Introduction: People with severe and persistent mental illness (SPMI) present unique challenges in mental healthcare due to the enduring nature and complexity of their conditions. This study evaluated the clinical effectiveness and potential cost benefits of a multidisciplinary community psychosocial rehabilitation team catering to individuals with SPMI in Nova Scotia, Canada. Method: The Canadian billing system of Medical Service Insurance (MSI) was used to compare inpatient service use and emergency department visits during the year before and the year after receipt of one year of community rehabilitation for patients referred to the team from September 2016 to September 2017. Result: Results demonstrated a statistically significant reduction in mean admission rates and length of inpatient admissions in the year following rehabilitation compared to the pre-rehabilitation year. A substantial percentage of patients experienced no inpatient admissions (88% v. 60%) or ED visits (82% v. 67%) in the post-rehabilitation year compared to the pre-rehabilitation year. There was a significant reduction in inpatient days by 90%, translating into substantial cost savings. The findings highlight the potential economic benefits of community rehabilitation for people with SPMI. Conclusion: This uncontrolled study suggests that community rehabilitation is associated with favourable clinical outcomes for individuals with SPMI in terms of reduced inpatient service use and related costs. Further research into community psychosocial rehabilitation services in the Canadian setting is needed, including controlled and cost-effectiveness studies.

We aimed to investigate the relationship between membrane material and development of membrane fouling in a membrane bioreactor (MBR) using membranes with different pore sizes and hydrophilicities. Batch filtration tests were performed using submerged single hollow fiber membrane ultrafiltration (UF) modules with different polymeric membrane materials including cellulose acetate (CA), polyethersulfone (PES), and polyvinylidene fluoride (PVDF) with activated sludge taken from a municipal wastewater treatment plant. The three UF hollow fiber membranes were prepared by a non-solvent-induced phase separation method and had similar water permeabilities and pore sizes. The results revealed that transmembrane pressure (TMP) increased more sharply for the hydrophobic PVDF membrane than for the hydrophilic CA membrane in batch filtration tests, even when membranes with similar permeabilities and pore sizes were used. PVDF hollow fiber membranes with smaller pores had greater fouling propensity than those with larger pores. In contrast, CA hollow fiber membranes showed good mitigation of membrane fouling regardless of pore size. The results obtained in this study suggest that the surface hydrophilicity and pore size of UF membranes clearly affect the fouling properties in MBR operation when using activated sludge.

The demand for improved service in mobile networks is always increasing. That means signal transmission with higher capacity is required. To achieve that goal a combined optical and wireless link using double polarization multiplexing has been developed. A high quality signal transmission is achieved by applying high polarization extinction ratio. The new concept is validated by experiments varying the bit rate and fiber length. A signal with 12 Gbit/s bit rate was transmitted over a 25 km long combined link with about 1.10-8 bit error rate. That result is much better than the already published data which were measured on links transmitting information with 2.5 Gbit/s bit rate. The polarization multiplexing technique is very practical for capacity enhancement in a specific section of an existing optical fiber by inserting a new link into it without deploying a new fiber.

Calcium phosphates and manganese phosphates play a significant role in biomedical and engineering applications, and these compounds are both synergistic. These compounds could have great potential for use in different applications, particularly as precursors of biomaterials. Therefore, the aim of this study was to explore the effect of the gradual replacement of Ca2+ with Mn2+ on the phase composition and crystal structure of brushite (CaHPO4·2H2O), which could be useful for the production of Mono- and Biphasic Ca1−xMnxHPO4·nH2O Compounds. In order to prepare the starting solutions required for this study, Ca(NO3)2·4H2O, (NH4)2·HPO4, and Mn(NO3)2·4H2O were used at various molar concentrations. Afterwards, the Ca1−xMnxHPO4·nH2O compounds were prepared using dissolution and precipitation methods. These compounds were characterized using XRD, SEM, FT-IR, XPS, and TGA techniques. The findings revealed that Mn substituted Ca partially at low Mn/Ca molar ratios, 0.25, and Mn doping increased the unit cell of CaHPO4·2H2O. The produced biphasic compound was composed of monoclinic CaHPO4·2H2O and nanostructured orthorhombic MnHPO4·(H2O)3 after a continuous increase in the Mn/Ca molar ratio to 1.5. When the Ca/Mn molar ratio was above 1.5, a monophasic compound of the MnHPO4·(H2O)3 phase was formed. The MnHPO4·(H2O)3 compound was successfully prepared for the first time using this dissolution-precipitation method. It was also established that the Mn/Ca ratio of the starting solution can be modified to produce CaHPO4·2H2O and MnHPO4·(H2O)3 phases with specific weight percent compositions.

Face milling is a well known commercial process highly used in heavy industries that consumes high amount of power. Besides power issue, modern manufacturing industries are aiming for per part cost reduction keeping the product quality unimpaired. Unexpectedly if the part is rejected in any stage of manufacturing, the cost of manufacturing dramatically increases. Major cause of part rejection is excessive tool wear that imparts poor surface profile or catastrophic tool failure that causes adherence of broken tool debris onto machined surface. Furthermore, the tool wear is associated with sliding distance (frictional distance) and the tool life quantifies the cost of tools. As such, from the perspective of manufacturing industries it is imperative to optimize the surface quality parameter, cost of part, power consumption, and material removal – this is exactly what is accomplished here. By this work, it is possible to conserve power consumption, produce parts with lower cost, manufacture with uncompromising surface quality and enhanced material removal rate. Moreover, as intermediate factors of interest, the influences of sliding distance, tool life and tool flank wear on the overall machining performance are evaluated. The multi-objective optimization by Grey Relational Analysis (GRA) revealed that for improved product performance and fast manufacturing (case 1) optimum results are: feed per tooth fz = 0.25 mm/tooth, cutting speed vc = 392.6 m/min and cutting length l = 0.5 mm; for resource conservation (case 2) the optimum results are: feed per tooth fz = 0.125 mm/tooth, cutting speed vc = 392.6 m/min, cutting length l = 0.5 mm.

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

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, which was grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while also preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, which showed up as reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

Background: Bacterial resistance to several antibiotic classes is seen as a grave threat worldwide. Bacterial resistance to antibiotics was mostly caused by the abuse and overuse of antibiotics, particularly penicillins and first-generation cephalosporins, in Egypt's primary healthcare facilities. Aim of the study: To investigate the main resistant bacteria to a few chosen penicillins and first-generation cephalosporins, as well as the characterization of these antibiotics' resistant genes and their detrimental effects in Egypt's main medical facilities. Methodology: Two hundred respiratory and urinary tract infection (RTI and UTI) specimens were gathered from Egyptian primary medical center patients. The turbidimetric assay at 630 nm wavelength, the broth dilution technique, and the nanopore sequencing homology approach were used to characterize the major resistant pathogenic bacteria and their resistant genes to cefadroxil (first generation cephalosporins) and nafcillin (antipseudomonal penicillin). Moreover, adverse outcomes resulting from antibiotic resistance were noted. Results: Out of 200 specimens with RTI and UTI, 186 samples showed the proliferation of resistant bacteria isolates. Enterococcus faecium strain NFC and Staphylococcus aureus strain CDX were among them. Nanopore sequencing confirmed that the antibiotic-resistant gene in Enterococcus faecium was the NFC gene, whereas the antibiotic-resistant gene in Staphylococcus aureus was the CDX gene. Penicillin-binding proteins with modest affinity were encoded by both genes. These bacterial resistance patterns were linked to a low death rate of 5% and a high morbidity rate of 47%. Conclusion: By expressing low-affinity penicillin-binding proteins through resistant NFC and CDX genes, Enterococcus faecium strain NFC and Staphylococcus aureus strain CDX were found to be the predominant bacterial isolates that cause antibiotic resistance to first-generation cephalosporins and penicillins.

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

Background: Antibiotic resistance is an overwhelming serious difficulty globally. This necessitates the exploration of novel sources of antibiotics to overcome this challenge. Aim of the study: Bacterial Myxopyronin A production from various soil environments Egypt; as well as testing its antimicrobial activity in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Different soil environments in Egypt were screened for the growth of bacterial isolates producing Myxopyronin A as an antimicrobial agent. Purification of Myxopyronin A was performed via reversed-phase HPLC. Paper disc diffusion assay, as well as the Broth dilution technique, were exploited to assess the invitro antimicrobial and minimum inhibitory concentration( MIC) of the test antibiotic. Furthermore, in vivo antimicrobial spectrum, adverse drug reactions, and pharmacokinetics were detected during animal model testing stages and human randomized clinical trials phases 1/2. Results: From the culture supernatant of the Myxobacterium Myxococcus fulvus 124B02 which was the predominant soil bacterial isolate grown on the Casein yeast peptone plate, Myxopyronin A was produced. The test antibiotic blocked the growth of many Gram +ve bacteria with MICs less than 100 mcg/ ml. In contrast, it inhibited the growth of a few Gram -ve bacteria such as Escherichia coli at MICs greater than 100 mcg/ ml. On the other hand, Eukaryotic cells such as fungal and human cells were not affected. Prokaryotic DNA-dependant-RNA polymerase( RNLP) was noticed to be inhibited via the test antibiotic suggesting its bactericidal action. The maximum concentration was 7-8 mcg/ ml at a maximum time of 2 hours when 600 mg dose was orally administered in randomized human clinical trials phases 1/2, and T1/2 reached 2.5 hours following first-order kinetics of elimination. The duration of its action was nearly 12 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and cholestatic jaundice in less than 5 % of experimental candidates. Conclusion: The present study was promising due to the bactericidal antibiotic Myxopyronin A production from Myxococcus fulvus 124B02 isolated from different soil environments in Egypt.

The non-structural protein NS3/4A protease is a critical factor for hepatitis C virus (HCV) maturation that requires activation by NS4A. Synthetic peptide mutants of NS4A were found to inhibit NS3 function. The bridging from peptide inhibitors to heterocyclic peptidomimetics of NS4A has not been in consideration in literature, and therefore, we decided to explore this strategy to develop a new class of NS3 inhibitors. In this report, a structure-based design approach was used to convert the bound form of NS4A into 1H-imidazole-2,5-dicarboxamide derivatives as first generation peptidomimetics. This scaffold mimics the buried amino acid sequence Ile-25` to Arg-28` at the core of NS4A21`-33` needed to activate the NS3 protease. Some of the synthesized MOC compounds were able to compete with and displace NS4A21`-33` for binding to NS3. For instance, N5-(4-guanidinobutyl)-N2-(n-hexyl)-1H-imidazole-2,5-dicarboxamide (MOC-24) inhibited the binding of NS4A21`-33` with a competition IC50 of 1.9 ± 0.12 µM in a fluorescence anisotropy assay, stabilized the denaturation of NS3 by increasing the aggregation temperature by ΔTagg 0.6 ± 0.140 ℃. MOC-24 also inhibited NS3 protease activity in a fluorometric assay. Molecular dynamics simulations rationalized the structure-activity relationship (SAR) differences between the active MOC-24 and the inactive MOC-26. Our data shows that MOC compounds are possibly the first examples of NS4A peptidomimetics that demonstrated promising activities against NS3 proteins.

المستخلص تصنيع لقاح مكون من الحمض النووي الريبوزي الرسول الخاص بالبروتينات المسئولة عن انتاج البروتينات نيورامنيديز والهيم اجليوتونين لفيروسي الانفلونزا الخنازير والطيورمحاط بجزيئات دهنية بحجم النانوميتر عدوى انفلونزا الخنازير وانفلونزا الطيور مشكلة خطيرة تؤرق العالم كله هذه الايام خصوصا انها مميتة لكثير من اطفال العالم . بعد فترة التعافي من الاصابة تتكون المناعة المكتسبة ضدها لمدة عام تقريبا. هذه الانفلونزا تسبب تسمم فيروسي في الدم بالاضافة للالتهاب الرئوي وهذامن بين اكبرالاسباب للوفاة بين الاطفال قبل سن عامين عالميا بشكل مباشر. الهدف من الدراسة هو انتاج لقاح الحمض النووي الريبوزي الرسول من نوع الام بالنانوتكنولوجي لبروتينات الهيم اجليوتونين والنيورامنيديز الموجودة على سطح هذه الفيروسات التي تساعدتها في الاتصاق بالعائل الذي ستتكاثر داخل خلاياه بالجهاز التنفسي. هذه الدراسة دراسة استكشافية ومن خلالها استطاعنا تصميم هذا اللقاح باستعمال نظام توصيل للقاح بالنانوتكنولوجي حجم جزيئاته 70نانوميمتر. اللقاح الجديد اظهر فاعلية بنسبة 60% واظهر فاعلية حيوية مقاربة واثار جانبية اقل بالمقارنة باللقاحات المتوفرة حاليا بالسوق الدوائي ضد هذا النوع من الفيروسات الوبائية. ABSTRACT Background: Worldwide, Swine and Avian influenza, or the H1N1 and H5N1 serotypes of the Influenza A virus, is a highly contagious illness. In recent years, the global incidence of mortality rate has surpassed 284,000 fatalities. Aim of the study: The production of mRNA vaccine lipid nanoparticles (LNP) to combat the deadly strains of Avian and Swine influenza (H1N1 and H5N1 of the influenza A serotype). Methodology: Polymerase chain reaction (PCR) was used to clone genes of interest encoding Haemagglutinin (HA) and Neuraminidase (NA) of Influenza A virus strains (H5N1 and H1N1) known as Avian flu and Swine flu, respectively. The genes were then inserted using the EcoR1, BAM Hind II restriction endonuclease type II, and Ligase enzyme into the pET-21(+) transcription vector plasmid. On the other hand, the hybrid transcription vectors were mixed with T7 RNA polymerase and ribonucleotides within a test tube after being linearized using EcoR II. Following their purification via reversed-phase high-performance liquid chromatography (RP-HPLC), the mRNAs of the HA and NA were encased in 70 nm LNPs and subjected to reverse-phase high-performance liquid chromatography (RP-HPLC). Lastly, immunogenicity studies were performed in stages 1/2 of randomized human and preclinical clinical trials. Results: The bivalent vaccination had around 63% efficacy in preclinical studies and approximately 60% efficacy in randomized human clinical trials. As shown by the ELISA test, strong neutralizing antibodies against HA were prevalent. Conclusion: The current study is a promising effort because of the development of the novel LNP-mRNA vaccine, which could lower the incidence of Avian and Swine flu infectious disorders.

Diabetes mellitus is one of the most common endocrinopathies, estimated to affect about 5.4% of the world's population around 2025. It is thought that nearly a third of diabetic patients have some type of skin condition. Frequently, the cutaneous effects of this heterogeneous syndrome are ac-curately detected late in the progressive form of the disease. The main objective of the present study was to identify the main cellular characteristics of the cutaneous microenvironment in exper- imentally induced diabetes mellitus. Skin fragments were harvested from adult white Wistar rats of both sexes, with the weight of 200 g, 12 weeks after streptozotocin diabetes was induced. In parallel with histopathological diagnosis by using hematoxylin and eosine staining, samples were processed by transmission electron microscopy technique and examined with a Philips CM100 microscope. In the apparently macroscopically unchanged tegument, photon microscopy revealed both progres ive thinning of the epidermis in the early stages of diabetes and a significant process of fibrosis and collagen hyalinization in the dermis. In addition, in the early stages, the electron microscopic study provided ultrastructural details characteristic of a senescent phenotype with reduced cell proliferation. The morphological changes in the skin may be the first signs of disruption of carbohydrate metabolism and in the case of established diabetes may reflect its progression and the efficacy of therapy.

Background: Breast cancer and other neoplasms like acute lymphocytic leukemia pose a serious threat to public health worldwide. Treatment for malignancies including acute lymphocytic leukemia and breast cancer requires enzymes that break down L-glutamine. An amidohydrolase called L-glutaminase can be an effective chemotherapeutic tool for treating various cancers. Methods: On mineral L-glutamine agar selective medium (MGA), a few bacterial isolates were examined in the current investigation to see if they produced L-glutaminase. However, the most effective positive bacterial isolates generating L-glutaminase were identified using morphological and biochemical testing. Molecular detection using the direct Southern blotting approach was also used to determine the main positive isolate that produces L-glutaminase. L-glutaminase synthesis by bacteria was evaluated for its characteristics. Using an MTT test, the anticancer activity was evaluated. Results: exclusive bacterial isolates that used L-glutamine as their sole source of metabolic nitrogen exhibited favorable growth on MGA. PH 7.4 and a temperature of 37 0C were the ideal environmental and physiological conditions for developing positive bacterial isolates. From the soil samples taken from various soil conditions in Egypt, the morphological and biochemical analyses showed that Bacillus cereus 14579 was the main positive bacterial generating L-glutaminase isolate. At a pH of 7.4 and a temperature of 37 °C, the following activators—KCL, ZnSO4, FeSO4, K2HPO4, and MgSO4—provided the high-grade circumstances for characterizing L-glutaminase synthesis. Bacillus cereus-produced L-glutaminase has shown excellent bioavailability and effectiveness as an anticancer therapy. The yield [productivity] was 5.2 U/ml during the original manufacture from MGA, but it increased to 42.96 U/ ml by bacterial recombinant DNA manufacturing. The molecular mass of L-glutaminase was roughly 37 KDa. L-glutaminase was purified, yielding final enzyme recovery of 55 1.23%, total activity 12,990± 19.76 ( U), specific activity 384.66± 8.92( U/ mg of protein), and purification fold 2± 2.99. Furthermore, the L-glutaminase activity was raised by 19%, 23%, 15%, and 9%, respectively, by the enzymatic activators Mn2+, K+, Na+, and Fe3+. It demonstrated strong DPPH scavenging activity (IC50 = 61 μg/ mL) and anticancer activity( IC50 = 40.72, 9.7, 7.39, 20.61, 51.28, and 11.55 μg/ mL, respectively) against human liver (HepG-2), colon ( HCT-116), breast ( MCF-7), lung( A-549), lymphocytic( CCL-120), and cervical( Hela) cancer cell lines. A stronger affinity for its substrate was shown by the kinetic parameters of Km and Vmax, which were 13.2 10-5 M and 119.86 μmol/ ml/ min, respectively. Conclusion: Acute lymphocytic leukemia and breast cancer are examples of auxotrophic malignancies for which L-glutamine serves as the only metabolic source, and L-glutaminase generated by Bacillus cereus was an appropriate enzyme in the therapy of these diseases.

Background: RSV, or respiratory syncytial virus, is a deadly condition that is present all over the world today. The infection is initially contained in the lower respiratory tract without systemic transmission. The objective of the study: Bioinformatics was used in Egypt to create an mRNA vaccine against the Respiratory syncytial virus (RSV). Methodology: In the present screening experimental study, a lipid nanoparticles vaccine of mRNA of the surface fusion protein of Respiratory syncytial virus was manufactured. The present vaccine delivery system was lipid nanoparticles with a particle size of approximately 90 nanometres, manufactured by the hot micro-emulsion method. In stages 1 and 2 of clinical trials, the immunogenicity of the current mRNA RSV vaccine was evaluated. Results: The current vaccine demonstrated 81% immunogenicity in animal testing, but only 69% in stages 1 and 2 of clinical trials. Its side effects were manageable. The results persisted for a while. In the current trial, the vaccination proved effective as a preventative measure against RSV infection. The current vaccination lacked antibody-dependent enhancement, which causes non-protective antibodies to develop. These non-neutralizing antibodies exacerbate infection by activating cytokines and complement cascade through the formation of immune complexes or enhancement of the virus entry and replication in the host cells. On the other hand, the current RSV mRNA vaccine of the surface fusion protein consequent on the production of powerful neutralizing antibodies with prolonged immunity especially to infants and elderly candidates who received the optimal dosage regimen.

The PAX8/PPARγ rearrangement, producing the PAX8–PPARγ fusion protein (PPFP), is thought to play an essential role in the oncogenesis of thyroid follicular tumors. To identify PPFP-targeted drug candidates and establish an early standard of care for thyroid tumors, we performed ensemble docking-based compound screening. Specifically, we investigated which pocket structure should be adopted to search for a promising ligand compound for the PPFP; the position of the ligand binding pocket on the PPARγ side of the PPFP is common to that of PPARγ; however, the shape is slightly different between them due to environmental factors. We developed a method for selecting a PPFP structure with a relevant pocket and high prediction accuracy for ligand binding. This method was validated using PPARγ, whose structure and activity values are known for many compounds. Then, we performed docking calculations to PPFP for 97 drug or drug-like compounds with a thiazolidine backbone, which is one of the characteristics of ligands that bind well to PPARγ, registered in the DrugBank database. Furthermore, the binding affinities of promising ligand candidates were estimated more reliably using the molecular mechanics-Poisson–Boltzmann surface area method. Thus, we propose promising drug candidates for the PPFP with a thiazolidine backbone.

Multimedia resources, such as instructional videos, are currently enjoying a certain popularity in training programmes for medical and dental students. The major challenge is to create such resources that have quality content and are acceptable to students. We investigated the opinions of a sample of 551 students from 4 medical universities in Romania in order to identify the characteristics of the instructional videos that students prefer and we comparatively analysed these characteristics according to gender, age group, but also according to their general preferences for using Internet services. We used univariate (hypothesis testing) and multivariate (Two-Step Clustering) data analysis techniques and revealed three clusters of students, primarily determined by perceptions of the visual appearance of instructional videos. The structure of the clusters by gender and age group is relatively similar, but we recorded differences between them associated with students' expressed preferences for certain Internet services compared to others. Students who prefer instructional videos to contain images used only for aesthetic purposes, to fill in breaks, use Internet services mainly for communication, while students who prefer in videos the use of already drawn explanatory diagrams are slightly younger than the others and use Internet services mainly for information and communication.

Software engineering is a comprehensive process that requires developers and team members to collaborate across multiple tasks. In software testing, bug triaging is a tedious and time-consuming process. Assigning bugs to the appropriate developers can save time and maintain their motivation. However, without knowledge about a bug's class, triaging is difficult. Motivated by this challenge, this paper focuses on the problem of assigning the suitable developer to new bug by analyzing the history of developers’ profiles and analyzing history of bugs for all developers using machine learning-based recommender systems. Explainable AI (XAI) is AI that humans can understand. It contrasts with "black box" AI, which even its designers can't explain. By providing appropriate explanations for results, users can better comprehend the underlying insight behind the outcomes, boosting the recommender system's effectiveness, transparency, and confidence. In this paper, we propose two explainable models for recommendation. The first one is an explainable recommender model for personalized developers generated from bug history to know what the preferred type of bug is for each developer. The second model is an explainable recommender model based on bugs to generate the best developer for each bug from bug history.

This article is a continuity of prevouse two reserch in daylight harvastion control that were deigned using classical control apoproach and then fuzzy logic technique, In this article ANN controller is designed and its response is compared with the performance of the other two controllers. Detailed compression for the different error type is illustrated, however, the results show that the three controller operate with satisfactory accuracy.

1) Background- Coronary artery bypass grafting (CABG) is a common surgical intervention for patients with severe coronary artery disease. The Model for End-Stage Liver Disease (MELD) score has been widely used to predict mortality risk in patients with end-stage liver disease, but its utility in predicting postoperative outcomes in cardiac surgery patients is less well-established. 2) Methods-This retrospective study aims to investigate the association between preoperative MELD score and post-operative complications, length of hospital stay, and mortality in patients under-going coronary artery bypass grafting. This is a single-center, retrospective cohort study conducted at a tertiary care academic medical center. The study includes all adult patients who underwent elective coronary artery bypass grafting between January 2011 and December 2020. Preoperative MELD scores were calculated for each patient, and postoperative outcomes including major ad-verse cardiac events, length of hospital stay, and 30-day mortality was assessed. To ensure a homogeneous study cohort, we excluded patients who underwent emergent cardiac procedures or had incomplete data necessary for the calculation of MELD scores and assessment of postoperative outcomes. Data was extracted from the electronic medical records, including patient de-mographics, comorbidities, preoperative laboratory values, operative details, and postoperative outcomes. The study protocol was approved by the Institutional Review Board, and the require-ment for informed consent was waived due to the retrospective nature of the study.3) Results- This study reveals a statistical association between the MELD score calculated at admission and the length of hospital stay, duration in the ICU, patient age, and the duration of aortic clamping and extracorporeal circulation. Specifically, there is an exponential increase in the MELD score corre-lating with the rise in these factors, both collectively and individually, highlighting a significant relationship between the duration of extracorporeal circulation and aortic clamping time. 4) Conclusion-Patients with a high MELD score had an increased risk of postoperative complications and mortality compared to those with a low MELD score. Careful preoperative patient selection and optimization of the patient's clinical condition may improve outcomes in patients with advanced liver disease undergoing cardiac surgery.

(1) Background: The RDW-CV has predictive value in many pregnancy-related conditions. Re-search question: Can the RDW-CV be utilized predictively in pregnant patients with thrombo-philia? Aim of the study: To carry out a detailed analysis of the RDW-CV in pregnant patients with treated thrombophilia as compared with pregnant patients without thrombophilia who de-livered via cesarean section at term. (2) Methods: We studied 160 pregnant patients, including 80 pregnant patients with treated thrombophilia in the study group, and another 80 patients of a similar age and parity. The patients were referred to our hospital for delivery at term by means of a cesarean section between 1/10/2017 and 1/12/2021. Every patient received a sonogram during the first 1–2 days after the cesarean section, and their uterine evaluation was interpreted using the PUUS (Postpartum Uterine Ultrasonographic Scale). (3) Results: Our PUUS≥1 pregnant and postpartum patients with treated thrombophilia were the only group with an RDW-CV value over 14. No deep vein thrombosis was observed during hospitalization, showing that the antico-agulant treatment was necessary and effective. An RDW-CV of 14.5 was the highest value in the Rh-negative group of pregnant patients with treated thrombophilia. An RDW-CV of 14.48 was the highest level in the Rh-negative postpartum patients with treated thrombophilia. (4) Conclu-sion: An RDW-CV of ≥14 can predict uterine hematometra (PUUS≥1). The RDW-CV values were higher in Rh-negative patients.

Abstract: Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that encode the ATP-sensitive potassium channel (KATP). We present the correlation between genetic heterogeneity and the variable phenotype in patients with early-onset hyperinsulinemic hypoglycemia caused by ABCC8 gene mutations. In the first patients, which presented persistent severe hypoglycemia since the first day of life, molecular genetic testing revealed the presence of a homozygous mutation in the ABCC8 gene [deletion in the ABCC8 gene c.(2390+1_2391-1)_(3329+1_3330- 1)del] correlated with a diffuse form of hyperinsulinism (the parents being healthy heterozygous carriers). In the second patient, the onset was on the third day of life with severe hypoglycemia, and genetic testing identified a heterozygous mutation in the ABCC8 gene c.1792C>T (p.Arg598*) inherited on the paternal line, which led to the diagnosis of focal form of hyperinsulinism. To locate the focal lesions, (18)F-DOPA (3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine) PET/CT was recommended (an investigation that cannot be carried out in the country), but the parents refused to carry out the investigation abroad. In this case, early surgical treatment could have been curative. In addition, the second child also presented secondary adrenal insufficiency requiring replacement therapy. At the same time, she developed early recurrent seizures that required antiepileptic treatment. We emphasize the importance and of molecular genetic testing for diagnosis, management and genetic counseling in patients with HH.

Abstract Purpose of review: RNA therapeutics are a new and rapidly expanding class of drugs to prevent or treat a wide spectrum of diseases. We discuss the defining characteristics of the diverse family of molecules under the RNA therapeutics umbrella. Recent findings:RNA therapeutics are designed to regulate gene expression in a transient manner. For example, depending upon the strategy employed, RNA therapies offer the versatility to replace, supplement, correct, suppress, or eliminate the expression of a targeted gene. RNA therapies include antisense nucleotides, microRNAs and small interfering RNAs, RNA aptamers, and messenger RNAs. Further, we discuss the mechanism(s) by which different RNA therapies either reduce or increase the expression of their targets. Summary: We review the RNA therapeutics approved (and those in trials) to treat cardiovascular indications. RNA-based therapeutics are a new, rapidly growing class of drugs that will offer new alternatives for an increasing array of cardiovascular conditions.

This article introduces new method using ANN to control SVC in order to correct the source power factor of low voltage network. Two ANN approaches are investigated to design accurate and fast power factor correction (PFC) controller. First approach uses simple ANN (SANNA). Second approach uses cascaded ANN (CANNA). ANN regression, performance and the calculated error for both approaches are investigated to select between the two approaches. CANNA is selected as a better solution and it used to build the ANN PFFC controller using database, generated by MATLAB-Simulink, for standard three low voltage levels (240V, 220V and 110V). Nine test cases are carried out to validate the performance of proposed ANN PFC controller with a network has variable loads and low power factor (0.6 approximately). In order to extend the use of the controller to other voltage levels not included in the training process of the cascaded ANN, only the SVC is resized. Another nine cases are carried out with the same loads using the same ANN controller, as it is, to test its performance with the extended voltage level range (415V, 230V and 120V). The results show accurate and fast response in all test cases.

Abstract. This article proposes new fuzzy controller to regulation the voltage, damp the oscillations and limit the overshoot behavior in single-machine infinite-bus power system. Two different independent MISO fuzzy controllers are designed. First controller, is voltage stabilizer and it composes of two adaptive fuzzy modules and proportional gain AVR. The voltage stabilizer is designed to regulate the terminal voltage, damp the voltage oscillation and limit the voltage overshoot to the industrial maximum allowable limit. The input signals of this stabilizer is are taken from the terminal voltage and the imposed voltage disturbance that can be read from any smart relay. The fuzzy output is used as feedback signal to control the AVR in order to achieve stabilized voltage equal to the reference voltage. The second fuzzy controller is designed with two input signals; “mechanical angle” and its derivative, and one output which is used as feedback signal to adapt the damping torque in order to damp the mechanical oscillation fast and with maximum overshoot not exceeding 10%, and hence damp the power angle oscillation that is important in the PSS improvement. MATLAB-SIMULINK was used for modelling and the test cases simulation. The results show very good performance for the proposed fuzzy controllers.

This paper attempts to compare two different approaches to solve the problem of accident rates prediction based on human factors for industrial workers. One of the methods has already been done using Fuzzy c-Means Clustering and proved to be working with decent results. The second method which will be covered in this paper is using Artificial Neural Networks. The primary goal of this work is to insure that ANN will work efficiently in such prediction problem. The second goal is to reveal the fact that which one of the two selected methodologies is better at defining the estimation of accident rates among people who work in different industrial fields. The purpose has been achieved when the outcome of the ANN was obtained and compared accordingly with the output of the research previously carried out with Fuzzy c-means clustering method. Comparing the outcomes of these two different methods gave an immense insight on which features are more important than others when it comes to laborers properties with completely different background such as varying levels of health, knowledge, experience, training and physical properties. At the end of the research, it becomes clear that accident rates estimation for laborers with properly trained Artificial Neural Network gives better results when it is compared with Fuzzy c-Means Clustering method. Standard deviation method was used to calculate the validity of ANN technique. The result was compared with Fuzzy c-mean clustering technique. Impressive improvement of 8.8% in the accident rate prediction was achieved using Tailored-Made-ANN.

Global temperature rise due to hydrocarbon gases emission that are produced by generating the electrical power has a great attention by the researchers to reduce it till zero emission is successfully achieved. Sustainable energy source such as solar energy, wind, hydro-energy and sea wave energy are focal areas to replace the fossil fuel by clean energy. In this article, daylight is used to minimize the power consumption that required for indoor lighting using electric roller blind. Smart controller is designed to adjust the position of the roller blind stepper motor, and hence, adjust the roller blind opening, based on the preset light intensity, to achieve precise utilization of daylight inside the room. If the desired Lux is not achieved for any reason, the smart controller adjusts the LED circuit current to boost the light intensity to achieve precisely the desired Lux. Comprehensive test cases using MATLAB-Simulink is carried out to verify the performance of the proposed smart controller. Techno-economic analysis is introduced to evaluate the benefits of installing the controller. Summary and recommendation are given at the end.

This paper is an extension to previous work that introduced successful classical-control for indoor lighting system that simultaneously control LED system and roller curtain to achieve accurate light intensity for indoor lighting applications. In this paper, Multi Input Multi Output Fuzzy Logic Controller (MIMO FLC) is proposed to replace the classical-controller. Detailed method is provided to illustrate the steps to design the required MIMO FLC that has two fuzzy input, two fuzzy output and forty-five fuzzy rules with mamdani fuzzy engine. The proposed MIMO FLC is simulated in Matlab using Simulink tools. The results are illustrated, analyzed and compared with the classical-control. The response showed very close performance to the classical-controller. The maximum average error and the maximum error with respect to “Desired Lux” inside the room is -6% and -10% respectively.

This review provides an understanding of the teaching and practising of forensic accounting across the globe. It includes a review of published forensic accounting studies that conclude that forensic accounting is of benefit to both students and professionals. Despite this, there are areas of concern; namely, the insufficiency of an appropriate structure of regulation and a lack of control over the academic qualifications to enter the profession. This review of both the teaching and practising of forensic accounting provides an overview of the vital issues and concerns that must be understood in order to advance the essential application of forensic accounting. It is expected that this review will influence future policy that will advance business and limit episodes of fraud. The amount of published literature on the subject of forensic accounting is widespread and diverse. However, there is a lack of comprehensive understanding regarding the strengths and weaknesses of forensic accounting; this review will address this and provide policymakers with a thorough explanation of the subject.

We study L_2-approximation problems in the weighted Hilbert spaces in the worst case setting. Three interesting weighted Hilbert spaces appear in this paper, whose weights are equipped with two positive parameters $\ga_j$ and $\az_j$ for $j=1,\,2,\dots,\,d$. We consider the worst case error of algorithms that use finitely many arbitrary continuous linear functionals. We discuss the exponential convergence-(t,s)-weak tractability (EC-(t,s)-WT) of these L_2-approximation problems under the absolute or normalized error criterion. In particular, we obtain the sufficient and necessary conditions for EC-(1,1)-WT and EC-(t,1)-WT with t

This study explores the complexities involved in the extraction and purification of catechins, prominent bioactive compounds found in plant extracts and tea. It addresses challenges arising from the intricate molecular structure of catechins and their inherent variability across botanical sources. Despite these obstacles, catechins present significant potential, particularly in healthcare. Their potent antioxidant properties have been extensively investigated and associated with numerous health benefits, positioning them as promising therapeutic agents for combating chronic diseases. Furthermore, catechins have diverse applications across various industries, including food and beverage, cosmetics, agriculture, and materials science. This abstract emphasizes the importance of continued research and innovation in catechin extraction and utilization, which hold promise for advancing human health and technological progress across multiple domains.

This article is about a framework for determining the degree of realism of any given 1 passenger ride motion discomfort measurement formula. After providing some context and reviewing 2 evidence of deficiency in currently popular ride motion discomfort measurement formulas, the article 3 outlines the research program that needs to be carried out in order to establish such a framework. 4 The research begins with gathering recordings of uncomfortable ride motion episodes encountered in 5 a chosen type of passenger transport service. It then has test subjects compare the episodes via a ride 6 motion simulator and adjust their amplitudes pair wise until they cause equal discomfort. It explains 7 how to take the pair wise amplitude adjustments and determine amplitude adjustments that bring all 8 of the motion episode recordings to a common level of discomfort so that they form a normalized set. 9 Then, the lower the scatter of the scores assigned by any given discomfort measurement formula to 10 the members of that set, the more realistic that formula will be for the chosen service.

The positional cloning of single nucleotide polymorphisms (SNPs) of the neutrophil cytosolic factor 1 (Ncf1) gene, advocating that a low oxidative burst drives autoimmune disease, demands an understanding of the underlying molecular causes. A cellular target could be T cells, which have been shown to be regulated by reactive oxygen species (ROS). However, the pathways by which ROS mediate T cell signaling remain unclear. The adaptor molecule linker for activation of T cells (LAT) is essential for coupling T cell receptor-mediated antigen recognition to downstream responses, and it contains several cysteine residues that have previously been suggested to be involved in redox regulation. To address the possibility that ROS regulate T cell-dependent inflammation through LAT, we established a mouse strain with cysteine-to-serine mutations at positions 120 and 172 (LATSS). We found that redox regulation of LAT through C120 and C172 mediate its localization and phosphorylation. LATSS mice had reduced numbers of double-positive thymocytes and naïve peripheral T cells. Importantly, redox insensitivity of LAT enhanced T cell-dependent autoimmune inflammation in collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA). This effect was reversed on an NCF1-mutated (NCF1m1j), ROS-deficient, background. Overall, our data shows that LAT is redox-regulated, acts to repress T cell activation, and is targeted by ROS induced by NCF1 in antigen-presenting cells (APCs).

A comprehensive kinetic model of the Fischer-Tropsch synthesis (FTS) is developed in a fixed bed reactor under operating conditions (temperature, 230–235°C, pressure, 20–25 bar, gas hourly space velocity, 4000–5000 cm³(STP)/h/g_catalyst ,H₂/CO feed molar ratio, 2.1) over a Co based catalyst. Reaction rate equations based on Eley-Rideal (ER) type model for initiation step and Langmuir-Hinshelwood-Hougen-Watson (LHHW) type model for propagation and termination steps of the FTS reactions have been considered and the readsorption of olefins were taken into account. The model that was reported in the literature was modified in order to explain many significant deviations from the ASF distribution. Optimum parameters have been obtained by Genetic Algorithms (GA). The calculated activation energies to produce n-paraffins and 1-olefins were in the range of 82.24 to 90.68 kJ/mol and 100.66 to 105.24 kJ/mol, respectively. The hydrocarbon distribution in FTS reactions was satisfactorily predicted particularly for paraffins.

(1) Background: Thrombophilia is a tendency towards hypercoagulability, and it is increased by pregnancy, peaking around delivery. Research question: does thrombophilia stimulate the in-flammatory state of the patient, already suppressed by pregnancy? (2) Methods: Eighty thrombo-philia patients admitted for delivery between 1/10/2017 and 1/12/2021 were prospectively stud-ied, together with eighty age- and para-matched control patients. Patients were admitted for de-livery at term by means of cesarean section. The inflammation indexes from the complete blood count values analysis during both the 24 hours before and after labor—extracted from the hospi-tal’s medical records—were calculated and then correlated with uterine involution. (3) Results: Except for the PLR, most of the numerous inflammation indexes studied were not significantly different in treated thrombophilia patients, before and after delivery, compared to non-thrombophilia patients. Only when we split the patients, based on the uterine haematometra in the first 24-48 hours postpartum, we found out that the few treated thrombophilia patients with haematometra (14 with haematometra out of 79 with treated thrombophilia) had elevated SII and AISI antepartum. In pregnant patients treated for thrombophilia, MLR is higher in pa-tients without the Rh factor than in those with the Rh factor. In non-thrombophilia patients, MCVL and NLPR increased with age and before labor, while SII and AISI increased with age postpartum. (4) Conclusions: Thrombophilia did not stimulate the inflammatory state of the pa-tient, already suppressed by pregnancy.

Dirofilariosis is an infectious disease caused by species of the Dirofilaria genus. It is manifested by the appearance of a subcutaneous swelling, especially in the eye region. We present the case of a 29-year-old patient that accused facial asymmetry in the right genian region. Following clinical and paraclinical evaluations, the diagnosis of parasitic cyst was established in the context of dirofilariosis with Dirofilaria repens (D. repens). Treatment consisted of surgical excision of the formation associated with prophylactic antibiotic medication. Macroscopic analysis of the excision piece revealed a structure that contains a cystic cavity and a filamentous form with a length of approximately 10 mM and a diameter of 1 mM. This is the first case of dirofilariosis located in the genian region reported in Romania. The overview of this pathology is important to raise awareness among physicians about its presence and its clinical variations.

The topical therapy with rifampicin (RF)-based formulations is beneficial to treat infections and to healing the wounds. Despite recent research highlighting the antibiotic's significant an-ti-inflammatory properties, limited topical wound healing products are currently available. Present study aimed to prove that the newly synthesized nanoparticles based on grafted alginate and poly(N-vinylcaprolactam (pNVCL) and poly-lactic-co-glycolic acid (PLGA) contributes to the healing process of a wound. The methods used were at first the synthesis of the copolymer of al-ginate and pNVCL via grafting from technique and radical polymerization followed by wa-ter-in-oil-in water (W/O/W) emulsification by using as oil phase PLGA dissolved in dichloromethane (DCM). The formed nanoparticles were than characterized. The loaded RF was determined to be 160 µg/mL for a 20 mg formulation and within a four-hour time frame approximately 10% of the total loaded amount was released. The inhibitory concentrations (IC50) were 192 µg/mL for the nanoparticle, 208 µg/mL for pure rifampicin, and 718 µg/mL for the rifampicin-loaded nanopar-ticles. Considering the double role Rifampicin was used for, the result was considered satisfactory in the way that these formulations could be used more with the wound irrigation post-surgery to avoid infections and to contribute to the healing.

Background and Aims: Sustained virologic response (SVR) lead to the decrease of portal hypertension, the regression of fibrosis, the improvement of the hepatic synthesis of procoagulant and anticoagulant factors. We aimed to assess the influence of SVR on coagulation parameters in HCV cirrhotic patients treated with DAAs. Methods: We performed a prospective study in the Institute of Gastroenterology and Hepatology Iasi, Romania, between January 2022 and February 2024. We included patients diagnosed with compensated and decompensated HCV-related liver cirrhosis, treated with direct antivirals (PrOD ± RBV or SOF/LED ± RBV) for 12/24 weeks. Blood samples for biochemical, immunological and coagulation tests were collected at baseline, EOT and SVR12/24. Results: We analyzed a group of 52 patients with HCV-related liver cirrhosis, predominantly female (68.0%), the degree of severity of cirrhosis placed the patients mainly in Child-Pugh classes B (40%) and C (36%). All patients achieved SVR. The MELD score decrease at EOT (13.48 ± 4.273; p =0.001), and SVR (9.88 ± 2.774; p = 0.000), compared to baseline (14.92 ± 4.707). Fibroscan values decreased at SVR (17.596 ± 3.7276; p = 0.000) compared to baseline (26.068 ± 7.0954). For all common coagulation parameters (platelets, INR, PT, fibrinogen, aPTT) there was a trend towards improvement during treatment, changes that were statistically significant for the majority of patients. Factor II low at baseline (75.40 ± 7.506), increases at EOT (87.40 ± 9.587), and later at SVR (99.12 ± 11.695; p = 0.000). FVIII values increased at baseline (175.52 ± 16.414) decrease at EOT (151.48 ± 13.703) and SVR (143.40 ± 13.937). FvW values decreased during treatment (146.84 ± 9.428 – baseline, 141.32 ± 9.690; p =0.000 – EOT, 126.68 ± 17.960 – SVR). In regards to the anticoagulant factors (PC, PS, ATIII), a significant improvement was brought on by SVR. Advanced stages of liver disease showed the most diminished FII activity, while at baseline and in Child-Pugh C patients we recorded the highest values of FVIII and FvW. Conclusions: Our study proved that the “reset” of the coagulopathy might be due to the improving of the liver function due to viral eradication secondary to AAD therapy.

This paper discusses domestic problem of waiting hot water for the shower use till it reaches satisfactory temperature, which result a lot of wastage in fresh water. The outcome from research survey shows that there is no satisfactory solution till now as all solutions were either expensive or with no effective results. Local small inline electric heater equipped with fuzzy logic controller is proposed in this paper to be installed just before the showerhead to measure the water temperature and flow before the showerhead, as control input-variables, and decide the operating voltage of the heater, as control output-variable (MISO). MATLAB Simulink is used to model the proposed system. Different test cases are simulated to prove the performance and the safe operation of the system. Techno-economic study is carried out to determine the “Direct Benefits” and “Indirect Benefits” that can be achieved if such system is implemented in wide range. Azerbaijan data is taken as an example to calculate the economic benefits. The results show important benefits not only for economy but also for climate and the reduction of CO₂ gas emission. Different economic indices are provided to be an easy reference for decision makers and project managers.

Background and Objectives: Metastases are the most common tumors of the spine. As an important increase in the annual incidence of spinal metastases (SM) has been observed in the last decade, the aim of this study was to describe the epidemiology and histopathological types of SM surgically treated in the neurosurgery clinics of a regional hospital in North-Eastern Romania over a period of 5 years, in order to define a certain tumor profile that would benefit from an early screening. Materials and Methods: We retrospectively evaluated 115 adult patients, searching for demographic data (gender and age of the patients), primary tumor characteristics (location and histological type), topography and histopathological type of the spinal metastasis, and the time interval between the diagnosis of the primary tumor and the surgery for the spinal metastasis. Results: The patients were elderly (average age = 58.96 years), with a male predominance (67.82%). Main location of SM was in thoracic region (44.34%), with multiple vertebral metastases in 30.43% patients. Only 33.04% of the patients had a known cancer at the time of admission. Primary tumor was located mainly in lung (47.82%), gastrointestinal tract (15.65%), breast (11.30%), prostate (10.43%) and kidney (9.56%). SM from lung cancer mostly expressed squamous cell carcinoma (19.13%), and those from the digestive system mostly exhibited a moderately/poor colorectal adenocarcinoma (8.69%). Conclusions: Our data suggest the need for close surveillance of patients diagnosed with lung cancer and colorectal cancer because these malignancies most frequently develop spinal metastases. Smoking prevention actions and screening programs for the detection and removal of precancerous colorectal lesions must be developed and expanded.

Identifying influential actors within social networks is pivotal for optimizing information flow and mitigating the spread of both rumors and diseases. Several methods have emerged to pinpoint these influential entities in networks that are represented as graphs. In these graphs, nodes corre-spond to individuals and edges indicate their connections. This study focuses on centrality measures, prized for their straightforwardness and effectiveness. We categorize structural central-ity into two: local, considering a node's immediate vicinity, and global, accounting for overarching path structures. Some techniques blend both centralities to highlight nodes influential at both mi-cro and macro levels. Our paper presents a novel centrality measure, accentuating node degree and incorporating the network's broader features, especially paths of different lengths. Through Spearman and Pearson's correlations tested on seven standard datasets, our method proves its merit against traditional centrality measures. Additionally, we employ the SIR model, portraying disease spread, to further validate our approach. The ultimate influential node is gauged by its capacity to infect the most nodes during the SIR model's progression. Our results indicate a nota-ble correlative efficacy across various real-world networks relative to other centrality metrics.

Deep sky observation is a fascinating activity, but it requires favourable conditions in order to be fully appreciated. Complex equipment, light pollution around urban areas, lack of contextual information often prevents newcomers from making the most of their observations, restricting the field to a niche expert audience. In this paper, we show how combining the usage of smart telescopes with eXplainable Artificial Intelligence makes the practice of astronomy even more accessible and educative, and how it has been applied during outreach sessions In Luxembourg Greater Region.

In recent years, the implementation of artificial intelligence (AI) in accounting has grown in many domains, including auditing. AI permits auditors to evaluate large data sets and rapidly identify discrepancies and sequences in audit. This means auditors can review all of a client's transactions via a low time and effort. This entails auditing firms investing heavily in technological infrastructure as well as training their human resources to use cutting-edge AI technologies. Thus, this research sought to investigate the impact of the use of AI techniques by Jordanian external auditors in fraud risk assessment, the moderating effect of auditor size. The descriptive analytical method was used by distributing 280 questionnaires electronically to auditors employed in auditing firms operating in Jordan, The result reveals that AI techniques are extremely beneficial in fraud risk assessment at all levels, and the relationship between the use of AI techniques and the assessment of fraud risk has improved as auditor size has increased.

This article aims to analyze the relationship between non-obstructive coronary artery disease (NOCAD) and atrial fibrillation (AF), exploring the underlying pathophysiological mechanisms and implications for clinical management. NOCAD and AF are prevalent cardiovascular conditions that often coexist, yet their interrelation is not well understood. NOCAD, characterized by the presence of atherosclerotic plaques without significant luminal stenosis, can lead to ischemic necrosis of cardiomyocytes and their replacement with fibrous tissue, in this way sustaining the focal ectopic activity in atrial myocardium. Atrial fibrillation, on the other hand, is the most common sustained cardiac arrhythmia, associated with an increased risk of stroke and heart failure, which may accelerate atherosclerosis and may increase oxygen consumption in the myocardium, creating a mismatch between supply and demand, thus promoting the development or worsening of coronary ischemia. Therefore, NOCAD and AF seems to be a complex Interplay with one begets another.

This research addresses a gap in the literature by conducting a comprehensive analysis of patients’ level of satisfaction with dental care. Methods: By combining quantitative and qualitative survey methods with the PSQ questionnaire this study aims to augment ongoing initiatives to enhance dental patients’ experiences by painting a more comprehensive depiction of patients' level of satisfaction; Results: When asked about their overall level of satisfaction 77,1% of the patients said they received excellent services from the office personnel and 72,2% said they trust their doctors; Conclusions: Assessing patient satisfaction in the realm of dental services quality is crucial for enhancing service quality and accuracy, benefiting both patients and dentists, and ultimately improving public health.

The concept of this prototype is to create a cold air film layer, in indoor side of the window. The function of this extra cold air layer is to increase the amount of window resistance and decrease its U-Value. It provide air film layer by using the same concept of desert cooler or wind catcher. They both bring the hot air from outside then let it go throw straw miost with cold water. After hot air move through straw, it would become cold, thus increase the window resistance and decrease the haet gian, therefore, decrease the cooling load. So, this window model works by heating the air in air room by sun radiation, then after a while, air pressure will rise and its volume will increase then it will impulse to wet hay, and become cold. Then there is fins to guide air flow to its correct direction, thus inner side of window will become cold, not like other type of window which when temperature rise, the inner side of window become hot. So, this window prevents heat transition and creare regenereted trubouland air flim in the inner side of the window. Using calculation to find air film characteristics and WINDOW7.7 software to calculate heat gain through window, shows that it is expected from this prototype to reduce heat gain by 6.85 % for double glazed clear window.

Keywords: Knowledge; Attitudes; Practices; Salt intake.

Background: Virtual Reality (VR) is an emerging tool in the management of anxiety, one of the most disturbing symptoms of Alcohol Use Disorder (AUD), which often leads to relapse. Still, patients with Alcohol Use Disorder frequently have a history of Acute Symptomatic Seizures, and they are subsequently excluded from studies using VR because of the hypothesized fear of inducing photosensitive seizures. The first part of this narrative review explores the pathophysiological mechanisms of seizures associated with AUD, specifically acute symptomatic seizures. In contrast, the second part explores virtual reality’s safe use in seizure-prone individuals, highlighting that the current state-of-the-art is based on a biased per-ception and old epidemiological data from studies conducted on photosensitive seizures in the late 90s. VR exposure has yet to be reported as triggering seizures within known pharmacovigilance databases. Significance: The implications weigh heavily on VR research currently associated with this significant adverse event. Further studies are necessary to address the risk of seizures triggered by VR in patients predisposed to developing seizures, like alcohol use disorder patients with a history of acute symptomatic seizures. Such research is essential to ensure that the potential benefits of Virtual Reality as a tool for managing anxiety in individuals with alcohol use disorder and acute symptomatic seizures are not unduly restricted. Furthermore, AUD can also serve as an intervention model feasible to de-bias attitudes toward the current lack of evidence base concerning the significant adverse events of VR-induced seizures, therefore facilitating the clinical implementation of this unharnessed digital treatment interface.

This article discuss the estimation of electrical stresses input that is required to determine lifetime degradation of the HV cables installed within overhead transmission lines (OHTL’s). Abort from lightning effects, these electrical stresses are mainly generated due to repetitive switching operation of the transmission line that produces transient overvoltage (TOV) stress and high frequency stress. The transient overvoltage (TOV) due to switching-off the transmission line at the interface points between the cable and OHTL is estimated using artificial neural network (ANN). PSCAD software is used to build the transmission line model for 749 different case in order to build the required database for ANN training. Two different algorithm input to train ANN with one hidden layer and one output layer using different number of nodes are modeled in MATLAB. The results performance is continuously compared and evaluated till acceptable Regression is achieved to insure the error is less than +/-1.5%. The high frequency due to switching-on the transmission line is also recorded and analyzed. The results show that this new method is efficient, accurate and useful as there is no cable monitoring system is available for each HV cable installed within the transmission line.

This paper proposes a novel deterministic methodology for estimating the optimal sampling frequency (SF) of water quality monitoring systems. The proposed methodology is based on employing two-dimensional contaminant transport simulation models to determine the minimum SF considering all the potential changes in the boundary conditions of a water body. A two-dimensional contaminant transport simulation model (RMA4) was implemented to estimate the distribution patterns of the total dissolved solids (TDS) within the Al-Hammar Marsh in the southern part of Iraq for 30 cases of potential boundary conditions. Using geographical information system (GIS) tools, a spatiotemporal analysis approach was applied to the results of the RMA4 model to determine the minimum SF of the monitoring stations with an accuracy level of detectable change in TDS concentration (ALC) of 5%, 10% and 15%. The proposed methodology specified a minimum and maximum SF for each monitoring station (MS) that ranged between 12 and 33 times per year, respectively. Additionally, increasing the ALC to 10% and 15% increase the minimum SF for some MSs by approximately 18% and 21%, respectively. However, the proposed methodology includes all the potential values and cases of boundary conditions, which increases the certainty of monitoring the system and the efficiency of the SF schedule. Moreover, the proposed methodology can be effectively applied to all types of surface water resources.

Landiolol is an ultra-short-acting, selective ß1- adrenergic receptor blocker that was originally approved by Japan for the treatment of intraoperative tachyarrhythmias. It has gained attention for its use in the management of tachyarrhythmias and perioperative tachycardia, especially atrial fibrillation for both cardiac and non-cardiac surgeries. It can be the ideal agent for heart rate control due to its high β1‐selectivity, the potent negative chronotropic effect, a limited negative inotropic potential, and an ultrashort elimination half‐life (around 4 min); moreover, it may have a potential therapeutic effect for sepsis and pediatric patients. Landiolol seems to be superior to other short‐acting and selective beta‐blockers such as esmolol. This review aims to provide a comprehensive overview of landiolol, a new ultra-short-acting ß1 selective antagonist, including its pharmacology, clinical applications, efficacy, safety profile, and future directions in research and clinical data.

Despite being under development for decades, RNA therapeutics have only recently emerged as viable platform technologies. The COVID-19 mRNA vaccines have demonstrated the promise and power of the platform technology. In response, novel RNA drugs are entering clinical trials at an accelerating rate. As the skin is the largest and most accessible organ, it has always been a preferred target for drug discovery. This holds true for RNA therapies as well, and multiple candidate RNA-based drugs are currently in development for an array of skin conditions. In this mini review, we catalog the RNA therapies currently in clinical trials for different dermatological diseases. We summarize the main types of RNA-related drugs and use examples of drugs currently in development to illustrate their key mechanism of action.

Global rapidly evolving events, e.g., COVID-19, are usually followed by countermeasures and policies. As a reaction, the public tends to express their emotions on social media platforms. Therefore, predicting emotional responses to events is critical to put a plan to avoid risky behaviors. This paper proposes a machine learning-based framework to detect public emotions based on social media posts in response to specific events. It presents a precise measurement of population-level emotions which can aid governance in monitoring public response and guide it to put in place strategies such as targeted monitoring of mental health, to react to a rise in negative emotions in response to lockdowns, or information campaigns, for instance in response to elevated rates of fear in response to vaccination programs. We evaluate our framework by extracting 15,455 tweets. We annotate and categorize the emotions into 11 categories based on Plutchik’s study of emotion and extract the features using a combination of Bag of Words and Term Frequency-Inverse Document Frequency. We filter 813 COVID-19 vaccine-related tweets and use them to demonstrate our framework’s effectiveness. Numerical evaluation of emotions prediction using Random Forest and Logistic Regression shows that our framework predicts emotions with an accuracy up to 95%.

As new vaccines reduce P. falciparum (Pf) cases, clinicians can focus on rescuing more children with cerebral malaria (CM). Adjunctive “therapeutically-rational exchange transfusion” (T-REX) refers to using special “Pf-resistant” donor red blood cells (RBCs) that secrete nano-sized RBC extracellular vesicles (EVs). Can some RBC EVs rapidly dislodge Pf-infected RBCs (iRBCs) sequestered in blood vessels and reduce inflammation? Does post-exchange “rebound parasitemia” reflect sequestration-reversal? We reviewed case-reports, EV and liposome studies, expert perspectives, and time-sequence data. In the AQUAMAT study, median coma-recovery time was 20 hours for artesunate. In contrast, a CM patient treated with type-O T-REX quickly began speaking (during the procedure). For other rapid-recovery CM patients, donor RBC variables had not been specified. Despite rapid Pf-killing, drugs need 20 hours to substantially reduce iRBC cytoadhesion while EVs can selectively bind distant inflamed tissues within 15 minutes. RBCs stressed by blood-bank storage and Pf infection secrete EVs. Post-exchange “rebound parasitemia” can occur within 60 minutes and may reflect release of sequestered iRBCs. Sequestration-reversal can be assessed by monitoring Pf parasitemia and total Pf biomass. New data suggest clinicians, working with transfusion- and laboratory-medicine physicians, can, and should, assess T-REX options and publish their findings to help clarify how RBC EVs may serve as therapeutic “decoy ligands.”

Cancer ranks second among the causes of mortality worldwide,following cardiovascular diseases.Brain cancer, in particular, has lowest survival rate of any kind of cancer. Brain tumours vary in their morphology, texture, and location, which determine their classification. Accurate diagnosis of the tumour category enables physicians to select optimal treatment strategies and potentially prolong patients’ lives. Researchers who also implemented deep learning models for diagnosing diseases in recent years largely focused on deep neural network optimization to enhance neural network performance. This implicates implementing models with the best performance and incorporating various network architectures by configuring their hyperparameters. This paper presents a novel hybrid approach method for improved brain tumour classification by combining CNN and EfficientNetV2B3 as feature extraction, followed by (KNN) for classification. To evaluate the recommended method’s efficacy, two widely known benchmark MRI datasets were utilized in the experiments. The initial dataset consisted of 3064 MRI images depicting meningiomas,pituitary,and gliomas tumours.Images from two classes of normal brain and brain tumour were included in the second dataset, which was obtained from Kaggle.In order to enhance performance even more, the study concatenates the CNN and EfficientNetV2B3 flattened outputs before feeding them into the KNN classifier. The proposed framework run on two different dataset and demonstrates outstanding performance with an accuracy of 99.51% and 99.8% on each dataset.

This paper aims to provide an adaptation of the TL-moments method to censored data. The present study concentrates on Type-I censored data. The idea of using TL-moments with censored data may seem conflicting. But our perspective in that, we may use data censored from one side and trimmed from the other side. This study is applied to estimate the two unknown parameters of the Weibull distribution. The suggested point is compared with Direct L-moments and ML methods. A Monte Carlo simulation study is carried out to compare these method in terms of estimate average, root of mean square error (RMSE) and relative absolute biases (RAB).

The research aims to discover the natural occurrence of patulin (PAT) in selected citrus fruits from the central cities of Punjab and Pakistan's Northern cities. Total 2970 samples of twelve citrus fruits; kinnow, orange, grapefruits, bitter orange, mausami, red blood, pineapple, sweet orange, rough lime, sweet lime, kagzi lime and lemon were examined using liquid chromatography fitted with UV detector. The limit of detection (LOD) and quantification limit was 0.04 and 0.12 µg/kg, respectively. The results have shown that 56% of samples of citrus fruits from Punjab's central cities, Pakistan, were discovered to be infected from PAT. The elevated amounts of PAT ranging from 0.04 to 1150 µg/kg were found in citrus fruit samples from Multan cities. Furthermore, 31.7% of samples of citrus fruits from Northern cities of Pakistan were discovered to be infected with PAT, and the elevated amounts were found ranging from 0.04-320 µg/kg from Swat city. About 22.1% of samples of citrus fruits have levels of PAT greater than the suggested limits established by the European Union (EU). PAT's dietary intake levels ranged from 0.10-1.11 µg/kg bw/day from the central cities of Punjab, Pakistan, and 0.13-1.93 µg/kg bw/day were documented from Northern cities of Pakistan.

Background. Respiratory distress syndrome (RDS) is the primary cause of respiratory failure in preterm infants, but it also affects 5-7% of term infants. Dysfunctions in pulmonary surfactant metabolism, resulting from mutations of the lung surfactant genes, are rare diseases, ranging from fatal neonatal RDS to interstitial lung disease, associated with increased morbidity and mortality. This study aims to clarify the clinical significance of ABCA3 variants found in a specific family case, as existing data in the literature is inconsistent. Material and methods: A family case report was conducted; targeted panel genetic testing identified a variant of the SFTPB gene and two variants of ABCA3 genes. Comprehensive research involving a systematic review of PubMed, Google Scholar databases, and genome browsers was used to clarify the pathogenicity of the two ABCA3 variants found in the index patient. Advanced prediction tools were employed to assess the pathogenicity of the two ABCA3 variants, ensuring the validity and reliability of our findings. Results: The index case exhibited fatal neonatal RDS. Genetic testing revealed the presence of the SFTPB p.Val267Ile variant, not previously reported, a benign variant based on family genetic testing and history. Additionally, two ABCA3 gene variants were identified: c.697C>T, not yet reported, and c.838C>T. These variants were found to affect ABCA3 protein function and were likely associated with neonatal RDS. Prediction tools and data from nine other cases in the literature supported this conclusion. Conclusions: Based on in silico predictors, analysis of the presented family, and cases described in the literature, it is reasonable to consider reclassifying the two ABCA3 variants identified in the index case as pathogenic/pathogenic. Reclassification will improve genetic counseling accuracy and facilitate correct diagnosis.

A milk drink flavored with dates syrup produced at a lab scale level was evaluated. The production process of date syrup involves a sequence of essential unit operations, commencing with the extraction, filtration, and concentration processes from two cultivars: Sukkary and Khlass. Date syrup was then mixed with cow’s and camel’s milk at four percentages to form a nutritious, natural, sweet, and energy milk drink. Sensory, physical, and chemical characteristics of the milk drinks flavored with date syrup were examined. The objective of this work was to measure physiochemical properties of dates fruits and milk drinks flavored with dates syrup, then to evaluate the physical properties of milk drinks utilizing a non-destructive NIR spectra. The study assessed the characteristics of the milk drink enhanced with date syrup by employing near-infrared spectra (NIR) spectra and analyzed utilizing partial least-square regression (PLSR) and artificial neural network (ANN) analysis. The NIR spectrum proved to be highly effective in estimating the physiochemical attributes of the flavored milk drink. The ANN model outperformed the PLSR model in this context. RMSECV is considered a more reliable indicator of a model's future predictive performance compared to RMSEC, R2 ranged between 0.946 and 0.989. Consequently, non-destructive NIR technology demonstrates significant promise for accurately predicting and contributing to the entire production process of the product's properties examined.

Full depth precast deck panel (FDDP) is one element of the prefabricated bridge element and systems (PBES) that allows for quick un-shored assembly of the bridge deck on-site as part of the accelerated bridge construction (ABC) technology. This paper investigates the structural response of full-depth precast deck panels (FDDPs) constructed with new construction materials and connection details. FDDP is cast with normal strength concrete (NSC) and reinforced with high modulus (HM) glass fiber reinforced polymer (GFRP) ribbed bars. The panel-to-girder V-shape connections use the shear pockets to accommodate the clustering of the shear connectors. A novel transverse connection between panels has been developed, featuring three distinct female-to-female joint configurations, each with 175-mm projected GFRP bars extending from the FDDP into the closure strip, complemented by a female vertical shear key and filled with cementitious materials. The ultra-high performance fiber reinforced concrete (UHPFRC) was selectively used to joint-fill the 200-mm transverse joint between adjacent precast panels and the shear pockets connecting the panels to the supporting girders to ensure full shear interaction. Two actual-size FDDP specimens for each type of the three developed joints were erected to perform fatigue tests under the footprint of the Canadian Highway Bridge Design Code (CHBDC) truck wheel loading. The FDDP had a 200-mm thickness, 2500-mm width, and 2400-mm length in traffic direction; the rest was over braced steel twin girders. Two types of fatigue tests were performed; incremental variable amplitude fatigue (VAF) loading and constant amplitude fatigue (CAF) loading, followed by monotonically loading the slab ultimate-to-collapse. It was observed that fatigue test results showed that the ultimate capacity of the slab under VAF loading or after 4 million cycles of CAF exceeds the factored design wheel load specified into the CHBDC. Also, punching shear failure mode was dominant in all the tested FDDP specimens.

Precise monitoring of individual crop growth and health status is crucial for precision agriculture practices. However, traditional manual inspection methods are time-consuming, labor-intensive, and often lack the spatial resolution required for detailed analysis. This research addresses the need for efficient and high-resolution crop monitoring by leveraging Unmanned Aerial Vehicle (UAV) imagery and advanced computational techniques. The primary objective was to develop a methodology for precise identification, extraction, and monitoring of individual corn crops throughout their growth cycle. This was achieved by integrating UAV-derived data with image processing, computational geometry, and machine learning techniques. UAV imagery was ac-quired bi-weekly at altitudes of 40m and 70m, capturing the entire growth cycle of a corn crop from planting to harvest. A time-series Canopy Height Model (CHM) was generated by analyzing the differences between the Digital Terrain Model (DTM) and the Digital Surface Model (DSM) derived from the UAV data. Local spatial analysis and image processing techniques were em-ployed to determine the local maximum height of each crop. Subsequently, a Voronoi data model was developed to delineate individual crop canopies, successfully identifying 13,000 out of 13,050 corn crops in the study area. For enhanced accuracy in canopy size delineation, vegetation indices were incorporated into the Voronoi model segmentation, refining the initial canopy area esti-mates by eliminating interference from soil and shadows. The proposed methodology enables precise estimation and monitoring of crop canopy size, height, biomass reduction, lodging, and stunted growth over time, providing valuable insights for precision agriculture practices. This work contributes to the scientific community by demonstrating the potential of integrating UAV technology, computational geometry, and machine learning for accurate and efficient crop mon-itoring at the individual plant level.

There is a need to develop enriched milk drinks with healthy and natural additives. A consumer test was conducted to compare milk (cow and camel) flavored with date syrup (Khlass and Sukkary varieties) at different percentage. The objective of the present work was to study consumers liking patterns for flavored milk drinks from dates syrup (from Khlass and Sukkary dates), at different percentages, added to milk (cow and camel) utilizing preference mapping analysis. A total of sixteen trained panelists took part in the test. The obtained data were used to develop an internal preference map for these samples. Principal component analysis (PCA) and Agglomerative hierarchical clustering (AHC) algorithms were used to construct the preference map. The first component signifies overall acceptance of taste and color, while the second focuses on texture and flavor. Consumers were grouped into five clusters based on preferences. Cluster two favored both components positively, while cluster four leaned negatively on both. A factorial ANOVA was performed and the results showed a significant effect of the main factors as well as the interactions. Panelists preferred cow's milk over Camel’s milk in all aspects. For taste, cow’s milk with 20% Khlass syrup or 10% Sukkary syrup was favored, while in flavor, it was cow’s milk with 5% Khlass syrup and Camel’s milk with 10% Sukkary syrup. Texture-wise, Camel’s milk with 5% Khlass syrup and 15% Sukkary syrup, along with cow’s milk with 10% Khlass syrup, received top marks. In color evaluation, cow’s milk with 15% Sukkary syrup was the preferred choice. Finally, for overall color score, cow’s milk with 10% Sukkary syrup led, followed by cow’s milk with 5% Sukkary syrup. This research suggests that dairy companies may have more impact if they use date syrup as a natural and healthy flavor. The preference map includes two main dimensions; the first represents overall acceptance, taste, and color while the second is related to flavor and texture attributes. The preference map can be used in product optimization and development.

The purpose of this paper is to explore the impact on corporate social responsibility when Jordanian banks disclose risks. The main objective of the study is to investigate the relationship between risk disclosure and corporate social responsibility in the banking sector in Jordan. To achieve this goal, data was collected from 23 Jordanian banks listed on the Amman Stock Exchange (ASE) over a period of 10 years, from 2010 to 2019. The data was analyzed using a regression model with four independent variables that represent the risk disclosure; corporate social responsibility was used as the dependent variable. The study also built in controls for the age of each bank, its size, leverage, and ROE, to ensure that the results were not affected by these factors. The results of the study show that all independent variables are positively correlated with corporate social responsibility. This suggests that disclosing risks is an effective way to improve corporate social responsibility in the banking industry. The findings of this study have important practical implications for bank managers, future researchers, and policymakers. The study also highlights the importance of future research in this field in order to understand the relationship between risk disclosure and corporate social responsibility in other countries and within other sectors of industry.

The primary objective of this study is to determine the existence of a significant correlation between inflammation levels, as measured by inflammatory markers IL-6, IL-1β, and TNF-α, and the severity of depressive symptoms assessed using HAM-D assessment scale. This could provide additional evidence supporting the hypothesis that inflammation plays a notable role in the pathogenesis of depression. The data analysis supports the hypothesis that the biological mechanisms of inflammation contributes to the clinical manifestations of depression. Elevated levels of inflammatory markers, especially interleukins (IL6, IL1β), tumor necrosis factor-alpha (TNFα), and C-reactive protein (CRP) have been identified in patients with major depressive disorder compared to the findings in healthy controls. Materials and Methods: Inflammatory markers (IL-6, IL-1β, and TNF-α) were measured in a sample of 31 patients hospitalized at the Socola Institute of Psychiatry in Iasi, Romania, and compared to a control group with no psychiatric or inflammatory conditions. One of the main objectives is to determine if there is a significant correlation between inflammation levels, measured by inflammatory markers (IL-6, IL-1β, and TNF-α), and the severity of depressive symptoms assessed using HAM-D scores. Conclusions: The study results suggest a significant correlation between inflammation levels measured by inflammatory markers IL-1β and IL-6 and the severity of depressive symptoms evaluated by HAM-D scores in the study group. These findings support the hypothesis that inflammation may play an important role in the development or exacerbation of depressive symptoms. The relationship between inflammation and depression is also influenced by risk and protective factors that require further research.

The study focused on investigating the natural incidence of deoxynivalenol (DON) in corn and products from corn producing districts of Punjab, Pakistan. The analysis was carried out using HPLC with UV detector and immunoaffinity cleanup columns. The detection limit (LOD) and limit of quantification were 25 and 50 µg/kg, respectively. Total 1220 samples of corn and products were analyzed to detect the DON, and 539 (44.2%) samples were observed to be contaminated with DON (n ≥ LOD). Furthermore, 92 (7.5%) samples of corn & products have DON levels, elevated than the proposed limits of the EU. The data is significantly different from a normal distribution for DON in corn and products samples and from different locations (p < 0.05) for Shapiro-Wilk and Kolmogorov-Smirnov values. However, a significant difference in DON levels was found between corn and corn derived-products types (p ≤ 0.05). The lowest and highest exposure & hazard quotient (HQ) of 0.92 and 9.68 µg/kg bw/d were documented in cornflour samples.

Hyaluronic acid, in the form of a gel or viscoelastic colloidal solution, is currently used for viscosupplementation of joints affected by osteoarthritis, but its effectiveness is under debate in relation to newer alternatives. Based on meta-analytical arguments, the present article reinforces the opinion that there are still no decisive arguments for its complete replacement, but for its use adapted to the peculiarities of the disease manifestation and of the patients. A “broad” comparison is first made with almost all alternatives studied in the last decade, and then a meta-regression study is performed to compare and predict the effect size induced by viscosupplementation and platelet-rich plasma therapies. If they are computerized, the developed models can represent tools for clinicians in determining the appropriateness of the option or not for viscosupplementation, in a manner adapted to the pain felt by the patients, to their age, or to other clinical circumstances. The models were generated using the latest algorithms for meta-analysis and meta-regression implemented in the R language and assembled in different R packages. All primary data and necessary R scripts are provided in accordance with the philosophy of reproducible research. Finally, HA-based products, currently under circumspection, are still clinically useful.

This study investigates the comparative performance of autoencoders and traditional machine learning (ML) algorithms in predicting tumor dynamics following Gamma Knife radiosurgery (GKRS) for brain metastases (BMs). The research retrospectively analyzed clinical data from 77 patients (median age: 64 years; 45 males, 32 females) treated at the “Prof. Dr. NicolaeOblu” Emergency Clinic Hospital-Iasi. The dataset comprised 12 variables, including socio-demographic, clinical, treatment, and radiosurgery-related factors. The primary outcome was tumor progression or regression within three months post-GKRS, with 71 cases of regression and 6 cases of progression observed. Traditional ML models—Logistic Regression, Support Vector Machine (SVM), K-Nearest Neighbors (KNN), Extra Trees, Random Forest, and XGBoost—were evaluated, achieving accuracy rates ranging from 0.91 (KNN) to 1.00 (Extra Trees). When incorporating features extracted by autoencoders, the performance of these models generally improved, especially with compression in the bottleneck layer. For instance, Logistic Regression's accuracy increased from 0.91 to 0.94, while SVM's accuracy improved significantly from 0.85 to 0.96. XGBoost consistently performed well across both traditional and hybrid setups, maintaining an accuracy of 0.94 with an AUC of 0.98. The findings suggest that hybrid approaches combining deep learning with traditional ML techniques can significantly enhance predictive accuracy and robustness, particularly in the context of GKRS for BMs. This improved performance has potential implications for more informed clinical decision-making in personalized medicine.

Hand gesture recognition has many valuable applications in engineering and health care. This study proposes a novel model which can accurately distinguish hand gestures using forearm muscles' surface electromyogram (sEMG) signals. A deep learning algorithm with hyper parameters impacting the final model’s accuracy and a convolutional neural network (CNN) were employed in the recognition stage. The number of convolutional layers, kernels per layer, and neurons in the dense layer were selected for optimization, while the remaining parameters, such as the learning rate, batch size, and number of epochs, were chosen based on trial and error and prior knowledge. The optimal values for the selected hyperparameters were obtained using a genetic algorithm to achieve maximum recognition accuracy. The UC2018 Dual-Myo database was used for training and testing the model based on EMG signals characterizing the activity of eight different hand gestures. The final structure of the model consisted of two convolutional layers with 131 and 28 kernels, a dense layer with 111 neurons, and a softmax layer with eight neurons. Upon optimizing the hyperparameters using the genetic algorithm, the accuracy of the proposed model increased from 91.86% to 96.4% at best and 95.3% on average in real-time applications and 99.6% in an offline mode. Future work is warranted towards improving the architecture and the computational cost.

Background: By 2025, road traffic injuries are projected to rank third in the global burden of disease, posing a significant challenge that affects health, social well-being, and economic aspects. According to data from the Romanian Police National Statistics Center, there has been an average of 342 traffic accidents per year involving pediatric patients over the past 10 years. Materials and Methods: A retrospective research study was conducted, encompassing 358 cases of road traffic accidents identified for the study. Data collection was conducted at "St. Mary’s" Emergency Hospital for Children in Iasi, Romania, from January 2015 to December 2022. To facilitate statistical analyses, participants were categorized into three specific age groups, correlating between the anatomical region affected and different types of accidents was examined, and the classification of injury types was determined based on the characteristics of the harm inflicted. Results: An oscillating trend is observed from 2015 to 2020, with its lowest value recorded in 2017 at around 6.8% and its peak in 2019 at 20.1%. Notably, post-pandemic (Covid-19), the cases underwent a substantial decline of approximately 50%. At least 78.7% of those who did not undergo orthopedic reduction required surgery, whereas among those who underwent orthopedic reduction, only 23.4% needed surgery. Regarding the frequency of complications 7,9% of the total cases experienced complications. Conclusion: The increased frequency of pediatric traffic accidents is attributed to the extensive services provided by "St. Mary’s" Emergency Hospital for Children, Iasi, to a significant number of patients from both rural and urban areas across the seven counties of the Moldova, Romania.

(1) Background: The prediction of cervical lesions evolution is a challenge for clinicians. The prospective study aimed to determine and compare the predictive accuracy of cytology, HPV genotyping, and p16/Ki67 dual staining alone or in combination with personal risk factors for the prediction of progression, regression or persistence of cervical lesions in human papillomavirus (HPV)-infected patients; (2) Methods: This prospective study included HPV-positive patients with or without cervical lesions that underwent follow-up. Descriptive statistics and sensitivity analysis for individual or combined index tests were used for data analysis; (3) Results: The highest predictive performance for the progression of cervical lesions was achieved by a model that comprised a Pap smear suggestive of high-grade squamous intraepithelial lesion (HSIL), the presence of 16/18 HPV strains, a positive p16/Ki67 dual staining result along with the presence of at least 3 clinical risk factors, which had a sensitivity (Se) of 74.42%, a specificity of 97.92%, an area under the receiver operating curve (AUC) of 0.961, and an accuracy of 90.65%. The prediction of cervical lesions regression or persistence was modest; (4) Conclusions: Multiple testing or new biomarkers should be used to improve HPV-positive patient surveillance, especially for cervical lesion regression or persistence prediction.

In the present study, fish were exposed to sub-lethal doses of CuONPs (68.92 ± 3.49 nm) (10, 20, and 50 mg/L) for a long exposure period (25 days). Compared to the control group (0.0 mg/L CuONPs), a significant dose-dependent elevation in blood urea and creatinine values, serum alanine transaminase, aspartate transaminase, and alkaline phosphatase enzyme activities were evident in CuONPs-exposed groups (P &lt; 0.05). Fish exposure to 50 mg/L CuONPs significantly upregulated the transcription of pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta, interleukin 12, and interleukin 8), heat shock protein 70, apoptosis-related gene (caspase 3), and oxidative stress-related (superoxide dismutase, catalase, and glutathione peroxidase) genes in liver and gills of the exposed fish in comparison with those in the control group (P &lt; 0.05). Moreover, varying histopathological injuries were noticed in the hepatopancreatic tissues, posterior kidneys, and gills of fish groups correlated to the examined exposure dose of CuONPs. In summary, our results provide new insights and helpful information for better understanding the mechanisms of CuONPs toxicity in Nile tilapia at hematological, molecular levels, and tissue levels.

Histone deacetylase inhibitors (HDACis) are being recognized as a potentially effective treatment approach for peripheral T-cell lymphoma (PTCL), which is a diverse group of aggressive lymphomas with a bleak prognosis. Recent evidence has shown that HDACi are effective in treating PTCL, especially in cases where the disease has relapsed or is resistant to other treatments, and there are few available options. Several clinical trials have demonstrated that HDACi, such as romidepsin and belinostat, can elicit long-lasting positive outcomes in individuals with PTCL, either when used alone or in conjunction with conventional chemotherapy. They exert their anti-tumor actions by regulating gene expression through inhibiting histone deacetylases, which results in the halting of cell division, programmed cell death, and the transformation of cancerous T-cell, as indicated by gene expression profile studies. Importantly, besides clinical trials, real-world evidence indicated that the utilization of HDACi presents a significant and beneficial treatment choice for PTCL. However, although HDACi showed potential effectiveness, they couldn’t cure most patients. Therefore, new combination with conventional drugs as well as new targeted agents are under investigation.

COVID-19, the infectious disease caused by SARS-CoV-2, has spread on a pandemic scale. The virus infection can evolve asymptomatically or generate severe symptoms, influenced by the presence of comorbidities. Lymphopenia in patients affected with COVID-19 according to the severity of symptoms is frequent. However, the profile of CD4+ and CD8+ T-cells regarding cytotoxicity and antiviral factor expression has not yet been completely elucidated in acute SARS-CoV-2 infections. The purpose of this study is to evaluate the phenotypic and functional profile of T-lymphocytes in patients with moderate and severe/critical COVID-19. During this pandemic period, we analyzed a cohort of 62 confirmed patients with SARS-CoV-2 (22 moderate cases and 40 severe/critical cases). Albeit lymphopenia, we observed an increase in the expression of CD28, co-stimulator molecule, and activation markers (CD38 and HLA-DR) in T-lymphocytes as well as an increase in the frequency of CD4+ T-cells, CD8+ T-cells, and NK cells that express the immunological checkpoint protein, PD-1, in patients with severe/critical condition compared to healthy controls. Regarding the cytotoxic profile of peripheral blood mononuclear cells, an increase in the response of CD4+ T-cells already at baseline level was observed, scarcely changed upon PMA and Ionomycin stimulation. Meanwhile, CD8+ T-lymphocytes decreased cytotoxic response, evidencing a profile of exhaustion in patients with severe COVID-19. As observed in the t-SNE technique CD4+ T-cytotoxic and CD8+ T with low granzyme production evidencing their dysfunctionality in severe/critical conditions. In addition, purified CD8+ T-lymphocytes from patients with severe COVID-19 showed an increased constitutive expression of differentially expressed genes associated with the caspase pathway, inflammasome, and antiviral factors, and curiously, reduced expression of TNF-α. The cytotoxic profile, by CD4+ T-cells, may compensate for the dysfunction/exhaustion of TCD8+ in acute SARS-CoV-2 infection. These findings may provide an understanding of the interplay of cytotoxicity between CD4+ T-cells and CD8+ T-cells in the severity of acute COVID-19 infection.

A set of polymer composite bolted T-joints with novel configuration consisting of internal skeleton and external skin was fabricated using a prepreg-RTM co-curing molding process. Experiments were conducted to study their mechanical properties under bending load. A finite element model with a polymer resin area between the skin and skeleton was established and verified by the experimental results. Then, the damage propagation process and failure mechanism of the joint and the influence of three factors related to the layer characteristics of the skin and skeleton were investigated by the validated models. The results show that the bending stiffness and the yield limit load of the novel composite T-joint are 0.81 times and 1.65 times that of the 2A12 aluminum T-joint respectively, while at only 55.4% of its weight. The damage of the joint initiates within the resin area and leads to a degradation of the joint bending performances. The preferred stacking sequence of the skeleton is [0/+45/90/-45]ns when primarily subjected to bending loads. The decrease in bending performances is within 5% with the inclining angle of the skeleton less than 12 degrees. The more layers of 90° in the skin, the better bending performances of the joints, while the more layer of 0°, the poorer bending performances.

The present paper presents findings from the follow-up of 185 of these nurses who had been involved in the front-line care of COVID-19 patients in urban centres in Northern England, during and after the “second wave” of COVID patients in November, 2020. Measures of adjustment, stress (including PTSD), and Maslowian self-actualization were added to earlier measures of personality, adjustment, work-life stress, and career intention. Cluster analysis identified three types in the 2020-2023 cohort: I ‘Actualizing Professionals’; (N=62); II ‘Strong Professionals’ (N=56); III ‘Highly Stressed Nurses’ (N=45). These latter very stressed nurses included all nurses (N=16) identified as having PTSD symptoms.

Background: The purpuse was to investigate the influence induced by magnesium chloride (MgCl2) and zinc gluconate (ZnG) supplementation on liver and kidney injuries experimentally-induced with acetaminophen (AAPh) and potentiated by ciprofloxacin addition in rats. Material and methods: The experiment was performed on 5 animals groups: group 1 – control, treated for 6 weeks with normal saline, 1mL/kg; group 2 – AAPh, treated for 6 weeks with AAPh, 100 mg/ kg/day; group 3 – AAPh+C, treated AAPh 100 mg/kg/ day for 6 weeks and ciprofloxacin, 50mg /kg/day, only in the last 14 days of the experiment; group 4 – AAPh+C+Mg, with the same treatment as group 3, but, and in the last 14 days, MgCl2 10 mg/ kg/day was added; group 5 – AAPh+C+Zn, with the same treatment as group 3, but, and in the last 14 days, zinc gluconate (ZnG),10 mg/kg/day was added. All administrations were performed by oral gavage. At the end of the experiment, the animals were sacrificed and blood samples were collected for biochemistry examinations. Results: Treatment with AAPh for 6 weeks determined an alteration of the liver function (increases in alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase and, and gamma-glutamyl transferase) and of renal function (increases in serum urea and creatinine) (P < 0.001 group 2 vs. group 1 for all mentioned parameters). Also, the antioxidant defense capacity was impaired in group 2 vs. group 1 (superoxide dismutase and glutathione peroxidase activity decreased in group 2 vs. group 1, 0.001 < P < 0.01, respectively 0.01 < P < 0.05). The addition of ciprofloxacin, 50 mg/kg/day during the last 14 days resulted in further increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea and creatinine (0.01 < P < 0.05, group 3 vs. group 2). MgCl2 provided a slight protection against liver enzymes increase and a more pronounced protection against the increase in serum urea and creatinine (0.001 < P < 0.01 group 4 vs. group 3). MgCl2 provided a slight protection against the decrease in superoxide dismutase (0.01 < P < 0.05 group 4 vs. group 3), but not against decrease of glutathione peroxidase. The improvement of mentioned parameters could also be seen in case of ZnG, to a higher extent especially in the case of alanine aminotransferase and lactic dehydrogenase (0.01 < P < 0.05 group 5 vs. group 4). Conclusions: This study represents a furthermore proof for beneficial effect of magnesium and zinc salts against toxicity induced by different agents, including antibacterials added to the analgesic and antipyretic acetaminophen; the protection is proven on the liver and kidney’s function; the antioxidant profile improvement has a key role, especially in case of zinc gluconate.

This initial report of a longitudinal study of 192 English hospital nurses has measured Nursing Values (the 6Cs of nursing); Personality, Self-Esteem and Depression; Burnout Potential; Work-Life Balance Stress; ‘Hardy Personality’; and Intention to Leave Nursing. Correlational, component and cluster analysis identifies four groups: “The Soldiers” (N = 79) , with medium scores on most measures, who bravely ‘soldier on’ in their nursing roles, in the face of numerous financial cuts to the National Health Service, and worsening nurse-patient ratios; “Cheerful Professionals” (N = 54), coping successfully with nursing roles, and a variety of challenges, in upwardly mobile careers; “High Achievers” (N = 39), senior nurses with strong profiles of a ‘hardy personality’, and commitment to fundamental nursing values; “Highly Stressed, Potential Leavers” (N = 20), with indicators of significant psychological distress, and difficulty in coping with nursing role challenges. We propose a model of co-counselling and social support for this distressed group, by nurses who are coping more successfully with multiple challenges. We discuss the role of nurse educators in fostering nursing values, and developing and supporting ‘hardy personality’ and emotional resilience in recruits to nursing. This study is framed within the disciplinary approach of Critical Realism, which identifies the value basis for research and dialogue in developing strategies for social change.

In this work, we study the existence of strange star in the background of f(T,T) gravity in the Einstein spacetime geometry, where T is the torsion tensor and T is the trace of the energy-momentum tensor. The equations of motion are derived for anisotropic pressure within the spherically symmetric strange star. We explore the physical features like energy conditions, mass-radius relations, modified TOV equations, principal of causality, adiabatic index, redshift and stability analysis of our model. These features are realistic and appealing to further investigation of properties of compact objects in f(T,T) gravity as well as their observational signatures.

Adjunctive treatment of periodontitis lacks solutions allowing enough time for wound healing in the periodontal pockets by avoiding a fast re-colonization. Such a solution might be an antibiotic containing formulation with a controlled release over weeks. Here, a recently described minocycline containing approach is qualified for further clinical development by focusing on proof-of-concept, systemic burden, resistance development and degradation studies. Animal studies were done in two different (mouse-chamber, rat Porphyromonas gingivalis challenging) models, including effects on inflammation markers, bone loss and bone structure. Also, serum concentrations of minocycline after local application were determined by HPLC-MS/MS. The resistance status of bacterial clinical isolates against minocycline was investigated and the degradation of the formulation was characterized by laser scanning- and scanning electron microscopy. Animal studies clearly demonstrated the applicability of the new formulation in the investigated models. Inflammation markers decreased dosage dependent and reduced bone loss compared to non-treated group was observed. Thereby, the systemic burden of the antibiotic was neglectable. Minocycline is still effective against oral pathogens; resistance development was not seen. The biodegradable thread was first swollen and subsequently degraded over weeks. The results support the continued clinical development of this new formulation. A phase I clinical trial is planned to further evaluate its safety and efficacy.

Electrolyte disturbances are common in patients with traumatic brain injury (TBI), particularly affecting sodium, potassium, chloride and calcium levels. This study aims to provide insights into these disturbances within the first 24 hours post-injury. We conducted a cross-sectional analysis of 50 TBI patients, excluding those with conditions affecting electrolyte balance. Electrolyte levels were measured, and correlations with demographic data, trauma mechanisms, imaging findings, and Glasgow Coma Scale (GCS) scores were analyzed. Results indicated that chloride levels inversely correlated with GCS scores (ρ = -0.515; p = 0.002), suggesting that elevated chloride may indicate severe neurological impairment. Potassium levels were significantly associated with subdural hematoma (p = 0.032) and subarachnoid hemorrhage (p = 0.043), highlighting their potential as markers for severe brain injuries. No significant associations were found between sodium or calcium levels and the studied variables. These findings underscore the importance of early monitoring of chloride and potassium levels in TBI patients to improve management and outcomes. Future research should focus on larger, multi-center studies to validate these findings and develop comprehensive guidelines for managing electrolyte imbalances in TBI patients.

In this paper, we report a comprehensive and consistent annotation of the locus encoding the horse T cell receptor b-chain (TRB), as inferred from the most recent genome assembly. The horse TRB locus spans approximately 1 Mb, making it the largest locus among the mammalian species stud-ied to date, with a significantly higher number of genes related to extensive duplicative events. In the region, 136 TRBV, belonging to 29 subgroups, 2 TRBD, 13 TRBJ and 2 TRBC genes, were iden-tified. The general genomic organization resembles that of other mammals, with a V-cluster of 135 TRBV genes, located upstream of two in-tandem aligned TRBD-J-C clusters, and an inverted TRBV gene at the 3’ end of the last TRBC gene. However, the horse b-chain repertoire would be affected by a high number of non-functional TRBV genes. Thus, we queried a transcriptomic da-taset derived from splenic tissue of a healthy adult horse, using each TRBJ gene as a probe to ana-lyse clonotypes encompassing the V(D)J junction. This analysis provided insights into the usage of the TRBV, TRBD and TRBJ genes and the variability of the juxtaposition region. Our results clearly demonstrated that the horse β-chain constitutes a complex level of variability broadly like that described in other mammalian species.

Follicular helper CD4+ T cells (TFH) are a major cellular pool for the maintenance of HIV reservoir. Therefore, the delineation of the follicular (F)/germinal center (GC) immune landscape will significantly advance our understanding of HIV pathogenesis. We have applied multiplex confocal imaging, in combination with relevant computational tools, to investigate, F/GC in situ immune dynamics in viremic (vir-HIV), antiretroviral treated (cART HIV) People Living With HIV (PLWH) and compare them to reactive, non-infected controls. Lymph nodes (LNs) from viremic and cART PLWH could be further grouped based on their TFH cell densities in high-TFH and low-TFH subgroups. These subgroups were also characterized by different in situ distribution of PD1hi TFH cells. The significantly accumulated follicular, compared to extrafollicular, FOXP3hi CD4+ T cells found in the low-TFH cART-HIV group were characterized by a less scattered in situ distribution and strongly correlated with the cell density of CD8+ T cells in this group. An inverse correlation between plasma viral load and LN GrzBhiCD8+ T and CD16hiCD15lo cells was found. Our data reveal the complex GC immune landscaping in HIV infection and suggest that follicular FOXP3hi CD4+ T cells could be negative regulators of TFH cell prevalence in cART-HIV.

Background: Existing human cell immortalization methods made the cells obtain oncogenesis phenotype and/or caused the cells gain and/or lose chromosomes. Immortalized normal human T cells lines provide critical in vitro models for basic research and therapeutic products development.Methods: We utilized a CRISPR/Cas9 system to replace a single copy of the exon 2 of the cell cycle inhibitor gene CDKN2A (encoding p16 and p14 proteins) with a single copy of human telomerase reverse transcriptase (hTERT) to immortalize human primary CD8⁺ T cells (hCD8⁺T-TERT). By using Cas9 protein and low donor DNA copies/cell, we successfully immortalized hCD8⁺T cells with a single copy of hTERT transgene, which also avoided uncontrolled insertion of Cas9 gene and guide RNA vector.Results: Human primary CD8+ cells were immortalized and expanded more than 2.6 × 10⁷ times. Characterization of the cells revealed that the immortalized CD8⁺ T-TERT cells retained most of the cell surface markers and normal karyotype. The CD8⁺ T-TERT cells also retained the dependence of IL-2 and CD3/CD28 activator for survival and expansion.Conclusion: we established a stable immortalized CD8⁺ T cell line that had a phenotype consistent with T cells and will be a useful research model.

The enhancement of early diagnosis of lung cancer is mandatory to improve prognosis. We observed the increase cancer stem cells (CSC) and circulating tumor cells (CTC) in blood of mice on d3 after Lewis lung carcinoma (LLC) cell implantation before disease symptom. Besides we have developed an approach to reprogramming immune cells by inhibiting the MAPK/ERK pathway through MEKi and the PD-1/PD-L1 immune checkpoint signaling pathway. We hypothesized that reprogramming of spleen CD8+ T-cells could also create a population of immune cells with high antitumor activity. We reprogrammed CD8+ T-cells derived from the spleen of C57BL/6 mice (rsCD8+T-cells). The rsCD8+T-cells were able to migrate to lung and were more resistant after the exhaustion in vitro in comparison with naïve sCD8+T-cells. In the orthotopic LLC model, the rsCD8+T-cells therapy increased the amount of proliferating CD8+ and CD4+ T-cells in blood and lung from mice. The amount of CSC decreased in the blood and lung of mice treated with rsCD8+ T-cells. A morphological study revealed a decrease in the number of metastases in lung tissue. The antitumor effects of rsCD8+T-cells are based on the activation of the host immune response by increasing the populations of CD8+ and CD4+ T-cells and apoptosis of CSCs.

We investigate and discuss in detail the structure of the restricted singular value decomposition for a tensor triplet under t-product (T-RSVD). The algorithm is provided with a numerical example illustrating the main result. For applications, we consider color image watermarking processing with T-RSVD.

In spite of prevalence gaps in several micronutrients supporting immune function, significance of their deficits/supplementation for efficacy of vaccines is underinvestigated. Thus, influence of supplementation combining vitamins C and D, zinc, selenium and manganese, and N-acetyl-cysteine on mouse IgG responses and underlying mechanisms to seasonal quadrivalent influenza vaccine (QIV) was investigated. QIV was given in two doses (28 days apart). The supplementation starting 5 days before the first injection increased the total serum IgG titre, through stimulation of germinal centre (GC) reaction in secondary lymphoid organs (SLOs), as indicated by increase in the frequency of GC B cells and follicular CD4+ T helper (Th) cells, and IL-21-producing Th cells. Additionally, the supplementation “optimized” IgG response following the second QIV injection by supporting more favorable (in respect to virus clearance) IgG2a response through favoring Th1 differentiation as indicating by Th1 (INF-γ) /Th2 (IL-4) signature cytokine level ratio upon QIV restimulation in SLO cell cultures. This most likely reflected partly their antioxidant action (as indicated by redox status analyses) on Th cell differentiation. Thus, the study forms solid base for further research aimed at repurposing use this safe and inexpensive micronutrient combination as an adjuvant for virus influenza vaccine.

Immune cells such as T cells and macrophages express α7 nicotinic acetylcholine receptors (α7 nAChRs), which contribute to the regulation of immune and inflammatory responses. Earlier findings suggest α7 nAChR activation promotes the development of regulatory T cells (Tregs) in mice. Using human CD4+ T cells, we investigated the mRNA expression of the α7 subunit and the human-specific dupα7 nAChR subunit, which functions as a dominant-negative regulator of ion channel function, under resting conditions and T cell receptor (TCR)-activation. We then explored the effects of the selective α7 nAChR agonist GTS-21 on proliferation of TCR-activated T cells and Treg development. Varied levels of mRNA for both the α7 and dupα7 nAChR subunits were detected in resting human CD+ T cells. mRNA expression of the α7 nAChR subunit was profoundly suppressed on days 4 and 7 of TCR-activation as compared to day 1, whereas mRNA expression of the dupα7 nAChR subunit remained nearly constant. GTS-21 did not alter CD4+ T cell proliferation but significantly promoted Treg development. These results suggest the potential ex vivo utility of GTS-21 for preparing Tregs for adoptive immunotherapy, even with high expression of the dupα7 subunit.

Uterine leiomyosarcoma (LMS) is a rare and aggressive form of uterine cancer, with a poor prognosis and high number of uterine cancer-related deaths. Chimeric Antigen Receptor (CAR) T-cell therapy is an immunotherapy approach to antigen specific of cancer cell, thereby enhancing the immune system's ability to target and destroy cancer cells. This study aims to investigate the potential of targeting differentially expressed genes (DEGs) as a novel therapeutic strategy using CAR T-cell technology in LMS. Genome datasets were obtained from NCBI-GEO database, Of the five datasets, genes that experienced significant overexpression in at least three datasets were categorized as DEGs, and DEGs were evaluated for protein localization, Gene Ontology, bioactivity, interaction, and overexpression. The results identified 25 DEGs, with ten of them expressed on the plasma membrane; four of them—HMMR, KIF20A, PRC1, and ZWINT—were part of the main protein network derived from the 25 DEGs. The dominant bioactivity of these PMGs involves influencing the cell cycle, particularly processes related to chromosome segregation. In conclusion, HMMR, KIF20A, PRC1, and ZWINT are high-potential DEGs as candidates for tumor-associated antigen CAR T-cell therapy. Further research, both in vitro and in vivo, is needed to enhance the validity of these findings.

Using multi-color flow cytometry analysis, we studied the immunophenotypical differences between leukemic blasts/LSCs from patients with AML/MDS and hematopoietic stem and progenitor cells (HSPCs) from patients in complete remission (CR) following their successful treatment. The panel of markers included CD34, CD38, CD45RA, CD123 as representatives for a hierarchical hematopoietic stem and progenitor cell (HSPC) classification as well as programmed death ligand 1 (PD-L1). Rather than restricting the evaluation on a 2- or 3-dimensional analysis, we applied a t-distributed stochastic neighbor embedding (t-SNE) approach to get a deeper insight and segregation between leukemic and normal HPSCs. For that purpose, we created a t-SNE map, which resulted in the visualization of 27 cell clusters based on their similarity concerning the composition and intensity of antigen expression. Two of these clusters were “leukemia-related” containing a great proportion of CD34⁺/CD38^- hematopoietic stem cells (HSCs) or CD34⁺ cells with a strong coexpression of CD45RA/CD123, respectively. CD34⁺ cells within the latter cluster were also highly positive for PD-L1 reflecting their immunosuppressive capacity. Beyond this proof of principle study, the inclusion of additional markers will be helpful to refine the differentiation between normal HSPCs and leukemic cells, particularly in the context of minimal disease detection and antigen-targeted therapeutic interventions. Furthermore, we suggest a protocol for the assignment of new cell ensembles in quantitative terms, via a numerical value, the Pearson coefficient, based on a similarity comparison of the t-SNE pattern with a reference.

The rock joint fissure slope in cold regions is prone to deformation and failure problems such as relaxation, tension and collapse under freeze-thaw (F-T) cycles. Based on the ideology of clean production and promoting the structural integrity of geotechnical projects in cold areas, this study designed and prepared aeolian-sand (AS) to replace part of river sand as a filling mortar material by taking advantage of the low cost and easy availability of AS. Investigations were carried out to determine the impact of varying proportions of AS in mortar on the microstructure and shear properties of the mortar-rock interface under F-T cycles. Therefore, F-T cycle testing, nuclear magnetic resonance (NMR) testing and shear testing were carried out on grout with different proportions of AS. The results show that the right proportion of AS replacement could enhance the shear deformation resistance and F-T resistance of the mortar-rock interface, and 30% proportion is the optimal proportion. By increasing of F-T cycles, the three types of specimens showed different degrees of particle spalling, shedding and cracking. The slurry-rock interface layer in the A (0%) group exhibited the most severe F-T deterioration, while the B (15%) group showed a lesser degree, and the C (30%) group performed the best. T2 spectrum curve and total spectrum area change law from the microscopic point of view to verify the 30% AS proportion mortar-rock interface F-T resistance is the strongest, followed by 15% AS proportion mortar, the weakest is ordinary mortar. The degradation of the mortar-rock bond is primarily due to the conversion of solid to liquid phases and the movement of internal water caused by fluctuating temperatures. The extent of F-T deterioration in the slurry-rock interface layer is greatly affected by the varying proportions of AS. The shear strength and shear stiffness of specific proportion of AS decreased with the increase of F-T cycles. For same F-T cycles, the shear strength and shear stiffness of group C (30%) were the highest, followed by group B (15%) and group A (0%). The grout material not only reinforces the F-T joint fissure slope, but also reduces the cost of grout reinforcement and promotes the clean production of geotechnical structures.

Fire hazards present a multifaceted global challenge that endangers human lives and environmental safety. Despite advancements in fire risk management technologies and methods, fires continue to be a prime concern for human security. The Arabian Gulf region, influenced by its climatic and environmental conditions, is especially susceptible to these threats. The Emirate of Sharjah, part of the United Arab Emirates, has made significant progress in reinforcing fire safety measures within residential structures, achieving a decrease in the number of fire-related accidents compared to neighboring Emirates. However, the incidence rate remains relatively high. This study undertook a thorough review and assessment of the existing Fire Management System (FMS) for Sharjah's residential sector, leading to the recommendation of a more robust framework. Through a series of literature reviews, interviews with stakeholders, and surveys, using analytical techniques such as the Delphi method and Failure Mode Effect and Criticality Analysis, vital factors that influence the FMS's effectiveness were pinpointed. The study exposed that the current FMS was largely reactive. In response, a proactive framework incorporating nine essential components was designed to strengthen the Sharjah FMS. These components span across various domains such as fire assurance, assessment of fire risks, management of accidents, evaluation of performance, training programs, research and development initiatives, digital services, monitoring of regulatory compliance, firefighting strategies, automated responses to fires, recovery processes, as well as the use of resilient materials and architectural design considerations. Furthermore, the research introduced two specific fire indexes, the HRBFI and the EFRI. Anchored in the principles of Systems Thinking and Industry 4.0, this proposed framework is aimed at streamlining Sharjah's approach to fire management in dwellings, with the objective of diminishing the frequency of fire incidents yearly. The ultimate aspiration of this framework is to enhance the Emirate's standing in terms of safety and to guarantee a living environment that is safeguarded against the risk of fires..

The Dubai Digital Government launched its recent guidelines, which call for artificial intelligence systems to be subject to legal accountability. This study discusses the extent to which autonomous robots can be granted legal personality in UAE law and the consistency of this approach with the provisions of Islamic jurisprudence. This research paper answered two main questions: First, the extent to which these guidelines are considered the beginning of work on granting legal personality to AI systems in the UAE. Second, what form of legal personality can be given to autonomous robots in UAE law to be consistent with the provisions of Islamic jurisprudence as a primary source of legislation in the country? The research concluded the impossibility of considering autonomous robots as a "thing" and classifying them within the concept of "persons." It also concluded that it is possible to give them legal personality according to two legislative solutions: granting them partial or incomplete performance eligibility like minors.

Electronic text stylometry is a collection of forensics methods that analyze the writing styles of input electronic texts in order to extract information about authors of the input electronic texts. Such extracted information could be the identity of the authors, or aspects of the authors, such as their gender, age group, ethnicity, etc. This survey paper presents the following contributions: 1) A description of all stylometry problems in probability terms, under a unified notation. To the best of our knowledge, this is the most comprehensive definition to date. 2) A survey of key methods, with a particular attention to data representation (or feature extraction) methods. 3) An evaluation of 23,760 feature extraction methods, which is the most comprehensive evaluation of feature extraction methods in the literature of stylometry to date. The importance of this evaluation is two fold. First, identifying the relative effectiveness of the features (since, currently, many are not evaluated jointly; e.g. syntactic n-grams are not evaluated against k-skip n-grams, and so forth). Second, thanks to our generalizations, we could evaluate novel grams, such as what we name compound grams. 4) The release of our associated Python feature extraction library, namely Fextractor. Essentially, the library generalizes all existing n-gram based feature extraction methods under the "at least l-frequent, dir-directed, k-skipped n-grams'', and allows grams to be diversely defined, including definitions that are based on high-level grammatical aspects, such as POS tags, as well as lower-level ones, such as distribution of function words, word shapes, etc. This makes the library, by far, the most extensive in this domain to date. 5) The construction, evaluation, and release of the first dataset for Emirati social media text. This evaluation represents the first evaluation of author identification against Emirati social media texts. Interestingly, we find that, when using our models and feature extraction library (Fextractor), authors could be identified significantly more accurately than what is reported with similarly sized datasets. The dataset also contains sub-datasets that represent other languages (Dutch, English, Greek and Spanish), and our findings are consistent across them.

This manuscript explores significant advancements and emerging challenges in CAR T cell therapies, focusing on the production methodologies and regulatory complexities. The discussion highlights ongoing challenges like the lack of in vivo persistence, lengthy production times, and elevated costs associated with current CAR T cell therapies. It analyzes innovative solutions such as genetic engineering techniques aimed at enhancing cellular efficacy and endurance, alongside cutting-edge manufacturing processes, including closed systems and development of allogeneic products. These advancements hold promise for reducing costs and improving production efficiency, potentially increasing patient access to these transformative therapies globally. Furthermore, the manuscript underscores the necessity for expanding ongoing research and enhancing regulatory frameworks to fully realize and implement these innovations in CAR T cell manufacturing and bring these innovations to fruition.

Dr. Jurg Tschopp created the word "inflammasome" in 2002. Inflammasome activation and its function in disease processes have been the subject of significant investigation over the last 15 years. Four important inflammasomes have been identified: NLRP1, NLRP3, NLRC4, and AIM2. When these inflammasomes are activated, they process and secrete inflammatory cytokines such as IL-1b and IL-18, as well as cause pyroptosis, an inflammatory form of cell death. In this review, we will look at how these inflammasomes have been connected to Periodontitis pathogenesis.

This study presents an advanced defect detection approach for solar cells using the YOLOv10 deep learning model. Leveraging a comprehensive dataset of 10,500 solar cell images, annotated with 12 distinct defect types, our model integrates Compact Inverted Blocks (CIB) and Partial Self-Attention (PSA) modules to enhance feature extraction and classification accuracy. Training on the Viking cluster with state-of-the-art GPUs, our model achieved remarkable results, including a mean Average Precision ([email protected]) of 98.5%. Detailed analysis of the model's performance revealed exceptional precision and recall rates for most defect classes, notably achieving 100% accuracy in detecting black core, corner, fragment, scratch, and short circuit defects. Even for challenging defect types such as thick line and star crack, the model maintained high performance with accuracies of 94% and 96%, respectively. The recall-confidence and precision-recall curves further demonstrate the model's robustness and reliability across varying confidence thresholds. This research not only advances the state of automated defect detection in photovoltaic manufacturing but also underscores the potential of YOLOv10 for real-time applications. Our findings suggest significant implications for improving the quality control process in solar cell production.

This study examines the relationship between firm-level and macroeconomic variables and stock prices (SP) in Iran, Saudi Arabia (KSA), and Iraq, where economic conditions are uncertain. The sample consists of all firms listed on these countries' stock exchanges between 2015 and 2019, yielding a comprehensive dataset from 154 Iranian firms, 82 KSA firms, and 33 Iraqi firms. Using a fixed effect model, intriguing relationships are uncovered between firm-level and macroeconomic factors on SP. The findings indicate that, at a 1% significance level, there is a strong link between Iran and Iraq's GDP and their respective SP. In KSA, the association between GDP and SP is positive and significant at a 5% level. In addition, there is a positive and statistically significant correlation between the inflation rate and SP in all three countries. Moreover, the association between exchange rates and SP is significant and positive in KSA and Iraq but negative and significant at the 1% significance level in Iran. Furthermore, in KSA, the connection between oil prices and SP is positive and significant, whereas, in Iran, the relationship is negative at the 1% level. Surprisingly, there is no association between the price of oil and Iraqi SP. Regarding intangible assets, their impact on SP in Iran and KSA is negligible. In Iraq, however, there is a negative and significant relationship at the 5% level, indicating that intangible assets have a detrimental impact on SP. These findings highlight the complex link among macroeconomic factors, intangible assets, and SP in the examined countries. Policymakers and governments should prioritize implementing measures to foster sustainable economic growth, manage inflation, and stabilize exchange rates. These actions can boost investor confidence and contribute to the stock market's overall development.

Abstract: Background: Aging is an important risk factor for cardiovascular diseases and con-vincing data has shown that chronic low-grade inflammation, which develops with advanced age, contributes significantly to cardiovascular risk. Objectives: The present study aimed to use ¹⁸F-FDG/¹⁸F-NaF-PET/CT imaging to respectively gauge arterial inflammation and microcalcifi-cation in healthy elderly and to assess the potential benefits of a tyrosol- and hydroxytyrosol-rich diet on these two markers of atherosclerotic plaque fragility. Methods: Eleven healthy partici-pants (mean age 75 ± 5.67 years) were supplemented for 6 months with high polyphenol-rich extra virgin olive oil (HP-EVOO), extra virgin olive oil (EVOO), or refined olive oil (ROO). The partic-ipants underwent PET/CT imaging with ¹⁸F-FDG and ¹⁸F-NaF radiotracers at baseline and after 6 months. ¹⁸F-FDG and ¹⁸F-NaF uptakes were quantified using standardized uptake values (SUV) and were categorized based on artery calcification and olive oil type. Results: A total of 324 slices of the aortas of the imaged participants were analyzed for arterial inflammation and 327 slices were analyzed for microcalcification. 18F-FDG uptake was significantly higher in the non-calcified segments than in the calcified segments (SUVmax = 2.70  0.62 and SUVmax = 2.54  0.44, respectively, p<0.042). Conversely, the non-calcified segments displayed significantly lower 18F-NaF uptake than the calcified segments (SUVmax = 1.90 0.37 and 2.09  0.24, respec-tively, p<0.0001). The 6-month supplementation with HP-EVOO induced a significant reduction in 18F-FDG uptake in both the non-calcified (2.93  0.23 to 2.75  0.38, p<0.004) and calcified seg-ments of the aortas (2.25  0.29 to 2.15  0.19, p<0.02). 18F-NaF uptake was also significantly low-er in patients supplemented with HP-EVOO (SUVmax = 1.98  0.33 at baseline compared to 1.85  0.28, after the 6-month supplementation, p<0.004), whereas no significant effect was observed with EVOO. Conversely, participants supplemented with ROO displayed a significant increase in 18F-NaF uptake (SUVmax = 1.78  0.34 to 1.95  0.34, p<0.0001). Conclusion: The present study confirmed that ¹⁸F-FDG/¹⁸F-NaF-PET/CT imaging is a valuable approach for assessing age-related arterial damage and demonstrated that a phenolic compound-rich diet reduces both arterial inflammation and atherosclerotic lesion microcalcification.

Background: Nutritional rickets is still considered as a global health problem especially in low-resource countries and immigrant societies of developed countries. Generalized skeletal deformities including angular knee deformities as genu varum and genu valgum are prominent features of nutritional rickets. Angular knee deformities can cause gait difficulties. However, the true remodelling potential of the healed knee deformities is largely unknown to the pediatric and orthopedic community. Aims: The primary objective of this study protocol is to investigate the natural history of disease in regard to the remodelling potential of angular knee deformities in children and adolescents with healed nutritional rickets. And determine the potential patient- and deformity-related factors that are associated with a favorable deformity remodelling as age and sex of patients and type, severity, laterality of deformities etc. Methods: This will be a prospective observational analytical cohort natural history of disease study. A minimum of at least 140 knees with healed nutritional rickets and angular knee deformities will be observed at regular three-monthly intervals over a period of at least one year. We will report two outcome variables namely; clinical and radiological tibio-femoral angle. And independent patient and deformity-related variables as age, sex, deformity type, severity and laterality. Inferential statistics namely bivariate and multivariate analysis will be employed accordingly to identify the relation between outcome variables and the different independent variables. Ethics and dissemination: This protocol study has been approved by the institutional research ethics committee. Results will be presented at conferences and submitted to relevant international and society publications. Authors will also communicate the results to their scholarly networks and post them on scholarly networking sites. Conclusions: This study has the potential for improving the decision-making process as to which patients deserve conservative treatment and which deserve surgical deformity correction. Results are expected to have an impact on the clinical practice of pediatricians, orthopedic surgeons and family physicians alike.

Background: The effectiveness of the anti-COVID-19 vaccine remains a matter to be clarified. Methods: The humoral and cellular immunity after the administration of three doses of the Pfizer–BioNTech and Oxford AstraZeneca vaccines against SARS-CoV-2 over one year and the appearance of post-vaccination COVID-19 have been studied. Results: Anti-SARS-CoV-2 IgG and IgA antibodies showed a progressive increase throughout the vaccination period. This increase was greatest after the third dose. The highest levels were observed in subjects who had anti-SARS-CoV-2 antibodies prior to vaccination. There was an increase in CD4+ αβ, CD8+ γδ and TEM CD8+ γδ T cells, and a decrease in apoptosis in CD4+CD8+ and CD56+ αβ and γδ T cells. Post-vaccination SARS-CoV-2 infection was greater than 60%. The symptoms of COVID-19 were very mild and were related to γδ T cell deficit, specifically CD8+ TEMRA and CD56+ γδ TEM, as well as lower pre-vaccine apoptosis levels. Conclusions: Those results demonstrate the important role that γδ T cells play in SARS-CoV-2 vaccine immunization.