Deep learning detection of hand motion during microvascular anastomosis simulations performed by expert cerebrovascular neurosurgeons.

OBJECTIVE: Deep learning enables precise hand tracking without the need for physical sensors, allowing for unsupervised quantitative evaluation of surgical motion and tasks. We quantitatively assessed the hand motions of experienced cerebrovascular neurosurgeons during simulated microvascular anastomosis using deep learning. We explored the extent to which surgical motion data differed among experts. METHODS: A deep learning detection system tracked 21 landmarks corresponding to digit joints and the wrist on each hand of 5 expert cerebrovascular neurosurgeons. Tracking data for each surgeon was analyzed over long and short time intervals to examine gross movements and micromovements, respectively. Quantitative algorithms assessed the economy and flow of motion by calculating mean movement distances from the baseline median landmark coordinates and median times between sutures, respectively. RESULTS: Tracking data correlated with specific surgical actions observed in microanastomosis video analysis. Economy of motion during suturing was calculated as 19, 26, 29, 27, and 28 pixels for surgeons 1, 2, 3, 4, and 5, respectively. Flow of motion during microanastomosis was 31.96, 29.40, 28.90, 7.37, and 47.21 secs for surgeons 1, 2, 3, 4, and 5, respectively. CONCLUSIONS: Hand tracking data showed similarities among experts, with low movements from baseline, minimal excess motion, and rhythmic suturing patterns. The data revealed unique patterns related to each expert's habits and techniques. The results showed that surgical motion can be correlated with hand motion and assessed using mathematical algorithms. We also demonstrated the feasibility and potential of deep learning-based motion detection to enhance surgical training.

The physical activity in cancer survivors (PACES) trial: a factorial randomized trial to optimize intervention for breast cancer survivors.

Multiple intervention strategies have been found effective for increasing physical activity among breast cancer survivors, yet most breast cancer survivors fail to meet physical activity recommendations. Optimization of interventions can facilitate real word implementation to ensure effective and efficient intervention delivery. Using a full-factorial design based on the Multiphase Optimization Strategy, 337 breast cancer survivors were randomized to receive a combination of four intervention components: (1) supervised exercise sessions, (2) facility membership, (3) Active Living Every Day (ALED), and (4) Fitbit. Moderate-to vigorous (MVPA) and light-intensity physical activity (LPA) were measured at baseline, 3 months, and 6 months with a hip-worn Actigraph GT3X+. Normal linear mixed models with separate intercepts for each subject were fit in the SAS 9.4 Mixed procedure. Participants who received supervised exercise sessions engaged in more MVPA, 153.58 min/week vs. 133.0 min/week (F = 3.97, p = 0.048) and LPA, 170.26 min/day versus 160.98 light PA minutes/day (F = 4.67, p = 0.032), compared to participants who did not receive supervised exercise. The effects of the three other intervention components on MVPA were not significant; however, those that received ALED engaged in less LPA (F = 6.6, p = 0.011). Supervised exercise sessions resulted in significant increases in MVPA and LPA in a sample of breast cancer survivors. Of note, these sessions were provided only during the first 6 weeks of the intervention and effects remained significant at 6 months. Results of this trial could inform future implementation efforts to ensure effective and efficient delivery of physical activity programs for breast cancer survivors.

Analysis of PFAS and further VOC from fluoropolymer-coated cookware by thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS).

Per- and polyfluoroalkyl substances (PFAS) are used in the production of PTFE based coatings for cookware. In this study, emission of PFAS and further volatile organic compounds (VOC) from kitchenware articles were investigated. First, method development for thermal extraction of baking trays, frying pans and baking mats at 250 °C was done by testing three different extraction devices. A thermal desorption oven showed the best blank and highest recoveries of PFAS analytes (70-101% for 12 perfluorocarboxylic acids (PFCAs), 2 fluorotelomer alcohls (FTOHs), 3 per- and polyfluoroether carboxylic acids (PFECAs), 1 polyfluoroether (PFE)). Second, 18 cookware samples, a PTFE micro powder and 2 lab made coating strips have been investigated. No PFAS were detected in 12 samples (limits of detection: 1-13 ng/dm2). PFCAs (C5-C23) were detected in a baking tray in amounts up to 34 ng/dm2. A baking mat contained 3 ng/dm2 PFOA. FTOHs were not detected in the samples. A PFECA (bC7O2) and its hydride (bC6O2H PFE) were detected in one coating intended for use in frying pans. The hydrides of the PFECA mixture, b(C3O1)nC3 PFECA (Krytox 157FSH), were detected in five baking trays. The PFAS target analytes were not detectable in the five investigated frying pans. Analysing further VOC in the emissions of coatings, 175 compounds could be identified, including alkanes, alkenes, aromatic substances, esters, aldehydes, ketones, ethers, alcohols, carboxylic acids, siloxanes and sulphur, nitrogen, as well as chlorine containing compounds (< 10 µg/dm2). The identified substances cannot be connected to the basic coating polymer of the kitchenware articles, which were PTFE and PES. All samples have undergone a threefold thermal extraction. No substances could be detected in the second and third consecutive extraction, which means that a removal and no new formation of the investigated PFAS as well as the further VOC at 250 °C has occurred.

Alcohol and fear conditioning produce strain-specific changes in the dorsal hippocampal transcriptome of adolescent C57BL/6J and DBA/2J mice.

BACKGROUND: Adolescent sensitivity to alcohol is influenced by genetic background. Data from our laboratory suggested that adolescent C57BL/6J and DBA/2J inbred mice differed in susceptibility to alcohol-induced deficits in dorsal hippocampus-dependent contextual fear learning. METHODS: To investigate the biological underpinnings of this strain difference, we examined dorsal hippocampus gene expression using RNA-sequencing after alcohol or saline administration followed by Pavlovian fear conditioning across male and female C57BL/6J and DBA/2J adolescents. RESULTS: Strains exhibited dramatic differences in dorsal hippocampus gene expression. Specifically, C57BL/6J and DBA/2J strains differed by 3526 transcripts in males and 2675 transcripts in females. We identified pathways likely to be involved in mediating alcohol's effects on learning, including networks associated with Chrna7, a gene encoding the nicotinic cholinergic receptor alpha 7 subunit, and Fmr1, a gene encoding the fragile X messenger ribonucleoprotein. CONCLUSIONS: These findings provide insight into the mechanisms underlying strain differences in alcohol's effects on learning and suggest that different biological networks are recruited for learning based on genetics, sex, and alcohol exposure.

Ethanol Inhalation as a Method to Denature the Spike Protein of SARS-CoV-2.

The SARS-CoV-2 virus caused the 2019 COVID pandemic by infecting almost eight hundred million people worldwide. Because it was a new viral infection, there were no vaccines or small molecule medications that could prevent or treat the disease.  This chapter provides some details for an obscure treatment for COVID-19, that has decades of anti-viral activity data both in vitro and in vivo in the literature. The medicinal molecules are compared to other small molecules that were identified as possible medications for COVID-19.  We developed a computational method that ranks small molecules and their ability to penetrate mucus in the lungs of a COVID-19 patient. Our focus is ethanol as a COVID-19 treatment. The results discussed here are based on Lipinski Rules and QSAR computational methods as well as in vitro and in vivo data. These parameters indicate that ethanol should be a strong candidate for future evaluations.

Real-world experience with circulating tumor DNA in cerebrospinal fluid from patients with central nervous system tumors.

The characterization of genetic alterations in tumor samples has become standard practice for many human cancers to achieve more precise disease classification and guide the selection of targeted therapies. Cerebrospinal fluid (CSF) can serve as a source of tumor DNA in patients with central nervous system (CNS) cancer. We performed comprehensive profiling of CSF circulating tumor DNA (ctDNA) in 711 patients using an FDA-authorized platform (MSK-IMPACT™) in a hospital laboratory. We identified genetic alterations in 489/922 (53.0%) CSF samples with clinically documented CNS tumors. None of 85 CSF samples from patients without CNS tumors had detectable ctDNA. The distribution of clinically actionable somatic alterations was consistent with tumor-type specific alterations across the AACR GENIE cohort. Repeated CSF ctDNA examinations from the same patients identified clonal evolution and emergence of resistance mechanisms. ctDNA detection was associated with shortened overall survival following CSF collection. Next-generation sequencing of CSF, collected through a minimally invasive lumbar puncture in a routine hospital setting, provides clinically actionable cancer genotype information in a large fraction of patients with CNS tumors.

Novel evidence that elk were historically native to the Sierra Nevada, and recent range expansions into the region.

Elk (Cervus canadensis) have been considered non-native to the Sierra Nevada mountain range of California and Nevada. However, elk have steadily increased their range southward from the Cascade Range into the northern Sierra Nevada over the last century. Recent reports also reveal Rocky Mountain elk moving northwards into the southern Sierra Nevada. Dispersals of lone bull elk from 2019-2022 have occurred to the central Sierra Nevada south of Lake Tahoe. These recent range expansions of elk herds and long-distance dispersals of individual elk raised questions about the possible historical presence of elk throughout this mountain range. Herein we conducted a broad investigation into historical newspaper accounts and other early explorer and naturalist observer records, museum specimens, Late Holocene zooarchaeological records, and indirect evidence including toponomastic references and Native American ethnographic and ethnolinguistic information. Taken in total, a variety of data sources suggest elk inhabited portions of the Sierra Nevada and the adjacent northwest Great Basin from the Late Holocene through historical times. Positive records were not numerous, suggesting that historically elk were not abundant, and nearly extirpated during the California Fur Rush of the early nineteenth century.

Beyond Medical Bills: The Indirect Costs of Prostate Cancer.

PURPOSE: Both direct and indirect costs contribute to financial toxicity in prostate cancer. Indirect costs are difficult to assess and quantify and therefore remain understudied. We sought to describe the indirect costs of prostate cancer across risk groups as well as identify any associated sociodemographic factors. MATERIALS AND METHODS: Patients with localized prostate cancer were surveyed regarding their indirect costs at baseline and 3, 6, 12, and 24-month follow-ups. "Out-of-pocket indirect costs" were defined as costs paid for medication, parking, transportation, meals outside the home, and caregivers. "Imputed indirect costs" were calculated based on hour estimates for traveling time, missed work, additional time spent on work, and additional time dedicated to their care by caregivers. Generalized linear model regressions were performed to evaluate for potential associations between sociodemographic or clinical features with these indirect costs, stratifying by prostate cancer risk group. RESULTS: Four hundred and ninety five localized prostate cancer patients were included in the analysis. Indirect costs ranged from $154.00 to $717.40 for out-of-pocket and $352 to $3389 for imputed per month and did tend to be higher for higher-risk disease. In regression models, sociodemographic factors did not appear to play a strong role in variation in indirect costs. CONCLUSIONS: Within a 24-month follow-up period, we observed that indirect costs of localized prostate cancer range from $608 to $4107 per month when including lost productivity costs. Further work must be done to identify what factors contribute to increased indirect costs and financial toxicity.

Electrochemical Sensors for Antibiotic Detection: A Focused Review with a Brief Overview of Commercial Technologies.

Antimicrobial resistance (AMR) poses a significant threat to global health, powered by pathogens that become increasingly proficient at withstanding antibiotic treatments. This review introduces the factors contributing to antimicrobial resistance (AMR), highlighting the presence of antibiotics in different environmental and biological matrices as a significant contributor to the resistance. It emphasizes the urgent need for robust and effective detection methods to identify these substances and mitigate their impact on AMR. Traditional techniques, such as liquid chromatography-mass spectrometry (LC-MS) and immunoassays, are discussed alongside their limitations. The review underscores the emerging role of biosensors as promising alternatives for antibiotic detection, with a particular focus on electrochemical biosensors. Therefore, the manuscript extensively explores the principles and various types of electrochemical biosensors, elucidating their advantages, including high sensitivity, rapid response, and potential for point-of-care applications. Moreover, the manuscript investigates recent advances in materials used to fabricate electrochemical platforms for antibiotic detection, such as aptamers and molecularly imprinted polymers, highlighting their role in enhancing sensor performance and selectivity. This review culminates with an evaluation and summary of commercially available and spin-off sensors for antibiotic detection, emphasizing their versatility and portability. By explaining the landscape, role, and future outlook of electrochemical biosensors in antibiotic detection, this review provides insights into the ongoing efforts to combat the escalating threat of AMR effectively.

Eiken syndrome with parathyroid hormone resistance due to a novel parathyroid hormone receptor type 1 mutation: clinical features and functional analysis.

We report two patients of east African ancestry with the same novel homozygous variant in the parathyroid hormone receptor type 1 (PTH1R). Both patients shared skeletal features including brachydactyly, extensive metacarpal pseudoepiphyses, elongated cone-shaped epiphyses, ischiopubic hypoplasia, deficient sacral ossification, suggestive of Eiken syndrome. Strikingly, both patients exhibited clinically manifest parathyroid hormone (PTH) resistance with hypocalcaemia and elevated serum phosphate levels. These laboratory and clinical abnormalities initially suggested pseudohypoparathyroidism, which is typically associated with GNAS abnormalities. In both patients, however, a homozygous novel PTH1R variant was identified (c.710 T > A; p.IIe237Asn, p.I237N) that is located in the second transmembrane helical domain. Previously, others have reported a patient with a nearby PTH1R mutation (D241E) who presented with similar clinical features, e.g. delayed bone mineralization as well as clinical PTH resistance. Functional analysis of the effects of both novel PTH1R variants (I237N- and D241E-PTH1R) in HEK293 reporter cells transfected with plasmid DNA encoding the wild-type or mutant PTH1Rs demonstrated increased basal cAMP signalling for both variants, with relative blunting of responses to both PTH and PTH-related peptide (PTHrP) ligands. The clinical presentation of PTH resistance and delayed bone mineralization combined with the functional properties of the mutant PTH1Rs suggest that this form of Eiken syndrome results from alterations in PTH1R-mediated signalling in response to both canonical ligands, PTH and PTHrP.

Eiken syndrome is an extremely rare genetic disorder of skeletal development, previously reported in only 7 people in the medical literature. It is due to alterations in the gene for the parathyroid hormone receptor type 1 (PTH1R). This receptor can bind two different hormones; parathyroid hormone (PTH), which is the body's main regulator of the level of calcium in the blood, and parathyroid hormone related peptide (PTHrP), a smaller hormone that regulates bone development. We report two new cases of Eiken syndrome sharing the exact same change in the PTH1R gene. This genetic change has not been previously reported. The patients had many of the typical findings in the skeleton reported in previous cases of Eiken syndrome, but with some variation in the features. However, unlike any previously reported people with Eiken syndrome, the two patients we describe had low levels of calcium in the blood causing significant symptoms. Low calcium has been reported in some cases of Eiken syndrome before, but this has been mild and not associated with symptoms. We wanted to explore how this new mutation affects the function of the PTH receptor, particularly how it might affect the signals generated when the receptor binds to its two different hormones, PTH and PTHrP. We did this by genetically reprogramming a cell line with the new mutation, and then testing those cells' responses to stimulation by the two hormones. We showed that the altered receptor appears to be unable to bind both hormones in a stable fashion, explaining why the patients showed changes both in the skeleton (due mostly to altered PTHrP signalling) and in the blood level of calcium (mostly due to altered PTH signalling).

Spatiotemporal Forecasting of Opioid-Related Fatal Overdoses: Towards Best Practices for Modeling and Evaluation.

To inform public health interventions, researchers have developed models to forecast opioid-related overdose mortality. These efforts often have limited overlap in the models and datasets employed, presenting challenges to assessing progress in this field. Furthermore, common error-based performance metrics, such as root mean squared error (RMSE), cannot directly assess a key modeling purpose: the identification of priority areas for interventions. We recommend a new intervention-aware performance metric, Percentage of Best Possible Reach (%BPR). We compare metrics for many published models across two distinct geographic settings, Cook County, Illinois and Massachusetts, assuming the budget to intervene in 100 census tracts out of 1000s in each setting. The top-performing models based on RMSE recommend areas that do not always reach the most possible overdose events. In Massachusetts, the top models preferred by %BPR could have reached 18 additional fatal overdoses per year in 2020-2021 compared to models favored by RMSE. In Cook County, the different metrics select similar top-performing models, yet other models with similar RMSE can have significant variation in %BPR. We further find that simple models often perform as well as recently published ones. We release open code and data for others to build upon.

Plant versus pollinator protection: balancing pest management against floral contamination for insecticide use in Midwestern US cucurbits.

Controlling crop pests while conserving pollinators is challenging, particularly when prophylactically applying broad-spectrum, systemic insecticides such as neonicotinoids. Systemic insecticides are often used in conventional agriculture in commercial settings, but the conditions that optimally balance pest management and pollination are poorly understood. We investigated how insecticide application strategies control pests and expose pollinators to insecticides with an observational study of cucurbit crops in the Midwestern United States. To define the window of protection and potential pollinator exposure resulting from alternative insecticide application strategies, we surveyed 62 farms cultivating cucumber, watermelon, or pumpkin across 2 yr. We evaluated insecticide regimes, abundance of striped and spotted cucumber beetles (Acalymma vittatum [Fabricius] and Diabrotica undecimpunctata Mannerheim), and insecticide residues in leaves, pollen, and nectar. We found that growers used neonicotinoids (thiamethoxam and imidacloprid) at planting in all cucumber and pumpkin and approximately half of watermelon farms. In cucumber, foliar thiamethoxam levels were orders of magnitude higher than the other crops, excluding nearly all beetles from fields. In watermelon and pumpkin, neonicotinoids applied at planting resulted in 4-8 wk of protection before beetle populations increased. Floral insecticide concentrations correlated strongly with foliar concentrations across all crops, resulting in high potential exposure to pollinators in cucumber and low-moderate exposure in pumpkin and watermelon. Thus, the highest-input insecticide regimes maintained cucumber beetles far below economic thresholds while also exposing pollinators to the highest pollen and nectar insecticide concentrations. In cucurbits, reducing pesticide inputs will likely better balance crop protection and pollination, reduce costs, and improve yields.

Neu5Gc binding loss of subtype H7 influenza A virus facilitates adaptation to gallinaceous poultry following transmission from waterbirds.

Between 2013 and 2018, the novel A/Anhui/1/2013 (AH/13)-lineage H7N9 virus caused at least five waves of outbreaks in humans, totaling 1,567 confirmed human cases in China. Surveillance data indicated a disproportionate distribution of poultry infected with this AH/13-lineage virus, and laboratory experiments demonstrated that this virus can efficiently spread among chickens but not among Pekin ducks. The underlying mechanism of this selective transmission remains unclear. In this study, we demonstrated the absence of Neu5Gc expression in chickens across all respiratory and gastrointestinal tissues. However, Neu5Gc expression varied among different duck species and even within the tissues of the same species. The AH/13-lineage viruses exclusively bind to acetylneuraminic acid (Neu5Ac), in contrast to wild waterbird H7 viruses that bind both Neu5Ac and N-glycolylneuraminic acid (Neu5Gc). The level of Neu5Gc expression influences H7 virus replication and facilitates adaptive mutations in these viruses. In summary, our findings highlight the critical role of Neu5Gc in affecting the host range and interspecies transmission dynamics of H7 viruses among avian species.IMPORTANCEMigratory waterfowl, gulls, and shorebirds are natural reservoirs for influenza A viruses (IAVs) that can occasionally spill over to domestic poultry, and ultimately humans. This study showed wild-type H7 IAVs from waterbirds initially bind to glycan receptors terminated with N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc). However, after enzootic transmission in chickens, the viruses exclusively bind to Neu5Ac. The absence of Neu5Gc expression in gallinaceous poultry, particularly chickens, exerts selective pressure, shaping IAV populations, and promoting the acquisition of adaptive amino acid substitutions in the hemagglutinin protein. This results in the loss of Neu5Gc binding and an increase in virus transmissibility in gallinaceous poultry, particularly chickens. Consequently, the transmission capability of these poultry-adapted H7 IAVs in wild water birds decreases. Timely intervention, such as stamping out, may help reduce virus adaptation to domestic chicken populations and lower the risk of enzootic outbreaks, including those caused by IAVs exhibiting high pathogenicity.

Disseminated Varicella-Zoster Virus Presenting With Pneumonitis and Diffuse Alveolar Hemorrhage in an Immunocompetent Patient.

Varicella pneumonitis is typically seen in individuals with risk factors such as male gender, smoking history, and immunocompromised state and is often associated with disseminated infection, whereas primary varicella-zoster virus (VZV) infection usually involves a diffuse vesicular rash and rarely progresses to viral pneumonia. VZV pneumonitis accompanied by disseminated VZV infection is associated with a high mortality rate and may progress to diffuse alveolar hemorrhage in severe cases. In addition to cutaneous lesions, patients typically develop dyspnea, cough, tachypnea, chest pain, fever, and hemoptysis. Here, we present a rare case of disseminated VZV infection in an immunocompetent patient with pneumonitis and diffuse alveolar hemorrhage.

Cervical Spine Myelopathy Caused by Calcium Pyrophosphate Dihydrate Deposition of the Ligamentum Flavum: A Case Report.

Calcium pyrophosphate dihydrate deposition (CPPD), commonly known as pseudogout, is an inflammatory arthropathy primarily affecting the knee, wrist, hip, and shoulder joints. However, it can occasionally deposit in various structures surrounding the spinal column, including the facet joints, ligamentum flavum, bursae, and intervertebral discs. Such occurrences are typically asymptomatic or associated with mild neck pain. Nonetheless, severe cases may lead to myeloradiculopathy, characterized by severe neck pain and upper extremity weakness. Conservative management with nonsteroidal anti-inflammatory drugs is often sufficient for mild cases, while surgical decompression remains the gold standard for severe cases with significant spinal cord compression. Herein, we present a rare case of pseudogout, manifesting as cervical spine myelopathy due to calcium pyrophosphate dihydrate deposition in the ligamentum flavum and facet joints at C1-2. This was found incidentally during cervical spine decompression and fusion and subsequentially confirmed through pathological examination. Following the removal of the compressive pathology, the patient reported significant improvements in neck pain and neurological symptoms. This case underscores the importance of considering pseudogout in the differential diagnosis of acute neck pain presenting with myelopathy or radiculopathy.

Carotid artery assessment in dual-source photon-counting CT: impact of low-energy virtual monoenergetic imaging on image quality, vascular contrast and diagnostic assessability.

PURPOSE: Preliminary dual-energy CT studies have shown that low-energy virtual monoenergetic (VMI) + reconstructions can provide superior image quality compared to standard 120 kV CTA series. The purpose of this study is to evaluate the impact of low-energy VMI reconstructions on quantitative and qualitative image quality, vascular contrast, and diagnostic assessability of the carotid artery in patients undergoing photon-counting CTA examinations. MATERIALS AND METHODS: A total of 122 patients (67 male) who had undergone dual-source photon-counting CTA scans of the carotid artery were retrospectively analyzed in this study. Standard 120 kV CT images and low-keV VMI series from 40 to 100 keV with an interval of 15 keV were reconstructed. Quantitative analyses included the evaluation of vascular CT numbers, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). CT number measurements were performed in the common, external, and internal carotid arteries. Qualitative analyses were performed by three board-certified radiologists independently using five-point scales to evaluate image quality, vascular contrast, and diagnostic assessability of the carotid artery. RESULTS: Mean attenuation, CNR and SNR values were highest in 40 keV VMI reconstructions (HU, 1362.32 ± 457.81; CNR, 33.19 ± 12.86; SNR, 34.37 ± 12.89) followed by 55-keV VMI reconstructions (HU, 736.94 ± 150.09; CNR, 24.49 ± 7.11; SNR, 26.25 ± 7.34); all three mean values at these keV levels were significantly higher compared with the remaining VMI series and standard 120 kV CT series (HU, 154.43 ± 23.69; CNR, 16.34 ± 5.47; SNR, 24.44 ± 7.14) (p < 0.0001). The qualitative analysis showed the highest rating scores for 55 keV VMI reconstructions followed by 40 keV and 70 keV VMI series with a significant difference compared to standard 120 kV CT images series regarding image quality, vascular contrast, and diagnostic assessability of the carotid artery (all comparisons, p < 0.01). CONCLUSIONS: Low-keV VMI reconstructions at a level of 40-55 keV significantly improve image quality, vascular contrast, and the diagnostic assessability of the carotid artery compared with standard CT series in photon-counting CTA.

SLC4A11 mediates ammonia import and promotes cancer stemness in hepatocellular carcinoma.

End stage liver disease is marked by portal hypertension, systemic elevations in ammonia, and development of hepatocellular carcinoma (HCC). While these clinical consequences of cirrhosis are well described, it remains poorly understood whether hepatic insufficiency and the accompanying elevations in ammonia contribute to HCC carcinogenesis. Using preclinical models, we discovered that ammonia entered the cell through the transporter SLC4A11 and served as a nitrogen source for amino acid and nucleotide biosynthesis. Elevated ammonia promoted cancer stem cell properties in vitro and tumor initiation in vivo. Enhancing ammonia clearance reduced HCC stemness and tumor growth. In patients, elevations in serum ammonia were associated with an increased incidence of HCC. Taken together, this study forms the foundation for clinical investigations using ammonia lowering agents as potential therapies to mitigate HCC incidence and aggressiveness.