Daniel Joseph Goldberg

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Journals/Publications

• Eckel, S. P., Chen, F., Silva, S. J., Goldberg, D. L., Johnston, J., Palinkas, L. A., Campos, A., Franco, W., & Garcia, E. (2026). Zero-emissions vehicle adoption and satellite-measured NO air pollution in California, USA, from 2019 to 2023: a longitudinal observational study. The Lancet. Planetary health, 101379.
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  Electrifying the transportation sector is a key climate-change mitigation strategy. Reductions in exhaust emissions have anticipated air quality co-benefits; yet, evidence is primarily based on projections. Using observed data in California, USA, we aimed to investigate whether reductions in exhaust emissions from the transition to zero-emissions vehicles (ZEVs: battery electric, plug-in hybrid, and hydrogen fuel cell) were detectable using Tropospheric Monitoring Instrument (TROPOMI) satellite measurements of nitrogen dioxide (NO) air pollution.
• Ockenden, H., Bingham, R. G., Goldberg, D., Curtis, A., & Morlighem, M. (2026). Complex mesoscale landscapes beneath Antarctica mapped from space. Science (New York, N.Y.), 391(6782), 314-319.
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  The landscape shrouded by the Antarctic Ice Sheet provides important insights into its history and influences the ice response to climate forcing. However, knowledge of this critical boundary has depended on interpolation between irregularly distributed geophysical surveys, creating major spatial biases in maps of Antarctica's subglacial landscape. As stress changes associated with ice flow over bedrock obstacles produce ice surface topography, recently acquired, high-resolution satellite maps of the ice surface offer a transformative basis for mapping subglacial landforms. We present a continental-scale elevation map of Antarctica's subglacial topography produced by applying the physics of ice flow to ice surface maps and incorporating geophysical ice thickness observations. Our results enrich understanding of mesoscale (2 to 30 kilometers) subglacial landforms and unmask the spatial distribution of subglacial roughness and geomorphology.
• Burkart, K., Wozniak, S., Anenberg, S., Pereda, A., Gilbertson, N., Ashbaugh, C., Goldberg, D., Hystad, P., Kerr, G. H., McLaughlin, S. A., Mohegh, A., & Brauer, M. (2025). Global, regional and national estimates of the burden of childhood asthma attributable to NO exposure for 204 countries and territories from 1990 to 2023: a Global Burden of Disease study 2023. EClinicalMedicine, 90, 103580.
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  Asthma, a chronic lung condition characterised by inflammation and airway constriction, has been associated with nitrogen dioxide (NO) exposure, an association that particularly impacts children. Our study rigorously assessed this relationship and estimated the global burden of childhood asthma attributable to NO exposure in 204 countries and territories from 1990 to 2023.
• Farzad, K., Zhang, Y., Wang, K., Chen, X., Goldberg, D. L., Lyapustin, A., Wang, Y., & Bell, M. L. (2025). Statistical downscaling of coarse-resolution fine particulate matter predictions over the contiguous United States: model development, evaluation, and implication in health impact assessment. The Science of the total environment, 999, 180302.
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  Fine particulate matter (PM) predictions at a high spatial resolution (i.e., neighborhood scale) are critically needed to better understand the health impacts of air pollution, especially at neighborhood scales. This work develops a statistical downscaling approach to predict PM at a 1-km grid resolution over the contiguous United States (CONUS) under baseline and future energy transition scenarios and estimate health benefits utilizing the Environmental Benefits Mapping and Analysis Program (BenMAP). To this end, we incorporate the satellite-based high-resolution aerosol optical depth (AOD), land use data, and PM composition predicted by the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) at 36-km into daily multi-linear regressions over different climate regions of the CONUS. Compared to the WRF-Chem baseline predictions in 2008-2012, 1-km PM estimates enhance the accuracy by increasing the yearly correlation coefficients from ~0.4 to ~0.8 and reducing normalized mean errors from ~47 % to ~27 %. Future 1-km PM is projected by combining the baseline 5-yr (2008-2012) monthly-averaged training coefficients with high-resolution statistically improved projected AOD and PM subsets from WRF-Chem. BenMAP with WRF-Chem predictions under future energy scenarios shows an average of 2478 fewer deaths per year in 2050 in New York City and Boston due to PM, while the downscaled PM shows less PM reduction and about half the health benefit of the WRF-Chem projections. The downscaling approach is more computationally efficient than running the 3-D air quality model with a 1-km spatial grid resolution. This work uniquely combines WRF-Chem outputs and statistical downscaling to provide high-resolution and high-fidelity PM predictions.
• Godinez-Macias, K. P., Chen, D., Wallis, J. L., Siegel, M. G., Adam, A., Bopp, S., Carolino, K., Coulson, L. B., Durst, G., Thathy, V., Esherick, L., Farringer, M. A., Flannery, E. L., Forte, B., Liu, T., Godoy Magalhaes, L., Gupta, A. K., Istvan, E. S., Jiang, T., , Kumpornsin, K., et al. (2025). Revisiting the druggable genome using predicted structures and data mining. NPJ drug discovery, 2(1), 3.
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  Identification of novel drug targets is a key component of modern drug discovery. While antimalarial targets are often identified through the mechanism of action studies on phenotypically derived inhibitors, this method tends to be time- and resource-consuming. The discoverable target space is also constrained by existing compound libraries and phenotypic assay conditions. Leveraging recent advances in protein structure prediction, we systematically assessed the genome and identified 867 candidate protein targets with evidence of small-molecule binding and blood-stage essentiality. Of these, 540 proteins showed strong essentiality evidence and lack inhibitors that have progressed to clinical trials. Expert review and rubric-based scoring of this subset based on additional criteria such as selectivity, structural information, and assay developability yielded 27 high-priority antimalarial target candidates. This study also provides a genome-wide data resource for and implements a generalizable framework for systematically evaluating and prioritizing novel pathogenic disease targets.
• Goldberg, D. S., Brou, L., & Hemeida, S. (2025). Targeting Addiction Structural Stigma Embodied in Law ("TASSEL"): Findings from an intrastate legal mapping study. The International journal on drug policy, 146, 105033.
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  Stigma is a fundamental cause of disease that reflects and intensifies health inequalities. Laws are powerful mediators for stigma; to correct them, it is critical to know which laws promote stigma. This paper deploys legal epidemiology methods to map addiction stigma in California law. Robust policy surveillance methods can assist policymakers in identifying stigmatizing laws, providing a path to their remediation.
• Goldberg, D., Fitzgerald, Z., Sag, A., Abramyan, A., Vittoria De Martini, I., Struycken, L., Hannallah, J., Woodhead, G., & Young, S. (2025). Comparison of Outcomes in Splanchnic Nerve and Celiac Plexus Cryoneurolysis for the Treatment of Refractory Abdominal Pain. The American journal of hospice & palliative care, 10499091251397400.
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  BackgroundVisceral upper abdominal pain caused by malignant and non-malignant etiologies can be treated by neurolysis of the splanchnic nerves and the celiac plexus. The purpose of this report is to compare the effect of cryoneurolysis of the celiac plexus vs the splanchnic nerves in patients with intractable upper abdominal pain as well as report outcomes and adverse events (AEs) of these procedures.MethodsA retrospective study of 36 patients who underwent either CT-guided celiac plexus (n = 9) or CT-guided splanchnic nerve (n = 27) cryoneurolysis for treatment of intractable upper abdominal pain. Pre- and post-procedural pain scores, supplemental analgesic use, procedural length, and AEs were assessed.ResultsPre-treatment Visual Analog Scale (VAS) pain scores were significantly improved at 1 week (7.7 ± 2.2 vs 3.5 ± 3, < 0.001), 1 month (7.7 ± 2.2 vs 4.3 ± 2.8, < 0.001) and 3 months (7.7 ± 2.2 vs 3.6 ± 3.2, < 0.001) after cryoneurolysis in patients undergoing splanchnic cryoneurolysis. Similarly, in the celiac cohort VAS pain scores at 1 week (7.6 ± 2.5 vs 4.8 ± 3, = 0.024), 1 month (7.6 ± 2.5 vs 3 ± 2.4, = 0.003) and 3 months ((7.6 ± 2.5 vs 4 ± 3.3, = 0.025) after cryoneurolysis were significantly improved as compared to pre-treatment. No significant difference in post-procedural numeric pain improvement, percentage pain improvement, procedural length, changes in supplemental analgesics, and AEs was observed between the two cohorts ( > 0.05, for all).ConclusionBoth celiac plexus and splanchnic nerve cryoneurolysis provide significant analgesia in patients with intractable upper abdominal with no significant difference in analgesic effect or safety profile between the two techniques.
• Jiang, L., Tucker, A., Sepehri, C., Patel, D., Wang, Q., Yuan, S., Sherman, E., Chen, Y., Beh, J., Downey, A., Goldberg, D., Gniadzik, W., & Ma, X. (2025). Inhibition of N6-Methyladenosine Accumulation by Targeting METTL3 Mitigates Tau Pathology and Cognitive Decline in Alzheimer's Disease. Research square.
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  Dysregulation of N6-methyladenosine (m6A) modification of RNA has emerged as a novel feature of Alzheimer's disease (AD). Here, we investigate the relationship between m6A modification and AD pathology, and the therapeutic potential of modulating excessive m6A via its "writer" methyltransferase METTL3 in a humanized P301S tau transgenic mouse model of AD (PS19). We observed significantly elevated m6A levels in human post-mortem AD frontal cortex tissue compared to healthy controls, which positively correlated with hyperphosphorylated tau and amyloid-β (Aβ) deposition. These effects were recapitulated in the PS19 tau mice model of AD. Importantly, treatment of PS19 mice with the METTL3 inhibitor STM2457 reduced excessive m6A, alleviated tau pathology, and attenuated neurodegeneration. Behavioral assessments further demonstrated that STM2457-treated PS19 mice exhibited significantly improved learning and memory relative to untreated PS19 mice. Our results identify m6A as a critical contributor to AD pathogenesis and demonstrate that pharmacological inhibition of METTL3 represents a promising therapeutic strategy to improve cognition in AD.
• Lawal, A. S., Skipper, T. N., Ivey, C. E., Goldberg, D. L., Kaiser, J., & Russell, A. G. (2025). Potential Errors in CMAQ NO:NO Ratios and Upper Tropospheric NO Impacting the Interpretation of TROPOMI Retrievals. ACS ES&T air, 2(6), 998-1008.
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  Although Chemical Transport Models (CTMs) such as the Community Multiscale Air Quality Model (CMAQ) have been used in linking observations of trace gases to emissions and developing vertical column distributions, there remain consistent biases between CTM simulations and satellite retrievals. Simulated tropospheric NO vertical column densities (VCDs) are generally higher over areas with large NO sources when compared with retrievals, while an opposite bias is found over low NO regions. Artificial (i.e., numerical) dilution in the model, where emissions are mathematically dispersed uniformly within the originating CTM grid, can impact modeled NO:NO ratios, while lower CTM VCD levels often observed over rural areas can be attributed to missing emission sources of NO or flawed horizontal/vertical transport. Potential causes of both low and high biases are assessed in this study using CMAQ and Tropospheric Monitoring Instrument (TROPOMI) NO retrievals. It was found that more detailed modeling of NO plumes to assess the NO:NO ratio in two power plant plumes can mitigate the effect of artificial computational dilution, reducing the bias and overall differences in the observed vs modeled plumes (errors reduced by 30%). Adjustments of upper tropospheric NO led to overall improvements, with a reduction in CMAQ bias (-43% to -29%) and improved spatial correlation (0.81 to 0.86). This study highlights the importance of having accurate modeled NO:NO ratios when comparing models to retrievals and the impact of unintentional numerical dilution.
• Nawaz, M. O., Goldberg, D. L., Kerr, G. H., & Anenberg, S. C. (2025). TROPOMI Satellite Data Reshape NO Air Pollution Land-Use Regression Modeling Capabilities in the United States. ACS ES&T air, 2(2), 187-200.
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  Nitrogen dioxide (NO) pollution is associated with adverse health effects, but its spatial variability between ground monitors is poorly characterized. NO column observations from the Tropospheric Monitoring Instrument (TROPOMI) have unprecedented spatial resolution and high accuracy over the globe. Land-use regression (LUR) models predict surface-level NO with relevance for epidemiological and environmental justice studies. We use TROPOMI NO columns in a land use regression (LUR) model to improve surface NO concentration estimates over the United States. The TROPOMI LUR predictions have improved correlation with ground monitors (Adj. = 0.72) and bias (Mean Bias, MB = 14.2%) compared with an existing LUR using less granular NO data from a legacy satellite instrument (Adj. = 0.54 and MB = 49%; for North America). Removing TROPOMI NO from the LUR decreased by 29.1%, 8.1 times the impact of removing road system information. These findings reveal that novel Earth observing satellites can enhance surface NO surveillance by capturing pollution variation between monitors without relying heavily on other data sources.
• Niknam, K., Goldberg, D., Markes, A. R., Feeley, B. T., Zhang, A. L., Ma, C. B., & Lansdown, D. A. (2025). Concomitant Medial Collateral Ligament Injury Increases the Risk of Revision Anterior Cruciate Ligament Reconstruction. Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association, 41(5), 1423-1433.e4.
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  To compare rates of revisions between patients with isolated anterior cruciate ligament (ACL) reconstruction and those who had concomitant medial collateral ligament (MCL) injuries managed either operatively or nonoperatively at the time of index anterior cruciate ligament reconstruction (ACLR).
• Ref, J., El-Aini, T., Insel, M., Acharya, T., Hannallah, J., Goldberg, D., Struycken, L., Young, S., & Woodhead, G. (2025). What the Interventional Radiologist Needs to Know about Imaging Studies for the Detection, Risk Stratification, and Short- and Long-Term Follow-up of Pulmonary Embolism. Seminars in interventional radiology, 42(3), 383-388.
• Rosenthal, M. R., & Goldberg, D. E. (2025). Quinolines interfere with heme-mediated activation of artemisinins. bioRxiv : the preprint server for biology.
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  Artemisinin-based combination therapies (ACTs) remain the mainstay of treatment for malaria, despite reports of ACT treatment failure. ACTs consist of an artemisinin and a longer-lived partner drug, which is often a quinoline. Given that heme is central to the mechanism of action of artemisinins and some quinolines, we hypothesized that these antimalarials would exhibit strong drug-drug interactions. Previous studies using standard 48 h or 72 h assays identified additive to mildly antagonistic interactions between artemisinins and quinolines. Here, we sought to re-evaluate these interactions using a pulsing assay that better mimics the short in vivo half-life of artemisinins. We found that chloroquine (CQ), piperaquine (PPQ), and amodiaquine substantially antagonize dihydroartemisinin (DHA), the active metabolite of artemisinins. CQ-DHA antagonism was notably exacerbated in CQ-resistant parasites, resulting in a superantagonistic phenotype in isobolograms. Further, we found that CQ co-treatment conferred artemisinin resistance to Kelch 13 wild type parasites in the ring stage survival assay. Using a small molecule probe to measure chemically reactive heme in live parasites, we determined that quinolines block artemisinin activation by rendering cytosolic heme inert. Finally, we probed beyond traditional ACTs, evaluating interactions of the proposed triple ACT, DHA-PPQ-Mefloquine, as well as OZ439-quinoline combinations, which were all found to be antagonistic. Collectively, these data raise concerns for the clinical use of peroxide-quinoline combination therapies.
• Young, S., Abramyan, A., Vittoria De Martini, I., Hannallah, J., Woodhead, G., Struycken, L., & Goldberg, D. (2025). Cryoneurolysis: An Emerging Personalized Treatment Strategy for Significant Pelvic Pain. Journal of personalized medicine, 15(12).
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  Significant pelvic pain is a fairly common malady in the United States. At the same time, the opioid epidemic has changed how pain is thought about and treated, resulting in a clear call for alternative treatment strategies. One of the promising techniques that has emerged over the last several years is cryoneurolysis. Cryoneurolysis allows for personalization of treatment through targeting of specific peripheral nerves, which correspond to a patient's pain. In the setting of pelvic pain, several viable targets, namely the pudendal nerve and impar ganglion, have been described. This review delineates the mechanism of action in cryoneurolysis, reviews the pertinent literature and describes patient workup and technique. Finally, future directions are discussed.
• Abramyan, A., Schaub, D., Kalarn, S., Fitzgerald, Z., Goldberg, D., Hannallah, J., Woodhead, G., & Young, S. (2024). Including the Hollow Viscera (Stomach or Bowel) within the Ice Ball during Cryoablation: A Review of Adverse Events. Journal of vascular and interventional radiology : JVIR.
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  To evaluate the safety of including hollow viscus (stomach or bowel) in the ice ball during cryoablation.
• Arias, J. J., & Goldberg, D. S. (2024). Integrating Public Health Ethics into Public Health Policymaking: Being in the Room Where It Happens. The Journal of law, medicine & ethics : a journal of the American Society of Law, Medicine & Ethics, 52(1), 183-187.
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  This commentary takes up a challenge posed by Franklin Miller in a 2022 essay in Bioethics Forum. Dr. Miller queried whether bioethicists could be useful in public health policy contexts and while he refrained from issuing an ultimate opinion, did identify several challenges to such utility. The current piece responds to the challenges Dr. Miller identifies and argues that with appropriate training, public health ethicists can be of service in virtually any context in which public health policies are deliberated and decided.
• Berman, M. L., Arias, J. J., Berner Wong, N., Crespo, J., Goldberg, D., Mason Meier, B., Satchell, T., Silverman, R. D., Tobin-Tyler, E., & Chriqui, J. F. (2024). How to Advance Legal Education for Future Public Health Professionals. Public health reports (Washington, D.C. : 1974), 333549241274565.
• Blackwell, A. M., Jami-Alahmadi, Y., Nasamu, A. S., Kudo, S., Senoo, A., Slam, C., Tsumoto, K., Wohlschlegel, J. A., Caaveiro, J. M., Goldberg, D. E., & Sigala, P. A. (2024). Malaria parasites require a divergent heme oxygenase for apicoplast gene expression and biogenesis. bioRxiv : the preprint server for biology.
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  Malaria parasites have evolved unusual metabolic adaptations that specialize them for growth within heme-rich human erythrocytes. During blood-stage infection, parasites internalize and digest abundant host hemoglobin within the digestive vacuole. This massive catabolic process generates copious free heme, most of which is biomineralized into inert hemozoin. Parasites also express a divergent heme oxygenase (HO)-like protein (PfHO) that lacks key active-site residues and has lost canonical HO activity. The cellular role of this unusual protein that underpins its retention by parasites has been unknown. To unravel PfHO function, we first determined a 2.8 Å-resolution X-ray structure that revealed a highly α-helical fold indicative of distant HO homology. Localization studies unveiled PfHO targeting to the apicoplast organelle, where it is imported and undergoes N-terminal processing but retains most of the electropositive transit peptide. We observed that conditional knockdown of PfHO was lethal to parasites, which died from defective apicoplast biogenesis and impaired isoprenoid-precursor synthesis. Complementation and molecular-interaction studies revealed an essential role for the electropositive N-terminus of PfHO, which selectively associates with the apicoplast genome and enzymes involved in nucleic acid metabolism and gene expression. PfHO knockdown resulted in a specific deficiency in levels of apicoplast-encoded RNA but not DNA. These studies reveal an essential function for PfHO in apicoplast maintenance and suggest that repurposed the conserved HO scaffold from its canonical heme-degrading function in the ancestral chloroplast to fulfill a critical adaptive role in organelle gene expression.
• Blackwell, A. M., Jami-Alahmadi, Y., Nasamu, A. S., Kudo, S., Senoo, A., Slam, C., Tsumoto, K., Wohlschlegel, J. A., Manuel Martinez Caaveiro, J., Goldberg, D. E., & Sigala, P. A. (2024). Malaria parasites require a divergent heme oxygenase for apicoplast gene expression and biogenesis. eLife, 13.
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  Malaria parasites have evolved unusual metabolic adaptations that specialize them for growth within heme-rich human erythrocytes. During blood-stage infection, parasites internalize and digest abundant host hemoglobin within the digestive vacuole. This massive catabolic process generates copious free heme, most of which is biomineralized into inert hemozoin. Parasites also express a divergent heme oxygenase (HO)-like protein (PfHO) that lacks key active-site residues and has lost canonical HO activity. The cellular role of this unusual protein that underpins its retention by parasites has been unknown. To unravel PfHO function, we first determined a 2.8 Å-resolution X-ray structure that revealed a highly α-helical fold indicative of distant HO homology. Localization studies unveiled PfHO targeting to the apicoplast organelle, where it is imported and undergoes N-terminal processing but retains most of the electropositive transit peptide. We observed that conditional knockdown of PfHO was lethal to parasites, which died from defective apicoplast biogenesis and impaired isoprenoid-precursor synthesis. Complementation and molecular-interaction studies revealed an essential role for the electropositive N-terminus of PfHO, which selectively associates with the apicoplast genome and enzymes involved in nucleic acid metabolism and gene expression. PfHO knockdown resulted in a specific deficiency in levels of apicoplast-encoded RNA but not DNA. These studies reveal an essential function for PfHO in apicoplast maintenance and suggest that repurposed the conserved HO scaffold from its canonical heme-degrading function in the ancestral chloroplast to fulfill a critical adaptive role in organelle gene expression.
• Brunson, C., Struycken, L., Schaub, D., Ref, J., Goldberg, D., Hannallah, J., Woodhead, G., & Young, S. (2024). Comparative outcomes of trans-arterial radioembolization in patients with non-alcoholic steatohepatitis/non-alcoholic fatty liver disease-induced HCC: a retrospective analysis. Abdominal radiology (New York), 49(8), 2714-2725.
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  Tumorigenesis in NAFLD/NASH-induced HCC is unique and may affect the effectiveness of trans-arterial radioembolization in this population. The purpose of this study was to retrospectively compare the effectiveness of trans-arterial radioembolization for the treatment of hepatocellular carcinoma (HCC) between patients with non-alcoholic steatohepatitis (NASH)/non-alcoholic fatty liver disease (NAFLD) and non-NASH/NAFLD liver disease.
• Goldberg, D. L., de Foy, B., Nawaz, M. O., Johnson, J., Yarwood, G., & Judd, L. (2024). Quantifying NO Emission Sources in Houston, Texas Using Remote Sensing Aircraft Measurements and Source Apportionment Regression Models. ACS ES&T air, 1(11), 1391-1401.
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  Air quality managers in areas exceeding air pollution standards are motivated to understand where there are further opportunities to reduce NO emissions to improve ozone and PM air quality. In this project, we use a combination of aircraft remote sensing (i.e., GCAS), source apportionment models (i.e., CAMx), and regression models to investigate NO emissions from individual source-sectors in Houston, TX. In prior work, GCAS column NO was shown to be close to the "truth" for validating column NO in model simulations. Column NO from CAMx was substantially low biased compared to Pandora (-20%) and GCAS measurements (-31%), suggesting an underestimate of local NO emissions. We applied a flux divergence method to the GCAS and CAMx data to distinguish the linear shape of major highways and identify NO underestimates at highway locations. Using a multiple linear regression (MLR) model, we isolated on-road, railyard, and "other" NO emissions as the likeliest cause of this low bias, and simultaneously identified a potential overestimate of shipping NO emissions. Based on the MLR, we modified on-road and shipping NO emissions in a new CAMx simulation and increased the background NO, and better agreement was found with GCAS measurements: bias improved from -31% to -10% and r improved from 0.78 to 0.80. This study outlines how remote sensing data, including fine spatial information from newer geostationary instruments, can be used in concert with chemical transport models to provide actionable information for air quality managers to identify further opportunities to reduce NO emissions.
• Kerr, G. H., Meyer, M., Goldberg, D. L., Miller, J., & Anenberg, S. C. (2024). Air pollution impacts from warehousing in the United States uncovered with satellite data. Nature communications, 15(1), 6006.
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  Regulators, environmental advocates, and community groups in the United States (U.S.) are concerned about air pollution associated with the proliferating e-commerce and warehousing industries. Nationwide datasets of warehouse locations, traffic, and satellite observations of the traffic-related pollutant nitrogen dioxide (NO) provide a unique capability to evaluate the air quality and environmental equity impacts of these geographically-dispersed emission sources. Here, we show that the nearly 150,000 warehouses in the U.S. worsen local traffic-related air pollution with an average near-warehouse NO enhancement of nearly 20% and are disproportionately located in marginalized and minoritized communities. Near-warehouse truck traffic and NO significantly increase as warehouse density and the number of warehouse loading docks and parking spaces increase. Increased satellite-observed NO near warehouses underscores the need for indirect source rules, incentives for replacing old trucks, and corporate commitments towards electrification. Future ground-based monitoring campaigns may help track impacts of individual or small clusters of facilities.
• Luth, M. R., Godinez-Macias, K. P., Chen, D., Okombo, J., Thathy, V., Cheng, X., Daggupati, S., Davies, H., Dhingra, S. K., Economy, J. M., Edgar, R. C., Gomez-Lorenzo, M. G., Istvan, E. S., Jado, J. C., LaMonte, G. M., Melillo, B., Mok, S., Narwal, S. K., Ndiaye, T., , Ottilie, S., et al. (2024). Systematic in vitro evolution in reveals key determinants of drug resistance. Science (New York, N.Y.), 386(6725), eadk9893.
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  Surveillance of drug resistance and the discovery of novel targets-key objectives in the fight against malaria-rely on identifying resistance-conferring mutations in parasites. Current approaches, while successful, require laborious experimentation or large sample sizes. To elucidate shared determinants of antimalarial resistance that can empower in silico inference, we examined the genomes of 724 clones, each selected in vitro for resistance to one of 118 compounds. We identified 1448 variants in 128 recurrently mutated genes, including drivers of antimalarial multidrug resistance. In contrast to naturally occurring variants, those selected in vitro are more likely to be missense or frameshift, involve bulky substitutions, and occur in conserved, ordered protein domains. Collectively, our dataset reveals mutation features that predict drug resistance in eukaryotic pathogens.
• Morlighem, M., Goldberg, D., Barnes, J. M., Bassis, J. N., Benn, D. I., Crawford, A. J., Gudmundsson, G. H., & Seroussi, H. (2024). The West Antarctic Ice Sheet may not be vulnerable to marine ice cliff instability during the 21st century. Science advances, 10(34), eado7794.
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  The collapse of ice shelves could expose tall ice cliffs at ice sheet margins. The marine ice cliff instability (MICI) is a hypothesis that predicts that, if these cliffs are tall enough, ice may fail structurally leading to self-sustained retreat. To date, projections that include MICI have been performed with a single model based on a simple parameterization. Here, we implement a physically motivated parameterization in three ice sheet models and simulate the response of the Amundsen Sea Embayment after a hypothetical collapse of floating ice. All models show that Thwaites Glacier would not retreat further in the 21st century. In another set of simulations, we force the grounding line to retreat into Thwaites' deeper basin to expose a taller cliff. In these simulations, rapid thinning and velocity increase reduce the calving rate, stabilizing the cliff. These experiments show that Thwaites may be less vulnerable to MICI than previously thought, and model projections that include this process should be re-evaluated.
• Woodhead, G., Lee, S., Struycken, L., Goldberg, D., Hannallah, J., & Young, S. (2024). Interventional Radiology Locoregional Therapies for Intrahepatic Cholangiocarcinoma. Life (Basel, Switzerland), 14(2).
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  Surgical resection remains the cornerstone of curative treatment for intrahepatic cholangiocarcinoma (iCCA), but this option is only available to a small percentage of patients. For patients with unresectable iCCA, systemic therapy with gemcitabine and platinum-based agents represents the mainstay of treatment; however, the armamentarium has grown to include targeted molecular therapies (e.g., FGFR2 inhibitors), use of adjuvant therapy, liver transplantation in select cases, immunotherapy, and locoregional liver-directed therapies. Despite advances, iCCA remains a challenge due to the advanced stage of many patients at diagnosis. Furthermore, given the improving options for systemic therapy and the fact that the majority of iCCA patients succumb to disease progression in the liver, the role of locoregional therapies has increased. This review will focus on the expanding role of interventional radiology and liver-directed therapies in the treatment of iCCA.
• Yaari, L., Singer, J., Goldberg, D., Yassin, M., Agar, G., Lindner, D., Beer, Y., & Haviv, B. (2024). Eighteen-year outcome of anterior cruciate ligament reconstruction with patellar tendon or hamstring autograft. Archives of orthopaedic and trauma surgery, 144(5), 2189-2195.
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  To evaluate patient reported outcomes and radiographic arthritic changes of transtibial anterior cruciate ligament reconstruction (ACLR) with either bone-patellar tendon-bone (BPTB) or hamstrings (HS) auto-grafts at a minimum of 15-year follow-up.
• Zhang, Z., Lyu, M., Han, X., Bandara, S., Cui, M., Istvan, E. S., Geng, X., Tringides, M. L., Gregor, W. D., Miyagi, M., Oberstaller, J., Adams, J. H., Zhang, Y., Nieman, M. T., von Lintig, J., Goldberg, D. E., & Yu, E. W. (2024). The NCR1 transporter is an antimalarial target that exports cholesterol from the parasite's plasma membrane. Science advances, 10(51), eadq6651.
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  Malaria, a devastating parasitic infection, is the leading cause of death in many developing countries. Unfortunately, the most deadliest causative agent of malaria, , has developed resistance to nearly all currently available antimalarial drugs. The Niemann-Pick type C1-related (PfNCR1) transporter has been identified as a druggable target, but its structure and detailed molecular mechanism are not yet available. Here, we present three structures of PfNCR1 with and without the functional inhibitor MMV009108 at resolutions between 2.98 and 3.81 Å using single-particle cryo-electron microscopy (cryo-EM), suggesting that PfNCR1 binds cholesterol and forms a cholesterol transport tunnel to modulate the composition of the parasite plasma membrane. Cholesterol efflux assays show that PfNCR1 is an exporter capable of extruding cholesterol from the membrane. Additionally, the inhibition mechanism of MMV009108 appears to be due to a direct blockage of PfNCR1, preventing this transporter from shuttling cholesterol.
• Goldberg, D., Woodhead, G., Hannallah, J., & Young, S. (2023). Role of the Interventional Radiologist in the Treatment of Desmoid Tumors. Life (Basel, Switzerland), 13(3).
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  Desmoid tumors are locally aggressive soft tissue tumors with variable clinical presentation. As is the case with most relatively rare tumors, a multidisciplinary team approach is required to best manage these patients. Surgical resection, systemic therapy, and radiation therapy have classically been mainstays of treatment for desmoid tumors; however, a more conservative "wait-and-see" approach has been adopted given their high recurrence rates and significant morbidity associated with the aforementioned therapies. Given the challenges of classical treatment methods, interventional radiologists have begun to play a significant role in minimally invasive interventions for desmoid tumors. Herein, the authors review imaging characteristics of desmoid tumors, current management recommendations, and minimally invasive therapeutic intervention options.
• Young, S., Abamyan, A., Goldberg, D., Hannallah, J., Schaub, D., Kalarn, S., Fitzgerald, Z., & Woodhead, G. (2023). Cryoablation in the liver: how accurately does the iceball predict the ablation zone?. Abdominal radiology (New York).
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  To evaluate the accuracy with which the iceball predicts the realized ablation zone in patients undergoing cryoablation of the liver.
• Young, S., Hannallah, J., Goldberg, D., Khreiss, M., Shroff, R., Arshad, J., Scott, A., & Woodhead, G. (2023). Liver-Directed Therapy Combined with Systemic Therapy: Current Status and Future Directions. Seminars in interventional radiology, 40(6), 515-523.
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  In the past several decades, major advances in both systemic and locoregional therapies have been made for many cancer patients. This has led to modern cancer treatment algorithms frequently calling for active interventions by multiple subspecialists at the same time. One of the areas where this can be clearly seen is the concomitant use of locoregional and systemic therapies in patients with primary or secondary cancers of the liver. These combined algorithms have gained favor over the last decade and are largely focused on the allure of the combined ability to control systemic disease while at the same time addressing refractory/resistant clonal populations. While the general concept has gained favor and is likely to only increase in popularity with the continued establishment of viable immunotherapy treatments, for many patients questions remain. Lingering concerns over the increase in toxicity when combining treatment methods, patient selection, and sequencing remain for multiple cancer patient populations. While further work remains, some of these questions have been addressed in the literature. This article reviews the available data on three commonly treated primary and secondary cancers of the liver, namely, hepatocellular carcinoma, cholangiocarcinoma, and metastatic colorectal cancer. Furthermore, strengths and weaknesses are reviewed and future directions are discussed.
• Young, S., Hannallah, J., Goldberg, D., Sanghvi, T., Arshad, J., Scott, A., & Woodhead, G. (2023). Friend or Foe? Locoregional Therapies and Immunotherapies in the Current Hepatocellular Treatment Landscape. International journal of molecular sciences, 24(14).
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  Over the last several decades, a number of new treatment options for patients with hepatocellular carcinoma (HCC) have been developed. While treatment decisions for some patients remain clear cut, a large numbers of patients have multiple treatment options, and it can be hard for multidisciplinary teams to come to unanimous decisions on which treatment strategy or sequence of treatments is best. This article reviews the available data with regard to two treatment strategies, immunotherapies and locoregional therapies, with a focus on the potential of locoregional therapies to be combined with checkpoint inhibitors to improve outcomes in patients with locally advanced HCC. In this review, the available data on the immunomodulatory effects of locoregional therapies is discussed along with available clinical data on outcomes when the two strategies are combined.
• Cockburn, M., Mills, P., Zhang, X., Zadnick, J., Goldberg, D., & Ritz, B. (2011). Prostate cancer and ambient pesticide exposure in agriculturally intensive areas in California. American journal of epidemiology, 173(11), 1280-8.
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  In a population-based case-control study in California's intensely agricultural Central Valley (2005-2006), the authors investigated relations between environmental pesticide/fungicide exposure and prostate cancer. Cases (n = 173) were obtained from a population-based cancer registry, and controls (n = 162) were obtained from Medicare listings and tax assessor mailings. Past ambient exposures to pesticides/fungicides were derived from residential history and independently recorded pesticide and land-use data, using a novel geographic information systems approach. In comparison with unexposed persons, increased risks of prostate cancer were observed among persons exposed to compounds which may have prostate-specific biologic effects (methyl bromide (odds ratio = 1.62, 95% confidence interval: 1.02, 2.59) and a group of organochlorines (odds ratio = 1.64, 95% confidence interval: 1.02, 2.63)) but not among those exposed to other compounds that were included as controls (simazine, maneb, and paraquat dichloride). The authors assessed the possibility of selection bias due to less-than-100% enrollment of eligible cases and controls (a critical methodological concern in studies of this kind) and determined that there was little evidence of bias affecting the estimated effect size. This study provides evidence of an association between prostate cancer and ambient pesticide exposures in and around homes in intensely agricultural areas. The associations appear specific to compounds with a plausible biologic role in prostate carcinogenesis.