Infrared spectroscopy of isomers of C3H4+ in superfluid helium droplets.

Superfluid helium nanodroplets are unique nanomatrices for the isolation and study of transient molecular species, such as radicals, carbenes, and ions. In this work, isomers of C3H4+ were produced upon electron ionization of propyne and allene molecules and interrogated via infrared spectroscopy inside He nanodroplet matrices. It was found that the spectrum of C3H4+ has at least three distinct groups of bands. The relative intensities of the bands depend on the precursor employed and its pickup pressure, which indicates the presence of at least three different isomers. Two isomers were identified as allene and propyne radical cations. The third isomer, which has several new bands in the range of 3100-3200 cm-1, may be the elusive vinylmethylene H2C=CH-CH+ radical cation. The observed bands for the allene and propyne cations are in good agreement with the results of density functional theory calculations. However, there is only moderate agreement between the new bands and the theoretically calculated vinylmethylene spectrum, which indicates more work is necessary to unambiguously assign it.

Photo-Induced Generation of Oxygenated Quaternary Centers via EnT Enabled Singlet O2 Addition to C3-Maleimidated Quinoxaline: A Reagent-Less Approach.

Demonstrated here is an external photo-sensitizer-free (auto-sensitized) singlet oxygen-enabled solvent-dependent tertiary hydroxylation and aryl-alkyl spiro-etherification of C3-maleimidated quinoxalines. Such "reagent-less" photo-oxygenation at Csp3-H and etherification involving Csp3-H/Csp2-H are unparalleled. Possibly, the highly π-conjugated N-H tautomer allows the substrate to get excited by irradiation, and subsequently, it attains the triplet state via ISC. This excited triplet-state sensitized molecule then transfers its energy to a triplet-state oxygen (3O2) generating reactive singlet oxygen (1O2) for hydroxylation and spirocyclization depending on the solvent used. In HFIP, the generated alkoxy radical accepts a proton via HAT giving hydroxylated product. In contrast, in an aprotic PhCl it underwent a radical addition at the ortho-position of the C2 aryl to provide spiro-ether. An unprecedented orthogonal spiro-etherification was observed via the displacement of o-substitutents for ortho (-OEt, -OMe, -F, -Cl, -Br) substituted substrates. The order of ipso substitution follows the trend -OMe>-OEt>-F>-H>-Cl>-Br. Both these oxygenation reactions can be carried out with nearly equal ease using direct sunlight without the requirement of any elaborate reaction setup. Demonstration of large-scale synthesis and a few interesting transformations have also been realized. Furthermore, several insightful control experiments and quantum chemical computations were performed to unravel the mechanism.

Feasibility of Achieving Dose Constraints for Dysphagia Aspiration-Related Structures and Its Clinical Significance in Intensity-Modulated Radiotherapy Planning of Head and Neck Cancer.

Introduction Dysphagia is commonly seen in patients with head and neck cancers after undergoing chemoradiotherapy and is often under-reported and also not given clinical importance. The quality of life of the patients can be significantly improved if the required dose constraints to the dysphagia aspiration-related structures (DARS) are achieved. The present study was conducted in order to determine the feasibility of achieving the dose constraints to DARS between the standard intensity-modulated radiotherapy (st-IMRT) arm and the dysphagia-optimized IMRT (do-IMRT) arm. Material and methods Sixty patients with head and neck cancer were recruited and randomized into two groups: In one group called the st-IMRT, constraints were not given to DARS, and in the other group called the do-IMRT, constraints were given to DARS. Treatment was given in the form of chemoradiation with a dose of 70 Gy in 35 fractions by IMRT technique, over seven weeks, 2 Gy per fraction along with weekly concurrent Cisplatin (35 mg/m2) in both the groups. Step and shoot IMRT setup was used for planning, and the system used for planning was Eclipse 13.6 (Varian Medical System, Inc., Palo Alto, CA, US); progressive resolution optimizer algorithm was used for optimization, and Anisotropic Analytical Algorithm algorithm was used for dose calculation. Truebeam was used for treatment delivery. DARS dosimetric parameters assessed were Dmean, V30, V50, V60, V70, D50, and D80. Radiation-induced toxicities to the skin, mucosa, larynx, salivary gland, and dysphagia and hematological toxicities were assessed in between both the groups during and after radiotherapy up to six months based on Common Terminology Criteria for Adverse Effects v5.0. p-values were calculated using the unpaired T-test. Results In the cohort of 60 patients with head and neck cancers, 95% were males. Dosimetric parameters of the planning target volume (PTV) were compared but were not found to be significant. In the dosimetry of the organs at risk, a p-value of some structures was found to be significant although the doses received were well within the tolerable limits in both arms. DARS dosimetry V60 and V70 of the inferior constrictor muscle was found to be statistically significant (p=0.01 and 0.008, respectively). V60 and V70 of larynx were also statistically significant (p=0.009 and 0.000, respectively). V70 and D50 of cricopharyngeus were found to be statistically significant (p=0.01 and 0.03, respectively), V30 and V60 for combined pharyngeal constrictor muscles were found to be statistically significant (p=0.02 and 0.01), and lastly, V60 for combined DARS was also significant (p=0.004). Post-treatment 33.3% of patients in the st-IMRT arm required Ryle's tube placement. No grade 4 toxicities were seen in either arm regarding hematological toxicities, acute or chronic radiation-induced toxicities. In site-wise comparison of doses, the p-value was not found to be significant in patients with oropharyngeal and oral cavity carcinomas but was found to be statistically significant in the larynx and hypopharynx subsites. Conclusion The feasibility of achieving dose constraints to the DARS was seen in cases of laryngeal and hypopharyngeal cancers where the constrictor muscles were at a distance from the PTV. Further, the feasibility of achieving dose constraints may be seen in lower-dose prescriptions either in postoperative cases or in low-risk clinical target volume nodal volumes.

GIFNet: an effective global infection feature network for automatic COVID-19 lung lesions segmentation.

The ongoing COronaVIrus Disease 2019 (COVID-19) pandemic carried by the SARS-CoV-2 virus spread worldwide in early 2019, bringing about an existential health catastrophe. Automatic segmentation of infected lungs from COVID-19 X-ray and computer tomography (CT) images helps to generate a quantitative approach for treatment and diagnosis. The multi-class information about the infected lung is often obtained from the patient's CT dataset. However, the main challenge is the extensive range of infected features and lack of contrast between infected and normal areas. To resolve these issues, a novel Global Infection Feature Network (GIFNet)-based Unet with ResNet50 model is proposed for segmenting the locations of COVID-19 lung infections. The Unet layers have been used to extract the features from input images and select the region of interest (ROI) by using the ResNet50 technique for training it faster. Moreover, integrating the pooling layer into the atrous spatial pyramid pooling (ASPP) mechanism in the bottleneck helps for better feature selection and handles scale variation during training. Furthermore, the partial differential equation (PDE) approach is used to enhance the image quality and intensity value for particular ROI boundary edges in the COVID-19 images. The proposed scheme has been validated on two datasets, namely the SARS-CoV-2 CT scan and COVIDx-19, for detecting infected lung segmentation (ILS). The experimental findings have been subjected to a comprehensive analysis using various evaluation metrics, including accuracy (ACC), area under curve (AUC), recall (REC), specificity (SPE), dice similarity coefficient (DSC), mean absolute error (MAE), precision (PRE), and mean squared error (MSE) to ensure rigorous validation. The results demonstrate the superior performance of the proposed system compared to the state-of-the-art (SOTA) segmentation models on both X-ray and CT datasets.

Super-hydrophilic LaCoO3/g-C3N4 nanocomposite coated beauty sponge for solar-driven seawater desalination with simultaneous volatile organic compound removal.

Interfacial solar steam generation (ISSG) is emerging as a promising, environment-friendly solution for fulfilling freshwater and energy demands. However, a critical challenge for ISSG lies in the presence of harmful volatile organic compounds (VOCs) in the feedwater which are co-evaporated with water, leading to more enriched concentration in condensed water. Herein, lanthanum cobaltate-graphitic carbon nitride (LaCoO3/g-C3N4, LCO/g-CN) nanocomposite decorated beauty sponge (LCO/g-CN@BS) is proposed as an efficient photothermal/photocatalytic material for solar-driven seawater desalination and simultaneous VOC degradation. The hydrophobic surface of the beauty sponge after LCO/g-CN coating becomes super-hydrophilic, ensuring sufficient water supply and our LCO/g-CN@BS delivers an evaporation rate of 1.94 kg m-2 h-1 under 1 sun irradiation. This LCO/g-CN@BS shows excellent seawater desalination capacity with a self-cleaning ability when employed for saltwater purification for a salt (NaCl) concentration as high as 15 wt%. Moreover, fast photocarrier transfer between LCO and g-CN leads to enhanced photocatalytic degradation of over 90% of phenol simultaneously, which is about 60% for only an LCO-based beauty sponge. This work presents a promising approach to combining novel nanocomposites with microporous structures for efficient solar desalination, offering simultaneous VOC degradation.

Analysis of the Efficacy of Elastography in Comparison with Dynamic Renal Nuclear Scintigraphy in the Evaluation of Unilateral Pelvi-Ureteric Junction Obstruction.

INTRODUCTION: In hydronephrosis due to pelviureteric junction obstruction (PUJO), an obstruction to urine flow may lead to increased pelvic pressure, which may cause interstitial fibrosis and renal impairment. Recently, there have been reports on renal pelvic assessment using ultrasound elastography (USE). This study was conducted to see if USE can evaluate PUJO and if it can be correlated to the findings of the dynamic renal nuclear scan. MATERIAL AND METHODS: In this observational study, only patients with unilateral PUJO underwent acoustic radiation force impulse (ARFI) elastography. A rectangular region of interest (ROI) measuring 5 × 10 mm was positioned on the cortex region of the upper, mid, and lower poles of the affected kidney. Three valid measurements were obtained, from which a mean value was calculated. A dynamic renal nuclear scan using Technetium-99m ethylene dicysteine (EC or TC99 m EC) was obtained and split renal function (SRF) was used for comparison. RESULTS: In the group of 20 patients, the mean age was 3.37 years. The mean SRF of the affected kidney was 26.65 %, and the corresponding USE value was 0.45 kpa. The Spearman's rho correlation coefficient for SRF and USE was 1 and 0.672, respectively (p = 0.001). Elastography was not feasible if SRF was less than 20 %. CONCLUSION: USE may be able to comment on the renal functional status of hydronephrosis. If USE is reported as non-feasible, it may suggest that renal function is grossly compromised. It may serve as an alternative diagnostic modality for renal functional evaluation. LEVEL OF EVIDENCE: Level II, Prospective Cohort Study.

Advancing Vaccine Strategies against Candida Infections: Exploring New Frontiers.

Candida albicans, along with several non-albicans Candida species, comprise a prominent fungal pathogen in humans, leading to candidiasis in various organs. The global impact of candidiasis in terms of disease burden, suffering, and fatalities is alarmingly high, making it a pressing global healthcare concern. Current treatment options rely on antifungal drugs such as azoles, polyenes, and echinocandins but are delimited due to the emergence of drug-resistant strains and associated adverse effects. The current review highlights the striking absence of a licensed antifungal vaccine for human use and the urgent need to shift our focus toward developing an anti-Candida vaccine. A number of factors affect the development of vaccines against fungal infections, including the host, intraspecies and interspecies antigenic variations, and hence, a lack of commercial interest. In addition, individuals with a high risk of fungal infection tend to be immunocompromised, so they are less likely to respond to inactivated or subunit whole organisms. Therefore, it is pertinent to discover newer and novel alternative strategies to develop safe and effective vaccines against fungal infections. This review article provides an overview of current vaccination strategies (live attenuated, whole-cell killed, subunit, conjugate, and oral vaccine), including their preclinical and clinical data on efficacy and safety. We also discuss the mechanisms of immune protection against candidiasis, including the role of innate and adaptive immunity and potential biomarkers of protection. Challenges, solutions, and future directions in vaccine development, namely, exploring novel adjuvants, harnessing the trained immunity, and utilizing immunoinformatics approaches for vaccine design and development, are also discussed. This review concludes with a summary of key findings, their implications for clinical practice and public health, and a call to action for continued investment in candidiasis vaccine research.

Advances in optical and electrochemical sensing of bisphenol a (BPA) utilizing microfluidic Technology: A mini perspective.

Continuous exposure to toxic pollutants highlights the need for sensitive detection technologies that can be rapidly applied in the current world for quick screening of real samples. Bisphenol A (BPA) is one of the most common environmental contaminants, and it has the potential to harm both the environment and human health, notably causing reproductive disorders, cancer, heart disease, infertility, mental disorders, etc. Thus, significant attention has been paid to the detection of BPA and microplastics to promote food safety, environmental health, and human health on a sustainable earth. Among the current technologies, microfluidic based systems have garnered a lot of interest as future diagnostic tools for healthcare applications. Microfluidic devices can be deployed for quick screening and real-time monitoring, with inherent advantages like portability, miniaturisation, highly sensing tool and ease of integration with various detection systems. Optical and electrochemical sensors are two major analytical tools found in almost all microfluidic-based devices for ultrasensitive BPA and microplastics determination. In this review, we have evaluated and discussed microfluidic-based detection methods for BPA and microplastics.

Artificial Intelligence in Gynaecological Malignancies: Perspectives of a Clinical Oncologist.

Gynecological malignancies are treated with a multi-disciplinary approach. There are two important factors, the stage and Karnofsky performance status scale (KPS) of patients, which guide the treatment strategy by single or multiple modalities in terms of surgery, radiotherapy, or chemotherapy. Various aspects are included in the workflow of gynecological malignancies, like screening, diagnosis in each individual, treatment modalities, and finally, follow-up to see for outcomes leading to the development of new research protocols. The quality data plays an important role in every step. Artificial Intelligence (AI) will play an important role if it is developed in the above-mentioned steps. AI is already established partially in every aspect of the management of gynecological cancer. It needs to be strengthened and incorporated further in a more robust form. This needs an association between clinicians, software engineers, and stakeholders. This article reviews the role of AI in various steps of the workflow of gynecological malignancies and discusses a few clinical aspects that may be researched to find solutions by AI.

Microcomputed Tomography for the Microstructure Evaluation of 3D Bioprinted Scaffolds.

This study implemented the application of microcomputed tomography (micro-CT) as a characterization technique for the study and investigation of the microstructure of 3D scaffold structures produced via three-dimensional bioprinting (3DBP). The study focused on the preparation, characterization, and cytotoxicity analysis of gold nanoparticles (Au-NPs) incorporated into 3DBP hydrogels for micro-CT evaluation. The Au-NPs were characterized by using various techniques, including UV-vis spectrometry, dynamic light scattering (DLS), zeta potential measurement, and transmission electron microscopy (TEM). The characterization results confirmed the successful coating of the Au-NPs with 2 kDa methoxy-PEG and revealed their spherical shape with a mean core diameter of 66 nm. Cytotoxicity analysis using live-dead fluorescent microscopy indicated that all tested Au-NP solutions were nontoxic to AC16 cardiomyocytes in both 2D and 3D culture conditions. Scanning electron microscopy (SEM) showed distinguishable differences in image contrast and intensity between samples with and without Au-NPs, with high concentrations of Au-NPs displaying nanoparticle aggregates. Micro-CT imaging demonstrated that scaffolds containing Au-NPs depicted enhanced imaging resolution and quality, allowing for visualization of the microstructure. The 3D reconstruction of scaffold structures from micro-CT imaging using Dragonfly software further supported the improved visualization. Mechanical analysis revealed that the addition of Au-NPs enhanced the mechanical properties of acellular scaffolds, including their elastic moduli and complex viscosity, but the presence of cells led to biodegradation and reduced mechanical strength. These findings highlight the successful preparation and characterization of Au-NPs, their nontoxic nature in both 2D and 3D culture conditions, their influence on imaging quality, and the impact on the mechanical properties of 3D-printed hydrogels. These results contribute to the development of functional and biocompatible materials for tissue engineering and regenerative medicine applications.

Synergistic Combination of Letrozole and Berberine in Ascorbic Acid-Stabilized AuNPs: A Promising Solution for Breast Cancer.

Breast cancer is a deadly disease that affects countless women worldwide. The most conventional treatments for breast cancer, such as the administration of anticancer medications such as letrozole (LTZ), pose significant barriers due to the non-selective delivery and low bioavailability of cytotoxic drugs leading to serious adverse effects and multidrug resistance (MDR). Addressing these obstacles requires an innovative approach, and we propose a combined strategy that synergistically incorporates LTZ with berberine (BBR) into stabilised AuNPs coated with ascorbic acid (AA), known as LTZ-BBR@AA-AuNPs. The LTZ-BBR@AA-AuNPs, a novel combined drug delivery system, were carefully designed to maximise the entrapment of both LTZ and BBR. The resulting spherical nanoparticles exhibited remarkable efficiency in trapping these two compounds, with rates of 58% and 54%, respectively. In particular, the average hydrodynamic diameter of these nanoparticles was determined to be 81.23 ± 4.0 nm with a PDI value of only 0.286, indicating excellent uniformity between them. Furthermore, their zeta potential was observed to be -14.5 mV, suggesting high stability even under physiological conditions. The release profiles showed that after being incubated for about 24 h at pH levels ranging from acidic (pH = 5) to basic (pH = 7), the percentage released for both drugs ranged from 56-72%. This sustained and controlled drug release can reduce any negative side effects while improving therapeutic efficacy when administered directly to cancer. MDA-MB-231 cells treated with LTZ-BBR@AA-AuNPs for 48 h exhibited IC50 values of 2.04 ± 0.011 µg/mL, indicating potent cytotoxicity against cells. Furthermore, the nanoparticles demonstrated excellent stability throughout the duration of the treatment.

Photochemistry of 2-Iodobenzothiazole and Iodine-Triggered 2-Isocyanophenylthiyl Radical Cyclization in Argon Matrices.

The photochemistry of 2-iodobenzothiazole (IBT) was investigated in an argon matrix at 4 K. Irradiating matrix-isolated IBT at λ = 254 nm led to the formation of 2-isocyanophenylthiyl radical 3 and benzothiirene 4; surprisingly, the 2-dehydrobenzothiazole radical 1 was not detected. A subsequent 365 nm irradiation or annealing of matrix containing 3 and iodine atom (at 30 K) reverted the precursor IBT, indicating an iodine-triggered thiyl radical-based cyclization, which was confirmed by computations using density functional theory. For gaining mechanistic insights, similar investigations were performed using benzothiazole BT as a precursor. Once again, the 254 nm light-induced C-S scission accompanied by H-shift led to 2-isocyanothiophenol 7. A conformational analysis of 2-isocyanothiophenol 7 and its photochemistry was also carried out with the help of IR spectroscopy under cryogenic conditions and computations. Considering the importance of thiyl radicals in biomolecular pathways, the investigations on its photochemical generation and a rare, reversible phenomenon of iodine-mediated cyclization under cryogenic conditions are insightful for fundamental photochemistry and sulfur chemistry.

Structural and functional insights in polysaccharides coated cerium oxide nanoparticles and their potential biomedical applications: A review.

Cerium oxide nanoparticles have now significant presence in biomedical fields due to their wide applications; however, challenges regarding their safety and biocompatibility persist. Polysaccharides based biopolymers have inherent hydroxyl and carboxyl groups, enabling them to govern the surface functionalization of cerium oxide nanoparticles, hence their chemical and physical characteristics. Because of this, polysaccharides such as dextran, alginate, pullulan, chitosan, polylactic acid, starch, and pectin are practical substitutes for the conventional coatings used to synthesize cerium oxide nanoparticles. This review discusses the effect of biopolymer coatings on the properties of cerium oxide nanoparticles, such as size, stability, aggregation, and biocompatibility. Additionally, it also summarises various biomedical applications of polysaccharides coated cerium oxide nanoparticles, such as in bone tissue regeneration, liver inflammation, wound healing, and antibacterial and anticancer activities. Biocompatible cerium oxide nanoparticles will surely improve their applications in the biomedical field.

A novel Gateaux derivatives with efficient DCNN-Resunet method for segmenting multi-class brain tumor.

In hospitals and pathology, observing the features and locations of brain tumors in Magnetic Resonance Images (MRI) is a crucial task for assisting medical professionals in both treatment and diagnosis. The multi-class information about the brain tumor is often obtained from the patient's MRI dataset. However, this information may vary in different shapes and sizes for various brain tumors, making it difficult to detect their locations in the brain. To resolve these issues, a novel customized Deep Convolution Neural Network (DCNN) based Residual-Unet (ResUnet) model with Transfer Learning (TL) is proposed for predicting the locations of the brain tumor in an MRI dataset. The DCNN model has been used to extract the features from input images and select the Region Of Interest (ROI) by using the TL technique for training it faster. Furthermore, the min-max normalizing approach is used to enhance the color intensity value for particular ROI boundary edges in the brain tumor images. Specifically, the boundary edges of the brain tumors have been detected by utilizing Gateaux Derivatives (GD) method to identify the multi-class brain tumors precisely. The proposed scheme has been validated on two datasets namely the brain tumor, and Figshare MRI datasets for detecting multi-class Brain Tumor Segmentation (BTS).The experimental results have been analyzed by evaluation metrics namely, accuracy (99.78, and 99.03), Jaccard Coefficient (93.04, and 94.95), Dice Factor Coefficient (DFC) (92.37, and 91.94), Mean Absolute Error (MAE) (0.0019, and 0.0013), and Mean Squared Error (MSE) (0.0085, and 0.0012) for proper validation. The proposed system outperforms the state-of-the-art segmentation models on the MRI brain tumor dataset.

A Study of Intraoperative Incidence of Fallopian Canal Dehiscence in Cases of Cholesteatoma.

Aims: Our study aimed to find the incidence of fallopian canal dehiscence during surgery for cholesteatoma, to compare this incidence with a homogenous control group (otosclerosis) and to find the incidence of a labyrinthine fistula if fallopian canal dehiscence is present. Material and Methods: Prospective case control study design was used in the setting of a tertiary care referral center. Subjects included 60 patients. 30 patients diagnosed with cholesteatoma were taken as cases and 30 patients with conductive or mixed hearing loss suspected of otosclerosis were taken as controls. The method was identification of bony dehiscence under operating microscope. In case of finding of dehiscence of fallopian canal, presence of labyrinthine fistula was searched. The cases underwent modified radical mastoidectomy and controls underwent exploratory tympanotomy after giving a written informed consent. Institutional ethics committee clearance was obtained. Results: Fallopian canal dehiscence was recorded in all subjects. 50% of cases and 3.3% of controls showed presence of fallopian canal dehiscence. This correlation was statistically significant (p < 0.001). Also 26.7% cases with fallopian canal dehiscence had a semicircular canal fistula (4 out of 15),but this finding was not significant (p = 0.100). Conclusion: From our study it was evident that there were very high chances of finding a fallopian canal dehiscence in cases of cholesteatoma than in cases undergoing exploratory tympanotomy. Also, presence of labyrinthine fistula with fallopian canal dehiscence was likely but not significant.

3D culture of fibroblasts and neuronal cells on microfabricated free-floating carriers.

3D cell culture is a relatively recent trend in biomedical research for artificially mimicking in vivo environment and providing three dimensions for the cells to grow in vitro, particularly with regard to surface-adherent mammalian cells. Different cells and research objectives require different culture conditions which has led to an increase in the diversity of 3D cell culture models. In this study, we show two independent on-carrier 3D cell culture models aimed at two different potential applications. Firstly, micron-scale porous spherical structures fabricated from poly (lactic-co-glycolic acid) or PLGA are used as 3D cell carriers so that the cells do not lose their physiologically relevant spherical shape. Secondly, millimetre-scale silk fibroin structures fabricated by 3D inkjet bioprinting are used as 3D cell carriers to demonstrate cell growth patterning in 3D for use in applications which require directed cell growth. The L929 fibroblasts demonstrated excellent adherence, cell-division and proliferation on the PLGA carriers, while the PC12 neuronal cells showed excellent adherence, proliferation and spread on the fibroin carriers without any evidence of cytotoxicity from the carriers. The present study thus proposes two models for 3D cell culture and demonstrates, firstly, that easily fabricable porous PLGA structures can act as excellent cell carriers for aiding cells easily retain their physiologically relevant 3D spherical shape in vitro, and secondly, that 3D inkjet printed silk fibroin structures can act as geometrically-shaped carriers for 3D cell patterning or directed cell growth in vitro. While the 'fibroblasts on PLGA carriers' model will help achieve more accurate results than the conventional 2D culture in cell research, such as drug discovery, and cell proliferation for adoptive cell transfer, such as stem cell therapy, the 'neuronal cells on silk fibroin carriers' model will help in research requiring patterned cell growth, such as treatment of neuropathies.

Optimized Carbohydrate-Based Nanogel Formulation to Sensitize Hypoxic Tumors.

Solid tumors are often poorly vascularized, which impairs oxygen supply and drug delivery to the cells. This often leads to genetic and translational adaptations that promote tumor progression, invasion, metastasis, and resistance to conventional chemo-/radiotherapy and immunotherapy. A hypoxia-directed nanosensitizer formulation of a hypoxia-activated prodrug (HAP) was developed by encapsulating iodoazomycin arabinofuranoside (IAZA), a 2-nitroimidazole nucleoside-based HAP, in a functionally modified carbohydrate-based nanogel, facilitating delivery and accrual selectively in the hypoxic head and neck and prostate cancer cells. Although IAZA has been reported as a clinically validated hypoxia diagnostic agent, recent studies have pointed to its promising hypoxia-selective anti-tumor properties, which make IAZA an excellent candidate for further exploration as a multimodal theranostic of hypoxic tumors. The nanogels are composed of a galactose-based shell with an inner core of thermoresponsive (di(ethylene glycol) methyl ethyl methacrylate) (DEGMA). Optimization of the nanogels led to high IAZA-loading capacity (≅80-88%) and a slow time-controlled release over 50 h. Furthermore, nanoIAZA (encapsulated IAZA) displayed superior in vitro hypoxia-selective cytotoxicity and radiosensitization in comparison to free IAZA in the head and neck (FaDu) and prostate (PC3) cancer cell lines. The acute systemic toxicity profile of the nanogel (NG1) was studied in immunocompromised mice, indicating no signs of toxicity. Additionally, growth inhibition of subcutaneous FaDu xenograft tumors was observed with nanoIAZA, demonstrating that this nanoformulation offers a significant improvement in tumor regression and overall survival compared to the control.

Microfluidic Formulation of Curcumin-Loaded Multiresponsive Gelatin Nanoparticles for Anticancer Therapy.

Current anticancer research shows that a combination of multiple treatment methods can greatly improve the killing of tumor cells. Using the latest microfluidic swirl mixer technology, combined with chemotherapy and photothermal-ablation therapy, we developed multiresponsive targeted antitumor nanoparticles (NPs) made of folate-functionalized gelatin NPs under 200 nm in size and with encapsulated CuS NPs, Fe3O4 NPs, and curcumin (Cur). By exploring gelatin's structure, adjusting its concentration and pH, and fine-tuning the fluid dynamics in the microfluidic device, the best preparation conditions were obtained for gelatin NPs with an average particle size of 90 ± 7 nm. The comparative targeting of the drug delivery system (DDS) was demonstrated on lung adenocarcinoma A549 cells (low level of folate receptors) and breast adenocarcinoma MCF-7 cells (high level of folate receptors). Folic acid helps achieve targeting and accurate delivery of NPs to the MCF-7 tumor cells. The synergistic photothermal ablation and curcumin's anticancer activity are achieved through infrared light irradiation (980 nm), while Fe3O4 is guided with an external magnetic field to target gelatin NPs and accelerate the uptake of drugs, thus efficiently killing tumor cells. The method described in this work is simple, easy to repeat, and has great potential to be scaled up for industrial production and subsequent clinical use.

Assessment of Setup Errors in Gynecological Malignancies Treated With Radiotherapy Using Onboard Imaging.

Introduction  Radiotherapy plays a vital role in the management of gynecological malignancies. However, maintaining patient position poses a challenge during daily radiotherapy treatment of these patients. This study identifies and calculates setup errors in interfraction radiotherapy and optimum clinical target volume-planning target volume (CTV-PTV) margins in patients with gynecological malignancies. Material and methods  A total of 38 patients with gynecological malignancies were included in the study. They were treated with a dose of 50 Gy in 25 fractions for five weeks, followed by brachytherapy. All patients were immobilized using a 4-point thermoplastic cast. Anteroposterior and lateral images were taken thrice weekly for five weeks. Setup verification was done using kilovoltage images obtained using Varian On-board Imager (Varian Medical System, Inc., Palo Alto, CA). Manual matching was done utilizing bony landmarks such as the widest portion of the pelvic brim, anterior border of S1 vertebrae, and pubic symphysis in the X, Y, and Z axes, respectively. Results A total of 1140 images were taken. The individual systematic errors ranged from -0.24 to 0.17 cm (LR), -0.15 to 0.19 cm (AP) and -0.36 to 0.29 cm (CC) while the individual random errors ranged from 0.04 to 0.36 cm (LR), 0.06 to 0.33 cm (AP) and 0.10 to 0.29 cm (CC). The calculated CTV-PTV margins in LR, AP and CC directions were 0.17, 0.18, and 0.25 cm (ICRU-62); 0.28, 0.31 and 0.47 cm in LR, AP and CC directions (Stroom's), and 0.32, 0.36 and 0.55 cm (Van Herk) respectively. Conclusion Based on this study, the calculated CTV-PTV margin is 6 mm in gynecological malignancies, and the present protocol of 7 mm of PTV margin is optimum.