Biomass RNA for the Controlled Synthesis of Degradable Networks by Radical Polymerization.

Nucleic acids extracted from biomass have emerged as sustainable and environmentally friendly building blocks for the fabrication of multifunctional materials. Until recently, the fabrication of biomass nucleic acid-based structures has been facilitated through simple crosslinking of biomass nucleic acids, which limits the possibility of material properties engineering. This study presents an approach to convert biomass RNA into an acrylic crosslinker through acyl imidazole chemistry. The number of acrylic moieties on RNA was engineered by varying the acylation conditions. The resulting RNA crosslinker can undergo radical copolymerization with various acrylic monomers, thereby offering a versatile route for creating materials with tunable properties (e.g., stiffness and hydrophobic characteristics). Further, reversible-deactivation radical polymerization methods, such as atom transfer radical polymerization (ATRP) and reversible addition-fragmentation chain transfer (RAFT), were also explored as additional approaches to engineer the hydrogel properties. The study also demonstrated the metallization of the biomass RNA-based material, thereby offering potential applications in enhancing electrical conductivity. Overall, this research expands the opportunities in biomass-based biomaterial fabrication, which allows tailored properties for diverse applications.

Red-Light-Driven Atom Transfer Radical Polymerization for High-Throughput Polymer Synthesis in Open Air.

Photoinduced reversible-deactivation radical polymerization (photo-RDRP) techniques offer exceptional control over polymerization, providing access to well-defined polymers and hybrid materials with complex architectures. However, most photo-RDRP methods rely on UV/visible light or photoredox catalysts (PCs), which require complex multistep synthesis. Herein, we present the first example of fully oxygen-tolerant red/NIR-light-mediated photoinduced atom transfer radical polymerization (photo-ATRP) in a high-throughput manner under biologically relevant conditions. The method uses commercially available methylene blue (MB+) as the PC and [X-CuII/TPMA]+ (TPMA = tris(2-pyridylmethyl)amine) complex as the deactivator. The mechanistic study revealed that MB+ undergoes a reductive quenching cycle in the presence of the TPMA ligand used in excess. The formed semireduced MB (MB•) sustains polymerization by regenerating the [CuI/TPMA]+ activator and together with [X-CuII/TPMA]+ provides control over the polymerization. This dual catalytic system exhibited excellent oxygen tolerance, enabling polymerizations with high monomer conversions (>90%) in less than 60 min at low volumes (50-250 µL) and high-throughput synthesis of a library of well-defined polymers and DNA-polymer bioconjugates with narrow molecular weight distributions (D < 1.30) in an open-air 96-well plate. In addition, the broad absorption spectrum of MB+ allowed ATRP to be triggered under UV to NIR irradiation (395-730 nm). This opens avenues for the integration of orthogonal photoinduced reactions. Finally, the MB+/Cu catalysis showed good biocompatibility during polymerization in the presence of cells, which expands the potential applications of this method.

Synthesis of RNA-Amphiphiles via Atom Transfer Radical Polymerization in the Organic Phase.

The combination of hydrophobic polymers with nucleic acids is a fascinating way to engineer the self-assembly behavior of nucleic acids into diverse nanostructures such as micelles, vesicles, nanosheets, and worms. Here we developed a robust route to synthesize a RNA macroinitiator with protecting groups on the 2'-hydroxyl groups in the solid phase using an oligonucleotide synthesizer. The protecting groups successfully solubilized the RNA macroinitiator, enabling atom transfer radical polymerization (ATRP) of hydrophobic monomers. As a result, the RNA-polymer hybrids obtained by ATRP exhibited enhanced chemical stability by suppressing cleavage. In addition, we demonstrated evidence of controlled polymerization behavior as well as control over the molecular weight of the hydrophobic polymers grown from RNA. We envision that this methodology will expand the field of RNA-polymer conjugates while vastly enhancing the possibility to alter and engineer the properties of RNA-based polymeric materials.

The Role of PET-CT-Guided Metabolic Biopsies in Improving Yield of Inconclusive Anatomical Biopsies: A Review of 5 Years in a Teaching Hospital.

Tumour sampling is indispensable to diagnostic and therapeutic decision making. Thus, 18F-FDG PET/CT has the potential to accurately discriminate between viable and non-viable tissues due to its ability to characterise the metabolism of visible tissues. This study's objective was to evaluate the incremental utility of 18F-FDG PET-CT-guided metabolic biopsy in individuals with suspected lesions and a previous negative anatomical biopsy. This study included a total of 190 consecutive patients with probable malignancy and who had experienced a previous unsuccessful anatomical biopsy who underwent PET-CT-guided metabolic biopsy. We retrospectively analysed the patients' medical records and imaging investigations to assess demographics, complications, pathologies, and final clinical diagnoses. Using multivariate logistic regression, correlation between several confounding factors that lead to post-procedural problems was evaluated. Adequate material was obtained in all patients, and 162 (85%) were found to be positive for malignancy with a diagnostic yield of 96.9%. In 25 (13.1%) patients, post-procedural complications were reported, with pneumothorax being the most prevalent issue. In evaluating oncological patients, metabolic biopsy provides a safer alternative therapy with a high diagnostic yield and comparable complications. PET-CT, being an essential component of cancer staging, may serve as a one-stop shop for the management of these patients' conditions.

RNA-Polymer Hybrids via Direct and Site-Selective Acylation with the ATRP Initiator and Photoinduced Polymerization.

Combining synthetic polymers with RNA paves the way for creating RNA-based materials with non-canonical functions. We have developed an acylation reagent that allows for direct incorporation of the atom transfer radical polymerization (ATRP) initiator into both short synthetic oligoribonucleotides and natural biomass RNA extracted from torula yeast. The acylation was performed in a quantitative yield. The resulting initiator-functionalized RNAs were used for grafting polymer chains from the RNA by photoinduced ATRP, resulting in RNA-polymer hybrids with narrow molecular weight distributions. The RNA initiator was used for the polymerization of oligo(ethylene oxide) methyl ether methacrylate, poly(ethylene glycol) dimethacrylate, and N-isopropylacrylamide monomers, resulting in RNA bottlebrushes, hydrogels, and stimuli-responsive materials. This approach, readily applicable to both post-synthetic and nature-derived RNA, can be used to engineer the properties of a variety of RNA-based macromolecular hybrids and assemblies providing access to a wide variety of RNA-polymer hybrids.

Validation of In-House Kit-Like Synthesis of 68Ga-Trivehexin and Its Biodistribution for Targeting the Integrin αvß6 Expressing Tumors.

Background: Integrin αvß6 has become an extremely promising theranostic target for precise delineation of fast-growing malignant cells in the recent years. The aim of the study was to validate the in-house kit-like synthesis of 68Ga-Trivehexin (integrin αvß6) and to evaluate its uptake in patients with integrin αvß6 expressing head and neck and pancreatic cancer. Materials and Methods: 68Ga-Trivehexin was synthesized by adding the variable amount of integrin αvß6 (30-50 µg) to full volume (4-5 mL) Ga-68 in 0.05 M HCl and heating the reaction mixture at 90°C for 12 min at pH 3.5-4 to obtain the radiotracer with high radiochemical purity (RCP) and high yield. Quality control procedures were done to assess the RCP, stability, pyrogenicity and sterility of the radiotracer. 68Ga-Trivehexin was then administered in patients who met the eligibility criteria. Whole body PET/CT scans were done at variable time points post intravenous (i.v.) injection of 84-185 MBq of 68Ga-Trivehexin to assess its biodistribution and maximum uptake time. Results: 0.2 mCi of 68Ga/µg of Trivehexin at 90°C for 12 min was the optimal parameter to obtain 85%-88% of noncorrected yield and 99% of RCP. The 68Ga-Trivehexin showed in vitro stability upto 6 h and was also found to be sterile and pyrogen free. Intense radiotracer uptake was noticed in the tumor and no uptake was noticed in healthy tissues. PET/CT imaging at 60 min post injection was found to be the optimal time for imaging the tumors with 68Ga-Trivehexin. Conclusion: The protocol for in-house kit-like labeling of 68Ga-Trivehexin was safe, reproducible, and cost-effective. 68Ga-Trivehexin is an extremely promising agent for noninvasive molecular imaging of integrin αvß6 expressing tumors.

Extracorporeal Shockwave Therapy Versus Platelet Rich Plasma Injection in Patients of Chronic Plantar Fasciitis: A Randomized Controlled Trial From a Tertiary Center of Eastern India.

Introduction Plantar fasciitis is a degenerative condition of the plantar fascia that leads to heel and sole pain. Physical modalities, physiotherapy, medication, and orthoses have been tried before as treatments. Extracorporeal shockwave therapy (ESWT) and the injection of autologous platelet-rich plasma (PRP) are generally effective in the treatment of plantar fasciitis, which might be resistant to other conservative measures. The present study compares the efficacy of ESWT and PRP injection in respect of symptomatic relief, functional improvement, and change in plantar fascia thickness (PFT). Methods Seventy-two patients were enrolled and randomized into two groups. Patients in the first group received ESWT, whereas patients in the second group received PRP injections. Patients were evaluated using the Visual Analog Scale (VAS) and the American Orthopedic Foot and Ankle Society (AOFAS) score, along with PFT measurement (using ultrasonography) before the treatment and at days 15, 30, and 90 after the treatment. The X2 test was used to compare qualitative variables, and the paired T-test was used to evaluate quantitative data. Quantitative variables had a normal distribution with a standard deviation, and the significance level was set at P-value=0.05. Results On day 0, the mean VAS of the ESWT and PRP groups were 6.44±1.11 and 6.78±1.17, respectively (p=0.237). On day 15, the mean VAS of the ESWT and PRP groups were 4.67±1.45 and 6.67±1.35, respectively (p<0.001). At day 30, the mean VAS of the ESWT and PRP groups were 4.97±1.46 and 4.69±1.39, respectively (p=0.391). On day 90, the mean VAS of the ESWT and PRP groups were 5.47±1.63 and 3.36±0.96 (p<0.001). On day 0, the mean PFTs of the ESWT and PRP groups were 4.73±0.40 and 5.19±0.51, respectively (p<0.001). At day 15, the mean PFT of the ESWT and PRP groups were 4.64±0.46 and 5.11±0.62, respectively (p<0.001) which changed to 4.52±0.53 and 4.40±0.58 at day 30 (p<0.001), and to 4.40±0.50 and 3.82±0.45 at day 90 (p<0.001). The mean AOFAS of the ESWT and PRP groups were 68.39±5.88 and 64.86±8.95 on day 0 (p=0.115), 72.58±6.26 and 67.22±10.47 on day 15 (p=0.115), 73.22±6.92 and 74.72±7.52 on day 30 (p=0.276), and 72.75±7.90 and 81.08±6.01 on day 90, respectively (p<0.001). Conclusion Both PRP injection and ESWT are very effective methods to improve pain and cause reduced plantar fascia thickness in patients with chronic plantar fasciitis non-responsive to other conservative measures. PRP injection is more effective at a longer duration as compared to ESWT.

ICTV Virus Taxonomy Profile: Yadokariviridae 2023.

The family Yadokariviridae, with the genera Alphayadokarivirus and Betayadokarivirus, includes capsidless non-segmented positive-sense (+) RNA viruses that hijack capsids from phylogenetically distant double-stranded RNA viruses. Yadokarivirids likely replicate inside the hijacked heterocapsids using their own RNA-directed RNA polymerase, mimicking dsRNA viruses despite their phylogenetic placement in a (+) RNA virus lineage. Yadokarivirids can have negative or positive impacts on their host fungi, through interactions with the capsid donor dsRNA viruses. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) report on the family Yadokariviridae, which is available at ictv.global/report/yadokariviridae.

Visible-Light-Mediated Controlled Radical Branching Polymerization in Water.

Hyperbranched polymethacrylates were synthesized by green-light-induced atom transfer radical polymerization (ATRP) under biologically relevant conditions in the open air. Sodium 2-bromoacrylate (SBA) was prepared in situ from commercially available 2-bromoacrylic acid and used as a water-soluble inibramer to induce branching during the copolymerization of methacrylate monomers. As a result, well-defined branched polymethacrylates were obtained in less than 30 min with predetermined molecular weights (36 000

Feasibility of 18F-FDG Labelling of Leucocytes in a Centre Without an On-Site Cyclotron and Monitoring of Radiation Dose to Occupational Worker in the Labelling Procedure.

Objectives: Differentiation of infection from sterile inflammation is still a major concern for clinicians. The 18F-WBC positron emission tomography/computed tomography scan has been considered a promising tool for accurate diagnosis of infection owing to its high specificity, but it renders the availability of a medical cyclotron a necessity. The aim of the present study was to determine the feasibility of labeling leukocytes and establish the protocol in a center without the availability of an on-site medical cyclotron. The secondary aim was to monitor radiation doses to occupational workers involved in labeling of leukocytes with 18F-FDG. Materials and Methods: Leukocyte separation was performed and leukocytes were radiolabeled with 18F-FDG in a sterile environment according to the procedure described by Bhattacharya et al. In vitro leukocyte viability was assessed using the trypan dye exclusion technique. Labeling efficiency and yield were also estimated for all radiolabeling procedures. Whole-body and extremity doses received by the personnel involved in the radiolabeling procedure were also estimated using pocket dosimeters. Results: Leukocyte labeling was carried out in 35 runs, during which there were two failed labeling attempts due to clotting of the blood sample. The total time involved in the whole procedure was around 2.5 h. The average labeling efficiency was 78.01% ± 6.99% (range 63.46%-86.54%), cell viability was 98%, and the cell suspension was stable up to 4 h. The mean dose was measured as 17 µSv at the chest level and 32 µSv at the extremity level, per procedure. Conclusions: Labeling of leukocytes with 18F-FDG is possible at a tertiary nuclear medicine setup without the availability of an on-site medical cyclotron, with reasonable labeling efficiency of 78.01% ± 6.99%. In addition, in-house labeling of leukocytes with 18F-FDG is safe and the radiation doses incurred by the personnel during the labeling procedure are well within the occupational dose limits established by the national regulatory authority.

Factors Associated With Persistence of Dyspnea and Change in Health-Related Quality of Life in Patients With COVID-19 After Discharge.

Introduction Coronavirus disease 2019 (COVID-19) is a deadly virus affecting multiple organ systems, predominantly the respiratory system. Dyspnea along with the deterioration of health-related quality of life (HRQoL) is common in COVID-19 patients discharged from a dedicated Coronavirus disease (COVID) hospital. Very few studies in India used HRQoL for the assessment of COVID-19 patients after discharge. Our article aims to assess the factors associated with the persistence of dyspnea and HRQoL in discharged patients of COVID-19. Methods A total of 48 patients were included in this prospective observational study. Ethical approval from Institutional Ethics Committee was obtained before the enrolment of patients. Patients having dyspnea at exertion and during discharge were selected for this study. Modified Medical Research Council (mMRC) scale and modified Borg scale were used for assessing dyspnea on activity, and Saint George's Respiratory Questionnaire (SGRQ) was used to assess HRQoL. Data were collected on the day of discharge (D0) and after 60 days (D60) post-discharge. The significance of changes in parameters from D0 to D60 was evaluated by paired t-test. Results The mean mMRC, modified Borg, and SGRQ scores at D0 were 2.38±0.98, 3.15±2.12, and 45.36±27.32, respectively, which were improved to 0.94±0.86, 0.94±1.27, and 19.22±18.96 at D60. Age showed significant positive correlations with initial modified Borg (r=0.292, p=0.044) and SGRQ (r=0.332, p=0.021) scores. Body mass index showed significant positive correlations with initial mMRC (r=0.352, p=0.014) and SGRQ (r=0.419, p=0.003) scores. Conclusion Our study showed that on discharge, many COVID patients have impaired HRQoL. Many of them also have dyspnea on exertion. With the early institution of standard pulmonary rehabilitation protocol, symptoms and HRQoL improves rapidly in a month. Different influencing factors were identified. Long-term follow-up with a bigger sample size is needed to formulate a management strategy for these patients.

Open-air green-light-driven ATRP enabled by dual photoredox/copper catalysis.

Photoinduced atom transfer radical polymerization (photo-ATRP) has risen to the forefront of modern polymer chemistry as a powerful tool giving access to well-defined materials with complex architecture. However, most photo-ATRP systems can only generate radicals under biocidal UV light and are oxygen-sensitive, hindering their practical use in the synthesis of polymer biohybrids. Herein, inspired by the photoinduced electron transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization, we demonstrate a dual photoredox/copper catalysis that allows open-air ATRP under green light irradiation. Eosin Y was used as an organic photoredox catalyst (PC) in combination with a copper complex (X-CuII/L). The role of PC was to trigger and drive the polymerization, while X-CuII/L acted as a deactivator, providing a well-controlled polymerization. The excited PC was oxidatively quenched by X-CuII/L, generating CuI/L activator and PC˙+. The ATRP ligand (L) used in excess then reduced the PC˙+, closing the photocatalytic cycle. The continuous reduction of X-CuII/L back to CuI/L by excited PC provided high oxygen tolerance. As a result, a well-controlled and rapid ATRP could proceed even in an open vessel despite continuous oxygen diffusion. This method allowed the synthesis of polymers with narrow molecular weight distributions and controlled molecular weights using Cu catalyst and PC at ppm levels in both aqueous and organic media. A detailed comparison of photo-ATRP with PET-RAFT polymerization revealed the superiority of dual photoredox/copper catalysis under biologically relevant conditions. The kinetic studies and fluorescence measurements indicated that in the absence of the X-CuII/L complex, green light irradiation caused faster photobleaching of eosin Y, leading to inhibition of PET-RAFT polymerization. Importantly, PET-RAFT polymerizations showed significantly higher dispersity values (1.14 ≤ D ≤ 4.01) in contrast to photo-ATRP (1.15 ≤ D ≤ 1.22) under identical conditions.

Recent Emergence of Bovine Coronavirus Variants with Mutations in the Hemagglutinin-Esterase Receptor Binding Domain in U.S. Cattle.

Bovine coronavirus (BCoV) has spilled over to many species, including humans, where the host range variant coronavirus OC43 is endemic. The balance of the opposing activities of the surface spike (S) and hemagglutinin-esterase (HE) glycoproteins controls BCoV avidity, which is critical for interspecies transmission and host adaptation. Here, 78 genomes were sequenced directly from clinical samples collected between 2013 and 2022 from cattle in 12 states, primarily in the Midwestern U.S. Relatively little genetic diversity was observed, with genomes having >98% nucleotide identity. Eleven isolates collected between 2020 and 2022 from four states (Nebraska, Colorado, California, and Wisconsin) contained a 12 nucleotide insertion in the receptor-binding domain (RBD) of the HE gene similar to one recently reported in China, and a single genome from Nebraska collected in 2020 contained a novel 12 nucleotide deletion in the HE gene RBD. Isogenic HE proteins containing either the insertion or deletion in the HE RBD maintained esterase activity and could bind bovine submaxillary mucin, a substrate enriched in the receptor 9-O-acetylated-sialic acid, despite modeling that predicted structural changes in the HE R3 loop critical for receptor binding. The emergence of BCoV with structural variants in the RBD raises the possibility of further interspecies transmission.

Sulfoxide-Containing Polyacrylamides Prepared by PICAR ATRP for Biohybrid Materials.

Water-soluble and biocompatible polymers are of interest in biomedicine as the search for alternatives to PEG-based materials becomes more important. In this work, the synthesis of a new sulfoxide-containing monomer, 2-(methylsulfinyl)ethyl acrylamide (MSEAM), is reported. Well-defined polymers were prepared by photoinduced initiators for continuous activator regeneration atom transfer radical polymerization (PICAR ATRP). The polymerizations were performed in water under biologically relevant conditions in a small volume without degassing the reaction mixture. DNA-PMSEAM and protein-PMSEAM hybrids were also synthesized. The lower critical solution temperature (LCST) of PMSEAM was estimated to be approximately 170 °C by extrapolating the LCST for a series of copolymers with variable content of N-isopropylacrylamide. The cytotoxicity studies showed excellent biocompatibility of PMSEAM, even at concentrations up to 2.5 mg/mL. Furthermore, the MSEAM monomer exhibited relatively lower toxicity than similar (meth)acrylate-based monomers at comparable concentrations.

A Transfectable Fusagravirus from a Japanese Strain of Cryphonectria carpinicola with Spherical Particles.

A novel dsRNA virus (Cryphonectria carpinicola fusagravirus 1, CcFGV1), isolated from a Japanese strain (JS13) of Cryphonectria carpinicola, was thoroughly characterized. The biological comparison of a set of isogenic CcFGV1-infected and -free (JS13VF) strains indicated asymptomatic infection by CcFGV1. The sequence analysis showed that the virus has a two open reading frame (ORF) genome of 9.6 kbp with the RNA-directed RNA polymerase domain encoded by ORF2. The N-terminal sequencing and peptide mass fingerprinting showed an N-terminally processed or degraded product (150 kDa) of the 5'-proximal ORF1-encoded protein (1462 amino acids) to make up the CcFGV1 spherical particles of ~40 nm in diameter. Interestingly, a portion of CcFGV1 dsRNA co-fractionated with a host protein of 70 kDa. The purified CcFGV1 particles were used to transfect protoplasts of JS13VF as well as the standard strain of an experimental model filamentous fungal host Cryphonectria parasitica. CcFGV1 was confirmed to be associated with asymptomatic infection of both fungi. RNA silencing was shown to target the virus in C. parasitica, resulting in reduced CcFGV1 accumulation by comparing the CcFGV1 content between RNA silencing-competent and -deficient strains. These results indicate the transfectability of spherical particles of a fusagravirus associated with asymptomatic infection.

Incremental Value of 18 F-FDG-Labeled Leukocytes PET/CT Over 18 F-FDG PET/CT Scan in the Detection of Occult Infection.

PURPOSE: Differentiating infection and sterile inflammation is the main clinical concern of clinicians as they are closely related to each other. Although 18 F-FDG PET/CT imaging is widely used, its main disadvantage is its lack of specificity to discriminate aseptic from septic inflammation. 18 F-WBC PET/CT scan is a promising tool for the accurate diagnosis of infection owing to its high specificity. The aim of the present study is to determine the utility of 18 F-WBC PET/CT in the diagnosis of occult infections and to assess its incremental value over routine 18 F-FDG PET/CT scan. PATIENTS AND METHODS: This prospective observational diagnostic accuracy study included 33 patients with fever of unknown origin or suspected periprosthetic infection and raised C-reactive protein and total leukocyte count. All the patients underwent both 18 F-WBC PET/CT scan and 18 F-FDG PET/CT scan using a standard protocol on 2 different days. Images of both the scans were evaluated by both visual analyses based on uptake intensity and quantitative grading based on lesion-to-background SUV max values. For interpretation of FDG PET/CT images, visual scoring of grade 0 (undetectable or no uptake), grade 1a (less than liver uptake), grade 1b (equivalent to liver uptake), grade 2 (higher than liver uptake), and grade 3 (higher than cerebellum uptake) was used. 18 F-WBC PET/CT images were also interpreted visually as grade 0 (undetectable or no uptake), grade 1a (significantly less than lumbar vertebrae or liver uptake for truncal lesions, and in case of extremity lesion slightly higher than neighboring soft tissue uptake or less than neighboring bone marrow uptake), grade 1b (equivalent to liver or lumbar vertebrae uptake for truncal lesions, and in case of extremity lesion significantly higher than neighboring soft tissue uptake or higher than neighboring bone marrow uptake), grade 2 (higher than liver or bone marrow uptake), and grade 3 (higher than twice the liver or bone marrow uptake). Similarly, a quantitative grading was also done based on lesion-to-background SUV max using a circular region of interest manually drawn. For both 18 F-FDG and 18 F-WBC PET/CT, the lesion-to-background ratio of <1.5 was recorded as grade 0, 1.5-2.5 as grade 1a, 2.5-3.5 as grade 1b, 3.5-4.5 as grade 2, and >4.5 as grade 3. Final diagnosis was made by histopathological, microbiological analysis, or clinical-radiological workup. RESULTS: Twenty-nine foci of suspected infection were found in 25/33 patients by either 18 F-FDG PET/CT or 18 F-WBC PET/CT scan. No abnormal uptake of either 18 F-FDG or 18 F-FDG WBC scan was seen in 8 patients. There was a concordance of 18 F-FDG PET/CT and 18 F-WBC PET/CT in 28 sites each using grade 1b of visual and quantitative analysis, respectively. Of the 29 suspicious infected foci, 18 were proven positive for infection (14/18 sites by the histopathological/microbiological culture and the rest 4/18 sites by clinical/radiological workup). Culture of aspirates or biopsy from 11/29 suspicious sites was proven noninfective. Seven of 11 suspicious sites were proven noninfective by clinical/radiological workup. The mean clinical follow-up was 8 months (1-15 months).Overall significantly higher diagnostic accuracy was demonstrated with 18 F-WBC PET/CT in comparison to 18 F-FDG PET/CT for the detection of infection ( P < 0.05). The highest diagnostic accuracy of 18 F-WBC PET/CT scan was reported with both grade 1b of visual as well as of quantitative analysis (lesion-to-background SUV max , 2.5-3.5) and grade 2 for both visual and quantitative analysis for 18 F FDG PET/CT. CONCLUSIONS: 18 F-WBC PET/CT has a higher diagnostic accuracy over 18 F-FDG PET/CT for the diagnosis of occult infection.

18F-Labeled WBC PET/CT Scan in a Case of Recurrent Glioblastoma Multiforme, Presented as Pyrexia of Unknown Origin.

ABSTRACT: Neoplastic causes account for approximately 10% to 20% cases of PUO (pyrexia of unknown origin). The mechanisms by which malignancies induce fever are not fully understood. The release of pyrogenic cytokines either directly from tumor cells or from macrophages responding to tumor are likely to play a major role, which acts on the hypothalamus, causing a change in the thermostatic set point. We present a case of recurrent glioblastoma multiforme, who presented with PUO. 18F-FDG-labeled leukocyte PET/CT scan done for localization of infective focus demonstrated significant tracer accumulation at the periphery of the recurrent brain lesion. Subsequent excisional biopsy from the lesion was suggestive of noninfected recurrent glioblastoma multiforme.

Controlled Release of Exosomes Using Atom Transfer Radical Polymerization-Based Hydrogels.

Exosomes are 30-200 nm sized extracellular vesicles that are increasingly recognized as potential drug delivery vehicles. However, exogenous exosomes are rapidly cleared from the blood upon intravenous delivery, which limits their therapeutic potential. Here, we report bioactive exosome-tethered poly(ethylene oxide)-based hydrogels for the localized delivery of therapeutic exosomes. Using cholesterol-modified DNA tethers, the lipid membrane of exosomes was functionalized with initiators to graft polymers in the presence of additional initiators and crosslinker using photoinduced atom transfer radical polymerization (ATRP). This strategy of tethering exosomes within the hydrogel network allowed their controlled release over a period of 1 month, which was much longer than physically entrapped exosomes. Exosome release profile was tuned by varying the crosslinking density of the polymer network and the use of photocleavable tethers allowed stimuli-responsive release of exosomes. The therapeutic potential of the hydrogels was assessed by evaluating the osteogenic potential of bone morphogenetic protein 2-loaded exosomes on C2C12 and MC3T3-E1 cells. Thus, ATRP-based exosome-tethered hydrogels represent a tunable platform with improved efficacy and an extended-release profile.

Invasive Fungal Infection in COVID-19-Recovered Patient Detected on 18F-FDG-Labeled Leukocytes PET/CT Scan.

ABSTRACT: Occurrence of invasive fungal infections has gained significant attention during recent times in patients with COVID-19. Patients with severe form of COVID-19, such as those treated in the intensive care unit with prolonged steroid use, are particularly vulnerable to secondary bacterial and fungal infections. Disseminated systemic mycosis is a life-threatening condition, especially in immunocompromised patients. Here, we report a case of a recovered severe COVID-19 patient, who presented with persistent fever. 18F-FDG-labeled leukocyte scan revealed focal accumulation of radiotracer in the small intestine and right lung lower lobe. Subsequently, performed biopsy revealed mucormycosis.

Upfront Use of 177Lu-Labeled PSMA Radioligand Therapy and Treatment Response Assessment in Treatment-Naive Prostate Cancer.

ABSTRACT: Prostatic malignancy is the most common type of nonskin cancer and associated with significant morbidity and mortality. Early androgen deprivation therapy (ADT) is the treatment of choice in metastatic prostate cancer, whereas ADT delays progression of disease, but it is associated with significant adverse effects and frequently impairs the quality of life. Therefore, there is growing interest in treatments to postpone ADT while achieving a good progression-free survival. We present a case of oligometastatic prostate cancer, who was treated upfront with 177Lu-labeled PSMA radioligand therapy and demonstrated excellent response to a single dose of 177Lu-PSMA-617.