ADU-Net: An Attention Dense U-Net based deep supervised DNN for automated lesion segmentation of COVID-19 from chest CT images.

An automatic method for qualitative and quantitative evaluation of chest Computed Tomography (CT) images is essential for diagnosing COVID-19 patients. We aim to develop an automated COVID-19 prediction framework using deep learning. We put forth a novel Deep Neural Network (DNN) composed of an attention-based dense U-Net with deep supervision for COVID-19 lung lesion segmentation from chest CT images. We incorporate dense U-Net where convolution kernel size 5×5 is used instead of 3×3. The dense and transition blocks are introduced to implement a densely connected network on each encoder level. Also, the attention mechanism is applied between the encoder, skip connection, and decoder. These are used to keep both the high and low-level features efficiently. The deep supervision mechanism creates secondary segmentation maps from the features. Deep supervision combines secondary supervision maps from various resolution levels and produces a better final segmentation map. The trained artificial DNN model takes the test data at its input and generates a prediction output for COVID-19 lesion segmentation. The proposed model has been applied to the MedSeg COVID-19 chest CT segmentation dataset. Data pre-processing methods help the training process and improve performance. We compare the performance of the proposed DNN model with state-of-the-art models by computing the well-known metrics: dice coefficient, Jaccard coefficient, accuracy, specificity, sensitivity, and precision. As a result, the proposed model outperforms the state-of-the-art models. This new model may be considered an efficient automated screening system for COVID-19 diagnosis and can potentially improve patient health care and management system.

Evaluation of drug carrier hepatotoxicity using primary cell culture models.

This study aims to establish a primary rat hepatocyte culture model to evaluate dose-dependent hepatotoxic effects of drug carriers (lipopolymer nanoparticles; LPNs) temporal. Primary rat hepatocyte cell cultures were used to determine half-maximal Inhibition Concentrations (IC50) of the drug-carrier library. Drug-carrier library, at concentrations <50 µg/mL, is benign to primary rat hepatocytes as determined using albumin and urea secretions. Albumin, as a hepatic biomarker, exhibited a more sensitive and faster outcome, compared to urea, for the determination of the IC50 value of LPNs. Temporal measurements of hepatic biomarkers including urea and albumin, and rigorous physicochemical (hydrodynamic diameter, surface charge, etc.) characterization, should be combined to evaluate the hepatotoxicity of drug carrier libraries in screens.

Versatile Detection and Monitoring of Ionizing Radiation Treatment Using Radiation-Responsive Gel Nanosensors.

Modern radiation therapy workflow involves complex processes intended to maximize the radiation dose delivered to tumors while simultaneously minimizing excess radiation to normal tissues. Safe and accurate delivery of radiation doses is critical to the successful execution of these treatment plans and effective treatment outcomes. Given extensive differences in existing dosimeters, the choice of devices and technologies for detecting biologically relevant doses of radiation has to be made judiciously, taking into account anatomical considerations and modality of treatment (invasive, e.g., interstitial brachytherapy vs noninvasive, e.g., external-beam therapy radiotherapy). Rapid advances in versatile radiation delivery technologies necessitate new detection platforms and devices that are readily adaptable into a multitude of form factors in order to ensure precision and safety in dose delivery. Here, we demonstrate the adaptability of radiation-responsive gel nanosensors as a platform technology for detecting ionizing radiation using three different form factors with an eye toward versatile use in the clinic. In this approach, ionizing radiation results in the reduction of monovalent gold salts leading to the formation of gold nanoparticles within gels formulated in different morphologies including one-dimensional (1D) needles for interstitial brachytherapy, two-dimensional (2D) area inserts for skin brachytherapy, and three-dimensional (3D) volumetric dose distribution in tissue phantoms. The formation of gold nanoparticles can be detected using distinct but complementary modes of readout including optical (visual) and photothermal detection, which further enhances the versatility of this approach. A linear response in the readout was seen as a function of radiation dose, which enabled straightforward calibration of each of these devices for predicting unknown doses of therapeutic relevance. Taken together, these results indicate that the gel nanosensor technology can be used to detect ionizing radiation in different morphologies and using different detection methods for application in treatment planning, delivery, and verification in radiotherapy and in trauma care.

Study of epidemiological behaviour of malaria and its control in the Purulia district of West Bengal, India (2016-2020).

Purulia is a malaria-prone district in West Bengal, India, with approximately half of the blocks defined as malaria endemic. We analyzed the malaria case in each block of the Purulia district from January 1, 2016, to December 31, 2020. As per the API, 20 blocks of Purulia were assigned to four different categories (0-3) and mapped using ArcGIS software. An exponential decay model was fitted to forecast the trend of malaria cases for each block of Purulia (2021-2025). There was a sharp decrease in total malaria cases and API from 2016 to 2020 due to the mass distribution of LLINs. The majority of cases (72.63%) were found in ≥ 15-year age group. Males were more prone to malaria (60.09%). Malaria was highly prevalent among Scheduled Tribes (48.44%). Six blocks were reported in Category 3 (high risk) and none in Category 0 (no risk) in 2016, while no blocks were determined to be in Category 3, and three blocks were in Category 0 in 2020. The exponential decay model prediction is oriented towards gaining malaria-free status in thirteen blocks of Purulia by 2025. This study will incite the government to uphold and strengthen the current efforts to meet the malaria elimination goals.

Radiation-Responsive Amino Acid Nanosensor Gel (RANG) for Radiotherapy Monitoring and Trauma Care.

Accurate detection of doses is critical for the development of effective countermeasures and patient stratification strategies in cases of accidental exposure to ionizing radiation. Existing detection devices are limited by high fabrication costs, long processing times, need for sophisticated detection systems, and/or loss of readout signal over time, particularly in complex environments. Here, we describe fundamental studies on amino acid-facilitated templating of gold nanoparticles following exposure to ionizing radiation as a new colorimetric approach for radiation detection. Tryptophan demonstrated spontaneous nanoparticle formation, and parallel screening of a library of amino acids and related compounds led to the identification of lead candidates, including phenylalanine, which demonstrated an increase in absorbance at wavelengths typical of gold nanoparticles in the presence of ionizing radiation (X-rays). Evaluation of screening, i.e., absorbance data, in concert with chemical informatics modeling led to the elucidation of physicochemical properties, particularly polarizable regions and partial charges, that governed nanoparticle formation propensities upon exposure of amino acids to ionizing radiation. NMR spectroscopy revealed key roles of amino and carboxy moieties in determining the nanoparticle formation propensity of phenylalanine, a lead amino acid from the screen. These findings were employed for fabricating radiation-responsive amino acid nanosensor gels (RANGs) based on phenylalanine and tryptophan, and efficacy of RANGs was demonstrated for predicting clinical doses of ionizing radiation in anthropomorphic thorax phantoms and in live canine patients undergoing radiotherapy. The use of biocompatible templating ligands (amino acids), rapid response, simplicity of fabrication, efficacy, ease of operation and detection, and long-lasting readout indicate several advantages of the RANG over existing detection systems for monitoring radiation in clinical radiotherapy, radiological emergencies, and trauma care.

A library of aminoglycoside-derived lipopolymer nanoparticles for delivery of small molecules and nucleic acids.

Simultaneous delivery of small molecules and nucleic acids using a single vehicle can lead to novel combination treatments and multifunctional carriers for a variety of diseases. In this study, we report a novel library of aminoglycoside-derived lipopolymers nanoparticles (LPNs) for the simultaneous delivery of different molecular cargoes including nucleic acids and small-molecules. The LPN library was screened for transgene expression efficacy following delivery of plasmid DNA, and lead LPNs that showed high transgene expression efficacies were characterized using hydrodynamic size, zeta potential, 1H NMR and FT-IR spectroscopy, and transmission electron microscopy. LPNs demonstrated significantly higher efficacies for transgene expression than 25 kDa polyethyleneamine (PEI) and lipofectamine, including in presence of serum. Self-assembly of these cationic lipopolymers into nanoparticles also facilitated the delivery of small molecule drugs (e.g. doxorubicin) to cancer cells. LPNs were also employed for the simultaneous delivery of the small-molecule histone deacetylase (HDAC) inhibitor AR-42 together with plasmid DNA to cancer cells as a combination treatment approach for enhancing transgene expression. Taken together, our results indicate that aminoglycoside-derived LPNs are attractive vehicles for simultaneous delivery of imaging agents or chemotherapeutic drugs together with nucleic acids for different applications in medicine and biotechnology.

PolyRad - Protection Against Free Radical Damage.

The effects of elevated levels of radiation contribute to the instability of pharmaceutical formulations in space compared to those on earth. Existing technologies are ineffective at maintaining the therapeutic efficacies of drugs in space. Thus, there is an urgent need to develop novel space-hardy formulations for preserving the stability and efficacy of drug formulations. This work aims to develop a novel approach for the protection of space pharmaceutical drug molecules from the radiation-induced damage to help extend or at least preserve their structural integrity and potency. To achieve this, free radical scavenging antioxidant, Trolox was conjugated on the surface of poly-lactic-co-glycolic acid (PLGA) nanoparticles for the protection of a candidate drug, melatonin that is used as a sleep aid medication in International Space Station (ISS). Melatonin-PLGA-PLL-Trolox nanoparticle as named as PolyRad was synthesized employing single oil in water (o/w) emulsion solvent evaporation method. PolyRad is spherical in shape and has an average diameter of ~600 nm with a low polydispersity index of 0.2. PolyRad and free melatonin (control) were irradiated by UV light after being exposed to a strong oxidant, hydrogen peroxide (H2O2). Bare melatonin lost ~80% of the active structure of the drug following irradiation with UV light or treatment with H2O2. In contrast, PolyRad protected >80% of the active structure of melatonin. The ability of PolyRad to protect melatonin structure was also carried out using 0, 1, 5 and 10 Gy gamma radiation. Gamma irradiation showed >98% active structures of melatonin encapsulated in PolyRads. Drug release and effectiveness of melatonin using PolyRad were evaluated on human umbilical vein endothelial cells (HUVEC) in vitro. Non-irradiated PolyRad demonstrated maximum drug release of ~70% after 72 h, while UV-irradiated and H2O2-treated PolyRad showed a maximum drug release of ~85%. Cytotoxicity of melatonin was carried out using both live/dead and MTT assays. Melatonin, non-radiated PolyRad and irradiated PolyRad inhibited the viability of HUVEC in a dose-dependent manner. Cell viability of melatonin, PolyRad alone without melatonin (PolyRad carrier control), non-radiated PolyRad, and irradiated PolyRad were ~98, 87, 75 and 70%, respectively at a concentration [Formula: see text] 0.01 [Formula: see text] ([Formula: see text]). Taken together, PolyRad nanoparticle provides an attractive formulation platform for preventing damage to pharmaceutical drugs in potential space mission applications.

Metabolite releasing polymers control dendritic cell function by modulating their energy metabolism.

Metabolites control immune cell functions, and delivery of these metabolites in a sustained manner may be able to modulate function of the immune cells. In this study, alpha-ketoglutarate (aKG) and diol based polymeric-microparticles (termed paKG MPs) were synthesized to provide sustained release of aKG and promote an immunosuppressive cellular phenotype. Notably, after association with dendritic cells (DCs), paKG MPs modulated the intracellular metabolic-profile/pathways, and decreased glycolysis and mitochondrial respiration in vitro. These metabolic changes resulted in modulation of MHC-II, CD86 expression in DCs, and altered the frequency of regulatory T cells (Tregs), and T-helper type-1/2/17 cells in vitro. This unique strategy of intracellular delivery of key-metabolites in a sustained manner provides a new direction in immunometabolism field-based immunotherapy with potential applications in different diseases associated with immune disorders.

Plasmonic gel nanocomposites for detection of high energy electrons.

Radiation therapy is a common treatment modality employed in the treatment of cancer. High energy photons are the primary source of radiation but when administered, they leave an exit dose resulting in radiation damage to the adjacent healthy tissues. To overcome this, high energy electrons are employed in cases of skin cancer to minimize radiation induced toxicity. Despite these advances, measurement of delivered radiation remains a challenge due to limitations with existing dosimeters including labor intensive fabrication, complex read-out techniques and post-irradiation instability. To overcome these limitations, we have developed a novel colorimetric plasmonic gel nanocomposite for the detection of therapeutic levels of radiation delivered in electron beam therapy. The plasmonic nanocomposite consists of an agarose gel matrix encapsulating precursor gold ions, which are reduced to gold nanoparticles as a result of exposure to high energy electrons. The formation of gold nanoparticles renders a change in color to the agarose matrix, resulting in the formation of plasmonic gel nanocomposites. The intensity of the color formed exhibits a linear relation with the delivered electron dose, which can be quantified using absorbance spectroscopy. The plasmonic gel nanocomposites were able to detect doses employed in fractionated electron therapy, including in an anthropomorphic phantom used for planning radiation treatments in the clinic. Furthermore, the use of glutathione as a quenching agent facilitated qualitative and quantitative spatial mapping of the delivered dose. Our results indicate that the ease of fabrication, simplicity of detection and quantification using absorbance spectroscopy, determination of spatial dose profiles, and relatively low cost make the plasmonic gel nanocomposite technology attractive for detecting electron doses in the clinic.

Determination of topographical radiation dose profiles using gel nanosensors.

Despite the emergence of sophisticated technologies in treatment planning and administration, routine determination of delivered radiation doses remains a challenge due to limitations associated with conventional dosimeters. Here, we describe a gel-based nanosensor for the colorimetric detection and quantification of topographical radiation dose profiles in radiotherapy. Exposure to ionizing radiation results in the conversion of gold ions in the gel to gold nanoparticles, which render a visual change in color in the gel due to their plasmonic properties. The intensity of color formed in the gel was used as a quantitative reporter of ionizing radiation. The gel nanosensor was used to detect complex topographical dose patterns including those administered to an anthropomorphic phantom and live canine patients undergoing clinical radiotherapy. The ease of fabrication, operation, rapid readout, colorimetric detection, and relatively low cost illustrate the translational potential of this technology for topographical dose mapping in radiotherapy applications in the clinic.

Effect of feed supplementation with biosynthesized silver nanoparticles using leaf extract of Morus indica L. V1 on Bombyx mori L. (Lepidoptera: Bombycidae).

Herein, we report the synthesis of silver nanoparticles (AgNPs) by a green route using the aqueous leaf extract of Morus indica L. V1. The synthesized AgNPs exhibited maximum UV-Vis absorbance at 460 nm due to surface plasmon resonance. The average diameter (~54 nm) of AgNPs was measured from HR-TEM analysis. EDX spectra also supported the formation of AgNPs, and negative zeta potential value (-14 mV) suggested its stability. Moreover, a shift in the carbonyl stretching (from 1639 cm-1 to 1630 cm-1) was noted in the FT-IR spectra of leaf extract after AgNPs synthesis which confirm the role of natural products present in leaves for the conversion of silver ions to AgNPs. The four bright circular rings (111), (200), (220) and (311) observed in the selected area electron diffraction pattern are the characteristic reflections of face centered cubic crystalline silver. LC-MS/MS study revealed the presence of phytochemicals in the leaf extract which is responsible for the reduction of silver ions. MTT assay was performed to investigate the cytotoxicity of AgNPs against two human cell lines, namely HepG2 and WRL-68. The antibacterial study revealed that MIC value of the synthesized AgNPs was 80 µg/ml against Escherichia coli K12 and Staphylococcus aureus (MTCC 96). Finally, the synthesized AgNPs at 10 µg/ml dosages showed beneficial effects on the survivability, body weights of the Bombyx mori L. larvae, pupae, cocoons and shells weights via enhancing the feed efficacy.