Miracle-dz/UniFAR-FTUs huggingface dataset:
Predictive parameter estimation for Bayesian filtering

In this thesis, I develop CELLO, an algorithm for predicting the covariances of any Gaussian model used to account for uncertainty in a complex system. The primary motivation for this work is state estimation; often, complex raw sensor measurements are processed into low dimensional observations of a vehicle state. I argue that the covariance of these observations can be well-modelled as a function of the raw sensor measurement, and provide a method to learn this function from data. This method is computationally cheap, asymptotically correct, easy to extend to new sensors, and noninvasive, in the sense that it augments, rather than disrupts, existing filtering algorithms. I additionally present two important variants; first, I extend CELLO to learn even when ground truth vehicle states are unavailable; and second, I present an equivalent Bayesian algorithm. I then use CELLO to learn covariance models for several systems, including a laser scan-matcher, an optical flow system, and a visual odometry system. I show that filtering using covariances predicted by CELLO can quantitatively improve estimator accuracy and consistency, both relative to a fixed covariance model and relative to carefully tuned domain-specific covariance models. Thesis Supervisor: Nicholas Roy Title: Associate Professor Thesis Supervisor: John Leonard Title: Professor
Tea consumption and the risk of abdominal aortic aneurysm

Abstract Background Tea has the potential to lower the risk of abdominal aortic aneurysm (AAA) owing to its high antioxidant capacity. AAA risk factors including smoking, hypertension, and hypercholesterolaemia, may modify this association. Methods The study population included 45 047 men in the Cohort of Swedish Men (COSM) and 36 611 women in the Swedish Mammography Cohort (SMC), aged 45–83 years at baseline. The COSM was established in 1997 with all men who lived in two central Swedish counties (Västmanland and Örebro), and the SMC was established in 1987–1990 with women residing in Västmanland county. Tea consumption was assessed by means of food frequency questionnaires in 1997 and 2009. Results During 17.5 years of follow-up, 1781 AAA cases (1496 men, 285 women; 1497 non-ruptured, 284 ruptured) were ascertained via Swedish registers. Tea consumption was inversely associated with total AAA incidence in men and women. Women had a 23 (95 per cent c.i. 8 to 36) per cent lower risk of AAA per each cup per day increment, whereas men had a 9 (0 to 17) per cent lower risk (Pinteraction = 0.029). Tea consumption was associated with a lower risk of both non-ruptured (hazard ratio (HR) 0.93, 95 per cent c.i. 0.85 to 1.01) and ruptured (HR 0.84, 0.71 to 0.98) AAA. Smoking status modified the association (Pinteraction < 0.001), whereby tea consumption was associated with lower risk of AAA in ex-smokers (per cup per day, HR 0.89, 0.80 to 0.98) and in never smokers (HR 0.88, 0.77 to 1.00), but not in current smokers (HR 0.95, 0.84 to 1.06). Tea consumption was associated with a lower risk in participants with (HR 0.88, 0.80 to 0.98) and without (HR 0.93, 0.88 to 1.00) hypertension, and in those with (HR 0.82, 0.67 to 1.01) and without (HR 0.92, 0.86 to 0.98) hypercholesterolaemia. Conclusion Tea consumption was associated with a reduced risk of AAA. The association was more pronounced for ruptured than non-ruptured AAA, and in patients with hypertension and hypercholesterolaemia than those without. The association was also observed in ex-smokers and never smokers, but not in current smokers.
Phenotypic and molecular characterization of five patients with PIK3CA‐related overgrowth spectrum (PROS)

Somatic and germline PI3K‐AKT‐mTOR pathway pathogenic variants are involved in several segmental overgrowth phenotypes such as the PIK3CA‐related overgrowth spectrum (PROS), Proteus syndrome, and PTEN hamartoma tumor syndrome. In this study, we describe five patients with PROS. We identified by high‐throughput sequencing four different somatic PIK3CA pathogenic variants in five individuals. The Glu726Lys variant, which was previously reported in megalencephaly‐capillary malformation‐polymicrogyria (MCAP) syndrome, was identified in two patients with unclassified PROS. The Cys420Arg substitution, which was previously reported in CLOVES, was found in a patient with fibroadipose hyperplasia. Additionally, relatively rare pathogenic variants, His1047Tyr and Tyr1021Cys, were detected in two patients with MCAP. Therefore, we suggest performing deep sequencing of PIK3CA in all patients with suspected PROS, instead of targeted polymerase chain reaction for hotspot pathogenic variants.
Drug overdose death rates in different countries: Who should be alarmed?

Objectives This study aims to assess how many nations, in addition to the United States and Canada, report alarmingly high drug overdose death rates, and to compare how those rates have changed. Conclusions Drug overdose death rates exceed four per 100,000 in over 10% of the world’s nations, including Libya (where rates are increasing) and in Russia (where rates have fallen). A comparison of data from five well-resourced nations with high drug death rates showed recently accelerated and alarming increases in rates in the United States and Canada (attributed to influx of fentanyl, plus increased stimulant use). A reported recent fall in Canada’s drug suicide rate may be attributable to misclassification of some suicides as accidents. There is an urgent need to ensure accuracy and better understanding concerning drug overdose deaths and how to prevent them.
Emerging drugs for the treatment of cutaneous T-cell lymphoma

ABSTRACT Introduction Cutaneous T cell lymphoma (CTCL) is a rare and incurable group of non-Hodgkin lymphomas that manifest as patches, plaques, tumors, and/or erythroderma in the skin. Standard skin-directed therapies for CTCL are effective in patients with indolent early-stage disease, but more advanced/refractory stage patients require systemic therapies. However, none of the treatments are considered curative and most patients suffer from relapses. Biologic therapies and immunotherapy provide novel treatment options for patients with advanced or refractory disease. Areas covered This review provides a discussion of recently approved biological and novel therapeutics that are actively developed for the management of the heterogeneous group of CTCL. Expert opinion Mogamulizumab and brentuximab vedotin have reached the market and are approved for the treatment of CTCL, providing valuable options. Additionally, therapies utilizing immune checkpoint inhibitors, miRNA inhibitors, and peptide inhibitors show promising results in clinical trials. Durvalumab, pembrolizumab, TTI-621, BNZ-1, and MRG-106 are several of the emerging treatments still in trials. Further combinatorial studies are needed as none of the treatments have demonstrated long-term remissions.
Sustainable production of eicosapentaenoic acid‐rich oil from microalgae: Towards an algal biorefinery

Utilization of sustainable natural resources such as microalgae has been considered for the production of biofuels, aquaculture feed, high‐value bioactives such as omega‐3 fatty acids, carotenoids, etc. Eicosapentaenoic acid (EPA) is an omega‐3 fatty acid present in fish oil, which is of physiological importance to both humans and fish. Marine microalgae are sustainable sources of lipid rich in EPA, and different species have been explored for the production of EPA as a single product. There has been a rising interest in the concept of a multi‐product biorefinery, focusing on the maximum valorization of the algal biomass. Targeting one or more value‐added compounds in a biorefinery scenario can improve the commercial viability of low‐value products such as triglycerides for biofuel. This approach has been viewed by technologists and experts as a sustainable and economically feasible possibility for the large‐scale production of microalgae for its potential applications in biodiesel and jet fuel production, nutraceuticals, animal and aquaculture feeds, etc. In this review paper, we describe the recent developments in the production of high‐value EPA‐rich oil from microalgae, emphasizing the upstream and downstream bioprocess techniques, and the advantages of considering an EPA‐rich oil‐based biorefinery.
Predictive biomarkers of response to immune checkpoint inhibitors in hepatocellular carcinoma

ABSTRACT Introduction Hepatocellular carcinoma (HCC) is the most common primary liver cancer and fourth-leading cause of cancer death. While drug discovery to improve disease survival was historically poor, there is now evidence of significant potential for immune checkpoint inhibitors (ICPIs) in treatment of the disease, and indeed such drug approvals are beginning to emerge. Areas covered HCC typically arises in the context of cirrhosis and chronic liver disease (CLD), and HCC exhibits significant biological heterogeneity, in part reflecting the broad range of etiologies of CLD. Different classes and combinations of ICPI-based therapy exist, but not all patients will respond and predictive biomarkers are not yet available to guide clinician decision-making, unlike some other cancer types. In this review, we discuss the emerging biomarkers for ICPI sensitivity in HCC, including tumor genomic features, perturbation of the gut microbiome, and systemic inflammatory markers. Expert opinion Additional profiling studies are required to appreciate existing trends with clinical outcome and to further drive clinical studies in disease stratification by response. This will only be possible within collaborative and international efforts, especially regarding biopsy collection. A close collaboration between basic scientists and clinicians will be the key to shape the next future of HCC biomarker research.
Kynurenine-3-monooxygenase (KMO) broadly inhibits viral infections via triggering NMDAR/Ca2+ influx and CaMKII/ IRF3-mediated IFN-β production

Tryptophan (Trp) metabolism through the kynurenine pathway (KP) is well known to play a critical function in cancer, autoimmune and neurodegenerative diseases. However, its role in host-pathogen interactions has not been characterized yet. Herein, we identified that kynurenine-3-monooxygenase (KMO), a key rate-limiting enzyme in the KP, and quinolinic acid (QUIN), a key enzymatic product of KMO enzyme, exerted a novel antiviral function against a broad range of viruses. Mechanistically, QUIN induced the production of type I interferon (IFN-I) via activating the N-methyl-d-aspartate receptor (NMDAR) and Ca2+ influx to activate Calcium/calmodulin-dependent protein kinase II (CaMKII)/interferon regulatory factor 3 (IRF3). Importantly, QUIN treatment effectively inhibited viral infections and alleviated disease progression in mice. Furthermore, kmo-/- mice were vulnerable to pathogenic viral challenge with severe clinical symptoms. Collectively, our results demonstrated that KMO and its enzymatic product QUIN were potential therapeutics against emerging pathogenic viruses.
Efficient cascaded V‐net optimization for lower extremity CT segmentation validated using bone morphology assessment

Semantic segmentation of bone from lower extremity computerized tomography (CT) scans can improve and accelerate the visualization, diagnosis, and surgical planning in orthopaedics. However, the large field of view of these scans makes automatic segmentation using deep learning based methods challenging, slow and graphical processing unit (GPU) memory intensive. We investigated methods to more efficiently represent anatomical context for accurate and fast segmentation and compared these with state‐of‐the‐art methodology. Six lower extremity bones from patients of two different datasets were manually segmented from CT scans, and used to train and optimize a cascaded deep learning approach. We varied the number of resolution levels, receptive fields, patch sizes, and number of V‐net blocks. The best performing network used a multi‐stage, cascaded V‐net approach with 1283−643−323 voxel patches as input. The average Dice coefficient over all bones was 0.98 ± 0.01, the mean surface distance was 0.26 ± 0.12 mm and the 95th percentile Hausdorff distance 0.65 ± 0.28 mm. This was a significant improvement over the results of the state‐of‐the‐art nnU‐net, with only approximately 1/12th of training time, 1/3th of inference time and 1/4th of GPU memory required. Comparison of the morphometric measurements performed on automatic and manual segmentations showed good correlation (Intraclass Correlation Coefficient [ICC] >0.8) for the alpha angle and excellent correlation (ICC >0.95) for the hip‐knee‐ankle angle, femoral inclination, femoral version, acetabular version, Lateral Centre‐Edge angle, acetabular coverage. The segmentations were generally of sufficient quality for the tested clinical applications and were performed accurately and quickly compared to state‐of‐the‐art methodology from the literature.
Feature Extraction of Fault Transient and Fault Type Determination for EHV Transmission Lines

Aimed at the requirement of post-fault analysis, the hypostasis and features of different fault transients in extra high voltage (EHV) transmission line were analyzed. Using information theory and taking advantage of information entropy measurement and complexity measurement, a new algorithm for fault feature extraction based on multiple- information measurements was proposed. The proposed algorithm can extract the fault features with different fault transients under different work conditions, and can solve the feature-extraction issue when the fault inception angle is around zero and the high-frequency transient is very low. Application in fault classification proved the algorithm to be available and effective.
High-Sensitivity Troponin I after Cardiac Surgery and 30-Day Mortality.

BACKGROUND Consensus recommendations regarding the threshold levels of cardiac troponin elevations for the definition of perioperative myocardial infarction and clinically important periprocedural myocardial injury in patients undergoing cardiac surgery range widely (from >10 times to ≥70 times the upper reference limit for the assay). Limited evidence is available to support these recommendations. METHODS We undertook an international prospective cohort study involving patients 18 years of age or older who underwent cardiac surgery. High-sensitivity cardiac troponin I measurements (upper reference limit, 26 ng per liter) were obtained 3 to 12 hours after surgery and on days 1, 2, and 3 after surgery. We performed Cox analyses using a regression spline that explored the relationship between peak troponin measurements and 30-day mortality, adjusting for scores on the European System for Cardiac Operative Risk Evaluation II (which estimates the risk of death after cardiac surgery on the basis of 18 variables, including age and sex). RESULTS Of 13,862 patients included in the study, 296 (2.1%) died within 30 days after surgery. Among patients who underwent isolated coronary-artery bypass grafting or aortic-valve replacement or repair, the threshold troponin level, measured within 1 day after surgery, that was associated with an adjusted hazard ratio of more than 1.00 for death within 30 days was 5670 ng per liter (95% confidence interval [CI], 1045 to 8260), a level 218 times the upper reference limit. Among patients who underwent other cardiac surgery, the corresponding threshold troponin level was 12,981 ng per liter (95% CI, 2673 to 16,591), a level 499 times the upper reference limit. CONCLUSIONS The levels of high-sensitivity troponin I after cardiac surgery that were associated with an increased risk of death within 30 days were substantially higher than levels currently recommended to define clinically important periprocedural myocardial injury. (Funded by the Canadian Institutes of Health Research and others; VISION Cardiac Surgery ClinicalTrials.gov number, NCT01842568.).
Localization during Pursuit Eye Movement

markdownabstract__Abstract__ Humans are very good at acquiring complex skills. More than probably any other species they learn a large array of new capabilities after they are born. Special institutions (e.g. schools, sporting clubs, handwork courses, etc.) have been put into operation to optimize the learning of such skills. It can be very pleasurable to acquire or optimize your skills, as is evident from the popularity of sporting clubs. In sports, precise coordination of different body parts is generally important. You must be somewhere at exactly the right time, for example to catch a ball when playing baseball. In other cases you must bring an object like a ball or a dart in such a condition that after you lose contact with it (and thus control over it) the object will move to some intended position. The timing and positioning requirements in sports can be very demanding (e.g. Regan 1992), but ordinary actions in daily life also require precise co-ordination. For example, when grasping an object that has a width of 10 centimeters while you are walking at a moderate speed (i.e. 5 km/hour), your hand will move past the object in less than one tenth of a second. In order to be successful you not only have to position your hand at the right place but it also has to be there at the right time, which is often a very short period. Knowing "the right place" is also far from easy, because at the moment that the brain sends the movement commands to the muscles, the object of interest is not there yet. So, obviously, some kind of prediction must be made. Eye movements are very important to gather the required information for such a prediction. For example, Land and Fumeaux (1997) argue that the eyes move in ways that optimize the uptake of information that is useful in such diverse activities as playing table tennis, reading music and driving a car. Moreover, knowing where and knowing when are not independent. Planning to contact a moving object later also means that it must be contacted at another position. For example, when walking past a stationary object you could plan to grasp the object when it is to the right and in front of your body, which would require the arm to move obliquely forwards. Alternatively, you could plan to grasp the object when it is purely to the right of your body, which would require the arm to move rightwards. When you are walking past the object you should start your movement earlier in the first than in the second case.
Assessment of Clinical Effectiveness of BNT162b2 COVID-19 Vaccine in US Adolescents

Key Points Question What is the association between the BNT162b2 COVID-19 vaccine and SARS-CoV-2 positivity among adolescents? Findings This case-control study of 542 adolescents was conducted when the Delta variant of SARS-CoV-2 was predominant and within 4 months of the vaccine rollout for adolescents. Overall, the estimated effectiveness of the BNT162b2 vaccine was 91%, with 93% protection against symptomatic infections and 85% effectiveness against asymptomatic infection. Meaning These findings suggest that the BNT162b2 vaccine was effective in adolescents within 4 months of immunization, including against infections caused by the Delta variant.
Role of the X and Y Chromosomes in the Female Germ Cell Line Development in the Mouse (Mus musculus)

Background: In eutherian mammals, the sex chromosome complement, XX and XY, determines sexual differentiation of gonadal primordia into testes and ovaries, which in turn direct differentiation of germ cells into haploid sperm and oocytes, respectively. When gonadal sex is reversed, however, the germ cell sex becomes discordant with the chromosomal sex. XY females in humans are infertile, while XY females in the mouse (Mus musculus) are subfertile or infertile dependent on the cause of sex reversal and the genetic background. This article reviews publications to understand how the sex chromosome complement affects the fertility of XY oocytes by comparing with XX and monosomy X (XO) oocytes. Summary: The results highlight 2 folds disadvantage of XY oocytes over XX oocytes: (1) the X and Y chromosomes fail to pair during the meiotic prophase I, resulting in sex chromosome aneuploidy at the first meiotic division and (2) expression of the Y-linked genes during oocyte growth affects the transcriptome landscape and renders the ooplasmic component incompetent for embryonic development. Key Message: The XX chromosome complement gives the oocyte the highest competence for embryonic development.
Circular RNA F-circEA-2a expression is increased in gastric adenocarcinoma and inhibits the transition from premature microRNA-3940-5p to mature microRNA-3940-5p

ABSTRACT Circular RNA (circRNA) F-circEA-2a and micorRNA (miR)-3940-5p are two non-coding RNAs with critical roles in cancer biology. However, their participation in gastric adenocarcinoma (GA) is unclear. We predicted that miR-3940-5p could bind to F-circEA-2a and speculated that miR-3940-5p may interact with F-circEA-2a to participate in cancer biology. This study was conducted to explore the interaction between F-circEA-2a and miR-3940-5p in GA. F-circEA-2a and miR-3940-5p (mature and premature) levels in GA were detected using RT-qPCR. Their correlations were analyzed by Pearson’s correlation coefficient. The role of F-circEA-2a in miR-3940-5p maturation was analyzed using overexpression assay. The direct binding of premature miR-3940-5p to F-circEA-2a was analyzed by RNA-RNA pulldown. Proliferation was analyzed with BrdU assay. We found that F-circEA-2a and premature miR-3940-5p were overexpressed in GA, while mature miR-3940-5p was under-expressed in GA. F-circEA-2a suppressed miR-3940-5p maturation in GA cells. MiR-3940-5p directly bound to F-circEA-2a wild type (-wt), but not mutant (-mut). F-circEA-2a promoted GA cell proliferation and inhibited the role of miR-3940-5p in reducing cell proliferation. Therefore, F-circEA-2a might suppress mature miR-3940-5p formation by sponging premature miR-3940-5p to promote cell proliferation in GA. Our study characterized a novel circRNA regulating miR-3940-5p maturation in GA. Graphical Abstract
Impact of C-reactive protein and albumin levels on short, medium, and long term mortality in patients with diffuse large B-cell lymphoma

Abstract Objectives and study design: In this population-based study of 602 patients, we amended C-reactive protein (CRP) and plasma albumin (PA) levels around the diagnosis of diffuse large B-cell lymphoma (DLBCL) to the International Prognostic Index (IPI) and assessed 0–90, 91–365, and +365-day survival. Results: The CRP did not contribute to the IPI's prognostic or discriminatory ability, regardless of time period, particularly not in models with PA. In contrast, the PA was an important contributor, especially in the 0–90 day period, but also up to one year after the diagnosis. For day 0–90, the model with the IPI only had an Area Under the Receiver Operating Characteristics (AUROC) of 0.742, whereas the IPI with PA as a continuous variable rendered an AUROC of 0.841. Especially the lower PA quartile (18–32 g/L) contributed to the worse prognosis. Conclusions: The amendment of PA to the IPI may significantly improve the short-term prognostic and discriminative ability. Key messages The amendment of the plasma albumin (PA) level to the International Prognostic Index significantly improved the prediction of mortality up to one year after the diagnosis of diffuse large B-cell lymphoma. It was especially the lower quartile of the PA level (18–32 g/L) that contributed to the worse prognosis.