Large language models (LLMs) show potential to support antimicrobial prescribing but require simulation-based, institution-specific safety evaluation prior to any consideration of clinical use. In Australia, antimicrobial prescribing represents a high-risk domain for digital decision-support systems due to patient safety and antimicrobial resistance implications. To characterise prescribing accuracy, error phenotypes and antimicrobial stewardship risk associated with a LLM that was provided with publicly available surgical prophylaxis guidelines during inference (without fine-tuning or model modification) across 20 simulated surgical scenarios. Twenty simulated surgical scenarios were tested using a LLM that was prompt-conditioned with publicly available guideline text during inference, without any fine-tuning or modification of model weights. For each case, the model generated recommendations for agent, dose, timing, re-dosing and guideline citation. Outputs were independently assessed by two local clinicians familiar with the guideline, with accuracy scored across five domains and harm classified using a modified National Coordinating Council for Medical Error Reporting and Prevention (NCC MERP) Index. Clinically significant antimicrobial prescribing risk was identified in 10% of simulated scenarios (2/20), recognising wide confidence intervals due to the small sample size. These included omission of required anaerobic coverage and failure to redose prophylaxis in prolonged procedures. Overall guideline concordance was 4/5, with perfect dose accuracy but lower performance for timing (70%) and guideline citation (45%). This study demonstrates the feasibility of constructing institutionally governed, guideline-based AI systems while identifying stewardship-relevant safety risks that currently preclude clinical use without further validation.
The Western Himalayan states of India (J&K, Himachal Pradesh, and Uttarakhand) possess substantial renewable energy resources, yet deployment remains far below potential due to region-specific barriers. This Trend Editorial critically synthesizes government data and peer-reviewed literature (2000-2025) to evaluate five renewable energy technologies (solar, hydro, wind, biomass, and geothermal) across three analytical dimensions: resource availability, deployment feasibility, and climate resilience. Our findings reveal three key insights. First, solar energy has the highest untapped potential (111 GW in J&K alone) but utilization is negligible (0.06% in J&K) except in Uttarakhand (3.42%), highlighting state-level policy disparities. Second, hydropower remains the dominant renewable source (10.5 GW installed in Himachal Pradesh) but faces growing climate risks from glacier melt and hydrological variability, favoring small-scale and run-of-river projects over large dams. Third, biomass and wind energy play niche roles, while geothermal remains largely unexplored despite promising sites (e.g., Puga Valley). Major barriers include terrain-blind subsidy mechanisms, capacity-based (rather than performance-based) policy metrics, weak institutional coordination, and the absence of an off-grid-specific framework for remote Himalayan villages. Based on this analysis, we offer a few actionable policy recommendations including terrain-adjusted subsidies, performance-based metrics, single-window clearances, a dedicated Himalayan Off-grid Renewable Mission, climate-resilient design standards, and state-specific renewable energy targets. The Western Himalayan region can transition from a clean energy frontier to a clean energy leader, but only through targeted, region-sensitive, and climate-informed policy reforms.
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Lithium, a long-established cornerstone therapy for bipolar disorder, is a biologically plausible disease-modifying agent for neurodegenerative disorders, including mild cognitive impairment (MCI) and Alzheimer disease (AD). Rather than targeting a single pathology like amyloid or tau, lithium acts across multiple cellular resilience pathways. Chronic lithium exposure induces the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2), enhances brain-derived neurotrophic factor (BDNF) signaling, inhibits glycogen synthase kinase-3β (GSK-3β), stabilizes mitochondrial function, and reduces oxidative stress. These convergent mechanisms promote neuronal survival and synaptic integrity. In humans, proton magnetic resonance spectroscopy studies found that lithium increased N-acetylaspartate levels, consistent with improved neuronal viability, and structural magnetic resonance imaging (MRI) studies found that lithium preserved gray matter and/or reversed illness-related atrophy in hippocampal and corticolimbic regions. In addition, extensive evidence demonstrates that low-dose lithium (approximately 0.3mM)-significantly lower than traditional psychiatric doses (0.6-1.0mM)-exerts robust neurotrophic and neuroprotective effects. Preclinical models have found that these concentrations stimulate hippocampal neurogenesis, promote structural plasticity, and protect against proteotoxic injury. Furthermore, epidemiological studies have associated cumulative lithium exposure with reduced dementia risk, and early randomized clinical trials in MCI suggest cognitive stabilization and favorable tau biomarker changes at low, well-tolerated doses. The recent repletion hypothesis suggests that lithium may also function as a physiological trace element, but these findings await independent replication. These convergent data support a prospective clinical trial of low-dose lithium orotate to slow disease progression in MCI. Such an approach would prioritize established neuroprotective mechanisms while potentially mitigating the kidney and thyroid risks associated with higher-dose carbonate formulations. If low-dose lithium can indeed meaningfully alter disease trajectory, it would represent a much-needed, accessible, and inexpensive treatment that may be especially relevant in low- and middle-income countries.
This cohort study examines emergency department visits and hospitalizations for cold-related illness among older adults experiencing homelessness compared with socioeconomically disadvantaged adults with housing in Ontario, Canada.
Patients with multiple sclerosis (MS) have a higher incidence of heart failure and myocardial infarction. In patients with MS, autonomic dysregulation may cause detrimental hemodynamic instability perioperatively. However, data on outcomes of cardiac surgery in patients with MS are scarce. To describe US nationwide morbidity and mortality in patients with MS undergoing cardiovascular surgery. This cross-sectional study included records of patients who underwent coronary artery bypass grafting, valve, aortic, or combined cardiovascular surgery between 2016 and 2022 in the National Inpatient Sample database. The association between MS and surgical outcomes at admission was evaluated using a balancing-score matched cohort. Data were analyzed between November 1 and 26, 2025. Multiple sclerosis. In-hospital mortality, complications, length of stay, costs, and discharge disposition. Records for 1 766 170 patients (3605 with MS and 1 762 565 without) were included. The MS cohort was younger (median [IQR] age, 63 [57-69] years vs 67 [58-70] years) and had a larger proportion of women (2025 [56%] vs 488 850 [28%]). Patients with MS, vs those without, exhibited higher frequencies of comorbidities, including chronic lung disease, depression, hypothyroidism, paralysis, psychosis, and valvular disease. In the matched cohorts of 3530 patients, mortality did not differ significantly between patients with MS and those without MS (70 [2.0%] vs 130 [3.7%]; P = .05). The prevalence of a composite complication end point was also comparable between groups (1770 [50%] vs 1810 [51%]; P = .67). This included similarities in prevalence of stroke, acute kidney failure, pulmonary embolism, deep vein thrombosis, gastrointestinal (GI) bleeding, non-GI bleeding, prolonged mechanical ventilation, tracheostomy, pneumonia, surgical site infection, sepsis, blood transfusion, pericardial effusion, fluid overload, and pacemaker requirement. However, discharge disposition differed significantly, with a lower prevalence of routine home discharges in the MS cohort (985 [28%] vs 1265 [36%]; P < .001). Median hospitalization cost ($41 285 [IQR, $31 508-$56 040] vs $40 328 [IQR, $30 604-$56 202]; P = .44) and median length of stay (8 [IQR, 6-12] days in both groups; P = .33) did not differ between cohorts. This cross-sectional study suggests that MS is not associated with increased in-hospital mortality or complications in patients undergoing cardiovascular surgery, although the prevalence of routine home discharges was lower among patients with MS. Surgeons may consider a team approach with neurological experts to optimize perioperative care and increase routine home discharges.
Although taxanes are a mainstay treatment for locally advanced or metastatic breast cancer (LABC/MBC), they often impair quality of life (QoL). Treatments that avoid taxane-related QoL deteriorations would be valuable. The JBCRG-M06/EMERALD trial (NCT03264547, UMIN000027938) compared eribulin with a taxane, each combined with trastuzumab and pertuzumab, in patients with human epidermal growth factor receptor type 2 (HER2)-positive LABC/MBC. QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Module C30 (EORTC QLQ-C30) version 3.0. QoL deterioration was defined as a decrease in the Global Health Status (GHS) score by ≥ 10 points (minimum clinically important difference), disease progression, or death. QoL data were available for 210 (of 224 randomized) and 205 (of 222 randomized) patients in the eribulin and taxane groups, respectively. The median (95% confidence interval) time to QoL deterioration was 7.16 (6.28-8.34) months in the eribulin group versus 4.57 (4.17-6.14) months in the taxane group, with a hazard ratio of 0.80 (95% confidence interval 0.65-0.98; log-rank P = 0.08). QoL was maintained at 6 and 12 months in greater proportions of the eribulin group (62.7% and 30.5%) compared with the taxane group (43.5% and 25.5%). GHS scores remained stable over time in the eribulin group. GHS deteriorated between weeks 9 and 27 in the taxane group (i.e. during treatment) with subsequent recovery toward baseline. Eribulin could help avoid the early deteriorations in QoL that occur during taxane therapy and maintain QoL for longer in patents with HER2-positive LABC/MBC receiving trastuzumab and pertuzumab.
A common, often unstated paradigm in T-cell engager (TCE) translation assumes that target-antigen density and drug exposure are the main efficacy drivers, with effector context secondary. This paradigm is visible in dose-escalation strategies and in the use of high-E:T screens as principal preclinical assays. We tested whether an alternative, receptor-saturation framework better organizes the published AMG 330 record in acute myeloid leukemia (AML). Receptor-saturation arguments motivate two qualitative expectations: at sufficiently high CD33 densities, EC 50 should show little systematic dependence on additional antigen density, and response should become increasingly constrained by effector availability and functional state. We tested these expectations using two statistical reanalyses of published AMG 330 data-log-linear regression of EC 50 on CD33 density across 11 AML cell lines, and a comparative effect-size analysis of effector-to-target (E:T) ratio versus CD33 expression in 38 primary AML samples-integrated with clinical exposure-response findings and effector-augmenting rescue studies. Both expectations were supported. CD33 density did not significantly predict EC 50 across the 3.9-fold range tested ( p = 0.13 ; bootstrap 95% CI on slope includes zero). In primary samples, E:T ratio dominated sustained lysis by approximately an order of magnitude over CD33 expression (92.4 vs. 8.5 percentage points; CD33 effect p = 0.7 , not significant). Clinical exposure-response analyses identified baseline E:T ratio and T-cell PD-1 expression as response correlates. A similar target-effector dissociation has been reported in several other TCE programs. The AMG 330 record is more coherently organized by an effector-context framework than by the conventional target-density-and-exposure paradigm. These findings indicate that endogenous-effector assays, paired target-effector biomarkers, and rational effector-support strategies are likely to be clinically informative complements to conventional cell-line potency and dose-escalation approaches in future CD33 TCE development.
Sulfur dioxide is a molecule of broad atmospheric and astronomical relevance, playing a central role in greenhouse warming and ozone chemistry. It is widely detected in planetary and interstellar environments and further participates in sulfur plasma and shock-driven processes. For this purpose, the ab initio R-matrix method within the close-coupling approximation is employed to investigate the photoionization dynamics of sulfur dioxide. Total and state-resolved cross sections for the three lowest ionic states, arising from ionization of the valence orbitals, are calculated, revealing rich autoionizing resonances in the near-threshold region. The high-resolution computed cross sections are benchmarked against available experimental datasets, including both direct measurements and reconstructed data, with the reported partial-channel cross sections representing the first direct state-resolved theoretical results for the dominant photoionization channels. In the absence of fully state-resolved experimental measurements for the cationic states of SO2, the results are interpreted through comparison with fragment-resolved data, enabling a direct correspondence between the computed ionic states and dominant molecular ion production channels, where the lowest three ionic states, X2A1(8a1-1), A2B2(5b2-1), and B2A2(1a2-1), contribute solely to the formation of the parent molecular ion SO2+. To assess the reliability of the results, a series of systematic benchmarks with respect to active space size, basis set, target-state expansion, and R-matrix radius confirms the convergence and robustness of the computed cross sections. The present results provide reliable reference data for modeling photochemical and radiative processes in planetary atmospheres and the interstellar medium and establish SO2 as a benchmark system for molecular photoionization studies.
Programmed death-ligand 1 (PD-L1) expression assessed by the combined positive score (CPS) is required for eligibility to first-line pembrolizumab-based therapy in metastatic triple-negative breast cancer (mTNBC). However, the predictive value of CPS beyond treatment eligibility, particularly for disease control, response kinetics and response durability in real-world practice, remains uncertain. This study evaluated the association between CPS analyzed as a continuous variable and clinical outcomes in a Polish real-world mTNBC population. This multicenter retrospective study included patients with PD-L1-positive (CPS ≥ 10) mTNBC treated with first-line pembrolizumab plus chemotherapy across 13 oncology centers in Poland (2022-2025). CPS was assessed locally and primarily analyzed as a continuous variable with exploratory categorical analyses performed for descriptive and visualization purposes. Primary endpoints included objective response rate (ORR), disease control rate (DCR), and progression as best response. Secondary endpoints were time to best response (TTBR) and duration of response (DoR). Seventy-two patients were eligible for analysis. Median age was 57 years (IQR 48-67) and median CPS was 20 (IQR 15-50). After a median follow-up of 11.6 months, ORR was 48.6% and DCR was 88.9%. CPS did not differ between patients achieving ORR versus no ORR (p = 0.58) or DCR versus no DCR (p = 0.56), nor was it associated with progression as best response. CPS showed no correlation with TTBR (ρ = 0.02, p = 0.9) or DoR (ρ = -0.33, p = 0.05). In univariable analysis, CPS was not associated with PFS. However, in multivariable Cox regression, CPS showed a statistically significant association with PFS, although the effect size was minimal (HR 1.01 per CPS unit). In real-world PD-L1-positive mTNBC, CPS was not significantly associated with response outcomes. Although statistically linked to PFS, the effect was minimal and likely not clinically meaningful, supporting its role as a threshold-based rather than quantitative biomarker.
To assess prospective associations between media parenting practices and screen time and problematic screen use in early adolescents. We used data from the Adolescent Brain Cognitive Development Study, a prospective cohort of 7947 adolescents [Mage 12.9 years]. Media parenting practices from Year 3 (2019-2021) and adolescent-reported screen time, app-reported smartphone time (subsample N = 840), and problematic screen use from Year 4 were analyzed using linear regression models adjusted for potential confounders. Use of screens to control behaviour (e.g., as a reward or punishment) and adolescent bedroom screen use were associated with greater screen and smartphone time. Parental screen time modelling and family mealtime screen use were associated with greater screen time. Parental monitoring and limiting of screen time were associated with lower adolescent screen time. Parental monitoring was also associated with lower smartphone time. Parental screen time modelling and use of screens to control behaviour were associated with problematic social media use, while family mealtime screen use, adolescent bedroom screen use, and use of screens to control behaviour were associated with problematic mobile phone use. These findings suggest that counselling families on specific media parenting practices may help reduce adolescent screen exposure and problematic screen use.
Alternative splicing generates multiple mRNA isoforms, driving protein diversity and tumor heterogeneity. However, achieving multiplexed quantification of splice variants at single-cell resolution remains a significant challenge. Herein, we present a programmable self-priming lanthanide-labeled DNA probe (PSPLn) strategy for sensitive, multiplexed single-cell quantification of MDM2 splice variants in glioma-related cell models. By precisely tuning the number of adenines in the probe sequence and conjugating distinct lanthanide-DOTA complexes through click chemistry, we achieve junction-specific recognition and tunable signal amplification for splice-variant-resolved analysis. Coupling these probes with laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), PSPLn enables high-throughput, single-cell readout of multiple MDM2 splice variants within individual cells. Application to U87 and U251 glioblastoma cell lines and the oligodendrocytic MO3.13 cell line reveals variant-dependent expression profiles and intervariant correlation patterns reflecting tumor heterogeneity. This platform overcomes the limitations of bulk and sequencing methods, offering a versatile tool for splice biomarker discovery and precision diagnostics in oncology.
Patients with cancer are routinely prescribed extended-spectrum antibiotics despite overall low multidrug-resistant organism (MDRO) prevalence. Evidence for effective strategies to reduce antibiotic overuse in this population is limited. To evaluate the association of computerized provider order entry (CPOE) prompts providing patient- and pathogen-specific MDRO risk estimates with empiric extended-spectrum antibiotic use in patients with cancer. This secondary analysis of the 4 Intelligent Stewardship Prompts to Improve Real-Time Empiric Antibiotic Selection (INSPIRE) cluster randomized clinical trials identified non-critically ill hospitalized adults (aged ≥18 years) with discharge diagnosis codes for hematologic or solid organ malignant tumors in the INSPIRE pneumonia, urinary tract infection (UTI), abdominal, and skin and soft tissue infection (SSTI) trials. Each trial evaluated the effect of CPOE prompts that used real-time patient-specific electronic health record data to estimate MDRO infection risk for patients prescribed extended-spectrum antibiotics during the first 3 hospital days; the prompt recommended standard-spectrum antibiotics when the risk of antibiotic-resistant infection was less than 10%. Extended-spectrum antibiotic days of therapy were evaluated using as-randomized, adjusted difference-in-difference analyses with generalized linear mixed-effects models and clustering by patient, hospital, and period. Days to intensive care unit transfer, hospital length of stay, hospital readmissions, and in-hospital mortality were also assessed. In all trials, 36 861 patients (mean [SD] age, 69.0 [13.6] years; 19 076 [52%] female), including 18 272 baseline and 18 589 intervention patients, had cancer. Extended-spectrum antibiotic days of therapy decreased by 27% (rate ratio [RR], 0.73; 95% CI, 0.67-0.80; P < .001) in the pneumonia trial, 24% (RR, 0.76; 95% CI, 0.68-0.84; P < .001) in the UTI trial, 17% (RR, 0.83; 95% CI, 0.74-0.92; P < .001) in the SSTI trial, and 24% (RR, 0.76; 95% CI, 0.69-0.84; P < .001) in the abdominal infection trial. Pre-post changes in hospital length of stay, intensive care unit transfers, readmissions, and in-hospital mortality were similar in the 2 groups. In this secondary analysis of randomized clinical trials, an antibiotic stewardship bundle that included CPOE prompts recommending standard-spectrum antibiotics for patients at low risk for antimicrobial-resistant infections was associated with reduced extended-spectrum antibiotic use in non-critically ill patients with cancer who were hospitalized with community-acquired pneumonia, UTI, SSTI, or abdominal infection, without observed differences in safety outcomes. The findings support scalable, low-burden strategies to improve antimicrobial use in patients with cancer, a population with limited evidence to guide stewardship. ClinicalTrials.gov Identifiers: NCT05423756, NCT05423743, NCT03697070, NCT03697096.
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This study investigates the production and characterization of pellets incorporating sewage sludge as a partial substitute for lignocellulosic biomass, aiming at its valorization as an alternative energy source and environmentally sustainable solution. Pellets were produced using different proportions of sewage sludge and Pinus wood powder (0%, 25%, 50%, 75%, and 100%) in a pilot-scale pellet mill (1,500 kg·h⁻1). The samples were characterized in terms of moisture content, ash content, volatile matter, fixed carbon, higher calorific value (HHV), elemental composition (TXRF), thermal behavior (TGA), and gaseous emissions during pyrolysis (EGA-FTIR). Moisture content ranged from 1.89 to 6.76%, complying with ISO 18134-2 standards. Ash content increased proportionally with sludge incorporation (0.85 to 29.96%), reflecting the inorganic fraction of the residue. The HHV varied between 14.45 and 19.01 MJ·kg⁻1, with formulations containing up to 50% sludge meeting the ISO 18125 requirement (≥ 16.56 MJ·kg⁻1). Thermogravimetric analysis indicated increased thermal stability with higher sludge content, attributed to elevated mineral matter. Gas analysis revealed the predominance of CO₂, CH₄, and oxygenated compounds, with no detection of toxic gases at critical levels under the evaluated conditions. The results demonstrate that the incorporation of sewage sludge up to 50% in pellet formulations is technically feasible for energy applications, contributing to waste management strategies and circular economy practices while maintaining acceptable fuel properties.
Highly efficient Si-O bond-forming macrocyclization has recently emerged as a powerful platform for the selective construction of structurally precise macrocycles. Here, we demonstrate that modification of the diol linker structure completely alters the preferred reaction outcome. Whereas the previously reported Ar-O-Si-O-Ar system exclusively afforded cyclic tetramers, introduction of methylene spacers into the linker overturns this inherent selectivity to achieve the selective formation of cyclic trimers in high yields. A series of silyl ether macrocycles were synthesized with outstanding efficiencies even at high concentrations. These results show that the outcome of Si-O-based macrocyclization can be effectively tuned by rational linker design.
Vitamin K supplementation can reduce progression of vascular calcification in patients with diabetes or end-stage kidney disease. Presently, it is unknown whether vitamin K is also beneficial in patients with symptomatic atherosclerotic coronary artery disease (CAD). To evaluate whether supplementation with the vitamin K homologue menaquinone-7 (MK-7) for a period of 2 years attenuates the progression of coronary artery calcification (CAC) compared with placebo. This randomized placebo-controlled clinical trial including symptomatic patients with CAC score between 50 and 400 Agatston units (AU) with 2 years of follow-up (VitaK-CAC study). The study was conducted at 1 university hospital and 1 community-dwelling hospital in the Netherlands. Data were collected from January 2012 through October 2022 with a few interruptions; analyses were performed from January 2023 to April 2024. Supplementation with either the vitamin K homologue menaquinone-7 (MK-7) in a daily dose of 360 µg or identical placebo. The primary outcome of the study was the evolution of the CAC score and calcium mass at 1 and 2 years of follow-up, as measured with computed tomography (CT) scanning. Additionally, CT angiography was performed. The incidence of new calcifications was a secondary outcome measure. Data were analyzed using a generalized estimation equations model, adjusted for covariates. Altogether, 180 patients could be randomized (90 patients per group), with 85 patients receiving MK-7 (median [IQR] age, 59 [54-65] years; 36 [42%] female) and 82 receiving placebo (median [IQR] age, 61 [54-65] years; 34 [42%] female). Baseline characteristics were comparable for the 2 groups. Plasma levels of MK-7 rose significantly in the active treatment group (median [IQR], 0.50 [0.32-0.77] µg/L to 6.56 [2.04-10.35] µg/L; P < .001). In the placebo group, CAC scores increased from a median (IQR) of 145 (99-217) AU to 173 (119-297) AU after the first year and to 214 (148-344) AU after the second. In the active treatment group, these values were 135 (89-226), 150 (110-254) and 184 (122-298) AU, respectively. The difference between the groups was significant (P = .02), even after adjustment for covariates. A similar result was seen for calcium mass. The increase in CAC score correlated with the number of noncalcified plaques that became partially calcified during the study (R2 = 0.17; P = .04). No significant adverse effects were observed. The findings of this study suggest that supplementation with MK-7 for 2 years may slow calcification in noncalcified plaques of patients with symptomatic CAD. The clinical significance of this finding in terms of plaque stability remains to be determined. ClinicalTrials.gov Identifier: NCT01002157.
Artificially sweetened beverages (ASBs) and sugar-sweetened beverages (SSBs) are widely consumed worldwide and have been linked to metabolic disorders, including obesity and type 2 diabetes, which are established risk factors associated with liver cancer. However, prospective evidence examining beverage consumption and liver cancer subtypes remains limited and inconsistent. To examine associations between ASB and SSB consumption and risk of incident liver cancer overall and by subtype, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). In this pooled analysis of 11 prospective cohort studies (10 US cohorts and 1 European cohort, comprising adults without a history of cancer at baseline), participants were enrolled across cohorts between 1980 and 2009 and followed up through end-of-study dates ranging from 2000 to 2019. The median (IQR) duration of follow-up was 11.4 (10.8-27.9) to 31.4 (27.6-31.5) years. This analysis was conducted between September 2024 and August 2025. Participants were followed up via linkage to state cancer registries or follow-up surveys for incident liver cancer. Self-reported intake of ASB and SSB assessed at baseline using validated food frequency questionnaires and analyzed per 1-beverage/day increment. Incident liver cancer overall and by subtype (HCC and ICC) identified through cancer registries or medical record review. Cox proportional hazards regression models were used to estimate multivariable hazard ratios (HRs) and 95% CIs for liver cancer incidence, adjusting for potential confounders, including demographics and lifestyle factors, and weighted-mean meta-analysis of estimates. A total of 1 518 411 participants (mean [SD] age, 57.8 [10.1] years; 883 832 female [58.2%]) were included in this analysis. During a median (IQR) of 17.8 (12.8-23.5) years of follow-up, 2811 incident liver cancer cases were identified, including 1699 HCC and 444 ICC cases. After multivariable adjustment, ASB intake per 1-beverage/day increase was not associated with liver cancer risk, HCC (10 cohorts), or ICC (6 cohorts). SSB intake per 1-beverage/day increase was not associated with overall liver cancer risk but was associated with increased risk of HCC (HR, 1.10; 95% CI, 1.03-1.18; 10 cohorts) and ICC (HR, 1.15; 95% CI, 1.00-1.32; 6 cohorts). There was no evidence of effect modification by diabetes status. In this study, increased SSB consumption was associated with increased risk of HCC and ICC. There was little evidence that ASB intake was associated with liver cancer risk overall or by subtype.
The development of hybrid metal nanoparticles (NPs) for use as computed tomography (CT) contrast agents is a promising area of research. Achieving optimal in vivo performance of imaging for NPs is challenging and depends on their geometry, materials properties, bioreactivity, and biocompatibility. In this study, we designed and developed a novel CT contrast agent composed of gold nanoparticles (AuNPs) coordinated on the surface of bismuth sulfide-core nanorods (Au@Bi2S3 NRs) utilizing a solvothermal synthesis approach. We conducted solid-state characterization of Au@Bi2S3 NRs, demonstrating their structural configuration, excellent stability, uniformity, and high crystallinity. We also tested their biocompatibility with mesenchymal stem cells and found that they were well tolerated at lower tested concentrations, with reduced viability observed at higher concentrations. To evaluate the imaging potential of Au@Bi2S3 NRs, we tested them in small animals using CT imaging. Our results showed contrast enhancement in soft tissues, indicating the retention of the particles at these locations with no local inflammatory responses. Taken together, our study provides a proof-of-concept for the robust synthesis and use of Au@Bi2S3 NRs as effective CT imaging contrast agents. Future work will explore the potential to functionalize Au@Bi2S3 NRs with therapeutic molecules for theranostic applications.