Investigating the antioxidant potential and mechanism of a hydrazide bioactive component of garlic: insights from density functional theory calculations, drug-likeness and molecular docking studies.

Glutathione remains one of the most efficient antioxidant compounds in living systems, and the biological abilities of hydrazides have been well documented in literature. This study highlights the phytochemical constituents of garlic and the separation of the bioactive benzoic acid, 4-chloro- 1-(4-methoxyphenyl) hydrazide (BA4C) using gas chromatography-mass spectroscopy (GC-MS) technique. Preliminary phytochemical screening reveals the presence of alkaloids, saponins, flavonoids, tannins, terpenoids, steroids and phenols. Computationally, compound BA4C was optimized using the B3LYP/aug-cc-PVDZ DFT method. Spectroscopic studies of the compound involved analysis of the vibrational FT-IR frequencies and the modes of vibrations. Frontier molecular orbitals analysis records an energy gap of 4.3391 eV; NBO studies reveal that the compound has strong perturbation energies of 246 kcal/mol and 269 kcal/mol among its intramolecular interactions such as π *C12 - C13 to π *C14 - C15 and π *C11 - C16 to π *C14 - C15, respectively. According to the visualization of non-covalent interactions, steric repulsions were observed at the core of the phenyl and benzene rings. However, other regions of the compound depict a significant balance of forces between steric repulsions and van der Waals forces. To significantly deduce the reducing power of compound BA4C, electrons were found to be highly localized at the methoxy and hydrazide moieties significantly implying their propensity to donate electrons to oxidized systems. Furthermore, ADMET analysis reveals that the compound has two hydrogen donors. Most significantly, the compound binds to NADPH dehydrogenase (5V4P) and glutathione reductase (1XAN) with binding energies of - 6.0 kcal/mol and - 8.0 kcal/mol showing considerable favourable binding feasibility as well as forming plural hydrogen bonds with the amino acid residues. Notably, BA4C was bonded at the active site of 1XAN, which implies the ability of the compound for the reduction of oxidized glutathione.

Emulations of Oncology Trials Using Real-World Data: A Systematic Literature Review.

By evaluating published emulations of oncology RCTs studies in which both the active and comparator groups are sourced from RWD and target trial results are available for benchmarking, this systematic review aims to gain insight into factors related to emulation performance. Thirteen oncology emulation studies using various types of RWD were identified through an online database search of PubMed through 2022. Based on the ROBINS-I tool, most studies (N=8) had a serious risk of overall bias driven by risk of bias from confounding. Approximately half of the studies (N=6) fully proxied the RCT entry criteria. Of 11 RWD studies that provided sufficient detail to quantify emulation performance, the emulation HR estimate fell within the 95% CI of the trial estimate in 9 of the studies. There were no clear trends between risk of bias or degree to which the entry criteria were proxied and emulation performance. Findings may have been influenced by publication bias and researcher degrees of freedom, as only one emulation study pre-registered its protocol. Tools for comprehensively characterizing factors that affect emulation performance, including the real-world clinical context as it relates to the RCT research question, are needed to evaluate the feasibility of a RCT emulation.

Proteostasis perturbation of N-Myc leveraging HSP70 mediated protein turnover improves treatment of neuroendocrine prostate cancer.

N-Myc is a key driver of neuroblastoma and neuroendocrine prostate cancer (NEPC). One potential way to circumvent the challenge of undruggable N-Myc is to target the protein homeostasis (proteostasis) system that maintains N-Myc levels. Here, we identify heat shock protein 70 (HSP70) as a top partner of N-Myc, which binds a conserved "SELILKR" motif and prevents the access of E3 ubiquitin ligase, STIP1 homology and U-box containing protein 1 (STUB1), possibly through steric hindrance. When HSP70's dwell time on N-Myc is increased by treatment with the HSP70 allosteric inhibitor, STUB1 is in close proximity with N-Myc and becomes functional to promote N-Myc ubiquitination on the K416 and K419 sites and forms polyubiquitination chains linked by the K11 and K63 sites. Notably, HSP70 inhibition significantly suppressed NEPC tumor growth, increased the efficacy of aurora kinase A (AURKA) inhibitors, and limited the expression of neuroendocrine-related pathways.

The Job Demands and Accommodation Planning Tool (JDAPT): A Nine-Month Evaluation of Use, Changes in Self-efficacy, Presenteeism, and Absenteeism in Workers with Chronic and Episodic Disabilities.

PURPOSE: Enhancing workplace communication and support processes to enable individuals living with disabilities to sustain employment and return to work is a priority for workers, employers, and community stakeholders. The objective of this study was to evaluate a new resource that addresses support challenges, the Job Demands and Accommodation Planning Tool (JDAPT), and assess its use, relevance, and outcomes over a nine-month follow-up period. METHODS: Workers with physical and mental health/cognitive conditions causing limitations at work were recruited using purposive sampling. Online surveys were administered at baseline (prior to using the JDAPT), and at three and nine months post-baseline. Information was collected on demographics (e.g., age, gender) and work characteristics (e.g., job sector, organization size). Outcomes included assessing JDAPT use and relevance, and changes in self-efficacy, work productivity difficulties, employment concerns, difficulties with job demands, and absenteeism. RESULTS: Baseline participants were 269 workers (66% women; mean age 41 years) of whom 188 (69.9%) completed all three waves of data collection. Many workers reported using JDAPT strategies at and outside of work, and held positive perceptions of the tool's usability, relevance, and helpfulness. There were significant improvements (Time 1-2; Time 1-3) in self-efficacy, perceived work productivity, and absenteeism with moderate to large effect sizes in self-efficacy and productivity (0.46 to 0.78). Findings were consistent across gender, age, health condition, and work context variables. CONCLUSIONS: The JDAPT can enhance support provision and provide greater transparency and consistency to workplace disability practices, which is critical to creating more inclusive and accessible employment opportunities.

Patient-reported outcomes and functional assessments of patients with Alkaptonuria in a 3-year Nitisinone treatment trial.

Alkaptonuria is a rare disorder of tyrosine catabolism caused by deficiency of homogentisate 1,2-dioxygenase that leads to accumulation of homogentisic acid (HGA). Deposition of HGA-derived polymers in connective tissue causes progressive arthropathy of the spine and large joints, cardiac valvular disease, and genitourinary stones beginning in the fourth decade of life. Nitisinone, a potent inhibitor of the upstream enzyme, 4-hydroxyphenylpyruvate dioxygenase, dramatically reduces HGA production. As such, nitisinone is a proposed treatment for alkaptonuria. A randomized clinical trial of nitisinone in alkaptonuria confirmed the biochemical efficacy and tolerability of nitisinone for patients with alkaptonuria but the selected primary outcome did not demonstrate significant clinical benefit. Given that alkaptonuria is a rare disease with slow progression and variable presentation, identifying outcome parameters that can detect significant change during a time-limited clinical trial is challenging. To gain insight into patient-perceived improvements in quality of life and corresponding changes in physical function associated with nitisinone use, we conducted a post-hoc per protocol analysis of patient-reported outcomes and a functional assessment. Analysis revealed that nitisinone-treated patients showed significant improvements in complementary domains of the 36-Item Short-Form Survey (SF-36) and 6-min walk test (6MWT). Together, these findings suggest that nitisinone improves both quality of life and function of patients with alkaptonuria. The observed trends support nitisinone as a therapy for alkaptonuria.

Distal Radius Fracture Rehabilitation.

Distal radius fracture (DRF) is arguably the most common upper extremity fracture resulting from a fall accident. These clinical practice guidelines (CPG) were developed to guide all aspects of the management of DRF by physical therapists and other rehabilitation practitioners, such as certified hand therapists. This CPG employed a systematic review methodology to locate, appraise, and synthesize contemporary evidence while developing practice recommendations for determining the prognosis of outcomes, examination, and interventions while managing individuals with DRF. The quality of the primary studies found in the literature search was appraised using standardized tools. The strength of the available evidence for a particular practice domain (e.g., prognosis or intervention) was graded as strong, moderate, weak, or conflicting, where such gradings guided the level of obligation for each practice recommendation. Lastly, the CPG also provided the gaps in the evidence pool for the rehabilitation of DRF that future research efforts can address. J Orthop Sports Phys Ther 2024;54(9):CPG1-CPG78. doi:10.2519/jospt.2024.0301.

Evolving Trends in the Management of Diabetic Foot Ulcers: A Narrative Review.

The prevalence of diabetic foot ulcers (DFUs) is projected to increase worldwide, which necessitates a review of the current management principles and the development of new approaches to care. The principles of management involve proper glycemic control, infection control, pressure redistribution, wound care debridement, and revascularization. Other modalities of management, such as hyperbaric oxygen therapy and negative wound pressure therapy, are also being explored. While some aspects of DFU care lack high-quality evidence, a multidisciplinary approach incorporating these evolving trends has the potential to improve outcomes and prevent lower extremity amputations in this challenging condition. This review highlights the need for further research to establish definitive treatment protocols for optimal DFU management.

The Validity and Responsiveness of the Patient-Specific Functional Scale in Patients With First Carpometacarpal Osteoarthritis.

PURPOSE: The purpose of this study was to assess the content, construct, and discriminative validity and responsiveness of the Patient-Specific Functional Scale (PSFS) in patients with thumb carpometacarpal arthritis. METHODS: Data were collected at Xpert Clinics, comprising 34 outpatient hand surgery and hand therapy clinics in the Netherlands. We included 267 patients for content validity and 323 patients for construct validity and responsiveness. The PSFS items were classified into the International Classification of Function Core Set for Hand Conditions to assess content validity. We used hypothesis testing to investigate the construct validity and responsiveness. The Michigan Hand Outcomes Questionnaire was used as a comparator instrument. The standardized response mean was calculated to evaluate the magnitude of change. For discriminative validity, we used independent t tests to discriminate between satisfied and dissatisfied patients. RESULTS: We classified 98% of the PSFS items in the International Classification of Function "activities" and "participation" domains, indicating good content validity. Two of six hypotheses for construct validity and three of six hypotheses for responsiveness were confirmed. The standardized response mean for the PSFS was 0.57 (0.46-0.68) and 0.47 (0.35-0.58) for the Michigan Hand Outcomes Questionnaire total score. The mean PSFS score showed good discriminative validity because it could distinguish between satisfied and dissatisfied patients at the 3-month follow-up. CONCLUSIONS: The PSFS scores showed good content and discriminative validity in patients with first carpometacarpal arthritis. Hypothesis testing for responsiveness and construct validity indicates that the PSFS measures a unique construct different from the Michigan Hand Outcomes Questionnaire. CLINICAL RELEVANCE: The PSFS may be a useful scale for measuring the patient-specific status of individuals with thumb carpometacarpal arthritis.

Plexin D1 emerges as a novel target in the development of neural lineage plasticity in treatment-resistant prostate cancer.

Treatment-induced neuroendocrine prostate cancer (t-NEPC) often arises from adenocarcinoma via lineage plasticity in response to androgen receptor signaling inhibitors, such as enzalutamide. However, the specific regulators and targets involved in the transition to NEPC are not well understood. Plexin D1 (PLXND1) is a cellular receptor of the semaphorin (SEMA) family that plays important roles in modulating the cytoskeleton and cell adhesion. Here, we found that PLXND1 was highly expressed and positively correlated with neuroendocrine markers in patients with NEPC. High PLXND1 expression was associated with poorer prognosis in prostate cancer patients. Additionally, PLXND1 was upregulated and negatively regulated by androgen receptor signaling in enzalutamide-resistant cells. Knockdown or knockout of PLXND1 inhibited neural lineage pathways, thereby suppressing NEPC cell proliferation, patient derived xenograft (PDX) tumor organoid viability, and xenograft tumor growth. Mechanistically, the heat shock protein 70 (HSP70) regulated PLXND1 protein stability through degradation, and inhibition of HSP70 decreased PLXND1 expression and NEPC organoid growth. In summary, our findings indicate that PLXND1 could serve as a promising therapeutic target and molecular marker for NEPC.

The proteome of Nicotiana benthamiana is shaped by extensive protein processing.

Processing by proteases irreversibly regulates the fate of plant proteins and hampers the production of recombinant proteins in plants, yet only few processing events have been described in agroinfiltrated Nicotiana benthamiana, which has emerged as the main transient protein expression platform in plant science and molecular pharming. Here, we used in-gel digests and mass spectrometry to monitor the migration and topography of 5040 plant proteins within a protein gel. By plotting the peptides over the gel slices, we generated peptographs that reveal where which part of each protein was detected within the protein gel. These data uncovered that 60% of the detected proteins have proteoforms that migrate at lower than predicted molecular weights, implicating extensive proteolytic processing. This analysis confirms the proteolytic removal and degradation of autoinhibitory prodomains of most but not all proteases, and revealed differential processing within pectinemethylesterase and lipase families. This analysis also uncovered intricate processing of glycosidases and uncovered that ectodomain shedding might be common for a diverse range of receptor-like kinases. Transient expression of double-tagged candidate proteins confirmed processing events in vivo. This large proteomic dataset implicates an elaborate proteolytic machinery shaping the proteome of N. benthamiana.

Comparative Pharmacokinetics and Safety Assessment of 1st- and 2nd-Generation Zinpentraxin Alfa Drug Products in Healthy Volunteers: A Randomized Crossover Study.

Zinpentraxin alfa is a recombinant form of the human pentraxin-2 that was studied in idiopathic pulmonary fibrosis (IPF). To improve the purity and yield of the drug material, a 2nd-generation drug product was developed. To characterize and compare the pharmacokinetic (PK) properties of the 1st- and 2nd-generation zinpentraxin alfa, PK studies were conducted in healthy volunteers (HVs). In a phase 1 randomized, double-blind, 2-sequence crossover, sequential 2-stage study (ISRCTN59409907), single intravenous (IV) doses of 1st- and 2nd-generation zinpentraxin alfa at 10 mg/kg were studied with a blinded interim analysis (IA) at the end of stage 1. Bioequivalence (BE) was achieved for the maximum observed plasma concentration (Cmax), but the overall exposure was higher for the 2nd- compared to the 1st-generation zinpentraxin alfa. The study was stopped after stage 1 as the gating criteria were met based on the result of the blinded IA. Safety profiles were similar for the 1st- and 2nd-generation drug products, and antidrug antibody (ADA) was not observed in this study.

Latent Profile Analysis of Canadian Military Veterans With Chronic Pain Identifies 5 Meaningful Classes Through Self-Report Measures.

The purpose of this study was to identify meaningful response patterns in self-report survey data collected from Canadian military veterans with chronic pain and to create an algorithm intended to facilitate triage and prioritization of veterans to the most appropriate interventions. An online survey was presented to former members of the Canadian military who self-identified as having chronic pain. Variables collected were related to pain, physical and mental interference, prior traumatic experiences, and indicators from each of the 7 potential drivers of the pain experience. Maximum likelihood estimation-based latent profile analysis was used to identify clinically and statistically meaningful profiles using the 7-axis variables, and classification and regression tree (CRT) analysis was then conducted to identify the most parsimonious set of indicators that could be used to accurately classify respondents into the most relevant profile group. Data from N = 322 veterans were available for analysis. The results of maximum likelihood estimation-based latent profile analysis indicated a 5-profile structure was optimal for explaining the patterns of responses within the data. These were: Mood-Dominant (13%), Localized Physical (24%), Neurosensory-Dominant (33%), Central-Dominant with complex mood and neurosensory symptoms (16%), and Trauma- and mood-dominant (14%). From CRT analysis, an algorithm requiring only 3 self-report tools (central symptoms, mood screening, bodily coherence) achieved 83% classification accuracy across the 5 profiles. The new classification algorithm requiring 16 total items may be helpful for clinicians and veterans in pain to identify the most dominant drivers of their pain experience that may be useful for prioritizing intervention strategies, targets, and relevant health care disciplines. PERSPECTIVE: This article presents the results of latent profile (cluster) analysis of responses to standardized self-report questionnaires by Canadian military veterans with chronic pain. It identified 5 clusters that appear to represent different drivers of the pain experience. The results could be useful for triaging veterans to the most appropriate pain care providers.

A Phase 1a Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7303509, an Anti-TGFß3 Antibody, in Healthy Volunteers.

INTRODUCTION: Transforming growth factor beta (TGFß) cytokines (TGFß1, TGFß2, and TGFß3) play critical roles in tissue fibrosis. However, treatment with systemic pan-TGFß inhibitors have demonstrated unacceptable toxicities. In this study, we evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of RO7303509, a high-affinity, TGFß3-specific, humanized immunoglobulin G1 monoclonal antibody, in healthy adult volunteers (HVs). METHODS: This phase 1a, randomized, double-blind trial included six cohorts for evaluation, with each cohort receiving single doses of placebo or RO7303509, administered intravenously (IV; 50 mg, 150 mg, 240 mg) or subcutaneously (SC; 240 mg, 675 mg, 1200 mg). The frequency and severity of adverse events (AEs) and RO7303509 serum concentrations were monitored throughout the study. We also measured serum periostin and cartilage oligomeric matrix protein (COMP) by immunoassay and developed a population pharmacokinetics model to characterize RO7303509 serum concentrations. RESULTS: The study enrolled 49 HVs, with a median age of 39 (range 18-73) years. Ten (27.8%) RO7303509-treated subjects reported 24 AEs, and six (30.8%) placebo-treated subjects reported six AEs. The most frequent AEs related to the study drug were injection site reactions and infusion-related reactions. Maximum serum concentrations (Cmax) and area under the concentration-time curve from time 0 to infinity (AUC0-inf) values for RO7303509 appeared to increase dose-proportionally across all doses tested. Serum concentrations across cohorts were best characterized by a two-compartment model plus a depot compartment with first-order SC absorption kinetics. No subjects tested positive for anti-drug antibodies (ADAs) at baseline; one subject (2.8%; 50 mg IV) tested positive for ADAs at a single time point (day 15). No clear pharmacodynamic effects were observed for periostin or COMP upon TGFß3 inhibition. CONCLUSION: RO7303509 was well tolerated at single SC doses up to 1200 mg in HVs with favorable pharmacokinetic data that appeared to increase dose-proportionally. TGFß3-specific inhibition may be suitable for development as a chronic antifibrotic therapy. TRIAL REGISTRATION: ISRCTN13175485.

Exploring differences between gender expressions in exercise self-efficacy and outcome expectations for exercise in individuals with stroke.

Gender expression may be associated with exercise self-efficacy and outcome expectations for exercise in the general population. Exercising for challenge and enjoyment are associated with the instrumental traits typically held by individuals with masculine gender expressions. Conversely, exercising for weight loss to receive validation from others are in line with the expressive traits most commonly held by individuals with feminine gender expressions. Moreover, possessing neither dominant nor expressive traits (undifferentiated gender expressions) have been linked to poorer psychological outcomes. Exercise is important after stroke, but gender differences in psychosocial factors for exercise in this population were unknown. The purpose of this study was to explore whether gender expression differences exist in exercise self-efficacy and outcome expectations for exercise post-stroke. Gender expression (masculine, feminine, androgynous, undifferentiated) was assessed using the Bem Sex-Role Inventory-12 (BSRI-12) in 67 individuals with stroke. Self-efficacy and outcomes expectations for exercise were assessed using the Self-Efficacy for Physical Activity Scale and Short Outcome Expectations for Exercise Scale, respectively. One-way analysis of covariance models were conducted, adjusting for biological sex, age, and time post-stroke. There were differences in exercise self-efficacy across the four gender expression groups (F(3,60) = 4.28, p<0.01), where individuals with masculine gender expressions had higher self-efficacy than those with undifferentiated gender expressions (adjusted mean: 3.56 [SE: 0.17] vs. 2.72 [SE:0.18], p<0.01). There were no differences in outcome expectations for exercise (F(3,57) = 1.08, p = 0.36) between gender expressions. In our pairwise comparisons, we found that individuals with masculine gender expressions had higher exercise self-efficacy than individuals possessing undifferentiated gender expressions. Strategies to enhance exercise self-efficacy after stroke are needed, particularly for individuals with undifferentiated gender expression. There were no associations between gender expression and outcome expectations for exercise after stroke. Clinicians may continue reinforcing the positive expectations towards exercise across all gender expressions.

Valorization of Agricultural Rice Straw as a Sustainable Feedstock for Rigid Polyurethane/Polyisocyanurate Foam Production.

Agricultural rice straw (RS), often discarded as waste in farmlands, represents a vast and underutilized resource. This study explores the valorization of RS as a potential feedstock for rigid polyurethane/polyisocyanurate foam (RPUF) production. The process begins with the liquefaction of RS to create an RS-based polyol, which is then used in a modified foam formulation to prepare RPUFs. The resulting RPUF samples were comprehensively characterized according to their physical, mechanical, and thermal properties. The results demonstrated that up to 50% by weight of petroleum-based polyol can be substituted with RS-based polyol to produce a highly functional RPUF. The obtained foams exhibited a notably low apparent density of 18-24 kg/m3, exceptional thermal conductivity ranging from 0.031-0.041 W/m-K, and a high compressive strength exceeding 250 kPa. This study underlines the potential of the undervalued agricultural RS as a green alternative to petroleum-based feedstocks to produce a high-value RPUF. Additionally, the findings contribute to the sustainable utilization of abundant agricultural waste while offering an eco-friendly option for various applications, including construction materials and insulation.

Framing Physical Literacy for Adults Through a Rehabilitation Lens: An Expert Consensus Study.

Research indicates a positive relationship between physical literacy and healthy aging; however, there is no consensus on the components required to become a physically literate adult. The objective of this study was to understand how physical literacy for adults with chronic conditions is characterized from the perspective of healthcare professionals. Physiotherapy leaders and physical literacy researchers within North America were invited to an online consensus panel and presented with questions related to physical literacy and rehabilitation. A nominal group technique was used for idea generation, clarification, and ranking. Confidence and safety with movements, motivation and commitment to physical activity, the ability to self-monitor changes in function, and understanding the benefits of physical activity were key components when defining physical literacy. There is a need to reconceptualize physical literacy to include the rehabilitation needs of adults living with chronic conditions, and to design programs that promote physical literacy to enhance function and mobility.

Which Remote Rehabilitation Interventions Work Best for Chronic Musculoskeletal Pain and Depression? A Bayesian Network Meta-Analysis.

OBJECTIVE: To evaluate the effectiveness of remote rehabilitation interventions for people living with chronic musculoskeletal pain and depression. DESIGN: A systematic review with network meta-analysis (NMA) of randomized controlled trials. LITERATURE SEARCH: We searched the Cochrane Central Register of Controlled Trials, CINAHL, EMBASE, LILACS MEDLINE, PSYNDEX, and PsycINFO databases from inception to May 2023. STUDY SELECTION CRITERIA: Randomized controlled trials that evaluated the effectiveness of remote rehabilitation interventions in people with chronic musculoskeletal pain and depression. DATA SYNTHESIS: We used Bayesian random-effects models for the NMA. Effect estimates were comparisons between rehabilitation interventions and waitlist. We performed a sensitivity analysis based on bias in the randomization process, large trials (>100 patients per arm) and musculoskeletal condition. RESULTS: Fifty-eight randomized controlled trials involving 10 278 participants (median sample size: 137; interquartile range [IQR]: 77-236) were included. Interactive voice response cognitive behavioral therapy (CBT; standardized mean difference [SMD] -0.66, 95% credible interval [CrI] -1.17 to -0.16), CBT in person (SMD -0.50, 95% CrI -0.97 to -0.04), and mobile app CBT plus exercise (SMD -0.37, 95% CrI -0.69 to -0.02) were superior to waitlist at 12-week follow-up for reducing pain (> 98% probability of superiority). For depression outcomes, Internet-delivered CBT and telecare were superior to waitlist at 12-week follow-up (SMD -0.51, 95% CrI -0.87 to -0.13) (> 99% probability of superiority). For pain outcomes, the certainty of evidence ranged from low to moderate. For depression outcomes, the certainty of evidence ranged from very low to moderate. The proportion of dropouts attributed to adverse events was unclear. No intervention was associated with higher odds of dropout. CONCLUSION: Interactive voice response CBT and mobile app CBT plus exercise showed similar treatment effects with in-person CBT on pain reduction among people living with chronic musculoskeletal pain and depression had over 98% probability of superiority than waitlist control at 12-week follow-up. Internet-delivered CBT and telecare had over 99% probability of superiority than waitlist control for improving depression outcomes at 12-week follow-up. J Orthop Sports Phys Ther 2024;54(6):1-16. Epub 26 February 2024. doi:10.2519/jospt.2024.12216.

Radiation Oncology in the Philippines: Current State and Future Directions.

Purpose: As global cancer incidence continues to rise, low- to middle-income countries like the Philippines are projected to experience a disproportionate increase in cancer burden, further straining already limited resources. Radiation therapy (RT) is an essential and cost-effective modality in cancer care, both in the curative and palliative settings. In this article, we provide a brief narrative on the history of the field of radiation oncology in the Philippines and review the current challenges to effective and equitable RT service delivery in the country. Methods and Materials: We gathered data from the official websites of the Philippine government's health and statistics agencies, the Philippine Radiation Oncology Society, and the Directory of Radiotherapy Centers of the International Atomic Energy Agency, to review available human and infrastructure resources related to RT delivery in the country. Using the 6 health care dimensions of the World Health Organization's Building Blocks of Health Systems framework, we identified barriers to access and proposed possible initiatives for development. Results: Despite the remarkable growth of radiation oncology in the country in the past 2 decades, many challenges remain in the areas of human resources, infrastructure, policymaking, health economics, education, and service delivery. Radiation health workers and facilities are concentrated in the National Capital Region, limiting accessibility in rural areas. Out-of-pocket spending on RT-related expenditures remains high. The proper allocation of resources according to varying regional needs is impeded by the lack of a robust national cancer registry. Legislative reforms have been initiated but have yet to be fully implemented. Conclusions: Addressing these gaps in RT access will require in-depth study and multi-sectoral commitment aimed at establishing and implementing a nationwide framework for RT service delivery that can be readily adapted to varying regional needs. Despite many complex geographic, social, and economic obstacles, efforts by private and public sectors of society to provide ready access to RT services for all Filipinos continue to gain momentum.