Tensor-valued diffusion MRI detects brain microstructure changes in HIV infected individuals with cognitive impairment.

Despite advancements, the prevalence of HIV-associated neurocognitive impairment remains at approximately 40%, attributed to factors like pre-cART (combination antiretroviral therapy) irreversible brain injury. People with HIV (PWH) treated with cART do not show significant neurocognitive changes over relatively short follow-up periods. However, quantitative neuroimaging may be able to detect ongoing subtle microstructural changes. This study aimed to investigate the sensitivity of tensor-valued diffusion encoding in detecting such changes in brain microstructural integrity in cART-treated PWH. Additionally, it explored relationships between these metrics, neurocognitive scores, and plasma levels of neurofilament light (NFL) chain and glial fibrillary acidic protein (GFAP). Using MRI at 3T, 24 PWH and 31 healthy controls underwent cross-sectional examination. The results revealed significant variations in b-tensor encoding metrics across white matter regions, with associations observed between these metrics, cognitive performance, and blood markers of neuronal and glial injury (NFL and GFAP). Moreover, a significant interaction between HIV status and imaging metrics was observed, particularly impacting total cognitive scores in both gray and white matter. These findings suggest that b-tensor encoding metrics offer heightened sensitivity in detecting subtle changes associated with axonal injury in HIV infection, underscoring their potential clinical relevance in understanding neurocognitive impairment in PWH.

idh-1 neomorphic mutation confers sensitivity to vitamin B12 in Caenorhabditis elegans.

In humans, a neomorphic isocitrate dehydrogenase mutation (idh-1neo) causes increased levels of cellular D-2-hydroxyglutarate (D-2HG), a proposed oncometabolite. However, the physiological effects of increased D-2HG and whether additional metabolic changes occur in the presence of an idh-1neo mutation are not well understood. We created a Caenorhabditis elegans model to study the effects of the idh-1neo mutation in a whole animal. Comparing the phenotypes exhibited by the idh-1neo to ∆dhgd-1 (D-2HG dehydrogenase) mutant animals, which also accumulate D-2HG, we identified a specific vitamin B12 diet-dependent vulnerability in idh-1neo mutant animals that leads to increased embryonic lethality. Through a genetic screen, we found that impairment of the glycine cleavage system, which generates one-carbon donor units, exacerbates this phenotype. In addition, supplementation with alternate sources of one-carbon donors suppresses the lethal phenotype. Our results indicate that the idh-1neo mutation imposes a heightened dependency on the one-carbon pool and provides a further understanding of how this oncogenic mutation rewires cellular metabolism.

The Caenorhabditis elegans cuticle and precuticle: a model for studying dynamic apical extracellular matrices in vivo.

Apical extracellular matrices (aECMs) coat the exposed surfaces of animal bodies to shape tissues, influence social interactions, and protect against pathogens and other environmental challenges. In the nematode Caenorhabditis elegans, collagenous cuticle and zona pellucida protein-rich precuticle aECMs alternately coat external epithelia across the molt cycle and play many important roles in the worm's development, behavior, and physiology. Both these types of aECMs contain many matrix proteins related to those in vertebrates, as well as some that are nematode-specific. Extensive differences observed among tissues and life stages demonstrate that aECMs are a major feature of epithelial cell identity. In addition to forming discrete layers, some cuticle components assemble into complex substructures such as ridges, furrows, and nanoscale pillars. The epidermis and cuticle are mechanically linked, allowing the epidermis to sense cuticle damage and induce protective innate immune and stress responses. The C. elegans model, with its optical transparency, facilitates the study of aECM cell biology and structure/function relationships and all the myriad ways by which aECM can influence an organism.

C. elegans Hedgehog-related proteins are tissue- and substructure-specific components of the cuticle and pre-cuticle.

In C. elegans, expanded families of divergent Hedgehog-related and Patched-related proteins promote numerous processes ranging from epithelial and sense organ development to pathogen responses to cuticle shedding during the molt cycle. The molecular functions of these proteins have been mysterious since nematodes lack a canonical Hedgehog signaling pathway. Here we show that Hedgehog-related proteins are components of the cuticle and pre-cuticle apical extracellular matrices that coat, shape, and protect external epithelia. Of four Hedgehog-related proteins imaged, two (GRL-2 and GRL-18) stably associated with the cuticles of specific tubes and two (GRL-7 and WRT-10) labelled pre-cuticle substructures such as furrows or alae. We found that wrt-10 mutations disrupt cuticle alae ridges, consistent with a structural role in matrix organization. We hypothesize that most nematode Hedgehog-related proteins are apical extracellular matrix components, a model that could explain many of the reported functions for this family. These results highlight ancient connections between Hedgehog proteins and the extracellular matrix and suggest that any signaling roles of C. elegans Hedgehog-related proteins will be intimately related to their matrix association.

idh-1 neomorphic mutation confers sensitivity to vitamin B12 via increased dependency on one-carbon metabolism in Caenorhabditis elegans.

The isocitrate dehydrogenase neomorphic mutation ( idh-1neo ) generates increased levels of cellular D-2-hydroxyglutarate (D-2HG), a proposed oncometabolite. However, the physiological effects of increased D-2HG and whether additional metabolic changes occur in the presence of an idh-1neo mutation are not well understood. We created a C. elegans model to study the effects of the idh-1neo mutation in a whole animal. Comparing the phenotypes exhibited by the idh-1neo to Δdhgd-1 (D-2HG dehydrogenase) mutant animals, which also accumulate D-2HG, we identified a specific vitamin B12 diet-dependent vulnerability in idh-1neo mutant animals that leads to increased embryonic lethality. Through a genetic screen we found that impairment of the glycine cleavage system, which generates one-carbon donor units, exacerbates this phenotype. Additionally, supplementation with an alternate source of one-carbon donors suppresses the lethal phenotype. Our results indicate that the idh-1neo mutation imposes a heightened dependency on the one-carbon pool and provides a further understanding how this oncogenic mutation rewires cellular metabolism.

Pharmacy Assistance Programs for Oral Anticancer Drugs: A Narrative Review.

Oral anticancer medications (OAMs) are high priced with a significant cost-sharing burden to patients, which can lead to catastrophic financial, psychosocial, and clinical repercussions. Cost-conscious prescribing and inclusion of low-cost alternatives can help mitigate this burden, but cost transparency at the point of prescribing remains a major barrier to doing so. Pharmacy assistance programs, including co-payment cards and patient assistance programs administered by manufacturers and foundation-based grants, remain an essential resource for patients facing prohibitive co-payments for OAMs. However, access to these programs is fraught with complexities, including lack of trained financial navigators, limited transparency on eligibility criteria, onerous documentation burdens, and limits in available funding. Despite these drawbacks and the potential for such programs to incentivize manufacturers to keep list prices high, assistance programs have been demonstrated to improve financial well-being for patients with cancer. The increasing development of integrated specialty pharmacies with dedicated, trained pharmacy staff can help improve and standardize access to such programs, but these services are disproportionately available to patients seen at tertiary care centers. Multistakeholder interventions are needed to mitigate the burden of cost sharing for OAMs, including increased clinician knowledge of financial resources and novel assistance mechanisms, investment of institutions in trained financial navigation services and centralized platforms to identify assistance programs, and policies to cap out-of-pocket spending and improve transparency of rates charged by pharmacy benefit managers to a health plan.

Access to Financial Assistance Programs and Their Impact on Overall Spending on Oral Anticancer Medications at an Integrated Specialty Pharmacy.

PURPOSE: Financial assistance (FA) programs are increasingly used to help patients afford oral anticancer medications (OAMs), but access to such programs and their impact on out-of-pocket (OOP) spending has not been well explored. This study aimed to (1) characterize the impact of receipt of FA on both OOP spending and likelihood of catastrophic spending on OAMs and (2) evaluate racial/ethnic disparities in access to FA programs. METHODS: Patients with a cancer diagnosis prescribed an OAM anytime between January 1, 2021, and December 31, 2021 were included in this retrospective, single-center study at an integrated specialty pharmacy affiliated with a tertiary academic cancer center. Fixed-effect regression models were used to characterize the impact of receipt of FA on overall spending and likelihood of catastrophic spending on OAMs, as well as explore the association of race/ethnicity with receipt of FA. RESULTS: Across 1,186 patients prescribed an OAM, 37% received FA. Receipt of FA was associated with lower annual spending on OAMs (ß = -$1,236 US dollars [USD; 95% CI, -$1,841 to -$658], P < .001) but not reduced risk of catastrophic spending (odds ratio [OR], 0.442 [95% CI, 0.755 to 3.199], P = .23). Non-White patients (OR, 0.60 [95% CI, 0.43 to 0.85], P = .004) and patients who spoke English as a second language (OR, 0.46 [95% CI, 0.23 to 0.90], P = .02) were less likely to receive FA compared with White and English-speaking patients, respectively. CONCLUSION: FA programs can mitigate high OOP spending but not for patients who spend at catastrophic levels. There are racial/ethnic and language disparities in access to such programs. Future studies should evaluate access to FA programs across diverse delivery settings.

Clinical validity and utility of circulating tumor DNA (ctDNA) testing in advanced non-small cell lung cancer (aNSCLC): a systematic literature review and meta-analysis.

Purpose: Circulating tumor DNA (ctDNA) testing has become a promising tool to guide first-line (1L) targeted treatment for advanced non-small cell lung cancer (aNSCLC). This study aims to estimate the clinical validity (CV) and clinical utility (CU) of ctDNA-based next-generation sequencing (NGS) for oncogenic driver mutations to inform 1L treatment decisions in aNSCLC through a systematic literature review and meta-analysis. Methods: A systematic literature search was conducted in PubMed/MEDLINE and Embase to identify randomized control trials or observational studies reporting CV/CU on ctDNA testing in patients with aNSCLC. Meta-analyses were performed using bivariate random-effects models to estimate pooled sensitivity and specificity. Progression-free/overall survival (PFS/OS) was summarized for CU studies. Results: Eighteen studies were identified: 17 CV only, 2 CU only, and 1 both. Thirteen studies were included for the meta-analysis on multi-gene detection. The overall sensitivity and specificity for ctDNA detection of any mutation were 0.69 (95% CI, 0.63-0.74) and 0.99 (95% CI, 0.97-1.00) respectively. However, sensitivity varied greatly by driver gene, ranging from 0.29 (95% CI, 0.13-0.53) for ROS 1 to 0.77 (95% CI, 0.63-0.86) for KRAS . Two studies compared PFS with ctDNA versus tissue-based testing followed by 1L targeted therapy found no significant differences. One study reported OS curves on ctDNA-matched and tissue-matched therapies but no hazard ratios were provided. Conclusion: ctDNA testing demonstrated an overall acceptable diagnostic accuracy in aNSCLC patients, however, sensitivity varied greatly by driver mutation. Further research is needed, especially for uncommon driver mutations, to better understand the CU of ctDNA testing in guiding targeted treatments for aNSCLC.

The Health Inequality Impact of Liquid Biopsy to Inform First-Line Treatment of Advanced Non-Small Cell Lung Cancer: A Distributional Cost-Effectiveness Analysis.

OBJECTIVES: To perform a distributional cost-effectiveness analysis of liquid biopsy (LB) followed by, if needed, tissue biopsy (TB) (LB-first strategy) relative to a TB-only strategy to inform first-line treatment of advanced non-small cell lung cancer (aNSCLC) from a US payer perspective by which we quantify the impact of LB-first on population health inequality according to race and ethnicity. METHODS: With a health economic model, quality-adjusted life-years (QALYs) and costs per patient were estimated for each subgroup. Given the lifetime risk of aNSCLC, and assuming equally distributed opportunity costs, the incremental net health benefits of LB-first were calculated, which were used to estimate general population quality-adjusted life expectancy at birth (QALE) by race and ethnicity with and without LB-first. The degree of QALYs and QALE differences with the strategies was expressed with inequality indices. Their differences were defined as the inequality impact of LB-first. RESULTS: LB-first resulted in an additional 0.21 (95% uncertainty interval: 0.07-0.39) QALYs among treated patients, with the greatest gain observed among Asian patients (0.31 QALYs [0.09-0.61]). LB-first resulted in an increase in relative inequality in QALYs among patients, but a minor decrease in relative inequality in QALE. CONCLUSIONS: LB-first to inform first-line aNSCLC therapy can improve health outcomes. With current diagnostic performance, the benefit is the greatest among Asian patients, thereby potentially widening racial and ethnic differences in survival among patients with aNSCLC. Assuming equally distributed opportunity costs and access, LB-first does not worsen and, in fact, may reduce inequality in general population health according to race and ethnicity.

Initiation of combined antiretroviral therapy confers suboptimal beneficial effects on neurovascular function in people with HIV.

Introduction: Due to advances in combined anti-retroviral treatment (cART), there is an increased burden of age-related cerebrovascular disease (CBVD), in people living with HIV (PWH). The underlying CNS injury can be assessed by measuring cerebral blood flow (CBF) and cerebrovascular reactivity (CVR). Methods: 35 treatment-naïve PWH and 53 HIV negative controls (HC) were enrolled in this study. Study participants underwent T1-weighted anatomical, pseudo-continuous arterial spin labeling, and resting-state functional MRI to obtain measures of CBF and CVR prior to starting cART treatment and at two-time points (12 weeks and 2 years) post-cART initiation. Controls were scanned at the baseline and 2-year visits. We also measured plasma levels of microparticles of endothelial and glial origin and well-known endothelial inflammation markers, ICAM-1 and VCAM-1, to assess HIV-associated endothelial inflammation and the interaction of these peripheral markers with brain neurovascular function. Results: HIV infection was found to be associated with reduced CVR and increased levels of endothelial and glial microparticles (MPs) prior to initiation of cART. Further, CVR correlated negatively with peripheral MP levels in PWH. Discussion: Our results suggest that while cART treatment has a beneficial effect on the neurovascular function after initiation, these benefits are suboptimal over time.

The proprotein convertase BLI-4 promotes collagen secretion prior to assembly of the Caenorhabditis elegans cuticle.

Some types of collagens, including transmembrane MACIT collagens and C. elegans cuticle collagens, are N-terminally cleaved at a dibasic site that resembles the consensus for furin or other proprotein convertases of the subtilisin/kexin (PCSK) family. Such cleavage may release transmembrane collagens from the plasma membrane and affect extracellular matrix assembly or structure. However, the functional consequences of such cleavage are unclear and evidence for the role of specific PCSKs is lacking. Here, we used endogenous collagen fusions to fluorescent proteins to visualize the secretion and assembly of the first collagen-based cuticle in C. elegans and then tested the role of the PCSK BLI-4 in these processes. Unexpectedly, we found that cuticle collagens SQT-3 and DPY-17 are secreted into the extraembryonic space several hours before cuticle matrix assembly. Furthermore, this early secretion depends on BLI-4/PCSK; in bli-4 and cleavage-site mutants, SQT-3 and DPY-17 are not efficiently secreted and instead form large intracellular puncta. Their later assembly into cuticle matrix is reduced but not entirely blocked. These data reveal a role for collagen N-terminal processing in intracellular trafficking and the control of matrix assembly in vivo. Our observations also prompt a revision of the classic model for C. elegans cuticle matrix assembly and the pre-cuticle-to-cuticle transition, suggesting that cuticle layer assembly proceeds via a series of regulated steps and not simply by sequential secretion and deposition.

Apical-basal polarity of the spectrin cytoskeleton in the C. elegans vulva.

The C. elegans vulva is a polarized epithelial tube that has been studied extensively as a model for cell-cell signaling, cell fate specification, and tubulogenesis. Here we used endogenous fusions to show that the spectrin cytoskeleton is polarized in this organ, with conventional beta-spectrin ( UNC-70 ) found only at basolateral membranes and beta heavy spectrin ( SMA-1 ) found only at apical membranes. The sole alpha-spectrin ( SPC-1 ) is present at both locations but requires SMA-1 for its apical localization. Thus, beta spectrins are excellent markers for vulva cell membranes and polarity.

The proprotein convertase BLI-4 promotes collagen secretion during assembly of the Caenorhabditis elegans cuticle.

Some types of collagens, including transmembrane MACIT collagens and C. elegans cuticle collagens, are N-terminally cleaved at a dibasic site that resembles the consensus for furin or other proprotein convertases of the subtilisin/kexin (PCSK) family. Such cleavage may release transmembrane collagens from the plasma membrane and affect extracellular matrix assembly or structure. However, the functional consequences of such cleavage are unclear and evidence for the role of specific PCSKs is lacking. Here, we used endogenous collagen fusions to fluorescent proteins to visualize the secretion and assembly of the first collagen-based cuticle in C. elegans and then tested the role of the PCSK BLI-4 in these processes. Unexpectedly, we found that cuticle collagens SQT-3 and DPY-17 are secreted into the extraembryonic space several hours before cuticle matrix assembly. Furthermore, this early secretion depends on BLI-4/PCSK; in bli-4 and cleavage-site mutants, SQT-3 and DPY-17 are not efficiently secreted and instead form large intracellular aggregates. Their later assembly into cuticle matrix is reduced but not entirely blocked. These data reveal a role for collagen N-terminal processing in intracellular trafficking and in the spatial and temporal restriction of matrix assembly in vivo . Our observations also prompt a revision of the classic model for C. elegans cuticle matrix assembly and the pre-cuticle-to-cuticle transition, suggesting that cuticle layer assembly proceeds via a series of regulated steps and not simply by sequential secretion and deposition.

Private Payer and Medicare Coverage Policies for Use of Circulating Tumor DNA Tests in Cancer Diagnostics and Treatment.

BACKGROUND: Circulating tumor DNA (ctDNA) is used to select initial targeted therapy, identify mechanisms of therapeutic resistance, and measure minimal residual disease (MRD) after treatment. Our objective was to review private and Medicare coverage policies for ctDNA testing. METHODS: Policy Reporter was used to identify coverage policies (as of February 2022) from private payers and Medicare Local Coverage Determinations (LCDs) for ctDNA tests. We abstracted data regarding policy existence, ctDNA test coverage, cancer types covered, and clinical indications. Descriptive analyses were performed by payer, clinical indication, and cancer type. RESULTS: A total of 71 of 1,066 total policies met study inclusion criteria, of which 57 were private policies and 14 were Medicare LCDs; 70% of private policies and 100% of Medicare LCDs covered at least one indication. Among 57 private policies, 89% specified a policy for at least 1 clinical indication, with coverage for ctDNA for initial treatment selection most common (69%). Of 40 policies addressing progression, coverage was provided 28% of the time, and of 20 policies addressing MRD, coverage was provided 65% of the time. Non-small cell lung cancer (NSCLC) was the cancer type most frequently covered for initial treatment (47%) and progression (60%). Among policies with ctDNA coverage, coverage was restricted to patients without available tissue or in whom biopsy was contraindicated in 91% of policies. MRD was commonly covered for hematologic malignancies (30%) and NSCLC (25%). Of the 14 Medicare LCD policies, 64% provided coverage for initial treatment selection and progression, and 36% for MRD. CONCLUSIONS: Some private payers and Medicare LCDs provide coverage for ctDNA testing. Private payers frequently cover testing for initial treatment, especially for NSCLC, when tissue is insufficient or biopsy is contraindicated. Coverage remains variable across payers, clinical indications, and cancer types despite inclusion in clinical guidelines, which could impact delivery of effective cancer care.

The costs and inequities of precision medicine for patients with prostate cancer: A call to action.

Financial toxicity is a growing problem in the delivery of cancer care and contributes to inequities in outcomes across the cancer care continuum. Racial/ethnic inequities in prostate cancer, the most common cancer diagnosed in men, are well described, and threaten to widen in the era of precision oncology given the numerous structural barriers to accessing novel diagnostic studies and treatments, particularly for Black men. Gaps in insurance coverage and cost sharing are 2 such structural barriers that can perpetuate inequities in screening, diagnostic workup, guideline-concordant treatment, symptom management, survivorship, and access to clinical trials. Mitigating these barriers will be key to achieving equity in prostate cancer care, and will require a multi-pronged approach from policymakers, health systems, and individual providers. This narrative review will describe the current state of financial toxicity in prostate cancer care and its role in perpetuating racial inequities in the era of precision oncology.

Role of non-classical monocytes in HIV-associated vascular cognitive impairment.

Despite antiretroviral treatment (cART), people living with HIV (PLWH) are more susceptible to neurocognitive impairment (NCI), probably due to synergistic/additive contribution of traditional cerebrovascular risk factors. Specifically, altered blood brain barrier (BBB) and transmigration of inflammatory monocytes are risk factors for developing cerebral small vessel disease (CSVD). In order to investigate if inflammatory monocytes exacerbate CSVD and cognitive impairment, 110 PLWH on cART and 110 age-, sex- and Reynold’s cardiovascular risk score-matched uninfected individuals were enrolled. Neuropsychological testing, brain magnetic resonance imaging and whole blood analyses to measure platelet-monocyte interaction and monocyte, endothelial activation were performed. Results demonstrated that PLWH exhibited increased levels of platelet-monocyte complexes (PMCs) and higher expression of activation molecules on PMCs. PLWH with CSVD had the poorest cognitive performance and the highest circulating levels of non-classical monocytes which exhibited significant inverse correlation with each other. Furthermore, markers of monocyte and endothelium activation were significantly positively correlated indicating BBB impairment. Our results confirm that interaction with platelets activates and drives monocytes towards an inflammatory phenotype in PLWH. In particular, elevated levels of non-classical monocytes may represent a common pathway to neuroinflammation, CSVD and subsequent cognitive impairment, warranting further longitudinal studies to evaluate responsiveness of this potential biomarker.

Impact of a Comprehensive Financial Resource on Financial Toxicity in a National, Multiethnic Sample of Adult, Adolescent/Young Adult, and Pediatric Patients With Cancer.

PURPOSE: Financial toxicity is a well-recognized problem for patients with cancer. However, a crucial gap remains in describing and implementing mitigation strategies. We conducted a national survey of a multiethnic adolescent/pediatric and adult patient population served by Family Reach, a nonprofit organization focused on removing financial barriers to cancer care, to evaluate the impact of a comprehensive financial resource on patient-reported financial toxicity. METHODS: An electronic survey was administered to characterize patients' current financial health and the impact of Family Reach's resources on financial toxicity. The survey was e-mailed to all patients or caregivers who received resources from Family Reach between January 1, 2020, and June 30, 2020. Factors associated with higher financial stress and higher potential impact of resources on financial burden were evaluated through separate multivariate regression models. Qualitative responses were analyzed using manual coding and thematic analysis. RESULTS: Three hundred thirty socioeconomically and racially diverse respondents (overall response rate 40%; 46% non-Hispanic White; 48% with incomes below the federal poverty line) completed the survey and were included in the analysis. More than half of respondents reported high financial stress in the previous week. Hispanic ethnicity, Black race, and low annual household income were associated with higher financial toxicity. A greater amount of financial assistance was associated with a higher confidence rating that resources provided would decrease financial stress. In open-ended comments, respondents highlighted the impact of the COVID-19 pandemic and resulting job loss on financial toxicity, the importance of financial navigation, the benefits of financial assistance, and anxiety about long-term financial health. CONCLUSION: A comprehensive financial resource, particularly financial assistance, alleviated financial toxicity in a multiethnic national sample of patients with cancer. Ongoing work is critical to address sustainable funding sources and financial navigation to support patients during treatment and survivorship.

C. elegans Hedgehog-related proteins are tissue- and substructure-specific components of the cuticle and pre-cuticle.

In C. elegans, divergent Hedgehog-related (Hh-r) and Patched-related (PTR) proteins promote numerous processes ranging from epithelial and sense organ development to pathogen responses to cuticle shedding during the molt cycle. Here we show that Hh-r proteins are actual components of the cuticle and pre-cuticle apical extracellular matrices (aECMs) that coat, shape, and protect external epithelia. Different Hh-r proteins stably associate with the aECMs of specific tissues and with specific substructures such as furrows and alae. Hh-r mutations can disrupt matrix structure. These results provide a unifying model for the function of nematode Hh-r proteins and highlight ancient connections between Hh proteins and the extracellular matrix.

Facile encapsulation of nano zero-valent iron with calcium carbonate: synthesis, characterization and application for iron remediation.

In this study, CaCO3 was used as a modifier for nano zero-valent iron (nZVI) surface to prevent rapid aggregation and effectively utilized for iron remediation from aqueous solution. Surface chemistry and morphology of CaCO3 encapsulated nZVI (CaCO3-nZVI) before and after treatment of contaminant iron solution were characterized by scanning electron microscopy-energy dispersive X-ray (SEM-EDX), X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). The mechanisms of surface modification as well as iron remediation were well depicted with the help of these characterisation tools. Iron removal efficacy of 96.4% was achieved with 0.25 g/L adsorbent dose for an influent iron of 0.5 mg/L at pH 10 after a 3 h treatment process. When the influent concentration was increased to 10 mg/L, the removal capacity decreased to 92.1%. The study demonstrates that CaCO3 and nZVI in the encapsulated nanoparticle have a significant synergistic effect. The pseudo-second- order reaction kinetics and Freundlich isotherm model correctly portrayed the experimental data for iron removal by CaCO3-nZVI. The CaCO3-nZVI is a viable option for iron removal from various aqueous media due to its facile preparation, high iron removal capability, and reusability.