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Purpose: Black men in the United States suffer significantly higher incidence of and mortality from prostate cancer (PCa) than non-Black men. The cause of this disparity is multifactorial, though inequitable access to curative radiation modalities, including low-dose-rate (LDR) brachytherapy, may contribute. Despite this, there are few analyses evaluating the potential of different radiation therapies to mitigate outcome disparities. Therefore, we examined the clinical outcomes of Black and non-Black patients treated with definitive LDR brachytherapy for prostate cancer.Methods: Data were collected for all patients treated with definitive LDR brachytherapy between 2005 and 2018 on a retrospective IRB-approved protocol. Pearson Chi-Squared analysis was used to assess demographic and cancer differences between Black and non-Black cohorts. Freedom from biochemical failure (FFBF) was calculated using Kaplan-Meier analysis. Univariate and multivariate analyses were used to identify factors predictive of biochemical failure.Results: One hundred and sixty-seven patients were included in the analysis (Black: n=81 [48.5%]) with a median follow-up of 88.4 months. Black patients were from lower income communities (P <0.01), had greater social vulnerability (P <0.01), and had a longer interval between diagnosis and treatment (P = 0.011). Overall cumulative FFBF was 92.3% (95% CI: 87.8% - 96.8%) at 5 years and 87.7% (95% CI: 82.0% - 93.4%) at 7 years. There was no significant difference in FFBF in Black and non-Black patients (P = 0.114) and Black race was not independently predictive of failure (HR 1.51 [95% CI: 0.56 - 4.01]; P = 0.42). Overall survival was comparable between racial groups (P = 0.972). Only nadir PSA was significantly associated with biochemical failure on MVA (HR = 3.57 [95% CI: 02.44 - 5.22]; P <0.001).Conclusions: Black men treated with LDR brachytherapy achieved similar FFBF to their non-Black counterparts despite poorer socioeconomic status. This suggests that PCa treatment with brachytherapy may eliminate some disparities clinical outcomes. [ABSTRACT FROM AUTHOR]

The manuscript revealed the ameliorative effects of exogenous melatonin in two distinct reproductive stages, i.e., developing grains (20 days after pollination) and matured grains (40 days after pollination) in two contrasting indica rice genotypes, viz., Khitish (arsenic-susceptible) and Muktashri (arsenic-tolerant), irrigated with arsenic-contaminated water throughout their life-cycle. Melatonin administration improved yield-related parameters like rachis length, primary and secondary branch length, number of grains per panicle, number of filled and empty grains per panicle, grain length and breadth and 1000-grain per weight. Expression of GW2 , which negatively regulates grain development, was suppressed, along with concomitant induction of positive regulators like GIF1 , DEP1 and SPL14 in both Khitish and Muktashri. Melatonin lowered arsenic bioaccumulation in grains and tissue biomass, more effectively in Khitish. Unregulated production of reactive oxygen species, leading to cellular necrosis caused by arsenic, was reversed in presence of melatonin. Endogenous melatonin level was stimulated due to up-regulation of the key biosynthetic genes, SNAT and ASMT. Melatonin enhanced the production of diverse antioxidants like anthocyanins, flavonoids, total phenolics and ascorbic acid and also heightened the production of thiol-metabolites (cysteine, reduced glutathione, non-protein thiols and phytochelatin), ensuring effective chelation and arsenic detoxification. Altogether, our observation, supported by principal component analysis, proved that melatonin re-programs the antioxidative metabolome to enhance plant resilience against arsenic stress to mitigate oxidative damages and reduce arsenic translocation from the soil to tissue biomass and edible grains. [Display omitted] • Arsenic accumulates in rice grains due to conventional waterlogged irrigation. • Exogenous melatonin improved agronomic yield attributes more efficiently in Khitish. • Melatonin elevated antioxidant and thiol-metabolites to minimize oxidative stress. • Key genes involved in melatonin biosynthesis were induced. • Oxidative injuries were mitigated in both rice genotypes. [ABSTRACT FROM AUTHOR]

Drought is undoubtedly a major environmental constraint that negatively affects agricultural yield and productivity throughout the globe. Plants are extremely vulnerable to drought which imposes several physiological, biochemical and molecular perturbations. Increased generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in different plant organs is one of the inevitable consequences of drought. ROS and RNS are toxic byproducts of metabolic reactions and poise oxidative stress and nitrosative stress that are detrimental for plants. In spite of toxic effects, these potentially active radicals also play a beneficial role in mediating several signal transduction events that lead to plant acclimation and enhanced survival under harsh environmental conditions. The precise understanding of ROS and RNS signaling and their molecular paradigm with different phytohormones, such as auxin, gibberellin, cytokinin, abscisic acid, ethylene, brassinosteroids, strigolactones, jasmonic acid, salicylic acid and melatonin play a pivotal role for maintaining plant fitness and resilience to counteract drought toxicity. Therefore, the present review provides an overview of integrated systemic signaling between ROS, RNS and phytohormones during drought stress based on past and recent advancements and their influential role in conferring protection against drought-induced damages in different plant species. Indeed, it would not be presumptuous to hope that the detailed knowledge provided in this review will be helpful for designing drought-tolerant crop cultivars in the forthcoming times. [Display omitted] • Drought can cause serious threat to agricultural crop production, thereby affecting global food security. • Excess generation of ROS and RNS during drought act as a signal for phytohormone accumulation for ROS and RNS scavenging. • Crosstalk between ROS, RNS and phytohormone signaling plays pivotal role in understanding drought stress tolerance mechanism. • Drought-induced overproduction of ROS and RNS regulates stomatal closure. [ABSTRACT FROM AUTHOR]

Purpose: Radiation injury to the bronchial tree is an important yet poorly understood potential side effect in lung stereotactic ablative radiation therapy (SAbR). We investigate the integration of virtual bronchoscopy in radiation therapy planning to quantify dosage to individual airways. We develop a risk model of airway collapse and develop treatment plans that reduce the risk of radiation-induced airway injury.Methods and Materials: Pre- and post-SAbR diagnostic-quality computerized tomography (CT) scans were retrospectively collected from 26 lung cancer patients. From each scan, the bronchial tree was segmented using a virtual bronchoscopy system and registered deformably to the planning CT. Univariate and stepwise multivariate Cox regressions were performed, examining factors such as age, comorbidities, smoking pack years, airway diameter, and maximum point dosage (Dmax). Logistic regression was utilized to formulate a risk function of segmental collapse based on Dmax and diameter. The risk function was incorporated into the objective function along with clinical dosage volume constraints for planning target volume (PTV) and organs at risk (OARs).Results: Univariate analysis showed that segmental diameter (P = .014) and Dmax (P = .007) were significantly correlated with airway segment collapse. Multivariate stepwise Cox regression showed that diameter (P = .015), Dmax (P < .0001), and pack/years of smoking (P = .02) were significant independent factors associated with collapse. Risk management-based plans enabled significant dosage reduction to individual airway segments while fulfilling clinical dosimetric objectives.Conclusion: To our knowledge, this is the first systematic investigation of functional avoidance in lung SAbR based on mapping and minimizing doses to individual bronchial segments. Our early results show that it is possible to substantially lower airway dosage. Such dosage reduction may potentially reduce the risk of radiation-induced airway injury, while satisfying clinically prescribed dosimetric objectives. [ABSTRACT FROM AUTHOR]

Reduced intensity conditioning (RIC) regimens decrease the risk for nonrelapse mortality (NRM) in adult patients undergoing allogeneic hematopoietic stem cell transplantation for hematologic malignancies but increase the risk for relapse. The aim of this study was to compare the outcomes of fludarabine–total body irradiation (TBI) with fludarabine among patients with hematologic diseases. This retrospective study of 137 patients with different hematologic malignancies compared the outcomes of 63 patients who received a conventional RIC regimen with 2 days of IV busulfan (3.2 mg/kg/d × 2 days) and fludarabine with 74 patients who received the same regimen plus 400 cGy of fludarabine and busulfan (FB)-TBI divided in 2 doses over 1 day (200 cGy BID). Median follow-up was 4.62 years. The donors were either HLA-matched siblings (36%) or HLA-matched unrelated donors (64%). The FB-TBI showed trends toward improvement in progression-free survival (PFS) and overall survival (OS) over FB (5-year PFS rates 50% vs 34%, P =.06, and 5-year OS rate 53% vs 39%, P =.13). Acute graft-vs-host disease (aGVHD), relapse, and NRM were similar between the 2 groups. The 5-year cumulative incidence of chronic GVHD (cGVHD) was lower in the FB-TBI group compared with the FB group (29% vs 52%, P =.003). Multivariable analysis revealed that grade III-IV aGVHD was the only independent risk factor for worse OS (P =.001) in both groups. A high disease risk index was possibly associated with inferior OS (P =.07) in both groups. The FB-TBI is a safe and effective intensified RIC regimen for adult patients with hematologic malignancies. It predicted a lower risk for cGVHD and showed possibly improved PFS and OS compared with FB. [ABSTRACT FROM AUTHOR]

• Many head/neck squamous cell cancer patients develop recurrence or second primary. • Re-irradiation is a curative treatment option for these patients. • However, it is associated with significant risk of toxicity. • Pulsed Reduced Dose Rate radiation may reduce re-irradiation toxicity. Pulsed reduced dose rate (PRDR) radiation (RT) is a re-irradiation (Re-RT) technique that potentially overcomes dose/volume constraints in the setting of previous RT. There is minimal data for its use for recurrent or secondary primary head and neck squamous cell carcinoma (HNSCC). In this study, we report preliminary data from our institution of a consecutive cohort of HNSCC patients who received PRDR Re-RT. Nine patients received PRDR Re-RT from August 2020 to January 2023 and had analyzable data. Intensity modulated RT was used for treatment delivery and a wait time between 20 cGy arc/helical deliveries was used to achieve the effective low dose rate. Data collected included patient demographic information, prior interventions, diagnosis, radiation therapy dose and fractionation, progression free survival, overall survival, and toxicity rates. The median time to PRDR-RT from completion of initial RT was 13 months (range, 6–50 months). All but one patient underwent salvage surgery prior to PRDR-RT. The median follow-up after Re-RT was 7 months. The median OS from PRDR-RT was 7 months (range, 1–32 months). Median PFS was 7 months (range, 1–32 months). One patient (11.1 %) had acute grade 3 toxicity, and two patients (22.2 %) had late grade 3 toxicities. There were no grade 4+ toxicities. PRDR Re-RT is a feasible treatment strategy for patients with recurrent or second primary HNSCC. Initial findings from this retrospective review suggest reasonable survival outcomes and potentially improved toxicity; prospective data is needed to establish the safety and efficacy of this technique. [ABSTRACT FROM AUTHOR]

Purpose/objectives: Radiation-induced erectile-dysfunction (RiED) is one of the most common side effects of radiation therapy (RT) and significantly reduces the quality of life (QoL) of cancer patients. Approximately 50% of prostate cancer patients experience RiED within 3 to 5 years after completion of RT. A series of vascular, muscular, and neurogenic injuries after prostate RT lead to RiED; however, the precise role of RT-induced neurogenic injury in RiED has not been fully established. The cavernous nerves (CN) are postganglionic parasympathetic nerves located beside the prostate gland that assist in penile erection. This study was designed to investigate the role of CN injury, tissue damage, and altered signaling pathways in an RiED rat model.Methods and Materials: Male rats were exposed to a single dose of 25 Gy prostate-confined RT. Erectile function was evaluated by intracavernous pressure (ICP) measurements conducted both 9 and 14 weeks after RT. Neuronal injury was evaluated in the CN using quantitative polymerase chain reaction, conduction studies, transmission electron microscopy, and immunoblotting. Masson trichrome staining was performed to elucidate fibrosis level in penile tissues.Results: There were significant alterations in the ICP (P<.0001) of RT rats versus non-RT rats. TEM analysis showed decreased myelination, increased microvascular damage, and progressive axonal atrophy of the CN fibers after RT. Electrophysiologic analysis showed significant impairment of the CN conduction velocity after RT. RT also significantly increased RhoA/Rho-associated protein kinase 1 (ROCK1) mRNA and protein expression. In addition, penile tissue showed increased apoptosis and fibrosis 14 weeks after RT.Conclusions: RT-induced CN injury may contribute to RiED; this is therefore a rationale for developing novel therapeutic strategies to mitigate CN and tissue damage. Moreover, further investigation of the RhoA/ROCK pathway's role in mitigating RiED is necessary. [ABSTRACT FROM AUTHOR]