Background: The efficacy of local therapies for lung cancer patients with postoperative oligo-recurrence has been reported. However, whether local therapies should be chosen over molecular targeted therapies for oligo-recurrence patients with driver mutations remains controversial. We hence aimed to investigate the optimal initial treatment strategy for oligo-recurrence in lung cancer patients with driver mutations. Methods: Among 2,152 patients with lung adenocarcinoma who underwent surgical resection at our institute between 2008 and 2020, 66 patients with driver mutations who experienced cancer oligo-recurrence after surgery, and were treated with local or molecularly targeted therapy as an initial therapy after recurrence were evaluated. Oligo-recurrence was characterized by the presence of 1 to 3 recurrent lesions. These patients were investigated focusing on their post-recurrence therapies and prognoses. Results: The median follow-up period was 71 months. Local and molecular targeted therapies were administered to 41 and 25 patients, respectively. The number of recurrence lesions tended to be lower in the initial local therapy group than in the molecular targeted therapy group. In the initial local therapy group, 23 patients (56%) subsequently received molecular targeted therapies. The time from recurrence to the initiation of molecular targeted therapy was significantly longer in the local therapy group than in the molecular targeted therapy group (p < 0.001). There was no significant difference in post-recurrence overall survival (hazard ratio, 1.429; 95% confidence interval, 0.701–2.912; log-rank, p = 0.324), and post-recurrence progression-free survival (hazard ratio, 0.799; 95% confidence interval, 0.459–1.390; log-rank, p = 0.426) in the initial local ablative therapy group compared with the initial molecular targeted therapy group. Conclusions: Local therapies as a first-line treatment did not show statistically significant differences in post-recurrence survival or progression-free survival compared with molecular targeted therapies. However, local therapies as an initial treatment should be considered preferably, as it can cure the recurrence and can delay the start of administration of molecular-targeted therapies.

Understanding microbial composition in upper respiratory infections (URIs) is critical for effective diagnosis and treatment. Precision Metagenomic next-generation sequencing p(mNGS) can provide a comprehensive yet clinically relevant profile of respiratory infection. The hybridization capture-based targeted sequencing generated a precision metagenomics profile of 29 patients with acute URIs. Nasopharyngeal samples were collected from the subjects suspected of respiratory infection, and p(mNGS) was performed using the Illumina®/IDbyDNA Respiratory Pathogen ID/AMR Panel (RPIP). The dataset obtained from the mNGS analysis contains a wealth of information on the composition of acute URI microbiota, including the relative abundance of known pathogens and potential clinical implications. The dataset represents a valuable resource for future research endeavors in respiratory medicine, infectious disease epidemiology, and therapeutic interventions. In addition, the dataset offers significant potential for reuse and integration with other omics datasets. The comprehensive nature of the mNGS data allows the exploration of associations between the respiratory microbiota and host factors such as clinical outcomes, immune responses, or genetic predisposition. Combining this dataset with other relevant datasets, such as transcriptomics or metabolomics, could provide a deeper understanding of the complex interactions between the microbiota and the host in acute URIs.

Immune-mediated bowel diseases (IMBD), including Ulcerative colitis and Crohn's disease, represent a significant global health burden with their complex etiology and increasing prevalence. The connection between intestinal parasites and the gut microbiome in immune-mediated bowel disease is a complex and evolving field of research. Several studies have demonstrated that intestinal parasites can modulate the composition and function of the gut microbiome. Parasitic infections can result in alterations in the gut microbial community, including changes in microbial diversity, abundance, and metabolic activity. These changes can influence the immune response and contribute to the development of IMBDs. In contrast, the gut microbiome serves a pivotal function in maintaining intestinal homeostasis and immune regulation. Dysbiosis, characterized by changes in the gut microbial composition, has been associated with the pathogenesis of IMBDs. Imbalances in the gut microbiota can result in increased gut permeability, chronic inflammation, and aberrant immune responses, all of which are hallmarks of IMBDs. The bidirectional interaction between intestinal parasites and the gut microbiome further complicates the understanding of immune-mediated bowel diseases. Certain parasites, such as hookworms and Necator americanus, have been found to downregulate immune responses and may have therapeutic potential in treating celiac disease. On the other hand, infections with parasites like Strongyloides stercoralis and Blastocystis have been shown to mimic the symptoms of IBD, highlighting the intricate relationship between parasites and the pathogenesis of these diseases. Additional investigation is required to comprehensively elucidate the mechanisms that underlie the association between intestinal parasites and the gut microbiome in immune-mediated bowel disease. This knowledge could potentially lead to the development of targeted therapeutic strategies that aim to restore gut microbiota homeostasis and alleviate the symptoms of these debilitating conditions. By understanding and harnessing the complex interplay between parasites, the gut microbiome, and the host immune system, researchers may uncover novel approaches for the management and treatment of immune-mediated bowel diseases.

Hepatocellular carcinoma (HCC) poses a significant global health concern, with its incidence steadily increasing. The development of HCC is a multifaceted, multi-step process involving alterations in various signaling cascades. In recent years, significant progress has been made in understanding the molecular signaling pathways that play central roles in hepatocarcinogenesis. In particular, the EGFR/PI3K/Akt/mTOR signaling pathway in HCC has garnered renewed attention from both basic and clinical researchers. Preclinical studies in vitro and in vivo have shown the effectiveness of targeting the key components of this signaling pathway in human HCC cells. Thus, targeting these signaling pathways with small molecule inhibitors holds promise as a potential therapeutic option for patients with HCC. In this review, we will explore recent advancements in understanding the role of the EGFR/PI3K/Akt/mTOR signaling pathway in HCC and assess the effectiveness of targeting this signaling cascade as a potential strategy for HCC therapy based on preclinical studies

Molecular therapies exploiting mRNA vectors embody enormous potential, as evidenced by the utility of this technology for the context of the COVID-19 pandemic. None-the-less, broad implementation of these promising strategies has been restricted by the limited repertoires of delivery vehicles capable of mRNA transport. On this basis, we explored a strategy based on exploiting the well characterized entry biology of adenovirus. To this end, we studied an adenovirus-polylysine (AdpL) that embodied “piggyback” transport of the mRNA on the capsid exterior of adenovirus. We hypothesized that the efficient steps of Ad binding, receptor-mediated entry, and capsid-mediated endosome escape could provide an effective pathway for transport of mRNA to the cellular cytosol for transgene expression. Our studies confirmed that AdpL could mediate effective gene transfer of mRNA vectors in vitro and in vivo. Facets of this method may offer key utilities to feasibilize the promise of mRNA-based therapeutics.

Boron Neutron Capture Therapy (BNCT) is a promising binary disease-targeted therapy, as neutrons preferentially kill cells labeled with boron (¹⁰B), which makes it a precision medicine treatment modality that provides a therapeutic effect exclusively on patient-specific tumor spread. Contrary to what is usual in radiotherapy, BNCT proposes cell-tailored treatment planning rather than to the tumor mass. The success of BNCT depends mainly on the sufficient spatial biodistribution of ¹⁰B located around or within neoplastic cells to produce a high-dose gradient between the tumor and healthy tissue. However, it is not yet possible to precisely determine the concentration of ¹⁰B in a specific tissue in real-time using noninvasive methods. Critical issues remain to be resolved if BNCT is to become a valuable, minimally invasive, and efficient treatment. Moreover, functional imaging technologies such as PET can be applied to determine biological information that can be used for the combined-modality radiotherapy protocol for each specific patient. Anyway, not only imaging methods but also proteomics and gene expression methods will facilitate BNCT becoming a modality of personalized medicine. This work provides an overview of the fundamental principles, recent advances, and future directions of BNCT as cell-targeted cancer therapy for personalized radiation treatment.

The KRAS mutant population has been undruggable for 40 years. G12C inhibitors and immunotherapy are the beginning of success. It is necessary to summarize the successful experience of the existing treatment model and explore the direction of the next treatment. In this review, we discuss the latest developments in targeted therapy and immunotherapy for KRAS-mutation NSCLC, aiming to provide direction or enlightenment for future treatment strategies.

Uveal melanoma (UM) is characterized by relatively few, highly incident molecular alterations and their association with metastatic risk is deeply understood. Nevertheless, this knowledge has so far not led to innovate therapies for the successful treatment of UM metastases or for adjuvant therapy, leaving survival after diagnosis of metastatic UM almost unaltered in decades. The driver mutations of UM, mainly in the G-protein genes GNAQ and GNA11, activate the MAP-kinase pathway as well as the YAP/TAZ pathway. At present, there are no drugs that target the latter and this likely explains the failure of MEK-inhibitors. Immune checkpoint blockers, despite the game changing effect in cutaneous melanoma (CM) show only marginal effects in UM probably because of the low mutational burden of 0.5 per megabase and the unavailability of antibodies targeting the main immune checkpoint active in UM. The highly pro-tumorigenic microenvironment of UM also contributes to therapy resistance. However, T-cell redirection by a soluble T cell receptor that is fused to an anti-CD3 single-chain variable fragment, local, liver specific therapy, new immune checkpoint blockers and YAP/TAZ specific drugs give new hope to repeat the success of innovative therapy obtained for CM.

Abstract Background The number of immune-related endocrine dysfunctions (irEDs) has concurrently increased with the widespread use of immunotherapy in clinical practice and further expansion of the approved indications for immune checkpoint inhibitor (ICI) combinations using different modalities of anti-cancer treatment. Method A retrospective analysis was conducted on consecutive patients >18 years of age with advanced solid malignancies who had received at least one dose of anti-programmed cell death protein 1 (anti-PD-1) and/or anti-CTLA4 antibodies between January 2014 and December 2019 at a Hong Kong university hospital. Patients were reviewed for up to two months after the last administration of an ICI. The types, onset times and grades of irEDs, including hypothyroidism, hyperthyroidism, adrenal insufficiency and immune-related diabetes mellitus, were recorded. Factors associated with irEDs were identified using multivariate analysis. Result A total of 953 patients (male: 603, 64.0%; median age: 62.0 years) received ICIs during the study period. Of these, 580 patients (60.9%) used ICI-alone, 132 (13.9%) used dual-ICI, 187 (19.6%) used an ICI combined with chemotherapy (chemo+ICI), and 54 (5.70%) used immunotherapy with a targeted agent (targeted+ICI). A significantly higher proportion of patients using targeted+ICI had irEDs and hypothyroidism; in contrast, a higher proportion of patients using dual-ICI had adrenal insufficiency. There was no significant difference in the incidence of irED between the younger (<65 years) and older (>65 years) patients. Using logistic regression, only treatment type was significantly associated with irEDs. Notably, older patients had a higher risk of having immune-related diabetes mellitus. Conclusions This large, real-world cohort demonstrates that combining ICI with targeted therapy has a higher risk of overall irED and hypothyroidism. Immunotherapy is safe and well-tolerated regardless of age, but close monitoring of fasting glucose is needed in older populations.

Among the different ways to reduce the secondary effects of antineoplastic drugs in cancer treatment, the use of nanoparticles has demonstrated good results due to the protection of the drug and the possibility of releasing compounds to a specific therapeutic target. The α-isoform of folate receptor (FR) is overexpressed on a significant number of human cancers; therefore, folate-targeted crosslinked nanoparticles based on BSA and alginate mixtures and loaded with paclitaxel (PTX) have been prepared to maximizing the proven antineoplastic activity of the drug against solid tumors. Nanometric-range sized particles (169 ± 28nm - 296 ± 57nm), with negative Z-potential values (between -0.12 ± 0.04 and -94.1± 0.4), were synthesized. The loaded PTX (2.63±0.19 - 3.56 ±0.13 µg PTX/mg Np) was sustainably released along 23 and 27h. Three cell lines (MCF-7, MDA-MB-231 and HeLa) were selected to test the efficacy of the folate-targeted PTX-loaded BSA/ALG nanocarriers. The presence of FR on cell membrane led to a significant larger uptake of BSA/ALG-Fol nanoparticles regarding to the equivalent nanoparticles without folic acid on its surface. The cell viability results demonstrated a cytocompatibility of unloaded nanoparticle-Fol and a gradual decrease in cell viability after treatment with PTX-loaded nanoparticles-Fol due to the sustainable PTX release.

Breast cancer (BC) is the most common malignancy and second only to lung cancer in terms of mortality in women. Despite the incredible progress made in this field, the metastatic breast cancer leaves a poor prognosis. In an era of personalized medicine, there is an urgent need for a better knowledge of the biology leading to the disease, which can lead to the design of always more accurate drugs against patients’ specific molecular aberrations. Among one of the actionable targets is the Fibroblast Growth Factor Receptor (FGFR) pathway, triggered by specific ligands. The FGFRs/FGFs axis offers interesting molecular targets to be pursued in clinical development. This mini-review will focus on the current knowledge of the FGFRs mutations leading to tumour formation and summarizes the state-of-the-art of therapeutic strategies for targeted treatments against the FGFRs/FGFs axis in the context of BC.

Dual quaternions have wide applications in automatic differentiation, computer graphics, mechanics and others. Due to its application in control theory, the matrix equation AXB=C has been extensively studied. However, there is currently limited information on matrix equation AXB=C over the dual quaternion algebra. In this paper, we provide the necessary and sufficient conditions for the solvability of the dual quaternion matrix equation AXB=C, and present the expression for the general solution when it is solvable. As an application, we derive the ϕ-Hermitian solutions for the dual quaternion matrix equation AXAϕ=C, where the ϕ-Hermitian extends the concepts of Hermiticity and η-Hermiticity. Lastly, we present a numerical example to verify the main research results of this paper.

The co-occurrence of substance use disorders (SUDs) and psychiatric conditions, often referred to as comorbidity or concurrent disorders, presents intricate challenges in both diagnosis and treatment. This comprehensive narrative review aims to synthesize and critically evaluate the existing evi-dence surrounding the management of individuals with comorbid SUDs and psychiatric disorders. Comorbidity in these domains carries profound implications for clinical practice, research, and policymaking, emphasizing the need for a holistic understanding of the intricate dynamics that arise when these conditions coexist. This review explores recent research findings, evidence-based guidelines, and emerging trends within the field, offering valuable insights for clinicians, re-searchers, and policymakers seeking to navigate the complex terrain of comorbidity in substance use and psychiatric disorders.

FV (finger vein) identification is a biometric identification technology that extracts the features of FV images for identity authentication. To address the limitations of CNN-based FV identification, particularly the challenge of small receptive fields and difficulty in capturing long-range dependencies, an FV identification method Let-Net(Large kernel and attention mechanism Network) was introduced, which combines local and global information. Firstly, Let-Net employs large kernels to broaden the receptive field and incorporates depthwise convolution with residual connections to reduce parameter count. Secondly, Let-Net integrates an attention mechanism to enhance the information flows in channels and spaces for more comprehensive and distinctive FV feature extraction. The experimental results on nine public datasets show that Let-Net has excellent identification performance, and the EER and accuracy rate on the FV_USM dataset can reach 0.04% and 99.77%. The parameter number and FLOPs of Let-Net are only 0.89M and 0.25G, which means that the time cost of training and reasoning of the model is low, and it is easier to deploy and integrate into various applications.

Intrauterine adhesions (IUA) has become one of the main causes of female infertility, how to effectively prevent postoperative re-adhesion has been a clinical challenge. In this study, a mussel-inspired dual-network hydrogel was proposed for postoperative anti-adhesion of IUA. First, calcium alginate/polyacrylamide (CA-PAM) hydrogel was prepared by covalent and Ca2+ cross-linking. Benefiting from abundant phenolic hydroxyl groups, polydopamine (PDA) was introduced to further enhance the adhesion ability and biocompatibility. This CA-PAM hydrogel immersed in 10 mg/mL dopamine solution possessed remarkable mechanical strength (elastic modulus > 5 kPa) and super stretchability (with a breaking elongation of 720%). At the same time, it shown excellent adhesion more than 6 kPa. Surprisingly, the coagulation index of the hydrogel was 27.27 ± 4.91, demonstrating attractive coagulation performance in vitro and the potential for rapid hemostasis after surgery.

The utilization of dual-potential mode of integrated array (IDA) electrodes and other two-electrode systems has revolutionized electrochemical detection by enabling the simultaneous and independent detection of two species, accompanied by the exhibition of unique characteristics. In contrast to conventional dual-potential electrodes, the rotating ring disk electrodes (RRDE), IDA electrodes demonstrate analogous yet vastly improved performance metrics, characterized by remarkable collection efficiency and sensitivity. Notably, due to the distinctive microscale structure of IDA electrode, the special “feedback” effect makes IDA a unique signal amplifier. In recent decades, the research surrounding IDA electrodes has garnered escalating interest due to their attractive attributes. This review centers its focus on the fabrication and applications of IDA electrodes. In the realm of fabrication, two critical breakthroughs are poised for realization: the achievement of reduced dimensions and the diversification of materials. Established fabrication methods for IDA electrodes encompass photolithography, inkjet printing, and direct laser writing, each affording distinct advantages in terms of size and precision in IDA construction. Predominantly employed materials for IDA electrodes include gold, platinum, and carbon, with the selection of fabrication methods guided by considerations such as material properties, desired dimensions, cost-efficiency, and specific application requisites. Within the domain of applications, IDA electrodes, capitalizing on their distinctive attributes, have found utility in diverse fields. This review summarizes the applications of IDA electrodes based on their fundamental working principles, encompassing redox cycling, resistance modulation, capacitance variations, and more. The potential for further development of this specialized tool to exhibit enhanced properties holds substantial promise.

Stevia rebaudiana (Bert.) is a natural sweetener with diterpenic glycosides, offering 300 times more sweetness than sucrose, and boasting low-calorie content, along with medicinal and therapeutic properties. To address a limited genetic diversity, a germplasm bank comprising 115 segregated lines of stevia was established in Colombia. Notwithstanding, the fungus Athelia rolfsii adversely impacted key stevia lines, leading to wilting and plant mortality. For this reason our study aimed to explore the biocontrol potential of native strains of Trichoderma spp., isolated from productive lots in Colombia's Cordoba department, as a solution to manage A. rolfsii. Soil samples underwent serial dilution technique (103 conidia.mL-1) to obtain Trichoderma spp. isolates, which were thoroughly morphologically and molecularly characterized. A total five native strains were identified through sequencing the PCR products using universal ITS primers, and comparisons with the GENBANK database confirmed their identity (OK310695.1, ON237703.1, ON238106.1, ON237737.1, and ON237923.1). Their biocontrol efficacy against A. rolfsii was evaluated using the dual culture technique. Remarkably, all strains exhibited significant biocontrol capacity against the A. rolfsii isolate INVEPAR-05 (OK271308.1), except for Trichoderma viride INVEPAR-T10 (ON237923.1). These findings suggest that Trichoderma spp. could be a potential option to manage the fungus in stevia.

The minimum dominating tree (MDT) problem consists of finding a minimum weight sub-graph from an undirected graph, such that each vertex not in this sub-graph is adjacent to at least one of the vertices in it, and the sub-graph is connected without any ring structures. This paper presents a Dual Neighborhoods Search (DNS) algorithm for solving the MDT problem, which integrates several distinguishing features, such as two neighborhoods collaboratively working for optimizing the objective function, a fast neighborhood evaluation method to boost the searching effectiveness, and several diversification techniques to help the searching process jump out of the local optimum trap thus obtaining better solutions. DNS improves the previous best-known results for 4 public benchmark instances while providing competitive results for the remaining ones. Several ingredients of DNS are investigated to demonstrate the importance of the proposed ideas and techniques.

The present paper provides a new definition for dual spline curves in a geometric intuitive way based on adaptive curve refinement techniques. The dual spline is an implementation of the interpolatory subdivision scheme for curve modeling, which is comprised of polynomial segments of different degrees. Specially, the dual spline curves are mainly aims to solve the difficult geometry defeaturing problems in the existing computer-aided technology. Dual spline curves maintain various desirable properties of conventional curve modeling methods, such as local adaptive subdivision, high interpolation accuracy and convergence, continuous and discontinuous boundary approximation. By adding fictitious and intrinsic nodes inside or at the vertices of interpolation elements, the dual spline is flexible and convenient for approximating a set of ordered points or discrete segments. Combined with the Lagrange interpolation polynomial and meshless method, the proposed approach is capable of approximating the non-smooth boundary for geometry defeaturing. Experimental results are given to verify the validity, robustness, and accuracy of the proposed method.

Duchenne muscular dystrophy (DMD) is a yet incurable rare genetic disease that affects the skeletal and cardiac muscles, leading to progressive muscle wasting and premature death. DMD is caused by the lack of dystrophin, a muscle protein essential for the biochemical support and integrity of muscle fibers. Gene replacement strategies for Duchenne muscular dystrophy (DMD) employing the adeno-associated virus (AAV) face the challenge imposed by the limited packaging capacity of AAV, only allowing the accommodation of a short version of dystrophin (µDys) that is still far removed from correcting human disease. The need to develop strategies leading to the expression of a best performing dystrophin variant led to only few studies reporting on the use of dual vectors, but none reported on a method to assess in vivo transgene reconstitution efficiency, the degree of which directly affects the use of safe AAV dosing. We report here on the generation of a dual AAV vector approach for the expression of a larger dystrophin version (quasidystrophin) based on homologous recombination, and the development of a methodology employing a strategic droplet digital PCR design, to determine the recombination efficiency as well as the occurrence of unwanted concatemerization events or aberrant expression from the single vectors. We demonstrated that, upon systemic delivery in the dystrophic DBA2mdx mice, our dual AAV approach led to high transgene reconstitution efficiency and negligible ITR-dependent concatemerization, with consequent remarkable protein restoration in muscles and improvement of muscle pathology. This evidence supports the suitability of our system for gene therapy application and the potential of this methodology to assess and improve the feasibility for therapeutic translation of multiple vector approaches

The study presents the synthesis and characterization of dual-layer sulfonated polyphenylenesulfone (SPPSu) nanocomposite hollow fiber nanofiltration membranes incorporating titanium dioxide (TiO2) nanoparticles using the phase inversion technique. The newly developed membranes were systematically characterized using advanced tools and methods to evaluate their properties and performance. The study focused on investigating the effects of TiO2 addition in the SPPSu inner layer on pure water permeability, and salt rejection. The nanocomposite hollow fiber nanofiltration membranes exhibited a significant enhancement in pure water permeability, with a three-fold increase compared to the pristine membranes, achieving a flux of 5.4 L/m2h.bar. The addition of TiO2 also led to an improvement in the mechanical properties of the membranes, as evidenced by the increase in the expected tensile strength from 2.4 to 3.9 MPa. To evaluate the salt rejection performance, rejection tests were conducted using a laboratory-scale filtration setup in recycle mode. Aqueous solutions containing different divalent ions, specifically magnesium sulfate (Mg2SO4) and sodium sulfate (Na2SO4) at a concentration of 500 ppm, were used as the feed solution. The modified dual-layer hollow fiber nanocomposite membranes exhibited a maximal rejection of 95% for Mg2SO4, demonstrating their effective separation capabilities for divalent ions. The findings of this study highlight the successful synthesis and characterization of dual-layer SPPSu nanocomposite hollow fiber nanofiltration membranes incorporating TiO2 nanoparticles. The incorporation of TiO2 resulted in improved pure water flux, mechanical strength, and salt rejection performance. These enhanced properties make the developed nanocomposite membranes promising candidates for applications in nanofiltration processes, particularly for the selective separation of divalent ions from aqueous solutions.

Objective: To evaluate two different DECT postprocessing protocols for detection of MSU deposits in foot tendons of cadavers with verification by polarizing light microscopy as gold standard.Material and Methods: A total of 40 embalmed cadavers (15 male; 25 female; median age, 82 years; mean, 80 years; range, 52 - 99; SD ± 10.9) underwent DECT to assess MSU deposits in foot tendons.Two postprocessing DECT protocols with different Hounsfield unit (HU) thresholds 150/500 (=established) versus 120/500 (= modified) HU were applied to dual source acquisition with 80 kV for tube A and 140 kV for tube B.Six fresh cadavers (4 male; 2 female; median age, 78; mean, 78,5; range 61 - 95 ) were examined by DECT. Tendon dissection of 2/6 fresh cadavers with positive DECT 120 and negative DECT 150 studies were used to verify MSU deposits by polarizing light microscopy.Results: The tibialis anterior tendon was found positive in 57.5%/100% (DECT 150/120), peroneus tendon in 35%/100%, achilles tendon in 25%/90%, flexor halluces longus tendon in 10%/100%, and tibialis posterior tendon in 12.5%/97.5%. DECT 120 resulted in increased tendon MSU deposit detection, when DECT 150 was negative, with an overall agreement between DECT 150 and DECT 120 of 80 % (P = 0.013). Polarizing light microscope confirmed MSU deposits detected only by DECT 120 in tibialis anterior, achilles, flexor halluces longus and peroneal tendons.Conclusion: The DECT 120 protocol showed a higher sensitivity when compared to DECT 150.

In this nano era, nanomaterials and nanostructures are popular in developing novel functional materials. However, the combinations of nanoproducts with materials at micro and macro scale can open new routes for conceiving novel materials with an improved or even new functional performances. In this study, a brand-new hybrid, containing both nanofibers and particles having a microsize, was fabricated using a sequential electrohydrodynamic atomization (EHDA) process. Firstly, the microparticles loaded with drug (berberine hydrochloride, BH) molecules in the cellulose acetate (CA) were fabricated using a solution electrospraying process. Later, these microparticles were suspended into a co-dissolved solution containned BH and a hydrophilic polymer (polypyrrolidone, PVP), and were co-electrospun into the nanofiber/microparticle hybrids. The EHDA processes were clearly recorded, and the resultant products showed a typical hybrid topography, with microparticles distributed all over the nanofibers, which was demonstrated by SEM assessments. FTIR and XRD demonstrated that the components within the hybrids were presented in an amorphous state and have fine compatibility with each other. In vitro dissolution tests verified that the hybrids were able to provide the designed dula-step drug release profiles, a combination of the fast release step of BH from the hydrophilic PVP nanofibers through an erosion mechanism and the sustained release step of BH from the insoluble CA microparticles via a typical Fickian diffusion mechanism. The present protocols pave a new way for developing trans-scale functional materials.

A low-profile broadband dual-polarized antenna is investigated for base station applications. It consists of two orthogonal dipoles, fork-shaped feeding lines, an artificial magnetic conductor (AMC), and parasitic strips. By utilizing the dispersion Brillouin diagram, the AMC is designed as the antenna reflector. It has a wide in-phase reflection bandwidth of 54.7% (1.54-2.70 GHz) and a surface wave bound range of 0-2.65 GHz. This design effectively reduces the antenna profile by over 50% compared to traditional antennas without an AMC. For demonstration, a prototype is fabricated for 2G/3G/LTE base station applications. Good agreement between simulations and measurements is observed. The measured -10-dB impedance bandwidth of our antenna is 55.4% (1.58 –2.79 GHz), with a stable gain of 9.5 dBi and high isolation of more than 30 dB across the impedance passband. As a result, this antenna is an excellent candidate for miniaturized base station antenna applications.

Human induced pluripotent stem cells (hiPSCs) have two characteristic abilities 1) self-renewal and 2) differentiation into all cell types in the human body. It is this ability of iPSCs to differentiate into any desired cell type that makes them amenable to disease modeling. iPSCs can further be engineered to carry a disease-specific mutation or be derived from patients to phenocopy the disease. To model neurodegenerative/neurodevelopmental disorders iPSCs are differentiated into neurons. This chapter describes protocols for two different approaches to generate neurons from iPSCs, first using dual SMAD inhibition to generate neural progenitor cells which are then differentiated into neurons, and second using single transcription factor (NGN2) over-expression to drive differentiation of iPSCs directly into neurons.

To promote low-carbon and green travel, this study proposes a tripartite evolutionary game model among new energy vehicle manufacturers, consumers, and government agencies. The game strategy combinations of each party and the stability conditions of the equilibrium point in the evolutionary game system are analyzed, and the validity of the conclusions is verified through simulation results. The study shows a strong correlation between the three parties in the evolutionary game system. From the perspective of car manufacturers, the probability of producing new energy vehicles is positively proportional to the subsidy received from new energy policy, the additional revenue gained from the management of the carbon trading scheme, and the fine received for producing conventional fuel vehicles. However, from the consumer perspective, the likelihood that consumers purchase new energy vehicles is positively related to the utility value to consumers and the coverage of public charging points in the city, and inversely related to the sales price of new energy vehicles. From the government perspective, a combination of direct subsidy policies and indirect support strategies should be considered to stimulate the rapid development of the new energy vehicle industry.

Nowadays, many Muslim-majority countries have implemented a dual banking system, namely the sharia and conventional systems. The development of Islamic banks is to fulfill the Muslims' need for the existence of halal transactions in financial institutions. However, in some countries, it turns out that conventional banks still dominate the country's economy. Because of that, it is necessary to see whether there are differences in financial risk and Earnings management between Islamic and conventional banks. The samples are conventional and Islamic banks in Southeast Asia, analyzed by the purposive sampling method from 2010-2019. The analytical tool used is the statistical difference test and economometrics analysis using generalized least square (GLS) regression with panel data (time series and cross-sectional data). These models are intended to forecasting the macroeconomics effects in applying dual banking system in one country or region. The results using non parametrics means difference test showed that the first hypothesis is accepted It means that Earnings management in conventional banks is greater than in Islamic banks. The Random Model Effect (REM) for second and third hypotheses testing on Conventional banks shows the Bankruptcy Risk and NPL do not affect the dependent variable Earnings Management (LLP). While fixed effect model testing on Islamic banks, the second and third hypothesis testing is rejected. Therefor Islamic Banks the value of Bankruptcy Risk (z-score) and the value of Non-Performing Loans (NPL) do not affect Earnings management. It also means that hypothesis 2 and 3 are rejected both in conventional as well as Islamic Banking. Sensitivity analysis for conventional as well as Islamic banking altogether using fixed effect model shows that the second and third hypotheses show that the independent variables (Bankruptcy Risk and NPL) do not affect the dependent variable Earnings Management (LLP). These results can be concluded that Islamic bank are enganged in less earnings management. Therefor in the the long run there are still more research that should conduct in comparing dual banking system in one region.

Introduction: A dual malignancy with both Ewing Sarcoma and Prostate Adenocarcinoma has not been reported in the English literature. We report a case of simultaneous diagnosis of Ewing sarcoma and prostate adenocarcinoma with profound clinical manifestation. Case presentation: A 53-year-old male with advanced metastatic prostate cancer (Gleason-9) admitted with classical presentation of cauda equina syndrome including incontinence, back pain, and paresis following bilateral nephrostomy insertion for the treatment of bilateral renal hy-dronephrosis. The patient was diagnosed with an epidural abscess at the level of L5-S1 and an emergency surgical spine decompression was performed. No abscess was found, and pathology results showed a concomitant primary Ewing sarcoma in the spine. Conclusions: Very rare occurrences of a dual primary malignancy, in this case, Ewing sarcoma and prostate adenocarcinoma, should be kept in mind in patients suffering from complex clinical course of malignancies.

Aims: In late December 2019, early reports predicted the onset of a potential Coronavirus outbreak in china, given the estimate of a reproduction number for the 2019 Novel Coronavirus (COVID-19). Because of high ability of transmission and widespread prevalence, the mortality of COVID-19 infection is growing fast worldwide. Absent of an anti-COVID-19 has put scientists on the urge to repurpose already approved therapeutics or to find new active compounds against coronavirus. Here in this study, a set of computational approaches were performed in order to repurpose antivirals for dual inhibition of the frontier proteases involved in virus replication, papain-like protease (PLpro; corresponding to nsp3) and a main protease (Mpro), 3C‑like protease (3CLpro; corresponding to nsp5). Materials and Methods: In this regard, a rational virtual screening procedure including exhaustive docking techniques was performed for a database of 160 antiviral agents over 3CLpro and PLpro active sites of SARS-CoV-2. The compounds binding energies and interaction modes over 3CLpro and PLpro active sites were analyzed and ranked with the aid of free Gibbs binding energy. The most potent compounds, based on our filtering process, are then proposed as dual inhibitors of SARSC-CoV-2 proteases. Key findings: Accordingly, seven antiviral agents including two FDA approved (Nelfinavir, Valaganciclovir) and five investigational compounds (Merimepodib, Inarigivir, Remdesivir, Taribavirine and TAS106-106) are proposed as potential dual inhibitors of the enzymes necessary for RNA replication in which Remdesivir as well as Inagrivir have the highest binding affinity for both of the active sites. Significance: The mentioned drug proposed to inhibit both PLpro and 3CLpro enzymes with the aim of finding dual inhibitors of SARSC-CoV-2 proteases.

Dislocation is one of the major challenges in unmanned aerial vehicle (UAV) image stitching. In this paper, we propose a new dynamic programming for seamlessly stitching UAV images using optical flow. Our solution consists of two steps: Firstly, an image-matching algorithm is used to correct the images so that they are in the same coordinate system. Secondly, a new dynamic programming algorithm is develop based on the concept of a stereo dual-channel energy accumulation using optical flow. A new energy aggregation and traversal strategy is adopted in our solution, which can find a more optimal seam line for adjacent image stitching. Our algorithm overcomes the theoretical limitation of the classical Duplaquet algorithm. Experiments show that the algorithm can effectively solve the dislocation problem in UAV image stitching. Beyond that, our solution is also direction-independent, which has more adaptability and robustness for UAV images.

In order to correct attenuated millimeter-wavelength (Ka-band) radar data and address the problem of instability, an attenuation correction methodology (attenuation correction with variation trend constraint; VTC) was developed. Using synchronous observation conditions and multi-band radars, the VTC method adopts the variation trends of reflectivity in X-band radar data captured with wavelet transform as a constraint to adjust reflectivity factors of millimeter-wavelength radar. The correction was evaluated by comparing reflectivities obtained by millimeter-wavelength cloud radar and X-band weather radar. Experiments showed that attenuation was a major contributory factor in the different reflectivities of the two radars when relatively intense echoes exist, and the attenuation correction developed in this study significantly improved data quality for millimeter-wavelength radar. Reflectivity differences between the two radars were reduced and reflectivity correlations were enhanced. Errors caused by attenuation were eliminated, while variation details in the reflectivity factors were retained. The VTC method is superior to the bin-by-bin method in terms of correction amplitude and can be used for attenuation correction of shorter wavelength radar assisted by longer wavelength radar data.

Wilms tumor (WT), the most prevalent type of renal cancer in children, exhibits overall survival rates exceeding 90%. However, chemotherapy resistance, which occurs in approximately 10% of WT cases, is a major challenge for the treatment of WT, particularly for advanced-stage patients. In this study, we aimed to discover potential mutation markers and drug targets associated with chemotherapy resistance in advanced stage WT. We performed exome sequencing to detect somatic mutations and molecular targets in 43 WT samples, comprising 26 advanced stage WTs, of which 7 cases are chemotherapy-resistant. Our analysis revealed four genes (ALPK2, C16orf96, PRKDC, and SVIL) that correlated with chemotherapy resistance and reduced disease-free survival in ad-vanced-stage WT. Additionally, we identified driver mutations in 55 genes within the chemo-therapy-resistant group, including 14 druggable cancer driver genes. Based on the mutation profile of the resistant WT samples, we propose potential therapeutic strategies involving platinum-based agents, PARP inhibitors, and antibiotic/antineoplastic agents. Our findings provide insights into the genetic landscape of WT and offer potential avenues for targeted treatment, particularly for patients with chemotherapy resistance.

Proteolysis Targeting Chimeras (PROTACs) describe compounds that bind to and induce degradation of a target by simultaneously binding to a ubiquitin ligase. More generally referred to as bifunctional degraders, PROTACs have led the way in the field of targeted protein degradation (TPD) with several compounds currently undergoing clinical testing. Alongside bifunctional degraders, single-moiety compounds, or molecular glue degraders (MGDs), are increasingly being considered as a viable approach for development of therapeutics, driven by advances in rational discovery approaches. This review focusses on drug discovery with respect to bifunctional and molecular glue degraders within the ubiquitin proteasome system, including analysis of mechanistic concepts and discovery approaches, with an overview of current clinical and pre-clinical degrader status in oncology, neurodegenerative and inflammatory disease.

Transcutaneous nerve stimulation has several neuromodulatory applications, including pain management, sensory restoration, and motor recovery. Transcutaneous stimulation delivered via electrode arrays offers ease of use and reconfigurability through non-invasive means. Also, employing electrode arrays allows regulation of the permeated electric fields for greater control over the stimulation performance. Field shaping involves the regulation of permeated electric fields and is a well-established practice for deep brain stimulation; however, its applicability to peripheral nerve stimulation still needs exploration. Adopting such techniques can help to overcome current limitations with transcutaneous stimulation, like poor targetability, early onset of fatigue, and perceived discomfort. This article provides a perspective on the applicability of field-shaping techniques in improving the overall stimulation outcome.

De-escalation is currently taking place both in surgical and systemic treatment of breast cancer. The introduction of trastuzumab, the first monoclonal antibody against the HER2 receptor over 20 years ago was a milestone in the treatment of HER2 positive breast cancer and marked the beginning of a new era in targeted tumor therapy. In the sense of de-escalation, omitting non-targeted cytotoxic chemotherapy altogether is often hailed as the ultimate goal of oncological research. Especially in case of small, node-negative, HER2 positive early breast cancer, it remains a challenge for clinicians to establish the safest and most efficient treatment plan while considering the significant potential for toxic side effects associated with chemotherapy and HER2 targeted therapy, and the generally excellent prognosis. In this context, several ongoing studies are currently assessing chemotherapy-free regimens as part of strategies aimed at de-escalating therapy in the field of HER2 positive early breast cancer. Despite promising early results from these studies, combination of anti-HER2 treatment with chemotherapy backbone remains standard of care.

Meningiomas are cerebral cancers that arise from abnormal cell development in the meninges and defensive layers covering the mind and spinal line. They can attack areas close to the cerebrum tissue and apply tension to neighboring designs, prompting different neurological side effects. Recent advances in atomic science and genomics have revealed insights into the fundamental subatomic adjustments and flagging pathways involved in the improvement of meningoma. Cabozantinib, a chemotherapeutic agent, has shown promising results in preclinical and clinical studies in various malignancies, including meningia. It inhibits angiogenesis, reduces cancer development, and prompts cell passage, providing areas of strength for clinical examination. Inhibition of VEGFR2 signaling has shown promise results in clinical trials in various cancer types, including a variety of cancers. This review summarizes the current knowledge on the pathophysiology and potential therapeutic effects of cabozanteb as a therapeutic agent for intracranial meninga.

Esophageal cancer is a formidable challenge in the realm of cancer treatment. Conventional methods such as surgery, chemotherapy, and immunotherapy have demonstrated limited success rates in managing this disease. In response, targeted drug therapies have emerged as a promising strategy to improve outcomes for patients. These therapies aim to disrupt specific pathways involved in the growth and development of esophageal cancer cells. This review explores various drugs used to target specific pathways, including cetuximab and monoclonal antibodies (gefitinib) that target the epidermal growth factor receptor (EGFR), trastuzumab that targets human epidermal growth factor receptor 2 (HER-2), drugs targeting the vascular endothelial growth factor receptor (VEGFR), mTOR inhibitors, and cMET inhibitors. Additionally, the article discusses the impact of drug resistance on the effectiveness of these therapies, highlighting factors such as cancer stem cells, cancer-associated fibroblasts, immune-inflammatory cells, cytokines, hypoxia, and growth factors. While drug targeting approaches do not provide a complete cure for esophageal cancer due to drug resistance and associated side effects, they offer potential for improving patient survival rates.

"Hidden hunger", the deficiency of important mineral micronutrients, affects more than 2 billion people globally. Adolescence is unquestionably a period of nutritional risk, given the high nutritional requirements for growth and development, erratic or capricious diets and the increased consumption of snacks. This study applied the rational food design approach to obtain micronutrient-dense biscuits by combining chickpea and rice flours to achieve an optimal nutritional profile, crunchy texture and appealing flavour. The perception of 33 adolescents of the suitability of such biscuits as a mid-morning snack was examined. Four biscuits were formulated, with different ratios of chickpea and rice flours (CF:RF): G100:0, G75:25, G50:50 and G25:75. Nutritional content, baking loss, acoustic-texture and sensory analyses were carried out. On average, the mineral content of biscuits with the CF:RF ratio of 100:0 doubled compared with the 25:75 formula. The dietary reference values for iron, potassium and zinc reached 100% in the biscuits with CF:RF ratios of 50:50, 75:25 and 100:0, respectively. The analysis of mechanical properties revealed that samples G100:0 and G75:25 were harder than the others. Sample G100:0 showed the highest sound pressure level (Smax). Sensory analysis showed that increasing the proportion of CF in the formulation augments the grittiness, hardness, chewiness and crunchiness. Most of the adolescents (72.7%) were habitual snack consumers; 52% awarded scores ≥ 6 to biscuit G50:50 for its overall quality, 24% described its flavour as "biscuit" and 12% as "nutty". However, 55% of the participants could not pinpoint any dominant flavour. In conclusion, it is possible to design nutrient-dense snacks that meet the micronutrient requirements and sensory expectations of adolescents by combining flours naturally rich in micronutrients.

This review of the meaningful data from 2021 on cervical, endometrial, and ovarian cancers aims to provide an update of the most clinically relevant studies presented at important oncologic congresses during the year [the American Society of Clinical Oncology (ASCO) Annual Meeting, the European Society for Medical Oncology (ESMO) Congress and the Society of Gynecologic Oncology (SGO) Annual Meeting]. Despite the underlying existence of the COVID-19 pandemic, the last year has been notable in terms of research, with significant and promising advances in gynecologic malignancies. Several major studies reporting the effects of innovative therapies for patients with cervical, endometrial, and ovarian cancers might change the medical practice in the future.

Cas endonuclease-mediated genome editing provides a long-awaited molecular biological approach to the modification of predefined genomic target sequences in living organisms. Although cas9/guide (g)RNA constructs are straightforward to assemble and can be customized to target virtually any site in the plant genome, the implementation of this technology can be cumbersome, especially in species like Triticale that are difficult to transform, for which only limited genome information is available and/or which carry comparatively large genomes. To cope with these challenges, we have pre-validated cas9/gRNA constructs (1) by frameshift restitution of a reporter gene co-introduced by ballistic DNA transfer to barley epidermis cells, and (2) via transfection in Triticale protoplasts followed by either a T7E1-based cleavage assay or by deep-sequencing of target-specific PCR amplicons. For exemplification, we addressed the Triticale ABA 8’-hydroxylase 1 gene, one of the putative determinants of pre-harvest sprouting of grains. We further show that in-del induction frequency in Triticale can be increased by TREX2 nuclease activity, which holds true for both well- and poorly performing gRNAs. The presented results constitute a sound basis for the targeted induction of heritable modifications in Triticale genes.

China is out of extreme poverty in 2020 on schedule and one decade in advance to fulfill the UN 2030 Agenda for Sustainable Development Goals (SDGs), and became the first developing country to alleviate poverty in half century. Therefore, a large numbers of effective approaches are emerging, and the intellectual’s technology-led poverty reduction, which locally known as the “Straw Hat University”initiated by “Farmer's professor”mode, is the most tried and tested approach motivated by the intellectual’s “Serve the people” tradition and supported by the all nation. This research conduct case analysis with three most remarkable organic intellectuals as Agronomist Yuan longping, Mycologist Lin Zhanxi and Plant pathologist Zhu Youyong with their bridging gaps in food security, regional imbalance and ethnic disparity respectively to sort out the sustainable modules and universal experiences. The conclusion indicates that“Farmer's Professor” Initiated “Straw Hat University” is an effective approach to solve human beings’ development problems and benefit the livelihoods, especially in the under development regions; and the authentic down to earth experiments into productivity as well as the Intellectual property transformation is the perfect path to deploy offline and online resources building the effective production and supply chain to integrate industries by intellectual’s critical innovation.

Seafood is considered one of the main food allergen sources by the European Food Safety Authority (EFSA). It comprises several distinct groups of edible aquatic animals including fish and shellfish such as crustacean and mollusks. Recently the EFSA recognized the high risk of food allergy over the world and established the necessity of developing new methodologies for its control. Consequently, accurate, sensitive and fast detection methods for seafood allergy control and detection in food products are highly recommendable. In this work, we present a comprehensive review of the applications of the proteomics methodologies for the detection and quantification of seafood allergens. For that, two consecutive proteomics strategies (Discovery and Targeted Proteomics) applied for the study and control of seafood allergy are reviewed in detail. In addition, future directions and new perspectives were also provided.

Hepatocellular carcinoma is the most common primary liver cancer and the fourth leading cause of cancer death worldwide. A total of 70-80% of patients are diagnosed at an advanced stage with a dismal prognosis. Sorafenib has been the standard of care for almost a decade until 2018 when FDA approved an alternative first-line agent namely lenvatinib. Whereas FOLFOX4 results an alternative first-line treatment for the chinese clinical oncology guidelines. In addition to cabozantinib, regorafenib, and ramucirumab, two therapeutics against the PD-L1/PD1 axis have been recently approved for subsequent-line therapy, as nivolumab and pembrolizumab. However, similar to other solid tumors, the response rate of single-agent targeting PD-L1/PD1 axis is low. Therefore a lot of combinatory approaches are under investigation, including the combination of different immune checkpoint inhibitors, the addition of immune checkpoint inhibitors after resection or during locoregional therapy, immune checkpoint inhibitors in addition to kinase inhibitors, anti-angiogenic therapeutics, and others. This review focuses on the use of ICIs for the hepatocellular carcinoma with an attent evaluation of new ICIs based combinatory approaches.

The PI3K-AKT-mTOR signal transduction pathway regulates a variety of biological processes including cell growth, cell cycle progression and proliferation, cellular metabolism and cytoskeleton reorganization. Fine-tuning of the PI3K pathway signaling output is essential for the maintenance of tissue homeostasis and uncontrolled activation of this cascade leads to a number of human pathologies including cancer. Inactivation of the tumour suppressor phosphatase PTEN and/or activating mutations in the proto-typical lipid kinase PI3K have emerged as some of the most frequent events associated with human cancer and as a result the PI3K pathway has become a highly sought-after target for cancer therapies. In this review we summarize the essential role of the PTEN-PI3K axis in controlling cellular behaviors by modulating activation of key proto-oncogenic molecular nodes and functional targets. Further, we highlight important functional redundancies and peculiarities of these two critical enzymes that over the last few decades have become a central part of the cancer research field and have instructed hundreds of pre-clinical and clinical trials to better cancer treatments.

The aim of this study was to develop a novel nanostructured lipid carriers (NLCs) with hepatocytes targeting as carriers for the magnetic resonance imaging (MRI) contrast agent (i.e., magnetic nanostructured lipid carriers, MNLCs), and to evaluate the targeting ability of the MNLCs with T2-weighted MRI both in vitro and in vivo. Here, the galactose-octadecylamine (Gal-ODA) conjugates were synthesized by chemical coupling reaction between lactose acid (LA) and octadecylamine (ODA). Then the superparamagnetic iron oxide (SPIO) loaded nanostructured lipid carrier (conjugated by Gal-ODA, Gal-NLC-SPIO) was prepared by emulsification-ultrasonic method using monoglyceride as lipid materials. The Gal-NLC-SPIO with a diameter of about 50 nm could specifically internalize into LO2 (human hepatic cell line) cells. In vitro MRI results also proved the specific targeting ability of Gal-NLC-SPIO to LO2 cells. The in vivo MR imaging experiments using an orthotopic intrahepatic xenograft tumor model further validated the hepatocytes targeted effect of Gal-NLC-SPIO. The results of this study suggested that Gal-NLC-SPIO can be used as a contrast agent to aid in the diagnosis of hepatic diseases.

Durability monitoring of insecticide-treated nets (ITNs) containing a pyrethroid in combination with a second active ingredient (AI) must be adapted so that the insecticidal bioefficacy of each AI can be monitored independently. An effective way to do this is to measure rapid knock down of a pyrethroid-susceptible strain of mosquitoes to assess the bioefficacy of the pyrethroid component and to use a pyrethroid-resistant strain to measure the bioefficacy of the second ingredient. To allow robust comparison of results across tests within and between test facilities, and over time, protocols for bioefficacy testing must include either characterisation of the resistant strain, standardisation of the mosquitoes used for bioassays, or a combination of the two. Through a series of virtual meetings, key stakeholders and practitioners explored different approaches to achieving these goals. Via an iterative process we decided on the preferred approach and produced a protocol consisting of characterising mosquitoes used for bioefficacy testing before and after a round of bioassays, for example at each time point in a durability monitoring study. We present the final protocol and justify our approach to establishing a standard methodology for durability monitoring of ITNs containing pyrethroid and a second AI.

Sleep quality is known to affect automatic and executive brain functions such as gait control and cognitive processing. This study aimed to assess the effect of dual tasks on gait spatiotemporal parameters among young adults with good and poor sleep quality in the United Arab Emirates. In total, 65 young adults with a mean age of 21.1±2.5 were assessed for gait analysis during single-task and dual-task conditions. The participants’ sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), and gait was assessed using the BTS Gaitlab System. The participants were asked to walk at natural speed as a single-task condition, followed by walking while performing a cognitive task as a dual-task condition. The parameters assessed included the gait velocity (m/s), cadence (steps/min), step width (m), and stride length (m). The DTC on each gait parameter was calculated. The Mann–Whitney U test was used to compare the differences in the DTC on gait variables between the good and poor sleep quality groups, and the Spearman correlation test was used to assess the correlation between total PSQI scores and the DTC. At a significance level of p&lt;0.05, a significant difference in cadence between the two sleep quality groups was observed, in addition to a positive correlation between sleep quality and the DTC effect on gait mean velocity, cadence, and stride length. Our findings also revealed a greater DTC on participants with poorer sleep quality. These findings contribute to our understanding of the significance of sleep quality in gait performance while multitasking in younger populations.

Computational simulations of three-dimensional flow around a NACA 0018 wing with an aspect ratio of AR=5 are carried out using the Unsteady Reynolds-Averaged Navier-Stokes (URANS) equations with the Shear-Stress Transport turbulence model closure. Simulations were performed to capture the aerodynamic stall hysteresis using a developed Pseudo-Transient Continuation (PTC) method based on a dual time step approach in the CFD code OpenFOAM. The flow was characterized by an incompressible Mach number of M=0.12 and a moderate Reynolds number Re=0.67×10^6. The results obtained indicate the presence of a noticeable aerodynamic hysteresis in the static dependencies of the force and moment coefficients, as well as the manifestation of bi-stable flow separation patterns, accompanied by the development of asymmetry in the stall zone. The URANS simulation results are in good agreement with the experimental data obtained for the NACA 0018 finite aspect ratio wing from the low-speed wind tunnel under the same test conditions. A new phenomenological bifurcation model of aerodynamic stall hysteresis under static and dynamic conditions is formulated, which is proven to be able to closely match the experimental data.

The dual-station Interferometric Synthetic Aperture Radar (InSAR) system can overcome the physical limitations imposed by the baseline of single-station dual-antenna InSAR. It provides greater flexibility and can enhance elevation measurement accuracy through a well-designed baseline configuration.Unmanned aerial vehicles (UAV) equipped with dual-station InSAR, with relatively low cost and high flexibility, are useful for mapping and land resource exploration. However, due to challenges including spatiotemporal synchronization and motion errors, there are limited reports on UAV-borne dual-station InSAR. This paper proposes a comprehensive method for processing data from small UAV-borne dual-station InSAR by integrating two-way synchronization chain signals. The proposed method includes compensation for time and phase synchronization errors, trajectory refinement with synchronized chain and Position and Orientation System (POS) data, high-precision dual-station InSAR imaging and interferometric processing. Height inversion results based on the proposed method is also provided, demonstrating the effectiveness of the proposed method and improving interferometric accuracy at calibration points from 0.66 meters to 0.42 meters.

The dual leucine zipper kinase (DLK) alias mitogen-activated protein 3 kinase 12 (MAP3K12) has gained much attention in recent years. DLK belongs to the mixed lineage kinases, characterized by homology to serine/threonine and tyrosine kinase but exerts serine/threonine kinase activity. DLK has been implicated in many diseases including several neurodegenerative diseases, glaucoma, and diabetes mellitus. As a MAP3K, it is generally assumed that DLK becomes phosphorylated and activated by upstream signals and phosphorylates and activates itself, the downstream serine/threonine MAP2K, and ultimately MAPK. In addition, other mechanisms such as protein-protein interactions, proteasomal degradation, dephosphorylation by various phosphatases, palmitoylation, and subcellular localization have been shown to be involved in the regulation of DLK activity or its fine-tuning. In the present review, the diverse mechanisms regulating DLK activity will be summarized to provide a better insight into DLK action and possibly new targets to modulate DLK function.

Pesticides are chemical products are used to protect crops to prevent or eliminate undesirable organisms. Pesticides can contaminate continental waters, air, soil and food products. The presence of pesticide residues must therefore be monitored in water and food using sensitive, reliable and broad-spectrum analytical methods, as there is a huge variety of pesticides. Biosensors are one of the screening methods with great potential for detecting residues below the maximum residue limits. The different sensing principles of enzymatic biosensors for pesticide analysis will be described. This review highlights the great potential of colorimetric, enzymatic biosensors for detecting pesticide residues in water and food. Moreover the development of dual colorimetric and fluorimetric sensors during the past years is presented. These methods are most often based on the enzyme acetylcholinesterase, whose activity is inhibited by pesticides. The different approaches used in the development of these biosensors will be detailed, based on different chemical substrates, fluorophores and nanomaterials. The advantages and disadvantages of each approach will be discussed. Finally, the development prospects for improving these biosensors will be presented.

Measuring pulmonary nodules accurately can help with early diagnosis of lung cancer, which can improve a patient’s chances of survival. Many methods for segmenting nodules have been developed, but they all rely on input from radiologists in the form of a 3D volume of interest (VOI) or use a constant region of interest (ROI) and only consider the presence of nodule within the given VOI. These approaches limit the networks’ ability to detect nodules outside the given VOI and can also include unnecessary structures in the VOI, leading to potentially inaccurate segmentation. In this work, we propose a novel approach for 3D lung nodule segmentation by using 2D region of interest (ROI) inputted from radiologist or computer-aided detection (CADe) system. Particularly, we design a dual-encoder-based hard attention network (DEHA-Net) which incorporates the full slice of thoracic computed tomography scan along with the ROI mask to produce an accurate segmentation mask of lung nodule in the given slice. The proposed architecture exploits the adaptive region of interest (A-ROI) algorithm to automatically investigates the penetration of lung nodule into surrounding slices while eliminating the need to drawing separate ROIs in each slice. Further, the framework performs the multi-view analysis, i.e., in sagittal and coronal views, to improve the segmentation performance. The proposed scheme has been rigorously evaluated on the lung image database consortium and image database resource initiative (LIDC/IDRI) dataset and an extensive analysis of results have been performed. The quantitative analysis shows that the proposed method not only improves the existing state-of-the-art in term of dice score but also, significantly robust against the different types, shape and dimensions of lung nodules.

In this paper a microstrip Wilkinson power divider with a 90^° phase delay at one output port is proposed to obtain circular polarization to feed a dual port RFID antenna. The 90^° phase delay was obtained by embedding an extra quarter wavelength at one port of the Wilkinson power divider. The feeding circuit is then mounted on the ground plane of the microstrip antenna feeding the radiating patch directly through the ground plane and dielectric layer thus reducing any fringing effect and resulting a mechanically compact unit. The proposed feeding method offers better expectation of antenna performance with minimal attenuation and coupling losses. The design process generalizes geometric pa- rameters of the Wilkinson power divider for variable port distances. The paper considers both UK and US RFID center frequencies, 870 MHz and 915 MHz respectively. Numeri- cally computed values for geometric design parameters for both frequencies are tabled as future design tools for port distances varying from 18 mm up to 34 mm at 870 MHz and 17 mm up to 32 mm at 915 MHz. Simulation results indicate a return loss (S11) of -20 dB and -26 dB at 870 MHz and 915 MHz operational frequencies respectively at 270^° angled quarter wavelength.

The kinetics and modeling of dual-wavelength controlled photopolymerization confinement (PC) are presented and measured data are analyzed by analytic formulas and numerical data. The UV-light initiated inhibition effect is strongly monomer-dependent and different monomers have different C=C bond rate constants and conversion efficacy. Without the UV-light, for a given blue-light intensity, higher initiator concentration (C₁₀) and rate constant (k’) lead to higher conversion, as also predicted by analytic formulas, in which the total conversion rate (R_T) is an increasing function of k’R, which is proportional to k[gB₁C₁]^0.5. However, the coupling factor b₁ plays a different role that higher b₁ leads to higher conversion only in the transient regime; whereas higher b₁ leads lower steady-state conversion. For a fixed initiator concentration C₁₀, higher inhibitor concentration (C₂₀) leads to lower conversion due to stronger inhibition effect. However, same conversion reduction was found for the same H-factor of H₀ = [b₁C₁₀ - b₂C₂₀]. Conversion of blue-only are much higher than that of UV-only and UV-blue combined, in which high C₂₀ results a strong reduction of blue-only-conversion, such that the UV-light serves as the turn-off (trigger) mechanism for the purpose of spatial confirmation within the overlap area of UV and blue light. For example, UV-light controlled methacrylate conversion of a glycidyl dimethacrylate resin formulated with a tertiary amine co-initiator, and butyl nitrite, subject to a continuous exposure of a blue light, but an on-off exposure of a UV-light. Finally, we developed a theoretical new finding for the criterion of a good material/candidate governed by a double ratio of light-intensity and concentration, [I₂₀C₂₀.]/[I₁₀C₁₀].

Lung cancer remains the leading cancer killer worldwide. Early diagnosis can effectively increase the patient cure rate but existing diagnostic methods limit early lung cancer diagnosis. Therefore, development of a simple but efficient lung cancer screening method is important to improvement of both the diagnosis rate and the survival rate of lung cancer patients. In this study, ten photosensitive materials with high sensitivity and high specificity were screened accurately to construct a microarray sensor that can rapidly identify six types of lung cancer biomarkers in exhaled breath. Results from hierarchical cluster analysis (HCA), principal component analysis (PCA) and difference maps showed that the classification of the analytes agreed with structure similarity laws. The detection results from parallel experiments and structurally similar analytes, in turn, cluster into a group; the fingerprints of the different analytes have specific response regions. The well-screened sensor chip fabrication workload and cost were both reduced by approximately two thirds, while the microfluidic device sensitivity and stability increased by approximately 1.3 times their corresponding values before optimization. The dual-channel device also offers real-time contrast detection and synchronous parallel detection functions and has potential application prospects for use in extensive screening of high-risk populations for lung cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related death worldwide. It is commonly diagnosed in advanced stages and therapeutic interventions are typically constrained to systemic chemotherapy, which yields only modest clinical outcomes. In this review, we examine recent developments in targeted therapy tailored to address distinct molecular pathway alteration required for PDAC. Our review delineates the principal signaling pathways and molecular mechanisms implicated in the initiation and progression of PDAC. Subsequently, we provide an overview of prevailing guidelines, ongoing investigations, and prospective research trajectories related to targeted therapeutic interventions, drawing insights from randomized clinical trials and other pertinent studies. This review focus on a comprehensive examination of preclinical and clinical data substantiating the efficacy of these therapeutic modalities, emphasizing the potential of combinatorial regimens and novel therapies to enhance the quality of life for individuals afflicted with PDAC. Lastly, the review delves into the contemporary application and ongoing research endeavors concerning targeted therapy for PDAC. This synthesis serves to bridge the molecular elucidation of PDAC with its clinical implications, the evolution of innovative therapeutic strategies, and the changing landscape of treatment approaches.

Drug resistance in tumor cells is a significant roadblock in the clinical management of advanced or recurrent diseases in endometrial cancers. As a part of the tumor-stromal ecosystem, tumor cells are ecologically connected to the cancer-associated fibroblasts (CAFs), which form contributory elements of the tumor microenvironment (TME). We recently reported a novel model of patient-derived CAF-based 2-cell Hybrid Co-Culture (HyCC) to evaluate CAFs' role in developing drug resistance and understanding personalized tumor cell-CAF dialogue. Using our 2-cell HyCC model of patient-derived endometrial CAFs, we present data to demonstrate the direct counter-inhibitory effect of CAFs to combinations of cytotoxic and targeted drugs in developing drug resistance. CAFs derived from resected endometrial tumor samples were first passage-wise characterized before and after freeze-thaw for their positive and negative CAF markers expression pattern. Paclitaxel and its combination with copanlisib, TAK228, lenvatinib, and trametinib were used to test the 3D clonogenic growth of endometrial AN3CA cells on endometrial CAFs. We demonstrate that CAF-mediated resistance to antitumor drugs occurs via direct and indirect contact with CAFs in HyCC. Our data established the strength of the 2-cell HyCC model of patient-derived CAFs in solid tumors and provided a model of resistance to antitumor drugs tailored on a patient-to-patient basis.

Targeted protein degradation is an attractive technology for cancer treatment due to its ability to overcome the unpredictability of small molecule inhibitors that cause resistance mutations. In recent years, various targeted protein degradation strategies have been developed based on the ubiquitin-proteasome system in the cytoplasm or the autophagy-lysosomal system during endocytosis. In this review, we describe and compare technologies for targeted inhibition and targeted degradation of the epidermal growth factor receptor (EGFR), one of the major proteins responsible for the onset and progression of many types of cancer. In addition, we have developed an alternative strategy, called alloAUTO, based on the binding of new heterocyclic compounds to an allosteric site located in close proximity to the EGFR catalytic site. These compounds cause targeted degradation of the transmembrane receptor, simultaneously activating both systems of protein degradation in cells. Damage to EGFR signaling pathways promotes inactivation of Bim sensor protein phosphorylation, which leads to disintegration of the cytoskeleton, followed by detachment of cancer cells from the extracellular matrix and, ultimately, to cancer cell death. This hallmark of targeted cancer cell death suggests an advantage over other targeted protein degradation strategies, namely that the fewer cancer cells survive, the fewer chemotherapy-resistant mutants appear.

Lung cancer is the leading cause of cancer death worldwide, with non-small cell lung cancer (NSCLC) making up 80% of cases. Some genetic factors leading to NSCLC development include genetic mutations and PD-L1 expression. PD-L1 proteins are targeted in an NSCLC treatment called targeted gene therapy. However, this treatment is effective in a low percentage of patients. This study aimed to create machine learning models to use features like the number of mutations and the level of PD-L1 proteins in cancer cells, along with others, to predict whether a patient will receive clinical benefit from gene therapy treatment. This was done by downloading and merging datasets from cbioportal.org to create a sample size for the model. Features with high correlations to clinical benefit were identified. Three machine-learning models were created using these features to predict clinical benefits in patients, and each model’s accuracy was evaluated. All three models were accurate between 55-85%, with two of the models averaging an accuracy around 75%. Doctors can use these models to more accurately predict whether gene therapy treatment is likely to work in a patient before prescribing it to them.

A unique two-column ²³⁰U/²²⁶Th generator has been developed. The focus was hold on obtaining ²²⁶Th of high purity in a solution amenable to further labeling. The first column of the proposed generator filled with TEVA Resin held ²³⁰U, from which ²²⁶Th was eluted with 7 M HCl solution. UTEVA Resin pretreated with nitric acid solution was used as a sorbent for the second column for thorium retention. ²²⁶Th was extracted with 0.01-0.05 M citric buffer solution. One cycle of generator milking took 5-7 minutes and produced > 90% of ²²⁶Th in 1.5 ml of eluate, pH 4.5-5.0. The proposed two-column ²³⁰U/²²⁶Th generator was tested over two months including a second loading of ²³⁰U additionally accumulated from ²³⁰Pa. The ²³⁰U impurity in ²²⁶Th eluate was less than 0.01% allowing to use it directly in synthesis of radiopharmaceutical compounds.

Each individual has a unique gut microbiota; therefore the genes in our microbiome outnumber the genes in our genome by about 150 to 1. Perturbation in host nutritional status influences gut microbiome composition and vice versa. The gut microbiome can help in producing vitamins, hormones, and other active metabolites that support the immune system; harvest energy from food; aid in digestion; protect against pathogens; improve gut transit and function; send signals to the brain and other organs, oscillating the circadian rhythm and coordinate with host metabolism through multiple cellular pathways. Gut microbiota can be influenced by host genetics, medications, diet, and lifestyle factors from preterm to aging. So before prescribing a customized treatment, it is crucial to monitor and count the gut flora as a focused biomarker. Many nutritional approaches that have been developed help in maintaining and restoring an optimal microbiome such as specific diet therapy, nutrition interventions and customized eating patterns. One of these approaches is time-restricted feeding/eating (TRF/E), a type of intermittent fasting (IF) in which a subject abstains from food intake for a specific time window. Such a dietary modification might alter and restore the gut microbiome for proper alignment of cellular and molecular pathways throughout the lifespan. In this review, we have highlighted that gut microbiota would be a targeted biomarker and TRF/E would be a targeted approach for restoring the gut microbiome associated molecular pathways like hormonal signaling, the circadian system, metabolic regulators, neural responses, and immune-inflammatory pathways. Consequently, modulation of gut microbiota through TRF/E could contribute in proper utilization and availability of the nutrients and in this way confer protection against diseases for harnessing personalized nutrition approaches to improve human health.

Up to 25% of early human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) patients will relapse despite the improvement achieved by the introduction of HER2-targeted therapy. Beyond trastuzumab, other agents approved for early HER2+ BC include the monoclonal antibody pertuzumab, the antibody-drug conjugate (ADC) trastuzumab-emtansine (T-DM1) and the reversible HER2 inhibitor lapatinib. New agents, such as trastuzumab-deruxtecan or tucatinib in combination with capecitabine and trastuzumab, have also shown an improvement in the metastatic setting. Other therapeutic strategies to overcome treatment resistance have been explored in HER2+ BC, mainly in HER2+ that also overexpress estrogen receptors (ER+). One strategy has been to target the cyclin-dependent kinases 4/6 (CDK4/6) as they are downstream of HER2 and many of the cellular pathways associated with resistance to HER2-targeted therapies play a key role in cell cycle and proliferation. Different trials have explored these strategies with encouraging results, but definitive results are needed. In addition, HER2+ BC is known to be more immunogenic than other BC subgroups, with high variability between tumors. Different immunotherapeutic agents have been investigated in this setting, with promising but controversial results obtained to date.

(1) Background: Targeted (TT) and immune checkpoint inhibitor (ICI) therapies have become available in the routine care of metastatic melanoma in recent years. (2) Objective: We compared mortality in patients with metastatic melanoma and different systemic therapies. (3) Methods: A retrospective cohort study, based on pseudonymized health insurance data of about 2 million individuals from Saxony, Germany, was conducted for the years 2010 to 2020. Only patients with an advanced stage, i.e. distant metastases were considered for the main analysis. Relative survival since metastasis and predicted survivor curves derived from a Cox model were used to assess potential differences in mortality. (4) Results: Relative survival was highest in the subgroup with sequential use of ICI and TT. All treatments except interferon had significant hazard ratios (HR) in the Cox model with time-dependent effects indicating a protective effect after treatment initiation (HR 0.01-0.146) but decreasing over time (HR 1.351-2.310). The predicted survivor curves revealed best survival under ICI-TT treatment and worst survival under TT treatment alone. (5) Conclusions: We found real-world evidence for survival benefits of patients with metastatic melanoma who received sequential ICI and TT treatment. It is conceivable that the observed high survival differences were overestimated due to bias, such as confounding by indication.

Background and aims: Despite recent advances in advanced prostate cancer treatments, there are no clinically useful biomarkers or treatments for men with such cancers. Targeted therapies have shown promise, but there remain fewer actionable targets in prostate cancer than in other cancers. This work aims to characterize BRD9, currently understudied in prostate cancer, and investigate its co-expression with other genes to assess its potential as a biomarker and therapeutic target in human prostate cancer. Materials and methods: Omics data from a total of 2053 prostate cancer patients across 11 independent datasets were accessed via Cancertool and cBioPortal. mRNA expression and co-expression, mutations, amplifications, and deletions were assessed with respect to key clinical parameters including survival, Gleason grade, stage, progression and treatment. Network and pathway analysis was carried out using Genemania, and heatmaps were constructed using Morpheus. Results: BRD9 is overexpressed in prostate cancer patients, especially those with metastatic disease. BRD9 expression did not differ in patients treated with second generation antiandrogens versus those who were not. BRD9 is co-expressed with many genes in the SWI/SNF and BET complexes, as well as those in common signaling pathways in prostate cancer. Summary and conclusions: BRD9 has potential as a diagnostic and prognostic biomarker in prostate cancer. BRD9 also shows promise as a therapeutic target, particularly in advanced prostate cancer, and as a co-target alongside other genes in the SWI/SNF and BET complexes, and those in common prostate cancer signalling pathways. These promising results highlight the need for wider experimental inhibition and co-targeted inhibition of BRD9 in vitro and in vivo, to build on the limited inhibition data available.

An elevated level of endoplasmic reticulum (ER) stress is considered an aggravating factor for inflammatory bowel disease (IBD). To develop an ER stress attenuator that is effective against colitis, 4-phenylbutyric acid (4-PBA), a chemical chaperone that alleviates ER stress, was conjugated with acidic amino acids to yield a 4-PBA-glutamic acid conjugate (PBA-GA) and a 4-PBA-aspartic acid conjugate (PBA-AA). The PBA derivatives were converted to 4-PBA in the cecal contents, where the conversion was greater with PBA-GA. After oral administration of PBA-GA (oral PBA-GA), millimolar levels of PBA were accumulated in the cecum, whereas 4-PBA was not detected in the blood, indicating the targeting of PBA-GA to the large intestine. At concentrations in the cecum achievable by oral PBA-GA, 4-PBA effectively attenuated ER stress in human colon epithelial cells. In 2,4-dinitrobenzenesulfonic acid-induced colitis in rats, oral PBA-GA alleviated the damage and inflammation in the colon. Moreover, oral PBA-GA substantially reduced the elevated levels of ER stress marker proteins in the inflamed colon. Moreover, PBA-GA was as effective as the currently used anti-IBD drug, sulfasalazine. In conclusion, PBA-GA is a colon-targeted prodrug of 4-PBA and is effective against rat colitis probably through the attenuation of ER stress in the inflamed colon.

Osteoporosis is considered a serious public health problem, particularly affecting the postmenopausal period. In 2018, in the Republic of Kazakhstan the total and primary incidence was 10 and 3.7 cases per 100,000 adults, respectively. The objective is to study osteoporosis prevalence and indicate main factors affecting low bone mineral density by screening adult population of Abay region, Kazakhstan. The target group were 641 respondents aged between 18 and 65 years old, Kazakh population living in Abay region since birth. All participants filled out questionnaire and had a bone mineral density measurement by dual energy X-ray absorptiometry (DXA) between July 15, 2023 and February 29, 2024. Logistic regression analysis was conducted to assess the association between low bone mineral density and key demographic characteristics, aforementioned lifestyle factors and nutrition habits. We identified the prevalence of low bone density and osteoporosis at the level of 34.1% with the highest prevalence in the older population group (50+ years) - 48.3%. Regression analysis revealed a number of indicators associated with the likelihood of bone sparing. However, only 4 of these showed significance in the final multivariate model (R2=22.4%). These included age (AOR 1.05), body mass index (AOR 0.92), fracture history (AOR 1.64), consumption of nuts and dried fruits were associated with lower prevalence of osteoporosis (AOR 0.48). Our study was the first in Kazakhstan that investigates the association of key demographic, behavior and anamnestic factors with low mineral density.

Ralstonia solanacearum is the pathogen responsible for Ralstonia solanacearum, which is soil-borne, infests plant conduits to cause disease.They are not easy to control and are harmful.Therefore the development of a controlled-release agent responsive to the pathogen's soil temperature and moisture conditions could aid in its control. Corn kernel powder is used as a carrier for Tetramycin biopesticide, with various compounds tested for bonding.They were then made by extrusion moulding.Temperature and wetness responsive components, including Pentaerythritol Tetrastearate, Pentaerythritol Tetraoleate, Polyethylene Glycol Stearate, and Polyethylene Glycol Monooleate,are compounded and coated onto Tetramycin cores to form an intermediate shell layer. Finally, Ethyl cellulose(EC)and Hydroxypropyl methyl cellulose(HPMC) are dissolved and sprayed onto the outermost layer to complete the pellet's shell layer.After the evaluation of texture performance test,DSC analysis,TG test,temperature and humidity response performance test, as well as pellet cross-section SEM observation, field effectiveness test, etc., the preferred formulations were screened.The results showed that the preferred Core formulation:Corn kernel powder:Tetramycin aqueous:Xanthan gum mass ratio=13.5:23:2; Intermediate Shell layer:PETS: PETO: PEG400MO mass ratio=10:30:10; and Outer Shell layer: Ethyl cellulose (EC):Hydroxypropyl methyl cellulose (HPMC) mass ratio=5:1.Under soil conditions of high incidence of Ralstonia solanacearum, i.e., sustained warmth (30-35℃) and high humidity (30% moisture content), the formulated pills showed a release rate of 95.18% to 96.24% over a period of 35 days. Moreover, they showed a stepwise cyclic release process under alternating warm and humid-dry and cold conditions.In field tests on tobacco, a relative preventive efficacy of 54.74% was achieved 106 days post-transplanting. Soil bacterial community structure analysis revealed a significant decrease (2.28-2.84 times) in the abundance of Solanaceae Raelia under Tetramycin pellet treatment compared to the control. Additionally, fungal community structure showed highter consistency initially across various soil depths, with diversity differences between soil layers reestablished later (106 days), while the predominant categories of bacteria and fungi remained unchanged.In this study, we successfully developed a nucleoshell-type slow-controlled release pill embedded with Tetramycin. This pill effectively responded to temperature and humidity changes, resulting in high efficacy in disease prevention.This development holds significant promise for effectively improving drug utilization and easing application challenges, offering broad prospects for Ralstonia solanacearum prevention and control in agriculture.

Chest X-ray (CXR) is the first tool globally employed to detect cardiopulmonary pathologies. These acquisitions are highly affected by scattered photons due to the large field-of-view required. Scatter in CXRs introduces background in the images, which reduces their contrast. We developed three deep learning-based models to estimate and correct the scatter contribution to CXRs. We used a Monte Carlo (MC) ray-tracing model to simulate CXRs from human models obtained from CT scans using different configurations (depending on the availability of dual-energy acquisitions). The simulated CXRs contained the separated contribution of direct and scattered X-rays in the detector. These simulated datasets were then used as the reference for the supervised training of several NN. Three NN models (single and dual energy) were trained with the MultiResUNet architecture. The performance of the NN models was evaluated on CXRs obtained with the MC code from chest CTs of patients affected by COVID-19. The results showed that the NN models were able to estimate and correct the scatter contribution to CXRs with an error &lt;5%, being robust to variations in the simulation setup and improving the contrast in soft tissue. The single-energy model was tested with real CXRs, providing robust estimations of the scatter-corrected CXRs.

Legume-rhizobial symbiosis leads to to the formation of root nodules, where rhizobia reside and develop into bacteroids to reduce nitrogen into ammonium for plant growth, which leaves an opening question as how plant immunity is attenuated in nodules in the presence of large number of foreign bacteria. In Medicago truncatula, mutation in NAD1 (Nodules with Activated Defense 1) only produces necrotic nodules with overactivated immunity, indicating NAD1 is an indispensable component required for suppressing immunity in nodules. In this study, a dual RNA-seq transcriptomic technology was performed to extensively analyze gene expressions in nad1-1 mutant nodules. We indenifited 89 DEGs in symbiotic nitrogen fixation and 89 DEGs in immunity in Medicago truncatula at 10 dpi. Simultaneously, we indenifited 27 DEGs in fix and nif genes in Sinorhizobium meliloti. Then we identified 56 DEGs related to stress, including ROS, NO, and NCR, most of which were upregulated in Sinorhizobium meliloti. Our analyses of nitrogen fixation-defective plant nad1-1 mutants with overactivated defense indicate that host use plant immunity to control massive bacterial colonization during early and late symbiotic stages. Our findings provide insight into the function of NAD1 in improvement or inhibition of plant immune response to maintain symbiosis during rhizobial endosymbiosis.

To compare the quality of low-energy VMIs obtained with three DECT platforms according to phantom diameter. Three sections of the Mercury Phantom 4.0 were scanned on two generations of split-filter CTs (SFCT-1st and SFCT-2nd) and on one Dual-source CT (DSCT). Noise power spectrum (NPS), task-based transfer function (TTF) and detectability index (d’) were assessed on VMIs from 40 to 70keV. Highest noise magnitude values were found with SFCT-1st and noise magnitude was higher with DSCT than with SFCT-2nd for 26-cm (10.2±1.3%) and 31-cm (7.0±2.5%), and the opposite for 36-cm (-4.2±2.5%). The highest average NPS spatial frequencies and TTF values at 50% (f50) values were found with DSCT. For all energy levels, f50 values were higher with SFCT-2nd than SFCT-1st for 26-cm (3.2±0.4%) and the opposite for 31-cm (-6.9±0.5%) and 36-cm (-5.6±0.7%). The lowest d’ values were found with SFCT-1st. For all energy levels, d’ values were lower with SFCT-2nd than with DSCT for 26-cm (-6.2±0.7%), similar for 31-cm (-0.3±1.9%) and higher for 36-cm (5.4±2.7%). In conclusion, compared to SFCT-1st, SFCT-2nd exhibited lower noise magnitude and higher detectability values. Compared with DSCT, SFCT-2nd had lower noise magnitude and higher detectability for the 26-cm but the opposite was true for the 36-cm.

Relay protection service is the most crucial service carried by the electric power communication network, which is directly linked to the safe operation of the power grid. In the route planning of power services, a route planning architecture for the power communication network is constructed in this paper, considering the operation and maintenance requirements, such as relay protection service overload (RPSO) and dual route. To minimize network risk variance, the problem of single-service route allocation is formulated by taking the factors into account such as service delay, link bandwidth utilization, and RPSO constraints. Based on $k$ shortest paths algorithm, a route planning scheme for the power services is proposed, which considers RPSO and risk balance, and a strategy for implementing multi-service route planning of the communication network is studied. The simulation results show that the proposed route planning strategy can effectively avoid relay protection service overload, reduce network risk variance, and balance network risk.

Cross-field innovation in faba bean breeding has added significant value to the traditional faba bean planting industry by allowing for the selection of faba bean varieties with a dual purpose as ornaments and food. In order to improve the selection efficiency, we determined 17 phenotypes related to ‘dual purpose’ faba beans and evaluated 37 new breeding lines, which were bred for 10 years by our team, and two traditional faba bean varieties by means of an Analytic Hierarchy Process. The lines and varieties were evaluated and sorted into five grades, from which two breeding lines with excellent comprehensive phenotypes and dual ornamental and food functions were selected. The new line GS5 passed the identification of Crop Identification Committee of Chongqing Seed Industry Association on November 25, 2021 and was renamed "Doumei 1 hao" with the identification number of " 202111". The results confirmed that the comprehensive evaluation system constructed in this study can be used for the effective selection of dual-purpose faba bean lines, providing an empirical approach for strategic decision-making by breeders.

Type 2 diabetes mellitus (T2DM) accounts for one-sixth of deaths, globally, whereas cancer is the second leading cause of death in the U.S. T2DM is a known risk factor for many cancers. This review examines the link of Reactive oxygen Species (ROS)-altered metabolic and signaling pathways in T2DM to cancer. These reprogrammed metabolic and signaling pathways are activated that contribute to diabetic complications, impact redox balance (Oxidative Stress), and have differential roles in early and late stages of cancer. If the respiratory chain is highly reduced (as under hyperglycemic conditions) or if reduced cofactors accumulate, ROS are greatly elevated. ROS may cause mutations in mitochondrial DNA (mtDNA) that result in further ROS elevation. Amplification of ROS results in activation of PKC, an overarching signaling pathway that activates MAPK with subsequent regulation of several factors that result in pathophysiological manifestations of T2DM and cancer. Upregulation of PKC leads to deregulation of NF-kß that regulates the PKB/P13/Akt pathway that orchestrates cell survival, growth, proliferation, and glucose metabolism manifested in cancer. It also affects Insulin Receptor Substrate (IRS-1), decreasing insulin stimulated glucose transport and glucose uptake, disrupting subsequent cell signaling pathways contributing to the development of T2DM. Dyslipidemia is a hallmark of T2DM and cancer. ROS-induced lipid peroxidation leads to systemic inflammation, producing inflammatory prostaglandins, cytokines and chemokines that result in tumor proliferation, rapid tumor growth, and modulation of immunity. The dual role of ROS in early and late stages of cancer make antioxidant therapy precarious and may be responsible for controversial results. A system that delivers an antioxidant directly to mitochondria may be useful in inhibiting formation of ROS early during the pre-diabetic stage whereas antioxidant therapy must be halted in later stages to retard metastasis.

Starch is widely applied in various industrial sectors, including the food industry. Starch is used as a thickener, stabilizer, or emulsifier. However, arrowroot starch generally has weaknesses, such as unstable under heating and acidic conditions, which are generally applied to processing in the food industry. Modifications were applied to improve the characteristics of native arrowroot starch. In this study, arrowroot starch was modified by heat-moisture treatment (HMT), octenylsuccinylation (OSA), and dual modification between OSA and HMT in a different sequence, namely HMT followed by OSA, and OSA followed by HMT. This study aims to determine the effect of different modification methods on the physicochemical and functional properties of native arrowroot starch. The result shows that both single HMT and dual modification caused damage to native starch granules, such as the formation of cracks and roughness. Especially for single OSA treatment, there is no significant change in granule morphology after modification. All modification treatments did not change the crystalline type of starch but reduced the RC of native starch. Both single HMT and dual modifications (HMT-OSA, OSA-HMT) increased pasting temperature and setback, conversely decreasing the peak and breakdown viscosity of native starch. Whereas, single OSA has the opposite trend compared with the other modifications. HMT played a greater role in increasing the thermal stability and retrogradation ability of arrowroot starch. Both single modifications (HMT and OSA) increase the hardness and gumminess of native starch, conversely for dual modifications. HMT has a greater effect on color characteristics, where decreased the lightness and whiteness index of native arrowroot starch. Single OSA modification increased swelling volume higher than dual modification. Both single HMT and dual modifications increase water absorption capacity and decrease the oil absorption capacity of native arrowroot starch.

Environmental regulation has dual effects on water resource utilization performance through various channels such as the "three red lines" and the "Porter hypothesis". Based on the detailed analysis of the impact path of environmental regulation on water resource utilization performance, the two-step system GMM method was adopted to test the dual effects of environmental regulation on water resource utilization performance by using panel data of 30 provinces and cities from 2004 to 2020. The results show that: (1) Environmental regulation has a significant direct impact on water resource utilization performance, and is currently in the stage of positive relationship of an inverted u-shaped relationship. (2) Environmental regulation has a significant indirect impact on water resource utilization Environmental regulation has dual effects on water resource utilization performance through various channels such as the "three-red lines" and the "Porter hypothesis". In accordance with a detailed examination of the influence path of environmental regulation on the performance of water resource utilization, the double effects of environmental regulation on water resource utilization performance were examined using panel statistics from 30 provinces and cities from 2004 to 2020 using the two-step system GMM approach. The results demonstrate that: (1) Environmental regulation has a direct effect on water resource utilization performance which is currently in the stage of the positive relationship of an inverted u-shaped relationship. (2) The influence of environmental regulation on water resource utilization performance through government intervention and industrial structure adjustment is indirect, among which government intervention can significantly improve water resource utilization performance, while the growth of the tertiary industry as a percentage can lower water resource utilization performance. (3) Both direct and indirect impacts indicate that enhancing the efficiency of the use of water resources is sustainable, and the water resource utilization performance of the preceding period had a major positive impact over the present phase. Therefore, the paper sets out a few policy suggestions, such as choosing reasonable environmental regulation tools, actively guiding the market-oriented reform with constraints, and upgrading the industrial structure in a green way.

The tumour-associated isoenzymes, hCA IX and hCA XII catalyze the hydration of carbon dioxide to bicarbonate and protons. These isoforms are highly overexpressed in many types of cancer, where they contribute for the acidification of the tumor environment promoting the tumor cell invasion and metastasis. In this work, in order to identify novel dual hCA IX and XII inhibitors, virtual screening techniques and biological assays were combined. A structure based virtual screening towards hCA IX and XII was performed using a database of approximately 26000 natural compounds. The best shared hits were submitted to a thermodynamic analysis and 3 promising best hits were identified and evaluated in terms of their hCA IX and XII inhibitor activity. In vitro biological assays are in line with the theoretical studies and revealed that Syringin, Lithospermic acid, and (-)- Dehydrodiconiferyl alcohol behave as good hCA IX and hCA XII dual inhibitors.

The hybrid numbers are a generalization of complex, hyperbolic and dual numbers. In this paper, we introduce the Horadam hybrid polynomials called Horadam hybrinomials. We also give some special cases and algebraic properties of the Horadam hybrinomials. Finally we obtain some applications related to the Horadam hybrinomials in matrices.

Though the energy density of lithium-ion batteries continues to increase, safety issues related with the internal short-circuit and the resulting combustion of highly flammable electrolyte impede the further development of lithium-ion batteries. It has been well-accepted that a thermal stable separator is important to postpone the entire battery short-circuit and thermal-runaway. Traditional methods to improve the thermal stability of separators includes surface modification and/or developing alternate material systems for separators which may always affect the battery performance negatively. Herein, a thermostable and shrink-free separator with little compromise in battery performance is prepared by coaxial electrospinning and tested. The separator consists of core-shell fiber networks where poly(vinylidene fluoride-hexafluoropropylene) (PVDF-HFP) layer serves as shell and polyacrylonitrile (PAN) as the core. This core-shell fiber network exhibits little or even no shrinking/melting at elevated temperature over 250 °C. Meanwhile, it shows excellent electrolyte wettability and can take large amount of liquid electrolyte three times more than that of conventional Celgard 2400 separator. In addition, the half-cell using LiNi1/3Co1/3Mn1/3O2 as cathode and the aforementioned electrospun core-shell fiber network as separator demonstrates superior electrochemical behavior, stably cycling for 200 cycles at 1 C with a reversible capacity of 130 mAh g-1 and little capacity decay.

Extracellular vesicles (EVs) are membrane-bound particles released from cells, and their cargo can alter the function of recipient cells. EVs from X-irradiated cells have been shown to play a likely role in non-targeted effects. However, EVs derived from proton irradiated cells have not yet been studied. We aimed to investigate and compare the proteome of EVs and their cell of origin after proton or X-irradiation. The EVs were derived from a human oral squamous cell carcinoma (OSCC) cell line exposed to 0, 4, or 8 Gy with either protons or X-rays. The EVs and irradiated OSCC cells underwent liquid chromatography-mass spectrometry for protein identification. Interestingly, we found different protein profiles both in the EVs and in the OSCC cells after proton irradiation compared to X-irradiation. In the EVs, we found that protons cause a downregulation of proteins involved in cell growth and DNA damage response compared to X-rays. In the OSCC cells, proton and X-irradiation induced dissimilar cell death pathways and distinct DNA damage repair systems. These results are of potential importance for understanding how non-targeted effects in normal tissue can be limited and for future implementation of proton therapy in the clinic.

Prostate-specific membrane antigen (PSMA) has been identified as a target for the development of theranostic agents. In our current work, we describe the design and synthesis of novel N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-(S)-L-lysine (DCL) urea-based PSMA inhibitors with a chlorine-substituted aromatic fragment at the lysine ε-nitrogen atom, a dipeptide as peptide fragment of the linker, including two phenylalanine residues in the L-configuration, and 3- or 4-(tributylstannyl)benzoic acid as prosthetic group in their structures for radiolabeling. The standard compounds ([127I]PSMA-m-IB and [127I]PSMA-p-IB) for comparative and characterization studies were firstly synthesized using two alternative synthetic approaches. An important advantage of the alternative synthetic approach in which the prosthetic group (NHS-activated esters of compounds) is first conjugated with the polypeptide sequence, followed by replacement of the Sn(Bu)3 group with radioiodine, is that the radionuclide is introduced in the final step of synthesis, thereby minimizing operating time with iodine-123 during the radiolabeling process. The obtained DCL urea-based PSMA inhibitors were radiolabeled with iodine-123. The radiolabeling optimization results showed that the radiochemical yield of [123I]PSMA-p-IB was higher than those of [123I]PSMA-m-IB, which were 74.9± 1.0% and 49.4 ± 1.2%, respectively. The radiochemical purity of [123I]PSMA-p-IB after purification was greater than 99.50%. The initial preclinical evaluation of [123I]PSMA-p-IB demonstrated a considerable affinity and specific binding to PC-3 PIP (PSMA-expressing cells) in vitro. The in vivo biodistribution of this new radioligand [123I]PSMA-p-IB showed less accumulation than [177Lu]Lu-PSMA-617 in several normal organs (liver, kidney and bone). These results warrants further preclinical development including toxicology evaluation and experiments in tumor-bearing mice.

Bacterial nitroreductase enzymes that convert prodrugs to cytotoxins are valuable tools for creating transgenic targeted ablation models to study cellular function and cell-specific regeneration paradigms. We recently engineered a nitroreductase (“NTR 2.0”) for substantially enhanced reduction of the prodrug metronidazole, which permits faster cell ablation kinetics, cleaner interrogations of cell function, ablation of previously recalcitrant cell types, and extended ablation paradigms useful for modelling chronic diseases. To provide insight into the enhanced enzymatic mechanism of NTR 2.0, we have solved the X-ray crystal structure at 1.85 Angstroms resolution and compared it to the parental enzyme, NfsB from Vibrio vulnificus. We additionally present a survey of reductive activity with eight alternative nitroaromatic substrates, to provide access to alternative ablation prodrugs, and explore applications such as remediation of dinitrotoluene pollutants. The predicted binding modes of four key substrates were investigated using molecular modelling.

TomoBreast hypothesized that hypofractionated 15 fractions/3 weeks image-guided radiation therapy (H-IGRT) can reduce lung-heart toxicity, as compared with normofractionated 25-33 fractions/5-7 weeks conventional radiation therapy (CRT). 123 women with stage I-II operated breast cancer were randomized to receive CRT (N=64) or H-IGRT (N=59). The primary endpoint used a four-items measure of the time to 10% alteration in any of patient self-reported measure, physician clinical evaluation, echocardiography or lung function tests, analyzed by intention-to-treat without exclusion. Results found comparable survivals, but H-IGRT significantly reduced the toxicity measured by lung diffusion capacity and alveolar volume as compared with CRT, G1 in 53% (31/59) versus 72% (44/61) patients, P=0.006; G2, 29% versus 48%, P=0.020. H-IGRT significantly reduced the risk of composite cardio-pulmonary alteration at 5 years, 10.2% versus 26.7%, P=0.024. In conclusion, TomoBreast is a proof-of-concept that image-guided radiation-therapy can improve the overall balance of lung-heart outcomes in breast cancer adjuvant therapy. Furthermore, the significance of the findings supports the efficacy of a small trial size design, which can be critical when clinical research resources are limited.

Through its suggestive name, non-targeted methods (NTMs) do not aim at a predefined "needle in the haystack". Instead, they exploit all the constituents of the haystack. This new form of analytical methods is increasingly finding applications in food and feed testing. However, the concepts, terms, and considerations related to this burgeoning field of analytical testing needs to be propagated for the benefit of ones associated in academic research, commercial development, and official control. This paper addresses the frequently asked questions around notations and terminologies surrounding NTMs. The widespread development and adoption of these methods also necessitates the need to develop approaches to NTM validation, i.e., evaluating the performance characteristics of a method to determine if it is fit-for-purpose. This work aims to provide a roadmap to approaching NTM validation. In doing so, the paper deliberates on the different considerations that influence the approach to validation and provides suggestions thereof.

Triple negative breast cancer (TNBC) is the most aggressive breast cancer accounting for around 15% of identified breast cancer cases. TNBC, by lacking estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), is unresponsive to current targeted therapies. Existing treatment relies on chemotherapeutic treatment but, despite an initial response to chemotherapy, the inception of resistance and relapse is unfortunately common. Dasatinib is an approved second-generation inhibitor of multiple tyrosine kinases and literature data strongly support its use in the management of TNBC. However, dasatinib binds to plasma proteins and undergoes extensive metabolism through oxidation and conjugation. To protect dasatinib from fast pharmacokinetic degradation and to prolong its activity, it was encapsulated on poly(styrene-co-maleic acid) (SMA) micelles. The obtained SMA-dasatinib nanoparticles (NPs) were evaluated for their physicochemical properties, in vitro antiproliferative activity in different TNBC cell lines, and in vivo anticancer activity in a syngeneic model of breast cancer. Obtained results showed that SMA-dasatinib is more potent against 4T1 TNBC tumor growth in vivo compared to free drug. This enhanced effect was ascribed to the encapsulation of the drug protecting it from a rapid metabolism. Our finding highlights the often-overlooked value of nanoformulations in protecting its cargo from degradation. Overall, results may provide an alternative therapeutic strategy for TNBC management.

We compared the efficacy of a tailored and a targeted intervention designed to increase clinical breast exam (CBE), mammography, and genetic services/testing among young breast cancer survivors (YBCS) (diagnosed <45 years old) and their blood relatives. A two-arm cluster randomized trial recruited a random sample of YBCS from the Michigan cancer registry and up to two of their blood relatives. Participants were stratified according to race and randomly assigned as family units to the tailored (n=637) or the targeted (n=595) intervention. Approximately 40% of participants were Black; 12% YBCS and 27% relatives were living in more than 20 different U.S. States. Higher screening rates were reported by YBCS (CBE p=0.05; mammography p=0.04) and relatives (CBE p<0.01; mammography p=0.04) in the tailored arm, and by White/Other YBCS (CBE p=0.02) and relatives (CBE p<0.01; mammography p=0.03). YBCS genetic testing rates increased from 22% to 26% (p=0.11). Black YBCS and relatives reported higher self-efficacy and intention for genetic testing, and higher satisfaction and intervention acceptance. The tailored intervention improved CBE and mammography uptake - despite having minimal contact with participants. Professional referrals will improve genetic testing uptake. Intervention materials increased self-efficacy and satisfaction for Black women but could not overcome multiple access barriers.

Breast Cancer (BC) is the second most common type of cancer worldwide and displays the highest cancer-related mortality among women worldwide. Targeted therapies have revolutionized the way BC has been treated in the last decades improving life expectancies of millions of women. Among the different molecular pathways that have been of interest for the development of targeted therapies are the Cyclin-Dependent Kinases (CDK). CDK inhibitors are a class of molecules that already exist in nature and those belonging to the INK4 protein family specifically inhibit the CDK4/6 proteins. CDK4/6 inhibitors specifically block the transition from the G1 to the S phase of the cell cycle by dephosphorylation of the retinoblastoma tumor suppressor protein. In the past four years CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib received their first FDA approval for the treatment of Hormone Receptor (HR)-positive and Human Epidermal growth factor Receptor 2 (HER2)-negative breast cancer after showing significant improvements in progression-free survival in the PALOMA-1, MONALEESA-2 and the MONARCH-2 randomized clinical trials, respectively. After the encouraging results from these clinical trials, CDK4/6 inhibitors have also been investigated in the other BC subtypes. In HER2-positive BC, combination of CDK4/6 inhibitors with HER2-targeted therapies showed promise in preclinical studies and their clinical evaluation is ongoing. Moreover, in triple-negative BC, CDK4/6 inhibitors efficacy has been investigated in combination with other targeted therapies or immunotherapies. This review summarizes the molecular background and clinical efficacy of CDK4/6 inhibitors as single agents or in combination with other targeted therapies for the treatment of BC. Future directions of ongoing clinical trials and predictive biomarkers will be further debated.

Neurofibromatosis type1 (NF1) is an autosomal dominant disorder caused by mutations in the NF1gene. Although congenital pseudarthrosis of the tibia (CPT) has frequently been associated with NF1, the underlying molecular mechanism of CPT in these NF1 patients is yet ill-understood. The aim of the present study was to detect NF1 mutations from genomic DNA and to harbor variants associated with CPT in NF1 patients. Whole-exome sequencing was first carried out with samples from two patients with CPT in one NF1 family, and a novel mutation c.2324A>G (p.E775G) in NF1 gene was identified. Additionally, a missense variant c.455C>T (p.P152L) in BCOR gene completely co-segregated with the CPT phenotype within this family. Subsequently, NF1 and NF2 genes in four other unrelated patients with both NF1 and CPT were screened using targeted sequencing. Four mutations in NF1 gene, including two known mutations (c.2288T>C/p.L763P, c.574 C>T/p.R192*) and two novel mutations (c.768delT/p.F256Lfs*25, c.2229_2230delTG/ p.V744Qfs*23) were detected. Further study confirmed that CPT was present in NF1 families, and NF1 mutations were closely associated with these complex phenotypes. Moreover, the data from the current study indicated that male gender might be a susceptibility factor for CPT in NF1. Therefore, we speculated that BCOR variants might be related to CPT phenotype among male NF1 patients.

This comprehensive analysis thoroughly examines the topic of adversarial attacks in artificial intelligence (AI), providing a detailed overview of the various methods used to compromise machine learning models. It explores different attack techniques, ranging from the simple Fast Gradient Sign Method (FGSM) to the intricate Carlini and Wagner Attack (C&W), emphasising the wide range of adversarial approaches and their intended goals. The discussion also distinguishes between targeted and non-targeted attacks, highlighting the adaptability and versatility of these malicious efforts. Additionally, the study delves into the realm of black-box attacks, revealing the capability of adversarial strategies to compromise models even with limited knowledge. Real-life examples illustrate the tangible consequences and potential dangers of adversarial attacks in various fields such as self-driving cars, multimedia, and voice assistants. These cases highlight the difficulties in ensuring the legitimacy and dependability of AI-powered technologies and programs. The article stresses the importance of ongoing research and innovation to address the growing difficulties posed by advanced methods like deepfakes and disguised voice commands in preserving the security of AI systems. This study provides valuable insights on how different adversarial strategies and defence mechanisms interact within AI. The results emphasise the urgent need for stronger and more secure AI models to combat the increasing number of adversarial threats in today's AI landscape. These findings can guide future research and innovations in developing more resilient AI technologies that can better withstand various adversarial vulnerabilities and challenges.

This study aimed to demonstrate the potential role of Dual Energy CT in assessing Bone Mineral Density (BMD) in postmenopausal women. A retrospective study was conducted on 51 postmenopausal female patients who underwent DXA and DECT examinations for other clinical reasons. DECT images were acquired with spectral imaging using a 256-slice system. These images were processed and visualized using an HAP(fat) map. Statistical analysis was performed using the Bland-Altman method to assess agreement between DXA and DECT HAP(fat) measurements. Mean BMD, vertebral and femoral T-scores were obtained. For vertebral analysis, the Bland-Altman plot showed an inverse correlation (R2: -0.042; RMSE: 0.690) between T-scores and DECT HAP(fat) values for measurements from L1 to L4, while a good linear correlation (R2: 0.341; RMSE: 0.589) it was found for measurements at the femoral neck. In conclusion, we demonstrated the enhanced accuracy of BMD calculation through DECT, finding a statistically significant correlation only at the femoral neck where BMD results do not seem to be influenced by the overlap of the measurements on cortical and trabecular bone. This outcome could be beneficial in the future by reducing radiation exposure for patients already undergoing follow-up for chronic conditions.

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

Background: Dual disorders (DD) involve the coexistence of substance use disorder (SUD) with another mental illness, often from psychotic and affective categories. This study explores the ef-fectiveness of brexpiprazole, a third-generation antipsychotic, in individuals diagnosed with schizophrenia spectrum disorder (DSM-V) and comorbid AUD/SUD (DSM-V). Methods: Eighteen enrolled patients underwent psychometric assessments at baseline and one month into brexpiprazole treatment administered at a mean dosage of 2 mg/day. Results: Brexpiprazole demonstrated significant reductions in psychopathological burden (PANSS total score, p=0.004), improved CGI total score (p=0.042), and decreased MOAS total score (p=0.012). Quality of life improved in SF-36 subscales (p<0.05). Substance craving reduction, though observed, did not reach statistical significance. Conclusions: This study provides initial evidence supporting brexpiprazole's efficacy and safety with positive effects on psychopathology and quality of life, emphasizing the need for tailored, comprehensive treatment strategies in this complex patient population.

In this paper we demonstrate first ever dual-period diffraction gratings that do not require electrical tuning to obtain the effect of period change. Our method allows for multiplication of the base period by proper modification of the subsequent slits of the grating. The proposed elements are fabricated by selective photopolymerization of a composite based on nematic liquid crystal. The gratings are formed by polymer stabilization of liquid crystal in different orientations of the molecules in selected grating slits to allow for period manipulation. The operating principle is based on changing the phase delay introduced by the slits depending on polarization direction of incident light with respect to the director in each type of slit, which allows to change the grating’s period. The proposed technique was successfully utilized to obtain diffraction gratings with either doubling or tripling of the period.

Dual antiplatelet therapy (DAPT), comprising aspirin and a P2Y12 receptor inhibitor, is the cornerstone of post-percutaneous coronary intervention treatment to prevent stent thrombosis and reduce the risk of adverse cardiovascular events. The selection of an optimal DAPT regimen, considering the interplay of various antiplatelet agents, patient profiles, and procedural characteristics, remains an evolving challenge. Traditionally, a standard duration of 12 months has been recommended for DAPT in most patients. While contemporary guidelines provide general frameworks, DAPT modulation with longer or shorter treatment courses followed by aspirin or P2Y12 inhibitor monotherapy are evolving towards an individualized strategy to optimize the balance between efficacy and safety. This review comprehensively examines the current landscape of DAPT strategies after coronary stenting, with a focus on emerging evidence for treatment individualization.

Dual localization or dual targeting refers to the phenomenon by which identical, or almost identical, proteins are localized to two (or more) separate compartments of the cell. From previous work in the field, we had estimated that a third of the mitochondrial proteome is dual targeted to extra-mitochondrial locations and suggested that this abundant dual targeting presents an evolutionary advantage. Here we set out to study how many additional proteins whose main activity is outside mitochondria are also localized, albeit at low levels, to mitochondria (eclipsed). To do this we employed two complementary approaches utilizing the α-complementation assay in yeast to uncover the extent of such eclipsed distribution: one systematic and unbiased and the other based on Mitochondrial Targeting Signal (MTS) predictions. Using these approaches, we suggest 280 new eclipsed distributed protein candidates. Interestingly, these proteins are enriched for distinctive properties compared to their exclusively mitochondrial-targeted counterparts. We focus on one unexpected eclipsed protein-family of the Triose-phosphate DeHydrogenases (TDH), and prove that indeed their eclipsed distribution in mitochondria is important for mitochondrial activity. Our work provides a paradigm of deliberate eclipsed mitochondrial localization, targeting and function, and should expand our understanding of mitochondrial function in health and disease.

Background and Aims. Most research on Parkinson's disease (PD) focuses on describing symp-toms and movement characteristics. Studies rarely focus on the early detection of PD and the search for suitable markers of a prodromal stage. Early detection is important, so treatments that may potentially change the course of the disease can be attempted early on. While gait disturb-ances are less pronounced in the early stages of the disease, the prevalence, and severity increase with disease progression. Therefore, postural instability and gait difficulties could be identified as sensitive biomarkers. The aim was to evaluate the discriminatory power of the Trail-Walking Test (Schott, 2015) as a potential diagnostic instrument to improve the predictive power of the clinical evaluation concerning the severity of the disease and record the different aspects of walking. Methods. 20 older healthy (M = 72.4 years, SD = 5.53) adults and 46 older adults with PD and the motor phenotypes postural instability/gait difficulty (PIGD; M = 69.7 years, SD = 8.68) and tremor dominant (TD; M = 68.2 years, SD = 8.94) participated in the study. The participants performed a motor-cognitive dual task (DT) of increasing cognitive difficulty in which they had to walk a given path (condition 1), walk to numbers in ascending order (condition 2), and walk to numbers and letters alternately and in ascending order (condition 3). Results. With an increase in the cognitive load, the time to complete the tasks (seconds) become longer in all groups, F(1.23, 73.5) = 121, p < .001, ɳ2p = .670. PD-PIGD shows the longest times in all conditions of the TWT, F(2, 60) = 8.15, p < .001, ɳ2p = .214. Mutual interferences in the cognitive and motor domain can be observed. How-ever, clear group-specific patterns cannot be identified. A differentiation between the motor phenotypes of PD is especially feasible with the purely motor condition (TWT-M; AUC = . 685, p = 0.44). Conclusions. PD patients with PIGD must be identified by valid, well-evaluated clinical tests that allow a precise assessment of the disease's individual fall risk, the severity of the dis-ease, and the prognosis of progression. The TWT covers various aspects of mobility, examines the relationship between cognitive functions and walking, and enables differentiation of the motor phenotypes of PD.

This paper presents two designs of high-efficiency polarizer reflectarray antennas able to generate a collimated beam in dual-circular polarization using a linearly polarized feed, with application to high-gain antennas for data transmission links from a Cubesat. First, an 18 cm x 18 cm polarizer reflectarray operating in the 17.2 - 22.7 GHz band has been designed, fabricated and tested. The measurements of the prototype show an aperture efficiency of 52.7% for right-handed circular polarization (RHCP) and 57.3% for left-handed circular polarization (LHCP), both values higher than those previously reported in related works. Then, a dual-band polarizer reflectarray is presented for the first time, which operates in dual-CP in the frequency bands of 20 and 30 GHz. The proposed antenna technology enables a reduction of the complexity and cost of the feed chain to operate in dual-CP, as a linear-to-circular polarizer is no longer required. This property, combined with the lightweight, flat profile and low fabrication cost of printed reflectarrays, makes the proposed antennas good candidates for Cubesat applications.

The aim of this work was to investigate the microstructure and the mechanical properties of la-ser-welded joints combined of DP800 and DP1000 high strength thin steel sheets. The welded joints (WJ) comprised of similar/dissimilar steels with similar/dissimilar thickness were consisted of different zones and exhibited similar microstructural characteristics. The trend of microhard-ness for all WJs was consistent, characterized of the highest value at hardening zone (HZ) and lowest at softening zone (SZ). The degree of softening was more severe and the size of SZ was wider in the WJ combinations of DP1000 than DP800. The tensile test fractures were located at the base material (BM) for all DP800 weldments, while the fractures occurred at the fusion zone (FZ) for the weldments with DP1000 and those with dissimilar sheet thicknesses. The DP800-DP1000 weldment presented similar yield strength (YS) and ultimate tensile strength (UTS) values but lower elongation (EI) in comparison with the DP800-DP800 weldment, which showed similar strength properties as the BM of DP800. However, the EI of DP1000-DP1000 weldment was much lower in comparison with the BM of DP1000. The DP800-DP1000 weldment with dissimilar thicknesses showed the highest YS and UTS values compared with the other weldments, but with the lowest EI. The fatigue fractures occurred at the WJ for all types of weldments. The DP800-DP800 weldment had the highest fatigue limit and DP800-DP1000 with dissimilar thick-nesses had the lowest fatigue limit. The fatigue crack initiated from the weld surface.

Dual-method use is the most reliable form of protection against unintended pregnancies and HIV/STIs. Although dual-method use remains uncommon among women in stable relationships, some women do practice it. In this study, we explored the barriers that make dual-method use rare and the behaviors of women who practice dual-method use using a positive deviance framework in Uganda. We screened 150 women using highly effective contraceptives at five health facilities. We identified nine women who practiced dual-method use and 141 women who did not. In a qualitative study, we conducted in-depth interviews with all nine women practicing dual-method use and 10 women randomly selected out of the 141 who did not. We performed a thematic analysis using the positive deviance framework. Regardless of practicing dual-method use or not, women faced perceived barriers against dual-method use, such as partner’s objection, distrust, shyness about introducing condoms into marital relationships, and limited access to condoms. However, women practicing dual-method use had higher levels of risk perception about unintended pregnancies and HIV/STIs. They also engaged in unique behaviors, such as influencing their partners’ condom use by initiating discussions, educating their partners on sexual risks and condom use, and obtaining condoms by themselves. These findings will be useful in developing effective community-led and peer-based interventions promoting dual-method use to reduce the dual burden of unintended pregnancies and HIV/STIs among women in Uganda.

Hot deformation at elevated temperature is essential to densify the particle reinforced Aluminum matrix composites (AMCs) and improve their performance. However, hot deformation behavior of the AMCs is sensitive to the variation of hot processing parameters. In this paper, optimal processing parameters of the dual-scale SiCp/A356 composites was determined to explore the control strategy of the microstructure. Hot compression tests were conducted at the temperature ranging from 460 to 520℃ under strain rates from 0.01 to 5 s−1. Constitutive equation and processing maps were presented to determine the hot processing parameters. Microstructure evolution of the dual-scale SiCp/A356 composites was analyzed. The strain rate of 0.62 ~ 5s-1 and deformation temperature of 495 ~ 518℃ is suitable for the hot processing. The number of DRX grains in the “safe” domains is larger and the dislocation density is lower compared to those of instability domains. DRX particles mainly occurred around SiC particles. The presence of SiC particles can promote effectively the DRX nucleation, which result in that the dynamic softening mechanism of the dual-scale SiCp/A356 composites is dominated DRX.

Vertical-channel organic dual-gate/base transistors would be highly interesting since vertical organic transistors are the fastest organic transistors demonstrated today. However, incorporating a dual gate/base structure into an ultra-short channel vertical architecture represents a substantial challenge. Here, we successfully realize a new device concept of vertical organic permeable dual-base transistors (OPDBTs), where either of both base electrodes can be used to change the on-currents and tune the threshold voltages. The optimized devices yield a high on-current density of 1.54 A cm^-2 and a large current gain of 9.2×10⁵, corresponding to a high transmission value of 99.998%. The detailed operation mechanisms are investigated by calibrated TCAD simulations with the Poole-Frenkel mobility model, Gaussian density of states and tunneling model. Finally, high-performance logic circuits, e.g. inverter, NAND/AND computation functions are demonstrated with one single OPDBT operating at supply voltages of < 2.0 V. We believe that OPDBTs offer a compact and technologically simple hardware platform with excellent application potential for vertical-channel organic transistors in complex logic circuits.