Background: Molecular genetic events are among the numerous factors affecting the clinical course of papillary thyroid carcinoma (PTC). Recent studies have demonstrated that aberrant expression of miRNA, as well as different thyroid-related genes, correlate with the aggressive clinical course of PTC and unfavorable treatment outcome, which opens up new avenues for using them in personalization of the treatment strategy for patients with PTC. In the present work, our goal was to assess the applicability of molecular markers in preoperative diagnosis of aggressive variants of papillary thyroid cancer. Methods: The molecular genetic profile (expression levels of 34 different markers and BRAF mutation) was studied for 108 cytology specimens collected by fine-needle aspiration biopsy in patients with PTC having different clinical manifestations. Results: Statistically significant differences with adjustment for multiple comparisons (p < 0.0015) for clinically aggressive variants of PTC were obtained for four markers: miRNA-146b, miRNA-221, FN1, and CDKN2A. Weak statistical correlation (0.0015< р<0.05) was observed for miRNA-31, -375, -551b, -148b, -125b, mtDNA, CITED1, TPO, HMGA2, CLU, NIS, SERPINA1, TFF3, and TMPRSS4. Conclusions: The recurrence risk of papillary thyroid carcinoma can be preoperatively predicted using miRNA-221, the fibronectin and cyclin-dependent kinase inhibitor 2A genes.

Papillary thyroid carcinoma (PTC) presents a significant health concern, particularly among Hispanic women in the United States, who exhibit a disproportionately higher chance of developing an advanced disease when compared to the non-Hispanic population. Emerging evidence suggests coagulation factor X, encoded by F10 gene, has a potential role in inhibiting cancer cell migration. However, comprehensive investigations into the differential expression patterns of F10 in Hispanic versus non-Hispanic females remain limited. RNA-sequencing data was acquired from the TCGA database for white female patients, 166 non-Hispanic and 25 Hispanic. A statistically significant (p < 0.05) 2.06-fold increase in F10 expression levels was detected in disease-free tumors compared to recurrent PTC tumors. Furthermore, an increase in F10 gene expression levels was also observed corresponding to approximately a 1.74-fold increase in non-Hispanic patients compared to Hispanic patients. The probability of tumor recurrence was 1.82 times higher in the cohort with low expression of F10 compared to the high expression cohort, correlating with the lower disease-free rates observed in Hispanic patients’ cohort when compared to non-Hispanics. This finding underscores the relevance of ethnic disparities in molecular profiles for understanding cancer susceptibility. Identifying F10 as a potential prognostic biomarker highlights avenues for targeted interventions and contributes to improving diagnostic and treatment strategies for diverse patient populations.

Epidemiological studies have shown a strong association between high body mass index (BMI) and papillary thyroid cancer (PTC). We assessed the clinical and histopathological features of PTC in patients with a higher BMI and compared them to analogous parameters in PTC patients with a normal BMI. We retrospectively analyzed 5,021 medical records of patients admitted and surgically treated for thyroid tumors in one center between 2008 and 2018. Finally, we extracted data from 523 adult patients with PTC and stratified patients into two groups according to BMI: Group 1 with BMI < 25 kg/m² and Group 2 with BMI ≥25 kg/m². Data stratification was performed to estimate the association of overweight and obesity with clinical and histopathological features of PTC in both univariate and multivariate binary logistic regression analyses. Overall, compared to patients with a normal BMI, overweight and obese patients had a greater risk of minimal extrathyroidal extension (minimal ETE), multifocality and bilaterality of PTC (p<0.001 for all). Analysis did not show that BMI was significantly associated with more advanced tumor-node-metastasis (TNM) stage (p=0.894). Obesity and overweight were significantly associated with higher aggressiveness of PTC. When considering various management options for PTC patients, these findings regarding overweight and obesity should be taken into consideration during the decision-making process.

Papillary thyroid carcinoma (PTC) has two main histologic variants: classical-PTC (CL-PTC) and follicular variant PTC (FV-PTC). Recently, due to its similar features to benign lesions, the encapsulated FV-PTC variant was reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Nonetheless, specific molecular signatures are not yet available. It is well known that telomere-related genome instability is caused by inappropriate DNA repair of dysfunctional telomeres and that mechanisms involved in the damaged telomere repair processing may led to detrimental outcomes, altering the 3D nuclear telomere and genome organization in cancer cells. This pilot study aimed to evaluate whether a specific nuclear telomere architecture might characterize NIFTP, potentially distinguishing it from other PTC histologic variants. Our findings demonstrate that 3D telomere profiles of CL-PTC and FV-PTC were different from NIFTP and that NIFTP more closely resembles follicular thyroid adenoma (FTA). NIFTP has longer telomeres than CL-PTC and FV-PTC samples and telomere length overlaps in NIFTP and FTA. There was no association between BRAF expression and telomere length in all tested samples. Our data showing that 3D nuclear telomere organization is altered differently in thyroid cancer variants, suggest that this parameter might guide clinical management of NIFTP. Although further investigations in a larger cohort of patients are necessary to corroborate our observations, telomere-related genomic instability might be of value in the diagnosis of NIFTP and allow for a more appropriate selection of the correct treatment.

The genetic causes of the differentiated, highly treatable and mostly non-fatal papillary thyroid cancer (PTC) are not yet fully known. The widely accepted PTC etiology blames altered sequence or/and expression level of certain biomarker genes. However, our previous studies found that the PTC biomarkers played significantly lower roles than the personalized PTC Gene Master Regulators. Our publicly accessible gene expression data from the cancer nodule and the surrounding normal tissue of surgically removed PTC tumor were re-analyzed to determine the transcriptomic effects on the genomic fabrics responsible for the DNA replication, repair and transcription. Tumor results were compared to the gene expression profiles of the papillary (BCPAP) and the anaplastic (8505C) human thyroid cancer cell lines. The analyses were carried out from the Genomic Fabric Paradigm (GFP) perspective that provides the most theoretically possible comprehensive characterization of the transcriptome and its alterations in disease. The study indicated that, in addition to regulating numerous genes, changes in the homeostatic control of transcript abundances and remodeling of the gene networks had major contributions to the PTC occurrence, resilience and proliferation. Therefore, the molecular mechanisms responsible for gene expression control and inter-coordination should also be considered when designing personalized anti-cancer gene therapies.

The Cancer Genome Atlas (TCGA) has classified papillary thyroid carcinoma (PTC) into indolent RAS-like and aggressive BRAF-like based on its distinct driver gene mutations. This study aimed to assess clinicopathology and pERK1/2 expression variations between BRAF-like and RAS-like PTCs and establish predictive models for BRAFV600E and RAS-mutated PTCs. A total of 222 PTCs underwent immunohistochemistry staining to assess pERK1/2 expression and Sanger sequencing to analyze the BRAF and RAS genes. Multivariate logistic regression was employed to develop prediction model. Independent predictors for the BRAFV600E mutation include a nuclear score of 3, the absence of capsules, an aggressive histology variant, and pERK1/2 levels exceeding 10% (X2=0.128, P&gt;0.05, AUC=0.734, P&lt;0.001). RAS mutation predictive model includes follicular histology variant and pERK1/2 expression &gt;10% (X2=0.174, P&gt;0.05, AUC=0.8, P&lt;0.001). We proposed using the prediction model concurrently with four potential combination group outcomes. PTC cases included in combination of low BRAFV600E-scoring group and high RAS-scoring group are categorized as RAS-like (adjOR=4.857, P=0.01, 95% CI=1.470-16.049). PTCs included in combination of high BRAFV600E-scoring group and low RAS-scoring group are categorized as BRAF-like PTCs (adjOR=3.091, P=0.001, 95% CI=1.594-5.995). The different prediction models indicate variations in biological behaviour between BRAF-like and RAS-like PTCs, necessitating adjustments in treatment approaches.

Papillary thyroid carcinoma (PTC) accounts for approximately 85%-90% of all thyroid cancers. BRAFV600E mutation is a highly specific target for papillary thyroid carcinoma (PTC) and may have a reciprocal causative relationship with iodide-metabolizing genes. Here, we performed a review of studies published in the past 10 years to determine the relationship between iodine intake and BRAFV600E mutation in patients with PTC. We searched the MEDLINE, PubMed, and EMBASE databases for studies published from 2009 to 2019; seven partially matched the selection criteria and were suitable for review, and five passed all selection criteria. We divided the patients into three groups by iodine intake: low (urinary iodine concentration [UIC] &lt;100 μg/L), adequate (UIC 100–200 μg/L), and high iodine intake groups (UIC ≥200 μg/L). Between-group analysis revealed no significant differences in the odds ratio of the prevalence of BRAFV600E mutation between the high and adequate/low iodine intake groups and between the adequate and low iodine intake groups. To further analyzed the results of studies, they exhibited U-shaped curves in the relation of deficient and excessive dietary iodine intake in BRAFV600E mutation. The results might suggest that iodine intake slightly influences the prevalence of BRAFV600E mutation in patients with PTC despite the heterogeneity of studies. Further research should explore potential mechanisms underlying the associations between iodine intake and BRAF mutation in PTC. The systematic review was registered in PROSPERO (CRD42021279462).

The diagnosis of papillary thyroid carcinoma has always been a concerned and challenging issue and it is very important and meaningful to have a definite diagnosis before the operation. In this study, we tried to use an artificial intelligence algorithm instead of medical statistics to analyze the genetic fingerprint from gene chip results to identify papillary thyroid carcinoma. We trained 20 artificial neural network models with differential genes and other important genes related to the cell metabolic cycle as the list of input features, and apply them to the diagnosis of papillary thyroid cancer in the independent validation data set. The results showed that when we used the DEGs and all genes lists as input features the models got the best diagnostic performance with AUC=98.97% and 99.37% and the accuracy were both 96%. This study revealed that the proposed artificial neural network models constructed with genetic fingerprints could achieve a prediction of papillary thyroid carcinoma. Such models can support clinicians to make more accurate clinical diagnoses. At the same time, it provides a novel idea for the application of artificial intelligence in clinical medicine.

Publically available (own) transcriptomic data were re-analyzed to quantify the alteration of functional pathways in the thyroid cancer, establish the gene hierarchy, identify potential gene targets and predict the effects of their manipulation. The expression data were generated from one case of papillary thyroid carcinoma (PTC) and from genetically manipulated BCPAP (papillary) and 8505C (anaplastic) human thyroid cancer cell lines. The study used the genomic fabric perspective that considers the transcriptome as a multi-dimensional mathematical object based on the three independent characteristics that can be derived for each gene from the expression data. We found remarkable remodeling of the thyroid hormone synthesis, cell cycle, oxidative phosphorylation and apoptosis pathways. Serine peptidase inhibitor, Kunitz type, 2 (SPINT2) was identified as the Gene Master Regulator of the investigated PTC. The substantial increase of the expression synergism of SPINT2 with apoptosis genes in the cancer nodule with respect to the surrounding normal tissue (NOR) suggests that its experimental overexpression may force the PTC cells into apoptosis with negligible effect on the NOR cells. The predictive value of the expression coordination for the expression regulation was validated with data from 8505C and BCPAP cells before and after lentiviral transfection with DDX19B.

Eosinophils in peripheral blood account for 0.3-5% of leukocytes, which is equivalent to 0.05-0.5 x 109/l. A count equal or above 0.5 x 109/l is considered eosinophilia, while a count equal or above 1.5 x 109/l is defined as hypereosinophilia. In bone marrow, eosinophilia is considered when eosinophils make up more than 6% of the total nuclear cells. In daily clinical practice, the most common causes of reactive eosinophilia are non- hematologic, whether non-neoplastic (allergic diseases, drugs, infections or immunological diseases) or neoplastic (solid tumors). Eosinophilia associated with a haematological malignancy may be reactive or secondary to the production of eosinophilopoietic cytokines, and this is mainly seen in lymphoid neoplasms (Hodgkin lymphoma, mature T-cell neoplasms, lymphoid variant of hypereosinophilic syndrome and B-acute lymphoblastic leukemia/lymphoma). Eosinophilia associated with a haematological malignancy may also be neoplastic or primary, derived from the malignant clone, usually in myeloid neoplasms or with origin in stem cell (myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions, acute myeloid leukemia with Core Binding Factor translocations, mastocytosis, myeloproliferative neoplasms, myelodysplastic/myeloproliferative neoplasms and myelodysplastic neoplasms). There are no concrete data in standardized cytological and cytometric procedures that could predict whether eosinophilia is reactive o clonal. The verification is usually indirect, based on the categorization of the accompanying hematologic malignancy. This review focuses on the broad differential diagnosis of haematological malignancies with eosinophilia.

Background: The incidence of various types of cancer, for example papillary thyroid carcinoma (PTC), is on the rise. Since therapeutic success depends greatly on early diagnosis, reliable diag-nostic biomarkers must be identified and easy-to-apply tools for detecting them must urgently be standardized. Here, we contribute to solving this medical challenge by assessing miRNAs sus-pected of promoting carcinogenesis in extracellular vesicles (EVs) that can be routinely obtained via liquid biopsy. We profit from current progress in cancerology that provides innovations in liquid biopsy and EVs analysis along with identification of miRNAs and chaperone system (CS) components implicated in carcinogenesis. Methods: We measured in EVs obtained from circulat-ing blood plasma from PTC patients the levels of three miRNAs implicated in thyroid cancer, miR-1, miR-206, and miR-221, and most likely involved in the regulation of two members of the CS, Hsp60 and CCT. EVs were isolated from the plasma of patients with PTC and controls with benign goiter (BG), and from the culture medium of a PTC cell line (MDAT32) and were duly characterized. Results: The levels of miRNAs determined by RT-qPCR were consistently higher in PTC patients and decreased down to control levels after thyroidectomy. Bioinformatics showed that the miRNAs target genes were associated to the molecular pathogenesis of PTC. Conclusions: Thus, our exploratory study reaffirms the potential in clinics of the selected miRNAs in EVs as useful biomarkers of PTC easily accessible via liquid biopsy, which is minimally invasive and amenable to periodic repetition, an improvement compared to the established fine-needle aspirate biopsy.

The frequency of concurrent thyroid cancer in patients with primary hyperparathyroidism (pHPT) varies. While the pathological association between thyroid and parathyroid disorders is frequently noted, the co-occurrence of parathyroid adenoma and papillary thyroid cancer is exceptionally rare. Furthermore, the occurrence of an ectopic parathyroid adenoma in the retropharyngeal space is exceedingly rare. Ectopic parathyroid glands present considerable complexities in both diagnosis and surgical management, especially within the realm of surgical intervention. The potential inability to accurately identify and excise ectopic parathyroid adenomas during the initial surgery may lead to an increased morbidity and recurrence, requiring high-risk reoperations. Therfore, the evaluation of anatomical variations through the utilization of relevant diagnostic tools plays a crucial role in guiding decisions pertaining to clinical manifestations, diagnostic methods, surgical interventions, and operative strategies for parathyroid tumors. We present the case of a 51-year-old female patient with papillary thyroid carcinoma in the right thyroid lobe and an ectopic parathyroid adenoma in the retropharyngeal space confirmed through surgical intervention. This case sheds light on the unusual occurrence of an ectopic parathyroid adenoma in the retropharyngeal region within a thyroid cancer patient, providing valuable insights within the realm of thyroid malignancies.

Papillary thyroid cancer (PTC) is commonly characterized by multifocality, which is associated with aggressive features and a less favorable prognosis. The current study aimed to compare the clinicopathologic characteristics and long-term oncological outcomes of bilateral and unilateral multifocal PTC. The medical records of 1745 patients with multifocal PTC who underwent thyroid surgery at Seoul St. Mary’s Hospital were retrospectively reviewed. The clinicopathological characteristics and recurrence rates were compared based on cancer laterality. Further, 357 patients who underwent total thyroidectomy were matched to investigate the recurrence risk and disease-free survival (DFS). Before propensity score matching (PSM), there was no significant difference in the recurrence rate between the bilateral and unilateral multifocal PTC groups. Cancer laterality was not a predictor of DFS based on the Cox regression analyses. However, after PSM, unilateral multifocality was associated with a significantly high risk of recurrence. Similarly, unilateral multifocality was associated with a significantly poor DFS based on the Kaplan–Meier analysis. Compared with bilateral PTC, unilateral multifocal PTC was associated with a poor DFS. A comprehensive preoperative examination should be performed to detect multifocality before the initial surgical intervention for optimal treatment. Postoperative short-term follow-up is recommended for unilateral multifocal PTC for recurrence surveillance.

In the surgical treatment of lung cancer, systemic mediastinal lymph node dissection, as one important routine procedure, has been accepted by most peers in the world. However, due to the special location of some mediastinal lymph nodes, the difficulty of dissection, and the negative preoperative CT results, the specific scope of lymph node dissection is still controversial. Especially the second group, which is located at the top of thorax, is likely to be overlooked for the above reasons. Here, we report a case of lung adenocarcinoma in which the preoperative CT showed no abnormal lymph nodes in the second group and also no enlarged lymph nodes of the second group were found during the surgery, yet lymphadenectomy was still performed according the routine with the lymph node of station 2 being sampled. In the postoperative pathological report, cancer cells were found in the second group, instead of lung adenocarcinoma, these cells come from thyroid and were proved to be papillary thyroid carcinoma, which is unusual because no obvious indication of thyroid carcinoma was found in preoperative color doppler ultrasound of superficial lymph nodes.

We aimed to assess the prognostic value of BRAFV600E mutation in a series of 127 papillary thyroid carcinoma (PTC) cases as a single factor, as well as in synergic interaction with other standard risk factors. All cases were tested for BRAFV600E mutation by real-time PCR. Event-free survival (EFS) was calculated between the date of the first evaluation and the date of occurrence of an adverse event (tumor recurrence/distant metastasis) or the date of the last known status. The prevalence of BRAFV600E mutation was 57.2%. The Kaplan-Meyer analysis showed a significant reduction of EFS among cases harboring BRAFV600E mutation compared to non-mutated cases (p=0.010). In addition, BRAFV600E mutation was found to better predict adverse outcomes when associated with the following risk factors: age≥55 years-old (p<0.001), male gender (p<0.001), conventional (p=0.005) and tall cell (p=0.014) histology, tumor size&gt;40mm (p=0.001), extrathyroidal extension (p=0.001), multifocality (p=0.001) and lymph node metastasis (p&lt;0.001). In univariate analysis, a 3.74-fold increased risk for a reduced EFS (p=0.018) was found for BRAFV600E mutated cases. Our results highlight the prognostic value of BRAFV600E mutation in PTCs. Moreover, the synergic interaction between BRAFV600E mutation and other risk factors seems more valuable in terms of prognosis, compared to BRAFV600E mutation alone.

Soft pneumatic actuators/robotics have received significant interest in the medical and health fields, due to their intrinsic elasticity and simple control strategies enabling desired interaction. However, current soft hand pneumatic exoskeletons often exhibit uniform deformation, mismatch the profile of the interacted objects, and seldom quantify the assistive effects during activities of daily life (ADL), such as extension angle and joint stiffness predicted. The lack of quantification poses challenges to the effective and sustainable advancement of rehabilitation technology. This paper introduces the design, modeling, and testing of pneumatic bioinspired Segmented Composite Proprioceptive Bending Actuators (SCPBAs) for hand rehabilitation in ADL tasks. The actuator’s soft-joint/rigid-bone segmented structure, inspired by the human finger anatomy, provides a superior fit compared to traditional continuous structures. A quasi-static model is established to predict the bending angles based on geometrical parameters. The SCPBAs also include a quantitative evaluation of joint stiffness and extension angle utilizing proprioceptive bending information. Additionally, a soft under-actuated hand exoskeleton equipped with SCPBAs demonstrates its potential in ADL rehabilitation scenarios.

Pretreatment of cells with proteolysis inhibitors diminished intensity and changed shape of DNICs specific EPR signal in a treatment time-dependent manner. The level of DNIC formation was significantly influenced by the presence of protein degradation products. Interestingly, formation of HMWDNICs depended on the availability of LMWDNICs. The extent of glutathione involvement in the in vivo formation of DNICs is minor yet noticeable, aligning with our prior research findings.

In this article, we have tried to extend the Neumann–Kopp law concerning the heat capacity of solid compounds to other physical observables for materials represented as mixtures of chemical compounds, alloys, and ceramics. The main goal of this study is to find the intervals of external or internal parameters for a solid compound, within which its physical observable - the magnetic transition temperature for this work, can be expressed in terms of the atomic or molar weighted sum of the magnetic transition temperatures of the constituent elements of a compound. Outside these intervals, we tried to figure out the structure of the variable by which the weighted sum should be multiplied. Thus, for USb–x(ThSb) mixtures with a mole fraction x from 0.36 to 0.55, the magnetic transition temperature of this mixture is expressed in term of the molar weighted sum of the temperature of uranium structural transition associated with a change in the magnetic properties of uranium and of the temperature at which the nature of the magnetic susceptibility of antimony changes. For the magnetic Laves phase compounds Er(Fe_0.8–xMn_0.2–yCo_x+y)₂, the Curie temperature of the compound is equal to the weighted sum of the Curie temperatures of all elements of the compound, except for Mn, at x = 0.1, y = 0 and y = 0.1. For the paramagnetic Curie temperature of intercalated dichalcogenides Cr_xМоSe₂, it can be expressed in terms of the weighted Neel temperature of chromium multiplied by a variable depending on x, on the atomic numbers of all elements of the compound, and on a parameter proportional to the derivatives with respect to x of the dichalcogenide’s crystal lattice parameters.

Purpose: This study aimed to investigate useful preoperative clinical and hematologic variables in predicting malignancy in patients with the atypia of undetermined significance (AUS) nodules, and to suggest a machine learning-based prediction model. Methods: We enrolled 280 patients who underwent surgery for the AUS nodules at Wonju Severance Christian Hospital between 2018 and 2022. We evaluated preoperative hematologic indices, including Delta Neutrophil Index (DNI), Neutrophil-to-Lymphocyte Ratio (NLR), and Platelet-to-Lymphocyte Ratio (PLR), as well as preoperatively identifiable clinical variables such as age and sex at diagnosis, history of radiation exposure, familial history of thyroid cancer, primary tumor size, and the 2016 Korean Thyroid Imaging Reporting and Data System (K-TIRADS) classification. Results: A total of 116 patients (41.4%) were finally diagnosed with various types of thyroid malignancy, excluding 32 patients (11.4%) with thyroid cancer incidentally identified. Age at diagnosis (p = 0.012), primary tumor size (p = 0.048), and the K-TIRADS classification (p = 0.003) were independent risk factors to predict the diagnosis of malignancy in patients with AUS nodules younger than 55 years, not in those aged of 55 years or older. Adding the NLR to these risk factors significantly improved the predictability for malignancy in the same patient group (p < 0.001). Conclusions: The inclusion of NLR in the ma-lignancy prediction model enhances the predictive accuracy for malignancy in younger patients with AUS nodules. This finding suggests that incorporating NLR into preoperative assessment could refine management strategies and improve decision-making for surgical interventions.

Uterine Tumor Resembling Ovarian Sex Cord Stromal Tumor (UTROSCT) is a rare uterine mesenchymal neoplasm, which resembles ovarian sex cord tumors of the ovary. Although, in general, UTROSCT exhibits benign behavior with a favorable prognosis, this neoplasm is nonetheless classified as being of an uncertain ma-lignant potential, given its low rate of recurrence and the fact that it rarely pro-duces metastases (lymph nodes, epiploic appendix, omentum, small bowel, subcutaneous, lungs). Its histogenesis too is uncertain. Typically, UTROSCT oc-curs in peri-menopausal or menopausal women but can sometimes be observed in young women. Usually, this neoplasm can be found in the uterine corpus as a nodular intramural lesion, less frequently submucosal, subserosal or poly-poid/intracavitary. UTROSCT can cause abnormal bleeding, pelvic pain, enlarged uterus, mass sensation, but sometimes it is found purely by chance. This neo-plasm can be considered polyphenotypic on morphological, immunohistochem-ical, and genetic analyses. Generally, on microscopic examination, UTROSCT shows a predominant pattern of the cords, nests, and trabeculae typical of sex cord tumors of the ovary while, immunohistochemically, it is characterized by a co-expression of epithelial, smooth muscle, and sex cord markers. The aim of this review is to report clinical and pathological data and genetic alterations to estab-lish its impact on the prognosis and management of patients affected by this rare entity.

The rapid and accurate detection of viruses and the discovery of single nucleotide polymorphisms (SNPs) are crucial for disease management and understanding viral evolution. In this study, a pipeline for virus detection, validation, and SNP discovery from next-generation sequencing (NGS) data is presented. By integrating state-of-the-art bioinformatics tools with artificial intelligence, the pipeline processes raw sequencing data to identify viral sequences with high accuracy and sensitivity. Before aligning the reads to the reference genomes, quality control measures and adapter trimming are performed to ensure the integrity of the data. Unmapped reads are subjected to de novo assembly to reveal novel viral sequences and genetic elements. The effectiveness of the pipeline is demonstrated by the identification of virus sequences, illustrating its potential for the detection of known and emerging pathogens. SNP discovery is performed using a custom Python script that compares the entire population of sequenced viral reads to a reference genome. This approach provides a comprehensive overview of viral genetic diversity and identifies dominant variants and a spectrum of genetic variations. The robustness of the pipeline is confirmed by the recovery of complete viral sequences, which improves our understanding of viral genomics. This study highlights the synergy between traditional bioinformatics techniques and modern approaches, providing a robust tool for analyzing viral genomes and contributing to the broader field of viral genomics.

We report a case of colloid carcinoma (CC) arising from an intestinal-type intraductal papillary mucinous neoplasm with high-grade dysplasia (IPMNHGD) of the pancreas, diagnosed with serial pancreatic juice aspiration cytological examination (SPACE). A rapidly growing intraductal papillary mucinous neoplasm (IPMN) in a 71-year-old Japanese man accelerated his hospitalization in our institute. Clinically, a large, ruptured pancreatic cyst was suspected. Cytologically, several mucin-positive signet-ring cells were scattered in the inflammatory, necrotic, or mucinous background. Signet-ring cells in cell block specimens were immunoreactive for MUC2, MUC5AC, maspin, S100P, and claudin-18. The final cytologic diagnosis was CC arising in an intestinal-type IPMNHGD with intraperitoneal penetration. The patient died two months postoperatively. The cytologic diagnosis was achieved through SPACE, and the presence of signet-ring cells was characteristic. Anti-claudin-18.2-specific monoclonal antibody therapy will likely be used to treat patients with IPMNHGD in the future. To our knowledge, this is the first report in English on mucin-positive signet-ring cells of CC arising in an intestinal-type IPMNHGD evaluated by SPACE cytology.

Bone is the second most frequent site of metastases from differentiated thyroid carcinoma (DTC). Bone metastases (BM) occurs in about 10% of all patients with DTC. They are more frequently observed in follicular thyroid carcinoma (FTC) (7-28%), than in thyroid papillary carcinoma (PTC) (1-7%) [1,2] and are associated to unfavorable clinical out-comes, mainly related to skeletal related events (SREs), such as pathologic fractures, bone pain, spinal cord compressions and hypercalcemia, which impair the quality of life and reduce life expectancy. BM from DTC require multimodal and comprehensive treatment, including radioiodine therapy (RAI), palliative treatment, surgical treatment, external beam radiation and target drug therapy. RAI is the first line treatment, but about two thirds of DTC patients with distant metastases are not definitively cured. This treatment is considered less effective in BM particularly in case of large metastases. The different response to RAI treatment alone or associated to BM focal treatment depends to RAI avidity of lesions [3]. We report the rare case of an excellent response to RAI of a metachronous bone metastasis of skull from FTC, in a 72 yrs old woman, diagnosed 15 years after the first treatment, followed by a complete regression of radioiodine up-taking area with persistence of excellent response to the treatment six years after it. This case confirms that the complete BM response to RAI treatment depends to the degree of dedifferentiation of cancers cells and enforce the concept of a long- life follow-up of FTC patients.

Coronavirus disease 2019 (COVID-19) has affected medical practice. More than 7,000,000 patients died worldwide after being infected with COVID-19; however, no specific laboratory markers have yet been established to predict death related to this disease. In contrast, electrocardiographic changes owing to COVID-19 include QT prolongation and ST-T changes; however, there have been no studies on ambulatory electrocardiographic markers of COVID-19. We encountered three patients diagnosed as having COVID-19 who did not have a prior history of significant structural heart diseases. All had abnormalities in ambulatory echocardiogram parameters detected by high-resolution 24-h electrocardiogram monitoring: positive late potentials (LPs) and T-wave alternans (TWA), abnormal heart rate variability (HRV), and heart rate turbulence (HRT). Case 1 involved a 78-year-old woman with a history of chronic kidney disease, Case 2 a 76-year-old man with hypertension and diabetes, and Case 3 a 67-year-old man with renal cancer, lung cancer, and diabetes. None of them had a prior history of significant structural heart disease. Although no significant consistent increases in clinical markers were observed, all three patients died, mainly because of respiratory failure with mild heart failure. LP, TWA, HRV, and HRT were all positive in three cases with no significant structural cardiac disease at the initial phase of admission. There is a possibility that LP, TWA, HRV, and HRT have the potential to be risk stratifiers of COVID-19 pneumonia in the early phase of admission. Further accumulation of data regarding ambulatory electrocardiographic markers in patients with COVID-19 is needed.

Lower cutoff levels in screening programs have led to an increase in the proportion of detected cases with transient hypothyroidism, leading to increase of the overall incidence of primary congenital hypothyroidism (CH) in several countries. We have performed retrospective evaluation on the data from 251,008 (96.72%) neonates screened for thyroid-stimulating hormone (TSH) level in dried blood spot specimens taken 48 hours after birth, between 2002 and 2015, using DELFIA method. A TSH value of 15 mIU/L was used as the cutoff point until 2010 and 10 mIU/L thereafter. Primary CH was detected in 127 newborns (1/1976) of which 81.1% had permanent and 18.9% had transient CH. The incidence of primary CH was increased from 1/2489 until to 2010 to 1/1585 thereafter (p=0.131). However, the incidence of permanent CH was slightly increased (p=0.922), while the transient CH incidence had 8-fold increasing after lowering the TSH cutoff level (p<0.001). In cases with permanent CH, we observed lower frequency for thyroid dysgenesis (82.7 vs. 66.7%) and higher frequency for normal in-situ thyroid gland (17.3 vs. 33.3%), for the period with reduced TSH cutoff value. Our findings support the impact of lower TSH cutoff on the increasing incidence of congenital hypothyroidism.

Background: beta blockers of three generations are first-line drugs in the treatment of chronic heart failure (CHF). However, to date there is no clear understanding of the effect of beta blockers on myocardial energy metabolism disorders in CHF. The aim of the study: to conduct a study of beta-blockers of different generations on myocardial energy metabolism in the experimental CHF. Methods: CHF was modeled in white outbred rats by administering doxorubicin. The study drugs were administered intragastrically – new drug Hypertril (1-(β-phenylethyl)-4-amino-1,2,4-triazolium bromide)-3.5 mg/kg, metoprolol - 15 mg/kg, Nebivolol -10 mg/kg, Carvedilol 50 mg/kg, Bisoprolol, 10 mg/kg. In the myocardium, the main indices of energy metabolism were determined - ATP, ADP, AMP, malate, lactate, pyruvate, succinate dehydrogenase (SDH) activity, NAD-dependent malate dehydrogenase (NAD-MDH) activity. Results: traditional second-generation beta-blockers (Metoprolol and Bisoprolol) did not affect the studied indices of energy metabolism, and third-generation beta-blockers with additional properties - Carvedilol and, especially, Nebivalol and Hypertril improved myocardial energy metabolism. Conclusions: obtained results will help to expand our understanding of the effect of beta-blockers of various generations used to treat cardiovascular diseases on energy metabolism, and are also an experimental justification for the practical choice of these drugs in the complex therapy of CHF.

Background/Objectives: Endometriosis represents substantial direct and indirect healthcare costs impacted by absent accurate, non-invasive uniformly diagnostic tools. We endeavored to demonstrate gastrointestinal myoelectrical activity (GIMA) biomarkers unique to endometriosis allow noninvasive, uniformly accurate diagnosis or exclusion of endometriosis. Methods: Prospective open-label comparative study of 154 patients, age &gt;18, with or without diagnosed endometriosis. Population included 62 non-endometriosis controls (Cohort 1), 43 subjects with surgically histologically-confirmed endometriosis (Cohort 2), and 49 subjects with abdominal pain and negative imaging (Cohort 3). Electroviscerography (EVG) recorded GIMA biomarkers from three abdominal electrodes before and 30-minutes post water-load protocol. Cohort 2 had postoperative EVG and Cohort 3 had preoperative EVG. Calculated specificity, sensitivity, NPV, PPV and predictive probability or C-Statistic used univariate, multivariate, linear and logistical regression analyses of the area under the curve (AUC) at all frequency and time points, including age and pain covariants. Results: Non-endometriosis cohort differed significantly from endometriosis cohorts (p&lt;0.001) for median (IQR), and AUC percent frequency distribution of power at baseline, 10-minute, 20-minute, and 30-minute post water-load at all frequency ranges 15-20cpm, 30-40cpm and 40-50cpm. Endometriosis cohorts were statistically similar (p&gt;0.05). GIMA biomarker threshold scoring demonstrated 95%/91% sensitivity and PPV, 96%/95% specificity and NPV and C-statistic of &gt;99%/98% respectively for age subsets. GIMA biomarkers in Cohort 3 predicted 47/49 subjects positive and 2/49 negative for endometriosis, confirmed surgically. Hormonal therapy, surgical stage, nor pain score affected diagnostic accuracy. Conclusions: Non-invasive electroviscerography with GIMA biomarker detection distinguished participants with and without endometriosis based upon endometriosis specific GIMA biomarkers threshold scoring.

This article utilizes the Canny edge extraction algorithm based on contour curvature and the cross-correlation template matching algorithm to extensively study the impact of high-repetition-rate CO2 pulsed Laser on the target extraction and tracking performance of the infrared imaging detector. It establishes a quantified dazzling pattern for lasers on infrared imaging systems. By conducting laser dazzling and damage experiments, a detailed analysis of the normalized correlation between target and dazzling images is performed to quantitatively describe laser dazzling effects. Simultaneously, an evaluation system, including target distance and laser power evaluation factors, is established to determine the dazzling level and whether the target is recognizable. The research results reveal that laser power and target position are crucial factors affecting the detection performance of infrared imaging-guided weapon systems under laser dazzling. Different laser powers are required to successfully interfere with the recognition algorithm of infrared imaging-guided weapons at different distances. And laser dazzling will produce a lot of false edge information, which seriously affects the performance of pattern recognition algorithm. In laser damage experiments, the detector experienced functional damage, with a quarter of the image displaying as completely black. The energy density threshold required for functional damage to the detector is approximately 3 J/cm2. The dazzling assessment conclusions also apply to evaluating damage results. Finally, the proposed evaluation formula aligns with experimental results, objectively reflecting the actual impact of laser dazzling on the target extraction and tracking performance of infrared imaging systems. This study provides an in-depth and accurate analysis for understanding the influence of lasers on the performance of infrared imaging-guided weapons.

The presented work offers a novel process scheme for valorizing historical Pb-Zn slag, which involves crushing, grinding, and then using separation techniques to concentrate valuable components (nonferrous metals). This methodology could have a significant impact on the global beneficiation of metallurgical slags since, in theory, it is significantly more simple, environmentally friendly, and cost-effective than standard pyrometallurgical or hydrometallurgical procedures. According to previous physicochemical and mineralogical studies, Pb-Zn slag from "Topilnica" Veles is a valuable secondary raw material. This inhomogeneous technogenic resource contains substantial amounts of nonferrous metals (Pb, Zn, Cu, and Ag). However, laboratory tests have indicated that the Pb-Zn slag contains a very uneven valuable metals amounts, ranging from several g/ton to several tens of g/ton. The main issue is that traditional metallurgical procedures for releasing beneficial elements are not commercially viable since the valuable elements are "trapped" within amorphous aluminosilicates or intergrowths of alloy grains and glassy phases. Gravity concentration (Wilfley 13 shaking table) and magnetic separation (Davis separator and disk separator) were used to obtain the final concentrate following comminution and grindability testing. The gravity concentration proved more effective. This streamlined approach of valorizing Pb-Zn slag can reduce the need for hazardous chemicals used in hydrometallurgical refinement operations, as well as the extremely high temperatures required for pyrometallurgical processing. This is the first investigation into the feasibility of this novel approach, which includes direct investigations of the Pb-Zn slag feed using these alternative technologies. After extracting the valuable metals, the amorphous aluminosilicate part of the Pb-Zn slag can be reapplied as an alternative raw material in the building sector, adding to the circularity of the suggested approach..

Continuous-wave photocathode guns are capable of delivering electron beams with high repetition rates and high average currents. However, they are limited by relatively low accelerating gradients and cathode fields. This limitation leads to a larger beam size at the gun exit due to space charge forces, making the beam more sensitive to optical aberrations and posing challenges for low-emittance electron beam transmission. This paper focuses on the aberrations induced by multipole fields. We analyze the effects of quadrupole, sextupole, and higher-order fields on beam profile and transverse emittance and propose a beam-based method for the rapid characterization and correction of these multipole fields. Furthermore, we present an experimental study conducted on the DC-SRF-II photocathode gun equipped with dedicated correctors. Both simulation and experimental results demonstrate that our approach effectively mitigates beam aberrations caused by multipole fields, resulting in improved beam symmetry and reduced emittance.

PET imaging of bacterial infection could potentially provide added benefit for patient care by non-invasive means. [68Ga]Ga-desferrioxamine B – a radiolabelled siderophore – shows specific uptake by human-pathogenic bacteria like Staphylococcus aureus or Pseudomonas aeruginosa as well as sufficient serum stability for clinical application. Here, we provide data for automated production of [68Ga]Ga-desferrioxamine B on two different cassette based synthesis modules (Modular-Lab PharmTracer and GRP 3V) using commercially available cassettes together with an approved 68Ge/68Ga radionuclide generator. Quality control including determination of radiochemical purity as well as a system suitability test was set up via RP-HPLC on a C18 column. The two described production processes, using an acetic acid/acetate buffer system with ascorbic acid as a radiation scavenger for radiolabelling, yield ready-to-use formulations with sufficient activity yield. Batch data showed radiochemical purity of &gt;95 % as determined by RP-HPLC and ITLC as well as excellent stability over 2 hours post production. Specifications for routine production were set up and validated with four master batches for each synthesis module. Based on this study, an academic clinical trial for imaging of bacterial infection was initiated. Both described synthesis methods enable reproducible, automated in-house production of [68Ga]Ga-desferrioxamine B for clinical application.

The causes of pediatric cancers often remain unknown; however, due to the development of medicine and technology, genetic disorders may play a crucial role in the genesis of neoplasms. Over time, the number of cancer predisposition syndromes (CPS) and awareness of them are increasing, providing the possibility of cancer prevention and early detection. In this study, we presented data concerning the number and type of oncological cases and their correlation with CPS occurrence in a cohort of Central and Eastern European pediatric population. The data were collected between 2000 and 2019 at the Karol Jonscher Clinical Hospital of Poznan University of Medical Sciences, resulting in a cohort of 2,190 cases in total, of which 193 children (8.81%) were confirmed to have CPS. CPS occurred most frequently in infancy (22.90% of all children suffering from any diagnosed cancer during the first year of life, p &lt; 0.0001), accounting for more than a quarter of all CPS cases in our cohort. CPS were least likely to be observed in patients aged 14 and 15 years (2.17% and 2.44% of children diagnosed with any of the listed cancers at the exact age, respectively, p &lt; 0.05). Among CPS, the most common were neurofibromatosis type I (NF1), Li-Fraumeni syndrome (LFS), and Down syndrome (DS). To conclude, it is important to emphasize the need for personalized treatment for each patient affected by both CPS and subsequent cancer in order to reduce the toxicity of therapy and improve quality of life by reducing the risk of side effect.

The study of biologically active substances from natural sources shows the prospect of obtaining a new type of antimicrobial agents, highly effective against pathogenic microorganisms and non-toxic to humans. Our study reveals for the first time that Cornu aspersum mucus has the potential to act as a source of antibacterial agents against bacterial pathogens such as Bacillus cereus 1085, Propionibacterium acnes 1897, Salmonella enterica 8691, Enterococcus faecalis 3915, and Enterococcus faecium 8754. Both mucus fractions with MW<20 kDa and MW>20 kDa showed antimicrobial activity and antioxidant properties that’s why they can be turned into an alternative agent to expensive synthetic antibacterial compounds. Using de novo sequencing 16 novel peptides with potential antibacterial activity were identified by in a fraction with MW<20 kDa. The results of electrophoretic and proteomic analysis of mucus fraction with MW >20 kDa presented proteins with potential antibacterial activity highly homologous to hemocyanins, mucus protein Aspernin, lectins, L-amino acid oxidase-like protein, and mucins (mucin-5AC, mucin-5B, mucin-2 and mucin-17). Thanks to the synergistic action of the bioactive components, the mucus fraction with MW > 20 kDa in low concentrations per 8–2 µg/mL showed promising antimicrobial activity against the tested bacteria, comparable to Vancomycin and without unwanted cytotoxic effects against non-target cells. Additionally, C. aspersum mucus fractions were found to have a positive effect on eukaryotic organisms by reducing the levels of intracellular oxidative damage and increasing the antioxidant capacity of the cell. These findings could serve as a basis for the development of a potent non-cytotoxic antibacterial agent to replace conventional antibiotics and avoid the development of antibiotic resistance.

This paper proposes a novel facial expression recognition network called the Lightweight Facial Network with Spatial Bias (LFNSB). The LFNSB model balances model complexity and recognition accuracy. It has two key components: a lightweight feature extraction network (LFN) and a Spatial Bias (SB) module for aggregating global information. The LFN introduces combined channel operations and depthwise convolution techniques, effectively reducing the number of parameters while enhancing feature representation capability. The Spatial Bias module enables the model to focus on local facial features while also capturing the dependencies between different facial regions. Additionally, a novel loss function called Cosine-Harmony Loss is designed. This function optimizes the relative positions of feature vectors in high-dimensional space, resulting in better feature separation and clustering. Experimental results on the AffectNet and RAF-DB datasets show that the proposed LFNSB model performs excellently in facial expression recognition tasks. It achieves high recognition accuracy while significantly reducing the number of parameters, thus substantially lowering model complexity.

Introduction: The balance of bioelements is crucial as it ensures the organism's homeostasis and proper execution of reactions within the body, nerve conductivity, and correct polarity of cell membranes, but it is also very important for fertility. It is known that disturbances in the balance of bioelements lead to reproductive dysfunction. In women, changes in the composition of follicular fluid can occur, which can lead to limited follicular growth and lack of oocyte activation. Objective: The main objective was to examine whether the concentration of bioelements Na, K, Ca, Mg, and Fe in follicular fluid influences the outcome of the in vitro fertilization process. Methods: The study involved 120 female patients undergoing in vitro fertilization. Follicular fluid obtained after follicle aspiration in the ovaries was used as biological material for analysis. The values of Na (selective electrode method), K (selective electrode method), Ca (arenajo method), Mg (spectrophotometric method), and Fe (colorimetric method) in follicular fluid were determined using the AU 680 apparatus, Beckman Coulter. Istanbul Consensus criteria for clinical embryologists were used to assess embryo quality. Statistical analysis was performed using the SPSS 20 software package. Results: Analysis of follicular fluid samples showed no correlation between the concentration of bioelements in follicular fluid and the quality of oocytes or the outcome of in vitro fertilization. Conclusion: Based on our results, it can be concluded that the concentration of bioelements in follicular fluid does not affect the outcome of in vitro fertilization.

The physical properties of a structure such stiffness although can be determined by some statical tests, the identification of damping parameter requires a dynamic test. In general, both theoretical prediction and experimental identification of damping are quite difficult. There are many different techniques available for damping identification, and each method gives a different damping parameter. The dynamic indentation method, rheometry, atomic force microscopy, and resonant vibration tests are commonly used to identify the damping of materials, including soft materials. While the viscous damping ratio, loss factor, complex modulus and viscosity are quite common to describe damping of materials, there are also other parameters such as the specific damping capacity, loss angle, half-power bandwidth, and logarithmic decrement to describe damping of various materials. Often one of these parameters is measured in practical applications and the measured damping parameter needs to be converted into another damping parameter for comparison purposes. In this review, the theoretical derivations of different parameters for the description and quantification of damping and their relationships, and the methods for damping identification are presented. The expressions for both high damping and low damping are included and evaluated. This paper could be a primary resource for damping research and teaching.

Currently, there is a tenacious need to find new ways to purify water by eliminating bacterial biofilms, textile dyes, and toxic water pollutants. These contaminants pose significant risks to both human health and the environment. To address this issue, in this study, we have developed an eco-friendly approach that involves synthesizing Cobalt-doped Cerium Iron Oxide (CCIO) nanocomposite (NC) using an aqueous extract of Gossypium arboreum L. stalks. The resulting nanoparticles can be used to effectively purify water and tackle the challenges associated with these harmful pollutants. Nanoparticles excel in water pollutant removal by providing high surface area for efficient adsorption, versatile design for simultaneous removal of multiple contaminants, catalytic properties for organic pollutant degradation, and magnetic features for easy separation, offering cost-effective and sustainable water treatment solutions. CCIO nanocomposite has been synthesized by green co-precipitation method due to biomolecules and co-enzymes present in the aqueous extract of Gossypium arboreum L. stalk; a single-step procedure completed in 5 h reaction time. Further, the synthesis of nanocomposites was confirmed by various characterization techniques such as Fourier-transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), Field emission scanning electron microscopy (FE-SEM), Transmission electron microscopy (TEM), Thermogravimetric analysis (TGA), Dynamic light scattering (DLS), and Energy Dispersive X-Ray (EDX). CCIO NCs were discovered to have a spherical shape and an average size of 40 nm. Based on DLS zeta potential analysis, CCIO NCs were found to be anionic. Also, CCIO NCs showed significant antimicrobial and antioxidant activity. Overall, considering the physical and chemical properties, the application of CCIO NCs in the adsorption of various dyes (~91 %) and water pollutants (chromium = ~ 60 %) has been considered since they exhibit great adsorption capacity owing to their microporous structure which can be a step forward in water purification.

In pattern recognition domain, deep architectures are widely used nowadays and they have achieved fine grades. However, these deep architectures need special demands, especially big datasets and GPU. Aiming to gain better grades without deep networks, we propose a simplified algorithm framework using fusion features extracted from the salient areas of faces. Furthermore, the proposed algorithm has achieved a better result than some deep architectures. For extracting more effective features, this paper firstly defines the salient areas on the faces. This paper normalizes the salient areas of the same location in the faces to the same size, therefore it can gain more similar features from different subjects. LBP and HOG features are extracted from the salient areas, fusion features’ dimensions are reduced by Principal Component Analysis( PCA) and we apply softmax to classify the six basic expressions at once. This paper proposes a salient areas definitude method which uses peak expressions frames to compare with their neutral faces. This paper also proposes and applies the idea of normalizing the salient areas to align the specific areas which express the different expressions. This makes the salient areas found from different subjects have the same size. Besides, gamma correction method is firstly applied on LBP features in our algorithm framework which improves our recognition rates significantly. By applying this algorithm framework, our research has gained state-of-the-art performances on CK+ database and JAFFE database.

Background/Aim: Uterine leiomyoma, also known as fibroids, is the most common benign neoplasm of the female genital tract. Leiomyoma, including its subtypes, is the most common uterine tumor. The subtypes account for approximately 10% of leiomyomas. Intravenous leiomyomatosis, a uterine leiomyoma subtype, is an intravascular growth of benign smooth muscle cells, occasionally with pelvic or extrapelvic extension. Uterine leiomyosarcoma, a malignant tumor, tends to metastasize hematogenously, and distant metastasis to the lungs and liver is common. Therefore, this intravenous leiomyomatosis’ oncological features resemble those of the malignant tumor uterine leiomyosarcoma. Cancer stem cells migrate to distant organs via intravascular infiltration, leading to micrometastases. Materials and Methods: We examined the oncological properties of intravenous leiomyomatosis using molecular pathological techniques on tissue excised from patients with uterine leiomyoma. Result: CD44-positive mesenchymal tumor stem-like cells were detected in both intravenous leiomyomatosis and uterine leiomyosarcoma. The oncological nature of intravenous leiomyomatosis was found to be similar to the oncological properties of uterine leiomyosarcoma. However, in intravenous leiomyomatosis, Cyclin E and Ki-67-positive cells were rare, and no pathological findings suspected to be malignant were observed. Conclusion: It is expected that establishing a treatment method targeting cancer stem cells will lead to the treatment of malignant tumors with a low risk of recurrence and metastasis.

The aim of the present study was to investigate the incidence of breast (females), prostate, testicular and thyroid cancer in the Italian National Priority Contaminated Sites (NPCSs), served by cancer registries, where the presence of endocrine disruptors (EDs), reported to be linked to these tumors, was documented. Evidence of carcinogenicity of EDs present in NPCs was assessed based on evaluation by international scientific institutions/committees. Standardized Incidence Ratios (SIRs) were computed for each NPCS and cancer site with reference to the time window 1996-2005. Excess incidence of one or more cancer site at study was found in twelve out of fourteen NPCSs. Significantly increased SIRs were found for breast cancer in eight NPCSs, for prostate cancer in six, for thyroid cancer (both gender) in four and for testicular cancer in two. Non significantly increased SIRs were found in five NPCSs for testicular cancer and in two for thyroid cancer (males). Even if increased incidence of one or more cancer sites at study were found in several NPCSs, the ecological study design and the multifactorial etiology of the considered tumors do not allow reaching conclusions in terms of causal links with environmental contamination. In light of the observation of some excesses in SIRs, continuing epidemiological surveillance is warranted.

MicroRNAs are small non-coding RNAs, which contribute to the regulation of many physiolog-ical and pathological processes. Conventionally, miRNAs perform their activity in the cyto-plasm, where they regulate gene expression by interacting in a sequence-specific manner with mature messenger RNAs. Recent studies point to the presence of mature miRNAs in the nucleus. This review summarizes current findings regarding the molecular activities of nuclear miRNAs. These molecules can regulate gene expression at the transcriptional level by directly binding DNA on the promoter or the enhancer of regulated genes. MiRNAs recruit to these regions dif-ferent protein complexes, resulting both in activation or repression of transcription, through a number of molecular mechanisms. Haematopoiesis is presented as a paradigmatic biological process whereby nuclear miRNAs possess a relevant regulatory role. Nuclear miRNAs may af-fect gene expression also acting on nuclear mRNA processing and on the biogenesis of miRNA themselves by regulating pri-miRNA maturation. Overall, nuclear miRNAs are biologically ac-tive molecules that can be critical for the fine tuning of gene expression and deserve further studies in a number of physiological and pathological conditions

This article presents a new input device for spastic patients and others with similar symptoms. The sensor consists of a disc used to determine positions and can replace standard joysticks in medical devices such as electric-powered wheelchairs. Using a standard joystick while operating a powered wheelchair can result in dangerous situations when spastic movements occur and extremities cramp making them uncontrollable. To avoid this, a disc was developed that can be controlled with any body part. By shifting weight (x- and y-axis) the disc can tilt in any direction creating a proportional output signal and can also be pushed down in the center (z-axis) to open a menu on a screen for example. When spasms occur it is impossible for users to get stuck on the input device because the disc is flat and can be mounted within a control panel. Body parts coming into contact with the disc would merely slide across the disc without triggering unintentional actions. The sensor presented here is also adaptive and can be adjusted to fit a user’s strength and range of motion. This proposal aims to develop an input device that enables spastic patients to operate sensitive systems safely.

In this paper, we consider the synchronization of chaotic oscillators interconnected via a second order dynamic coupling. The design of the proposed coupling is inspired in the ancient synchronization experiment of synchronized pendulum clocks, as described by the Dutch scientist Christiaan Huygens more than three centuries ago. It is demonstrated that the coupled chaotic systems may exhibit not only complete synchronization, but also mixed synchronization—some states synchronize in anti-phase whereas other states synchronize in-phase. In fact, a transition from complete synchronization to mixed synchronization or viceversa can be induced by just changing a single parameter in the coupling. Additionally, the stability of the synchronous solution is investigated by using the Master Stability Function approach and the largest transverse Lyapunov exponent. The Lorenz system is considered as particular application example. Finally, the performance of the proposed synchronization scheme is illustrated with computer simulations and validated by means of experiments using electronic circuits.

This work (in two parts) will review the recently developed predictive modeling methodology called “4th-BERRU-PM” and its applicability to energy systems as exemplified by an illustrative application to the Polyethylene-Reflected Plutonium (acronym: PERP) OECD/NEA reactor physics benchmark. The acronym 4th-BERRU-PM designates the “Fourth-Order Best-Estimate Results with Reduced Uncertainties Predictive Modeling” methodology, which yields best-estimate results with reduced uncertainties for the first fourth-order moments (mean values, covariance, skewness, and kurtosis) of the optimally predicted posterior distribution of model results and calibrated model parameters. The 4th-BERRU-PM uses the Maximum Entropy (MaxEnt) principle to incorporate fourth-order experimental and computational information, including fourth (and higher) order sensitivities of computed model responses to model parameters, thus incorporating, as particular cases, the results previously predicted by the second-order predictive modeling methodology 2nd-BERRU-PM, and vastly generalizing the results produced by extant data assimilation and data adjustment procedures. The 4th-BERRU-PM methodology encompasses the scopes of high-order sensitivity analysis (SA), uncertainty quantification (UQ), data assimilation (DA) and model calibration (MC). The application of the 4th-BERRU-PM methodology to energy systems is illustrated by means of the above-mentioned OECD/NEA reactor physics benchmark, which is modeled using the neutron transport Boltzmann equation involving 21976 imprecisely known parameters, the solution of which is representative of “large-scale computations.” The model result (“response”) of interest is the leakage of neutrons through the outer surface of this spherical benchmark, which can be computed numerically and measured experimentally. Part 1 of this work illustrates the impact of high-order sensitivities, in conjunction with parameter standard deviations of various magnitudes, on the determination of the expected value and variance of the computed response in terms of the first four moments of the distribution of the uncertain model parameters. Part 2 of this work will illustrate the capabilities of the 4th-BERRU-PM methodology for combining computational and experimental information, up to and including forth-order sensitivities and distributional moments, for producing best-estimate values for the predicted responses and model parameters while reducing their accompanying uncertainties.

Kisspeptin (KISS1) and its cognate receptor (KISS1R) are implicated in the progression of various cancers. However, a theranostic radiopharmaceutical targeting the KISS1 receptor (KISS1R) has yet to be explored. A gallium-68 labelled kisspeptin-10 (KP10) has potential as a pan-tumor radiopharmaceutical for the detection of cancers. Furthermore, a lutetium-177 labelled KP10 could find therapeutic application in treating oncological diseases. We attached DOTA to the NH2-terminus of KP10 as we posited that this modification would not impair biological activity and showed that receptor stimulation of inositol phosphate accumulation in HEK293 transfected with the KISS1R gene was similar for KP10 and DOTA-KP10. We describe optimization of radiolabeling with gallium-68 and lutetium-177 and stability in serum, plasma, and whole blood. Pharmacokinetics was established with µPET/CT and ex vivo measurements. Dynamic studies with µPET/CT demonstrated that background clearance for the radiopharmaceutical was rapid with a blood half-life of 18 ± 3 minutes. DOTA-KP10 demonstrated preserved functionality at KISS1R and good blood clearance. These promising results advocate the further development of KP10 structures which have high binding affinity along with proteolytic resistance.

Hereditary hemochromatosis (HH) is the main genetic cause of iron overload and is regarded as metal-related human toxicosis. HH may result from HFE and non-HFE gene mutations causing hepcidin deficiency or hepcidin resistance. The disorder has a high biochemical penetrance, but a low clinical prevalence. Unfortunately, the majority of patients with HH remain undiagnosed at their disease-curable stage. The main aim of HH therapy is to prevent iron overload in the early-phase disease and elimination of excess iron from the body by phlebotomy in its late stage. Raising global awareness of HH among health professionals, their training to pay attention to early HH signs and symptoms, and strict patient monitoring are critical management strategies for preventing treatment delays, upgrading its efficacy, and improving patient prognosis.

Objective: To determine the effect of sandblasting before and after sintering on the surface roughness of zirconia and the micro-tensile bond strength of a pressable veneering ceramic to zirconia. Methods: Pre-sintered zirconia blocks (IPS e.max ZirCAD, Ivoclar Vivadent) were divided into a control group (CTR, no surface treatment) and four test groups of three specimens each: Pre-S-30, Pre-S-50, Pre-S-110 were sandblasted with 30µm SiO2, 50µm Al2O3 and 110µm Al2O3 particles respectively, before sintering, Post-S-30 was sandblasted with 30µm SiO2 after sintering. For each treatment, the surface roughness was measured (Ra, Perthometer M4P, Mahr Perthen). After sintering the zirconia blocks, a liner and a pressable ceramic (IPS e.max ZirPress, Ivoclar Vivadent) were fired. Sixteen micro-bars were obtained from each block and submitted to the micro-tensile bond strength (µTBS) test. Data were analyzed with one-way ANOVA. Any correlation between Ra and µTBS was evaluated (Sperman test). Results: Sandblasting before sintering with 110µm Al2O3 (Ra=3.44±0.44µm), 50µm Al2O3 (Ra=2.32±0.46µm), and 30µm SiO2 (Ra=1.22±0.22µm) resulted in significantly higher roughness than sandblasting after sintering with 30µm SiO2 (Ra=0.46±0.11µm). The highest µTBS was measured when the sintered zirconia was sandblasted with 30μm SiO2 (26.79±14.80 MPa), which was significantly different from that of specimens that were sandblasted before sintering (Pre-S-30=20.90±11.70; Pre-S-50=21.27±15.19; Pre-S-110=23.99±16.83) or were not treated (CTR=17.44±14.03). Conclusions: Sandblasting zirconia before sintering enhances the surface roughness proportionally to the particle size of the sand used. Sandblasting with 30µm SiO2 after sintering appeared to improve bonding between the veneering ceramic and zirconia. Clinical Significance: Sandblasting with 30µm SiO2 after sintering may improve bonding between veneering ceramics and zirconia, thus reducing ceramic fractures/chippings.

The isotopic and nuclear techniques discussed, namely: Fallout Radionuclide, Fingerprint, and Isotope Hydrology, are linked to the evaluation of soil and water degradation processes. A traditional literature review was conducted to gain the most comprehensive understanding of both the current state of the art and the subject matter, with the aim of proposing a hypothesis that integrates the synergistic convergence of these techniques in order to offer results that are more reliable. A case study is presented as a synthesis of the preceding discussion.

Antimicrobial peptides represent a promising alternative to traditional drugs in relation to cost, toxicity and, primarily, the growing problem of drug resistance. Here we report on the activity against HSV-1 and HSV-2 of a previously described wide-spectrum synthetic decapeptide, Killer Peptide (KP). As determined by plaque reduction assays, treatment with KP at 100 μg/mL resulted in a reduction in the viral yield titer of 3.5 Logs for HSV-1 and 4.1 Logs for HSV-2. Further evaluation of KP antiviral activity focused on the early stages of virus replicative cycle, including the determination of the residual infectivity of viral suspensions treated with KP. A direct effect of the peptide on viral particles, impairing virus absorption and penetration, was shown. The toxicity profile proved to be extremely good with a selectivity index of 29.6 for HSV-1 and 156 for HSV-2. KP was also active against an acyclovir (ACV)-resistant HSV-1 strain, while HSV-1 subcultures in the presence of sub-inhibitory doses of KP did not lead to the emergence of resistant strains. Finally, the antiviral action of KP proved to be synergistic with that of ACV. Overall, these results demonstrate that KP could represent an interesting addition/alternative to acyclovir for antiviral treatment.

Depressions containing partially molten rocks were investigated in Quaternary pebbly sedi-ments in Alpine foreland in Bavaria, Germany. Ruins of limekilns from 18-19th centuries are abundant around Seeshaupt. They are usually associated with earthworks for fuel feeding and protection from wind. Depressions contain partially molten stones from furnace walls, with lime and burnt loam remnants. On the surface of pebbles (typically gneisses), green glass formed with chemical composition possibly affected by moderately volatile components of wood biomass, mainly K and Cu. Thermoplastic deformation of pebbles is limited and the sur-face melt deformation points to slow flow. At Emmerting, on the other hand, two walled circu-lar depressions which lack additional earthworks have been identified as possible impact cra-ters. Thermally affected pebbles show much more intense deformation. Colorless to greenish glass, also K and Cu enriched, usually forms only thin surface coatings, in places covered by younger melt extruded from pebble interior. Burnt loam is missing. At Grabenstätt-Kaltenbach, a depression of unclear origin was investigated. Morphologically, it matches craters rather than limekilns, but anthropogenic contamination (brick-like material) is probable. The rare molten samples do not display extreme deformation features. The thermally affected stones, mainly those from Emmerting, have elevated magnetic susceptibility.

This paper investigates the effects of various process parameters, specifically the substrate temperature, on weld track geometry in Directed Energy Deposition (DED) processes. A specialized experimental setup integrated within a DED machine facilitates controlled thermal conditioning of sample sheets. Through Design of Experiments (DoE) methods, individual weld marks are generated and analysed to assess geometric characteristics. Regression models are constructed to predict machine parameters for desired weld geometry at different substrate temperatures. Validation experiments confirm the accuracy and reliability of the regression models. Results show a consistent trend towards target geometric features across a broad range of substrate temperatures. Despite deviations in measured values, successful fabrication is achieved, demonstrating robust bonding between weld and substrate. Contact angle predictions exhibit precision within a partial temperature range for proper deposition. The developed model offers insights for optimizing DED process parameters to achieve desired weld characteristics, advancing the capabilities and reliability of additive manufacturing technology. Future work aims to refine the regression model and explore additional mathematical relationships for enhanced accuracy. An implication of this work is the potential to vary the local mechanical properties of parts by controlling the temperature profile while maintaining consistent geometric characteristics. By manipulating the substrate temperature, it may be possible to tailor the microstructure and mechanical properties of fabricated components in the future to meet specific requirements in different regions of the part.

Laser Photoacoustic Spectrometers (LPAS), which provide photoacoustic spectra for detecting food frauds or adulteration, and fluorescence-based systems for recognition of contamination by heavy metal ions in water are two important families of sensors for health and environmental purposes. Both sensor families require one or more low-frequency Lock-In Amplifiers (LIAs) to extract the signal of interest from background noise. In the cited applications, the required LIA frequency is quite low (up to 1kHz), and this leads to a simplification of the hardware with consequent good results in portability, economy, reduced size, weight and low-cost characteristics. The present system, called ENEA DSP Box Due, is based on a very inexpensive microcontroller proto-board and can replace four commercial LIAs, resulting in significant savings in both cost and space. Furthermore, it incorporates a dual-channel oscilloscope and a sinusoidal function generator. This article outlines the architecture of the ENEA DSP Box Due, its electrical characterization and its applications within a project concerning laser techniques for food and water safety.

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.

The evolution of human societal dynamics over the course of decades and centuries has led to an ever-increasingly complex digital modern life, one of the hallmark of which is the need for multi-tasking, inclusive of that with media. Is there an empirical mapping between this macroscopic (digital) evolution of the human societal dynamics (in terms of multi-tasking) and the microscopic evolution of the functional molecular units within cells (i.e., proteins) and their manifold cross-talks? Multi-tasking requires a certain degree of intrinsic or adapted flexibility which is as true at the bio-molecular level. Evolutionary diversification of structure-function relationship in proteins emphasizes the functional importance of intrinsically disordered entities (IDPs/IDRs) which are highly dynamic biological soft matters. Multi-functionality is favorably supported by their fluid-like shapes and other new malleable members of the protein family. The new wealth of knowledge coming from recent research on protein intrinsic disorder, fold-switching, moonlighting, hub proteins etc. has given us new insights into protein structure – functional relationship. This has led to a paradigm shift in protein science, clearly diverging from the traditional 'one structure – one function' model applicable to enzyme classes to a more complex understanding of protein functionality. This paradigm shift has caused scientists to delve deeper into the subject, exploring various evolutionary toys and tools to fit the cumulative multi-functional demands in higher organisms. This commentary covers the different evolutionary arsenals to achieve the growing multi-functionality and argues in favor of protein intrinsic disorder as probably the sharpest weapon of all.

The additional sex combs-like (ASXL) family, a mammalian homolog of the additional sex combs (Asx) of Drosophila, has been implicated in transcriptional regulation via chromatin modifications. Abnormal expression of ASXL family genes leads to myelodysplastic syndromes and various types of leukemia. De novo mutation of these genes also causes developmental disorders. Genes in this family and neighbor genes are evolutionary conserved in humans and mice. This review provides a comprehensive summary of epigenetic regulations associated with ASXL family genes. Their expression is commonly regulated by DNA methylation at CpG islands preceding transcription starting sites. Their proteins primarily engage in histone tail modifications through interactions with chromatin regulators (PRC2, trithorax complex, PR-DUB, SRC1, HP1α, and BET proteins), and with transcription factors, including nuclear hormone receptors (RAR, PPAR, ER, and LXR). Recently, non-coding RNAs have been identified following mutations in the ASXL1 or ASXL3 gene, along with circular ASXLs and microRNAs that regulate ASXL1 expression. The diverse epigenetic regulations linked to ASXL family genes collectively contribute to tumor suppression and developmental processes. Our understanding of ASXL-regulated epigenetics may provide insights into the development of therapeutic epigenetic drugs.

Background/Objectives: This study aimed to identify various risk factors associated with breast cancer and explore different treatment strategies based on socio-economic, hormonal, and clinical perspectives.; Methods: We analyzed socio-economic, hormonal, genetic, and clinical variables using data from 356 questionnaires obtained from breast cancer patients at Hassan II Regional Hospital in Agadir, Morocco ; Results:The study reveals that the average age of breast cancer patients is 50 ± 10.72 years, with a mode of 47 years and an age range from 29 to 94 years. Notably, women aged 38 are most frequently diagnosed with triple-negative breast cancer. Significant socio-economic trends were observed among the participants, with the majority being housewives (91%) and nearly half residing in rural areas (48.60%). High rates of illiteracy (74.72%) and financial difficulties (54.2%) pose challenges in accessing healthcare services. Psychological distress is prevalent, with 40.7% experiencing anxiety and 30.1% experiencing sadness. The use of oral contraceptives varies, with implications for breast cancer risk. Additionally, statistics on menarche and menopause suggest hormonal influences on breast cancer development. Histological analysis indicates a predominance of grade II invasive ductal carcinoma and left breast localization. Metastases are present in nearly 38.20% of cases. Notably, surgery as the primary treatment effectively treats medium-sized tumors while limiting metastasis. Furthermore, a comparison of treatment strategies reveals a preference for letrozole among postmenopausal patients and tamoxifen among premenopausal patients; Conclusions:These findings highlight the complexity of breast cancer risk factors and therapeutic approaches, emphasizing the importance of personalized care and targeted interventions.

The nuclear fusion reaction can be catalyzed in a suitable fusion fuel by muons(heavy electron)."For the fractal relation, ranging from DNA knots to solar neutrino flux signals" ever derived f scale-invariant properties distinguished between classical invariant theory & quantum invariant theory subfactors. Accompanying isomorphicity & Connes Fusion Tensor Product retrieved to muon-catalyzed fusions where surroundings of room temperature fusion driven by the balance in mt-Dna fusion &fission.

Semantic image segmentation has recently witnessed considerable progress by training deep convolutional neural networks (CNNs). The core issue of this technique is the limited capacity of CNNs to depict visual objects. Existing approaches tend to utilize approximate inference in a discrete domain or additional aides and do not have a global optimum guarantee. We propose the use of the multi-label manifold ranking (MR) method in solving the linear objective energy function in a continuous domain to delineate visual objects and solve these problems. We present a novel embedded single stream optimization method based on the manifold ranking (MR) model to avoid approximations without sacrificing expressive power. In addition, we propose a novel network, which we refer to as dual multi-scale manifold ranking (\textbf{DMSMR}) network, that combines the dilated, multi-scale strategies with the single stream MR optimization method in the deep learning architecture to further improve the performance. Experiments on high resolution images, including close-range and remote sensing datasets, demonstrate that the proposed approach can achieve competitive accuracy without additional aides in an end-to-end manner.

Introduction/Aim: Central sensitivity to thyroid hormones refers to the sensitivity of the hypothalamic-pituitary-thyroid (HPT) axis to changes in circulating free thyroxine (fT4). The relationship between fT4 levels and iodine intake is complex. The aim of the present study was to assess central sensitivity to thyroid hormones in pregnancy against iodine intake. Materials & Methods: One thousand one hundred two blood and urine samples were collected from pregnant women (with a mean age+SD of 30.4+4.6 years) during singleton pregnancies; women with known/diagnosed thyroid disease were excluded. Specifically, TSH & fT4 and 24-hour urinary iodine excretion (UI) were measured in each trimester and at two months postpartum. The Thyroid Feedback Quantile-based Index (TFQI) was calculated to assess central sensitivity to thyroid hormones. For the statistical analysis of TFQI by time period, analysis of variance (ANOVA) was used, while Pearson's correlation was used to assess TFQI versus UI. Results: The mean TFQI index ranged from -0.06 (first trimester) to -0.07 (two months postpartum), while the corresponding UI was 141 and 172 μg/L, respectively. The TFQI-UI correlation was negative (Pearson r: -0.325, p: 0.04 and r: -0.399, p: 0.023), for UI values over 250 μg/L, in the first and the third trimester of pregnancy, respectively. Discussion: TFQI is a new index reflecting central sensitivity to thyroid hormones. Lower TFQI indicates higher sensitivity to thyroid hormones. In our sample TFQI was inversely related to iodine intake, in the first trimester of pregnancy (the critical period of organogenesis) and the third trimester (the critical period of fetal growth). Thus, the observed changes in TFQI may reflect different ways of central action of thyroid hormones, according to the phase of pregnancy. The negative association between maternal TFQI (indicative of central sensitivity to thyroid hormone) and urine iodine levels during the third trimester of pregnancy may reflect the combined influence of maternal and fetal thyroid function. Our results are intriguing and have the potential to enhance our comprehension of the changes in the HPT axis’ function via variations in central sensitivity to thyroid hormones and its interplay with nutritional iodine status during pregnancy.

The oncogenes that are expressed in gliomas reprogram particular pathways of glucose, amino acid, and fatty acid metabolism. Mutations in isocitrate dehydrogenase genes (IDH1/2) in diffuse gliomas are associated with abnormally high levels of 2-hydroxyglutarate (2-HG) levels. The aim of this study was to determine whether metabolic reprogramming associated with IDH mutant gliomas leads to additional 1H MRS-detectable differences between IDH1 and IDH2 mutations and to identify metabolites correlated with 2-HG. A total of 21 glioma patients (age= 3711, 13 males) were recruited for MRS using a Semi-localization by adiabatic selective refocusing pulse sequence at ultra-high-field (7T). Tumour mutation subtype was confirmed by immunohistochemistry and DNA sequencing. LCModel analysis was applied for metabolite quantification. A two-sample t-test was used for metabolite comparisons between IDH1 (n=15) and IDH2 (n=5) mutant gliomas. The Pearson correlation coefficients between 2-HG and associated metabolites were calculated. A Bonferroni correction was applied for multiple comparison. IDH2 mutant gliomas have a higher level of 2-HG/tCho (total choline=phosphocholine+glycerylphosphorylcholine) (2.481.01vs.0.720.38, Pc<0.001) and myo-Inositol/tCho (2.700.90vs.1.460.51, Pc=0.011) compared to IDH1 mutation gliomas. Associated metabolites, myo-Inositol and glucose+taurine were correlated with 2-HG levels. These results show improved characterization of the metabolic pathways in IDH1 and IDH2 gliomas for precision medicine.

In this work, the surface of poly(ethylene terephthalate) track-etched membranes (PET TeMs) with pore sizes of 670-1310 nm was hydrophobized with 2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoroheptyl acrylate (DFHA) by photoinitiated graft polymerization. Attenuated total reflection FTIR spec-troscopy (ATR-FTIR), scanning electron microscopy (SEM) coupled to an energy-dispersive X-ray spectrometer (EDX), and contact angle measurement were used to identify and characterize the TeMs. The optimal parameters for graft polymerization were determined as follows: polymeriza-tion time 60 min, monomer concentration of 30% and distance from the UV-source 7 cm. The wa-ter contact angle of the modified membranes reached 97° which is 51o for pristine membranes. The modified membranes were tested for water desalination using direct contact membrane distillation (DCMD) method. The effect of membrane pore size, the degree of grafting and salt concentration on the performance of membrane distillation process was investigated. According to the results obtained, it has been concluded that large pore size hydrophobic TeMs modified by using DFHA could be used for desalinating water.

With reference to electromagnetic interaction and Abdus Salam’s strong (nuclear) gravity, 1) Square root of ‘reciprocal’ of the strong coupling constant can be considered as the strength of nuclear elementary charge. 2) ‘Reciprocal’ of the strong coupling constant can be considered as the maximum strength of nuclear binding energy. 3) In deuteron, strength of nuclear binding energy is around unity and there exists no strong interaction in between neutron and proton. $G_s\cong 3.32688\times {10}^{28}{\mathrm{m}}^3{\mathrm{kg}}^{-1}{\sec }^{-2}$ being the nuclear gravitational constant, nuclear charge radius can be shown to be, $R_0\cong \frac{2G_s{m}_p}{c^2}\cong 1.24\mathrm{fm}.$ $e_s\cong \left(\frac{G_s{m}_p^2}{\hslash c}\right)e\cong 4.716785\times {10}^{-19}\mathrm{C}$ being the nuclear elementary charge, proton magnetic moment can be shown to be, ${\mu }_p\cong \frac{e_s\hslash }{2m_p}\cong \frac{e{G}_s{m}_p}{2c}\cong 1.48694\times {10}^{-26}\mathrm{J}{.\mathrm{T}}^{-1}.$ ${\alpha }_s\cong {\left(\frac{\hslash c}{G_s{m}_p^2}\right)}^2\cong 0.1153795$ being the strong coupling constant, strong interaction range can be shown to be proportional to $\exp \left(\frac{1}{{\alpha }_s^2}\right).$ Interesting points to be noted are: An increase in the value of ${\alpha }_s$ helps in decreasing the interaction range indicating a more strongly bound nuclear system. A decrease in the value of ${\alpha }_s$ helps in increasing the interaction range indicating a more weakly bound nuclear system. From $Z\cong 30$ onwards, close to stable mass numbers, nuclear binding energy can be addressed with, ${\left(B\right)}_{A_s}\cong Z\times \left\{\left(\frac{1}{{\alpha }_s}+1\right)+\sqrt{\sqrt{30\times 31}}\right\}\left(m_n-m_p\right)c^2\approx Z\times 19.66\mathrm{MeV}.$ With further study, magnitude of the Newtonian gravitational constant can be estimated with nuclear elementary physical constants. One sample relation is, $\left(\frac{G_N}{G_s}\right)\cong \frac{1}{2}{\left(\frac{m_e}{m_p}\right)}^{10}\left[\sqrt{\frac{G_F}{\hslash c}}/\left(\frac{\hslash }{m_{e}c}\right)\right]$ where $G_N$ represents the Newtonian gravitational constant and $G_F$ represents the Fermi’s weak coupling constant. Two interesting coincidences are, ${\left(m_p/m_e\right)}^{10}\cong \exp \left(1/{\alpha }_s^2\right)$ and $2G_s{m}_e/c^2\cong \sqrt{G_F/\hslash c}.$

Diabetic patients need long-term and frequent glucose monitoring to assist in insulin intake. The current finger-prick devices are painful and costly which make noninvasive glucose sensors highly demanded. In this review paper, we discuss several advanced electromagnetic (EM) wave based technologies for noninvasive glucose measurement, including infrared (IR) spectroscopy, photoacoustic (PA) spectroscopy, Raman spectroscopy, fluorescence, optical coherent tomography (OCT) and microwave sensing. Development and progress of each method are discussed regarding fundamental principle, system setup and experimental results. Despite the promising achievements reported previously, there is no established product to obtain FDA approval or survive marketing test. Limitations and prospects of these techniques are discussed at the end of this review.

Dopaminergic replacement therapy remains the mainstay of symptomatic treatment for Parkinson’s disease (PD), but many unmet needs and gaps remain. Device based treatments or device-aided non-oral therapies are typically used in the advanced stages of PD, ranging from stereotactic deep brain stimulation to levodopa or apomorphine infusion therapies but there are concerns due to a number of procedural, hardware, or long-term treatment-related side effects of these treatments, and limited nonmotor benefit in PD. Therefore, there is an urgent unmet need for low risk adjuvants or standalone therapies which can address the range of burdensome motor and nonmotor symptoms that occur in PD. Recent studies suggest that non-invasive neurostimulation of the vestibular system may be able to address these gaps with stimulation of the vestibular brainstem sensory network which extensively innervates brain regions regulating both motor and a range of nonmotor functions. Therapeutic non-invasive vestibular stimulation is a relatively modern concept that may potentially improve a broad range of motor and nonmotor symptoms of PD, even at early stages of the disease. Here we review previous studies supporting the therapeutic potential of vestibular stimulation for the treatment of PD and discuss ongoing clinical trials and potential areas for future investigations.

Liver X receptors (LXR) are deemed as potential drug targets for atherosclerosis, whereas a role in adipose tissue expansion and its relation to insulin sensitivity remains unclear. To assess the metabolic effects of LXR activation, C57BL/6 mice on a high-fat diet (HFD) were treated with the dual LXRα/β agonist T0901317 (30 mg/kg per day) for 3 weeks. Differentiated 3T3-L1 was used for analysing the effect of T0901317 on glucose uptake.T0901317 reduced fat mass, accompanied by a massive fatty liver and lower adipokine levels in circulation of HFD mice. Increased adipocyte apoptosis and macrophage infiltration were found in epididymal fat of T0901317-treated HFD mice. In addition, T0901317 treatment promoted basal lipolysis, but blunted the anti-lipolytic action of insulin. Furthermore, LXR activation antagonized PPARγ target genes in epididymal fat and PPARγ-PPRE binding activity in 3T3-L1 adipocytes. Although the glucose tolerance was comparable to that in vehicle-treated HFD mice, the insulin tolerance was significantly decreased in T0901317-treated HFD mice, indicating decreased insulin sensitivity by T0901317 administration, and which was further supported by impaired insulin signalling found in epididymal fat and decreased insulin-induced glucose uptake in 3T3-L1 by T0901317administration. These findings reveal that LXR activation impairs adipose expansion which contributes to decreased insulin sensitivity.

This study investigates resource adequacy and renewable energy integration in the United States, European Union, and Pakistan amid global energy market liberalization and greenhouse gas re-duction efforts. It explores how these regions are adapting to the surge in renewable sources like wind and solar, which, despite their financial and environmental benefits, challenge resource adequacy and the economic viability of traditional energy sources. In the US and EU, significant improvements have been introduced in wholesale electricity markets and capacity accreditation mechanisms, which enhanced the large-scale deployment of renewables. This shift has prompted a reevaluation of resource adequacy, leading to increased deployment of battery storage and demand response. Presently, gas-based generation is largely upholding resource adequacy, however, future trends indicate a move towards greater consumer participation, energy efficiency, and utility-scale storage, with a decline in fossil fuel use. Pakistan aims to adopt a liberalized market structure by balancing competitive markets with legacy contracts. Public pressure is driving a shift from costly fossil-based generation to renewables. Similarly, a trend in the rise of behind-the-meter solar generation can be witnessed. In future, Pakistan may also experience resource adequacy challenges. It will likely need to implement battery storage, demand response, and modern capacity accreditation tools, by drawing lessons from developed markets.

In our recent publications pertaining to 4G model of final unification and based on strong and electroweak interactions, we have developed a completely new formula for estimating nuclear binding energy. With reference to currently believed Semi Empirical Mass Formula (SEMF), we call our formula as ‘Strong and Electroweak Mass Formula’ (SEWMF). Our formula constitutes 4 simple terms and only one energy coefficient of magnitude 10.1 MeV. First term is a volume term, second term seems to be a representation of free nucleons associated with electroweak interaction, third term is a radial term and fourth one is an asymmetry term about the mean stable mass number. Considering this kind of approach, nuclear structure can be understood in terms of strong and weak interactions and cold nuclear fusion like complicated concepts can be understood in a theoretical approach positively. In this paper, by considering the accountability of we are making an attempt to improve the applicability and effectiveness of SEWMF. Number 0.00125 being a workable electroweak coefficient for Z=6 to 132 and A=2Z to 3.5Z, number of free nucleons assumed to be associated with electroweak interaction can be expressed as Improved asymmetry term can be expressed as, where represents the light house like stable mass number. With reference to old version, our improved binding energy formula can be expressed as, We are working on its possible modification for mass numbers less than the stable mass numbers. Following this approach, it is possible to show that nuclear binding energy scheme is associated with strong and weak interactions and is practically independent of Coulombic repulsions. Proceeding further, currently believed cold nuclear fusion assumed be associated with hydrated metals can be understood and can be confirmed with strong and weak interactions independent of coulombic repulsions. We are very confident to say that our approach will certainly motivate modern science community in this new direction.

A widely discussed topic in the pathophysiology of thyroid nodules is the role of obesity that leads to increased systemic inflammatory markers. Leptin plays a vital role in forming thyroid nodules and cancer through several mechanisms. Together with chronic inflammation, there is an augmentation in the secretion of tumor necrosis factor (TNF) and cytokines interleukin 6 (IL-6), contributing to cancer development, progression and metastasis. In addition, leptin exerts a modulatory action in the growth, proliferation and invasion of thyroid carcinoma cell lines via activating various signal pathways, such as Janus kinase/signal transducer and activator of transcription, mitogen-activated protein kinase (MAPK) and/or phosphoinositide 3-kinase (PI3K) /protein kinase B (Akt). Through several proposed mechanisms, aberrant endogenous estrogen levels have been suggested to play a vital role in the development of both benign and malignant nodules. Metabolic syndrome triggers the development of thyroid nodules by stimulating thyroid proliferation and angiogenesis due to hyperinsulinemia, hyperglycemia and dyslipidemia. Insulin resistance influences the distribution and structure of the thyroid blood vessels. Insulin growth factor -1 (IGF-1) and insulin affect the regulation of the expression of thyroid genes and the proliferation and differentiation of thyroid cells. TSH can promote the differentiation of pre-adipocytes to mature adipocytes, but also, in the presence of insulin, TSH possesses mitogenic properties. This review aims to summarize the underlying mechanisms explaining the role of obesity in the pathophysiology of thyroid nodules and discuss potential clinical implications.

For centuries, humans have relied on natural products to prevent and treat numerous health issues. However, biologically active compounds from natural sources, such as polyphenols, face significant challenges, including low solubility, rapid metabolism, and instability, which hinder their effectiveness. Advances in science and nanotechnology have provided solutions to overcoming these problems through the use of porous silica materials. These materials possess unique properties, such as a high specific surface area, adjustable particle and pore sizes, and a surface that can be easily and selectively modified. In this review, we summarize and discuss findings on how the pore and particle size, structure, and surface modification of silica materials influence the preparation of efficient delivery systems for biologically active polyphenols from natural sources. The available data demonstrate how parameters such as adsorption capacity, release and antioxidant properties, bioavailability, solubility, stability, etc. of the studied delivery systems could be affected by the structural and chemical characteristics of the porous silica carriers.

In the last three decades the presence of phospholipids in the nucleus has been shown and thoroughly investigated. A great interest raised about nuclear inositol lipids mainly because of their role in signalling acting. Here we review the main issues of nuclear phospholipid localization and the role of nuclear inositol lipids and their related enzymes in cellular signaling both in physiological and pathological conditions.

Sustainable continuous cover forestry is defined and analyzed in several ways. The differential equation representing growth of the basal areas of individual trees, motivated by fundamental biological production theory by Lohmander (2017a), is analyzed and extended in different directions. From the solution of the differential equation, the basal area and the tree diameter are obtained as explicit functions of time. The diameter is a strictly increasing function of time. In the absence of competitors, the diameter increment is shown to be a strictly decreasing function of time. Hence, the diameter increment can also be interpreted as a strictly decreasing function of the diameter. Alternative forms of adjustment of the differential equation, with consideration of competition, are defined. If the competition is strong, with large trees in the vicinity of a particular tree, then the basal area increment, and the diameter increment, are reduced. The growth of a large tree is less sensitive than the growth of a small tree, to competition from other trees. Under strong competition, the basal area increment, and the diameter increment, are strictly concave functions of the size of the tree. The unique maximum of the diameter increment occurs at a higher diameter, if the competition increases. In dynamic equilibrium, the tree size frequency distribution is stationary. If natural tree mortality can be avoided via the harvest strategy, the tree size frequency distribution is a function of the size and competition dependent growth function, and the harvest strategy. Empirical tree size frequency data are used to simultaneously estimate parameters of a size and competition dependent growth function and the applied harvest strategy, via nonlinear optimization. The properties of the estimated growth function are consistent with the corresponding properties of the production theoretically motivated hypothetical function, and the properties of the estimated harvest strategy confirm the corresponding hypotheses. The R2 of the nonlinear regression exceeds 0.97. With access to an empirically estimated equilibrium tree size distribution, it is possible to: 1. Estimate size frequency relevant parameters of tree size and competition dependent growth functions for individual trees. 2. Estimate the applied harvest strategy. 3. Explain and reproduce the empirically estimated tree size equilibrium distribution.

Peptides, both natural and synthetic, are well suited for a wide range of purposes and offer versa-tile applications in different fields such as biocatalysts, injectable hydrogels, tumor treatment, and drug delivery. The rising prominence of therapeutic peptides encompasses anticancer, antiviral, antimicrobial, and anti-neurodegenerative properties. The metals Na, K, Mg, Ca, Fe, Mn, Co, Cu, Zn, and Mo are ten of the twenty elements that are considered essential for life. Crucial for under-standing the biological role of metals is the exploration of metal-bound proteins and peptides. Aside from essential metals, there are other, non-essential metals that also interact biologically, exhibiting either therapeutic or toxic effects. Irregularities in metal binding contribute to diseases like Alzheimer’s, neurodegenerative disorders, Wilson's, and Menkes disease. Certain metal com-plexes have potential applications as radiopharmaceuticals. The examination of these complexes was done by preforming UV-Vis, IR, EPR, NMR spectroscopy, and X-ray analysis.

The microstructure evolution during the cold rolling and subsequent annealing of Alloy 800H was investigated. Two distinct rolling methods, unidirectional rolling and cross-rolling, were intro-duced. Results show that better ductility was observed in the unidirectional rolling than in cross-rolling, whilst a higher volume fraction of large deformed grains was observed in the cross-rolled plates than in the unidirectionally rolled plates. Recrystallization occurred faster in plates from unidirectional rolling than from cross-rolling.

In this work, we studied light-output properties, efficiency function as well as PSD capability of p-Terphenyl scintillator. The selected solid cylindrical scintillation detector has a size of (45 x 45) mm with PSD properties. Recently presented studies of light-output functions have been meas-ured only for low neutron energies. Our motivation has been to determine more accurate the light output function for p-Terphenyl scintillator over a wider neutron energy range. The measurements have been carried out with mono-energetic neutron beams in the wide energy range from 2.5 to 19 MeV. The neutron-gamma spectrometric system, which we developed has been used for the measurement. The input analogue signal from the detector is digitized with fast 12-bits analogue to digital converter with sampling frequency of 1 GHz. Measured data from the detector are processed into gamma and neutron spectra. The light output function for protons has been determined by finding the position of the protons for given neutron energies. The more accurate light output function for p-Therphenyl scintillator has been calculated. The pulse-shape discrimination capability as well as efficiency of p-Terphenyl scintillator in comparison with NE-213 equivalent detector is lower.

Thyroid surgery rates have tripled over the past 3 decades making it one of the most frequently performed procedures within general surgery. They are associated with the possibility of serious postoperative complications having a significant impact on the patient's quality of life. The recurrent laryngeal nerve (RLN) palsy and the external branch of the superior laryngeal nerve (EBSLN) palsy are, next to hypoparathyroidism and bleeding after operation, one of the most common complications. The introduction of neuromonitoring into thyroid surgery, enabling both confirmation of anatomical integrity and assessment of laryngeal nerve function, was a milestone that has begun a new era in thyroid surgery. The International Neural Monitoring Study Group made standardization of the technique of RLN and EBSLN monitoring during thyroid and parathyroid surgery which increased prevalence of neural monitoring during thyroidectomy. Current status of IONM and benefits of its use have been presented in this publication.

During pregnancy, profound physiological changes occur in the maternal body, including those affecting oral health. Dental stem cells (DSCs) have emerged as promising candidates for regenerative therapies in dentistry. This manuscript delves into the intricate interplay between DSC behavior and maternal oral health during pregnancy. We provide an overview of current knowledge concerning the impact of pregnancy on DSCs, highlighting their potential roles in maintaining oral homeostasis and responding to pathological conditions. Additionally, we identify key research gaps and propose future directions for investigating novel therapeutic strategies leveraging DSCs to improve maternal and fetal oral health outcomes. By elucidating this relationship, we aim to pave the way for innovative approaches in preventive and regenerative dentistry tailored to the unique needs of pregnant women.

Molecular analysis of growing teratoma syndrome has not been extensively studied. Here, we report a 14-year-old boy with a growing mass during treatment for a mixed germ cell tumor of the pineal region. Tumor markers were negative; thus, growing teratoma syndrome was suspected. A radical resection via the occipital transtentorial approach was performed, and histopathological examination revealed a teratoma with malignant features. Methylation classifier analysis confirmed the diagnosis of teratoma, and DMRT1 loss and 12p gain were identified by copy number variation analysis, potentially elucidating the cause of growth and malignant transformation of the teratoma. The patient remains in remission after intense chemoradiation treatment as a high-risk germ cell tumor.

Multiphoton microscopy (MPM) is a cutting-edge nonlinear microscopy technique known for its exceptional capabilities in imaging dense tissues, making it an ideal tool for exploring human kidney tissue. This study delves into the application of MPM in evaluating renal cell tumors and characterizing tumor capsules. MPM encompasses two core methods: two-photon excitation fluorescence (TPEF) and second harmonic generation (SHG). It leverages femtosecond lasers to provide deep tissue imaging while minimizing phototoxicity, making it well-suited for live tissue analysis. The study analyzed 100 formalin-fixed paraffin-embedded (FFPE) kidney tissue samples, ensuring compliance with ethical standards. Using a Ti:Sapphire laser for femtosecond pulses and a variety of optical components and filters, the researchers captured TPEF and SHG signals, facilitating image analysis. Normal kidney tissue exhibited distinctive structures like glomeruli and tubules under MPM. Renal cell carcinoma (ccRCC) displayed unique TPEF patterns with eccentrically located nuclei and indistinct cytoplasmic membranes. Papillary RCC (pRCC) exhibited a papillary pattern with dark nuclei, while chromophobe RCC (chRCC) showcased distinct features like thick cell membranes, strong TPEF signal in nuclei, and granular cytoplasm. Renal oncocytoma (RO) presented strong TPEF signals in cuboidal cells with microcyst-like arrangements. Overall, MPM proved invaluable in assessing human kidney tissue, offering distinct TPEF patterns for different renal cell tumor types. This non-invasive technique has the potential to enhance pathological examinations and advance our understanding of complex biological processes, ultimately contributing to improved diagnostics and treatment strategies for renal diseases.

Background: We screened key genes involved in the dedifferentiation process of thyroid cancer by analyzing differentially expressed genes in anaplastic thyroid carcinoma (ATC) using Gene Expression Omnibus (GEO) database. Methods: We analyzed differentially expressed genes in ATC from GEO database and constructed a co-expression network using Weighted Gene Co-expression Network Analysis (WGCNA) . Cytoscape was used to calculate top ten key genes based on their gene scores. DEPDC1 was selected as interest gene for further validation, including examination of its prognostic relationship with thyroid cancer, correlation analysis with thyroid differentiation markers, immune cell infiltration, and tumor microenvironment. The impact of DEPDC1 on cancer cell migration, invasion, and proliferation was validated through downregulation and overexpression of DEPDC1 gene in thyroid cancer cell lines c643 and BCPAP. Results: We identified top 10 key genes in ATC: AURKA, TPX2, RACGAP1, MELK, DLGAP5, DEPDC1, KIF2C, NCAPG, CCNB1, and PBK. DEPDC1 showed a strong correlation with the prognosis of thyroid cancer. The odds ratio (OR) for overall survival was 3.5 (P=0.016) in individuals with high DEPDC1 expression, and the OR for disease-free survival was 2.6 (P=0.003). Additionally, the analysis revealed a significant negative correlation between the expression of DEPDC1 and thyroid differentiation markers. Gene Ontology enrichment analysis demonstrated that DEPDC1 co-expressed genes were enriched in cellular processes, cell cycle pathways, and dynamic protein groups. Matrix and immune scoring indicated tumor microenvironment and immune scores were associated with DEPDC1 expression. TIMER2.0 online analysis revealed a strong correlation between DEPDC1 expression and immune cell infiltration in papillary thyroid carcinoma. After downregulation of DEPDC1 expression, the invasion, migration, and proliferation abilities of tumor cells were significantly reduced. Conversely, overexpression of DEPDC1 exhibited the opposite effect. Conclusion: DEPDC1, a newly identified dedifferentiation gene in thyroid cancer, inversely correlated with the degree of differentiation. High expression of DEPDC1 promotes cancer progression and leads to poor prognosis in thyroid cancer.

Background: As noninvasive prenatal screening usage grows in the general obstetrics setting, proper patient education on the screen’s benefits and limitations is needed. Objective: Describe the use of a technology platform designed for large-scale dissemination of noninvasive prenatal screening information and results. Study Design: The technology platform functioned as follows: Patients were emailed a link to an noninvasive prenatal screening general-education video upon laboratory receipt of a test requisition. Providers were then notified upon availability of patients’ results. If noninvasive prenatal screening results were negative, the patient was sent an automated email with instructions to access results through a secure portal where she could watch tailored informational videos, request “on-demand” or scheduled genetic counseling, or decline any further services. If genetic counseling was elected, a summary of the session was sent to the ordering provider and patient upon completion. If noninvasive prenatal screening results were positive, either the ordering provider or a board-certified genetic counselor contacted the patient directly to communicate test results and provide counseling. The number and type of results issued through the platform, the number and type of genetic counseling consultations completed, and factors associated with requesting laboratory-delivered genetic counseling were tracked and analyzed for a 39-month period. Results: Over the study period, 67,122 noninvasive prenatal screening results were issued through the platform, and 4,673 patients elected genetic counseling consultations; 95.2% (n=4,450) of consultations were for patients receiving negative results. Over 70% (n= 3,370) of consultations were on-demand rather than scheduled. Median consultation time was 14 minutes for positive results and six minutes for negative results. A positive screen, advanced maternal age, family history, previous history of a pregnancy with a chromosomal abnormality, and other high-risk pregnancy were associated with the greatest odds of electing laboratory-delivered genetic counseling. Conclusions: By combining web education, automated notifications, and genetic counseling, we implemented a service that effectively facilitates results disclosure for ordering providers. These data demonstrate the capability to deliver noninvasive prenatal screening results, education, and counseling—congruent with management guidelines—to a large population, which is imperative to quality care as uptake increases.

At nuclear scale, we present three heuristic relations pertaining to strong and electroweak coupling constants. With these relations, close to beta stability line, it is possible to study nuclear binding energy with a single energy coefficient of magnitude $\left(\frac{1}{{\alpha }_s}\right)\left[\frac{e^2}{4\pi {\epsilon }_0{R}_0}\right]\approx 10.0\text{MeV}\text{.}$ With reference to up and down quark masses, it is also possible to interpret that, nuclear binding energy is proportional to the mean mass of $\left[\left(2m_u+m_d\right)\text{and}\left(m_u+2m_d\right)\right]\approx 10.0\text{MeV}.$

Multilayered metallic sheets fabricated by hot metal forming processes are attractive structural components in the aerospace and automobile industry. The strength of the mechanical bond between the different layers is critical to the applicability of such components in load bearing applications. While it is well understood that the process conditions such as temperature, deformation and rate of deformation influence the bond strength, a clear functional relationship between these conditions and the bond strength has yet to be established. The objective of the current study is to investigate the joining of Aluminum-6061 alloy specimens by hot compression bonding. Hot compression tests of beam specimen pairs were conducted at different temperatures (300-500℃), with different strains and strain rates (10-2-10-1 [1sec]). Coupled thermo-mechanical finite element models were utilized to compute the time dependent thermo-mechanical fields that develop along the specimen interface. The computed values were used to map the spatial distribution of a scalar parameter J which is hypothesized to govern bond formation. Mechanical tensile tests were used to determine the bond strength and expose the bonded surfaces. It is demonstrated that the computed J distribution can be correlated well with SEM observations of the debonded surface. It is also shown that the actual bonded area can be predicted from the computations for a certain range of critical J values.

The paper describes an application of machine learning approach for parameter optimization. The method is demonstrated for the elasto-viscoplastic model with both isotropic and kinematic hardening. It is shown that the proposed method based on long-short term memory networks enabled to obtain reasonable agreement of stress-strain curves for cyclic deformation in low-cycle fatigue regime. The main advantage of the proposed approach over traditional optimization schemes lies in the possibility to get parameters for a new material without the necessity to conduct any further optimizations. As the power and robustness of the developed method was demonstrated on the very challenging problem (cyclic deformation, crystal plasticity, self-consistent model, isotropic and kinematic hardening), it is directly applicable to other experiments and models.

Appropriate animal models of human diseases are a cornerstone in the advancement of science and medicine. To create animal models of neuropsychiatric and neurobehavioral diseases such as ASD necessitates the development of sufficient neurobehavioral measuring tools to translate human behavior to expected measurable behavioral features in animals. Indeed, at least in rodents, adequate neurobehavioral and neurological tests have been developed. Since ASD is characterized by a number of specific behavioral trends with significant severity, animal models of autistic-like behavior have to demonstrate the specific characteristic features, namely impaired social interactions, and communication, restricted, repetitive behavioral patterns with association to several additional impairments such as somatosensory, motor and memory impairments. Thus, an appropriate model must show behavioral impairment of a minimal number of neurobehavioral characteristics using an adequate number of behavioral tests. The proper animal models enable the study of ASD like-behavior from the etiologic, pathogenetic and therapeutic aspects. From the etiologic aspects, models have been developed by the use of immunogenic substances like polyinosinic-polycytidylic acid (PolyIC), Lipopolysaccharide (LPS) and propionic acid or other well-documented immunogens or pathogens, like mycobacterium tuberculosis. Another approach is the use of chemicals like valproic acid, Polychlorinated biphenyls (PCBs), organophosphate pesticides - chlorpyrifos (CPF) and others. These substances were administered either prenatally, generally after the period of major organogenesis, or, especially in rodents, during the early postnatal life. In addition, using modern genetic manipulation methods, genetic models have been created of almost all human genetic diseases that are manifested by autistic like behavior (i.e. fragile X, Rett syndrome, SHANK gene mutation Neuroligin genes and others). Ideally, we should not only evaluate the different behavioral modes affected by the ASD-like behavior but also assess the severity of the behavioral deviations by an appropriate scoring system, as applied to humans.

Based on PVDF (piezoelectric sensing techniques), this paper attempts to study the propagation law of shock waves in brittle materials during the process of three-wavelength laser irradiation of polysilicon, and discusses the formation mechanism of thermal shock failure. The experimental results show that the vapor pressure effect and the plasma pressure effect in the process of pulsed laser irradiation lead to the splashing of high temperature and high density melt. With the decrease of the laser wavelength, the laser breakdown threshold decreases and the shock wave is weakened. Because of pressure effect of the laser shock, the brittle fracture zone is at the edge of the irradiated area. The surface tension gradient and surface shear wave caused by the surface wave are the result of coherent coupling between optical and thermodynamics. The average propagation velocity of laser shock wave in polysilicon is 8.47×103m/s, and the experiment has reached the conclusion that the laser shock wave pressure peak exponentially distributes attenuation in the polysilicon.

The nuclear hormone family of receptors regulates gene expression. The androgen receptor (AR) shuttles upon ligand binding and homodimerization from the cytosol into the nucleus to activate gene expression. Thyroid hormone receptors(TR), retinoic acid receptors (RAR), and the vitamin D receptor (VDR) are present in the nucleus bound to chromatin as a heterodimer with the retinoid X receptors (RXR) and repress gene expression. Ligand binding leads to transcription activation. The hormonal ligands for these receptors play crucial roles to ensure the proper conduct of very many tissues and exert effects on prostate cancer (PCa) cells. Androgens support PCa proliferation and deprivation alone or with chemotherapy is the standard therapy for PCa. RAR activation and 3,5,3'-triiodo-L-thyronine (T3) stimulation of TR support the growth of PCa cells. Ligand stimulation of VDR drives growth arrest, differentiation, and apoptosis of PCa cells. Often these receptors are explored as separate avenues to find treatments for PCa and other cancers. However, there is accumulating evidence to support receptor interactions and crosstalk of regulatory events whereby a better understanding might lead to new combinatorial treatments.

Telomeres in epithelial tumours are usually maintained by telomerase, however, in the breast cancer MDA-MB-231 cell line, polyploid cells, induced by doxorubicin (DOX) were found, after mitotic slippage, transiently shifting to recombinatory alternative telomere lengthening (ALT) in PML bodies (APBs). The involvement of the meiotic recombination proteins was evidenced here by juxta-co-localisation of SPO11, DMC1 and RAD51/γH2AX with APBs in these and melanoma SkMel28-DOX-treated cells. Using sublethal doses of DOX we also observed the formation of the PML dimeric rod tandems linking γH2AX/TRF2 foci into ribbons discontinuously inserted into lamin B1 and circumventing cell nuclei. Next, we link these PML-lamin B1 insertions and peripheral rotation of the tandemly linked telomere repeats with the mobility of the nuclear envelope limited chromatin sheets (ELCS). ELCSs comprise two layers of the criss-crossed ~30 nm granules derived from surface heterochromatin (epichromatin) which contains telomere repeats enriched in GpC, PML, and ALU. ELCS protrude, circumvent, loop, split, fuse, and rejoin polyploid cell nuclei. We propose this gear-wheel-like turnover of telomere repeats to be used for the homology search. Interstitial and end-telomere repeats flanked by fragile ALU-Z flipons become recognised by SPO11 nuclease, attract TRF2, PML, and meiotic recombinases. Subsequently, they perform ALT recombining subtelomeres and telomeres or undergo non-homologous end-joining and chromosome rearrangements with ELCS. This mechanism increases the chance of cell survival and may be involved in chromothripsis.

The nuclear reactor measurement system is a crucial component of the nuclear measurement system in a nuclear power plant. Its primary function is to measure the power distribution within the reactor core using detectors, calibrate, and provide data on core fuel consumption. Therefore, the study of the detectors' reliability is crucial for ensuring the safe operation of the nuclear power system. The article describes the operational mechanism of the gas ionization chamber detector utilized in the intermediate-range detector of the off-board nuclear measurement system. It also analyzes the movement of particles between the plates during the ionization process of the nuclear reaction taking place in the detector. The functional relationship between the current in the recombination region and the ionization region involved in the actual working condition, and the change with the increase of voltage between the plates, is deduced. A mathematical model is established for the number of pulses generated between the plates and the magnitude of the voltage between the plates. Subsequently, the change in the offset of the voltage corresponding to the inflection point of the ping curve and the change rule of the slope of the ping curve are investigated. Combined with the analysis of experimental data, the results show that the initial particle energy of Ar+, the primary sensitive particle on the detector surface, follows a normal distribution and is influenced by the energy loss associated with the initial velocity and the voltage between the plates. The trends of the inflection points and slopes of the ping curves can be utilized to evaluate the performance and operational status of the detector. Combined with the results of the experimental data analysis, the fit is good, and the inflection point currents in the normal state decrease by about 1.5% annually. The intelligent diagnostic system, based on the method studied in this paper, has been successfully implemented in the RPN digital retrofit and upgrade project at Qinshan No. 2 Plant.

In this paper, the neural network is developed for solving the inverse photoacoustic problem aiming to estimate thermo-elastic properties and thickness of a semiconductor sample. The idea was that these sample properties be estimated from the phase characteristic because the phase measurements are more sensitive. The neural network has been trained on a large basis of photoacoustic phases calculated from a theoretical Si n-type model in the range of 20Hz to 20kHz, on which random Gaussian noise has been applied. It is shown that high accuracy and precision could be reached in solving of inverse photoacoustic problem using only phase measurement.

Aim: This study aimed to investigate the association between periampullary diverticulum (PAD) and difficult biliary cannulation, as well as to evaluate the impact of different types of PAD on the cannulation success rate and adverse events. Methods: A total of 636 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) during the study period were prospectively studied and divided into two groups based on the presence or absence of PAD. In group A, 126 patients had PAD compared with 510 patients in group B without PAD. The primary outcome measurements were ERCP procedures time, selective cannulation techniques, and cannulation difficulty in addition to cannulation success rate and ERCP-related adverse events. The difficult cannulation was analyzed using logistic regression considering age, co-morbidities, the presence of PAD types, and indications as independent factors. Results: The average cohort age was 65.30±16.67 years, and 52.7% were male. Significant higher rates of choledocholithiasis, cholangitis, and biliary pancreatitis were reported in the group of PAD (p<0.05). Successful selective cannulation was achieved in 97.6% in group A and 95.3% in group B (p>0.05). The cannulation time was significantly longer in the presence of PAD (5.1 min, vs. 4.09 min, p<0.05). There was no significant difference in the rate of overall adverse events and post ERCP pancreatic PEP. Conclusion: The presence of PAD did not affect the duration or success of the ERCP procedure. Furthermore, it was associated with longer cannulation time and increase in the cannulation difficulty, especially with PAD type 1.

To support the integration of renewable energy sources and preserve grid stability, this study examines several approaches for controlling the temperature of Battery Energy Storage Systems (BESS) in modern energy settings. Specifically, the usage of BESS in Virtual Power Plants (VPPs) is the focus of this study. The effectiveness, safety features, dependability, affordability, and suitability for VPP applications of these systems are examined. Among the various hybrid cooling alternatives, two particularly promising combinations emerge. Firstly, the integration of heat pipes and phase change materials leverages their ability to conduct heat efficiently away from heat sources with minimal temperature differences, making them excellent for rapid heat transfer. Secondly, an approach employing heat pipes and liquid passive cooling a combination that capitalizes on the efficient heat transfer capabilities of heat pipes and the consistent cooling offered by liquid passive systems. The study underscores the importance of improving BESS performance and sustainability within VPPs by providing useful recommendations for choosing the best thermal management system depending on climate conditions and geographic location.

Probiotics are living microbes that provide benefits to the host. The increasing data on health promotion following probiotics administration triggered growing interest among researchers and pharmaceutical companies looking for novel therapeutic or preventive tools. Infections of the lower genital tract in females are caused by a wide range of pathogens, they are widespread, and represent one of the main areas for the use of probiotics and postbiotics. Vulvovaginal candidiasis (VVC) affects 75% of women in their reproductive age at least once during their lifetime. Of these women 5-8% develop the recurrent form (RVVC). The disease onset is triggered by the overgrowth of Candida species on the vaginal mucosa. Here, we evaluated the beneficial properties of the Bacillus coagulans spore-producing LMG S-24828 against C. albicans and C. parapsilosis. Our results show that both alive B. coagulans and its Cell-Free-Supernatant (CFS) exerted antifungal activity against both fungi. Moreover, alive B. coagulans reduced hyphal formation, inhibited C. albicans adhesion to vaginal epithelial cells and showed co-aggregation capacity. Overall, B. coagulans LMG S-24828 exerted a protective effect on vaginal epithelial cells infected with C. albicans. These data suggest that B. coagulans LMG S-24828 may provide benefits in the context of Candida vaginal infections.

This review provides a comprehensive and updated information on chalcones, presenting their sources, methods of identification and properties putting emphasis on applications in agricultural industry. Vast exploitation of synthetic pesticides led to the weed and pest resistance issue, causing economic loss but more importantly health risk due to pesticide overuse. Because one of the aim of the European Green Deal 2030 is the Farm to Fork strategy which targets on reducing by 50% the use of chemical pesticides by 2030, and push towards natural pesticides which are more environmentally friendly and restore natural resources, chalcones and their derivatives seem to fit perfectly. They have herbicidal, fungicidal, bactericidal and antiviral properties. Moreover, chalcones are naturally occurring substances, known for their favorable health effect for years, working on many areas. This review is complementary to the previous ones describing chalcones use in agriculture, updates them but additionally shows methods of detection.

In this work SiC-Ti3AlC2 and TiC-Ti3AlC2 composites produced by additive manufacturing are investigated. The fused granules fabrication (FGF) method as one of the material extrusion additive manufacturing (MEAM) technology is used to obtain composite samples. Composites with different ratios between components and different powder:polymer ratios are investigated. The technological features of the additive formation of composites are investigated, as well as their structure and properties. The optimal sintering temperature to form the best mechanical properties for both composites is 1300 °C. The composites have a regulatable porosity. Ti3AlC2 content, sintering temperature, and polymer content in the feedstock are the main parameters that regulates the porosity of FGF samples.

Endocrine disruptor compounds are exogenous agents able to interfere with a gland function, exerting their action across different functional passages, from the synthesis to the metabolism and binding to receptors of the hormone produced. Several issues such as different levels and time of exposure and different action across different ages as well as gender, make the study of endocrine disruptors still a challenge. Thyroid is very sensitive to the action of disruptors, and considering the importance of a correct thyroid function for physical and cognitive functioning, addressing this topic should be considered a priority. In this review we examined the most recent studies, many of them concentrating on maternal and child exposure, conducted to assess the impact of industrial chemicals which showed an impact on thyroid function. So far, the number of studies conducted on that topic is not sufficient to provide solid conclusions and lead to homogeneous guidelines. The lack of uniformity is certainly due to differences in areas and populations examined, the different conditions of exposures and the remarkable inter-subject variability. Nonetheless, the European Commission for Health and Food Safety is implementing recommendations to ensure that substances identified as endocrine disruptors will be withdrawn from the market.

Chronic rhinosinusitis (CRS) is a complex inflammatory condition affecting the nasal and paranasal sinus mucosa. Gastroesophageal reflux disease (GERD) has been implicated as a potential exacerbating factor in CRS, but the specific endoscopic features of nasopharyngeal pathology in this context remain poorly understood. Background and Objectives: CRS is a multifactorial disease with various underlying etiologies, including inflammation, anatomical factors, and environmental triggers. While GERD has been suggested as a potential contributor to CRS, the specific endoscopic features indicative of nasopharyngeal pathology in CRS patients with GERD symptoms have not been clearly elucidated. Our aim is to identify specific endoscopic features of nasopharyngeal pathology in patients with CRS associated with GERD symptoms, and to propose a method for assessing the influence of GERD on the mucosal layer of the nose and nasopharynx. Materials and Methods: We conducted a cross-sectional observational study involving 521 adult patients presenting with symptoms suggestive of CRS. From this cohort, 95 patients with the highest scores on the Reflux Symptom Index (RSI) and Reflux Symptom Score-12 (RSS-12) questionnaires were selected as the main group. Endoscopic examinations were performed to assess the nasal and nasopharyngeal mucosa. Results: Our study revealed significant alterations in the nasopharyngeal mucosa of patients with CRS associated with GERD symptoms. Increased vascularity of the nasopharyngeal mucosa was observed in 91 patients (95.7%), while hypertrophy was noted in 83 patients (87.4%). Mucus was present in the nasopharynx of 77 patients (81.1%), exhibiting varying characteristics of color and consistency. Asymmetric hypertrophy of the oropharyngeal mucosa was noted in 62 patients (65.3%). Conclusions: We propose a method for assessing the influence of GERD on the mucosal layer of the nose and nasopharynx, which may aid in diagnostic and management decisions. Further research is warranted to explore the potential impact of GERD symptoms on the course and severity of CRS exacerbations.

In this work, we'll present the power spectra density, auto-correlation function, dentrended fluctuation analysis and multifractal spectrum are performed to the daily light curves of Blazars monitored by Fermi LAT. Some signs of power law are found.

Background and Objectives: Thyroid disease has been associated with autoimmune disorders. As systemic lupus erythematosus (SLE) is a systemic autoimmune disease with diverse manifestations spanning across all organ systems, the relationship of SLE with thyroid disorders needs investigation. In particular, the relationship of SLE with autoimmune thyroid disease has attracted the interest of the research community. The aim was to evaluate the relationship of SLE with autoimmune thyroid disease. Materials and Methods: A cohort of 45 consecutive patients, mean age 47,97 years (range 21-79 years) and 45 age and sex-matched controls were prospectively studied over a period of 12 months for the presence of thyroid disease and the prevalence of antithyroid antibodies. Results: Four patients (8.9%) were found to suffer from primary hypothyroidism, 5 (11.11%) from subclinical hypothyroidism and 1 (2.22%) from hyperthyroidism, whereas 1 (2.22%) of the controls had primary hypothyroidism and 1 (2.22%) had hyperthyroidism. Five patients (11.11%) had a thyroid hormone profile compatible with the presence of euthyroid sick syndrome. Thyroid peroxidase (TPOab) and thyroglobulin (Tgab) antibodies were detected in 20/45 and 15/45 of the SLE population and in 7/45 and 5/45 of the controls, respectively (p&lt;0.05, chi square test). Conclusions: In conclusion, the incidence of clinical thyroid disease is greater amongst SLE patients than in a control population and in a significant number of these patients antithyroid antibodies are detectable. Thus, a subset of lupus patients appears to be predisposed to the development of thyroid disease and this should be considered when evaluating patients with SLE.

Taking into account modern technologies in the mining industry and in the processing of industrial waste, we propose to reprocess cemented low- and intermediate level radioactive waste by extracting all chemical compounds from them. Because of the low cost of space flights in the near future, we propose to use chemical compounds, extracted from radioactive waste, in the production of space electronics and structural materials for automatic space probes and rovers. At the same time, since nano- and micro powders, as well as composites with these fillers, are widely used today in electronics and technology, including in the space industry, the production of radioactive powders and composites will provide new scientific results in the field of materials science and solid-state physics, since nothing is known today about the properties of radioactive powders and composites containing radioactive sources inside.

Investigation of functional magnetic resonance imaging (fMRI) data with machine learning (ML) techniques, including also deep learning (DL) methods, have been widely used to study Autism Spectrum Disorder (ASD). This disorder is characterized by symptoms that affect the individual’s behavioral aspects and social relationships. Early diagnosis is crucial for intervention, but the complexity of ASD poses challenges for treatment development. This study compares traditional ML techniques with deep learning (DL) methods in the analysis of functional connectivity measures obtained from the time series of multicentric ABIDE dataset. Specifically, Support Vector Machines (SVM) classifiers, with both linear and Radial Basis Function (RBF) kernels, as well as eXtreme Gradient Boosting (XGBoost) classifiers, are compared against the TabNet classifier, which is a DL architecture customized for tabular data analysis and a Multi Layer Perceptron (MLP). The findings suggest that DL classifiers may not be optimal for the type of data analyzed, as their performance trails behind that of standard classifiers. SVMs achieve performances, in terms of AUC, around 75%, compared to the best TabNet and MLP results, which are 65% and 71%, respectively. Additionally, this work investigates the brain regions that contribute most to the classification task, which are found to be those primarily responsible for sensory and spatial perception, as well as attention modulation, known to be altered in ASD.