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Progressive metastatic castration-resistant prostate cancer is a highly lethal disorder and new effective therapeutic agents that improve patient outcomes are urgently needed. Lutetium-177 [177Lu]-PSMA-617, a radiolabelled small molecule, binds with high affinity to prostate-specific membrane antigen (PSMA) enabling beta particle therapy targeted to metastatic castration-resistant prostate cancer. We aimed to investigate the safety, efficacy, and effect on quality of life of [177Lu]-PSMA-617 in men with metastatic castration-resistant prostate cancer who progressed after standard treatments. In this single-arm, single-centre, phase 2 trial, we recruited men (aged 18 years and older) with metastatic castration-resistant prostate cancer and progressive disease after standard treatments, including taxane-based chemotherapy and second-generation anti-androgens, from the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. Patients underwent a screening PSMA and FDG-PET/CT to confirm high PSMA-expression. Eligible patients had progressive disease defined by imaging (according to Response Evaluation Criteria In Solid Tumours [RECIST] or bone scan) or new pain in an area of radiographically evident disease, and were required to have an Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or lower. Eligible patients received up to four cycles of intravenous [177Lu]-PSMA-617, at six weekly intervals. The primary endpoint was PSA response according to Prostate Cancer Clinical Trial Working Group criteria defined as a greater than 50% PSA decline from baseline and toxicity according to CTCAE. Additional primary endpoints were imaging responses (as measured by bone scan, CT, PSMA, and FDG PET/CT) and quality of life (assessed with the EORTC-Q30 and Brief Pain Inventory-Short Form questionnaires), all measured up to 3 months post completion of treatment. This trial is registered with the Australian New Zealand Clinical Trials Registry, number 12615000912583. Between Aug 26, 2015, and Dec 8, 2016, 43 men were screened to identify 30 patients eligible for treatment. 26 (87%) had received at least one line of previous chemotherapy (80% docetaxel and 47% cabazitaxel) and 25 (83%) received prior abiraterone acetate, enzalutamide, or both. The mean administered radioactivity was 7·5 GBq per cycle. 17 (57%) of 30 patients (95% CI 37–75) achieved a PSA decline of 50% or more. There were no treatment-related deaths. The most common toxic effects related to [177Lu]-PSMA-617 were grade 1 dry mouth recorded in 26 (87%) patients, grade 1 and 2 transient nausea in 15 (50%), and G1–2 fatigue in 15 (50%). Grade 3 or 4 thrombocytopenia possibly attributed to [177Lu]-PSMA-617 occurred in four (13%) patients. Objective response in nodal or visceral disease was reported in 14 (82%) of 17 patients with measurable disease. Clinically meaningful improvements in pain severity and interference scores were recorded at all timepoints. 11 (37%) patients experienced a ten point or more improvement in global health score by the second cycle of treatment. Our findings show that radionuclide treatment with [177Lu]-PSMA-617 has high response rates, low toxic effects, and reduction of pain in men with metastatic castration-resistant prostate cancer who have progressed after conventional treatments. This evidence supports the need for randomised controlled trials to further assess efficacy compared with current standards of care. None.

PurposeWe analysed quantitative biomarkers derived from both baseline whole-body imaging and blood serum to identify prognostic markers in patients treated within the lutetium-177 prostate-specific membrane antigen (LuPSMA) phase 2 trial.MethodsPET image analysis was carried out using whole-body segmentation quantifying molecular tumour volume (SUV > 3 threshold for PSMA, SUV > liver+2sd for fluorodeoxyglucose (FDG) including SUVmax and SUVmean. For baseline bone scans, EXINI bone scan index (BSI) was used to calculate the percentage of involved bone. Baseline alkaline phosphatase (ALP), lactate dehydrogenase (LDH), prostate specific antigen (PSA) and PSA doubling time were also used in this analysis. We used univariate cox regression analysis and log-rank comparison with optimised cut-offs to find suitable biomarkers prognostic of overall survival from time of enrolment.ResultsThis analysis identified FDG-positive tumour volume (FDGvol; HR 2.6; 95% CI, 1.4–4.8), mean intensity of PSMA-avid tumour uptake (PSMAmean; HR 0.89; 95% CI, 0.8–0.98), bone scan index (BSI; HR 2.3; 95% CI, 1.2–4.4), ALP (HR 1.1; 95% CI, 1–1.2) and LDH (HR 1.2; 95% CI, 1–1.5) as biomarkers prognostic of overall survival.ConclusionsIn addition to established biomarkers, both FDG and PSMA PET/CT parameters have prognostic significance for survival in men undergoing LuPSMA therapy.

In this research work, carbon dots (CDs) were synthesized from the renewable leaves of an indigenous medicinal plant by the one-pot sand bath method, Azadirachta indica . The synthesized CDs were characterized for its optical properties using UV–Vis, Fluorescence and Fourier transform infrared (FT-IR) spectrophotometry and for structural properties using dynamic light scattering (DLS), X-ray Diffraction (XRD) and high resolution Transmission electron microscopy (HR-TEM). The synthesized CDs exhibited concentration dependent biocompatibility when tested in mouse fibroblast L929 cell line. The EC 50 values of biomedical studies, free radical scavenging activity (13.87 μgmL −1 ), and total antioxidant capacity (38 μgmL −1 ) proved CDs were exceptionally good. These CDs showed an appreciable zone of inhibition when examined on four bacterial (two gram-positive and gram-negative) and two fungal strains at minimum concentrations. Cellular internalisation studies performed on human breast cancer cells (MCF 7- bioimaging) revealed the applicability of CDs in bioimaging, wherein the inherent fluorescence of CDs were utilised. Thus, the CDs developed are potential as bioimaging, antioxidants and antimicrobial agents.

Rice is a highly consumed staple cereal cultivated predominantly in Asian countries, which share 90% of global rice production. Rice is a primary calorie provider for more than 3.5 billion people across the world. Preference and consumption of polished rice have increased manifold, which resulted in the loss of inherent nutrition. The prevalence of micronutrient deficiencies (Zn and Fe) are major human health challenges in the 21 st century. Biofortification of staples is a sustainable approach to alleviating malnutrition. Globally, significant progress has been made in rice for enhancing grain Zn, Fe, and protein. To date, 37 biofortified Fe, Zn, Protein and Provitamin A rich rice varieties are available for commercial cultivation (16 from India and 21 from the rest of the world; Fe > 10 mg/kg, Zn > 24 mg/kg, protein > 10% in polished rice as India target while Zn > 28 mg/kg in polished rice as international target). However, understanding the micronutrient genetics, mechanisms of uptake, translocation, and bioavailability are the prime areas that need to be strengthened. The successful development of these lines through integrated-genomic technologies can accelerate deployment and scaling in future breeding programs to address the key challenges of malnutrition and hidden hunger.

Artificial intelligence (AI) is a branch of science concerned with developing programs and computers that can gather data, reason about it, and then translate it into intelligent actions. AI is a broad area that includes reasoning, typical linguistic dispensation, machine learning, and planning. In the area of medicine and dentistry, machine learning is currently the most widely used AI application. This narrative review is aimed at giving an outline of cephalometric analysis in orthodontics using AI. Latest algorithms are developing rapidly, and computational resources are increasing, resulting in increased efficiency, accuracy, and reliability. Current techniques for completely automatic identification of cephalometric landmarks have considerably improved efficiency and growth prospects for their regular use. The primary considerations for effective orthodontic treatment are an accurate diagnosis, exceptional treatment planning, and good prognosis estimation. The main objective of the AI technique is to make dentists’ work more precise and accurate. AI is increasingly being used in the area of orthodontic treatment. It has been evidenced to be a time-saving and reliable tool in many ways. AI is a promising tool for facilitating cephalometric tracing in routine clinical practice and analyzing large databases for research purposes.

Aims The purpose of this retrospective analysis was to examine the association of left atrial (LA) strain (i.e. LA reservoir function) with left ventricular diastolic dysfunction (DD) in patients with heart failure with reduced and preserved left ventricular ejection fraction (LVEF). Methods and results We analysed the baseline echocardiographic recordings of 300 patients in sinus rhythm from the SOCRATES‐PRESERVED and SOCRATES‐REDUCED studies. LA volume index was normal in 89 (29.7%), of whom 60.6% had an abnormal LA reservoir strain (i.e. ≤23%). In addition, the extent of LA strain impairment was significantly associated with the severity of DD according to the 2016 American Society of Echocardiography recommendations (DD grade I: LA strain 22.2 ± 6.6, rate of abnormal LA strain 62.9%; DD grade II: LA strain 16.6 ± 7.4, rate of abnormal LA strain 88.6%; DD grade III: LA strain 11.1 ± 5.4%, rate of abnormal LA strain 95.7%; all P < 0.01). In line with these findings, LA strain had a good diagnostic performance to determine severe DD [area under the curve 0.83 (95% CI 0.77–0.88), cut‐off 14.1%, sensitivity 80%, specificity 77.8%], which was significantly better than for LA volume index, LA total emptying fraction, and the mitral E/e′ ratio. Conclusions The findings of this analysis suggest that LA strain could be a useful parameter in the evaluation of DD in patients with heart failure and sinus rhythm, irrespective of LVEF.

Lutetium-177 [177Lu]Lu-PSMA-I&T (177Lu-PSMA-I&T) and the bone-seeking α-emitter radium-223 (223Ra) are established life-extending therapies for patients with metastatic castration-resistant prostate cancer; however, resistance and progression are inevitable. We aimed to evaluate the safety and preliminary antitumour activity of 177Lu-PSMA-I&T combined with 223Ra in this patient group. We conducted an investigator-initiated, single-centre, single-arm, phase 1/2 trial (AlphaBet) at the Peter MacCallum Cancer Centre in Melbourne, Australia. Adults (aged ≥18 years) with a diagnosis of progressive, metastatic castration-resistant prostate cancer, an Eastern Cooperative Oncology Group performance status score of 0–2, at least two visible bone metastases not treated with radiotherapy, previous exposure to an androgen receptor pathway inhibitor, prostate-specific membrane antigen (PSMA)-positive disease (defined by maximum standardised uptake value ≥20 at a site of disease), and no discordant sites (ie, avid on 2-[18F]fluoro-2-deoxy-D-glucose-PET–CT with minimal PSMA expression and no uptake on bone scintigraphy) were eligible for inclusion. Phase 1 dose-escalation assessed two dose levels of 223Ra (27·5 kBq/kg and 55·0 kBq/kg) combined with 7·4 GBq 177Lu-PSMA-I&T, administered intravenously every 6 weeks for up to six cycles. Phase 2 dose expansion continued with the recommended phase 2 dose. Co-primary endpoints were the maximum tolerated or administered dose and the recommended phase 2 dose (phase 1), and the PSA response rate (phase 2), analysed in all patients treated at the maximum tolerated or administered dose in either phase. Safety was assessed in all patients who received at least one dose of either protocol treatment in phase 1 or 2. Herein, we report the results of an interim analysis, which was added to the protocol following an amendment on May 30, 2024. This trial is registered at ClinicalTrials.gov (NCT05383079) and follow-up is ongoing. Between Nov 3, 2022, and Nov 5, 2024, 37 patients were enrolled, of whom 36 (97%; median age 72·5 years [IQR 67·0–78·0]) were included in the safety analysis and 33 (89%) were included in the preliminary activity analysis. No dose-limiting toxicities were observed. The recommended phase 2 dose of 223Ra was 55·0 KBq/kg combined with 7·4 GBq 177Lu-PSMA-I&T, administered every 6 weeks. With a median follow-up of 13·3 months (IQR 8·7–17·1), 11 (31%) patients completed all six cycles of both treatments. 18 (50%) patients discontinued treatment early, primarily due to unequivocal disease progression (11 [61%]) or adverse events (three [17%]). A reduction in PSA of at least 50% was observed in 18 (55%; 95% CI 36–72) patients. Grade 3 or higher treatment-related adverse events occurred in five (14%) of 36 patients, including anaemia (four [11%]) and neutropenia (three [8%]), with no treatment-related deaths. Non-clinically significant grade 3 lymphopenia occurred in ten (28%) patients. The combination of 177Lu-PSMA-I&T and 223Ra is safe and feasible in patients with metastatic castration-resistant prostate cancer and bone metastases. These findings warrant further evaluation of combined α-emitting and β-emitting approaches. Prostate Cancer Foundation, Bayer, and National Health and Medical Research Council.

Background The aim of this study was to evaluate and compare the anti-inflammatory properties of silver nanoparticles (AgNPs) and zinc oxide nanoparticles (ZnONPs) that were synthesized utilizing African tulsi and black tulsi herbal formulations. The anti-inflammatory activity was assessed by the utilization of bovine serum albumin (BSA) denaturation and egg albumin denaturation tests. In addition, a membrane stabilization experiment was performed to evaluate their efficacy as anti-inflammatory drugs Methods This study was conducted at Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai, India. AgNPs and ZnONPs were synthesized using (African tulsi) and  (black tulsi) extracts. The BSA denaturation assay involved mixing serum albumin with different nanoparticle concentrations (10-50 µg/mL) and measuring absorbance at 660 nm. The egg albumin denaturation assay followed a similar procedure. The membrane stabilization assay utilized red blood cells and spectrophotometric measurements at 540 nm. Results In the BSA denaturation assay, AgNPs and ZnONPs showed concentration-dependent inhibition of protein denaturation. While these nanoparticles exhibited anti-inflammatory potential, diclofenac sodium consistently displayed slightly stronger inhibition. In the egg albumin denaturation assay, AgNPs and ZnONPs inhibited protein denaturation at various concentrations. Their anti-inflammatory effects were comparable to the standard drug, diclofenac sodium. In the membrane stabilization assay, both nanoparticle types demonstrated concentration-dependent membrane stabilization effects. Diclofenac sodium exhibited slightly stronger membrane stabilization. Conclusions AgNPs and ZnONPs synthesized using  and (African tulsi and black tulsi) possess anti-inflammatory potential, as demonstrated by their inhibition of protein denaturation and membrane stabilization. While these nanoparticles show promise as anti-inflammatory agents, further research is needed to explore their clinical applications and safety profiles.

Background This study deals with the antimicrobial efficacy of zinc oxide nanoparticles (ZnONPs) synthesized through green methods employing extracts from  and assessed for their antimicrobial properties against a range of oral pathogens. Methods Zinc oxide nanoparticles (ZnONPs) were synthesized using extracts from  and  through a green synthesis approach. Antimicrobial activity was determined using the agar-well diffusion assay to evaluate the consistency of inhibition zones against oral pathogens. Variations in sensitivity were assessed through the time-kill curve assay, quantifying the response of oral pathogens to zinc oxide nanoparticles (ZnONPs) exposure over time. Results The agar-well diffusion assay revealed uniform 9-mm zones of inhibition against all oral pathogens, signifying consistent antimicrobial activity of zinc oxide nanoparticles (ZnONPs). In the time-kill curve assay, Candida albicans exhibited the highest sensitivity, followed by  displayed lower sensitivity, suggesting potential selectivity. Discussion The observed variation in sensitivity implies the potential selectivity of zinc oxide nanoparticles (ZnONPs) against specific oral pathogens, which may have significant implications for oral health applications. These findings underscore the versatility of green-synthesized zinc oxide nanoparticles (ZnONPs) as promising antimicrobial agents, particularly for oral health applications. Conclusion This study provides promising results for the antimicrobial potential of zinc oxide nanoparticles (ZnONPs) synthesized using . The consistent antimicrobial activity and variations in sensitivity among oral pathogens highlight their promising utility in oral health care.

Sugarcane is a major industrial crop highly susceptible to parasitic weed ( Striga spp. ), causing a 38% reduction in cane yield due to a longer lag phase of 20–40 days, and wider spacing. Herbicides with a longer retention and slow-release nature could allow Striga seeds to germinate and be killed before attaching to the host. Therefore, a graphene oxide based nanoformulation loaded with atrazine was synthesized and evaluated under controlled and field conditions for its release kinetics, Striga control efficiency (SCE), and cane yield for two years (2018–2019) at two locations. In-vitro assays on release kinetics showed that the release rate of active ingredient (a.i.) from the nanocomposite loaded with atrazine (NCA) was slower (64.5%) than conventional atrazine (82.1%) on the 30th day in water. Similarly, cumulative release percentage of a.i. with NCA was 4.4% compared to atrazine (16.2%) at the initial 0–3 days in soil. Further, field evaluation (deep application in 12 cm furrows) of NCA at 1.25 kg a.i./ha at 95 days after planting (DAP) found superior in delaying Striga emergence by 18–20 days over atrazine. Furthermore, NCA recorded the highest efficacy (∼ 21%) across two locations owing to reduced Striga density (66.7–68.2%) and dry weight (39.3–48.9%). Consequently, NCA at 95 DAP produced higher cane (30.6–31.0%) and sugar (30.7–36.7%) yields. Therefore, carbon-based graphene oxide with a greater surface area and low production cost would offer an environmentally benign and alternative option in controlling Striga before its haustorium attaches to sugarcane roots. This formulation represents a novel direction for developing herbicides with enhanced performance and reduced environmental impact.