Nucleosomes are non-uniformly distributed across eukarytic genomes, with stretches of ‘open’ chromatin strongly associated with transcriptionally active promoters and enhancers. Understanding chromatin accessibility patterns in normal tissue and how they are altered in pathologies can provide critical insights to development and disease. With the advent of high-throughput sequencing, a variety of strategies have been devised to identify open regions across the genome, including DNase-seq, MNase-seq, FAIRE-seq, ATAC-seq, and NicE-seq. However, the broad application of such methods to FFPE (formalin-fixed paraffin embedded) tissues has been curtailed by the major technical challenges imposed by highly fixed and damaged genomic material. Here we review the most common approaches for mapping open chromatin regions, recent optimizations to overcome the challenges of working with FFPE tissue, and a brief overview of a typical data pipeline with analysis considerations.

Alzheimer’s disease (AD) is a progressive irreversible neurodegenerative disorder that represents a major global public health concern. Traditionally, AD is diagnosed using cerebrospinal fluid biomarker analysis or brain imaging modalities. Recently, less burdensome, more widely available blood biomarker (BBM) assays for amyloid-beta (Aβ42/40) and phosphorylated-tau concentrations have been found to accurately identify the presence/absence of brain amyloid plaques and tau tangles and have helped to streamline AD diagnosis. However, few BBMs have been rigorously analytically validated. Herein, we report the analytical validation of a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying plasma phosphorylated-tau217 (p-tau217) and non-phosphorylated-tau217 (np-tau217) peptide concentrations. We combined the p-tau217/np-tau217 concentrations ratio (%p-tau217) and the previously validated LC-MS/MS assay for plasma Ab42/40 into a new multiple analyte blood test and algorithm (PrecivityAD2™) that identifies brain amyloid status based on brain amyloid positron emission tomography. We found: (a) the %p-tau217 assay is precise, accurate, sensitive, linear over a wide analytical measurement range, and free from carryover and interference; (b) the pre-analytical specimen collection, processing, storage and shipping conditions that maintain plasma tau peptide stability; and (c) using the measured analytical imprecision for plasma Aβ42/40 and p-tau217/np-tau217 levels in a worst-case scenario model, the PrecivityAD2 test algorithm for amyloid pathology classification changed for only 3.5% of participants from brain amyloid positive to negative, or negative to positive. The plasma sample preparation and LC-MS/MS methods underlying the PrecivityAD2 test are suitable for use in the clinical laboratory and valid for the test’s intended purpose: to aid in the diagnostic evaluation of individuals aged 55 and older with signs or symptoms of mild cognitive impairment or dementia.

Computer vision is a rapidly developing field that focuses on highly sophisticated picture analysis, manipulation, and comprehension. Its objective is to analyze what is happening in front of a camera and utilize that understanding to control a computer or robotic system or to present users with fresh visuals that are more enlightening or appealing than the original camera images. Computer vision technologies make it feasible for new user interfaces, augmented reality gaming, biometrics, automobile, photography, movie creation, Web search, and many more applications. This essay seeks to explain how computer vision can be utilized to play blackjack successfully.

Abstract: Endoglin (ENG) is a causative gene of type 1 hereditary hemorrhagic telangiectasia (HHT1). HHT1 patients have arteriovenous malformations (AVMs) in multiple organs, including the brain. In mice, Eng deletion induced by R26RCreER or SM22aCre leads to AVM development in the brain and other organs. We have reported that the severity of brain AVM in mice with activin receptor-like kinase 1 (Alk1, an HHT2 causative gene) mutation is correlated with the number of Alk1 negative endothelial cells (ECs). We hypothesized that increase of Eng negative ECs will enhance AVM severity. To increase EC Eng deletion, we used a codon improved cre (icre), which is more potent in recombination of floxed alleles than the wild type (WT) cre. R26RCreER;Eng^f/f mice that have Rosa promoter driving and tamoxifen (TM) inducible WT cre expression globally and PdgfbiCreER;Eng^f/f that have Pdgfb promoter driving and TM inducible icre expression in ECs were treated with 3 intra-peritoneal injections of TM (2.5 mg/25g of body weight) to delete Eng globally or in the ECs. AAV-VEGF was stereotactically injected into the brain to induce brain focal angiogenesis and brain AVM. We found that iCre caused more Eng deletion in the brain indicated by lower level of Eng proteins (p<0.001) and fewer Eng positive ECs (p=0.01) than mice with WT cre. Mice with iCre mediated Eng deletion have more abnormal vessels (p=0.02), CD68⁺ macrophages (p=0.002), and hemorrhage (p=0.04), and less vascular pericyte and smooth muscle coverage than mice with WT cre. In addition, arteriovenous shunts were detected in the intestines of icre mice, a phenotype that have not been detected in WT cre mice before. RNAseq analysis showed that 8 out of the 10 top upregulated pathways identified by Gene Ontology (GO) analysis are related to the inflammation. Therefore, increase of Eng deletion in ECs exacerbates AVM severity, which is associated with enhanced inflammation. Strategies that can reduce Eng negative ECs could be used to develop new therapies to reduce AVM severity for HHT1 patients.

Lipids have not traditionally been considered likely candidates for catalyzing reactions in biological systems. However, there is significant evidence that aggregates of amphiphilic compounds are capable of catalyzing reactions in synthetic organic chemistry. Here we demonstrate the potential for the hydrophobic region of a lipid bilayer to provide an environment suitable for catalysis by means of a lipozyme, or lipid aggregate capable of speeding up a chemical reaction. By bringing organic molecules into the non-polar or hydrophobic region of a lipid bilayer, reactions can be catalyzed by collections of small, nonpolar or amphiphilic molecules. We demonstrate this concept by the ester hydrolysis of calcein-AM to produce a fluorescent product, which is a widely used assay for esterase activity in cells. The reaction was first carried out in a two phase octanol-water system with the organic phase containing the cationic amphiphiles cetyltrimethylammonium bromide (CTAB) or octadecylamine. The octanol was then replaced with DOPC added to the water in the form of vesicles, where the reaction was also found to be carried out. The reaction was monitored using quantitative fluorescence which revealed catalytic turnover numbers on a scale of 10−4s−1 for each system, which is comparable to some slow enzymes. The reaction product was characterized by 1H-NMR measurements which were consistent with ester hydrolysis. The implications of thinking about lipid aggregates as catalytic entities are discussed in the context of biochemistry, pharmacology and synthetic biology.

Hereditary Hemorrhagic Telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a rare and inherited vascular disorder, characterized by the development of arteriovenous malformations (AVMs) in various organs and telangiectasia (small AVM) in the mucocutaneous. The majority of HHT patients have haploinsufficiency of genes involved in the transforming growth factor-beta (TGFβ) signaling pathway, including endoglin (ENG), activin receptor-like kinase 1 (ALK1, also known as ACVRL1), or SMAD4. Active angiogenesis is also required for telangiectasia and AVM development. Anti-angiogenic strategies have been tested in patients and animal models extensively. However, the exact mechanisms for telangiectasia and AVM development remain unclear. In this review, we discuss recent advances in identifying disease mechanisms, and potential therapeutic targets.

Current sampling methods for detecting the presence of the invasive freshwater hydrozoan Craspedacusta sowerbii rely mainly on visual confirmation of the medusa stage. Confirming the presence of the polyp stage is equally important to observing medusae since typical late summer/early fall occurrences or observations of medusae are sporadic though becoming more frequent. The polyp stage is important as it is the organism’s primary stage and is present throughout the year depending on water temperatures. Therefore, sampling methods for the polyp stage are commonly the collection of substrates such as rocks, plants or pieces of wood in a given body of water and can be cumbersome to examine. Based on preliminary culturing of the polyp stage on glass and plastic microscope slides in the lab, we designed a novel sampling methodology based on submerging 4 substrate types (small glass petri dishes, Hester-Dendy plates, plastic and glass microscope slides) to confirm the presence of C. sowerbii polyps in the field. We tested this method in various lakes in the Illinois-Indiana region (USA). The sampling method we designed was effective in that C. sowerbii polyps (and sometimes colonies) were found on both plastic and glass slides. While this method can be sufficient for detection of the polyp stage, it also shows significant potential for improvement; we highlight water flow and competition and predation from other organisms as significant factors influencing the collection of C. sowerbii polyps for future methodologies.

Purpose: Investigation for the co-occurrence of two unrelated genetic disorders of muscular dystrophy and Prader-Willi syndrome (PWS) (OMIM # 176270) using joint whole genome sequencing (WGS). Methods: Trio WGS joint analysis was performed to investigate the genetic etiology in a proband with PWS, prolonged muscular hypotonia associated hyperCKemia, and early-onset obesity. The parents were unaffected. Results: Results showed maternal isodisomy uniparental disomy (UPD) in chromosome 15 expanding from 15q11.2 to 15q22.2, including PWS regions at 15q11.2-15q13. Maternal heterodisomy was detected from 15q22.2 to 15q26.3. A pathogenic variant, NM_000070.3(CAPN3):c.550del (p.Thr184fs), was identified at 15q15.1 in a heterozygous state in the mother that was homozygous in the proband due to maternal isodisomy. Conclusion: This is the first study of the concurrent molecular etiology of PWS and calpainopathy (OMIM # 253600) in the same patient. This report highlights the utility of joint analysis and need for the assessment of autosomal recessive disease in regions of isodisomy in patients with complex and unexplained phenotype.

Out-of-hospital cardiac arrest (OHCA) represents a significant global public health burden, characterized by low survival and few established diagnostic tools to guide intervention. OHCA presents with a wide variety of etiologies in a heterogeneous population, posing a clinical challenge to care teams. In this review, we describe evolving research focused on diagnostic approaches to OHCA following resuscitation, including electrocardiography, coronary angiography, computed tomography, ultrasonography, and serologic biomarker assessment. These diagnostic tools have been employed in post-resuscitative efforts for diagnosing ischemic and non-ischemic cardiac, respiratory, neurologic, vascular, traumatic, and metabolic causes of arrest.

With the increasing use of data-driven modeling methods new approaches to complex problems in the field of wind energy can be addressed. Topics reviewed through literature include wake modeling, performance monitoring and controls applications, condition monitoring and fault detection, and other data-driven research. Literature shows the advantages of data-driven methods reduce computational expense or complexity, particularly in the cases of wake modeling and controls, as well as various data-driven methodologies’ aptitude for predictive modeling and classification, as in the cases of fault detection and diagnosis. Significant work exists for fault detection while less work is found for controls applications. A methodology for creating data-driven wind turbine models for arbitrary performance parameters is proposed. Results are presented utilizing the methodology to create wind turbine models relating active adaptive twist to steady-state rotor thrust as a performance parameter of interest. Resulting models are evaluated by comparing root-mean-square-error (RMSE) on both the training and validation data sets, with Gaussian Process Regression (GPR), deemed an accurate model for this application. The resulting model undergoes particle swarm optimization to determine the optimal aerostructure twist shape at a given wind speed with respect to the modeled performance parameter, aerodynamic thrust load. The optimization process shows an improvement of 3.15% in thrust loading for the 10 MW reference turbine, and 2.66% for the 15 MW reference turbine.

Objective: To develop an algorithm that accurately identifies children with Down syndrome (DS) using administrative data. Methods: We identified a cohort of children born 2000-2017, enrolled in a state Medicaid program, who either had DS coded on the birth certificate or had a diagnosis listed using an International Classification of Diseases (ICD) code (suspected DS), and who received care at a comprehensive academic medical center in the United States. Children with suspected DS were defined as having DS if they had a) karyotype confirmed DS indicated on their birth certificate; b) karyotype pending DS indicated on their birth certificate (or just DS if test type was not specified) and at least two healthcare encounters for DS during the first 6 years of life; or c) at least three healthcare encounters for DS, with the first and last encounter separated by at least 30 days, during the first six years of life. Positive predictive value (PPV) of the algorithm and 95% confidence interval (CI) were reported. Results: Of the 411 children with suspected DS, 354 (86.1%) were defined as having DS by the algorithm. According to medical chart review, the algorithm correctly identified 347 children with DS (PPV=98%, 95%CI: 96.0%-99.0%). Of the 57 children the algorithm defined as not having DS, 50 (97.7%, 95%CI: 76.8%-93.9%) were confirmed not having DS by medical chart review. Conclusions: An algorithm that accurately identifies individuals with DS using birth certificate data and/or ICD codes provides a valuable tool to study DS using administrative data.

MicroRNAs, short non-protein coding RNAs, are overexpressed in GCTs. Circulating levels of germ cell tumor (GCT)- associated miRNAs, such as miR-371a-3p, can be utilized as efficient and cost-effective alternatives in diagnosing and managing patients presenting with GCTs. This quality of miRNAs has demonstrated favorable performance characteristics as a reliable blood-based biomarker with high diagnostic accuracy compared to current serum tumor markers (STMs) including α-fetoprotein (AFP), beta human chorionic gonadotropin (β-hCG), and lactate dehydrogenase (LDH). The conventional STMs exhibit limited specificity and sensitivity. Potential clinical implications of miRNAs include impact on de-escalating or intensifying treatment, detecting recurrence at earlier stages, and lessening the necessity of cross-sectional imaging or invasive tissue biopsy for non-teratomatous GCTs. Here we also highlight the outstanding issues that must be addressed prior to clinical implementation. Standards for measuring circulating miRNAs and determining ideal cutoff values are essential for integration into current clinical guidelines.

Fibrosis is a ubiquitous pathology, and prior studies have indicated that various artemisinin (ART) derivatives (including artesunate (AS), artemether (AM), and dihydroartemisinin (DHA)) can reduce fibrosis in vitro and in vivo. The medicinal plant, Artemisia annua L., is the natural source of ART and is widely used, especially in underdeveloped countries, to treat a variety of diseases including malaria, while A. afra contains no ART but is also antimalarial. Using human dermal fibroblasts (CRL-2097), we compared the effects of A. annua and A. afra tea infusions, ART, AS, AM, DHA, and a liver metabolite of ART, deoxyART (dART), on fibroblast viability and expression of key fibrotic marker genes after 1 and 4 days of treatment. AS, DHA, and Artemisia tea significantly reduced fibroblast viability at 1 and 4 d post-treatment. After 4 d post treatment, AS, DHA, and A. afra tea downregulated ACTA2, and upregulated MMP3, with other genes either being unaffected or differentially affected. ART and AM had no significant effect on either fibroblast viability or fibrotic gene expression. Although A. annua contains ART, it had a significantly greater anti-fibrotic effect than ART alone. Immunofluorescent staining for smooth muscle α-actin (α-SMA) correlated well with transcriptional responses of drug-treated fibroblasts. Together, proliferation, qPCR, and immunofluorescence results show that treatment with ART, AS, DHA, and the two Artemisia teas yield differing responses, including those related to fibrosis, in human dermal fibroblasts.

With advancements in remote sensing technology and affordable design, uncrewed aerial systems (UAS), commonly known as drones, have become prevalent in both civil and military applications, such as agriculture, public safety, and aerial imaging. However, the rise in unlawful UAS activities, such as non-compliance with legal standards and potential terrorist attacks, has raised significant public concern, necessitating effective detection and mitigation solutions. Despite the growing importance of this issue, comprehensive and detailed examinations of existing counter-UAS solutions are lacking. To address this gap, this study conducts a bibliometric analysis and scoping review of the current literature to identify key topics and emerging trends in counter-UAS approaches. Utilizing co-word and social network analyses, the study identifies strong and weak connections between selected keywords from academic articles. This study summarizes the limitations and potential opportunities within counter-UAS research, suggesting an increasing focus on multisensory fusion and machine-learning approaches for drone detection and mitigation. Additionally, areas such as swarm drone operations, UAS traffic management (UTM), and UAS networks are identified as important but promising fields for further investigation. The findings of this study provide a foundation for enhancing air and ground safety through improved counter-UAS applications.

In patients with heart failure, the evaluation of left ventricular (LV) diastolic function is vital, offering crucial insights into hemodynamic impact and prognostic accuracy. Echocardiography stands as the primary imaging modality for diastolic function assessment, and using it effectively requires a profound understanding of the underlying pathology. This review covers four main topics: first, the fundamental driving forces behind each phase of normal diastolic dynamics, along with the physiological basis of two widely used echocardiographic assessment parameters, E/e' and mitral annulus early diastolic velocity (e'); second, the intricate functional relationship between the left atrium and LV in patients with varying degrees of LV diastolic dysfunction (LVDD); third, the role of stress echocardiography in diagnosing LVDD and the significance of parameter changes in this context; and fourth, the clinical utility of evaluating diastolic function from echocardiography images across diverse cardiovascular care areas.

Prostate cancer (PCa) ranks as the second most fatal and sixth most prevalent cancer among males globally. This study focuses on leveraging deep learning networks to detect the Gleason grading of prostate cancer from histopathology images stained with Hematoxylin and Eosin (H&amp;E). Six pathologists annotated the images, resulting in six distinct labels for each input image. A common ground truth label was established through majority voting approach. Subsequently, the dataset was trained using architectures: UNeT, UNeT++, DeepLabV3, DeepLabV3+, and GAN based segmentation network. Notably, GAN based network demonstrated superior performance, achieving an F1-score of 0.872 and a Jaccard Index of 0.777, outperforming the other architectures considered in this study.

Neurodegeneration is a major problem in neuroscience and medicine as it causes and worsens many neurological and psychiatric disorders. It involves gradual loss of neurons at different levels of the brain, affecting cognition, emotion, behavior, consciousness, and attention. Understanding the causes and consequences of neurodegeneration is crucial for identifying the risk factors, biomarkers, and treatments. However, the current therapies are mostly symptomatic and ineffective. Therefore, new and innovative methods, such as noninvasive brain stimulation (NIBS), are needed to modulate brain activity and plasticity in a safe and reversible manner. This field is rapidly developing, with a focus on exploring new clinical applications, mechanisms, and combinations of NIBS and drugs. This special issue covers the latest progress and challenges in the study of neurodegeneration in cognitive impairment and mood disorders from the experimental, clinical, and translational perspectives. It addresses the complexity and diversity of these conditions, the lack of disease-modifying treatments, the ethical and practical issues of conducting research in vulnerable and diverse populations, the integration and interpretation of data from multiple sources and modalities, and the development and validation of novel methods such as NIBS, artificial intelligence, and drug repurposing. Collaborative efforts among various stakeholders are needed to improve our knowledge and treatment of neurodegeneration underlying cognitive impairment and mood disorders.

Entanglement is one of the most striking features in quantum systems. Today, quantum entanglement plays a vital role in quantum technology, the non-classical correlation of quantum entanglement is an important resource for quantum communication and quantum computing. Entanglement can be divided into two categories: between multi-particle systems and between various degrees of freedom in a single-particle system (intraparticle entangled states). This work first analogized the distinctions and connections between two kinds of entangled states. Then it designed three types of entanglement-swapping methods based on Bell state joint measurement, cross-Kerr medium, and linear optical elements for intraparticle entangled states by analogizing the entanglement swapping between multiple particles. Intraparticle entanglement swapping can be applied in super quantum dense encoding, quantum information transmission, and quantum teleportation. This work is beneficial for promoting the development of quantum information technologies.

Since the discovery of transposable elements (TEs) in Maize in the 1940s by Barbara McClintock [1] transposable elements have been described as junk, as selfish elements with no benefit to the host, and more recently as major determinants of genome structure and genome evolution. TEs are DNA sequences that are capable of moving to new sites in the genome and make additional copies while doing so. To limit the propagation of TEs, host silencing mechanisms are directed at transposon-encoded genes that are required for mobilization. The mutagenic properties of TEs, the potential of TEs to form new genes and affect gene expression, together with the host silencing mechanisms shape eukaryotic genomes and drive genome evolution. While TEs constitute more than half of the genome in many higher eukaryotes, transposable elements in the nematode C. ele-gans form a relatively small proportion of genome, about 15% [2]. Genetic studies of transposon silencing and the discovery of RNAi in C. elegans, propelled C. elegans to the forefront of studies of RNA-based mechanisms that silence TEs. Here, I will review the transposable elements that are present and active in the C. elegans genome, and the host defense mechanisms that silence these elements.

Smith-Magenis syndrome is a complex neurobehavioral genetic disorder. The spectrum of SMS phenotype is broad but commonly includes craniofacial, neurobehavioral, and otolaryngologic features. While the etiology of SMS is commonly attributed to one copy interstitial deletion in the 17p11.2 region (90-95% of cases), variants identified by sequence analysis in RAI1 have also been reported in 5-10% of cases. The phenotypic spectrum of patients with RAI1 sequence alterations is not clear. In this study, we report a 9-year-old male with global cognitive and psychomotor developmental delay, musculoskeletal and cardiovascular abnormalities, and dysmorphic craniofacial features. Whole genome quad analysis of the proband, unaffected parent, and unaffected brother identified a novel de novo RAI1:c.2736delC variant. This is the first report of this variant in the literature. This report also highlights the details of the genome analysis and this patient's phenotypic spectrum.

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.

Studies have established the crucial role of sleep among the students which plays a significant role in their mood. This study aimed to examine the mood disorders and sleep quality among undergraduate students at the University of Georgia (UG) and comparison between students’ nationality.This cross-sectional study was a self-reported questionnaire comprised of demographics including age, gender, year of study, current location, lifestyle data (Exercise and smoking), the Depression, Anxiety, and Stress Scale (DAS21) and the Pittsburgh Sleep Quality Index (PSQI). We performed a descriptive analysis, and the Chi-square was statistically significant at p<0.05. The prevalence was at a 95% confidence interval (95% CI) as multivariate analysis examined the multicollinearity. The female students were most of the respondents, below the age of 20 years. The student's mean age was 20.20 (SD± 3.0). DAS report presented 72.7% of students with depressive symptoms, 77.8% with anxiety symptoms, and 62.2% had stress. Georgian students were more at risk of having depressive complaints (95% Cl[1.567-3.788]), anxiety (95% Cl[1.612-4.285]), and stress symptoms (95% Cl[1.743-3.831]). There was a strong relationship between the students who experienced poor sleeping patterns and depressive complaints (aOR 0.10). The students who were smokers (aOR 0.39) were more likely to report anxiety symptoms than the students that do not exercise (aOR 1.68). It was observed that students with depressive symptoms, anxiety, and complaints of stress had a significantly high risk of poor sleep quality. Further studies are recommended to curb psychological symptoms of mood changes in association with sleep disorders among students.

We report the case of a 44-year-old woman who suffered gastric perforation after receiving bag-valve-mask (BVM) ventilation in the setting of alcohol intoxication. She had a markedly distended abdomen and cold, dusky lower extremities upon arrival to the emergency department. Imaging revealed a large volume intraabdominal accumulation of air with compression of the aorta. Needle decompression relieved symptoms of lower extremity arterial insufficiency. However, the patient quickly decompensated and subsequent exploratory laparotomy confirmed gastric rupture. A subtotal gastrectomy was performed but the patient ultimately passed on post-operative day two due to multi-organ dysfunction. Although BVM ventilation is commonplace in both the hospital and field, there is a lack of awareness of the serious complications of abdominal air accumulation due to their rareness in the adult population. Checking for abdominal distention during resuscitation ought to be routine in all patients. Signs of arterial insufficiency accompanying abdominal distention, once confirmed by diagnostic imaging that shows extensive pneumoperitoneum, are indicators of having reached a life-threatening level of air accumulation, calling for immediate needle decompression and exploratory laparotomy.

Prostate Cancer remains a prevalent health concern, emphasizing the critical need for early diagnosis and precise treatment strategies to mitigate mortality rates. Accurate prediction of cancer grade is paramount for timely interventions. This paper introduces an approach to prostate cancer grading, framing it as a classification problem. Leveraging ResNet models on multi-scale patch-level digital pathology and the Diagset dataset, the proposed method demonstrates notable success, achieving an accuracy of 0.999 in identifying clinically significant prostate cancer. The study contributes to the evolving landscape of cancer diagnostics, offering a promising avenue for improved grading accuracy and, consequently, more effective treatment planning. By integrating innovative deep-learning techniques with comprehensive datasets, our approach presents a step forward in the pursuit of personalized and targeted cancer care.

This retrospective study assesses the efficacy and tolerability of anti-CGRP therapy in adolescents and young adults (ages 12-21) with migraines and chronic daily headaches unresponsive to standard treatments. Migraines severely affect school performance, self-esteem, psychological well-being, and cognitive health in this demographic, who are also sensitive to the side effects of conventional medications often prescribed off-label and face high insurance denial rates. Medication overuse, including analgesics, triptans, and NSAIDs, is prevalent due to treatment failures. Elevated plasma CGRP levels during migraines suggest that anti-CGRP therapies, which have shown success in adults, might benefit this age group. Over three years, patients at a specialized headache center were evaluated for the impact of anti-CGRP treatments, including monoclonal antibodies (erenumab, fremanezumab, galcanezumab) and small molecule CGRP receptor antagonists (ubrogepant, rimegepant, atogepant), either alone or in combination with OnabotulinumtoxinA. The study found significant improvements in migraine management, especially among older adolescents, with reduced rescue medication use and emergency visits. Longer treatment courses and combination therapy with traditional medications were more effective than monotherapy, reducing migraine intensity and frequency. Adverse effects were minimal, and no significant medication interactions were noted. Anti-CGRP therapy demonstrates substantial potential in improving outcomes for this age group with chronic and episodic migraines.

The chiral optical Tamm state (COTS) is a special localized state at the interface of a handedness-preserving mirror and a structurally chiral medium such as a cholesteric liquid crystal or a chiral sculptured thin film. The spectral behavior of COTS, observed as reflection resonances, is described by the temporal coupled-mode theory. Mode coupling is different for two circular light polarizations because COTS has a helix structure replicating that of the cholesteric. The mode coupling for co-handed circularly polarized light exponentially attenuates with the cholesteric layer thickness since the COTS frequency falls into the stop band. Cross-handed circularly polarized light freely goes through the cholesteric layer and can excite COTS when reflected from the handedness-preserving mirror. The coupling in this case is proportional to anisotropy of the cholesteric and theoretically it is only anisotropy of magnetic permittivity that can ultimately cancel this coupling. These two couplings being equal results in a polarization crossover (the Kopp--Genack effect) for which a linear polarization is optimal to excite COTS. The corresponding cholesteric thickness and scattering matrix for COTS are generally described by simple expressions.

Cancer diagnosis and classification are pivotal for effective patient management and treatment planning. In this study, we present a comprehensive approach utilizing ensemble deep learning techniques to analyze breast cancer histopathology images. Our datasets are based on two widely employed datasets from different centers for two different tasks: BACH and BreakHis. Within the BACH Dataset, we deployed an ensemble strategy incorporating VGG16 and ResNet50 architec-tures to achieve precise classification of breast cancer histopathology images. Introducing a novel image patching technique, to preprocess a high-resolution image, which facilitates focused analysis of localized regions of interest. The annotated BACH dataset encompasses 400 WSIs across four distinct classes: Normal, Benign, In Situ Carcinoma, and Invasive Carcinoma. In addition, we employed the BreakHis dataset, utilizing VGG16, ResNet34, and ResNet50 models to classify mi-croscopic images into eight distinct categories (four benign and four malignant). For both models we leveraged a five-fold cross-validation approach for rigorous training and testing. Preliminary ex-perimental results indicate a Patch classification accuracy of 95.31% (on BACH dataset) and WSI image classification accuracy of 98.43% (BreakHis). This research significantly contributes to on-going endeavors in harnessing artificial intelligence to advance breast cancer diagnosis, potentially fostering improved patient outcomes and alleviating healthcare burdens.

KLEPTOSE® CRYSMEB is a methylated cyclodextrin derivative displaying less methylated group substitution than randomly methylated cyclodextrin. It has demonstrated an impact on atherosclerosis and neurological diseases. linked in part to cholesterol complexation and immune response, but the impact on inflammatory cascade pathways was not clear. Thus, the impact of KLEPTOSE® CRYSMEB on various pharmacological targets was assessed using human umbilical vein endothelial cells in physiological and inflammatory conditions, followed by screening against twelve human primary cell-based systems designed to model complex human tissue and disease biology of the vasculature, skin, lung, and inflammatory tissues using the BioMAP® Diversity PLUS® Panel. Finally, the anti-inflammatory mechanism was investigated on peripheral blood mononuclear cells to evaluate anti-inflammatory or pro-resolving properties. The results showed that KLEPTOSE® CRYSMEB can modulate the immune system in vitro and potentially manage vascular issues by stimulating the expression of molecules involved in the crosstalk between immune cells and other cell types. It showed anti-inflammatory effects driven by pro-inflammatory cytokine secretion inhibition and could have different impacts on different tissue types. Moreover, this cyclodextrin showed no clear impact on pro-resolving lipid mediators. Finally, it appeared that the mechanism of action of KLEPTOSE® CRYSMEB seems to not be shared by well-known anti-inflammatory molecules.

Background and Objectives: Most of the research of the BRCA1 inactivation is focused on monoallelic germline alterations and loss of heterozygosity in tumour. The aim of this study was to identify characteristic transcriptomic pattern of monoallelic somatic BRCA1 inactivation and estimate its impact to the event-free breast cancer survival prognosis. Materials and Methods: We conducted global transcriptome sequencing of breast cancer tissue samples to identify differentially expressed genes and signalling pathways associated with monoallelic somatic BRCA1 inactivation. The study group involved 36 patient samples categorized based on BRCA1 inactivation status. Subsequently, the differential gene expression and Kaplan-Meier analyses in the groups with and without monoallelic somatic BRCA1 inactivation were performed. Results: Kaplan-Meier analysis showed tendency for longer event-free survival in patients with monoallelic somatic BRCA1 inactivation, suggesting somatic BRCA1 inactivation is favourable prognostic. Differential gene expression analysis followed by the STRING tool enrichment analysis showed significant enrichment of proteins in the extracellular region and extracellular space. Conclusion: In this study we identified transcriptomic profile of differentially expressed genes TPSD1, FABP4, CARTPT and MMP9 as indicative for homologous recombination impaired tumours with tendency for better therapy results.

Clinical and laboratory diagnostics are particularly important in monitoring the internal homeostasis of the body in high-yielding animals, especially in dairy cows, whose metabolism is under constant pressure to obtain high parameters of milk production and reproduction. Knowledge of laboratory test results and relationships based on significant correlations between various milk and blood parameters may be very useful in veterinary diagnostics and helpful in cattle practice in order to protect animal health and the quality of milk production. The aim of the study was to analyze the correlation between selected hematological biomarkers such as white blood corpuscles (WBC), red blood corpuscles (RBC), hemoglobin concentration (HGB), hematocrit (HCT), platelets (PLT), erythrocyte mean corpuscular volume (MCV), mean corpuscular hemoglobin content (MHC), mean corpuscular hemoglobin concentration (MCHC) and selected quantitative-qualitative parameters of cow’s milk such as current milk production, somatic cells count (SCC), colony of bacteria forming units (CFU), milk fat (MF), milk protein (MP), milk lactose (ML), milk solids (S), solids non-fat in milk (SNF), daily milk production. Samples were collected three times at daily intervals from 11 clinically healthy late-lactation dairy cows obtaining 33 sets of test results. This repeated study of cows allowed for obtaining a homogeneous group in order to determine statistical correlations between selected blood and milk parameters. Many significant correlations were found between the examined parameters. In cows, significant positive correlations were recorded between milk production and HGB, HCT, MCV or MHC. Significant negative correlations were also found between SCC and HGB, SCC and HCT, SNF and MCV, SNF and MHC, and between MF and RBC.

This study aimed to evaluate the effect of three yeast strains, Pichia guilliermondii (Levica 27), Candida norvegensis (Levazoot 15), and a commercial product (Levucell® SC 10) containing Saccharomyces cerevisiae, on in vitro rumen fermentation of two substrates: corn stover and a total mixed ration (TMR). Samples were taken 24 hours post-fermentation to measure pH, ammonia nitrogen (NH3-N), gas production, and volatile fatty acid (VFA) concentrations. The addition of yeasts did not affect gas production at 24 hours for either diet. For pH, differences between yeast strains were noted when TMR was used. The lowest NH3-N concentration (6.1 mM) was recorded with corn stover, showing similar results across strains. Conversely, NH3-N levels with TMR ranged from 47 mM to 66 mM. The inclusion of all three yeast strains increased the molar concentrations of total VFA, as well as acetic (C2), propionic (C3), and butyric (C4) acids in the rumen fluid. The C2:C3 ratio remained unchanged with corn stover but decreased with the inclusion of Levica 27 and Levazoot 15 in the TMR. With the commercial product Levucell® SC 10, this ratio was comparable to the control treatment. In conclusion, Levica 27 and Levazoot 15 demonstrated a stimulatory effect on in vitro rumen fermentation for the evaluated diets, evidenced by increased VFA concentrations.

The Folla Redonda grape is indigenous to the region of Rias Bajas in Galicia, Spain. This grape is distinguished by its characteristic acid flavor and pulp of remarkable coloration. Despite the wine obtained from this grape is highly valued by consumers of this region for its surprising acidic notes and thickness, it is important to note that it is not a variety of Vitis vinifera and its production is not legally regulated. In the present study, an evaluation of the physicochemical properties of the Folla Redonda grape (pH, °Brix, °Bé, density, acidity, sugar content, etc.) as well as its content in bioactive compounds (total polyphenols and anthocyanins) was carried out. Additionally, the antioxidant potential of the extracts obtained from this grape was demonstrated. This study proved the interesting organoleptic characteristics of the grape, along with a high content of compounds of interest and an important antioxidant activity comparable to that of Vitis vinifera grapes. Therefore, the grape's natural consumption and its application in different industries such as nutraceutical or pharmacological would result in an important revaluation of the grape and significant health benefits. In case that the production of wine from this variety is legalized, consumers will not only be able to enjoy a wine with a characteristic dense reddish color and important acid tones, but also with interesting concentrations of bioactive compounds.

Brain aging causes a wide variety of changes at molecular and cellular levels, leading to the decline of cognitive functions and increased vulnerability to neurodegenerative disorders. The research aimed at understanding the aging of the brain has made much progress in recent decades. Technological innovations such as single-cell RNA-sequencing (scRNA-seq), proteomic analyses, and spatial transcriptomic analyses have facilitated the research on the dynamic changes occurring within neurons, glia, and other cells along with their impacts on intercellular communication during aging. In this review, we introduce recent trends of how neurons and glia change during aging and discuss the impact of the brain microenvironment such as the blood-brain barrier (BBB).

Vanilla planifolia is grown as a high-value orchid spice for its odor and savor attributes that increase due to the curing process associated with microbial colonization. This tends to influence the aromatic properties of vanilla. Hence, 11 Bacillus sp. strains were isolated from V. planifolia and identified with 16S rRNA gene sequencing. The liquid culture (1 mL of 107 CFU mL-1) of selected Bacillus vallismortis NR_104873.1:11-1518, B. velezensis ZN-S10, and B. tropicus KhEp-2 effectively fermented green-blanched vanilla pods kept at 10 ℃ during the sweating stage. GC-MS analysis showed that the methanol extract of non-coated, and B. vallismortis treated vanilla detected three (3) volatile compounds, whereas seven (7) components were obtained in B. tropicus and B. velezensis treatment. 4H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl was found in B. velezensis ZN-S10, B. tropicus KhEp-2, B. vallismortis while it was not present in the control samples. This ketone compound suggested a Maillard reaction resulting in brown-increased aroma pods. Linoleic acid and Hexadecanoic acid ethyl esters were detected only in ZN-S10 strain-coated vanilla. A novel 3--Deoxy-d-mannoic lactone was detected only in B. vallismortis treated vanilla characterized as a new compound in V. planifolia which suggested that the new compound can be altered with the coating of bacteria in vanilla during fermentation. Thus, the Bacillus strains improved the volatile profile and exhibited a new aroma and flavor profile of vanilla owing to bacteria fermentation during the curing process.

The emergence of antimicrobial resistance (AMR) Candida auris presents a formidable global health challenge, causing severe healthcare-associated infections with high mortality rates. Its ability to colonize surfaces and resist standard disinfectants undermines traditional hygiene practices, prompting an urgent need for novel strategies. Ultraviolet C (UVC) light offers a promising approach due to its rapid and broad-spectrum germicidal efficacy. This review comprehensively examines the current knowledge of UVC LED technology in combating C. auris, highlighting its effectiveness, limitations, and potential applications in healthcare hygiene. UVC light has potent activity against C. auris, including multidrug-resistant (MDR) strains. UVC can reduce C. auris on contaminated surfaces, aiding in transmission prevention. This review explores implementation strategies, including mobile UVC systems for targeted disinfection of high-risk areas and equipment, integration into air handling units (AHUs) to continuously disinfect recirculating air, and incorporation into water treatment systems. Current limitations in our understanding of UVC safety and effectiveness necessitate further research to optimize application protocols and ensure treatment safety while maintaining efficacy against C. auris. Integrating UVC disinfection technology into infection control programs holds promise for strengthening hygiene practices that will curb the global spread of C. auris and improve patient outcomes.

Accurate measurement of pedaling kinetics and kinematics is vital for optimizing rehabilitation, exercise training, and understanding musculoskeletal biomechanics. Pedal reaction force, the main external force in cycling, is essential for musculoskeletal modeling and closely correlates with lower limb muscle activity and joint reaction forces. However, sensor instrumentation like 3-axis pedal force sensors is costly and requires extensive post-processing. Recent advancements in machine learning (ML), particularly neural network (NN) models, provide promising solutions for kinetic analyses. In this study, an NN model was developed to predict radial and mediolateral forces, providing a low-cost solution to study pedaling biomechanics with stationary cycling ergometers. Fifteen healthy individuals performed a 2-minute pedaling task at two different self-selected (58±5 rpm) and higher (72±7 rpm) cadences. Pedal forces were recorded using a 3-axis force system. The dataset included pedal force, crank angle, cadence, power, and participants' weight and height. The NN model achieved an inter-subject normalized root mean square error (nRMSE) of 0.15±0.02 and 0.26±0.05 for radial and mediolateral forces at high cadence, respectively, and 0.20±0.04 and 0.22±0.04 at self-selected cadence. The NN model's low computational time suits real-time pedal force predictions, matching the accuracy of previous ML algorithms for estimating ground reaction forces in gait.

The motor protein Prestin found in the outer hair cells (OHCs) of the inner ear is responsible for producing high sensitivity and sharp frequency selectivity for mammalian hearing. Some studies have suggested that Prestin could serve as a serological biomarker for cochlear damage since OHCs are highly vulnerable to damage from various sources of insults. However, the reported data are inconsistent and lack appropriate negative controls. To investigate this further, we measured Prestin quantities in the bloodstream using ELISA kits from different companies. Wildtype (WT) mice were exposed to different ototoxic treatments, including noise exposure and ototoxic reagents that kill OHCs rapidly. Prestin-knockout (KO) mice were used as a negative control. Our data show that some ELISA kits were not able to detect Prestin specifically. The ELISA kit that could detect Prestin protein from cochlear homogenates failed to detect Prestin in the bloodstream despite significant damage to OHCs in cochleae. Furthermore, the optical densities of samples, which correlate to Prestin quantities, were significantly influenced by hemolysis in the samples. In conclusion, Prestin from OHCs is not a sensitive and reliable serological biomarker for detecting cochlear damage in mice.

The gut-brain axis (GBA) represents a complex, bidirectional communication network that intri-cately connects the gastrointestinal tract with the central nervous system (CNS). Understanding and intervening in this axis opens a pathway for therapeutic advancements. In light of this, the current review assesses the effectiveness of neuromodulation techniques in treating neurological and gastrointestinal disorders by modulating the GBA, involving key elements such as gut micro-biota, neurotrophic factors, and proinflammatory cytokines. Through a comprehensive literature review encompassing PubMed, Google Scholar, Web of Science, and the Cochrane Library, and analyzing 182 relevant articles, this research highlights how neuromodulation can positively impact the management of functional gastrointestinal disorders (FGIDs), chronic pain, inflammation, and a range of GI disorders like Crohn's disease and ulcerative colitis. Despite existing challenges, the ability of neuromodulation to adjust disrupted neural pathways, alleviate pain, and mitigate in-flammation is significant in improving the quality of life for patients, thereby offering exciting prospects for future advancements in patient care.

Vascular rings are a rare congenital anomaly of the aortic arch in which a ring-shaped structure forms surrounding the trachea and/or esophagus, potentially causing compression. We describe the case of a 14-month-old female patient with failure to thrive secondary to dysphagia, and a vascular ring formed by a right aortic arch, an aberrant left subclavian artery, and a left liga-mentum arteriosum. Surgical repair involved ligamentum arteriosum division, Kommerell’s di-verticulum obliteration, and left subclavian artery re-implantation into the left carotid artery. Endoscopy and EndoFLIPTM evaluated intraoperative improvement in esophageal narrowing and impedance, respectively. Postoperative period was uneventful and follow-up visits demonstrated dysphagia resolution and a patent re-implanted left subclavian artery.

With continuous increase in integration of the semiconductor devices, the requirements on size accuracy and surface quality of the etched lead frame are higher. The etchant is a key factor on etching process and etched surface quality, while effects of the difference in etchants on microscopic etched surface morphology of the Cu alloy have not been directly studied. In this study, the aqua regia, acidic FeCl3 and CuCl2 solutions were used as etchants, and the CuCrSn alloy specimens with different microstructure were etched and characterized. The results show that the etching rate in aqua regia is high, and the grain orientation, grain boundary (GB) and dislocation have significant influence on the local etching rate. The preferential etching of some atomic planes forms steps between grains with different orientations, and the preferential etching around the GB and dislocation group forms grooves, resulting in high surface roughness. For etching of the FeCl3 and CuCl2 etchants, the steps and grooves become blurred, and almost invisible on the surface etched by the CuCl2 etchant, thus the surface roughness is much lower. The CuCrSn alloy surface etched by the aqua regia is clean, with little Cr-rich particles, while high density Cr-rich particles are remained on the surfaces etched with the FeCl3 and CuCl2 etchants. For the same kind of etchant, the ion concentration can affect the etching mechanism and etching surface morphology.

Tomato brown rugose fruit virus (ToBRFV) is an emerging tobamovirus infecting tomatoes and peppers. Due to its ability to trigger seed contamination, efficient mechanical transmission, and to break the popular resistance genes (Tm-1, Tm-2 and Tm-22), the virus has resulted in a global pandemic on greenhouse tomato production in recent years despite the implementation of strict hygiene and disinfection measures. The objective of this study was to evaluate whether ToBRFV can be transmissible through recirculating hydroponic systems and search for effective approach to contain its spread under such circumstances. We not only detected the presence of ToBRFV in the runoff water solutions collected from ToBRFV-infected tomato greenhouses, but also demonstrated the infectivity of detected virus through initiating ToBRFV infection on tomato plants using bioassay. We then conducted treatment using cold plasma-generated ozone on ToBRFV-contaminated water reservoir and further assessed the efficacy of the treatment to inac-tivate the virus. Results showed the effectiveness of the cold-plasma ozone treatment was de-pendent on the ozone concentrations (0.1 mg/L to 1.0 mg/L), the periods of exposure (24 min to 72 min), and the relative virus titers (1:100 to 1:10,000 - dilution of virus-infected tissue extract), demonstrating the cold-plasma ozone treatment could offer a promising solution to cope with the potential ToBRFV spread through a recirculating hydroponic system in a greenhouse.

This review explores the crucial role of glycosphingolipids (GSLs) in the context of cardiovascular diseases (CVD), focusing on their biosynthesis, metabolic pathways, and implications for clinical outcomes. GSLs are pivotal in regulating a myriad of cellular functions that are essential for heart health and disease progression. Highlighting findings from both human cohorts and animal models, this review emphasizes the potential of GSLs as biomarkers and therapeutic targets. We advocate for more detailed mechanistic studies to deepen our understanding of GSL functions in cardiovascular health, which could lead to innovative strategies for diagnosis, treatment, and personalized medicine in cardiovascular care.

Aspalathin, a C-glucosyl dihydrochalcone, has previously been shown to protect cardiomyocytes against hyperglycemia-induced shifts in substrate preference and subsequent apoptosis. However, the precise gene regulatory network remains to be elucidated. To unravel the mechanism and provide insight into this supposition, the direct effect of aspalathin in an isolated cell-based system, without the influence of any variables, was tested using an H9c2 cardiomyocytes model. Cardiomyocytes were exposed to high glucose (33 mM) for 48 hours before post-treatment with or without aspalathin. Thereafter, RNA was extracted and RT2 PCR Profiler Arrays were used to profile the expression of 336 genes. Results showed that, 57 genes were differentially regulated in the high glucose or high glucose and aspalathin treated groups. STRING analysis revealed lipid metabolism and molecular transport as the biological processes altered after high glucose treatment, followed by inflammation and apoptosis. Aspalathin was able to modulate key regulators associated with lipid metabolism (Adipoq, Apob, Cd36, Cpt1, Pparγ, Srebf1/2, Scd1 and Vldlr), insulin resistance (Igf1, Akt1, Pde3 and Map2k1), inflammation (Il3, Il6, Jak2, Lepr, Socs3, and Tnf13) and apoptosis (Bcl2 and Chuk). Collectively, our results propose that aspalathin could reverse metabolic abnormalities by activating Adipoq while modulating the expression of Pparγ and Srebf1/2, decreasing inflammation via Il6/Jak2 pathway, which together with an observed increased expression of Bcl2 prevents myocardium apoptosis.

Contrasting results have suggested that the prevalence and intensity of post abortion emotional distress (PAD) either diminishes rapidly or persists over time. Few studies have followed women for longer than five years. This study examines retrospective population data on 226 ever aborting U.S. women aged 41-45, at an average of 20 years following the abortion, with extensive measures of PAD. Most post abortive women (55.2%) experienced little or no distress from their abortion(s) and 74.6% were confident it had been the right decision, but 44.8% reported moderate (20.7%) to high (24.1%) distress related to their abortion(s), including 37.7% who reported negative emotions; 31.2% “frequent feelings of loss, grief or sadness;” 24.6% “frequent thoughts, dreams, or flashbacks;” 23.2% for whom thoughts and feelings about their abortion “negatively interfered with life, work, or relationships.” Time since the abortion (mean 20 years, range 0-31 years) was not correlated with PAD (r = -.02, p .71). For the minority of women who experienced it, PAD did not diminish but persisted for decades. An estimated 7.5 million U.S. women currently experience persistent high PAD. Further research to specify risk factors and possible interventions for postabortion distress would be of value for this group of women.

High-precision conical threads are widely used in responsible joints in the drilling of oil and gas wells. Difficult underground drilling conditions due to the occurrence of significant mechanical loads and an aggressive environment in wells require the use of workable materials that are often difficult to machine. The huge need for such connections dictates the use of high-performance cutting tools, which means that high demands are placed on their effective geometric performance. The study describes the theoretical dependence of the profile precision of the tapered drill-string tool-joint threads of all standard sizes on the complex of a cutting tool geometric parameters and cutting tool setting accuracy. The experiments include an assessment of the geometric accuracy of the profile of the obtained NC23 thread connector, depending on the values of the installation angles and the declared tangential displacement of the standard threaded carbide insert.

Epilepsy is one of the most prevalent and serious brain disorders, affecting 70 million people worldwide. Antiseizure medications (ASMs) though relieve symptoms and prevent the occurrence of future seizures in epileptic patients have limited effect on epileptogenesis. Addressing the multifaceted nature of epileptogenesis and its association with Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated neuroinflammation requires a comprehensive understanding of the underlying mechanisms for development of targeted therapeutic strategies beyond conventional antiseizure treatments. Several types of NLRP3 inhibitors have been developed and their effect has been validated both in vitro and in vivo models of epileptogenesis. In this review, we discuss the advances in understanding the regulatory mechanisms of NLRP3 activation as well as progress made and challenges facing in the development of NLRP3 inhibitors for the treatment of epilepsy.

Although vitamin D deficiency has been correlated with an increased risk of cardiovascular disease (CVD), there are few data on the association between 25-hydroxyvitamin D (25(OH) D) and atherogenic indices predictive of CVD. This study aimed to investigate the relationship of vitamin D status with lipid profile and atherogenic indices in adult women in Morocco. Three hundred healthy women, aged 18 to 50 years, from Meknes were included. Fasting 25(OH) D and lipid concentrations were determined using a one-step electrochemiluminescence-based immunoassay and an enzymatic method, respectively. Atherogenic indices (Atherogenic index of plasma (AIP), non-HDL cholesterol (Non-HDL-C), Atherogenic coefficient (AC), Castelli risk indices I and II (CRI-I and II), and CHOLIndex (CI)) were calculated using conventional lipid parameters. Logistic regression models and operating characteristic curve (ROC) analysis were used to assess the relationship of the variables and estimate the threshold of 25(OH) D levels associated with high atherogenic indices. 25(OH) D below 20 ng/ml was significantly associated with an enhanced risk of hypertriglyceridemia and elevated values of AIP, AC, Non-HDL-C, and CRI-I with an OR (95% CI) of 4.904 (1.856-12.959); 3.637(2.149-6.158); 3.589(1.673-7.700); 2.074(1.215-3.540), and 2.481(1.481-4.123), respectively. According to ROC analysis, the likelihood of hypertriglyceridemia and high values of AIP, AC, Non-HDL-C, and CRI-I were associated with 25(OH)D thresholds ≤15.15 ng/ml, ≤ 17.5 ng/ml, ≤ 19.8 ng/ml, ≤ 20.1 ng/ml and ≤ 19.5 ng/ml, respectively, all p &lt; 0.01. Based on atherogenic indices, this study indicates that vitamin D below 20 ng/ml may increase the risk of cardiovascular disease in adult women. Additional health efforts are needed to raise awareness among women and healthcare providers in preventing and controlling cardiovascular risk factors.

Background: This study aimed to investigate the impact of the COVID-19 pandemic on breast reconstruction trends in the United States, focusing on implant-based and autologous techniques, as well as the timing of reconstruction (immediate vs. delayed). Methods: A retrospective analysis of data from the American Society of Plastic Surgeons' National Plastic Surgery Statistics from 2015 to 2022 was conducted. Annual trends in breast reconstruction procedures were analyzed, comparing the pre-pandemic (2015-2019) and pandemic (2020-2022) periods. Results: The total number of breast reconstructions increased from 106,338 in 2015 to 151,641 in 2022. The proportion of implant-based reconstructions decreased from 81.41% pre-pandemic to 76.51% during the pandemic (p < 0.001), with a notable rise in direct-to-implant procedures from 10.37% to 19.12% (p < 0.001). Autologous reconstructions increased from 18.59% to 23.49% (p < 0.001). Among autologous techniques, DIEP flaps remained the most popular. Immediate reconstruction rates increased from 72.61% pre-pandemic to 75.57% during the pandemic, while delayed recon-struction rates decreased from 27.39% to 24.43% (p < 0.001). Conclusions: The COVID-19 pandemic has significantly influenced breast reconstruction trends in the United States, with a shift towards autologous techniques, particularly DIEP flaps, and an in-crease in immediate reconstructions. These changes may reflect adaptations in surgical practice and decision-making processes in response to the unique challenges posed by the pandemic. Further research is needed to assess the long-term outcomes and patient satisfaction associated with these trends.

Sustainable water resource management in Bangladesh's Gumti River Basin faces challenges from climate change, urbanization, and population growth. This study aimed to calibrate and validate the HEC-HMS model for the Gumti River to enhance flood prediction and water resource planning. The model was set up using precipitation, temperature, and discharge data from 2019-2021, with SRTM elevation data for catchment delineation. Manual calibration was performed for 2019-2020, followed by validation for 2021, using parameters such as Muskingum routing and SCS Curve Number. Model performance was evaluated using R², Nash-Sutcliffe efficiency (NSE), RSR, and PBIAS metrics. Results showed satisfactory to good performance, with R² values of 0.64 and 0.68 for calibration and validation, respectively. NSE values were within the satisfactory range, while PBIAS indicated very good performance with slight underestimation. The study concludes that the calibrated HEC-HMS model provides a reliable tool for simulating the Gumti River's hydrology, though there's room for improvement. Integration with flood frequency analysis, water quality monitoring, and climate change projections is recommended for comprehensive water resource management, alongside the implementation of Sustainable Water Resource Management principles and community engagement strategies.

LC-SPIK is a liver cancer-specific isoform of Serine Protease Inhibitor Kazal and has been proposed as a new biomarker for the detection of HCC given its unique 3-D structure which differs from normal pancreatic SPIK. An ELISA technology based on its unique structure was developed to use LC-SPIK as an effective biomarker for the clinical diagnosis of HCC. AFP, the most widely used biomarker for HCC surveillance currently, suffers from poor clinical performance, especially in the detection of early-stage HCC. In one case-control study, which included 164 HCC patients and 324 controls, LC-SPIK had an AUC of 0.87 compared to only 0.70 for AFP in distinguishing HCC from liver disease controls (cirrhosis, HBV/HCV). LC-SPIK also performed significantly better than AFP for the 81 patients with early-stage HCC (BCLC stage 0 and A), with an AUC of 0.85 compared to only 0.61 for AFP. Cirrhosis is the major risk factor for HCC, about 80% of patients with newly diagnosed HCC have preexisting cirrhosis. LC-SPIK’s clinical performance was also studied in HCC patients with viral and non-viral cirrhosis including cirrhosis caused by nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). In a total of 163 viral cirrhosis patients with 93 HCC patients (50 early-stage), LC-SPIK had an AUC of 0.85, while AFP had an AUC of 0.70. For patients with early-stage HCC, LC-SPIK had a similar AUC of 0.83, while AFP had an AUC of only 0.60. For 120 patients with nonviral cirrhosis, including 62 HCC (23 early-stage) patients, LC-SPIK had an AUC of 0.84 while AFP had an AUC of only 0.72. For the 23 patients with early-stage HCC, LC-SPIK had a similar AUC of 0.83, while the AUC for AFP decreased to 0.65. All these results suggest that LC-SPIK has significantly better performance in the detection of HCC than AFP in all etiologies of liver diseases. In addition, LC-SPIK accurately detected the presence of HCC in 71%-91% of HCC patients with false-negative AFP test results in viral associated HCC and non-viral associated HCC.

Background/Objectives: Concurrent opioid (OPI) and benzodiazepine (BZD) use may exacerbate falls/fractures risk compared to no use or use alone. Yet, patients may need concurrent OPI-BZD use for co-occurring conditions (e.g., pain and anxiety). Therefore, we examined the association between longitudinal OPI-BZD dosing patterns and subsequent injurious falls risk. Methods: We conducted a retrospective cohort study including non-cancer fee-for-service Medicare beneficiaries initiating OPI and/or BZD in 2016-2018. We identified OPI-BZD use patterns during the 3 months following OPI and/or BZD initiation (i.e., trajectory period) using group-based multi-trajectory models. We estimated time to first injurious fall within 3 months post-trajectory period using inverse-probability-of-treatment-weighted Cox proportional hazards models. Results: Among 622,588 beneficiaries (age≥65=84.6%, female=58.1%, White=82.7%; having injurious falls=0.45%), we identified 13 distinct OPI-BZD trajectories: Group(A):Very-low OPI-only (early discontinuation)(44.9% of the cohort); (B):Low OPI-only (rapid decline)(15.1%); (C):Very-low OPI-only (late discontinuation)(7.7%); (D):Low OPI-only (gradual decline)(4.0%); (E):Moderate OPI-only (rapid decline)(2.3%); (F):Very-low BZD-only (late discontinuation)(11.5%); (G):Low BZD-only (rapid decline)(4.5%); (H):Low BZD-only (stable) (3.1%); (I):Moderate BZD-only (gradual decline)(2.1%); (J):Very-low OPI (rapid decline)/Very-low BZD (late discontinuation)(2.9%); (K):Very-low OPI (rapid decline)/Very-low BZD (increasing)(0.9%); (L):Very-low OPI (stable)/Low BZD (stable)(0.6%); and (M):Low OPI (gradual decline)/Low BZD (gradual decline)(0.6%). Compared with Group(A), 6 trajectories had increased 3-month injurious fall risks: (C): HR, 95%CI=1.78, 1.58-2.01; (D): 2.24, 1.93-2.59; (E): 2.60, 2.18-3.09; (H): 2.02, 1.70-2.40; (L): 2.73, 1.98-3.76; and (M): 1.96, 1.32-2.91. Conclusions: Our findings suggest that 3-month injurious fall risk varied across OPI-BZD trajectories, highlighting the importance of considering both dose and duration when assessing fall risks of OPI-BZD use among older adults.

With the rapid development of new energy vehicles and the digital electronics industry, the demand for lithium has surged, necessitating advanced lithium extraction technologies. Electrochemical methods, noted for their high selectivity and efficiency in extracting target ions from liquid sources in an environmentally friendly manner, have become increasingly vital. These methods are versatile, applicable in scenarios such as lithium extraction from saline lakes, mother liquor separation, and lithium enrichment. They include electrochemical deintercalation, electrochemical ion pumps, and electrodialysis, each offering unique benefits and challenges depending on the application context. This review provides a detailed exploration of the research progress in lithium extraction using electrochemical methods and discusses future prospects for these technologies, emphasizing their potential to meet the growing demand for lithium.

Introduction: Lower respiratory tract infections, including pneumonia, are one of the leading causes of child mortality, especially in low-resource settings. Current guidelines rely on clinical signs for diagnosis, leading to over-prescription of antibiotics, which in turn contribute to antimicrobial resistance. Lung point of care ultrasound (L-POCUS) offers potential to improve diagnostic accuracy and reduce unnecessary antibiotic use, but lacks standardized guidelines for diagnosis and management of paediatric pneumonia. Methods and Analysis: This study utilizes a modified Delphi process to develop expert consensus guidelines for L-POCUS interpretation in paediatric pneumonia that would constitute a framework for effective guidelines for judicious antibiotic prescribing. The 5-stage iterative process includes: i) creation of a literature summary and conceptual framework, ii) first round of online surveys for expert feedback, iii) virtual meetings to discuss survey results and refine guidelines, iv) second round of online surveys, v) final analysis and development of consensus guidelines. A panel of 12-15 experts, chosen for their paediatric POCUS experience, geographic diversity, and gender balance, will participate. Consensus will be defined as ≥75% agreement. Ethics and Dissemination: Participation is voluntary, with consent obtained at the start and the option to withdraw at any time. The protocol was approved by the Ethics Commission of Bern, Switzerland. Findings will be disseminated through open access publication.

This paper represents a groundbreaking paradigm shift in network optimization. Departing from traditional static methodologies, this innovative approach harnesses the power of Generative Artificial Intelligence (AI) and Large Language Models (LLMs) to optimize cloud networks dynamically. By integrating advanced AI algorithms, this framework continuously adapts and evolves, ensuring optimal real-time performance. This dynamic optimization enhances efficiency and resilience, allowing cloud networks to adjust seamlessly to changing demands and conditions. Through the fusion of cutting-edge technology and adaptive intelligence, this approach heralds a new era in network optimization, empowering organizations to achieve unprecedent-ed levels of agility and scalability in their cloud infrastructures.

Accidental arterial embolization of hyaluronic acid (HA) fillers can lead to severe complications, including skin ischemia, blindness, and stroke. Currently, the intra-arterial dispersal and fragmentation behavior of HA gels is unknown but is critical to our understanding of the pathomechanism of these injuries. This work introduces the Pulsatile Unit for the Laboratory Simulation of Arterioembolic Restrictions (PULSAR) and evaluates the intravascular behavior of different HA gels. The fragmentation and dispersal behaviors of four HA gels with distinct rheological properties were evaluated via high-resolution videography and ImageJ particle size and morphology analysis. The gels' elastic modulus (G'), loss modulus (G''), tan(δ), and HA concentration were subsequently correlated with their intra-arterial behaviors. This study effectively confirms the extensive fragmentation of HA gels upon arterial inoculation, with particle sizes ranging from &lt;50 µm to &gt;1 mm. Gel particle size and morphology correlate most significantly with tan(δ). Conversely, arterial flow rates do not significantly influence gel fragmentation behavior, though the probability of proximal, macrovascular obstruction is affected. Overall, this study validates the PULSAR model for simulation of arterial dynamics and the testing of intravascular filler kinematics. The findings highlight the importance of gel viscoelasticity and flow parameters in determining particle size, dispersibility, and occlusive potential.

This study aimed to determine shifts in microbial populations regarding richness and diversity from the daily use of a popular over-the-counter nasal spray. In addition, the finding of nasal commensal bacterial species that overlap with the oral microbiome may prove to be potential probiotics for the “gateway microbiomes.” Nasal swab samples were obtained before and after using the most popular over-the-counter (OTC) nasal spray in 10 participants aged 18–48. All participants were healthy volunteers with no significant medical histories. The participants were randomly assigned a number by randomizing software and consisted of five men and five women. The sampling consisted of placing a nasal swab atraumatically into the nasal cavity. The samples were preserved and sent to Northwestern University Sequencing Center for whole-genome deep sequencing. After 21 days of OTC nasal spray use twice daily, the participants returned for further nasal microbiome sampling. The microbial analysis included all bacteria, archaea, viruses, molds, and yeasts via deep sequencing for species analysis. The Northwestern University Sequencing Center utilized artificial intelligence analysis to determine shifts in species and strains following nasal spray use that resulted in changes in diversity and richness.

We assessed the impact of social determinants of health (SDOH) and psychosocial factors on screening behavior in a nationally representative sample of women in the US. A retrospective population-level cross-sectional sample was extracted from the 2022 Health Information National Trends Survey. Descriptive statistics were conducted for demographic characteristics and covariates. Population-based estimates with 95% confidence intervals (95% CI) were produced for Pap testing behaviors across study years. We used logistic regression models to assess Pap testing differences based on SDOH and psychosocial factors, adjusting for covariates, with a significance level of 0.05 for hypothesis testing. Women (n=2,224) with a mean age of 46.96 participated in the study. Our study found that 90% of women were interested in cervical cancer screening, with an 80% actual screening rate. Screening rates differed by age group and rurality. SDOH and psychosocial factors were associated with participants’ interest in screening and in actual screening behavior. The impacts of SDOH and psychosocial factors on screening behavior were 3% and 1%, respectively. The SDOH and psychosocial factors are associated with the uptake of cervical cancer screening among women in the United States. Policies must be directed at bridging the gap created by these SDOHs.

This study evaluated the effect of pig diet supplementation with an Olea europaea L. extract on the muscle fatty acid composition. Ten commercial hybrid pigs (Large White x (Landrace x Duroc)) were randomly assigned to two experimental treatments and fed either a standard diet (C) or diet with olive leaves extract (OL). For 90 days, the OL group received the olive leaf extract (300 mg/head/day), which mainly comprises oleuropein diglucoside, luteolin-7-glucoside, and verbascoside. The phenolic content, antioxidant activity, bioactive molecules’ characterization, and the fatty acids profile of meat and diet were performed. The results indicated that while the OL supplementation did not significantly alter the overall chemical composition of the meat or the pigs' performance, it did modify the lipid profile of the meat. The OL diet results in a significant reduction in SFA and an increase in oleic acid in meat, which correspondingly elevates the total MUFA content. Dietary treatment reduced the sum of n-6 PUFA in the meat of the OL group, and resulted in a significantly lower n-6/n-3 PUFA ratio. Therefore, these findings suggest that incorporating olive leaf extract into the pig diet enhances the nutritional and functional quality of the meat by improving its fatty acid profile.

The young adolescents’ sexual behaviors are under-investigated. In this quantitative descriptive study, we examined the 2019 Middle School Youth Risk Behavior Survey data of 66,366 young adolescents ages 10-14 from 10 states to determine the prevalence of early sexual debut among young adolescents. Complex sampling design was used to produce descriptive statistics and cross-tabulations to describe young adolescents' sexual behaviors. Early sexual debut was reported at nearly 8%, and 4% of those reporting the age of first sex had their first sexual intercourse before 13 years. Compared to the Whites, Black/African Americans (13.2% vs 5.1%, OR=4.51, 95% CI: 2.78-7.31) and Hispanic young adolescents (8.3 % vs 5.1 %, OR=1.44, 95% CI=1.13-1,84) were more likely to report having early sexual intercourse. Males were more likely to report having multiple sexual partners than females (48.1% vs 36.5%, OR = 1.68, 95% CI = 1.22-2.29) and were more likely to report using condoms during the last sex compared to their female counterparts (59.7% vs 50.8%, OR = 1.43, 95% CI = 1.06-1.94). This study suggests the need for more research on young adolescents’ sexual behaviors and develop sexual health interventions that target preadolescence.

This review paper presents a comprehensive synthesis of current knowledge on the contamination of water systems by polycyclic aromatic hydrocarbons (PAHs). PAHs, organic contaminants characterized by two or more fused aromatic rings, are notably problematic due to their persistence, bioaccumulation, and significant health risks. The review commences with an examination of various sources of PAHs in aquatic environments, encompassing both anthropogenic activities, such as industrial discharges, urban runoff, and oil spills, and natural phenomena including volcanic eruptions and wildfires. Subsequently, the discussion shifts to the distribution patterns of PAHs within different aquatic ecosystems, with an analysis of factors that influence their transport. Considerable focus is placed on the entry mechanisms of PAHs into water systems and their interactions with diverse environmental matrices. Additionally, the ecotoxicological effects of PAHs on aquatic life are scrutinized, with particular emphasis on molecular, individual, and ecosystemic impacts. This includes an exploration of PAH bioaccumulation in aquatic organisms and their potential mutagenic and carcinogenic consequences. The review further addresses the challenges associated with detecting and quantifying PAHs in aquatic settings, reflecting on the advancements in analytical methodologies and the complexities introduced by their varied physicochemical properties. The paper concludes with a summary of existing regulatory frameworks and guidelines governing PAH contamination in water systems, underscoring the imperative for global collaboration in the monitoring and management of PAH pollution.

Background: Regular moderate-vigorous intensity exercise is recommended for adults as it can improve longevity and reduce health risks associated with a sedentary lifestyle. However, there are barriers to achieving intense exercise that may be addressed using virtual reality (VR) as a tool to promote exercise intensity and adherence, particularly through visual feedback and competition. The purpose of this work is to compare visual feedback and competition within fully-immersive VR to enhance exercise intensity and user experience of exercise for young adults; and to describe and compare visual attention during each of the conditions. Methods: Young adults (21- 34 years old) bicycled in three 5-minute VR conditions (visual feedback, self-competition and competition against others). Exercise intensity (cycling cadence and % of maximum heart rate) and visual attention (derived from a wearable eye tracking sensor) were measured continuously. User experience was measured by an intrinsic motivation questionnaire, perceived effort and participant preference. A repeated measures ANOVA with paired t-test post-hoc tests was conducted to detect differences between conditions. Results: Participants exercised at a higher intensity and had higher intrinsic motivation in the two competitive conditions compared to visual feedback. Further, participants preferred the competitive conditions and only reached a vigorous exercise intensity during self-competition. Visual exploration was higher in visual feedback compared to self-competition. Conclusion: For young adults bicycling in VR, competition promoted higher exercise intensity and motivation compared to visual feedback.

Background/Objectives: Dengue is an arbovirus caused by a virus. It is an endemic infectious and occurs in warmer climates. It is not uncommon for the disease to be asymptomatic. However, the severe form can also be triggered and require intensive care. In this sense, patients present a wide variety of symptoms, which can trigger comorbidities such as arthritis, hematologic diseases, liver diseases, kidney diseases, autoimmune diseases, and, mainly, diabetes and hypertension. Among the symptoms, the presence of fever, myalgia, headache, nausea, vomiting, leukopenia, petechiae, retroorbital pain, arthralgia, rashes, skin eruptions, cardiovascular symptoms, respiratory symptoms and, depending on the severity, the presence of hemorrhages may occur. Methods: 235 patients' anonymized records from a secondary hospital were analyzed. Ethics approval was obtained and no patients’ consent was needed. Statistical analysis used frequency distributions and Chi-square tests, with SPSS software. Results: Similar to other studies, our results show that dengue can lead to complications. Furthermore, there was no significant difference in the distribution of the proportion of symptoms between patients with positive and negative serology. However, there was a significant association between age group and symptoms of fever and myalgia, with the occurrence of fever decreasing with increasing age and myalgia being more frequent in adults and less frequent in those &lt;10 years old. Conclusions: Dengue can lead to complications, with fever becoming less common and muscle pain increasing as people age. Climate change could spread dengue to new areas. To address this, we need better vaccines and more effective mosquito control.

Shiga toxin-producing Escherichia coli (STEC) is a significant public health threat due to its ability to cause severe gastrointestinal diseases in humans, ranging from diarrhea to life-threatening conditions such as hemorrhagic colitis and hemolytic uremic syndrome (HUS). As the primary reservoir of STEC, cattle play a crucial role in its transmission through contaminated food and water, posing a considerable risk to human health. This comprehensive review explores host-pathogen interactions during STEC colonization of the bovine gut, focusing on the role of gut microbiota in modulating these interactions and influencing disease outcomes. We integrated findings from published transcriptomics, proteomics, and genomics studies to provide a thorough understanding of how STEC adheres to and colonizes the bovine gastrointestinal tract. The insights from this review offer potential avenues for the development of novel preventative and therapeutic strategies aimed at controlling STEC colonization in cattle threby reducing the risk of zoonotic transmission.

Chymotrypsin from the digestive organs of bigfin reef squid, a major commercial squid species in Thailand, was purified to 41.27-fold with 5.74% yield by a sequential purification process including ammonium sulfate precipitation, size exclusion and ion exchange chromatography. According to SDS-PAGE, the molecular weight of purified chymotrypsin was 43 kDa. Native-PAGE analysis revealed a single band for this purified enzyme. Optimum pH and temperature for chymotrypsin activity of the purified enzyme were pH of 7.0 with a temperatures of 55°C. The purified chymotrypsin remained stable throughout a wide range of pH levels (6–11) and at relatively high temperature (50°C). It was significantly inhibited by PMSF and TPCK. The values of the kinetic constants Km and Kcat were found to be 1.33 mM and 31.46 s‒1, respectively. The purified chymotrypsin has the N-terminal amino acid IVGGQEATPGEWPWQAALQV. This study provided new information about the biochemical properties of pure chymotrypsin from bigfin reef squid, which is useful in the future investigation, aquaculture and application of bigfin reef squid.

The recent growth of wearable medical device technology in the form of fitness trackers, smart watches, smartphone apps, and patient monitoring systems has created people-generated health data (PGHD) that may benefit medical science with large amounts of continuous real-world data. The prevalence of these devices speaks to their broad popularity and user-friendliness and may lead us one day to a more fully “connected healthcare system.” Meanwhile, data security, confidentiality, and privacy issues have emerged in these hackable systems. Despite the promise of anonymized data, data can sometimes be re-identified, but even without that step, data breaches may reveal information (name, address, date of birth, social security number, and so on) sufficient for identity theft. Clinicians are often asked about the utility and value of wearable devices or monitors, but most are unaware that data from these systems may be transmitted, stored, and even sold without the user’s specific knowledge. Despite the confidentiality of medical information, cybersecurity surrounding wearables and monitors remains relatively lax, making them comparatively easy targets for cyber-villains. It is also important that efforts be taken to make PGHD more secure, since medical data may have great value to telehealth applications and AI-physician assistants. Clinicians should take an active role in informing patients about both risks and benefits of wearables and similar devices.

Adolescence is a critical period for the development of self-perception, emotional well-being, and health-related behaviors. During this stage, adolescents undergo significant physical, emotional, and social changes that influence their overall health and interactions with their environment. This study analyzes the prevalence of behaviors related to self-perceived health, mood, and substance use among adolescents, identifies risk factors, and draws comparisons between different groups. It also examines how these factors interact with family and community dynamics to inform strategies for improving mental health care. Method: A descriptive cross-sectional study using questionnaires was conducted. Participants were adolescents aged 14 to 18 years from a school in the Baix Llobregat province of Catalonia. Descriptive and bivariate statistical analyses were performed using the chi-square test and p-value calculations with R Project software. Frequency and percentage analyses were employed to describe the health behaviors and emotional states of the participants. Results: The study reveals significant variations in adolescents' self-perceived health, emotional management, and substance use patterns. Adolescents with lower self-perceived health and negative mood states tend to exhibit higher rates of substance use, particularly alcohol and tobacco. Gender differences were observed, with girls generally reporting better health awareness and emotional regulation compared to boys. Conclusions: This study highlights the need for integrated approaches to family, community, and mental health care. Findings emphasize the importance of early intervention programs addressing emotional well-being and substance use in a holistic manner. Public health policies should prioritize comprehensive strategies involving schools, families, and communities to foster healthier behaviors and improve adolescent mental health outcomes.

Previous reviews by the authors [1, 2] indicate the continuing development and improvement of thermal protective systems through the introduction of polymer nanocomposites into polymer matrix composites. These materials perform as thermal protective systems for a variety of aerospace applications, such as thermal protection systems (TPS), solid rocket motors (SRM) nozzles, internal insulation of SRM, leading edges of hypersonic vehicles, and missile launch structures. A summary of the most recent, global technical research is presented. Polymeric resin systems continue to emphasize phenolic resins and other materials. New high-temperature organic resins based on phthalonitrile (PN), and polysiloxane are described and extend the increased temperature range of resin matrix systems.

Time can be a difficult concept to understand. Albert Einstein, who viewed time as an illusion, explained the passage of time is relative to the observer’s frame of reference in the space-time continuum. However, the state of consciousness of the observer also influences the passage of time. This paper examines the relationship between the experience of time and different states of consciousness including near-death experiences, mystical states of consciousness, and psychedelic medicine-induced states of consciousness. Two different experiences of time are described. These are Chronos and Kairos. Chronos is described as 4th dimensional time whereas Kairos is 5th dimension time. Methods for facilitating the experience of Kairos are discussed and the potential benefits of experiencing Kairos are reviewed.

Oxidative stress plays an essential role in the pathological processes that trigger various chronic liver diseases and contributes to the development of hepatocarcinogenesis. Antioxidants from natural sources trap free radicals by converting them into non-harmful products and minimize oxidative stress, playing a crucial function in the treatment of free radical-induced diseases. However, the activity of these antioxidants is limited due their poor bioavailability, which is why various nano-drug delivery systems have been developed to improve their stability, promote smooth release, and targeted delivery for liver cancer treatment. Specifically, this review aims to report recent scientific findings of novel nano-formulations containing natural antioxidant molecules targeted for the treatment of liver cancer.

Background and Objectives. To examine trends in the links between induced abortion and subsequent mental health problems for U.S. women approaching completed fertility. Materials and Methods. Panel data on a nationally-representative cohort of 3,842 ever-pregnant women assessed at mean ages of 15, 22, 28 and 37 years from the National Longitudinal Study of Adolescent to Adult Health (Add Health) were examined for pregnancy outcome-related mental health disorders, with extensive adjustment for confounders including sociodemographic dif-ferences, mental health history, and unwanted pregnancies. Outcomes were defined using pub-lished diagnostic criteria or validated index for depression, anxiety disorder, post-traumatic stress disorder (PTSD), and suicide ideation (affective problems); alcohol abuse, drug abuse, opioid abuse, and cannabis abuse (substance abuse problems); and summary counts of affective problems, substance abuse problems and total disorders. Results were adjusted for abortion under-reporting using cross-wave analysis. Results. The relative risk of mental health disorder with exposure to induced abortion followed an inverted “V” pattern as women aged to midlife, increasing from Wave III (age 22; IRR 1.41) to Wave IV (age 28; IRR 1.67), then dropping sharply by Wave V (age 37; IRR 1.20). The population at-tributable fraction of mental health disorder due to abortion dropped from 18.1% at Wave IV to 8.0% at Wave V. Unlike previous Waves, at Wave V mental health risk was more strongly reduced by exposure to childbirth (IRR 0.70, 95% CI .63, .78, p < .001). Reduced relative metrics at Wave V were not due to reduced prevalence of mental health disorders for ever-aborting women, which increased from Wave IV to Wave V by 1.7%, but increased much more, by 20.5%, for never-aborting women. Conclusion. At midlife approaching completed fertility, differential negative psychological out-comes for ever-aborting U.S. women remained elevated but reduced from younger ages.

Pancreatic ductal adenocarcinoma (PDAC) is the fifth leading cause of cancer-related death in and presents the lowest 5-year survival rate for any form of cancer in the US. Only 20% of PDAC patients are suitable for surgical resection and adjuvant chemotherapy which remains the only curative treatment. Chemotherapeutic and genetherapy treatments are associated with adverse effects and lack specificity/efficacy. In this study we assess the oncolytic potential of immuno-oncolytic tanapoxvirus (TPV) recombinants expressing mouse monocyte chemoattractant protein (mMCP-1 or mCCL2), and mouse interleukin (mIL)-2, in human pancreatic BxPc-3 cells, using immunocompromised and CD-3+ T-cell reconstituted mice. Intratumoral treatment with TPV/∆66R/mCCL2 and TPV/∆66R/mIL-2 resulted in regression of BxPc-3 xenograft volume as compared to control in immunocompromised mice; mCCL-2 expressing TPV OV resulted in significant difference from control at p

The study of the impact of polyQ expansion driven proteotoxicity on cell metabolism has evi-denced NAD molecule as a central player in regulating metabolic response and cell repair in neurodegeneration. The decline in NAD intracellular levels represents a hallmark of ageing aris-ing from a dysregulation between NAD-consuming and biosynthetic enzymatic reactions in which NMNAT plays a key role. By an integrated bioanalytical and proteomic experimental design, the derangement of NAD metabolism deriving from the accumulation of polyQ-Htt protein has been analysed in Saccha-romices cerevisiae harbouring a 103Q-Htt and compared with wild-type Htt, in absence and in presence of a phenolic extract from EVOO, as a source of antioxidant bioactive compounds. Quantification of NAD and its precursors and proteomic analysis of the differential protein ex-pression has been performed by LC-DAD-MS. Chronological lifespan and NAD homeostasis was strongly impaired by proteotoxic polyQ-Htt, eliciting a depletion of NAD levels and accumulation of NaMN. In parallel a downregulation of Sirt2 expression levels has been observed. Phenolic extract administration had no meaningful ef-fects on NAD replenishment to prevent proteotoxicity. NaMN can represent a biomarker of accel-erated aging, and/or a signaling molecule for cell repair.

Acute myeloid leukemias are characterized by genetic alterations that lead to a complete or partial block at various stages of myeloid differentiation, leading to continual proliferation of myeloid progenitor cells. These alterations can include a well-documented chromosomal translocation that leads to the synthesis of the PML-retinoic acid receptor fusion protein that leads to a block in differentiation and the ability to induce differentiation with all-trans retinoic acid and other small molecules. In essence, in large part, the disease is due to stem cell-like cells that are blocked in their ability to undergo terminal differentiation to more mature, non-proliferative cell types. We discovered a long non-coding RNA (lncRNA), lncRNAp53int1, encoded from the first intron of the p53 tumor suppressor gene. Interestingly, lncRNAp53int1 appears to play an important regulatory role in maintaining the undifferentiated and proliferative state in a manner independent from p53 gene expression. lncRNAp53int1 is expressed at high levels in proliferating, undifferentiated promyelocytes and its levels fall significantly during their terminal differentiation to non-proliferating granulocytes or macrophages. Furthermore, forced overexpression of lncRNAp53int1 blocks terminal differentiation. The observation that the expression of this lncRNA is repressed during terminal differentiation of human leukemic cells and its expression blocks differentiation of leukemic myeloid progenitor cells, is likely to have clinical implications with regards to differentiation therapy for myeloid leukemia. Ongoing research aims to identify the molecular partners that it associates with and the signaling pathways that this lncRNA participates in with the long-term goal of identifying molecules that inhibit lncRNAp53int1 activity and serve as potential therapeutic drugs. The goal of this mini-review is to disseminate these novel and interesting findings to readers and to describe where we think this research is headed and the impact it can have on myeloid leukemias.

The nuclear magnetic resonance (NMR) metabolomic analysis was applied to investigate the differences within nineteen Sicilian Nocellara del Belice mono varietal Extra Virgin Olive Oils (EVOO), grown in two zones different for altitude and soil composition. Several classes of endogenous olive oil metabolites were quantified through a nuclear magnetic resonance (NMR) three-experiment protocol coupled with a yet developed data-processing called MARA-NMR. This method, taking around one-hour experimental time per sample, faces the possible quantification of different class of compounds at different concentration’s range which would require at least three alternative traditional methods. NMR results were compared with the data of traditional analytical methods to quantify free fatty acidity (FFA), fatty acid methyl esters (FAMEs), and total phenol content. The presented NMR methodology is compared with traditional analytical practices and its consistency is also tested through slightly different data treatment. Despite the rich literature about the NMR of EVOOs, the paper points out that there are still several advances potentially improving this general analysis and overcoming the other cumbersome and multi-devices analytical strategies. Monovarietal EVOO’s composition is mainly affected by pedoclimatic conditions in turn relaying upon the nutritional properties, quality, and authenticity. Data collection, analysis and statistical processing are discussed touching the important issues related to the climate changes in Sicily and to the specific influence of pedoclimatic conditions.

Introduction This study was conducted to validate the findings of a prior study published in JDD in September 2023, which reported that a topical firming and toning body lotion (FTB – SkinMedica®, Allergan Aesthetics, an AbbVie Company, Irvine, CA) upregulated several genes in a UV irradiated 3D full-thickness human skin model, outperforming other products, including TransFORM Body Treatment with TriHex Technology® (ATF – Alastin Skincare®, a Galderma company Fort Worth, Texas, USA ). Given the unique response reported for FTB, we conducted this study to assess the reproducibility of these results and explore gene expression at multiple time points, along with validating protein expression in an ex vivo model. Materials and Methods Experiments were conducted using an ex vivo model with photodamaged skin from facelift patients, under an Institutional Review Board approved study. Skin samples were processed, cultured in transwells with Skin Media, and treated daily with either TransFORM or FTB for 7 days. A control group was left untreated. Gene expression was assessed using RT-PCR on days 1 and 3, immunofluorescence after 3 and 7 days of treatment. Skin samples were fixed, paraffin-embedded, sectioned, and stained with an anti-tropoelastin antibody. Fluorescence detection and imaging were conducted to assess protein expression changes. Results Gene expression data from our study and the initial study showed a few similarities but multiple discrepancies. In particular, as opposed to results previously reported at only the 24-hour time point, additional time points showed complete reversal of many of these results. For example, COL1A1 expression at 24 hours was similar for FTB in both studies but differed for TransFORM which showed higher levels at 24 hours. However, at day 3, COL1A1 expression decreased markedly for FTB and was sustained for TransFORM. Other genes, such as COL3A1, COL5, ELN, VEGFC, ATG7, ATG12, BECN1, POMP, PSMB5, and PSMB6, exhibited varying expression patterns between the studies and across different time points. From a translational perspective, histological analysis showed that TransFORM enhanced elastin fiber presence in the dermal-epidermal junction (DEJ) more effectively than FTB at both day 3 and day 7. FTB-treated samples maintained a gap in the DEJ, while TransFORM-treated samples exhibited increased cellular proliferation and DEJ undulation, indicative of a healthier regenerative response. Conclusion This study highlights the problems of examining data and drawing conclusions using a single point of examination. In addition, when a study reports positive results for only 1 product among a range of 8 competitive products, further questioning is essential to exclude the possibility of the experimental model favoring that particular product. The additional 3-day timepoint and further translational examination of histological changes, paints a completely different picture to that reported in the prior publication TransFORM outperformed FTB in most gene expression and histological parameters when assessed over multiple time points in a physiologically relevant ex vivo model.

The gut microbiota (GM) communicates with the brain via biochemical signaling constituting the gut-brain axis, which significantly regulates the body's physiological processes. The GM dysbiosis can impact the digestive system and the functioning of the central nervous system (CNS) linked to the onset of neurodegenerative diseases. In this review, the scientific data compiled from diverse sources primarily emphasizes the neuropathological characteristics linked to the accumulation of modified insoluble proteins (such as β-Amyloid peptides and hyperphosphorylated tau proteins) in Alzheimer’s Disease (AD) and the potential impact of gut microbiota (GM) on AD susceptibility or resilience. The specific GM profile of human beings may serve as an essential tool for preventing or progressing neurodegenerative diseases like AD. This review focuses mainly on the effect of gut microfauna on the gut-brain axis in the onset and progression of AD. The GM produces various bioactive molecules that may serve as proinflammatory or anti-inflammatory signaling, contributing directly or indirectly to the repression or progression of neurodegenerative disorders by modulating the response of the brain axis. Human studies must focus on further understanding the gut-brain axis and venture to clarify microbiota-based therapeutic strategies for AD.

Introduction: The repertoire of microRNAs (miRNAs) in thyroid carcinomas starts to be elucidated. Among differentiated thyroid carcinomas (DTC), papillary thyroid carcinoma (PTC) is the most common. The assessment of miRNAs expression may contribute to refine the pre-surgical diagnosis, in order to obtain a personalized and more effective treatment of patients. Aims: This study aims to evaluated 1) miRNAs expression in a series of DTC, and the association with the presence of selected genetic mutations, in order to improve diagnosis and predict biologic behavior of DTC/PTC. 2) the reliability of molecular tests in Ultrasound-guided Fine Needle Aspiration Cytology (US-FNAC) for a more precise preoperative diagnosis. Material and methods: This series includes 176 samples (98 cytology samples and 78 formalin-fixed paraffin embedded (FFPE) tissues) obtained from 106 patients submitted to surgery, being 13 benign lesions (controls) and 93 DTCs (cases). The microRNA expression was assessed for miR-146b, miR-221, miR-222, and miR-15a by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and the results were analyzed using the 2- ΔΔCT method, using miR16 as an endogenous control. The discriminative ability of miRNAs expression regarding PTC diagnosis was evaluated using the area under the Receiver Operating Characteristic Curve (AUC). The association of miRNAs expression, clinicopatological features and genetic alterations (BRAF, RAS and TERTp) was evaluated in PTCs. Results/Discussion: All the analyzed miRNAs showed a tendency to be over expressed in DTCs/PTCs when compared with benign lesions, both in cytology and histology samples. In cytology, miRNAs expression levels were higher in malignant than in benign tumors. In histology, corresponding discriminative abilities regarding PTC diagnosis were: miR-146b (AUC0.94, 95%CI 0.87-1), miR-221 (AUC0.79, 95%CI 0.68-0.9), miR-222 (AUC0.76, 95%CI 0.63-0.89) and miR-15a (AUC0.85, 95%CI 0.74-0.97). miR-146b showed 89% sensitivity (se) and 87% specificity (sp); mi-R221 se=68.4, sp=90; miR222 se=73, sp=70, and mi-R15a se=72, sp=80. MicroRNAs were associated with aggressive clinicopathological features and tumor progression in PTCs (p &lt; 0.05), particularly for miR-222. Our data reveals a significant association between higher expression levels of miR-146b, miR-221 and miR-222, with the presence of BRAF mutation (p&lt;0.001), and miR-146b (p=0.016) and miR-221 (p=0.010) with the presence of RAS mutation, suggesting an interplay of these mutations with miRNAs expression. Although this study has a relatively small sample size, over expression of miRNAs in cytology may contribute to a more precise preoperative diagnosis. The miRNAs showed a good discriminative ability in PTC diagnosis. The association between the miRNAs expression profile and genetic alterations results could be useful for an accurate diagnosis of DTCs/PTCs in FNAC.

White oak mortality is a significant concern in forest ecosystems due to its impact on biodiversity and ecosystem functions. Understanding the factors influencing white oak mortality is crucial for effective forest management and conservation efforts. In this study, we aimed to investigate the spatial pattern of white oak mortality rates at different locations of the eastern US and explore the underlying processes involved with the spatial distribution patterns. Multicycle Forest Inventory and Analysis data were compiled to capture white oak plots across the eastern US. White oak mortality data were collected across plot systems that utilized Diameter at Breast Height between two periods. Ripley’s K function was used to study the spatial pattern of white oak mortality rate. Results found clustered patterns at both local and broad scales and random patterns at broad scales only across the southern and northern regions. However, the central region indicated both clustered and random patterns at local scale only. We found uniform patterns at a broad scale across all regions. Our findings demonstrated the importance of the spatial pattern of the white oak mortality rate and the underlying factors associated with it. This research can inform forest management practices for the conservation of white oak populations at varying scales. Future research is needed for a comprehensive assessment of biotic and abiotic factors for forest management strategies at various spatial scales aimed at mitigating white oak mortality.

1) Landsat operational land imager (OLI) data and consequent laboratory measurements were used to predict Chlorophyll-a (Chl-a) concentration and the trophic states for an inland lake within the East Kolkata Wetland, India; 2) The most suitable band ratio was identified by performing Pearson correlation analysis between Chl-a concentrations and possible OLI band and band ratios from the study points; 3) The results showed highest correlation coefficient from the band ratio OLI5/OLI4 with an R value of 0.85. The prediction model was then developed by applying regression analysis between the band ratio OLI5/OLI4 and Chl-a concentration of the study points. The reflectance ratios of the validation points were given as input on the prediction model and the model output was considered as predicted Chl-a values of the validation points to check the efficiency of the prediction model. The regression model between laboratory-derived Chl-a value and model-fitted Chl-a value of the validation points revealed a high correlation with an R² value of 0.78. Trophic State Index (TSI) of the lake was also calculated from laboratory-derived Chl-a value and model-fitted Chl-a value of the validation points. The study presented a high correlation of TSI determined from predicted data with TSI from laboratory reference data (R = 0.88). The TSI values of the lake ranged from 65 to 75 which indicate that the lake is appeared to be eutrophic to hypereutrophic conditions. 4) This empirical study showed that Landsat 8 OLI imagery can be effectively applied to estimate Chl-a levels and trophic states for inland lakes.

Etiological factors involved in myelodysplastic syndrome (MDS) include immunologic, oxidative stress, and inflammatory factors, among others, and these are targets for microRNAs (miRNs). Here, we evaluated whether some miRNs may affect the tumor development comparing untreated and 5-azacitidine (5-AZA) MDS-treated patients. Peripheral blood samples were collected from 20 controls and 24 MDS patients, and selected miRNs related to redox balance and inflammation, including miR-18a, miR-21, miR-34a and miR-146a, were isolated and measured by quantitative real-time polymerase chain reaction (qRTPCR). A differential expression profile of miRNs was detected in untreated MDS patients and 5-AZA group. MiR-18a, miR-21, miR-34a and miR-146a were significantly overexpressed in untreated MDS, compared to controls. However, we did not observe any miRNs profile alteration during the progression of the disease. On the other hand, 5-AZA treatment tends to restore miRNs expression levels. Relating to prognostic risk factors, high risk MDS groups (high IPSS-R, high cytogenetic risk, high molecular risk (HMR) mutations tended to be related with higher expression levels of miR-18a and miR-34a. Higher miRNs expression is correlated with lower glutathione peroxidase activity, while they are related with a higher profile of pro-inflammatory cytokines (IL-2, IL-6, IL-8, TNF-α). Although our study was limited by the low number of MDS patients included, we identified miRNs deregulation involved in the MDS development, that could regulate redox sensors and inflammatory responses. Finally, 5-AZA treatment is related with lower miRNs expression levels in MDS patients.

Mississippi youth are demographically unique compared to that of the nation. The purpose of this study was to determine the trend of drug use among adolescents of the United States and Mississippi, and to estimate the differences of drug use prevalence as a whole, and by gender and by race. National and Mississippi YRBSS data from 2001 to 2021 were obtained for analysis. Summary statistics, prevalence ratio, and survey Chi-squared tests of independence statistics were generated for the comparison for all students, and by gender and race separately. Trend analysis was conducted using logistic regression combined with joinpoint regression. Six survey questions being studied were: have you ever used marijuana, inhalant, heroin, methamphetamines, injected drugs, and were you offered, sold, or given an illegal drug on school property during the last 12 months. Survey packages in R were used to account for the complex sampling design of YRBSS data. On the national level, all six drug related risk behaviors being studied showed significant decrease from 2001 to 2021. In Mississippi however, only “ever used marijuana” showed a trend of decrease, while three remain unchanged, and two increased. 2021 YRBSS data shows that Mississippi adolescents exhibited significantly higher prevalence of drug use, and are more likely to be offered, sold or given an illegal drug on school property. Our study suggests an urgent need for drug use intervention among Mississippi adolescents. More concerted actions at the community, school and government level are needed for reducing youth drug use and controlling the drug traffic on school property.

Postprandial glucose levels between 4 and 7.9 hours (PPG4–7.9h) correlate with mortality from various diseases including hypertension, diabetes, cardiovascular disease, and cancer. This study aimed to assess if predicted PPG4–7.9h could diagnose diabetes. Two groups of participants were involved: Group 1 (4420 participants) had actual PPG4–7.9h, while Group 2 (8422 participants) lacked this measure but had all the diabetes diagnostic measures. Group 1 underwent multiple linear regression to predict PPG4–7.9h using 30 predictors, achieving accuracy within 11.1 mg/dL in 80% of the participants. Group 2 had PPG4–7.9h predicted using this model. Receiver operating characteristic curve analysis showed that predicted PPG4–7.9h could diagnose diabetes with an accuracy of 87.3% in Group 2, with a sensitivity of 75.1% and specificity of 84.1% at the optimal cutoff of 102.5 mg/dL. Simulation on 10,000 random samples from Group 2 revealed that 175 participants may be needed to investigate PPG4–7.9h as a diabetes diagnostic marker with a power of at least 80%. In conclusion, predicted PPG4–7.9h appears to be a promising diagnostic indicator for diabetes. Future studies seeking to ascertain its definitive diagnostic value might require a minimum sample size of 175 participants.

Heavy rains result in significant threats to human health and life. Floods and other natural disasters, which have a global impact annually, can be attributed to extended periods of intense precipitation. Accurate rainfall prediction is crucial in nations such as Bangladesh, where agriculture is the predominant field of occupation. The efficiency of machine learning methods is enhanced by the nonlinearity of rainfall, surpassing the effectiveness of other approaches. This study proposes the novel combination of rainfall occurrence prediction, rainfall amount prediction, and daily average temperature prediction. This research implements machine learning techniques and an ensemble-based classifier to predict rainfall occurrence, as well as machine learning regressor models and an ensemble-based regressor to predict the rainfall amount and daily average temperature, using the Bangladesh Weather Dataset. The ensemble classifier demonstrated an accuracy of 83.41% and a recall of 78.17%, exhibiting the best performance in predicting when it will rain, but its precision was the lowest, at 51.16%. The ensemble regression model outperformed the base models, including linear regression, random forest, and support vector regression in rainfall amount prediction, with the lowest mean absolute error of 0.36 and root mean squared error of 0.90. Additionally, this model provided the most precise daily average temperature prediction results with the lowest mean absolute error of 0.42 and root mean squared error of 0.54, highlighting its superiority over the other regression models in forecasting temperature. Ensemble approaches consistently exhibit superior task performance metrics.

The worldwide competition to vaccinate against COVID-19 has highlighted the importance of immunization measures in containing the virus. Saudi Arabia, like the rest of the globe, must assess socio-demographic subtleties, chronic illnesses, vaccination effects, and public health policy implications as it navigates this complicated environment. This cross-sectional study examined Saudi COVID-19 vaccine in many ways. It examined the socio-demographic makeup of vaccine recipients, the prevalence of chronic conditions in this population, vaccine administration patterns, post-vaccination side effects, and vaccine-infection rates. A questionnaire-based online survey of 401 participants ensured gender, nationality, age, weight, and educational diversity. We analyzed vaccine manufacturer choice for each dosage, side effects after the first and second doses, and chronic diseases in the sample. Pfizer/BioNTech vaccines are preferred for all three doses, reflecting worldwide vaccination acceptance patterns. Side effects were not significantly different between vaccination kinds. Interestingly, immunization reduced infection rates, demonstrating the efficacy of COVID-19 vaccines. The data fills important information gaps and illuminates Saudi COVID-19 vaccination kinetics. These data support the global preference for mRNA vaccines, demonstrating the faith in this breakthrough technology. They also sponsor COVID-19 vaccine safety and effectiveness studies. The dramatic drop in infection rates among vaccinated people shows how vaccinations suppress the pandemic. These findings inform Saudi Arabia's immunization efforts. As booster doses become more common, long-term vaccination research is crucial. Vaccine reluctance, especially in certain demographics, must be addressed. Due to vaccines' protective potential, equitable vaccine distribution and large immunization programs are essential for herd immunity and pandemic management. This thorough cross-sectional study helps policymakers and healthcare practitioners build successful and inclusive COVID-19 immunization regimens in Saudi Arabia.

Rabbit hemorrhagic disease virus disease 2 (RHDV2) emerged in the United States in 2018 and has spread in both domestic and wild rabbits nationwide. The virus has a high mortality rate and can spread rapidly between infected individuals. Vaccination against RHDV2 provides the best protection against disease and should be considered by all rabbit owners. Here, we investigate the duration of immunity provided by vaccination with the Medgene Platform conditionally licensed commercial vaccine 6 months following the initial series. Rabbits received either the vaccination or a placebo and were challenged with RHDV2 6 months later. All vaccinated rabbits survived challenge whereas 18/19 non-vaccinated controls succumbed to infection within 10 or fewer days post-challenge. These results demonstrate lasting immunity following vaccination with the Medgene RHDV2 vaccine.

Chronic inflammation alters lipoprotein metabolism and causes changes in serum concentrations of lipids, C-reactive protein (CRP), and paraoxonase-1 activity (PON-1), an enzyme, which in the gastrointestinal tract may act as a local detoxifier, antioxidant, and immunomodulator. However, unlike in people with inflammatory bowel disease, scarce information is available in dogs with protein-losing enteropathy secondary to chronic inflammatory enteropathy (iPLE). The first aim was to describe and compare the lipid profile, CRP concentrations and PON-1 activity in healthy dogs and in dogs with iPLE. The second aim was to evaluate correlations among clinicopathological, histologic data, and lipid profiles in dogs with iPLE. Serum samples from 51 iPLE and 40 healthy dogs were used to study albumin, total protein, CRP, PON-1 activity, cholesterol, triglycerides, and lipoprotein classes obtained by electrophoretic separation. There was a significant difference of all serum analytes between iPLE and healthy dogs. Significant correlations between the lipid profile and the existing chronic enteropathy activity index were not found. Some lipoprotein classes correlated with CRP and PON-1. Triglycerides were significantly higher in dogs with both inflammation and lymphangiectasia. Lipoproteins, CRP and PON-1 activity are altered in dogs with iPLE. Results need to be confirmed in further studies.

A structure based analysis of the pion’s decay path reveals that neutrinos can show up in three eigenstates. It requires a proper understanding of the nature of charged leptons, such as why the loss of binding energy stops the lepton generation at the tauon level. The analysis quantifies this binding energy in terms of the weak interaction strength as embodied by the weak interaction boson and the strength of the energetic background field as embodied by the Higgs boson. Next to this it is shown that a reconstruction of Fermi’s neutrino theory allows a quantitative assessment of the Fermi constant straightforwardly from the weak interaction strength. The article ends with the conclusion that neutrino oscillation is not a physical phenomenon, but, instead, a measurement interpretation induced from projecting the statistical behaviour of a multi-particle ensemble onto a single particle.

Time evolution of the quantum correlation of the hybrid qubit-qutrit system in multilocal and global dephasing under the effect of a classical noises environment is presented. We considered the qutrit in z direction and the qubit x direction. In addition, our system presents two configurations: the different and the common environment and our discussion involves three types of noises: A Static Noise (SN), Random Telegraph Noise (RTN) and Ornstein- Uhlenbeck noise (OU). By using the density matrix approach to determine the evolution of the state of the system, the found that the static noise is fatal for the quantum entanglement, the quantum correlation and for RTN and OU noises the quantum entanglement, the quantum correlation decreases monotonically with a sufficiently long time. Therefore, we can say that, entanglement and the quantum correlation are more robust to the noise precisely those Random telegraph noise and Ornstein-Uhlenbeck noise.

Regular assessment of mood is used in Brazil for a wide variety of purposes, including screening athletes to provide an indicator of psychological wellbeing and risk of mental health issues. The present study tested the psychometric characteristics of the Brazil Mood Scale (BRAMS) using both “right now” and “past week” response time frames and investigated between-group differences in mood based on athlete sex, age, and social vulnerability. Participants were 898 athletes (511 male, 387 female, age range: 12–44 years) from eight sports. Structural equation modelling supported the BRAMS measurement model using both response time frames independently and in a multi-sample analysis. Subscale reliability was supported for both time frames. Fatigue, depression, and tension scores were higher using the past week time frame than the right now time frame. Males reported higher vigor scores than females, and younger participants (&lt;18 years) reported lower scores for anger and depression than older participants (18+ years). No significant between-group differences emerged for social vulnerability. Findings supported the psychometric integrity of the BRAMS and its use as a screening measure for psychological wellbeing among youth and elite athletes in Brazil.

Abstract: Giant Cell Arteritis (GCA) is an autoimmune/autoinflammatory disease affecting large vessels in patients over 50 years old. The disease presents as an acute inflammatory response with two phenotypes, cranial-GCA and Large Vessel Vasculitis (LV)-GCA, involving the thoracic aor-ta and its branches. 18F-fluorodeoxyglucose positron emission tomography-computed tomogra-phy (18F-FDG PET-CT) is among the imaging techniques contributing to diagnosis of patients with systemic disease. However, its association with soluble inflammatory markers is still elu-sive. This proof-of-concept study aims to identify novel soluble serum biomarkers in PET/CT pos-itive patients with LV-GCA and associate them with active (0 months) and inactive disease (6 months following treatment), in sequential samples. The Most-Disease-Segment Target-to-Background Ratio (TBRMDS) was calculated for 9 LV-GCA patients, while 12 cranial-GCA and 7 Polymyalgia Rheumatica patients with negative initial PET/CT served as disease controls. Serum macrophage-related cytokines were evaluated by Cytometric Bead Array (CBA). Finally, previously published NMR-metabolomics data acquired at the same blood sampling were associated with PET/CT findings. TBRMDS was significantly increased in active versus inactive disease (3.45 vs. 2.55, p=0.008). The analysis identified 6 serum metabolites, as more sensitive to change from the active to inactive state. Among them, choline levels were exclusively altered in the LV-GCA group, but not the disease controls. Cytokine levels were not associated with PET/CT activity. Combining with CRP, ESR, and TBRMDS a composite index was generated to depict well the differences between active and inactive systemic LV-GCA (25.45 vs 11.45, p=0.0039). These preliminary results could pave the way for more extensive studies integrating serum metabolomic parameters with PET/CT imaging data to extract sensitive composite disease indexes useful for the everyday clinical practice.

Atypical antipsychotic drugs were introduced in the early 1990th. Unlike typical antipsychotics, which are effective only against positive symptoms of schizophrenia, atypical antipsychotics show effectiveness against negative and cognitive symptoms as well. Furthermore, they are effective not only in psychotic, but also in affective disorders, by their own or as adjuncts to antidepressant drugs. While typical antipsychotics act, almost exclusively, via dopamine-2 (D2) receptors, atypical target serotonin-1A/1B/2A/2C (5-HT1A/1B/2A/2C), α1/2-adrenergic, and/or histamine-1 (H1) receptors as well. Blocking of 5-HT1A/1B autoreceptors, inducing their early desensitization, and/or activation of α1-adrenoceptors, allow some atypical drugs to enhance 5-HT transmission. Blocking of 5-HT2A/2C and/or α2-adrenoceptors enable some atypical antipsychotics to stimulate catecholamine transmission and/or diminish the inhibition of catecholamine neurons induced by some antidepressants. It is possible, that the activation of H1 and/or blocking of H3 boost monoamine transmission as well, via a mechanism involving stimulation of firing activity of dopamine neurons. The experimental drugs with antipsychotic potential, acting on adenosine and trace amino associated (TAAR) receptors, might be effective in mood disorders as well, because of the ability to modulate the excitability of monoamine-secreting neurons and to potentiate extracellular concentrations of monoamines in the limbic areas of the brain.

Pragmatic trials aim to assess intervention efficacy in usual patient care settings, contrasting with explanatory trials conducted under controlled conditions. In aging research, pragmatic trials are important designs for obtaining real-world evidence in elderly populations, which are often underrepresented in trials. In this review, we discuss statistical considerations from a frequentist approach for the design and analysis of pragmatic trials. When choosing the dependent variable, it is essential to use an outcome that is highly relevant to usual medical care while also providing sufficient statistical power. Besides traditionally used binary outcomes, ordinal outcomes can provide pragmatic answers with gains in statistical power. Cluster randomization requires careful consideration of sample size calculation and analysis methods, especially regarding missing data and outcome variables. Mixed effects models and generalized estimating equations (GEEs) are recommended for analysis to account for center effects, with tools available for sample size estimation. Multi-arm studies pose challenges in sample size calculation, requiring adjustment for design effects and consideration of multiple comparison correction methods. Secondary analyses are common but require caution due to the risk of reduced statistical power and false-discovery rates. Safety data collection methods should balance pragmatism and data quality. Overall, understanding statistical considerations is crucial for designing rigorous pragmatic trials that evaluate interventions in elderly populations under real-world conditions. In conclusion, this review focuses on various statistical topics of interest to those designing a pragmatic clinical trial, with consideration of aspects of relevance in the aging research field.

Abstract Background: Temporomandibular disorders (TMD) are a range of clinical problems related to the temporomandibular joint (TMJ), chewing muscles, and surrounding facial structures. Functional magnetic resonance studies suggest that these disorders affect over 5% of the population. The relationship between dental occlusion and TMD has been a topic of debate in dentistry; some researchers suggest using lateral cephalograms and cephalometric data to identify which morphological profiles and types of malocclusion are most likely to cause TMD. The aim of this study is to identify the morphological profiles and associated skeletal malocclusions that have the greatest influence on the development of TMD. This will be accomplished through the analysis of cephalometric data obtained from cephalograms and condylar section images of patients from the Orthognathodontics Department of Chieti, who underwent low-dose cbct during their initial visit. Matherial and methods: This study, conducted at the Orthognathodontics Department of Gabriele D’Annunzio University in Chieti, examined a group of 67 patients (both males and females) presenting with signs of temporomandibular joint disorders (TMD). The inclusion criteria for the study were first-time TMD diagnosis, age 18 and above, and accessible medical records, wide field of view cone beam low dosage, and photographs. Patients with a history of tumor, trauma, surgical interventions in the jaw and facial area, fractures, and other craniofacial anomalies were excluded from the study. The aim of the study is to further understand the morphological profiles and associated skeletal malocclusions that contribute to TMD. Results: male patients: sagittal profile: 56% exhibited a skeletal Class II profile due to mandibular retrognathia. Vertical Profile: 73% were brachyfacial with a hypodivergent pattern. Dental Relationships: Increased overjet and a tendency towards deep bite were observed. 23% exhibited deep bite, 20% were normodivergent, and 8% were dolichofacial. The soft tissue profile tended towards flatness. Condyle Position: in Class II hypodivergent males, the condyle was non-concentric and positioned more posteriorly. In mesiodivergent males, the condyle was concentric, while in hyperdivergent males, it was slightly anterior. Female Patients: Sagittal Profile: 79% had a skeletal Class II profile with mandibular retrognathia. Vertical Profile: 47% were hypodivergent with reduced anterior facial height (105°). Dental Relationships: 17% exhibited deep bite, and 48% of those with a Class II profile had increased overjet. 43% were mesofacial, and 10% were dolichofacial. Condyle Position: In Class II hypodivergent and normodivergent females, the condyle was non-concentric and positioned more posteriorly. In hyperdivergent females, the condyle was positioned more anteriorly and higher in the fossa. Conclusion: The study highlighted significant differences in cephalometric parameters and condyle positions between male and female patients with TMD. A posteriorly positioned condyle was associated with a flattened condylar head, particularly in Class II hypodivergent profiles. These findings underscore the importance of individualized diagnostic and treatment approaches based on detailed cephalometric and condylar assessments. Further research is needed to explore the implications of these variations for TMD management and outcomes.

The traditional practice of harvesting and processing raw date palm sap is not only culturally significant but also an essential nutritional source in South Asia. Yet, the potential for bacterial or viral contamination from animals and environmental sources during its collection remains a real and insufficiently studied risk. Implementing improved food safety measures and collection techniques could mitigate the risk of these infections. Additionally, the adoption of advanced food analytical methods has the potential to identify pathogens and uncover the natural bacterial diversity of these products. The advancement of NGS technologies, particularly nanopore sequencing, offers rapid and highly mobile capabilities. In this study, we employed nanopore sequencing for bacterial metabarcoding of a set of raw date palm sap samples collected without protective coverage against animals in Bangladesh in 2021. We identified several bacterial species with importance in the natural fermentation of the product and demonstrated the feasibility of this NGS method in the surveillance of raw palm sap products. We revealed two fermentation directions dominated by either Leuconostoc species or Lactococcus species in these products at the first 6 hours from harvest along with opportunistic human pathogens in the background, represented with low abundance. Plant pathogens, bacteria with the potential for opportunistic human infections and the sequences of the Exiguobacterium genus were also described and their potential role is discussed.

The marathon sport events and those who participate in these have grown over the last years reflecting notably an augmentation of women and master runners participation. The aim of the present narrative review was to briefly present the results of studies on anthropometric, physiological and training characteristics, as well as predictors of performance, in marathon runners. It was observed that performance was better in runners with small body weight, body mass index, body fat percentage, and rate of endomorphy. With regards to physiology, an increased maximal oxygen uptake, anaerobic threshold, and improved running economy could result in faster race time. The training variables that could predict performance involved weekly training volume (distance) and intensity (running speed), as well as history of training (years). A combination of these three broad categories of characteristics may offer an approximate estimation of the race speed considering that other aspects (e.g., nutrition, biomechanic and motivation) influence race performance, too. In summary, the findings of the present study provided an overview of anthropometric, physiological and training characteristics associated with marathon race time; thus, an optimization of any of these characteristics would be expected to improve race time.

Background: Mental health has a special relevance in adolescence. Therefore, this study aimed to analyze the possible association between emotional distress and suicidal ideation among adolescents. Methods: The article presents the results of a survey of secondary school students (N=1419) in the city of Tarragona, Spain. The aim of the analysis was to verify the existence of an association between suicidal ideation and risk factors such as emotional distress and low self-esteem. All the data were also analysed to determine the existence of statistically significant differences between girls and boys. Bivariate analyses were performed with chi-square, point-biserial coefficient and non-parametric tests for independent groups. Logistic regression analysis was also performed to calculate the probability of suicidal ideation. Results: These analyses showed that both emotional distress and low self-esteem increase the likelihood of suicidal ideation among adolescents. This was more evident among boys with high levels of emotional distress. Conclusion: Schools should develop suicide ideation prevention programs for adolescents based on situations that cause emotional distress.

Northern Nigeria has had historically low antenatal care (ANC) utilization rates with poor health outcomes. Group antenatal care (gANC) improves ANC behavior and pregnancy outcomes. The gANC has been adopted in Kaduna and Kano states, Nigeria. This paper presents baseline findings from the evaluation of the implementation of the gANC program to support scaling in real-world setting. Baseline data were collected from a cohort of 1,269 and 1,200 pregnant women enrolled in gANC at health facilities in Kaduna and Kano states respectively from March to April 2024. Analyses of socio-demographic and pregnancy behavior data were done. Participants were mostly between ages 19-31 years, married or living with a partner, with over 50% having their own businesses. Over 62% and 34% had completed secondary or higher-level education with 60% and 80% living in urban areas in Kaduna and Kano States, respectively. In Kano State, &gt;60% of the women had their last delivery at home with 41.6% not assisted by a skilled birth attendant. In Kaduna, &gt;63% delivered in the hospital and &gt;50% had skilled attendance during labor. Almost half had not used contraceptives previously. Subsequent longitudinal data will examine the impact of gANC utilization on perinatal outcomes.

Psychotherapy is a comprehensive biological treatment modifying complex underlying cognitive, emotional, behavioral, and regulatory responses in the brain, leading patients with mental illness to a new interpretation of the sense of self and others. Psychotherapy is an art of science integrated with psychology and/or philosophy. Neurological science studies the neurological basis of cognition, memory, and behavior as well as the impact of neurological damage and disease on the functions, and their treatment. Both psychotherapy and neurological science deal with the brain; nevertheless, they continue to stay polarized far. Existential phenomenological psychotherapy (EPP) has been in the forefront of meaning-centered counseling for almost a century. The phenomenological approach in psychotherapy originated in the works of Martin Heidegger, Ludwig Binswanger, Medard Boss and Viktor Frankl, and it has been committed to account for the existential possibilities and limitations of one’s life. EPP provides philosophically rich interpretations and empowers counseling techniques to assist mentally suffering individuals by finding meaning and purpose of life. The approach has proven to be effective in treating mood and anxiety disorders. This narrative review article demonstrates the development of EPP, the therapeutic methodology, evidence-based accounts of its curative techniques, current understanding of mood and anxiety disorders in neurological science, and a possible converging path to translate and integrate meaning-centered psychotherapy and neuroscience, concluding that the existential phenomenological psychotherapy potently plays a synergistic role with the currently prevailing medication-based approaches for the treatment of mood and anxiety disorders.

Metabolomics profiling for accurate and reliable quantification of organic acids that carry a carboxylic acid functional group in complex biological samples, remains a major analytical challenge in clinical chemistry research. Several procedural barriers associated with quantification of clinically important carboxylic containing metabolites (CCMs) including spontaneous decarboxylation during ionization, poor chromatographic resolution, and retention on a reverse-phase column, limit the sensitivity, specificity, and reproducibility of multiple-reaction monitoring (MRM) based LC-MS assay development. We report a targeted metabolomics-based analytical method for the quantification of CCMs using phenylenediamine derivatization. Accurate and sensitive quantification of CCMs is successfully demonstrated in an array of biological matrices. Recovery of metabolites from different matrices (plasma, serum, urine, saliva, tissues, and cell extracts), ranged from 90% to 105%, with all the CVs ≤ 10%. The method showed linearity over a broad dynamic range from 0.1 ng/mL to 10 µg/mL with linear regression coefficients of 0.99 for most of the metabolites tested herein, that covers broad-based applicability with the analysis of biological samples. In most cases the LODs were as low as 0.01 ng/mL. The phenylenediamine-based derivatization of carboxyl acid library consisting of more than 70 endogenous metabolites was constructed for metabolite identification, which spanned more than 40 biological pathways. The library included a wide-variety of structurally variant CCMs such as amino acids/conjugates, short to medium chain organic acids, di/tri-carboxylic acids/conjugates, fatty acids and some ring-containing CCMs. We compared the CCMs profiles of pancreatic cancer cells with normal pancreatic epithelial cells to test and validate the biological utility of this method. The comparative profiling between cancerous and normal cells resulted in the identification of potential biomarkers in pancreatic cancer, and their correlation with several key metabolic pathways such as central carbon energy metabolism, protein metabolism, including TCA cycle, glycolysis, Gln-Glu pathway, and biosynthesis of amino acids and unsaturated fatty acids was established. The method, described herein, for the first time enables the sensitive and highly specific quantification of CCMs on small sample size with high reproducibility in a high throughput manner. Given the biological and functional significance of this class of metabolites, this mass spectrometry based targeted quantitative assay, fills an important gap and is likely to support a wide range of applications for basic, clinical, and translational research.

Taekwondo has evolved from a traditional martial art into an official Olympic sport. This study introduces a novel action recognition model tailored for Taekwondo unit actions, utilizing joint motion data acquired via wearable inertial measurement unit (IMU) sensors. The utilization of IMU sensor-measured motion data facilitates the capture of the intricate and rapid movements characteristic of Taekwondo techniques. The model, underpinned by a conventional convolutional neural network (CNN)-based image classification framework, synthesizes action images to represent individual Taekwondo unit actions. These action images are generated by mapping joint motion profiles onto the RGB color space, thus encapsulating the motion dynamics of a single unit action within a solitary image. To further refine the representation of rapid movements within these images, a time-warping technique was applied, adjusting motion profiles in relation to the velocity of the action. The effectiveness of the proposed model was assessed using a dataset compiled from 40 Taekwondo experts, yielding remarkable outcomes: an accuracy of 0.998, precision of 0.983, recall of 0.982, and an F1-score of 0.982. These results underscore the time-warping technique's contribution to enhancing feature representation, as well as the proposed method's scalability and effectiveness in recognizing Taekwondo unit actions.