Kinetics of cardiovascular and inflammatory biomarkers in paediatric dengue shock syndrome.

Glycocalyx disruption and hyperinflammatory responses are implicated in the pathogenesis of dengue-associated vascular leak, however little is known about their association with clinical outcomes of patients with dengue shock syndrome (DSS). We investigated the association of vascular and inflammatory biomarkers with clinical outcomes and their correlations with clinical markers of vascular leakage. We performed a prospective cohort study in Viet Nam. Children ≥5 years of age with a clinical diagnosis of DSS were enrolled into this study. Blood samples were taken daily during ICU stay and 7-10 days after hospital discharge for measurements of plasma levels of Syndecan-1, Hyaluronan, Suppression of tumourigenicity 2 (ST-2), Ferritin, N-terminal pro Brain Natriuretic Peptide (NT-proBNP), and Atrial Natriuretic Peptide (ANP). The primary outcome was recurrent shock. Ninety DSS patients were enrolled. Recurrent shock occurred in 16 patients. All biomarkers, except NT-proBNP, were elevated at presentation with shock. There were no differences between compensated and decompensated DSS patients. Glycocalyx markers were positively correlated with inflammatory biomarkers, haematocrit, percentage haemoconcentration, and negatively correlated with stroke volume index. While Syndecan-1, Hyaluronan, Ferritin, and ST-2 improved with time, ANP continued to be raised at follow-up. Enrolment Syndecan-1 levels were observed to be associated with developing recurrent shock although the association did not reach the statistical significance at the P < 0.01 (OR = 1.82, 95% CI 1.07-3.35, P = 0.038). Cardiovascular and inflammatory biomarkers are elevated in DSS, correlate with clinical vascular leakage parameters and follow different kinetics over time. Syndecan-1 may have potential utility in risk stratifying DSS patients in ICU.

Eddy Current-Based Identification and Depth Investigation of Microdefects in Steel Filaments.

In the field of quality control, the critical challenge of analyzing microdefects in steel filament holds significant importance. This is particularly vital, as steel filaments serve as reinforced fibers in the use and applications within various component manufacturing industries. This paper addresses the crucial requirement of identifying and investigating microdefects in steel filaments. Eddy current signals are used for the identification of microdefects, and an in-depth investigation is conducted. The core objective is to establish the relationship between the depth of defects and the signals detected through the eddy current sensing principle. The threshold of the eddy current instrument was set at 10%, corresponding to a created depth of 20 µm, to identify defective specimens. A total of 30 defective samples were analyzed, and the phase angles between the experimental and theoretical results were compared. The depths of defects ranged from 20 to 60 µm, with one sample having a depth exceeding 75 µm. The calculated threshold of 10.18% closely aligns with the set threshold of 10%, with a difference of only 1.77%. The resulting root mean square error (RMSE) was found to be 10.53 degrees, equivalent to 3.49 µm for the difference in depth and phase between measured results and estimated results. This underscores the methodology's accuracy and its applicability across diverse manufacturing industries.

Virus-Induced Acute Respiratory Distress Syndrome Causes Cardiomyopathy Through Eliciting Inflammatory Responses in the Heart.

BACKGROUND: Viral infections can cause acute respiratory distress syndrome (ARDS), systemic inflammation, and secondary cardiovascular complications. Lung macrophage subsets change during ARDS, but the role of heart macrophages in cardiac injury during viral ARDS remains unknown. Here we investigate how immune signals typical for viral ARDS affect cardiac macrophage subsets, cardiovascular health, and systemic inflammation. METHODS: We assessed cardiac macrophage subsets using immunofluorescence histology of autopsy specimens from 21 patients with COVID-19 with SARS-CoV-2-associated ARDS and 33 patients who died from other causes. In mice, we compared cardiac immune cell dynamics after SARS-CoV-2 infection with ARDS induced by intratracheal instillation of Toll-like receptor ligands and an ACE2 (angiotensin-converting enzyme 2) inhibitor. RESULTS: In humans, SARS-CoV-2 increased total cardiac macrophage counts and led to a higher proportion of CCR2+ (C-C chemokine receptor type 2 positive) macrophages. In mice, SARS-CoV-2 and virus-free lung injury triggered profound remodeling of cardiac resident macrophages, recapitulating the clinical expansion of CCR2+ macrophages. Treating mice exposed to virus-like ARDS with a tumor necrosis factor α-neutralizing antibody reduced cardiac monocytes and inflammatory MHCIIlo CCR2+ macrophages while also preserving cardiac function. Virus-like ARDS elevated mortality in mice with pre-existing heart failure. CONCLUSIONS: Our data suggest that viral ARDS promotes cardiac inflammation by expanding the CCR2+ macrophage subset, and the associated cardiac phenotypes in mice can be elicited by activating the host immune system even without viral presence in the heart.

Ultrasensitive Carbon Monoxide Gas Sensor at Room Temperature Using Fluorine-Graphdiyne.

Currently, most carbon monoxide (CO) gas sensors work at high temperatures of over 150 °C. Developing CO gas sensors that operate at room temperature is challenging because of the sensitivity trade-offs. Here, we report an ultrasensitive CO gas sensor at room temperature using fluorine-graphdiyne (F-GDY) in which electrons are increased by light. The GDY films used as channels of field-effect transistors were prepared by using chemical vapor deposition and were characterized by using various spectroscopic techniques. With exposure to UV light, F-GDY showed a more efficient photodoping effect than hydrogen-graphdiyne (H-GDY), resulting in a larger negative shift in the charge neutral point (CNP) to form an n-type semiconductor and an increase in the Fermi level from -5.27 to -5.01 eV. Upon CO exposure, the negatively shifted CNP moved toward a positive shift, and the electrical current decreased, indicating electron transfer from photodoped GDYs to CO. Dynamic sensing experiments demonstrated that negatively charged F-GDY is remarkably sensitive to an electron-deficient CO gas, even with a low concentration of 200 parts per billion. This work provides a promising solution for enhancing the CO sensitivity at room temperature and expanding the application of GDYs in electronic devices.

Detection, Verification and Analysis of Micro Surface Defects in Steel Filament Using Eddy Current Principles, Scanning Electron Microscopy and Energy-Dispersive Spectroscopy.

In the current industrial revolution, advanced technologies and methods can be effectively utilized for the detection and verification of defects in high-speed steel filament production. This paper introduces an innovative methodology for the precise detection and verification of micro surface defects found in steel filaments through the application of the Eddy current principle. Permanent magnets are employed to generate a magnetic field with a high frequency surrounding a coil of sensors positioned at the filament's output end. The sensor's capacity to detect defects is validated through a meticulous rewinding process, followed by a thorough analysis involving scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS). Artificial defects were intentionally introduced into a sample, and their amplitudes were monitored to establish a threshold value. The amplitude signal of these created defect was identified at approximately 10% FSH, which corresponds to a crack depth of about 20 µm. In the experimental production of 182 samples covering 38 km, the defect ratio was notably high, standing at 26.37%. These defects appeared randomly along the length of the samples. The verification results underscore the exceptional precision achieved in the detection of micro surface defects within steel filaments. These defects were primarily characterized by longitudinal scratches and inclusions containing physical tungsten carbide.

Neosuberitenone, a New Sesterterpenoid Carbon Skeleton; New Suberitenones; and Bioactivity against Respiratory Syncytial Virus, from the Antarctic Sponge Suberites sp.

Respiratory syncytial virus (RSV) is a highly contagious human pathogen that poses a significant threat to children under the age of two, and there is a current need for new small molecule treatments. The Antarctic sponge Suberites sp. is a known source of sesterterpenes, and following an NMR-guided fractionation procedure, it was found to produce several previously unreported metabolites. Neosuberitenone (1), with a new carbon scaffold herein termed the 'neosuberitane' backbone, six suberitenone derivatives (2-7), an ansellane-type terpenoid (8), and a highly degraded sesterterpene (9), as well as previously reported suberitenones A (10) and B (11), were characterized. The structures of all of the isolated metabolites including absolute configurations are proposed on the basis of NMR, HRESIMS, optical rotation, and XRD data. The biological activities of the metabolites were evaluated in a range of infectious disease assays. Suberitenones A, B, and F (3) were found to be active against RSV, though, along with other Suberites sp. metabolites, they were inactive in bacterial and fungal screens. None of the metabolites were cytotoxic for J774 macrophages or A549 adenocarcinoma cells. The selectivity of suberitenones A, B, and F for RSV among other infectious agents is noteworthy.

Surveillance tools for detection of recurrent nasopharyngeal carcinoma: An evidence-based review and recommendations.

Objective: Nasopharyngeal carcinomas (NPC) are tumors arising from epithelium of the nasopharynx. The 5-year survival rate of primary NPC is 80% with significant risks of recurrence. The objective here is to provide an evidence-based systemic review of the diagnostic value of different modalities in detecting local, regional, and distal recurrent NPC, as well as the associated costs with these modalities. Methods: MEDLINE, EMBASE, and the Cochrane review database were queried. Two hundred and twenty-three abstracts were generated using the inclusion criteria: patients >18 years of age; histopathological reference standard; and modalities pertaining to imaging or microbiology. Results: Twenty-four manuscripts fulfilled the inclusion criteria and 5 surveillance tools identified: endoscopy, MR, FDG-PET, Tc-99m MIBI and 201TI SPECT, and EBV DNA. Conclusions: For local surveillance, endoscopy is the gold standard recommendation, with increased efficacy if Narrow Band Imaging or contact endoscopy are utilized. MRI and FDG-PET is also recommended to help with local to distal spread; however, Tc-99m MIBI and 201TI SPECT are options as well. EBV DNA is recommended as a cheap and accessible adjunct surveillance tool if an available as an option.

Do Sustainable Palliative Single Fraction Radiotherapy Practices Proliferate or Perish 2 Years after a Knowledge Translation Campaign?

In early 2017, the Canadian Partnership Against Cancer and CancerCare Manitoba undertook a comprehensive knowledge translation (KT) campaign to improve the utilization of single fraction radiotherapy (SFRT) over multiple fraction radiotherapy (MFRT) for palliative management of bone metastases. The campaign significantly increased short-term SFRT utilization. We assess the time-dependent effects of KT-derived SFRT utilization 12-24 months removed from the KT campaign in a Provincial Cancer Program. This study identified patients receiving palliative radiotherapy for bone metastases in Manitoba in the 2018 calendar year using the provincial radiotherapy database. The proportion of patients treated with SFRT in 2018 was compared to 2017. Logistic regression analyses identified risk factors associated with MFRT receipt. In 2018, 1008 patients received palliative radiotherapy for bone metastasis, of which 63.3% received SFRT, a small overall increase in SFRT use over 2017 (59.1%). However, 41.1% of ROs demonstrated year-over-year decreases in SFRT utilization, indicative of a time-dependent loss of SFRT prescription habits derived from KT. Although SFRT use increased slightly overall in 2018, evidence of compliance fatigue was observed, suggestive of a time-perishing property of RO prescription behaviours derived from KT methodologies. Verification of the study's findings in larger cohorts would be beneficial. These findings highlight the need for additional longitudinal KT reinforcement practices in the years following KT campaigns.

Low-cost electrochemical paper-based device for exosome detection.

Exosomes are vesicles released by healthy and cancer cells into the extracellular matrix and bodily fluid. Cancer cell-derived exosomes have attracted much attention in early-stage detection and prognostication of treatment response. Thus, detecting exosomes is of great interest to biology and medicine. However, many conventional detection methods require high-cost equipment and centralized laboratory facilities, making diagnostics inaccessible in limited-resource settings. This study reports a proof-of-concept low-cost electrochemical paper-based analytical device to quantify both the total bulk and cancer cell-derived exosomes in cell culture media. The device employs a sandwich immune assay design, where exosomes are initially captured using the electrode-bound generic antibodies (i.e. CD9) and subsequently detected via ovarian cancer-specific CA125 antibodies. Our proposed device quantifies the total bulk exosome concentration with a detection limit of 9.3 × 107 exosomes per mL and ovarian cancer cell-derived exosomes with a detection limit of 7.1 × 108 exosomes per mL, with a relative standard deviation of <10% (n = 3). We suggest that this low-cost and simple electrochemical paper-based device could be an alternative tool for detecting disease-specific exosomes in biological samples with the potential to be further developed for point-of-care diagnosis.

A bio-functional polymer that prevents retinal scarring through modulation of NRF2 signalling pathway.

One common cause of vision loss after retinal detachment surgery is the formation of proliferative and contractile fibrocellular membranes. This aberrant wound healing process is mediated by epithelial-mesenchymal transition (EMT) and hyper-proliferation of retinal pigment epithelial (RPE) cells. Current treatment relies primarily on surgical removal of these membranes. Here, we demonstrate that a bio-functional polymer by itself is able to prevent retinal scarring in an experimental rabbit model of proliferative vitreoretinopathy. This is mediated primarily via clathrin-dependent internalisation of polymeric micelles, downstream suppression of canonical EMT transcription factors, reduction of RPE cell hyper-proliferation and migration. Nuclear factor erythroid 2-related factor 2 signalling pathway was identified in a genome-wide transcriptomic profiling as a key sensor and effector. This study highlights the potential of using synthetic bio-functional polymer to modulate RPE cellular behaviour and offers a potential therapy for retinal scarring prevention.

BCG vaccination provides protection against IAV but not SARS-CoV-2.

Since the vast majority of species solely rely on innate immunity for host defense, it stands to reason that a critical evolutionary trait like immunological memory evolved in this primitive branch of our immune system. There is ample evidence that vaccines such as bacillus Calmette-Guérin (BCG) induce protective innate immune memory responses (trained immunity) against heterologous pathogens. Here we show that while BCG vaccination significantly reduces morbidity and mortality against influenza A virus (IAV), it fails to provide protection against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In contrast to IAV, SARS-CoV-2 infection leads to unique pulmonary vasculature damage facilitating viral dissemination to other organs, including the bone marrow (BM), a central site for BCG-mediated trained immunity. Finally, monocytes from BCG-vaccinated individuals mount an efficient cytokine response to IAV infection, while this response is minimal following SARS-CoV-2. Collectively, our data suggest that the protective capacity of BCG vaccination is contingent on viral pathogenesis and tissue tropism.

Mimic microgravity effect on muscle transcriptome under ionizing radiation.

Spaceflight imposes the risk of skeletal muscle atrophy for astronauts. Two main factors of a spaceflight that results in deleterious effects are microgravity and cosmic rays in outer space. To study spaceflight-induced muscle atrophy with ground-based models, we performed two models of microgravity, tail suspension and denervation, in a low dose radiation environment and studied transcriptional changes in rat soleus muscle using microarrays. Soleus muscle from rats in the denervation group had greater expression changes compared to that found in rats from the tail suspension group. However, there was a very similar pattern of expression of differentially expressed genes (DEGs) in both models. In total, we identified 144 differentially expressed genes common in both models. Our study yielded two main findings. First, a large number of genes involved in energy metabolism were transcriptionally suppressed including those involved in fatty acid transport and beta-oxidation, and oxidative phosphorylation. Second, slow-twitch contractile protein encoding genes were down-regulated while there was an up-regulation in the fast-twitch type transcription. These results were consistent with other spaceflight studies on the effects on muscle cells, hence showed the potential of our ground-based models in studying spaceflight effects. The genes that might be involved in spaceflight effects will serve as candidate genes for future studies in understanding the mechanism of spaceflight-induced muscle atrophy and result in the development of effective countermeasures.

Antiangiogenic Nanomicelles for the Topical Delivery of Aflibercept to Treat Retinal Neovascular Disease.

The traditional intravitreal injection delivery of antivascular endothelial growth factor (anti-VEGF) to the posterior segment of the eye for treatment of retinal diseases is invasive and associated with sight-threatening complications. To avoid such complications, there has been significant interest in developing polymers for topical drug delivery to the retina. This study reports a nanomicelle drug delivery system made of a copolymer EPC (nEPCs), which is capable of delivering aflibercept to the posterior segment topically through corneal-scleral routes. EPC is composed of poly(ethylene glycol) (PEG), poly(propylene glycol) (PPG), and polycaprolactone (PCL) segments. In this study, aflibercept-loaded nEPCs (nEPCs + A) are capable of penetrating the cornea in ex vivo porcine eye models and deliver a clinically significant amount of aflibercept to the retina in laser-induced choroidal neovascularization (CNV) murine models, causing CNV regression. nEPCs + A also demonstrate biocompatibility in vitro and in vivo. Interestingly, this study also suggests that nEPCs have intrinsic antiangiogenic properties. The ability to deliver anti-VEGF drugs and the intrinsic antiangiogenic properties of nEPCs may result in synergistic effects, which can be harnessed for effective therapeutics. nEPCs may be a promising topical anti-VEGF delivery platform for the treatment of retinal diseases.

Pairing denitrifying phosphorus accumulating organisms with anaerobic ammonium oxidizing bacteria for simultaneous N and P removal.

Coupling of denitrifying polyphosphate accumulating organisms (DPAO) with anaerobic ammonium oxidizing (Anammox) bacteria in a single treatment scheme has so far been unsuccessful but could offer substantial energy savings, minimize sludge production, while achieving simultaneous carbon, nitrogen and phosphate removal. However, both organisms compete for nitrite and have vastly different growth rates and therefore the goal of this study was to uncouple their solid retention time (SRT) by growing them in different sludge fractions and to determine their biomass specific kinetic properties. Anammox bacteria were grown in a biofilm for longer SRTs and DPAO in flocs to allow shorter SRTs. Exposure of DPAO to anaerobic conditions was accomplished by recycling the flocs to a separate reactor by which simultaneous P, N, and C removal was accomplished. The diffusion limited biofilm lowered the biomass specific nitrite affinity for Anammox (KsAMX = 0.091 mM), which gave DPAO a competitive edge to consume nitrite (KsDPAO = 0.022 mM) in the suspended floc fraction. However, DPAO are more sensitive to nitrite (KiDPAO = 0.377 mM) than Anammox bacteria and (KiAMX > 1.786 mM), and therefore the DPAO would be better suited to grow in the protective biofilm, showing that both biomass growth types (flocs and granules) have advantages (and disadvantages) depending on the setting. This work is an important steppingstone to understanding resource competition amongst Anammox and DPAO and SRT management strategies to allow their pairing in combined reactor configurations.

Blood pressure screening results from May Measurement Month 2019 in Vietnam.

Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. May Measurement Month (MMM) is a global initiative to raise awareness of high BP and act as a temporary solution to the lack of screening programmes worldwide. We aimed to screen for hypertension and cardiovascular risk factors in people aged ≥18 years in the community, thereby defining the proportion of subjects with elevated BP and assess the awareness and the effectiveness of its treatment. An opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2019. Blood pressure measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. From May 2019 to June 2019, through 10 cities/provinces in Vietnam, 25 887 individuals with mean age 48.7 (SD ±17.7) years were screened. After multiple imputations, 8758 (33.8%) had hypertension. Of individuals not receiving antihypertensive medication, 3025 (15.0%) were hypertensive. Of individuals receiving antihypertensive medication, 2800 (48.8%) had uncontrolled BP. Raised BP [systolic BP (SBP) ≥140 mmHg and/or diastolic BP (DBP) ≥90 mmHg] was also associated with additional risk factors including smoking, alcohol intake, previous hypertension in pregnancy, and obesity. May Measurement Month 2019 was the most extensive BP screening campaign ever undertaken in Vietnam. Undiagnosed and uncontrolled hypertension in Vietnam remains a substantial health problem. Local campaigns applying standardized methods such as MMM 2019 will be beneficial to screen for the significant number of individuals with raised BP and increase the awareness of hypertension.

Do Coordinated Knowledge Translation Campaigns Persuade Radiation Oncologists to Use Single-Fraction Radiation Therapy Compared With Multiple-Fraction Radiation Therapy for Bone Metastases?

PURPOSE: Although level 1 evidence supports the use of single-fraction radiation therapy (SFRT) compared with multiple-fraction radiation therapy (MFRT) for the palliative management of bone metastases, SFRT is underused. In early 2017, the Canadian Partnership Against Cancer and CancerCare Manitoba undertook a comprehensive knowledge translation campaign in Manitoba, Canada featuring educational outreach visits, local consensus meetings, and audit and feedback interventions to encourage greater use of SFRT. This study assessed the impact of this campaign on SFRT use and identified variables associated with MFRT usage. METHODS AND MATERIALS: This retrospective, population-based cohort study identified all patients treated with palliative radiation therapy for bone metastases in Manitoba, Canada, from January 1, 2017, to December 31, 2017, using the provincial radiation therapy database. Baseline characteristics were extracted and tabulated by fractionation schedule. The proportion of patients treated with SFRT in 2017 (postintervention) was compared with the 2016 (preintervention) levels. Univariable and multivariable logistic regression analyses were performed to identify risk factors associated with MFRT use. RESULTS: In 2017, 927 patients received palliative radiation therapy for bone metastasis, of which 548 (59.1%) received SFRT, a 21.1% absolute increase in SFRT use compared with 2016 levels (38.0%). With use of multivariable analysis, variables associated with receipt of MFRT included: complicated bone metastasis, soft tissue extension, hematological primary malignancy, and treatment at a subsidiary center. CONCLUSION: The comprehensive knowledge translation campaign carried out in Manitoba resulted in a significant increase in SFRT use for bone metastases. Continued audit/feedback strategies are recommended to further reinforce knowledge translation efforts supporting SFRT use in the future.

Incidence and mortality of cervical cancer in Vietnam and Korea (1999-2017).

OBJECTIVES: Cervical cancer is a major disease burden in Vietnam. This study aimed to estimate the incidence and mortality rates of cervical cancer in Vietnam (1999-2017) in comparison to those in Korea, where a population-based cancer registry and national cervical cancer screening program have been implemented. METHODS: The estimated incidence and mortality of cervical cancer in Vietnam and Korea (1999-2017) were collected from Global Burden of Disease 2017 study. Estimated age-standardized rates (ASRs) in both countries were calculated utilizing the 1999-2017 population of each country and the World Health Organization standard population. The reported ASRs in Korea were also computed using data on incidence and mortality (1999-2017) and the Korean population from the Korea Statistical Information Service. RESULTS: In Vietnam, the estimated incidence and mortality of cervical cancer decreased annually by 0.84% and 1.01%. In Korea, the trend of reported incidence showed a dramatic drop (1999-2007 annual percent change [APC], -4.53%) before stably declining (2007-2017 APC, -2.71%). Reported mortality also significantly decreased (2003-2008 APC, -6.63%), and then maintained a stable decline (2008-2017 APC, -3.78%). The incidence and mortality rates were higher in Vietnam than in Korea. The declining trend of incidence and mortality in Vietnam was slower than the corresponding trends in Korea. CONCLUSIONS: A national screening program should be implemented for Vietnamese women aged over 30 to maintain, or even hasten, the decline in cervical cancer incidence and mortality. A population-based cancer registry may help monitor the effectiveness of a cervical cancer screening program.

May Measurement Month 2018: an analysis of blood pressure screening results from Vietnam.

Vietnam in the Asia Pacific region has a high hypertension (HTN) prevalence. The May Measurement Month (MMM) program was enthusiastically responded to in Vietnam by launching and deploying it across the whole country from 2017. The aims of the MMM 2018 program in Vietnam were to screen at least 15 000 people aged 18 and over across the country; to inform participants of the risks associated with HTN; and thereby define the proportion of subjects with elevated blood pressure (BP) and assess the awareness and the effectiveness of its treatment. An opportunistic cross-sectional survey of volunteers aged ≥ 18 was carried out in May 2018. Blood pressure measurement, the definition of HTN, and statistical analysis followed the standard MMM protocol. From May 2018 to June 2018, through 10 cities/provinces in Vietnam, 17 332 individuals with mean age 47.0 ± 17.9 years were screened during MMM18. After multiple imputation, 5260 (30.3%) had HTN. Of individuals not receiving antihypertensive medication, 1956 (13.9%) were hypertensive. Of patients receiving antihypertensive medication, 1540 (46.6%) had uncontrolled BP. Those who had HTN also displayed many additional risk factors similarly to MMM 2017 including smoking, alcohol, overweight-obesity, and diabetes. In conclusion, MMM 2018 campaign is a continuation program of MMM 2017 that has promoted the strength of the BP screening survey in the community in Vietnam, which hopefully will influence on awareness of disease prevention in this century. The next steps of the program will have special innovations on how to reduce the frequency of focusing on variable risk factors to change the overall picture of HTN in Vietnam.

Statin use and risk of liver cancer: Evidence from two population-based studies.

Epidemiological studies of statin use and liver cancer risk have produced conflicting results. We examined the association between statin use and risk of primary liver cancer in two large independent study populations taking account of important covariates and main indications of statins such as high cholesterol and chronic liver disease. We performed a nested case-control study within the Scottish Primary Care Clinical Informatics Unit (PCCIU) database. Five controls were matched to cases with primary liver cancer and we used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations with statin use. We also conducted a prospective cohort study within the UK Biobank using self-reported statin use and cancer-registry recorded primary liver cancer outcomes. Cox regression was used to calculate hazard ratios (HRs) and 95% CIs. In the PCCIU case-control analysis, 434 liver cancer cases were matched to 2,103 controls. In the UK Biobank cohort, 182 out of 475,768 participants developed incident liver cancer. Statin use was associated with 39% lower risk of liver cancer in the PCCIU (adjusted OR 0.61, 95% CI 0.43-0.87). When we examined specific subtypes of liver cancer in the UK Biobank, statin use was associated with lower risk of hepatocellular carcinoma (HCC; adjusted HR, 0.48; 95% CI, 0.24-0.94) but not intrahepatic bile duct carcinoma (IBDC; adjusted HR, 1.09; 95% CI, 0.45-2.64). In conclusion, we found a consistent inverse relationship between statin use and risk of primary liver cancer which was only seen for HCC but not IBDC.