Zika virus (ZIKV) outbreaks in Central and South America caused severe public health problems in 2015 and 2016. These outbreaks were finally contained through several methods, including mosquito control using insecticides and repellents. Additionally, the development of herd immunity in these countries might have contributed to containing the epidemic. While ZIKV is mainly transmitted by mosquito bites, mucosal transmission via bodily fluids, including the semen of infected individuals, has also been reported. We evaluated the effect of mucosal ZIKV infection on continuous subcutaneous challenges in a cynomolgus monkey model. Repeated intravaginal inoculations of ZIKV did not induce detectable viremia or clinical symptoms, and all animals developed a potent neutralizing antibody, protecting animals from the subsequent subcutaneous superchallenge. These results suggest that viral replication at mucosal sites can induce protective immunity without causing systemic viremia or symptoms.

Regulatory T cells (Tregs) are major drivers behind immunosuppressive mechanisms and present a major hurdle for cancer therapy. Tregs are characterized by high expression of CD25, which is a potentially valuable target for Treg depletion to alleviate immune suppression. The preclinical anti-CD25 (αCD25) antibody, clone PC-61, has met with modest anti-tumor activity, due to its capacity to clear Tregs from circulation and lymph nodes but not those that reside in the tumor. Optimization of the Fc domain of this antibody clone has been shown to enhance intratumoral Treg depletion capacity. Here, we generated a stable cell line that produces optimized recombinant Treg depleting antibodies. A genome engineering strategy in which CRISPR-Cas9 was combined with homology directed repair (CRISPR-HDR) was utilized to optimize the Fc domain of the hybridoma PC-61 for effector functions by switching it from the original rat IgG1 to a mouse IgG2a isotype. In a syngeneic tumor mouse model the resulting αCD25-m2a antibody mediated effective depletion of tumor resident Tregs leading to a high effector T cell (Teff) to Treg ratio. Moreover, combination of the αCD25-m2a with αPD-L1 treatment augmented tumor eradication in mice, demonstrating the potential for αCD25 as a cancer immunotherapy.

Since the outbreak of SARS CoV-2 infection (Covid-19), healthcare professionals worldwide have been trying to find disease management and control alternatives to encourage immunotherapies. Immunotherapy is an efficient therapeutic option used against comparable viral contaminations such as MERS-CoV and SARS-CoV. The aim of the current study is to assess the existing knowledge associated with SARS-CoV-2 immunotherapy. Information available in published articles and their quality highlights the importance of following strict scientific rules for clinical outcomes. Thus, these studies have shown enough data to confirm that immunomodulation is the main topic investigated in research about Covid-19 therapy. Therefore, it is possible saying that immunotherapy is certainly the appropriate option against this virus.

To date, viral RNA detection is almost the only way to confirm SARS-CoV-2infectionin practice.However, variousreasons can cause low sensitivity for RNA detection, and thisposes aserious challenge to disease control. We tested the performance of detecting total antibody(Ab) and IgM levels in serum by the methods of chemiluminescence, enzyme-linked immunosorbent assay (ELISA), and colloidal golddetection. The datashowed that the sensitivity and specificity for detecting total Ab and IgM levels were high by all three methods, and the sensitivity was higher for detecting total Ab than for detecting IgM. Evidence from studieshas shown thatviral RNA testingcombinedwith serological testing could increase the diagnostic sensitivity while maintaining a high specificity. Specific serology testsfor SARS-CoV-2 havegreat value for clinical practice and public health.

If a subject learns about the properties of an alternative under a high state of food deprivation, it will prefer this alternative over a similar one in a later choice test, although the subject is currently under a relative state of satiety. In this experiment, we probe this effect in a delay-discounting task, where the reward of the experienced alternative is progressively delayed. Eight male Wistar rats were trained to respond to an alternative under a high state of deprivation and eight rats under a relative state of satiety. After 20 sessions, their weight was recalibrated to a state of relative satiety. Then, they were exposed to a delay-discounting task where the long-larger alternative was the one used during training. The group that experienced the alternative under a higher level of food deprivation preferred more this alternative, and its preference stayed across time. On the contrary, the group that experienced the alternative under a lower level of food deprivation systematically preferred the small-shorter alternative. Our results support that the reinforcement value may be sensitive to the organism's state at the moment an alternative is experienced for the first time.

The recent advances in Human-Computer Interaction and Artificial Intelligence have significantly increased the importance of identifying human emotions from different sensory cues. Hence, understanding the underlying relationships between emotions and sensory cues have become a subject of study in many fields including Acoustics, Psychology, Psychiatry, Neuroscience and Biochemistry. This work is a preliminary step towards investigating cues for human emotion on a fundamental level by aiming to establish relationships between tonal frequencies of sound and emotions. For that, an online perception test is conducted, in which participants are asked to rate the perceived emotions corresponding to each tone. The results show that a crossover point for four primary emotions lies in the frequency range of 417–440 Hz, thus consolidating the hypothesis that the frequency range of 432–440 Hz is neutral from human emotion perspective. It is also observed that the frequency dependant relationships between emotion pairs Happy—Sad, and Anger—Calm are approximately mirrored symmetric in nature.

Understanding the detailed timing of crop phenology and their variability enhances grain yield and quality by providing precise scheduling of irrigation, fertilization, and crop protection mechanisms. Advances in information and communication technology (ICT) provide a unique opportunity to develop agriculture-related tools that enhance wall-to-wall upscaling of data outputs from point-location data to wide-area spatial scales. Because of the heterogeneity of the worldwide agro-ecological zones where crops are cultivated, it is unproductive to perform plant phenology research without providing means to upscale results to landscape-level while safeguarding field-scale relevance. This paper presents an advanced, reproducible, and open-source software for plant phenology prediction and mapping (PPMaP) that inputs data obtained from multi-location field experiments to derive models for any crop variety. This information can then be applied consecutively at a localized grid within a spatial framework to produce plant phenology predictions at the landscape level. This software supports the development of process-oriented and temperature-driven plant phenology models by intuitively and interactively leading the user through a step-by-step progression to the production of spatial maps for any region of interest. Maize (Zea mays L.) was used to demonstrate the robustness, versatility, and high computing efficiency of the resulting modeling outputs of the PPMaP. The framework is implemented in R, providing a flexible and easy‐to‐use GUI interface. Since this allows appropriate scaling to the larger spatial domain, the software can effectively be used to determine the spatially explicit length of growing period (LGP) of any variety.

Measurements of copper and zinc in transfusion-dependent thalassemia (TDT) show contradictory results.Aim of the study: To examine serum levels of these minerals in TDT in relation to iron overload indices and erythron variables. Methods: This study recruited 60 children with TDT and 30 healthy children aged 3-12 years old.Results: Zinc was significantly higher in TDT children than in control children, whilst copper and the copper to zinc ratio were significantly lowered in TDT. Serum zinc was significantly associated with the number of blood transfusions and iron overload variables (including serum iron and TS%) and negatively with erythron variables (including hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin). Serum copper was significantly and negatively associated with the same iron overload and erythron variables. The copper to zinc ratio was significantly correlated with iron, TS%, ferritin, hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin. Albumin levels were significantly higher in TDT children than in control children. Conclusion: Our results suggest that the increase in zinc in children with TDT may be explained by iron loading anemia and hemolysis and the consequent shedding of high amounts of intracellular zinc into the plasma. Increased albumin levels and treatment with Desferral may further contribute towards higher zinc levels in TDT. We suggest that the elevations in zinc in TDT are a compensatory mechanism protecting against infection, inflammation, and oxidative stress. Previous proposals for prophylactic use of zinc supplements in TDT may not be warranted.

Background and Research Highlights: Despite all the concerns and initiatives, natural resources like forests, as well as biodiversity are decreasing at an alarming rate worldwide. Conservation is considered as one of the major tools to prevent such loss and rapid degradation. Evidence around the world shows the adverse effects of conservation laws and policies on indigenous peoples and other local communities. Objectives: This study was conducted in one of the forest-dependent communities situated in Sundarban (world’s largest mangrove forest) to understand the impact of conservation laws and policies on their livelihood. Materials and Methods: A qualitative methodology was designed to collect data, using focus group discussions and case study with community people, and individual interviews with the personnel from NGOs and relevant government departments. Findings: Strict conservation policies and restrictions in accessing forest resources made lives and livelihoods of the local community insecure and unstable, thus putting the community in a vulnerable situation. The had to leave their traditional mode of income and look for alternative livelihood options. Almost no evidence was found in relation to upkeeping their rights in conservation activities. Prohibited movement, provision of punishment for entering into the forest without proper permission and struggles in everyday life were some of the highlighted issues. They had no participation in conservation activities, management of alternative livelihood options, and even they were not sensitized before putting restrictions. Although they had a history of emotional and physical attachment with the forest, existing activities did not consider these issues. In addition, corruption and abuse of power by law enforcement agencies towards the local community intensified the sufferings. Conclusion: This study argues that the realization of human rights in conservation activities and the sensitization of the implementing stakeholders are prerequisites for ensuring the sustainability of both biodiversity and the affected people.

The aim was to identify if surface electromyography (sEMG) parameters are indicative of post-activation potentiation (PAP)/post-activation performance enhancement (PAPE), in terms of twitch potentiation and voluntary performance. Three databases were used in March 2024, with the following inclusion criteria: (a) original research, assessed in healthy human adults, (b) sEMG parameters were measured. The exclusion criteria were: (a) studies with no PAP/PAPE-protocol, (b) non-randomized control trials. The following data were extracted: study characteristics/demographics, PAP/PAPE-protocols, sEMG parameters, twitch/performance outcomes, and study findings. A modified physiotherapy evidence database (PEDro) scale was used for quality assessment. Fifteen randomized controlled trials (RCTs), with a total of 199 subjects were included. The M-wave amplitude (combined with a twitch torque outcome) was shown to generally be indicative of PAP. The sEMG amplitude (in some muscles) were found to be indicative of PAPE during ballistic movements, while a small decrease in the MdF (in certain muscles) were shown to reflect PAPE. Changes in the Hmax/Mmax ratio were found to contribute (temporally) to PAP, while the H-reflex amplitude was shown to be neither indicative of PAP nor PAPE. This review provides preliminarily findings suggesting that certain sEMG parameters could be indicative of PAP/PAPE. However, future research is warranted.

Pool boiling is extensively utilized in various fields, such as electronics cooling, battery cooling, nuclear power plants, and chemical processing. In the process of temperature control through boiling, the generation and transportation of bubbles play a crucial role in calculating the heat transfer capacity of the system. Therefore, it holds immense significance to gain a profound understanding of the mechanisms underlying bubble formation, growth, and detachment. Currently, numerous mechanistic explanations and empirical correlations have been proposed to elucidate various parameters of bubbles during the boiling process. These findings were considered valuable references in selecting appropriate boiling media and designing efficient heating surfaces. To comprehensively present the progress of bubble formation and heat transfer during the boiling process, the forces exerted on the bubbles was highlighted in this article. And a meticulous review on bubble force analysis and correlation formulas pertaining to various relevant parameters (e.g. nucleation sites density, bubble growth rate, detachment diameter, detachment frequency) were conducted. This review article also were expected to provide a novel foundation for further exploration of enhanced boiling heat transfer.

Taking advantage of fact that the surface electrons of metallic nanoparticles (NPs) can be effectively released even at a low voltage bias, we demonstrate an improvement in the electrochemical performance of nano-sized Prussian Blue (PB) based secondary batteries by the incorporation of bare Ag or Ni NPs onto the vicinity of the working PB NPs. It is found that the capacity for electrochemical energy storage of the 17-nm-PB-based battery is significantly higher than the capacity of 10-nm-PB-based, 35-nm-PB-based or 46-nm-PB-based batteries. There is a critical PB size for the highest electrochemical energy storage efficiency. The full specific capacity CF of the 17-nm-PB-based battery stabilized to 62 mAh/g after 130 charge-discharge cycles at a working current of IW = 0.03 mA. The addition of 14 mass-percent of Ag NPs in the vicinity of the PB NPs gives rise to a 32% increase in the stabilized CF. A 42% increase in the stabilized CF can be obtained with the addition of 14 mass-percent of Ag NPs on the working electrode of the 35-nm-PB-based battery. An enhancement of CF is also found for electrodes incorporating bare Ni NPs but the effect is smaller.

As one of the main equipment of coal transportation, the belt conveyor with detection system is an important direction for the development of intelligent mine. The occurrences of non-coal foreign objects making contact with belts are common phenomenon in complex production environments and improper human operations. In order to avoid major safety accidents caused by scratches, deviation and breakage of the belt, a foreign object detection method is proposed for belt conveyor in this work. Firstly, a foreign object image dataset is collected and established, and IAT image enhancement module and attention mechanism of CBAM are proposed to enhance image data sample. Moreover, to predict the angle information of foreign objects with large aspect ratios, a rotating decoupling head is designed, and a MO-YOLOX network structure is constructed. Some experiments are carried out with the belt conveyor in the mine intelligent mining equipment laboratory, and the detections of different foreign objects are analyzed. Experimental results show that the accuracy, recall, and mAP50 of the proposed rotating frame foreign object detection method reaches 93.87%, 93.69%, and 93.72%, and the average inference time of foreign object detection is 25 ms.

With the advent of deep learning, significant progress has been made in low-light image enhancement methods. However, deep learning requires enormous paired training data, which is challenging to capture in real-world scenarios.To address this limitation, this paper presents a novel unsupervised low-light image enhancement method, which first introduces the frequency domain features of images in low-light image enhancement tasks. Our work is inspired by imagining a digital image as a spatially varying metaphoric “field of light”, then subjecting the influence of physical processes such as diffraction and coherent detection back onto the original image space via a frequency-domain to spatial-domain transformation (inverse Fourier transform). However, the mathematical model created by this physical process still requires complex manual tuning of the parameters for different scene conditions to achieve the best adjustment. Therefore, we proposed a dual-branch convolution network to estimate pixel-wise and high-order spatial interactions for dynamic range adjustment of the frequency feature of the given low-light image. Guided by the frequency feature from the “field of light” and parameter estimation networks, our method enables dynamic enhancement of low-light images. Extensive experiments have shown that our method performs well compared to state-of-the-art unsupervised, and its performance approximates the level of the state-of-the-art supervised methods qualitatively and quantitatively. At the same time, the light network structure design allows the proposed method to have an extremely fast inference speed(nearly 150 FPS on an NVIDIA 3090 Ti GPU for an image of size 600×400×3 ). Furthermore, the potential benefits of our method to object detection in the dark are discussed.

We sought to compare native T1 mapping to conventional Late gadolinium enhancement (LGE) and T2-STIR techniques in a cohort of consecutive patients undergoing cardiac MRI (CMR).. CMR was performed in 323 patients, 206 males (64%), mean age 54±8 years and in 27 age- and sex- matched healthy controls. At T2-STIR images myocardial hyperintensity suggesting edema was found in 41 patients (27%). LGE images were positive in 206 patients (64%). T1 mapping was abnormal in 171 (49%). In 206 patients (64%) a matching between LGE and native T1 was found. T1 was abnormal in 32 out of 41 (78%) with edema at T2-STIR. Overall, LGE and/or T2-STIR were abnormal in 209 patients, whereas native T1 in 154(52%). Conventional techniques and T1 mapping were concordant in 208 patients (64%). In 39 patients T1 mapping was positive despite negative conventional techniques (12%). T1 mapping was able in conditions with diffuse myocardial damage as cardiac amyloidosis, scleroderma and Fabry disease (additive role in 42%). On contrast, T1 mapping was less effective in cardiac disease with regional distribution of myocardial damage as myocardial infarction, HCM, myocarditis. In conclusion, conventional LGE/T2-STIR and T1 mapping are complementary techniques and should be used together in every CMR examination.

Purposes: To provide abdominal contrast-enhanced MR image synthesis, we developed an image gradient regularized multi-modal multi-discrimination sparse-attention fusion generative adversarial network (GRMM-GAN) to avoid repeated contrast injections to patients and facilitate adaptive monitoring. Methods: With IRB approval, 165 abdominal MR studies from 61 liver cancer patients were retrospectively solicited from our institutional database. Each study included T2, T1 pre-contrast (T1pre), and T1 contrast-enhanced (T1ce) images. The GRMM-GAN synthesis pipeline consists of a sparse attention fusion network, an image gradient regularizer (GR), and a generative adversarial network with multi-discrimination. The studies were randomly divided into 115 for training, 20 for validation, and 30 for testing. The two pre-contrast MR modalities, T2 and T1pre images, were adopted as inputs in the training phase. The T1ce image at the portal venous phase was used as an output. The synthesized T1ce images were compared with the ground truth T1ce images. The evaluation metrics include peak signal-to-noise ratio (PSNR), structural-similarity-index (SSIM), and mean-squared-error (MSE). A Turing test and experts’ contours evaluated the image synthesis quality. Results: The proposed GRMM-GAN model achieved a PSNR of 28.56, an SSIM of 0.869, and an MSE of 83.27. The proposed model showed statistically significant improvements in all metrics tested with p-values <0.05 over the state-of-the-art model comparisons. The average Turing test score was 52.33%, close to random guessing, supporting the model's effectiveness for clinical application. In the tumor-specific region analysis, the average tumor contrast-to-noise ratio (CNR) of the synthesized MR images was not statistically significant from the real MR images. The average DICE from real vs. synthetic images was 0.90, compared to the inter-operator DICE of 0.91. Conclusion: We demonstrated the function of a novel multi-modal MR image synthesis neural network, GRMM-GAN, for T1ce MR synthesis based on pre-contrast T1 and T2 MR images. GRMM-GAN shows promise for avoiding repeated contrast injections during radiation therapy treatment.

The low water solubility of any pharmacoactive molecules limits their pharmacological potential but the solubility parameter cannot compromise, so different approaches are employed to enhance their bioavailability. Pharmaceutically active molecules with low solubility convey a higher risk of failure for drug innovation and development. Pharmacokinetics, pharmacodynamics, and several other parameters, such as drug distribution, protein binding and absorption, are majorly affected by their solubility. Among all pharmaceutical dosage forms, the oral dosage forms cover more than 50 %, and the drug molecule should be water-soluble. For good therapeutic activity by the drug molecule on the target site, solubility and bioavailability are crucial factors. The pharmaceutical industry screening programs identified that around 40% of new chemical entities (N.C.E.s) face various difficulties at the formulation and development step. These pharmaceuticals are attributed to their less solubility and bioavailability. The bioavailability and drug solubility enhancement are significant challenges in the area of pharmaceutical formulations. According to the Classification of Biopharmaceutics, Class II and IV drugs (APIs) exhibits poor solubility, lower bioavailability, and less dissolution. Various technologies are discussed in this article to improve the solubility of the poorly water-soluble drug, for example, complexation of active molecules, utilization of emulsion formation, micelles, microemulsions, cosolvents, polymeric micelles preparation, particle size reduction technologies, pharmaceutical salts, prodrugs, solid-state alternation technique, soft gel technology, drug nanocrystals, solid dispersion methods, crystal engineering techniques and nanomorph technology. This review mainly describes several other advanced methodologies for solubility and bioavailability enhancement, such as crystal engineering, micronization, solid dispersions, nano sizing, use of cyclodextrins, solid lipid nanoparticles, colloidal drug delivery systems and drug conjugates, by some appropriate research reports.

Enhancing underwater images in epicontinental sea is a challenging problem owing to the influence of ocean currents, the refraction, absorption and scattering of light by suspended particles, and the weak illumination intensity. Recently, different methods have relied on the underwater image formation model and deep learning techniques to restore the underwater image, but they tend to degrade underwater image, interference of background clutter and miss boundary details of blue regions. Improved image fusion and enhancement algorithm based on a priori dark channel is proposed in this paper. Image edge features sharpening and dark detail enhancement by homomorphism filtering in CIELab color space is realized. In RGB color space, the multi-scale retinal with color restoration (MSRCR) algorithm is used to improve color deviation and enhance color saturation, and the contrast-limited adaptive histogram equalization (CLAHE) algorithm is used to de fog and enhance image contrast. Finally, according to the dark channel images of the three processing results, the final enhanced image is obtained by linear fusion of multiple images and multiple channels. Experimental results demonstrate the effectiveness and practicality of the proposed method on various datasets.

To overcome the two-phase flow instability of traditional boiling heat dissipation technologies, a porous wick was used for liquid-vapor isolation, thus realizing efficient and stable boiling heat dissipation. A pump-assisted capillary phase-change loop with methanol as working medium was established to study the effect of liquid-vapor pressure difference and heating power on its start-up and steady-state characteristics. The results indicated that the evaporator undergoes four heat transfer modes including flooded, partial flooded, thin film evaporation and overheating. The thin film evaporation mode was the most efficient one with the shortest start-up period. Besides, the heat transfer modes were determined by liquid-vapor pressure difference and power. The heat transfer coefficient could be significantly improved and the thermal resistance could be reduced by increasing liquid-vapor pressure difference as long as it did not exceed 8 kPa. However, when the liquid-vapor pressure difference exceeded 8kPa, its influence on the heat transfer coefficient weakened. In addition, a two-dimensional heat transfer mode distribution diagram considering both liquid-vapor pressure difference and power was drawn through a great number of experiments. During engineering application, the liquid-vapor pressure difference can be controlled to maintain efficient thin film evaporation in order to achieve the optimum heat dissipation effect.

This studies the plasmonic properties of the bimetallic quantum dot Ag@Au core-shell nanostructures embedded in the non-absorbent host medium. Local field enhancement factor and coefficient of absorption of Ag-core and Au-shell are primarily studied based on quasi-static approximation of classical electrodynamics for 6-10 nm composite radius. In this quantum dot geometry, two set of plasmonic resonances in visible spectral region are observed: the first resonance associated with inner interface of gold (Ag@Au) and the second resonance associated with outer interface of gold (Au@medium). The two plasmonic resonances are close each other and enhanced when the size of composite decreased for a fixed core size while shifted to in opposite direction and the amplitude of peak decreased when the core size is increased for a fixed composite size. For the optimized size of core/composite or shell thickness and other parameters to the desired values, such type of composites are recommended for various applications like; photocatalysis, biomedical, nano-optoelectronics.

Speckle noise is one of the most difficult noises to remove especially in medical applications. It is a nuisance in ultrasound imaging systems which is used in about half of all medical screening systems. Thus, noise removal is an important step in these systems, thereby creating reliable, automated, and potentially low cost systems. Herein, a generalized approach MFNR (Multi-Frame Noise Removal) is used, which is a complete Noise Removal system using KDE (Kernal Density Estimation). Any given type of noise can be removed if its probability density function (PDF) is known. Herein, we extracted the PDF parameters using KDE. Noise removal and detail preservation are not contrary to each other as the case in single-frame noise removal methods. Our results showed practically complete noise removal using MFNR algorithm compared to standard noise removal tools. The Peak Signal to Noise Ratio (PSNR) performance was used as a comparison metric. This paper is an extension to our previous paper where MFNR Algorithm was showed as a general purpose complete noise removal tool for all types of noises

In order to improve contrast and restore color for underwater image captured by camera sensors without suffering from insufficient details and color cast, a fusion algorithm for image enhancement in different color spaces based on contrast limited adaptive histogram equalization (CLAHE) is proposed in this article. The original color image is first converted from RGB color space to two different special color spaces: YIQ and HSI. The color space conversion from RGB to YIQ is a linear transformation, while the RGB to HSI conversion is nonlinear. Then, the algorithm separately operates CLAHE in YIQ and HSI color spaces to obtain two different enhancement images. The luminance component (Y) in the YIQ color space and the intensity component (I) in the HSI color space are enhanced with CLAHE algorithm. The CLAHE has two key parameters: Block Size and Clip Limit, which mainly control the quality of CLAHE enhancement image. After that, the YIQ and HSI enhancement images are respectively converted backward to RGB color. When the three components of red, green, and blue are not coherent in the YIQ-RGB or HSI-RGB images, the three components will have to be harmonized with the CLAHE algorithm in RGB space. Finally, with 4 direction Sobel edge detector in the bounded general logarithm ratio operation, a self-adaptive weight selection nonlinear image enhancement is carried out to fuse YIQ-RGB and HSI-RGB images together to achieve the final fused image. The enhancement fusion algorithm has two key factors: average of Sobel edge detector and fusion coefficient, and these two factors determine the effects of enhancement fusion algorithm. A series of evaluate metrics such as mean, contrast, entropy, colorfulness metric (CM), mean square error (MSE) and peak signal to noise ratio (PSNR) are used to assess the proposed enhancement algorithm. The experiments results showed that the proposed algorithm provides more detail enhancement and higher values of colorfulness restoration as compared to other existing image enhancement algorithms. The proposed algorithm can suppress effectively noise interference, improve the image quality for underwater image availably.

Background and Objectives: Cancer as the second leading cause of death in the United States poses a huge healthcare burden. Barriers to access to advanced therapies influence the outcome of cancer treatment. In this study, we examined whether insurance types affect the quality of cancer clinical care regarding access to an important monoclonal antibody, ramucirumab. Materials and Methods: Data for 13,340 cancer patients with Purchased or Medicaid insurance from the All of Us Database were collected for this study. The Chi-square test of proportions was employed to determine the significance of patient cohort characteristics and ramucirumab usage between Purchased and Medicaid insurance groups. The independent t-test was utilized to assess the influences of other determinants on insurance types. Results: Cancer patients who are African American, with lower socioeconomic status, or with lower educational attainment are more likely to be insured by Medicaid. Analysis of survey questions demonstrated the relationship between income and education level with insurance type as Medicaid cancer patients were less likely to receive primary care and specialist physician access and more likely to request lower cost medications. In addition, those with Medicaid insurance were identified to have poorer access to expensive therapeutics like ramucirumab compared to those with Purchased insurance.  Conclusions: The inequities of the US healthcare system are observed for cancer patient care; access to physicians and therapeutics are highly varied and dependent on insurance types. Socioeconomic status determines insurance type, which unfortunately generates a significant impact on cancer treatment and disease outcome.

Currently, hepatitis B virus (HBV) core antibody (anti-HBc antibody) and HBV core-related antigen (HBcrAg) are widely used as serum markers for diagnosis based on the HBV core region. While anti-HBc is very significant for clinical diagnosis, the clinical significance of quantitative assay of anti-HBc antibody has been reevaluated with improvements in diagnostic performance, including its association with clinical stage and prediction of carcinogenesis and reactivation. In addition, concerning the new HBcrAg, a high-sensitivity assay method has recently been established, and its diagnostic significance, including the prediction of reactivation, is being reevaluated. On the other hand, the quantitative level of anti-HBc antibody expressed in different units among assay systems, complicating the interpretation of the results. However, it is difficult to standardize assay systems as they vary in advantages, and caution is needed in interpreting the assay results. In this review, the clinical usefulness and remaining problems of anti-HBc antibody and HBcrAg were summarized.

The aim of this study was to analyze the profile of IgG subclasses in COVID-19 convalescent Puerto Rican subjects and compare this profile with those exhibited by no-infected immunocompetent or immunocompromised subjects that received the mRNA vaccine. The most notable find-ngs from this study are: 1) Convalescent subjects that were not hospitalized developed high and long-lasting antibody response. 2) Both, IgG1 and IgG3 are the subclasses more prevalent in the SARS-CoV-2 infected population whereas IgG1 is more prevalent after vaccination. 3) Individuals that first had the infection and further received two doses of mRNA vaccines exhibited more robust neutralizing capacity against Omicron than those that were never infected and received two doses of Pfizer-BioNTech vaccine. 4) A class switch toward the “anti-inflammatory” anti-body isotype IgG4 is induced a few weeks after the third dose, which peaked abruptly and remained at high levels for a long period. Moreover, the high levels of IgG4 are concurrent with high neutralizing percentages against various VOC including Omicron. 5) Subjects with IBD also develop IgG4 after the third dose, although these antibody levels have limited effect on the neutralizing capacity. Knowing that the mRNA vaccines do not prevent reinfections, all Omicron sub-variants that are dominant worldwide have shown to be less pathogenic, and the IgG4 levels have been associated to immunotolerance and causative of numerous negative effects, the recommendations of successive administration of booster vaccinations to people should be revised.

C-C motif chemokine receptor 1 (CCR1/CD191) is a member of G-protein-coupled receptors, and is expressed on myeloid cells, such as neutrophils and macrophages. Because the CCR1 signaling promotes tumor expansion in the tumor microenvironment (TME), the modification of TME is an effective strategy for cancer therapy. Although CCR1 is an attractive target for solid tumors and hematological malignancies, anti-CCR1 therapeutic agents have not been approved. Here, we established a novel anti-mouse CCR1 (mCCR1) monoclonal antibody (mAb), C₁Mab-6 (rat IgG_2b, kappa), using the Cell-Based Immunization and Screening (CIBS) method. Flow cytometry and Western blot analyses showed that C₁Mab-6 recognizes mCCR1 specifically. The dissociation constant of C₁Mab-6 for mCCR1-overexpressed Chinese hamster ovary-K1 was determined as 3.9×10^-9 M, indicating that C₁Mab-6 possesses a high affinity to mCCR1. These results suggest that C₁Mab-6 could be a useful tool for targeting CCR1 in preclinical mouse models.

The use of antibiotics grown promoter has been banned, due led problems with drug residues in animal products and increased bacterial resistance. For several reasons there is a growing interest in the scientific community in immunoglobulin Y as antibiotic alternative and their oral administration in the polyclonal antibody (pAb) format, to maintain animal health and performance, do not require IgY purification for large-scale production, resulting in protein impurities and high concentration of biotin in the samples. The signal amplification through non-covalent interaction of biotin with streptavidin has been extensionally used by many laboratories for several diagnosis diseases and scientific research in enzyme-linked immunosorbent assay (ELISA). However, the riches sources of biotin as egg yolk, leading to high biotin concentrations in samples, harming the accuracy of diagnostic and proteins concentrations tests. This study aimed to evaluate the biotin influence on measurement of Immunoglobulin Y in egg yolk freeze dried samples from immunized laying hens by immunoassays using biotin-avidin/streptavidin. The IgY concentration changed down in immunoassays using biotin-avidin/streptavidin. The detection of IgY in yolk samples by ELISA using streptavidin–biotin binding as part of the assay methodology requires some technology to neutralize high concentration of biotin on sample or more steps beyond delipidation to isolate the target protein. Otherwise, an ELISA without the use of streptavidin-biotin binding would be more advisable to avoid biotin and targets protein relationship and prevent biotin interference on results.

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a high rate of mortality in kidney transplant recipients (KTRs). The current vaccine strategy for KTRs seems to be unable to provide effective protection against coronavirus disease 2019 (COVID-19) [2] and the occurrence of severe COVID-19 in some vaccinated KTRs suggested a lack of immunity. We analized here the antibody response in a group of 32 kidney transplant recipients (KTR) followed at the Nephrology and Dialysis unit of the Hospital Pio XI of Desio, Italy, compared with a group of 23 healthy workers classified as Late responders (HCW-LR) (10 males age 27-62) and 13 females (age 46-64). We observed that the patients need additional vaccine boosters due to their immunocompromised status and therapy to protect them from infections related to viral variants, in accordance with the literature.

Background: It is assumed that the prevalence of hepatitis D in HBsAg-positive individuals reaches 4.5-13% in the world, and on average about 3% in Europe. Data from several European countries, including Slovakia, are missing or are from an older period. Methods: We analyzed all available data on hepatitis D from Slovakia, including reports from the Slovak Public Health Authority and the results of one prospective study, and three smaller surveys. The determination of anti-HDV IgG and IgM antibodies and/or HDV RNA was used to detect hepatitis D. Results: In the years 2005-2022, no confirmed case of acute or chronic HDV infection was reported in Slovakia. The presented survey includes a total of 343 patients, of which 126 were asymptomatic HBsAg carriers, 33 acute hepatitis B, and 184 chronic hepatitis B cases. In a recent prospective study of 206 HBsAg-positive patients who were completely serologically and virologically examined for hepatitis B and D, only 1 anti-HDV IgG positive and no anti-HDV IgM or HDV RNA positive cases were detected. In other smaller surveys, 2 anti-HDV IgG positive patients were found without the possibility of HDV RNA confirmation. In total, only 3 of 329 HBsAg-positive patients (0.91%) tested positive for anti-HDV IgG antibodies and none of 220 tested positive for HDV RNA. Conclusion: The available data show that Slovakia is one of the countries with a very low prevalence of HDV infection reaching less than 1% in HBsAg-positive patients. Routine testing for hepatitis D is lacking in Slovakia, and therefore it is necessary to implement testing of all HBsAg-positive individuals according to international recommendations.

The number of applications for nanobodies is steadily expanding, positioning these molecules as fast-growing biologic products in the biotechnology market. Several of their applications require protein engineering, which in turn would greatly benefit from having a reliable structural model of the nanobody of interest. However, as with antibodies, structural modeling of nanobodies is still a challenge. With the rise of artificial intelligence (AI), several methods have been developed in recent years that attempt to solve the problem of protein modeling. In this study, we have compared the performance in nanobody modeling of several state-of-the-art AI-based programs, either designed for general protein modeling, such as AlphaFold2, OmegaFold, ESMFold and Yang-Server, or specifically designed for antibody modeling, such as IgFold, and Nanonet. While all these programs performed rather well in constructing the nanobody framework and CDRs 1 and 2, modeling of CDR3 sill represents a big challenge. Interestingly, tailoring an AI method for antibody modeling does not necessarily translate into better results for nanobodies.

CC chemokine receptor 6 (CCR6) is a member of the G protein-coupled receptor (GPCR) family that is highly expressed in B lymphocytes, effector and memory T cells, regulatory T cells, and immature dendritic cells. CCR6 has been revealed to have important functions in many pathological conditions, such as cancer, intestinal bowel disease, psoriasis, and autoimmune diseases. The only CCR6 chemokine ligand, CC motif chemokine ligand 20 (CCL20), is also involved in pathogenesis by interacting with CCR6. The CCL20/CCR6 axis is drawing attention as an attractive therapeutic target for various diseases. In this study, we developed novel monoclonal antibodies (mAbs) against human CCR6 (hCCR6) using the peptide immunization method, which are applicable to flow cytometry and immunohistochemistry. The established anti-hCCR6 mAb, clone C6Mab-19 (mouse IgG1, kappa), reacted with hCCR6-overexpressed Chinese hamster ovary-K1 (CHO/hCCR6), HepG2 (human liver carcinoma), and HuH-7 (human differentiated hepatoma) cells in flow cytometry. The dissociation constant (KD) of C6Mab-19 was determined as 3.0 × 10−10 M for CHO/hCCR6, 6.9 × 10−10 M for HepG2, and 1.8 × 10−10 M for HuH-7. Thus, C6Mab-19 could bind to exogenously and endogenously expressed hCCR6 with extremely high affinity. Furthermore, C6Mab-19 could stain formalin-fixed paraffin-embedded lymph node tissues from a patient with non-Hodgkin lymphoma by immunohistochemistry. Therefore, C6Mab-19 is suitable for detecting hCCR6-expressing cells and tissues, and could be useful for pathological analysis and diagnosis.

The overexpression of epidermal growth factor receptors (EGFRs) has been reported in various human tumors, including breast, gastric, lung, colorectal, and pancreatic cancers. Humanized anti‐EGFR and human epidermal growth factor receptor 2 (HER2) monoclonal antibodies (mAbs) have been shown to improve patients’ survival. Canine tumors resemble human tumors in the initiation and progression. We previously established a defucosylated mouse-dog chimeric anti‐EGFR mAb (E134Bf) and a mouse-dog chimeric anti‐HER2 mAb (H77Bf), which exerted antitumor activities in canine tumor xenograft models. Here, we produced E134Bf antibody fused to H77Bf single chain Fv at the light chains (E134Bf-H77scFv). The bispecific E134Bf-H77scFv recognized dog EGFR (dEGFR) and dog HER2 (dHER2)-overexpressed Chinese hamster ovary-K1 cells by flow cytometry. E134Bf-H77scFv also reacted with dEGFR and dHER2‐positive canine osteosarcoma D-17 cells, and possesses a high binding-affinity (KD: 1.3x10-9 M). Furthermore, E134Bf-H77scFv exerted antibody‐dependent cellular cytotoxicity and complement‐dependent cytotoxicity against D-17 cells in the presence of canine mononuclear cells and complement, respectively. Moreover, administration of E134Bf-H77scFv suppressed the development of D-17 xenograft tumor in mice early compared with the control dog IgG, E134Bf and H77Bf alone. These results indicate that E134Bf-H77scFv exerts antitumor activities against dEGFR/dHER2-positive canine tumors, and could be a valuable treatment regimen for canine tumors.

Antibodies constitute a major component of serum on protein mass basis. We also know that the structural diversity of these antibodies exceeds that of all other proteins in the body and they react with an immense number of molecular targets. What we still cannot quantitatively describe is, how antibody abundance is related to affinity, specificity and cross reactivity. This ignorance has important practical consequences: we also do not have proper biochemical units for characterizing polyclonal serum antibody binding. The solution requires both a theoretical foundation, a physical model of the system, and technology for the experimental confirmation of theory. Here we argue that the quantitative characterization of interactions between serum antibodies and their targets requires systems-level physical chemistry approach and generates results that should help create maps of antibody binding landscape.

Tilapia lake virus (TiLV), a major pathogen of farmed tilapia, is known to be vertically transmitted. Here, we hypothesize that Nile tilapia (Oreochromis niloticus) broodstock immunized with a TiLV inactivated vaccine can mount a protective antibody response and passively transfer maternal antibodies to their fertilized eggs and larvae. To test this hypothesis, three groups of tilapia broodstock, each containing 4 males and 8 females, were immunized with either a heat-killed TiLV vaccine (HKV), a formalin-killed TiLV vaccine (FKV) (both administered at 3.6 ×106 TCID50 per fish), or with L15 medium. Booster vaccination with the same vaccines was given 3-weeks later, and mating took place 1 week thereafter. Broodstock blood sera, fertilized eggs and larvae were collected from 6-14 weeks post-primary vaccination for measurement of TiLV-specific antibody (anti-TiLV IgM) levels. In parallel, passive immunization using sera from the immunized female broodstock was administered to naïve tilapia juveniles to assess if antibodies induced in immunized broodstock were protective. The results showed that anti-TiLV IgM was produced in the majority of both male and female broodstock vaccinated with either the HKV or FKV and that and that these antibodies could be detected in the fertilized eggs and larvae from vaccinated broodstock. Higher levels of maternal antibody were observed in fertilized eggs from broodstock vaccinated with HKV than those vaccinated with FKV. Low levels of TiLV-IgM were detected in some of the 1-3-day old larvae but were undetectable in 7-14-day old larvae from the vaccinated broodstock, indicating a short persistence of TiLV-IgM in larvae. Moreover, passive immunization proved that antibodies elicited by TiLV vaccination were able to confer 85% to 90% protection against TiLV challenge in naïve juvenile tilapia. In conclusion, immunization of tilapia broodstock with TiLV vaccines could be a potential strategy for the prevention of TiLV in tilapia fertilized eggs and larvae, with HKV appearing to be more promising than FKV for maternal vaccination.

Infectious bursal disease (IBD) is one of the most endemic diseases of commercial poultry in Ethiopia. Vaccination has been practiced as the major means of IBD prevention and control. A study was conducted to determine and compare the immunogenicity of two commercially available IBD vaccines in broiler chicken with maternally derived antibody (MDA). Day-old chickens of 270 were randomly assigned to three groups, group 1 vaccinated with brand 1 vaccine at 7^th and 19^th days and group 2 with brand 2 vaccine at 15^th and 22^nd days while group 3 were kept as control. Six chickens were also randomly selected and bled on day 1 for differential leukocyte count (DLC) and determination of MDA. Representative chickens from each group were bled at 24^th and 42^nd days of age for antibody titration using the indirect ELISA test. DLC scores were determined in the 1^st and 24^th days. The result revealed highly significant differences (P = 0.001) between group 1 and group 2 in DLC at 24^th days of age. Antibody titers against IBD were differed significantly (P = 0.02) at 24^th and 42^nd days of age in broilers vaccinated with brand 1 and brand 2 vaccines. It is concluded that although both brands of vaccine induce an adequate immunological response at the end of the experiment, brand 1 vaccine has shown significantly high antibody titers against the IBDV and DLC than brand 2.

The target of an antibody plays a significant role in the success of antibody-based therapeutics and diagnostics, and to an extent, that of vaccine development. This importance is focussed on the target binding site – epitope, where epitope selection as a part of design thinking beyond traditional antigen selection using whole cell or whole protein immunisation can positively impact success. With purified recombinant protein production and peptide synthesis to display limited/selected epitopes, intrinsic factors that can affect the functioning of resulting antibodies can be more easily selected for. Many of these factors stem from the location of the epitope that can affect accessibility of the antibody to the epitope at a cellular or molecular level, direct inhibition of target antigen activity, conservation of function despite escape mutations, and even non-competitive inhibition sites. Through the incorporation of novel computational methods for predicting antigen changes to model-informed drug discovery and development, superior vaccines and antibody-based therapeutics or diagnostics can now be more easily designed to mitigate failures. With detailed examples, this review highlights the new opportunities, factors and methods of predicting antigenic changes for consideration in sagacious epitope selection.

Alphaviruses are arboviruses that cause arthritis and encephalitis in humans. Eastern Equine Encephalitis Virus (EEEV) is a mosquito transmitted alphavirus that is implicated in severe encephalitis in humans with high mortality. However, limited insights are available into its fundamental biology of EEEV and residue-level details of its interactions with host proteins. In recent years, outbreaks of EEEV have been reported mainly in the United States, raising concerns about public safety. This review article summarizes recent advances in the structural biology of EEEV based mainly on recent single particle cryogenic electron microscopy (cryoEM) structures. Together with functional analyses of EEEV and related alphaviruses, these structural investigations provide clues to how EEEV interacts with host proteins, which may open avenues for the development of therapeutics.

As a non-antibody scaffold, monobodies based on the fibronectin type III (FN3) domain overcome antibody size and complexity while maintaining analogous binding loops. However, antibodies and their derivatives remain the gold standard for design of new therapeutics. In response, clinical therapeutic proteins based on the FN3 domain are beginning to use native fibronectin function as a point of differentiation. The small and simple structure of monomeric monobodies confers increased tissue distribution and reduced half-life, whilst the absence of disulphide bonds improves stability in cytosolic environments. Where multi-specificity is challenging with an antibody format that is prone to mis-pairing of chains, FN3 domains in the fibronectin assembly already interact with a large number of molecules. As such, multiple monobodies engineered for interaction with therapeutic targets are being combined in a similar beads-on-a-string assembly which improves both efficacy and pharmacokinetics. Furthermore, full length fibronectin is able to fold into multiple conformations as part of its natural function and a greater understanding of how mechanical forces allow for the transition between states will lead to advanced applications that truly differentiate the FN3 domain as a therapeutic scaffold.

N-glycosylation has been shown to affect the pharmacokinetic properties of several classes of biologics including monoclonal antibodies, blood factors, and lysosomal enzymes. In the last two decades, N-glycan engineering has been employed to achieve a N-glycosylation profile that is either more consistent or aligned with a specific improved activity (i.e. effector function or serum half-life). In particular, attention has focused on engineering processes in vivo or in vitro to alter the structure of the N-glycosylation of the Fc region of anti-cancer monoclonal antibodies in order to increase antibody-dependent cell-mediated cytotoxicity (ADCC). Here we applied the mannosidase I inhibitor kifunensine to the Nicotiana benthamiana transient expression platform to produce an afucosylated anti-CD20 antibody (rituximab). We determined the optimal concentration of kifunensine used in the infiltration solution, 0.375 µM, which was sufficient to produce exclusively oligomannose glycoforms, at a concentration 14 times lower than previously published levels. The resulting afucosylated rituximab revealed a 14-fold increase in ADCC activity targeting the lymphoma cell line Wil2-S when compared with rituximab produced in the absence of kifunensine. When applied to the cost-effective and scalable N. benthamiana transient expression platform, the use of kifunensine allows simple in-process glycan engineering without the need for transgenic hosts.

Determination of antibody titre of dogs vaccinated against canine distemper in Jos North and South local Government Areas of Plateau State was carried out by collection of sera of vaccinated dogs and administration of well-structured questionnaires to dog owners. The samples collected were analyzed using the immune-blot ELISA Kit to determining the antibody titre (immunoglobulin G). It indicated that dogs vaccinated against the disease mounted adequate protective immunity. The result revealed that 54 (90.0%) of the sampled dogs have protective immunity, with those given more than one dose having higher level of protective antibody. Statistically, the result showed that the antibody titre did not differ significantly in relation to immunity and sex, breed, age and location but significant difference was seen in relation to number of primary vaccination. The result also revealed that those dogs that received booster doses (secondary vaccination) had more protective antibody. The study was aimed at evaluating the antibody titre of dogs vaccinated against canine distemper in Jos, Plateau State.

Influenza viruses cause acute respiratory infections responsible for significant mortality and morbidity around the world. Various factors, such as antigenic drift, allow influenza strains to avoid being fully suppressed by seasonal vaccines. This has led to the increased scrutiny of antivirals as treatment and prophylaxis options for seasonal outbreaks and potential pandemics. Unfortunately, many influenza antivirals suffer from a lack of adequate clinical trials, as well as a lack of toxicity data. This is especially true of umifenovir (arbidol), a drug popularly used for the prevention and treatment of influenza strains in China and Russia. Neuraminidase inhibitors, though widely prescribed, display a potential for future resistance. Adamantanes, while proven to be effective in treating influenza A, are already encountering rapid and widespread cross-resistance and are effectively obsolete. Baloxavir marboxil, a newer antiviral, shows promise in treating acute uncomplicated influenza and may avoid the development of resistance when co-administered with other antiviral drugs. Indeed, the low genetic barrier to resistance associated with influenza antivirals could potentially be overcome by co-administration with other antivirals. This review explores the most widely prescribed antivirals for influenza treatment, their mechanisms of action, and the data currently available about their susceptibility to resistance and efficacy.

In this study, we investigated, for the first time, the effects of the spatially varying effective mass, asymmetry parameter, and well width on the electronic and optical properties of the quantum well which has an improved Rosen-Morse potential. Calculations are made within the framework of the effective mass and parabolic band approximations. We have used the diagonalization method by choosing a wave function based on the trigonometric orthonormal functions to find eigenvalues and eigenfunctions of the electron confined within the improved Rosen-Morse potential. Our results show that the position-dependence mass, asymmetry, and confinement parameters cause significant changes in the electronic and optical properties of the structure we focus on since these effects create a significant increase in electron energies and a blue shift in the absorption spectrum. The increase in energy levels enables the development of optoelectronic devices that can operate at wider wavelengths and absorb higher energy photons. This offers potential advancements in fields such as optical communication, imaging technology, and solar cells.

In this article, we delve into the intricate behavior of electronic mechanisms underlying NMR magnetic shieldings, σ, in molecules containing heavy atoms such as cadmium, platinum, and mercury. Specifically, we explore PtXn^{−2} (X = F, Cl, Br, I; n = 4, 6) and XCl2 Te2 Y2 H6 (X = Cd, Hg; Y = N, P) molecular systems. It is known that the leading electronic mechanisms responsible for the relativistic effects on σ are well characterized by the linear response with elimination of small components model (LRESC). In this study, we present results obtained from the innovative LRESC-Loc model, which offers the same outcomes as the LRESC model but employs localized molecular orbitals (LMOs) instead of canonical MOs. These LMOs provide a chemist’s representation of atomic core, lone pairs, and bonds. The whole set of electronic mechanisms responsible of the relativistic effects can be expressed in terms of both non-ligand-dependent and ligand-dependent contributions. We elucidate the electronic origins of trends and behaviors exhibited by these di- verse mechanisms in the aforementioned molecular systems. In PtX4^{−2} molecules, the predominant relativistic mechanism is the well-established one-body spin-orbit (σ^SO(1) ) mechanism, while the paramagnetic mass-velocity (σ^Mv ) and Darwin (σ^Dw ) contributing mechanisms also demand con- sideration. However, in PtX6−2 molecules, the σ Mv+ Dw contribution surpasses that of the SO(1) mechanism, thus influencing the overall ligand-dependent contributions. As for complexes con- taining Cd and Hg, the ligand-dependent contributions exhibit similar magnitudes when nitrogen is substituted with phosphorus. The only discrepancy arises from the σ^SO(1) contribution, which changes sign between the two molecules due to the contribution of bond orbitals between the metal and tellurium atoms.

The discovery of microRNAs (miRNAs) has fundamentally transformed our understanding of gene regulation. The competing endogenous RNA (ceRNA) hypothesis postulates that not only messenger RNAs but also other RNA transcripts, such as long non-coding RNAs and pseudogenes, can act as natural miRNA sponges. These RNAs influence each other’s expression levels by competing for the same pool of miRNAs through miRNA response elements on their target transcripts, thereby modulating gene expression and protein activity. In recent years, these ceRNA regulatory networks have gained considerable attention in cancer research. Several studies have identified cancer-specific ceRNA networks. Nevertheless, prior bioinformatic analyses have focused on long non-coding RNAs-associated ceRNA networks. Here, we identify an extended-ceRNA network (including both long non-coding RNAs and pseudogenes) shared across a group of four hormone-dependent (HD) cancers, i.e., prostate, breast, colorectal, and endometrial cancers, using data from The Cancer Genome Atlas (TCGA). We performed a functional enrichment analysis for differentially expressed genes in the shared ceRNA network of HD cancers, followed by a survival analysis to determine their prognostic ability. We identified two long non-coding RNAs, nine genes, and seventy-four miRNAs in the shared ceRNA network across four HD cancers. Among them, two genes and forty-one miRNAs were associated with at least one HD cancer survival. This study is the first to investigate pseudogene associated ceRNAs across a group of related cancers and highlights the value of this approach to understanding shared molecular pathogenesis in a group of related diseases.

River valley bottoms have hydrological, geomorphological, and ecological importance and are buffers for protecting the river from upland nutrient loading coming from agriculture and other sources. They are relatively flat, low-lying areas of the terrain that are adjacent to the river and bound by increasing slopes at the transition to the uplands. These areas have under natural conditions, a groundwater table close to the soil surface. The objective of this paper is to present a stepwise GIS approach for the delineation of river valley bottom within drainage basins and use it to perform a national delineation. We developed a tool that applies a concept called cost distance accumulation with spatial data inputs consisting a river network and slope derived from a digital elevation model. We then used wetlands adjacent to rivers as a guide finding the river valley bottom boundary from the cost distance accumulation. We present results from our tool for the whole country of Denmark carrying out a validation within three selected areas. The results reveal that the tool visually performs well and delineates both confined and unconfined river valleys within the same drainage basin. We use the most common forms of wetlands (meadow and marsh) in Denmark's river valleys known as Groundwater Dependent Ecosystems (GDE) to validate our river valley bottom delineated areas. Our delineation picks about half to two-thirds of these GDE. However, we expected this since farmers have reclaimed Denmark's low-lying areas during the last 200 years before the first map of GDE was created. Our tool can be used as a management tool, since it can delineate an area that has been the focus of management actions to protect waterways from upland nutrient pollution.

Transfusion dependent thalassemia (TDT) patients are treated with continued blood transfusions and show a higher prevalence of depression. TDT with consequent iron overload and inflammation is associated with increased severity of depressive symptoms in TDT children.Aim of the study: To construct a pathway-phenotype which combines iron overload and neuro-immune biomarkers with depressive symptom subdomains in TDT children.Methods: We measured iron status parameters (iron, ferritin, transferrin saturation percentage) and inflammatory (interleukin-1β and tumour necrosis factor-α) biomarkers in TDT (n=111) and healthy (n=53) children and analyzed the results using machine learning.Results: Cluster analysis separated TDT children with depression from those without depression and revealed two depressive subgroups one with low self-esteem and another with increased social-irritability scores. Exploratory factor analysis validated four depressive symptom dimensions as reliable constructs, namely key depressive, physiosomatic, lowered self-esteem and social-irritability dimensions. Partial Least Squares showed that 73.0% of the variance in a latent vector extracted from those four clinical subdomains, immune-inflammatory and iron overload biomarkers was explained by exposure variables including the number of blood transfusions and hospitalizations and use of deferoxamine. The exposure data, iron and immune biomarkers, and symptom subdomains are reflective manifestations of a single latent trait, which shows internal consistency reliability and predictive relevance.Conclusions: The nomological network combining exposure, pathways and behavioral phenome manifestations provides an index of overall severity and disease risk and, therefore, constitutes a new drug target, indicating that iron overload and immune activation should be targeted to treat depression due to TDT.

The transfer of protein-encoding genetic information from DNA to RNA to protein, a process formalized as the “Central Dogma of Molecular Biology”, has undergone a significant evolution since its inception. It was amended to account for the information flow from RNA to DNA, the reverse transcription, and for the information transfer from RNA to RNA, the RNA-dependent RNA synthesis. These processes, both potentially leading to protein production, were initially described only in viral systems, and although RNA-dependent RNA polymerase activity was shown to be present, and RNA-dependent RNA synthesisfound to occur, in mammalian cells, its function was presumed to be restricted to regulatory. However, recent results, obtained with multiple mRNA species in several mammalian systems, strongly indicate the occurrence of protein-encoding RNA to RNA information transfer in mammalian cells. It can result in the rapid production of the extraordinary quantities of specific proteins as was seen in cases of terminal cellular differentiation and during cellular deposition of extracellular matrix molecules. A malfunction of this process may be involved in pathologies associated either with the deficiency of a protein normally produced by this mechanism or with the abnormal abundanceof a protein or of its C-terminal fragment. It seems to be responsible for some types of familial thalassemia and may underlie the overproduction of beta amyloid in sporadic Alzheimer’s disease. The aim of the present article is to systematize the current knowledge and understanding of this pathway. The outlined framework introduces unexpected features of the mRNA amplification such as its ability to generate polypeptides non-contiguously encoded in the genome, its second Tier, a physiologically occurring intracellular polymerase chain reaction, iPCR, a Two-Tier Paradox and RNA Dark Matter. RNA-dependent mRNA amplification represents a new mode of genomic protein-encoding information transfer in mammalian cells. Its potential physiological impact is substantial, it appears relevant to multiple pathologies and its understanding opens new venues of therapeutic interference, it suggests powerful novel bioengineering approaches and its further rigorous investigations are highly warranted.

Passivating the grain boundaries is completely very crucial to achieve high power conversion efficiency in halide PSCs.

Accurate medical image segmentation is paramount for precise diagnosis and treatment in modern healthcare. This research presents a comprehensive study on the efficacy of Particle Swarm Optimization (PSO) combined with Histogram Equalization (HE) preprocessing for medical image segmentation, focusing on Lung CT-Scan and Chest X-ray datasets. Best Cost values reveal the PSO algorithm’s performance, with HE preprocessing demonstrating significant stabilization and enhanced convergence, particularly in complex Lung CT-Scan images. Evaluation metrics, including Accuracy, Precision, Recall, F-Score, Specificity, Dice, and Jaccard, show substantial improvements with HE preprocessing, emphasizing its impact on segmentation accuracy. Comparative analyses against alternative methods, such as Otsu, Watershed, and K-means, confirm the competitiveness of the PSO-HE approach, especially in Chest X-ray images. The study also underscores the positive influence of preprocessing on image clarity and precision. These findings highlight the promise of the PSO-HE approach in advancing the accuracy and reliability of medical image segmentation, paving the way for further research and method integration to enhance this critical healthcare application.

Crop yield enhancement is crucial for ensuring food security and meeting the growing global demand for agricultural products. The development of innovative technologies, such as CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats), has provided new avenues for precise genetic modifications in crops. In this research article, we explore the application of CRISPR technology for crop yield improvement. We discuss the methodology, present recent results, and engage in a comprehensive discussion of the potential benefits, challenges, and future prospects of CRISPR-mediated crop yield enhancement.

Gradient-domain image processing is a technique where, instead of operating directly on the image pixel values, the gradient of the image is computed and processed. The resulting image is obtained by reintegrating the processed gradient. This is normally done by solving the Poisson equation, most oftenly by means of a finite difference implementation of the gradient descent method. However, this technique in some cases lead to severe haloing artefacts in the resulting image. To deal with this, local or anisotropic diffusion has been added as an ad-hoc modification of the Poisson equation. In this paper, we show that a version of anisotropic gradient-domain image processing can result from a more general variational formulation through the minimisation of a functional formulated in terms of the eigenvalues of the structure tensor of the differences between the processed gradient and the gradient of the original image. Example applications of linear and non-linear local contrast enhancement and colour image daltonisation illustrate the behaviour of the method.

A characteristic feature of lightweight constructions is their low thermal mass which causes high internal temperature fluctuations that require high heating and cooling demand throughout the year. Phase Change Materials (PCMs) is effective in providing thermal inertia to low thermal mass buildings. The aim of this paper is to analyse the thermal behaviour of two proposed lightweight buildings designed for homeless people and to investigate the potential benefit achievable through the use of different types of PCM in the temperate climatic conditions of Christchurch, New Zealand. For this purpose, over 300 numerical simulations have been conducted using the simulation software DesignBuilder®. The bulk of the simulations were carried out under the assumption that the whole opaque building envelope is equipped with PCM. The results showed significant energy saving and comfort enhancement through the application of PCMs. Thereby, annual energy saving of over 50 % was reached for some of the PCMs considered. Additionally, the effectiveness of single, PCM-equipped structure components was investigated and substantial benefits between 19 and 27 % annual energy saving were achieved. However, occupant behaviour in terms of ventilation habits, occupancy of zones etc. remains one of the biggest challenges in any simulation work due to insufficient data.

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

CD44 is a type I transmembrane glycoprotein, which is associated with poor prognosis in various solid tumors. Since CD44 plays critical roles in tumor development by regulating cell adhesion, survival, proliferation, and stemness, it has been considered a target for tumor therapy. Anti-CD44 monoclonal antibodies (mAbs) have been developed and applied to antibody-drug conjugates and chimeric antigen receptor-T cell therapy. We previously developed anti‐pan-CD44 mAbs, C₄₄Mab-5 and C₄₄Mab-46, which can recognize both CD44 standard (CD44s) and variant isoforms. In the present study, a defucosylated mouse IgG_2a version of the anti-pan-CD44 mAbs (5-mG_2a-f and C₄₄Mab-46-mG_2a-f) was generated to evaluate the antitumor activities against CD44-positive cells. Both 5-mG_2a-f and C₄₄Mab-46-mG_2a-f recognized CD44s-overexpressed CHO-K1 (CHO/CD44s) cells and esophageal tumor cell line (KYSE770) in flow cytometry. Furthermore, both 5-mG_2a-f and C₄₄Mab-46-mG_2a-f could activate effector cells in the presence of CHO/CD44s cells and exhibited the complement‐dependent cytotoxicity against both CHO/CD44s and KYSE770 cells. Furthermore, the administration of 5-mG_2a-f and C₄₄Mab-46-mG_2a-f significantly suppressed CHO/CD44s and KYSE770 xenograft tumor development compared with the control defucosylated mouse IgG_2a. These results indicate that 5-mG_2a-f and C₄₄Mab-46-mG_2a-f could exert antitumor activities against CD44-positive cancers and could be a promising therapeutic regimen for tumors.

Our aim was to determine the secondary antibody deficiency profiles of patients in a mesoregion of São Paulo state, Brazil, focusing on infectious diseases. Demographic characteristics, clinical and laboratory data were obtained from electronic files; infections were classified as organ-specific and graded as mild, moderate, life-threatening, and fatal. Non-Hodgkin lymphoma (NHL) accounted for 30% of patients, nephrotic syndrome (NS) 25%; chronic lymphocyte leukemia 20%, and multiple myeloma 15%. Patients with NS were younger than those in other groups, and hypo-γ-globulinemia was detected in 94.1%, IgG <400 mg/dL in 60.0%, IgA <40 mg/dL in 55.0%, and CD19 <20 cells/mm³ in 30.0%. One hundred and one infections were found; 82.1% were classified as mild or moderate, 7.9% as life-threatening, and 1.9% as fatal. Respiratory tract infections were more prevalent (41.5%), and pneumonia accounted for 19.8%. Lower levels of infections were found in patients with NS compared with NHL (P=0.0001). Most patients progressed to hypo-γ-globulinemia and secondary antibody deficiency after treatment with immunosuppressants, and mild and moderate infections were predominant. These therapies are increasing in patients with different diseases, therefore monitoring hypo-γ-globulinemia and infections may help to identify patients at high risk for severe complications, antibiotic prophylaxis or treatment, and immunoglobulin replacement

Overexpression of human epidermal growth factor receptor 2 (HER2) in breast and gastric cancers is an important target for monoclonal antibody (mAb) therapy. All therapeutic mAbs, including anti-HER2 mAbs, exhibit adverse effects probably due to the recognition of antigens expressed in normal cells. Therefore, tumor-selective or specific mAbs can be beneficial in reducing the adverse effects. In this study, we established a novel cancer-specific anti-HER2 antibody, named H₂Mab-250/H₂CasMab-2 (IgG₁, kappa). H₂Mab-250 reacted with HER2-positive breast cancer BT-474 and SK-BR-3 cells. Importantly, H₂Mab-250 did not react with non-transformed normal epithelial cells (HaCaT and MCF 10A) and immortalized normal epithelial cells in flow cytometry. In contrast, most anti-HER2 mAbs including H₂Mab-119 (IgG₁, kappa) reacted with both cancer and normal epithelial cells. Furthermore, a core-fucose deleted IgG_2a-type H₂Mab-250 (H₂Mab-250-mG_2a-f) could trigger the antibody-dependent cellular cytotoxicity activity to BT-474, but not to HaCaT cells. Furthermore, H₂Mab-250-mG_2a-f exhibited an in vivo antitumor effect against BT-474 xenograft. Immunohistochemical analysis demonstrated that H₂Mab-250 possesses much higher reactivity to the HER2-positive breast cancer tissues compared to H₂Mab-119, and did not react with normal tissues, including heart, breast, stomach, lung, colon, kidney, and esophagus. The epitope mapping demonstrated that the Trp614 of HER2 domain IV mainly contributes to the recognition by H₂Mab-250. H₂Mab-250 could contribute to the development of chimeric antigen receptor-T or antibody-drug conjugates without adverse effects for breast cancer therapy.

The differentiation between Neuromyelitis optica spectrum disorder (NMOSD) and cervical spondylotic myelopathy (CSM) is necessary, because both diseases have similar symptoms, such as motor weakness and sensory disturbances. The challenge arises when NMOSD presents with short-segment spinal cord lesions, which can mimic the clinical presentation of CSM. This case report presents an NMOSD misdiagnosed as CSM. A 66-year-old woman presented with neck pain, left arm pain, and motor weakness. She was initially diagnosed with CSM based on MRI findings that revealed the increased signal intensity of the spinal cord at the C3 to 4 levels and underwent surgery. Three years later, she had sudden left upper extremity motor weakness and mild gait disturbance. Physical exam showed left-side weakness and altered reflexes, with longitudinally extensive transverse myelitis (LETM) findings on cervical MRI. The CSF study revealed a 2+ AQP4-Ab finding. Finally, NMO was diagnosed. Steroid pulsed therapy and immunosuppression therapy led to improved motor function and gait after 20 days. We present a case report of a NMO patient who initially exhibited clinical and radiological features CSM but was later diagnosed with NMO. This case underscores the diagnostic challenge in distinguishing NMO from CSM, especially in elderly patients who commonly experience spinal degeneration leading to cord compression and associated cord signal changes on MRI. The misinterpretation or confusion with transverse myelitis can occur as a result. This case highlights the importance of considering NMO as a potential differential diagnosis in elderly patients with spinal degeneration, emphasizing the significance of precise and timely diagnosis for guiding optimal treatment decisions.

Background and Objectives: Treatment for antineutrophil cytoplasmic antibody-associated vasculitis (AAV) must deal with immunosuppression as well as infections associated with compromised immune system, such as tuberculosis (TB). Our aim was to overcome the gap in the literature concerning the risk of incidental TB after diagnosis of AAV. Materials and Methods: This retrospective population-based cohort study was based on the data from the National Health Insurance Research Database in Taiwan. We used a novel algorithm to identify patients with newly diagnosed granulomatous polyangiitis (GPA) or microscopic polyangiitis (MPA) between January 1, 2000 and December 31, 2012. The primary outcome was risk of incidental TB. Cox proportional hazard models were used to evaluate the association between AAV and incidental TB. Results: A total of 2,257 patients with AAV and a propensity-score matched cohort of 9,028 patients were studied. Overall, patients with AAV were at a 1.48x higher risk of contracting incidental TB than were patients in the matched cohort (adjusted HR 1.48; 95% confidence interval [CI], 1.02-2.15). Note that the highest risk of contracting incidental TB was in the first two years following a diagnosis of AAV, with a nearly 1-fold increase in risk (adjusted HR, 1.91; 95% CI, 1.01-3.60). Female AAV patients were 3.24x more likely than females without AAV to develop TB (adjusted HR 3.24; 95%CI, 1.85-5.67). Conclusion: Patients with AAV face an elevated risk of contracting incidental TB, particularly within the first two years after AAV diagnosis. The risk of contracting TB is higher among female AAV patients than among females without AAV.

We investigated humoral immune responses in 222 unvaccinated Japanese people after recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in 2021. Anti-spike protein IgG antibody levels and neutralizing antibody titers were measured in serum samples obtained within 20–180 days after diagnosis. The geometric mean of antibody titers was 1555 ELU/mL (95% confidence interval [CI] = 1257-1923), and the neutralizing activities (50% inhibitory dilution) was 253 (95% CI = 204-313). The antibody titer and neutralizing activity both increased with increasing disease severity, and both values were approximately 4-fold higher for hospitalized patients than for non-hospitalized patients. However, these differences were smaller in older patients. The humoral immune response, which increased with increasing disease severity, gradually decreased over time after SARS-CoV-2 infection. Most patients with mild or moderate symptoms sustained neutralizing activity for up to 180 days after the infection, the decay of the neutralizing activity in the patients with asymptomatic was rather faster than other groups. 11.7% (26/222) of patients had very low neutralizing activity, and half of these were in the age of 20s. Our study results show the importance of measuring the neutralizing activity to confirm the immune status and also estimate the timing of vaccine.

The erythropoietin-producing hepatocellular carcinoma (Eph) receptors are the largest receptor tyrosine kinases family. EphB4 is essential for cell adhesion and motility during embryogenesis. Pathologically, EphB4 is overexpressed and contributes to poor prognosis in various tumors. Therefore, sensitive monoclonal antibodies (mAbs) should be developed to predict the prognosis for multiple tumors with high EphB4 expression, including breast and gastric cancers. This study aimed to develop highly sensitive and specific anti-EphB4 mAbs for several applications using the Cell-Based Immunization and Screening (CBIS) method. EphB4-overexpressed Chinese hamster ovary (CHO)-K1 (CHO/EphB4) cells were immunized into mice, and we established an anti-EphB4 mAb (clone B4Mab-7), which is applicable for flow cytometry, western blotting, and immunohistochemistry. B4Mab-7 reacted with endogenous EphB4-positive breast cancer cell lines, MCF-7 and MDA-MB-468, but did not react with EphB4-knockout MCF-7 (BINDS-52) in flow cytometry. Dissociation constant (KD) values were determined to be 2.9 × 10‑9 M, 1.3 × 10‑9 M, and 3.3 × 10‑9 M by flow cytometric analysis for CHO/EphB4, MCF-7, and MDA-MB-468 cells, respectively. B4Mab-7 detected the EphB4 protein bands from breast cancer cells in western blotting, and stained breast cancer tissues immunohistochemistry. Altogether, B4Mab-7 demonstrated high sensitivity and specificity against EphB4 in various applications.

CD44 is known as a cancer stem cell marker of head and neck squamous cell carcinoma (HNSCC) and plays a critical role in cancer malignant progression. Splicing variant isoforms of CD44 (CD44v) are overexpressed in cancers and considered a promising target for cancer therapy. Several monoclonal antibodies (mAbs) against CD44 have been developed by immunizing mice with CD44v3–10-overexpressed cancer cells. In this study, we characterized a novel clone, C₄₄Mab-18 (IgM, kappa). C₄₄Mab-18 reacted with CHO/CD44v3–10, but not with CHO/CD44s by flow cytometry. Enzyme-linked immunosorbent assay revealed that the epitope of C₄₄Mab-18 is determined to be the border sequence between variant 10 and the constant exon 16-encoded sequence. Flow cytometry showed that C₄₄Mab-18 recognizes HSC-3, an oral squamous cell carcinoma(OSCC) cell line. The apparent dissociation constant (K_D) of C₄₄Mab-18 for CHO/CD44v3–10 and HSC-3 was determined to be 1.6 × 10⁻⁷ M and 1.7 × 10⁻⁷ M, respectively. C₄₄Mab-18 detected CD44v3–10, but not CHO/CD44s in western blotting. Furthermore, C₄₄Mab-18 detected endogenous CD44v10 in immunohistochemistry using OSCC tissues. Taken together, C₄₄Mab-18 is useful for detecting CD44v10 in flow cytometry and immunohistochemistry.

Cluster of differentiation 44 (CD44) promotes tumor progression through the recruitment of growth factors, and the acquisition of stemness, invasiveness, and drug resistance. CD44 has multiple isoforms including CD44 standard (CD44s) and CD44 variants (CD44v), which have common and unique functions in tumor development. Therefore, the elucidation of each CD44 isoform’s function in tumor is essential for the establishment of CD44-targeting tumor therapy. We have established various anti-CD44s and anti-CD44v monoclonal antibodies (mAbs) through immunization of CD44v3–10-overexpressed cells. In this study, we established C44Mab-6 (IgG1, kappa), which recognized the CD44 variant 3-encoded region (CD44v3) determined by enzyme-linked immunosorbent assay. C44Mab-6 reacted with CD44v3–10-overexpressed Chinese hamster ovary (CHO)-K1 cells (CHO/CD44v3–10) or some cancer cell lines (COLO205 and HSC-3) by flow cytometry. The apparent KD of C44Mab-6 for CHO/CD44v3–10, COLO205, and HSC-3 was 1.5 × 10−9 M, 6.3 × 10−9 M, and 1.9 × 10−9 M, respectively. C44Mab-6 could detect the CD44v3–10 in western blotting, and stained the formalin-fixed paraffin-embedded tumor sections in immunohistochemistry. These results indicate that C44Mab-6 is useful for detecting CD44v3 in various experiments, and expected for the application of tumor diagnosis and therapy.

Pancreatic cancer exhibits a poor prognosis due to the lack of early diagnostic biomarkers and the resistance to conventional chemotherapy. CD44 has been known as a cancer stem cell marker, and plays tumor promotion and drug resistance in various cancers. Especially, the splicing variants are overexpressed in many carcinomas, and play essential roles in the cancer stemness, invasiveness or metastasis, and resistance to treatments. Therefore, the understanding of each CD44 variant (CD44v) function and distribution in carcinomas is essential for the establishment of CD44-targeting tumor therapy. In this study, we immunized mice with CD44v3–10-overexpressed Chinese hamster ovary-K1 (CHO) cells, and established various anti-CD44 monoclonal antibodies (mAbs). One of the established clones (C44Mab-3; IgG1, kappa) recognized peptides of the variant 5-encoded region, indicating that C44Mab-3 is a specific mAb for CD44v5. Moreover, C44Mab-3 reacted with CHO/CD44v3–10 cells or pancreatic cancer cell lines (PK-1 and PK-8) by flow cytometry. The apparent KD of C44Mab-3 for CHO/CD44v3–10 and PK-1 was 7.1 × 10−10 M and 1.9 × 10−9 M, respectively. C44Mab-3 could detect the exogenous CD44v3–10 and endogenous CD44v5 in western blotting, and stained the formalin-fixed paraffin-embedded pancreatic cancer cells, but not normal pancreatic epithelial cells in immunohistochemistry. These results indicate that C44Mab-3 is useful for detecting CD44v5 in various applications, and expected for the application of pancreatic cancer diagnosis and therapy.

CD44 has been known as a marker of tumor initiating cells, and plays pro-tumorigenic functions in many cancers. The splicing variants play critical roles in malignant progression of cancers by promoting the stemness, cancer cell invasion or metastasis, and resistance to chemo- and radiotherapy. To understand each CD44 variant (CD44v) function is essential to know the property of cancers and establishment of the therapy. However, the function of the variant 4-encoded region has not to be elucidated. Therefore, specific monoclonal antibodies (mAbs) against the variant 4 are indispensable for basic research, tumor diagnosis, and therapy. In this study, we established anti-CD44 variant 4 (CD44v4) monoclonal antibodies (mAbs) by immunizing mice with a peptide containing the variant 4-encoded region. We next performed flow cytometry, western blotting, and immunohistochemistry to characterized them. One of the established clones (C₄₄Mab-108; IgG₁, kappa) reacted with CD44v3-10-overexpressed Chinese hamster ovary-K1 cells (CHO/CD44v3-10). The K_D of C₄₄Mab-108 for CHO/CD44 v3-10 was 3.4 × 10⁻⁷ M. In western blot analysis, C₄₄Mab-108 detected CD44v3-10 in the lysate of CHO/CD44v3-10 cells. Furthermore, C₄₄Mab-108 stained formalin-fixed paraffin-embedded oral squamous carcinoma tissues in immunohistochemistry. These results indicated that C₄₄Mab-108 is useful to detect CD44v4 in various applications.

The blood-brain barrier (BBB), built by brain endothelial cells (BECs), is impermeable to biologics. Liposomes and other nanoparticles are good candidates for delivery of biologics across the BECs, as they can encapsulate numerous molecules of interest in an omnipotent manner. The liposomes need attachment of a targeting molecule, as BECs unfortunately are virtually incapable of uptake of non-targeted liposomes from the circulation. Experiments of independent research groups have qualified antibodies targeting the transferrin receptor as superior for targeted delivery of nanoparticles to BECs. Functionalization of nanoparticles via conjugation with anti-transferrin receptor antibodies leads to nanoparticle uptake by endothelial cells of both brain capillaries and post-capillary venules. Reducing the density of transferrin receptor-targeted antibodies conjugated to liposomes limits uptake in BECs. Opposing the transport of nanoparticles conjugated to high-affine anti-transferrin receptor antibodies, lowering the affinity of the targeting antibodies or implementing monovalent antibodies increase uptake by BECs and allows for further transport across the BBB. The novel demonstration of transport of targeted liposomes in post-capillary venules from blood to the brain is interesting and clearly warrants further mechanistic pursuit. The recent evidence for passing targeted nanoparticles through the BBB shows great promise for future drug delivery of biologics to the brain.

Background: Hepatocellular carcinoma (HCC) is one of most common cancers with a high mortality rate. HBV/HCV infection is an important risk factor to trigger HCC. Therefore, developing serum biomarkers for early diagnosis is crucial to prolong survival in HCC patients. Methods: An antibody array technology was utilized to detect serum from 20 HBV-related HCC patients, 20 chronic hepatitis B patients and 20 normal population, whose results were further validated by ELISA. Results: Both antibody array and ELISA showed that ten growth factors (SCF R, GDF-15, HGF, FGF-4, IGFBP-1, PIGF, GH, GDNF, BDNF and IGF-1) were significantly differential in HCC patients when compared to the non-HCC population. Among these growth factors, the levels of SCF R, GDF-15, HGF, GH and IGF-1 showed significant correlation with hepatitis B and its severity, indicating that these growth factors may promote HCC progression by an HBV-specific mechanism. A therapy targeting these growth factors in hepatitis B patients may help to prevent the development of HCC. FGF4 and GH were found, for the first time, to be upregulated in HCC, suggesting that these two growth factors may serve as novel serum biomarkers for the early diagnosis of HCC. Conclusion: The combined detection of all the differential growth factors may improve the diagnostic accuracy of HCC.

The need for antiserum for immunohistochemical (IHC) detection of enterovirus (EV) in formaldehyde fixed and paraffin-embedded (FFPE) specimens is increasing. The standard monoclonal antibody against EV-envelope protein (VP1), clone 5D8/1, was proven to cross-react with other proteins. Another candidate marker of EV proteins is 2A protease (2Apro), which is coded by the EV gene and translated by host cells during EV replication. We raised polyclonal antiserum by immunizing rabbits with an 18-mer peptide of Coxsackievirus B1 (CVB1)-2A protease (2Apro) and examined the specificity and sensitivity for EV on FFPE tissue samples. ELISA study showed a high titer of antibody for CVB1-2Apro. IHC demonstrated that antiserum against 2Apro reacted with CVB1-infected Vero-cells. Confocal microscopy demonstrated that 2Apro labelled by the antibody located in the same cell with VP1 stained with 5D8/1. IHC demonstrated dense positive reactions pancreatic islets of EV-associated fulminant type 1 diabetes (FT1DM), and located in the same cell stained positive with 5D8/1. Specificity of IHC staining FT1DM pancreas was confirmed by absorption with an excessive concentration of immunized peptide. In conclusion, our study provides a new polyclonal antiserum against CVB1 2Apro which may be useful for detection of EV-infected human tissues stored as archive of FFPE tissue samples.

SARS-CoV-2 continues to widely circulate in populations globally. Underdetection is acknowledged and is problematic when attempting to capture the true prevalence. Seroprevalence studies, where blood samples from a population sample are tested for SARS-CoV-2 antibodies that react to the SARS-CoV-2 virus, are a common method for estimating the proportion of people previously infected with the virus in a given population. However, obtaining reliable estimates from seroprevalence studies is challenging for a number of reasons, and the uncertainty in the results is often overlooked by scientists, policy makers and the media. This paper reviews the methodological issues that arise in designing these studies, and the main sources of uncertainty that affect the results. We discuss the choice of study population, recruitment of subjects, uncertainty surrounding the accuracy of antibody tests themselves, and the relationship between antibodies and infection over time. Understanding these issues can help the reader to interpret and critically evaluate the results of seroprevalence studies.

Trophoblast cell-surface antigen 2 (Trop 2) is a transmembrane glycoprotein that is highly expressed in various cancer types with relatively low or no baseline expression in most of normal tissues. Its overexpression is associated with tumor growth and poor prognosis; Trop 2 is therefore, an ideal therapeutic target for epithelial cancers. Several Trop 2 targeted therapeutics have recently been developed for the treatment of cancers, such as anti-Trop 2 antibodies and antibody-drug conjugates (ADCs), as well as Trop 2-specific cell therapy. In particular, the safety and clinical benefit of Trop 2-based ADCs have been demonstrated in clinical trials across multiple tumor types, including those with limited treatment options, such as triple-negative breast cancer, platinum-resistant urothelial cancer, and heavily pretreated non-small cell lung cancer. In this review, we elaborate on recent advances in Trop 2 targeted modalities and provide an overview of novel insights for future developments in this field.

The 2019 novel SARS-like coronavirus (SARS-CoV-2) entry depends on the host membrane serine protease TMPRSS2, which can be blocked by some clinically-proven drugs. Here we analyzed spatial relevance between glycosylation sequons and antibody epitopes and found that, different from SARS-CoV S, most high-surface-accessible epitopes of SARS-CoV-2 S are blocked by the glycosylation, and the optimal epitope with the highest surface accessibility is covered by the S1 cap. TMPRSS2 inhibitor treatments may prevent unmasking of this epitope and therefore prolong virus clearance and may induce antibody-dependent enhancement. Interestingly, a heparin-binding sequence immediately upstream of the S1/S2 cleavage site has been found in SARS-CoV-2 S but not in SARS-CoV S. Binding of SARS-CoV-2 with heparins may lead to exposure of S686, which then facilitates the S1/S2 cleavage, induces exposure of the optimal epitope, and therefore increases the antibody titres. A combination of heparin and vaccine (or convalescent serum) treatments thus is recommended.

The first exposure to influenza is thought to impact subsequent immune responses later in life. The consequences of this can be seen during influenza epidemics and pandemics with differences in morbidity and mortality for different birth cohorts. There is a need for better understanding of how vaccine responses are affected by early exposures to influenza viruses. In this analysis of hemagglutination inhibition (HI) antibody responses in two cohorts of military personnel we noticed differences related to age, sex, prior vaccination, deployment and birth year. These data suggest that HI antibody production, in response to influenza vaccination, is affected by these factors. The magnitude of this antibody response is associated with, among other factors, the influenza strain that circulated following birth.

In this essay, I revisit Neural Networks (NNs) through the lens of evolutionary dynamics. From the two most important features of NNs, I recover the two most general equations of evolutionary dynamics. These two equations may thus serve as a connection between NNs and a body of knowledge that has been built over multiple centuries and has found application across a vast range of disciplines. This connection may therefore also help explain why NNs with the two features in question are applicable across a much broader range of domains than initially envisioned.

Chromium poisoning strongly influences the performance of solid oxide fuel cell (SOFC) stacks. A three-dimensional, time-dependent, computational fluid dynamics model of a single channel of a F10 SOFC stack in Forschungszentrum Jülich GmbH is developed to investigate chromium poisoning for different stack designs, temperatures and absolute air humidities. The model takes into account both chemical and electrochemical mechanisms of chromium poisoning and is able to predict the spatial distribution of SrCrO4 and Cr2O3. The voltage degradation over 100 kh can be simulated quantitatively. According to the simulation results, chromium poisoning is almost eliminated by the application of the protective coating fabricated by the atmospheric plasma-spraying (APS) technology. Besides, with the help of the APS protective coating, operating a SOFC stack with less dehumidified air at 650 oC is possible according to the simulation.

Many studies on magnetorheological fluid (MRF) have been carried out over last three decades several salient advantages such as fast phase change, easy control of the yield stress and so forth. Especially, several review articles of MRF technology have been reported for last two decades summarizing the development of MRFs and their applications. As specific examples, the review articles including the optimization of the particles and carrier liquid to achieve minimum off-state viscosity and maximum yield stress at on-state, the formulation of many constitutive models in-cluding Casson model and Herschel-Bulkley (H-B) model, the sedimentation enhancement using additives and nanosized particles, many types of dampers for automotive suspension and civil structures, medical and rehabilitation devices, MRF polishing technology, the methods of mag-netic circuit design, and the synthesis of various controllers have been published. More recently, the effect of the temperature and thermal conductivity on the properties of MRFs and application systems are actively being investigated by several works. However, there is no review article on this issue so far despite of that the thermal problem is one of crucial factors to be seriously con-sidered for the development of advanced MRFs and commercial products of application systems. In this work, studies on the thermal conductivity and temperature in MRFs themselves and tem-perature-dependent application systems are reviewed, respectively, and principal results are summarized emphasizing on the followings: how to reduce the temperature effect on the field-dependent properties of MRFs and how to design application system to minimize the thermal effect. It is noted here that the review summary is organized in a chronological format using tables.

SARS-CoV-2 is the causative agent for the ongoing COVID19 pandemic, and this virus belongs to the Coronaviridae family. Like other members of this family, the virus possesses a positive-sense single-stranded RNA genome. The genome encodes for the nsp12 protein, which houses the RNA-dependent-RNA polymerase (RdRP) activity responsible for the replication of the viral genome. A homology model of nsp12 was prepared using the structure of the SARS nsp12 (6NUR) as a model. The model was used to carry out in silico screening to identify molecules among natural products, or FDA approved drugs that can potentially inhibit the activity of nsp12. This exercise showed that vitamin B12 (methylcobalamin) may bind to the active site of the nsp12 protein. A model of the nsp12 in complex with substrate RNA and incoming NTP showed that Vitamin B12 binding site overlaps with that of the incoming nucleotide. A comparison of the calculated energies of binding for RNA plus NTP and methylcobalamin suggested that the vitamin may bind to the active site of nsp12 with significant affinity. It is, therefore, possible that methylcobalamin binding may prevent association with RNA and NTP and thus inhibit the RdRP activity of nsp12. Overall, our computational studies suggest that methylcobalamin form of vitamin B12 may serve as an effective inhibitor of the nsp12 protein.

In this paper, we examine the mathematical and physical consistencies of the three primary couple stress theories: original Mindlin-Tiersten-Koiter couple stress theory (MTK-CST), modified couple stress theory (M-CST) and consistent couple stress theory (C-CST). As has been known for many years, MTK-CST suffers from some fundamental inconsistencies, such as the indeterminacy of the couple-stress tensor. Therefore, despite the fact that MTK-CST has a fundamental position in the evolution of size-dependent continuum mechanics, it is not a reliable theory within continuum mechanics, for example, in developing new size-dependent multi-physics formulations. We also observe that M-CST not only inherits all inconsistences from the original MTK-CST, but also suffers from new additional inconsistencies, such as the introduction of a new non-physical governing equation. These inconsistencies refute the claim of those who state that the couple-stress tensor may be chosen symmetric. Therefore, the apparent success of MTK-CST and M-CST in describing a size-effect for some problems, such as two-dimensional plate and beam bending, is not enough to justify these theories as suitable for general cases. In fact, the symmetric couple-stresses in M-CST create torsional or anticlastic deformation, not bending. On the other hand, C-CST, with a skew-symmetric couple-stress tensor, is the consistent continuum mechanics suitable for solving different size-dependent solid, fluid and multi-physics problems.

Arthropod-borne flaviviruses represent human pathogens of global medical importance, against which no effective small molecule-based antiviral therapy is currently available. Arbidol (umifenovir) is a broad spectrum antiviral compound approved in Russia and China for prophylaxis and treatment of influenza. This compound showed activity against numerous DNA and RNA viruses. Its mode of action is based predominantly on the impairment of critical steps of virus-cell interaction. Here we demonstrate that arbidol possesses a micromolar inhibition activity (EC50 values ranging from 10.57 ± 0.74 to 19.16 ± 0.29 µM) in Vero cells infected with Zika virus, West Nile virus, and tick-borne encephalitis virus, three medically important representatives of arthropod-borne flaviviruses. Interestingly, no antiviral effect of arbidol is observed in porcine stable kidney cells (PS), human neuroblastoma cells (UKF-NB-6), human hepatoma cells (Huh-7 cells) indicating that the antiviral effect of arbidol is strongly cell-type dependent. Arbidol presents a significant increasing in cytotoxicity profiles when tested in various cell lines in the order: Huh-7 < HBCA < PS < UKF-NB-6 < Vero with CC50 values ranging from 18.69 ± 0.1 to 89.72 ± 0.19 µM. Antiviral activity and acceptable cytotoxicity profiles suggest that arbidol could be a promising candidate for further investigation as a potential therapeutic agent in treating flaviviral infections.

Piezoelectric nanotransducers may offer key advantages in comparison with conventional piezoelectrics, including more choices for types of mechanical input, positions of the contacts, dimensionalities and shapes. However, since piezo-semiconductive nanostructures are generally much easier to fabricate and integrate into functional systems than insulating materials, modeling becomes significantly more intricate and the effects of free charges have been considered only in a few studies. The available reports are complicated by the absence of proper nomenclature and figures of merit. Besides, some analyses are incomplete. For instance, the local piezopotential and free charges within axially strained conical piezo-semiconductive nanowires have only been systematically investigated for very low doping (1016 cm-3) and under compression. Here we give the definitions for the enhancement, depletion, base and tip piezopotentials, their characteristic lengths and both the tip-to-base and the depletion-to-enhancement piezopotential-ratios. As an example, we use these definitions for analyzing the local piezopotential and free charges in n-type ZnO truncated conical nanostructures with different doping levels (intrinsic, 1016 cm-3, 1017 cm-3) for both axial compression and traction. The definitions and concepts presented here may offer insight for designing high performance piezosemiconductive nanotransducers.

The work aims to improve the battery performance in hybrid electric vehicles (HEVs) by reducing the vehicle speed. We develop a specific protocol for managing battery use and optimizing the energy consumption rate to achieve this goal. The protocol automatically controls the driving operation, avoiding incompatible driving patterns with energy-saving mode and performance improvement. The protocol is submitted to a simulation process to predict the energy rate lowering and battery performance enhancement. The proposed protocol applies to any hybrid electric vehicle type and route conditions since it uses vehicle mass, drag and rolling coefficients, and road slope as variable parameters to determine the minimum energy consumption rate. We run experimental tests to validate the simulation data and the proposed protocol. Furthermore, the protocol applies to variable starting vehicle speeds, from 10 to 50 km/h, corresponding to the current driving patterns, sport, normal, and eco, set up by car manufacturers. A reduction of 10% in vehicle speed in urban and peripheral routes achieves a minimum energy rate, enhancing battery management. Current vehicle speed shows a deviation from optimum management of 18% while applying the vehicle speed reduction limits the deviation to 0.2%. Experimental results show a good agreement with simulation data with 94% accuracy. We tested the protocol for urban and peripheral routes with maximum vehicle speed limits of 60 and 90 km/h.

In this work, two plasmonic structures with two different periodic nanostructures (nanodisk and nanostrip arrays) separated from the gold layer by an ultrathin dielectric Al2O3 layer are proposed, and their optical properties are simulated as 3-dimensional models using COMSOL Multiphysics software tool. The optical responses, such as the amplification of the electric field and the scattering, absorption and extinction cross sections of the two structures, are investigated and compared. The results show that both structures show strong field enhancement in their gap layer, and the structure with the periodic array of metal nanodisks shows stronger field enhancement and larger absorption, extinction, and scattering cross sections in its dipole resonance wavelength, which is defined as a bright plasmonic mode. In addition, some weaker resonant modes are observed for both structures and the reason for their generation is dis-cussed. The analysis of different possible modes in such structures is crucial for their application in various fields.

The aim of this retrospective study was to identify myocardial injury after COVID-19 inflamation and to explore whether myocardial damage could be a possible cause of the persistent symptoms following COVID-19 infection in previously healthy individuals. The study included 139 patients who were enrolled between January-June 2021, mean age 46.7±15.2 years, 68 were men, 71 were women without known cardiac or pulmonary diseases. All patients underwent clinical work up, lab. analyses, cardiac ultrasound, and CMR on 1.5 T scanner using a recommended protocol for morphological and functional assessment before and after contrast media application with multi-parametric sequences. In 39% of patients late gadolinium enhancement (LGE) was found as a sign of myocarditis. Fibrinogen was statistically significantly higher in patients with LGE than in those without LGE, (4.3±0.23 vs 3.2±0.14g/L, p<0.05; respectively), as well as D-dimer (1.8±0.3 vs 0.8±0.1 mg/L FEU). Also troponin was statistically significantly higher in patients with myocardial LGE (13.1±0.4ng/L) compared to those with normal myocardium (4.9±0.3ng/L, p<0.001). We demonstrated chest pain, fatigue and elevated troponin to be independent predictors for LGE. Septal LGE was shown to be predictor for arrhythmias. The use of CMR is a potential risk stratification tool in evaluating outcomes following COVID-19 myocarditis.

Drones have been used in a variety of scenarios such as atmospheric monitoring, fire rescue, agricultural irrigation, etc., in which accurate environmental perception is of crucial importance for both decision-making and control. Among the drone sensors, the RGB camera is indispensable for capturing rich visual information for vehicle navigation but encounters a grand challenge in high-dynamic-range scenes that occur frequently in real applications. Specifically, the recorded frames suffer from under-exposure and over-exposure simultaneously and degenerate the successive vision tasks. To solve the problem, we take object tracking as an example and leverage the superior response of event cameras over a large intensity range to propose an event-assisted object tracking algorithm that can achieve reliable tracking under large intensity variations. Specifically, we propose to pursue feature matching from dense event signals, and based on which to (i) design a UNet-based image enhancement algorithm to balance the RGB intensity with the help of neighboring frames in the time domain, and then (ii) construct a dual-input tracking model to track the moving objects from intensity balanced RGB video and event sequence. The proposed approach is comprehensively validated in both simulation and real experiments.

The theory of fractional calculus extends the order of classical integer calculus from integer to non-integer. As a new engineering application tool, it has made many important research achievements in many fields, including image processing. This paper mainly studies the application of fractional calculus theory in image enhancement and denoising, including the basic theory of fractional calculus and its amplitude frequency characteristics, the application of fractional differential operator in image enhancement, and the application of fractional integral operator in image denoising. The experimental results show that the fractional calculus theory has more special advantages in image enhancement and denoising. Compared with the existing integer order image enhancement operators, the fractional differential operator can more effectively enhance the "weak edge" and "strong texture" details of the image. The fractional order integral image denoising operator can not only improve the signal-to-noise ratio of the image compared to traditional denoising methods, but also better preserve detailed information such as edges and textures of the image.

Due to the numerous heat sources in electronic equipment, the periodic nature of stream-wise flow occurs in a cooling channel so often, necessitating the development of an effective technique to improve the heat-cooling convection in such a situation. This paper investigates thermal convection enhancement in a heated-block duct through the periodic boundary conditions using the element-by-element (EBE) treatment in a semi-implicit projection finite element method (FEM) through preconditioned conjugate gradient (PCG) solver. This paper used the time-mean Nusselt number ratio, friction factor, and thermal performance to study how installing rectangular cylinders in the channel works with periodic boundary conditions varying Reynolds numbers (100, 175, and 250). The outcomes show that the rectangular cylinders installed stream-wise above an upstream block promote thermal convection in the heated-block duct. However, increasing the number of rectangular cylinders can raise friction factor. As a result, the case for periodic boundary conditions with a rectangular cylinder above every two blocks has the best thermal performance.

Fabry disease (FD) is a X-linked inheritable storage disease caused by deficiency of al-pha-galactosidase causing lysosomal overload of sphingolipids. FD cardiomyopathy is character-ized by left ventricular (LV) hypertrophy and should be considered in differential diagnosis with all the other causes of LV hypertrophy. An early diagnosis of FD is very important because the enzyme replacement therapy (ERT) may change the fate of patients by blocking both cardiac and systemic involvement and improving prognosis. Diagnosis may be relatively easy in young patients with the typical signs ans symptoms of FD, but in male patients with late onset of disease and in females, diagnosis may be very challenging. Morphological and functional aspects are not specific for FD, which cannot be diagnosed or excluded by echocardiography. Cardiac magnetic resonance (CMR) with tissue characterization capability, is the preferred technique for the differential diagnosis of LV hypertrophy. The finding of decreased myocardial T1 value in LV hypertrophy is very specific for FD. Late gadolinium enhancement (LGE) is found in late stage of disease but it is useful to predict the cardiac response to ERT and to stratify the prognosis.

Fog, haze, or smoke are usual atmospheric phenomena that dramatically compromise the overall visibility of any scene, critically affecting features such as illumination, contrast, and contour detection of objects. The decrease in visibility compromises the performance of computer vision algorithms such as pattern recognition and segmentation, some of them very relevant for decision-making for the security or autonomous vehicle industries. Several dehazing methods have been proposed, however, to the best of our knowledge, all proposed metrics compare the defogged image to its ground truth for evaluation of the defogging algorithms, or need to estimate parameters through physical models. This fact hinders progress in the field as obtaining proper ground truth images is costly and time-consuming, and physical parameters greatly depend on the scene conditions. This paper aims to tackle this issue by proposing a contour-based metric for image defogging evaluation that does not need a ground truth image. The proposed metric only requires the original hazy RGB image and the RGB image after the defogging procedure. A comparison of the proposed metric with metrics currently used in the NTIRE 2018 defogging challenge is performed to prove its effectiveness in a general situation, showing comparable results to conventional metrics.

The pulsating flow is one of the techniques which can enhance heat transfer, therefore leading to energy saving in tubular heat exchangers. This paper investigates the heat transfer and flow characteristics in a two-dimensional in-line tube bundle with the pulsating flow by a numerical method using the Ansys Fluent. Numerical simulation is performed for Reynolds number Re = 500 with different frequencies and amplitude of pulsation. Heat transfer enhancement was estimated from the central tube of the tube bundle. Pulsation velocity had an asymmetrical character with a reciprocating flow. The technique developed by the authors to obtain asymmetric pulsations was used. This technique allows simulating an asymmetric flow in heat exchangers equipped with a pulsation generation system. Increase in both the amplitude and the frequency of the pulsations has a significant effect on heat transfer enhancement. Heat transfer enhancement is mainly observed in the front and back of the cylinder. At a steady flow in these areas, heat transfer is minimal due to the weak circulation of the flow. The increase in heat transfer in the front and back of the cylinder is associated with increased velocity and additional flow mixing in these areas.

During the few years, various algorithms have been developed to extract features from high-resolution satellite imagery. For the classification of these extracted features, several complex algorithms have been developed. But these algorithms do not possess critical refining stages of processing the data at the preliminary phase. Various satellite sensors have been launched such as LISS3, IKONOS, QUICKBIRD, and WORLDVIEW etc. Before classification and extraction of semantic data, imagery of the high resolution must be refined. The whole refinement process involves several steps of interaction with the data. These steps are pre-processing algorithms that are presented in this paper. Pre-processing steps involves Geometric correction, radiometric correction, Noise removal, Image enhancement etc. Due to these pre-processing algorithms, the accuracy of the data is increased. Various applications of these pre-processing of the data are in meteorology, hydrology, soil science, forest, physical planning etc. This paper also provides a brief description of the local maximum likelihood method, fuzzy method, stretch method and pre-processing methods, which are used before classifying and extracting features from the image.

In this study, we analyzed the feasibility of various carbon neutrality methods based on the first principles of carbon sequestration, namely energy use efficiency and elemental stoichiometry. We believe that wood burial is the only currently feasible carbon neutrality method because this method has no theoretical uncertainties, can be implemented immediately on a large scale, has a long sequestration time, low cost, low technical requirements, and relatively little impact on agriculture.

In this study dual PET and contrast enhanced MRI were combined to investigate their correlation per voxel in patients at initial diagnosis with suspected glioblastoma. Correlation with contrast enhancement (CE) as an indicator of BBB leakage was further used to evaluate whether PET signal is likely caused by BBB disruption alone, or rather attributable to specific binding after BBB passage. PET images with [18F]GE180 and the amino acid [18F]FET were acquired and normalized to healthy background (TBR). Contrast enhanced images were normalized voxel by voxel with the pre-contrast T1-weighted MRI to generate relative CE values (rCE). Voxel-wise analysis revealed a high PET signal even within the sub-volumes without detectable CE. No to moderate correlation of rCE with TBR voxel-values and a small overlap as well as a larger distance of the hotspots delineated in rCE and TBR-PET images were detected. In contrast, voxel-wise correlation between both PET modalities was strong for most patients and hotspots showed a moderate overlap and distance. The high PET signal in tumor sub-volumes without CE observed in voxel-wise analysis as well as the discordant hotspots emphasize the specificity of the PET signals and the relevance of combined differential information from dual PET and MRI images.

Biomass is an attractive energy source that can be used for production of heat, power, and transport fuels, and when produced and used on a sustainable basis, can make a large contribution to reducing greenhouse gas (GHG) emissions. Anaerobic digestion (AD) is a suitable technology for reducing organic matter and generating bioenergy in the form of biogas. This study investigates the factors allowing the optimization of the process of biogas production from the co-digestion of wheat straw (WS) and bovine manure. The statistical analysis of the experiments carried out show that ultrasonic processing plays a fundamental role by sonication density and solids concentration leading to improved characteristics of WS by reducing particle size and increasing concentration of soluble chemical oxygen demand. The higher the sonicating power used, the more the waste particles are disrupted. The optimality obtained under mesophilic conditions for WS pretreated with 4% w/w (weight by weight) H2O2 at temperature 36 °C under 10 minutes of ultrasonication at 25 kHz improves the methane yield by 64%.

In the present study Aprepitant (APT) ternary solid dispersions (SDs) were developed and evaluated for the first time. Specifically, ternary SDs of APT with Poloxamer 188 and Soluplus^® (SOL) were prepared via melt mixing and compared to binary APT/Poloxamer 188 and APT/SOL SDs. Initially, combined thermo-gravimetric and hot-stage polarized light microscopy studies indicated that all tested compounds were thermally stable up to 280 °C, while Poloxamer 188 acted as a plasticizer to SOL by significantly reducing the temperature required to fully solubilize the API during SD preparation. Differential scanning calorimetry combined with wide angle X-ray diffraction studies showed that crystalline API was dispersed in both binary and ternary SDs, while Fourier transformation-infrared spectroscopy studies revealed no molecular interactions among the components. Scanning electron microscopy combined with EDAX element analysis showed that the API was dispersed in nano-scale within the polymer matrices, while increasing APT content led to increasing API nano-crystals within the SDs. Finally, dissolution studies showed that the prepared formulations enhanced dissolution of Aprepitant and its mechanism analysis was further studied. A mathematical model was also investigated to evaluate the drug release mechanism

The plate fin heat exchanger is the compact heat exchanger applied in many industries because of its high thermal performance. To enhance the heat transfer of plate fin heat exchanger in further, three new kinds of wavy plate fins, namely perforated wavy fin, staggered wavy fin and discontinuous wavy fin are proposed and investigated by CFD simulations. The effects of key design parameters, including that of waviness aspect ratios, perforation diameters, stagger ratios and breaking distance are investigated, respectively, with the Reynolds number changes from 500 to 4500. It is found that due to the swirl flow and efficient mixing of fluid, the perforation, serration and breaking techniques are beneficial for the enhancement of heat transfer compared to the traditional wavy fin. At the same time, serration is beneficial to reduce the friction factor, and the breaking technique can reduce heat transfer area as well as enhance heat transfer performance. Through the performance evaluation criteria, the staggered wavy fin has an advantage over the small waviness aspect ratio compared to the perforated wavy fin. The maximum performance evaluation criteria (PEC), as high as 1.24, can be obtained for the perforated wavy fin at the largest waviness aspect ratio.

A difficult open problem that has never been fully resolved in the literature to date is the behaviour of the (TDCDP) third approximation. As a giant step towards modern control theory, this cutting-edge paper will advance control theory and other relevant inter-disciplinary subjects. Because control theory is important in industry and engineering, this study will be especially beneficial to anyone working in these disciplines who wish to understand more about recent advances in control theory settings. In contrast, the wealth of applications of Fokker Planck Kolmogorov (FPK) equations numerous disciplines As a result, the study instantly gains more taste and credibility. At the end of the paper, there are several challenging open problems, some concluding remarks, and recommendations for further investigation.

Neuronal timing is critical for many brain functions such as perception and learning. At the level of the chemical synapse, the synaptic delay is determined by the presynaptic release probability (Pr) and the waveform of the presynaptic action potential (AP). Depolarization-induced analogue-digital facilitation (d-ADF) is a form of context-dependent synaptic facilitation that is induced by constant depolarization of the presynaptic neuron and is mediated by voltage inactivation of presynaptic Kv1 channels. Whether synaptic delay is modulated during d-ADF remains unclear. We show here that despite Pr is elevated during d-ADF at L5-L5 synapses, the synaptic delay is surprisingly unchanged, suggesting that both Pr- and AP-dependent changes in synaptic delay compensate for each other. We conclude that in contrast with other short- or long-term modulation of presynaptic release, timing is not affected during d-ADF because of the opposite interaction of Pr- and AP-dependent modulations of synaptic delay.

An exposition is undertaken to reveal the significant impact of the time-dependent root parameter, on the stability of Pointwise Stationary Fluid Flow Approximation (PSFFA) model of the non-stationary queueing system. This opens new grounds to stability analysis of non-stationary queueing systems. Potential PSFFA applications of IoT are highlighted.

Drought stress imposes substantial constraints on the growth and production of wheat (Triticum aestivum L.), a globally important cereal crop that is essential for food security. To mitigate these adverse effects, researchers are intensifying their efforts to comprehend how different genotypes respond to drought stress, aiding in the development of sustainable breeding and management strategies. This review summarized past and recent research on genotype-dependent responses of wheat to drought stress, encompassing morphological, physiological, biochemical, molecular, genetic, and epigenetic reactions in plants. Screening of drought-affected features at early developmental stages can provide valuable insights into the adult growth stages that are closely linked to plant productivity. The review underscores the importance of identifying key traits associated with drought resistance, and the potential of leveraging wheat diversity to select cultivars with desirable agronomic characteristics. It also highlights recent advancements in investigating Bulgarian wheat genotypes with varying levels of drought tolerance, specifically in detecting essential features contributing to drought tolerance. Cultivating drought-resistant wheat genotypes and understanding stress stability determinants could markedly contribute to enhancing wheat production and ensuring stable yields under changing climate conditions.

The dynamic response of a Bell-and-Bloom magnetometer to a parallel (to the bias field) time-dependent field is modelled beyond the commonly assumed quasi-static regime. The results unveil features that are related to the parametric nature of the considered system. It is shown that a for low-amplitude time-dependent field different operating conditions are possible and that, beside the commonly reported low-pass-filter behaviour, a band-pass response emerges. Moreover, we numerically show that for larger field amplitude the system, due to its parametric nature, has a kind of ``non-linear'' response.

Natural gas hydrate has gained significant attention in recent years. To safely and sustainably exploit the natural gas from gas hydrate-bearing sediments, it is crucial to understand the long-term mechanical characteristics of the hydrate reservoir. In this study, the influence of hydrate and fine particles on the strain rate dependence of hydrate-bearing sediments under plane strain conditions has been studied. The experimental results show that the strain rate dependency of the mechanical properties of hydrate-bearing sediments is positively correlated with hydrate saturation instead of the morphology of hydrate in sediments. The residual strength of hydrate-bearing sediments is primarily controlled by the hydrate saturation and is independent of the strain rate. Changes in hydrate saturation, and fines content, can affect the relationship between the strain rate and shear band angle. Finally, the local volumetric expansion effect of hydrate-bearing sediments without fines content is more significant and shows a strong strain rate dependence characteristic. Overall, this study provides valuable insights into the long-term mechanical characteristics of hydrate reservoirs. These insights can contribute to the development of a constitutive model of hydrate-bearing sediments with time-dependence in the future, and which is meaningful to the exploitation of natural gas hydrate.

Glioblastoma multiforme (GBM) is one of the deadliest cancers. Temozolomide (TMZ) is the most common chemotherapy used for GBM patients. Recently, combination chemotherapy strategies have more effective antitumor effects and focus on slowing down the development of chemotherapy resistance. A combination of TMZ and cholesterol lowering medications (statins) is currently under investigation in in vivo and clinical trials. In our current investigation, we have used a triple combination therapy of TMZ, Simvastatin (Simva), and Acetylshikonin (ASH) and investigated its apoptotic mechanism in GBM cell lines (U87 and U251). We used viability, apoptosis, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), caspase-3/-7, acridine orange (AO) and immunoblotting autophagy assays. Our results showed that TMZ/Simva/ASH combination therapy significantly induced more apoptosis compared to TMZ, Simva, ASH, and TMZ/Simva treatments in GBM cells. Apoptosis via TMZ/Simva/ASH treatment induced mitochondrial damage (increase of ROS, decrease of MMP) and induced caspase-3/7 activation in both GBM cell lines. Compared to all single treatments and the TMZ/Simva treatment, TMZ/Simva/ASH significantly increased positive acidic vacuole organelles. We further confirmed that the increase of AVOs during the TMZ/Simva/ASH treatment was due to partial inhibition of autophagy flux (accumulation of LC3β-II and decrease in p62 degradation) in GBM cells. Our investigation also showed that TMZ/Simva/ASH-induced cell death was depended on autophagy flux as further inhibition of autophagy flux increased TMZ/Simva/ASH-induced cell death in GBM cells. Finally, our results showed that TMZ/Simva/ASH treatment potentially depends on an increase of Bax expression in GBM cells. Our current investigation might open new avenues for more effective treatment of GBM but further investigations are required for better identification of the mechanisms.