Risk Factors Associated with Spinal Cord Ischemia During Aortic Aneurysm Repair.

BACKGROUND: The risk of spinal cord ischemia (SCI) with aortic aneurysm repair can cause significant neurological morbidity. Prevention of SCI is critical. We sought to identify risk factors that predispose to SCI that may guide strategies to mitigate the occurrence of SCI during and following these procedures. METHODS: This study includes all adults who underwent atraumatic, unruptured, thoracic, and suprarenal aortic aneurysm repairs (endovascular or open) at our institution over 11 years (2010-2020). Our database included patient demographics, aneurysm anatomic features, and operative characteristics and an extreme gradient boost (XGB) machine method was used to develop a predictive model for SCI. The model was trained on an 80% randomly stratified cohort of the data and tested on the remaining 20% testing cohort. Shapley values were used to determine the most important predictive factors of SCI and decision trees were used to identify risk factor threshold values and highest risk factor combinations. RESULTS: Information was collected for 174 adult patients undergoing thoracic and suprarenal aortic repair from 2010 to 2020. Fifty eight percent of the patients were male. Ninety seven (55.7%) patients had open aortic repair and 87 (44.3%) had endovascular repair. Twenty seven (15%) of all patients had major complications and were considered to have SCI. The XGB model converged over the training cohort with a testing cohort accuracy of 0.841 [Sensitivity = 75%, Specificity = 68%] and area under the curve of receiver operating characteristic of 0.774. The XGB model identified older age (> 65 years), history of neurologic disease, hyperlipidemia, diabetes, coronary artery disease, heart failure, poor renal function, < 6 months since last aortic repair, chronic anticoagulant use, preoperational anemia (Hemoglobin < 9), thrombocytopenia (platelet < 90,000), coagulopathy (prothrombin time > 15s and activated partial thromboplastin time > 40s), hypotension (mean arterial pressure < 70 mm Hg), longer operations (> 100 min), aneurysms longer than 5 cm, and anatomic location of aneurysm caudal to T-11 as risk factors for SCI in all types of aortic repair. Diabetic and heart failure patients undergoing longer operations (> 100 min) with thrombocytopenia or aneurysms longer than 5 cm were at the highest risk. CONCLUSIONS: The XGB model accurately identified risk factors of SCI with aortic aneurysm repair that may guide patient selection, timing of surgery, and strategies to minimize the risk of SCI.

Cost-effectiveness and budget impact of heat-stable carbetocin compared to oxytocin and misoprostol for the prevention of postpartum hemorrhage (PPH) in women giving birth in India.

INTRODUCTION: Low- and middle-income countries (LMICs) are committed to achieving the Sustainable Development Goal 3.1 to reduce maternal mortality. The Ministry of Health and Family Welfare of India recommends prophylactic uterotonic administration to every woman following delivery to reduce the risk of postpartum hemorrhage (PPH), as PPH is the leading cause of maternal mortality in LMICs, including India. In 2018, the World Health Organization first recognized heat-stable carbetocin for PPH prevention. Governments are now considering its introduction into their public health systems. METHODS: A decision-tree model was developed from the public healthcare system perspective to compare the value of heat-stable carbetocin versus oxytocin and misoprostol among women giving birth in public sector healthcare facilities in India. The model accounted for differences in PPH risk and costs based on mode of delivery and healthcare setting, as well as provider behavior to mitigate quality concerns of oxytocin. Model outcomes for each prophylactic uterotonic included the number of PPH events, DALYs due to PPH, deaths due to PPH, and direct medical care costs. The budget impact was estimated based on projected uterotonic uptake between 2022-2026. RESULTS: Compared to oxytocin, heat-stable carbetocin avoided 5,468 additional PPH events, 5 deaths, and 244 DALYs per 100,000 births. Projected direct medical costs to the public healthcare system were lowered by US $171,700 (₹12.8 million; exchange rate of ₹74.65 = US$1 from 2 Feb 2022) per 100,000 births. Benefits were even greater when compared to misoprostol (7,032 fewer PPH events, 10 fewer deaths, 470 fewer DALYs, and $230,248 saved per 100,000 births). In the budget impact analysis, India's public health system is projected to save US$11.4 million (₹849 million) over the next five years if the market share for heat-stable carbetocin grows to 19% of prophylactic uterotonics administered. CONCLUSIONS: Heat-stable carbetocin is expected to reduce the number of PPH events and deaths, avoid more DALYs, and reduce costs to the public healthcare system of India. Greater adoption of heat-stable carbetocin for the prevention of PPH could advance India's efforts to achieve its maternal health goals and increase efficiency of its public health spending.

Time and productivity loss associated with immunotherapy infusions for the treatment of melanoma in the United States: a survey of health care professionals and patients.

INTRODUCTION: A new dosing schedule for the oncology immunotherapy pembrolizumab, every 6 weeks (Q6W), has been approved by the U.S. FDA, reducing the frequency of visits to infusion centers. We quantified the time spent by oncologists, nurses, patients, and caregivers per melanoma-related immunotherapy infusion visit to evaluate its potential impact. METHODS: Surveys were self-completed by 100 oncologists, 101 oncology nurses, and 100 patients with melanoma across the U.S. to quantify the time spent per infusion visit with pembrolizumab (Q3W or Q6W), nivolumab (Q2W or Q4W), or nivolumab+ipilimumab (nivolumab in combination: Q3W; nivolumab maintenance: Q2W or Q4W). Time measures included traveling, waiting, consultation, infusion, post-treatment observation, and caregiving. Respondents were also surveyed regarding the impact of the COVID-19 pandemic on infusion treatments. RESULTS: Responses deemed valid were provided by 89 oncologists, 93 nurses, and 100 patients. For each new [returning] patient treated with pembrolizumab, nivolumab or nivolumab+ipilimumab, oncologists reported to spend an average of 90 [64], 87 [60] and 101 [69] minutes per infusion visit (p-value for between-group difference = 0.300 [0.627]). For first [subsequent] treatment cycles, nurses reported spending 160 [145] average minutes per visit for nivolumab+ipilimumab, versus roughly 120 [110] for the single agents (p-value for between-group difference = 0.018 [0.022]). Patients reported to spend an average of 263, 382, and 224 minutes per visit at the center for pembrolizumab (N = 47), nivolumab (n = 34), and nivolumab+ipilimumab (n = 15) respectively (p-value for between-group difference = 0.0002). Patients also reported that their unpaid (N = 20) and paid caregivers (N = 41) spent with them an average of 966 and 333 minutes, respectively, from the day before to the day after the infusion visit. CONCLUSION: Less frequent immunotherapy infusion visits may result in substantial time savings for oncologists, nurses, patients, and caregivers.

The Glutamatergic System in Treatment-Resistant Depression and Comparative Effectiveness of Ketamine and Esketamine: Role of Inflammation?

The glutamatergic system is the primary excitatory pathway within the CNS and is responsible for cognition, memory, learning, emotion, and mood. Because of its significant importance in widespread nervous system function, it is tightly regulated through multiple mechanisms, such as glutamate recycling, microglial interactions, and inflammatory pathways. Imbalance within the glutamatergic system has been implicated in a wide range of pathological conditions including neurodegenerative conditions, neuromuscular conditions, and mood disorders including depression. Major depressive disorder (MDD) is the most common mood disorder worldwide, has a high prevalence rate, and afflicts approximately 280 million people. While there are numerous treatments for the disease, 30-40% of patients are unresponsive to treatment and deemed treatment resistant; approximately another third experience only partial improvement (World Health Organization, Depression fact sheet [Internet], 2020). Esketamine, the S-enantiomer of ketamine, was approved by the Food and Drug Administration for treatment-resistant depression (TRD) in 2019 and has offered new hope to patients. It is the first treatment targeting the glutamatergic system through a complex mechanism. Numerous studies have implicated imbalance in the glutamatergic system in depression and treatment resistance. Esketamine and ketamine principally work through inhibition of the NMDA receptor, though more recent studies have implicated numerous other mechanisms mediating the antidepressant efficacy of these agents. These mechanisms include increase in brain-derived neurotrophic factor (BDNF), activation of mammalian target of the rapamycin complex (mTORC), and reduction in inflammation. Esketamine and ketamine have been shown to decrease inflammation in numerous ways principally through reducing pro-inflammatory cytokines (e.g., TNF-α, IL-6) (Loix et al., Acta Anaesthesiol Belg 62(1):47-58, 2011; Chen et al., Psychiatry Res 269:207-11, 2018; Kopra et al., J Psychopharmacol 35(8):934-45, 2021). This anti-inflammatory effect has also been shown to be involved in the antidepressive properties of both ketamine and esketamine (Chen et al., Psychiatry Res 269:207-11, 2018; Kopra et al., J Psychopharmacol 35(8):934-45, 2021).

Co-Designing a Mobile-Based Game to Improve Misinformation Resistance and Vaccine Knowledge in Uganda, Kenya, and Rwanda.

Misinformation can decrease public confidence in vaccines, and reduce vaccination intent and uptake. One strategy for countering these negative impacts comes from inoculation theory. Similar to biological vaccination, inoculation theory posits that exposure to a weakened form of misinformation can develop cognitive immunity, reducing the likelihood of being misled. Online games offer an interactive, technology-driven, and scalable solution using an active form of inoculation that engages and incentivizes players to build resilience against misinformation. We document the development of the critical thinking game Cranky Uncle Vaccine. The game applies research findings from inoculation theory, critical thinking, humor in science communication, and serious games. The game content was iterated through a series of co-design workshops in Kampala (Uganda), Kitale (Kenya), and Kigali (Rwanda). Workshop participants offered feedback on cartoon character design, gameplay experience, and the game's content, helping to make the game more culturally relevant and avoid unintended consequences in East African countries. Our co-design methodology offers an approach for further adaptation of the Cranky Uncle Vaccine game to other regions, as well as a template for developing locally relevant interventions to counter future infodemics.

Revealing the role of the cathode-electrolyte interface on solid-state batteries.

Interfaces have crucial, but still poorly understood, roles in the performance of secondary solid-state batteries. Here, using crystallographically oriented and highly faceted thick cathodes, we directly assess the impact of cathode crystallography and morphology on the long-term performance of solid-state batteries. The controlled interface crystallography, area and microstructure of these cathodes enables an understanding of interface instabilities unknown (hidden) in conventional thin-film and composite solid-state electrodes. A generic and direct correlation between cell performance and interface stability is revealed for a variety of both lithium- and sodium-based cathodes and solid electrolytes. Our findings highlight that minimizing interfacial area, rather than its expansion as is the case in conventional composite cathodes, is key to both understanding the nature of interface instabilities and improving cell performance. Our findings also point to the use of dense and thick cathodes as a way of increasing the energy density and stability of solid-state batteries.

When Science Becomes Embroiled in Conflict: Recognizing the Public's Need for Debate while Combating Conspiracies and Misinformation.

Most democracies seek input from scientists to inform policies. This can put scientists in a position of intense scrutiny. Here we focus on situations in which scientific evidence conflicts with people's worldviews, preferences, or vested interests. These conflicts frequently play out through systematic dissemination of disinformation or the spreading of conspiracy theories, which may undermine the public's trust in the work of scientists, muddy the waters of what constitutes truth, and may prevent policy from being informed by the best available evidence. However, there are also instances in which public opposition arises from legitimate value judgments and lived experiences. In this article, we analyze the differences between politically-motivated science denial on the one hand, and justifiable public opposition on the other. We conclude with a set of recommendations on tackling misinformation and understanding the public's lived experiences to preserve legitimate democratic debate of policy.

High performance implementation of the hierarchical likelihood for generalized linear mixed models: an application to estimate the potassium reference range in massive electronic health records datasets.

BACKGROUND: Converting electronic health record (EHR) entries to useful clinical inferences requires one to address the poor scalability of existing implementations of Generalized Linear Mixed Models (GLMM) for repeated measures. The major computational bottleneck concerns the numerical evaluation of multivariable integrals, which even for the simplest EHR analyses may involve millions of dimensions (one for each patient). The hierarchical likelihood (h-lik) approach to GLMMs is a methodologically rigorous framework for the estimation of GLMMs that is based on the Laplace Approximation (LA), which replaces integration with numerical optimization, and thus scales very well with dimensionality. METHODS: We present a high-performance, direct implementation of the h-lik for GLMMs in the R package TMB. Using this approach, we examined the relation of repeated serum potassium measurements and survival in the Cerner Real World Data (CRWD) EHR database. Analyzing this data requires the evaluation of an integral in over 3 million dimensions, putting this problem beyond the reach of conventional approaches. We also assessed the scalability and accuracy of LA in smaller samples of 1 and 10% size of the full dataset that were analyzed via the a) original, interconnected Generalized Linear Models (iGLM), approach to h-lik, b) Adaptive Gaussian Hermite (AGH) and c) the gold standard for multivariate integration Markov Chain Monte Carlo (MCMC). RESULTS: Random effects estimates generated by the LA were within 10% of the values obtained by the iGLMs, AGH and MCMC techniques. The H-lik approach was 4-30 times faster than AGH and nearly 800 times faster than MCMC. The major clinical inferences in this problem are the establishment of the non-linear relationship between the potassium level and the risk of mortality, as well as estimates of the individual and health care facility sources of variations for mortality risk in CRWD. CONCLUSIONS: We found that the direct implementation of the h-lik offers a computationally efficient, numerically accurate approach for the analysis of extremely large, real world repeated measures data via the h-lik approach to GLMMs. The clinical inference from our analysis may guide choices of treatment thresholds for treating potassium disorders in the clinic.

Eighty-Five Percent of Improved Optical Power Delivery to Epiretinal Prostheses Using Rigid Body Compensation Algorithm.

Vision impairment caused by degenerative retinal pathologies such as age-related macular degeneration can be treated using retinal implants. Such devices receive power and data using cables passing through a permanent surgical incision in the eye wall (sclera), which increases the risk to patients and surgical costs. A recently developed retinal implant design eliminates the necessity of the implant cable using a photonic power converter (PPC), which receives optical power and data through the pupil and is directed by an ellipsoidal reflector and micro-electromechanical mirror. We present a misalignment compensation algorithm model that accounts for rigid-body motions of the reflector relative to the eye and applies the correction to the mirror coordinates in the presence of angular misalignment of the reflector. We demonstrate that up to 85% of the nominal optical power can be delivered to the implant with axial reflector misalignments up to 30 deg using the compensation algorithm.

SARS/CoV-2: Behavioral Host Manipulation.

INTRODUCTION: Though it has not been extensively studied, host manipulation has been documented for various pathogens. Examples of this phenomenon can be seen in cases of toxoplasmosis, rabies, and the influenza virus. An examination of the possible means by which SARS/CoV-2 alters the behavior of its host to spread among populations is elaborated. Indirect evidence that serves as indicators of this phenomenon is presented. METHODS: This is primarily a theoretical document. Many of the ideas raised are not amenable to direct testing due to ethical concerns. However, several indirect means by which to test the hypothesis are discussed. Primary data from cell phones regarding miles traveled, number of times leaving home, etc., are among the possible indirect measures. RESULTS: The rapid ability of the SARS/CoV-2 virus to spread through society suggests that it may cause behavioral changes of the host to increase its transmission. Numerous cases of super spreader events are noted that have provided meaningful measures of host manipulation. CONCLUSION: In the case of SARS/CoV-2, the largest advantage of the pathogen is likely that between 50% and 70% of those infected are asymptomatic (John's Hopkins Coronavirus Resource Center, John's Hopkins University Corona Virus Resource Center. Available at https://coronavirus.jhu.edu/map.html , 2020). This component is a threat to elderly individuals and those immunocompromised who are more likely to have severe complications from the virus and die. To spread within these groups, a seemingly healthy host is necessary to carry the virus to them. The goal of the virus is not to kill the host, but to survive and reproduce.

An Eye Tracking Approach to Understanding Misinformation and Correction Strategies on Social Media: The Mediating Role of Attention and Credibility to Reduce HPV Vaccine Misperceptions.

This study uses an unobtrusive eye tracking approach to examine understudied psychological mechanisms - message attention and credibility - when people are exposed to misinformation and correction on social media. We contrast humor versus non-humor correction strategies that point out rhetorical flaws in misinformation regarding the HPV vaccine, which was selected for its relevance and impact on public health. We randomly assigned participants to one of two experimental conditions: humor correction versus non-humor correction. Our analyses revealed that the humor correction increased attention to the image portion of the correction tweet, and this attention indirectly lowered HPV misperceptions by reducing the credibility of the misinformation tweet. The study also found that the non-humor correction outperformed the humor correction in reducing misperceptions via its higher credibility ratings. Practical implications for correcting misinformation on social media are discussed.

Radiation-Induced Senescence Reprograms Secretory and Metabolic Pathways in Colon Cancer HCT-116 Cells.

Understanding the global metabolic changes during the senescence of tumor cells can have implications for developing effective anti-cancer treatment strategies. Ionizing radiation (IR) was used to induce senescence in a human colon cancer cell line HCT-116 to examine secretome and metabolome profiles. Control proliferating and senescent cancer cells (SCC) exhibited distinct morphological differences and expression of senescent markers. Enhanced secretion of pro-inflammatory chemokines and IL-1, anti-inflammatory IL-27, and TGF-ß1 was observed in SCC. Significantly reduced levels of VEGF-A indicated anti-angiogenic activities of SCC. Elevated levels of tissue inhibitors of matrix metalloproteinases from SCC support the maintenance of the extracellular matrix. Adenylate and guanylate energy charge levels and redox components NAD and NADP and glutathione were maintained at near optimal levels indicating the viability of SCC. Significant accumulation of pyruvate, lactate, and suppression of the TCA cycle in SCC indicated aerobic glycolysis as the predominant energy source for SCC. Levels of several key amino acids decreased significantly, suggesting augmented utilization for protein synthesis and for use as intermediates for energy metabolism in SCC. These observations may provide a better understanding of cellular senescence basic mechanisms in tumor tissues and provide opportunities to improve cancer treatment.

Evaluation of Pathologic Complete Response as a Surrogate for Long-Term Survival Outcomes in Triple-Negative Breast Cancer.

BACKGROUND: Pathologic complete response (pCR) is a common efficacy endpoint in neoadjuvant therapy trials for triple-negative breast cancer (TNBC). Previous studies have shown that pCR is strongly associated with improved long-term survival outcomes, including event-free survival (EFS) and overall survival (OS). However, the trial-level associations between treatment effect on pCR and long-term survival outcomes are not well established. This study sought to evaluate these associations by incorporating more recent clinical trials in TNBC. METHODS: A literature review identified published randomized controlled trials (RCTs) of neoadjuvant therapy for TNBC that reported results for both pCR and EFS/OS. Meta-regression models were performed to evaluate the association of treatment effect on pCR and EFS/OS. Sensitivity analyses were conducted to assess the impact of divergent study designs. RESULTS: Ten comparisons from 8 RCTs (N=2,478 patients) were identified from the literature review. The log (odds ratio) of pCR was a significant predictor of the log (hazard ratio) of EFS (P=.003), with a coefficient of determination of 0.68 (95% CI, 0.41-0.95). There was a weaker association between pCR and OS (P=.18), with a coefficient of determination of 0.24 (95% CI, 0.01-0.77). Consistent results were found in the exploratory analysis and sensitivity analyses. CONCLUSIONS: This is the first study that has shown a trial-level association between pCR and survival outcomes in TNBC. By incorporating the most up-to-date RCTs, this study showed a significant trial-level association between pCR and EFS. A positive association between pCR and OS was also recorded.

Correction to: Science by social media: Attitudes towards climate change are mediated by perceived social consensus.

Confidence intervals and regression lines were omitted from Fig. 1 in this article as originally published. This error was introduced during production. The original article has been corrected.

Science by social media: Attitudes towards climate change are mediated by perceived social consensus.

Internet blogs have become an important platform for the discussion of many scientific issues, including climate change. Blogs, and in particular the comment sections of blogs, also play a major role in the dissemination of contrarian positions that question mainstream climate science. The effect of this content on people's attitudes is not fully understood. In particular, it is unknown how the interaction between the content of blog posts and blog comments affects readers' attitudes. We report an experiment that orthogonally varied those two variables using blog posts and comments that either did, or did not, support the scientific consensus on climate change. We find that beliefs are partially shaped by readers' perception of how widely an opinion expressed in a blog post appears to be shared by other readers. The perceived social consensus among readers, in turn, is determined by whether blog comments endorse or reject the contents of a post. When comments reject the content, perceived reader consensus is lower than when comments endorse the content. The results underscore the importance of perceived social consensus on opinion formation.

Oxygen vacancies enhance pseudocapacitive charge storage properties of MoO3-x.

The short charging times and high power capabilities associated with capacitive energy storage make this approach an attractive alternative to batteries. One limitation of electrochemical capacitors is their low energy density and for this reason, there is widespread interest in pseudocapacitive materials that use Faradaic reactions to store charge. One candidate pseudocapacitive material is orthorhombic MoO3 (α-MoO3), a layered compound with a high theoretical capacity for lithium (279 mA h g-1 or 1,005 C g-1). Here, we report on the properties of reduced α-MoO3-x(R-MoO3-x) and compare it with fully oxidized α-MoO3 (F-MoO3). The introduction of oxygen vacancies leads to a larger interlayer spacing that promotes faster charge storage kinetics and enables the α-MoO3 structure to be retained during the insertion and removal of Li ions. The higher specific capacity of the R-MoO3-x is attributed to the reversible formation of a significant amount of Mo4+ following lithiation. This study underscores the potential importance of incorporating oxygen vacancies into transition metal oxides as a strategy for increasing the charge storage kinetics of redox-active materials.

Cap-Score™ prospectively predicts probability of pregnancy.

Semen analysis (SA) poorly predicts male fertility, because it does not assess sperm fertilizing ability. The percentage of capacitated sperm determined by GM1 localization ("Cap-Score™"), differs between cohorts of fertile and potentially infertile men, and retrospectively, between men conceiving or failing to conceive by intrauterine insemination (IUI). Here, we prospectively tested whether Cap-Score can predict male fertility with the outcome being clinical pregnancy within ≤3 IUI cycles. Cap-Score and SA were performed (n = 208) with outcomes initially available for 91 men. Men were predicted to have either low (n = 47) or high (n = 44) chance of generating pregnancy using previously-defined Cap-Score reference ranges. Absolute and cumulative pregnancy rates were reduced in men predicted to have low pregnancy rates versus high ([absolute: 10.6% vs. 29.5%; p = 0.04]; [cumulative: 4.3% vs. 18.2%, 9.9% vs. 29.1%, and 14.0% vs. 32.8% for cycles 1-3; n = 91, 64, and 41; p = 0.02]). Only Cap-Score, not male/female age or SA results, differed significantly between outcome groups. Logistic regression evaluated Cap-Score and SA results relative to the probability of generating pregnancy (PGP) for men who were successful in, or completed, three IUI cycles (n = 57). Cap-Score was significantly related to PGP (p = 0.01). The model fit was then tested with 67 additional patients (n = 124; five clinics); the equation changed minimally, but fit improved (p < 0.001; margin of error: 4%). The Akaike Information Criterion found the best model used Cap-Score as the only predictor. These data show that Cap-Score provides a practical, predictive assessment of male fertility, with applications in assisted reproduction and treatment of male infertility.

Comparing three regularization methods to avoid extreme allocation probability in response-adaptive randomization.

We examine three variations of the regularization methods for response-adaptive randomization (RAR) and compare their operating characteristics. A power transformation (PT) is applied to refine the randomization probability. The clip method is used to bound the randomization probability within specified limits. A burn-in period of equal randomization (ER) can be added before adaptive randomization (AR). For each method, more patients are assigned to the superior arm and overall response rate increase as the scheme approximates simple AR, while statistical power increases as it approximates ER. We evaluate the performance of the three methods by varying the tuning parameter to control the extent of AR to achieve the same statistical power. When there is no early stopping rule, PT method generally performed the best in yielding higher proportion to the superior arm and higher overall response rate, but with larger variability. The burn-in method showed smallest variability compared with the clip method and the PT method. With the efficacy early stopping rule, all three methods performed more similarly. The PT and clip methods are better than the burn-in method in achieving higher proportion randomized to the superior arm and higher overall response rate but burn-in method required fewer patients in the trial. By carefully choosing the method and the tuning parameter, RAR methods can be tailored to strike a balance between achieving the desired statistical power and enhancing the overall response rate.

Using X-ray Microscopy To Understand How Nanoporous Materials Can Be Used To Reduce the Large Volume Change in Alloy Anodes.

Tin metal is an attractive negative electrode material to replace graphite in Li-ion batteries due to its high energy density. However, tin undergoes a large volume change upon alloying with Li, which pulverizes the particles, and ultimately leads to short cycling lifetimes. Nevertheless, nanoporous materials have been shown to extend battery life well past what is observed in nonporous material. Despite the exciting potential of porous alloying anodes to significantly increase the energy density in Li-ion batteries, the fundamental physics of how nanoscale architectures accommodate the electrochemically induced volume changes are poorly understood. Here, operando transmission X-ray microscopy has been used to develop an understanding of the mechanisms that govern the enhanced cycling stability in nanoporous tin. We found that in comparison to dense tin, nanoporous tin undergoes a 6-fold smaller areal expansion after lithiation, as a result of the internal porosity and unique nanoscale architecture. The expansion is also more gradual in nanoporous tin compared to the dense material. The nanoscale resolution of the microscope used in this study is ∼30 nm, which allowed us to directly observe the pore structure during lithiation and delithiation. We found that nanoporous tin remains porous during the first insertion and desinsertion cycle. This observation is key, as fully closed pores could lead to mechanical instability, electrolyte inaccessibility, and short lifetimes. While tin was chosen for this study because of its high X-ray contrast, the results of this work should be general to other alloy-type systems, such as Si, that also suffer from volume change based cycling degradation.