solar cell to non-concentrating installation. It was shown that this super-multi-junction cell configuration was found robust and can keep the maximum potential efficiency (50 % in realistic spectrum fluctuation) up to 10 junctions. The super-multi-junction cell is also robust in the bandgap engineering of each junction. Therefore, the future multi-junction may not be needed to tune the bandgap for matching the standard solar spectrum, as well as relying upon artificial technologies like ELO (Epitaxial lift-off), wafer-bonding, mechanical-stacking, and reverse-growth, but merely uses up-right and lattice-matching growth technologies. We have two challenging techniques; one is the optical cap layer that may be the directional photon coupling layer in the application of the photonics technologies, and another is the high-quality epitaxial growth with almost 100 % of the radiative efficiency.

Cachexia is a syndrome characterized by an ongoing loss of skeletal muscle mass associated with poor patient prognosis in non-small cell lung cancer (NSCLC). However, prognostic cachexia biomarkers in NSCLC are unknown. Here, we analyzed computed tomography (CT) images and tumor transcriptome data to identify potentially secreted cachexia biomarkers (PSCB) in NSCLC patients with low-muscularity. We integrated radiomics features (pectoralis muscle, sternum, and T10 vertebra) from CT of 89 NSCLC patients, which allowed us to identify an index for screening muscularity. Next, a tumor transcriptomic-based secretome analysis from these patients (discovery set) was evaluated to identify potential cachexia biomarkers in patients with low-muscularity. The prognostic value of these biomarkers for predicting recurrence and survival outcome was confirmed using expression data from eight lung cancer datasets (validation set). Finally, C2C12 myoblasts differentiated into myotubes were used to evaluate the ability of the selected biomarker, IL-8, in inducing muscle cell atrophy. We identified 75 over-expressed transcripts in patients with low-muscularity, which included IL6, CSF3, and IL8. Also, we identified NCAM1, CNTN1, SCG2, CADM1, IL8, NPTX1, and APOD as PSCB in the tumor secretome. These PSCB were capable of distinguishing worse and better prognosis (recurrence and survival) in NSCLC patients. IL8 was confirmed as a predictor of worse prognosis in all validation sets. In vitro assays revealed that IL-8 promoted C2C12 myotube atrophy. Tumors from low-muscularity patients presented a set of upregulated genes encoding for secreted proteins, including pro-inflammatory cytokines that predict worse overall survival in NSCLC. Among these up-regulated genes, IL8 expression in NSCLC tissues was associated with worse prognosis and the recombinant IL-8 was capable of triggering atrophy in C2C12 myotubes.

Interactions of soil moisture with plant root systems are very important for plant growth. For non-invasive determination of volumetric soil moisture in a rhizobox, a microwave system based on transmittance of electromagnetic waves in the microwave frequency range was developed using microstrip patch antennas. Vector Network Analyzers (VNAs) were used to measure the S-parameters at frequency ranges close to 5 GHz. A transmission system with microstrip patch antennas was developed. The result of this attenuation is in the frequency domain. The antennae were designed as resonant microstrip antennae. The antennae were placed on both sides of a rhizobox, which allowed non-invasive measuring soil moisture in the box. The attenuation (S21(dB)) was used to measure the effect of temperature, and different types of soil; as well as sensitivity, reproducibility and repeatability of the system. In this work we present quantitative results of soil moisture in rhizobox. The microwave technique, using microstrip patch antennas, is a reliable and accurate system, and showed very promising potential applications for rhizobox-based investigations of root performance.

The present reality about the Nigerian economy calls for investment and development in the non-oil sector. This becomes necessary as a result of fall in the oil price in the global market. This paper examined the Bayesian Vector Autoregression (BVAR) modeling and forecasting of the dynamic interrelationship between Economic growth and revenue from the oil and non-oil sectors in Nigeria. To achieve this, annual data on Gross Domestic Product (GDP), revenue from oil and non-oil sectors were collected from Central Bank of Nigeria (CBN) bulletin, the sample from 1981 to 2008 was used for analysis, while sample from 2009 to 2014 was used for model validation. Six (6) versions of Sims-Zha BVAR models were compared for out-of-sample forecast, the result revealed the superiority of the BVAR6 model over the other BVAR models. Lastly, evidence from the decomposition forecast errors revealed that revenue of oil sector contributed 7.69% to GDP while revenue from non-oil sector contributed 0.12% to GDP in Nigeria. This paper therefore recommended that the present government should encourage investment that is geared toward development in the non-oil sector, of which it has the capacity to improve the Economic growth of the Nigerian economy.

Omega-3 polyunsaturated fatty acids (ω3-PUFAs), including docosahexaenoic acid (DHA), have been shown to exert anticancer effects by inducing apoptotic cell death. However, the mechanism for DHA-induced cell death in lung cancer is not fully understood. Here, we show that DHA induces apoptosis in two human EGFR mutant non-small cell lung cancer (NSCLC) cell lines, and that DHA-induced cell death is accompanied by SIRT6 activation and attenuated Hedgehog (Hh) signaling. Knockdown of SIRT6 using siRNAs inhibited DHA-induced apoptosis, whereas SIRT6 overexpression increased apoptotic cell death. DHA-induced SIRT6 activation was associated with downregulation of Hh signaling, and knockdown of SIRT6 resulted in augmentation of Hh signaling. Pretreatment of NSCLC cells with a Smoothened agonist prevented DHA-induced decreases in the levels of Hh signaling proteins and increases in cleaved PARP levels. Moreover, endogenous production of ω3-PUFAs in PC9 cells via fat-1 expression resulted in elevated SIRT6 levels and reduced levels of Hh signaling molecules, including Gli, following DHA treatment. Overall, these results implicate that ω3-PUFAs induce apoptosis by downregulating Hh signaling via SIRT6 activation in human EGFR mutant NSCLC cells. These findings suggest that ω3-PUFAs potentially represent an effective therapy for the chemoprevention and treatment of NSCLC.

Most of the pore-scale imaging and simulations of non-Newtonian fluid are based on the simplifying geometry of network modeling and overlook the fluid rheology and heat transfer. In the present paper, we developed a non-isothermal and non-Newtonian numerical model of the flow properties at pore-scale by direct simulation of the 3D micro-CT images using a Finite Volume Method (FVM). The numerical model is based on the resolution of the momentum and energy conservation equations. Owing to an adaptive meshing technique and appropriate boundary conditions, rock permeability and mobility are accurately computed. A temperature and concentration-dependent power-law viscosity model in line with the experimental measurement of the fluid rheology is adopted. The model is first applied at isothermal condition to 2 benchmark samples, namely Fontainebleau sandstone and Grosmont carbonate, and is found to be in good agreement with the Lattice Boltzmann method (LBM). Finally, at non-isothermal conditions, an effective mobility is introduced that enables to perform a numerical sensitivity study to fluid rheology, heat transfer, and operating conditions. While the mobility seems to evolve linearly with polymer concentration, the effect of the temperature seems negligible by comparison. However, a sharp contrast is found between carbonate and sandstone under the effect of a constant temperature gradient. Besides concerning the flow index and consistency factor, a good master curve is derived when normalizing the mobility for both the carbonate and the sandstone.

Diabetes mellitus is a chronic metabolic disease that affects over 10.5 percent of the global adult population. Biochemical and hematological parameters such as albumin (ALB) and red cell dis-tribution width (RDW) have been shown to be altered in diabetic patients. This study aims to cor-relate hematological and biochemical parameters with glycated hemoglobin (HbA1c). 777 adult individuals (372 women and 405 men, aged 19-85 years) were divided into three groups: 218 par-ticipants with HbA1c < 5.7% (group A: non diabetic), 226 with HbA1c ≥ 5.7% and < 6.5% (group B: prediabetic) and 333 with HbA1c ≥ 6.4% (group C: diabetic). Biochemical and hematological parameters were compared among the 3 groups. Analysis of variance was performed to deter-mine the correlations of the parameters among groups. ALB and sodium (Na) levels were signifi-cantly decreased in group C compared to groups A (ALB: 3.8 g/dL vs. 4.1 g/dL, p < 0.0001, Na: 138.4 mmol/L vs. 139.3 mmol/L, p < 0.001), and B (ALB: 3.8 g/dL vs. 4.0 g/dL, p < 0.0001, Na: 138.4 mmol/L vs. 139.6 mmol/L, p < 0.0001), while RDW-standard deviation (RDW-SD) and urea were increased in group C compared to group A ( RDW: 45.8 vs. 43.9 fL, p < 0.0001, Urea: 55.6 mg/dL vs. 38.5 mg/dL, p < 0.0001) . Mean platelet volume (MPV) was increased in group C com-pared to group A (9.3 fL vs. 9.1 fL, p < 0.05, respectively). Τhe increase of RDW-SD from group A towards B and C demonstrates the impact of hyperglycemia on red blood cells. RDW may be re-garded as a potential innovative biomarker for improving risk assessment of developing diabetes. These results highlight the potential role of these parameters as an indication for prediabetes that would alert for measurement of HbA1c.

This study addresses the critical issue of cardiovascular diseases (CVD) as the leading cause of death globally, emphasizing the importance of stent delivery catheter manufacturing. Traditional manufacturing processes, reliant on destructive end-of-batch sampling, present significant financial and quality challenges. The research highlights the need for non-destructive Process Analytical Technologies (PAT) to meet the increasing demand for these life-saving devices. The study employs a mixed-method approach, combining qualitative literature review and quantitative artefact development, to propose a closed-loop Cyber Physical Production System (CPPS). The proposed system aims to enhance real-time quality control, minimize costs, and improve manufacturing efficiency. Initial results demonstrate the system's effectiveness in reducing cycle times, improving stability, and significantly decreasing production misses. The findings suggest substantial financial savings and quality improvements, underscoring the potential of advanced control strategies in regulated medical device manufacturing. This study proposes a generalized CPPS framework to be applicable across diverse regulated manufacturing environments, ensuring optimal processing conditions and adherence to regulatory standards. The research concludes with the successful demonstration of innovative approaches and technologies, leading to improved product quality, patient safety, and operational efficiency in the medical device industry.

This paper aims to explore differences between the perception of dark traits in formal leaders and levels of workplace stress among employees working in family and non-family businesses. Furthermore, we assess if the company nature (family-owned versus non-family-owned) moderates the relationship between the employees' perception of dark triad traits in their formal leaders and their workplace stress levels. The empirical evidence is provided by a sample of 220 Portuguese employees who responded to a questionnaire that included their perceptions of their formal leaders’ dark triad traits and workplace stress measures. All respondents work in small and medium-sized private companies with no management responsibilities and under formal hieratical supervision. The initial ideas that family firms’ employees perceive higher levels of dark triad traits in their formal leaders than non-family firms’ employees and that they also show higher levels of workplace stress than non-family firms’ employees were confirmed. The results also support the notion that higher perceptions of dark triad traits in formal leaders are related with higher levels of workplace stress of employees and that the company nature significantly moderates this relationship. These findings contribute to the research literature by addressing two aspects under-addressed in the comparison between family and non-family firms, while offering insights on the relationship between dark triad traits in formal leaders and workplace stress levels of employees.

Quantum thermal engines are receiving much attention in recent years, due to their potential applications.~For a candidate group, harmonically trapped gases under Bose-Einstein condensation (BEC), we see little investigation on the energy transference around that transition.~Therefore, we present an empirical study with rubidium-87 gas samples in a magnetic harmonic trap.~We developed an empirical Equation of State model to fit to our experimental dataset, expressing the pressure parameter ($\mathcal{P}$) in terms of temperature ($T$) and six technical coeffcients ($\{a_i\}_{0,\dots,4}$, $T_\mathrm{th}$), functions of volume parameter ($\mathcal{V}$) and number of atoms ($N$).~For weakly interacting gases, the internal energy is $U\cong3\mathcal{P}\mathcal{V}$, thus we determine the entropy with $U = TS - \mathcal{P}\mathcal{V}$ for fixed $N$.~As expected, we show that the entropy at the BEC transition ($S_c$) is constant for varying $\mathcal{V}$.~Being isentropic makes BEC transition an energy source for non-mechanical work.~Hence, we observed that the enthalpy at the BEC transition $H_c = E_c + \mathcal{P}_c\mathcal{V} = T_cS_c$, at fixed values of $\mathcal{V}$ and varying $N$, grows fairly linearly with $N$.~We fitted $H_c=\eta{N}-H_c^0$ to that data, being $\eta$ the specific enthalpy of BEC transformation and $H_c^0$ an intrinsic enthalpic loss.~We deem this study to be a step closer to practical quantum-based engines.

Background: Alzheimer's Disease (AD) is a progressive and incurable condition that prompts the exploration of interventions to slow its advancement and enhance the quality of life. The cortical brain waves could have a role in the process of executive function deterioration, increasing dementia symptoms. Objective: To interrogate the effects of physical exercise, and non-invasive brain stimulation, both in electrophysiological behavior of the brain, the executive functions, and dementia symptoms in older adults with AD. Methods: One hundred and sixteen older adults were grouped (n=22 each): GAE (AD, PMED+NIBS), GCP (AD, PMED), GCN (AD, NIBS), GCS (control, no intervention). Binaural beats were used as a non-invasive brain stimulation, physical exercise, or both, were applied during 16 weeks. Pre/post measurements included Alpha Band, and SMR Rhythms, executive functions, and dementia symptoms. Results: GCS showed no significant changes (p>0.05). GCN and GCS slightly enhanced inhibitory control (p>0.05) and working memory (p>0.05). In contrast, GCP and GAE improved executive function (p

Background: The aim of this study was to investigate a series of complete blood cell count – based biomarkers of systemic inflammation as predictors of clinical outcomes in patients who underwent first-line chemoimmunotherapy for advanced NSCLC. Methods: Consecutive patients with pathologically diagnosed stage III/IV NSCLC who underwent first-line chemoimmunotherapy were retrospectively enrolled. The clinical outcomes used for biomarker evaluation were Objective Response Rate (ORR) and Overall Survival (OS). Results: Non-responders had significantly higher values of neutrophil to lymphocyte ratio (NLR, median: 5.36; IQR: 2.78–10.82 vs. 3.31; IQR: 2.15–4.12, p = 0.019), neutrophil to monocyte ratio (NMR, median: 14.00; IQR: 8.82–21.20 vs. 9.20; IQR: 7.45–11.20, p = 0.013), and systemic inflammation index (SII, median: 1,395; IQR: 929–3,334 vs. 945; IQR: 552–1,373, p = 0.025), but only NLR and NMR remained independently related with clinical response in multivariate logistic regression. In univariate analysis white blood cells (OR:1.2202; 95% CI: 1.0339 - 1.4400, p=0.019), neutrophils (OR:1.2916; 95% CI: 1.0692 - 1.5604, p=0.008), NLR (OR:1.3601: 95% CI: 1.0949 - 1.6896, p=0.005) and NMR (OR:1.2159; 95% CI: 1.00396 - 1.4221, p=0.015) were significantly associated with survival; Cox regression models confirmed that neutrophils, NLR and MLR were independently associated with survival; NLR at a cut-off value of 4.0 showed the better AUC (0.749) in predicting survival. Conclusions: Baseline complete blood cell count biomarkers, especially the NLR, can predict clinical outcomes in patients with advanced NSCLC treated with first-line chemoimmunotherapy.

The current work reports the upper bound of the state variable of the of the Pointwise Steady Fluid Flow Approximation (PSFFA) model of non-stationary M/Ek/1 queueing system.