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Metabolomics has a long history of using cosine similarity to match experimental tandem mass spectra to databases for compound identification. Here we introduce the Blur-and-Link (BLINK) approach for scoring cosine similarity. By bypassing fragment alignment and simultaneously scoring all pairs of spectra using sparse matrix operations, BLINK is over 3000 times faster than MatchMS, a widely used loop-based alignment and scoring implementation. Using a similarity cutoff of 0.7, BLINK and MatchMS had practically equivalent identification agreement, and greater than 99% of their scores and matching ion counts were identical. This performance improvement can enable calculations to be performed that would typically be limited by time and available computational resources.

Thermal properties of nanomaterials are crucial to not only improving our fundamental understanding of condensed matter systems, but also to developing novel materials for applications spanning research and industry. Since quantum effects arise at the nano-scale, these systems are difficult to simulate on classical computers. Quantum computers can efficiently simulate quantum many-body systems, yet current quantum algorithms for calculating thermal properties of these systems incur significant computational costs in that they either prepare the full thermal state on the quantum computer, or they must sample a number of pure states from a distribution that grows with system size. Canonical thermal pure quantum (TPQ) states provide a promising path to estimating thermal properties of quantum materials as they neither require preparation of the full thermal state nor require a growing number of samples with system size. Here, we present an algorithm for preparing canonical TPQ states on quantum computers. We compare three different circuit implementations for the algorithm and demonstrate their capabilities in estimating thermal properties of quantum materials. Due to its increasing accuracy with system size and flexibility in implementation, we anticipate that this method will enable finite temperature explorations of relevant quantum materials on near-term quantum computers.

There is increasing evidence that acylsugars deter insect pests and plant virus vectors, including the western flower thrips (WFT), Frankliniella occidentalis (Pergande), vector of tomato spotted wilt virus (TSWV). Acylsugars are sugar-polyesters composed of saturated, un-saturated, and variously branched short and long chain fatty acids (FAs) esterified to a glucose (acylglucose) or sucrose (acylsucrose) moiety. We sought to understand how acylsucrose amount and composition of associated FA profiles interacted to mediate resistance to WFT oviposition and TSWV inoculation on tomato leaves. Towards this goal, we examined WFT oviposition and TSWV inoculation behavior on tomato lines bred to exude varying amounts of acylsucrose in association with diverse FA profiles. Our data show that as acylsucrose amounts increased, WFT egg-laying (oviposition) decreased and TSWV inoculation was suppressed. Western flower thrips also responded to FA profiles that included iC4, iC11, nC12 and nC10 FA. These findings support improving acylsugar-mediated resistance against WFT by breeding tomatoes exuding greater amounts of acylsucrose associated with specific FA profiles. We show that increasing acylsucrose amount output by type IV trichomes and selecting for particular FA profiles through advanced breeding profoundly affects WFT behavior in ways that benefit management of WFT as direct pests and as TSWV vectors.

Abstract While vaccination against HIV-1 has been so far unsuccessful, recently broadly neutralizing antibodies (bNAbs) against HIV-1 envelope glycoprotein were shown to induce long-term suppression in the absence of antiretroviral therapy in patients with antibody-sensitive viral reservoirs. The requirement of neutralizing antibodies indicates that the antibody mediated removal (clearance) of HIV-1 in itself is not efficient enough in these immune compromised patients. Here we present a novel, alternative approach that is independent of a functional immune system to clear HIV-1, by capturing the virus and redirecting it to non-target cells where it is internalized and degraded. We use bispecific antibodies with domains derived from small single chain Llama antibodies (VHHs). These bind with one domain to HIV-1 envelope proteins and with the other domain direct the virus to cells expressing epidermal growth factor receptor (EGFR), a receptor that is ubiquitously expressed in the body. We show that HIV envelope proteins, virus-like particles and HIV-1 viruses (representing HIV-1 subtypes A, B and C) are efficiently recruited to EGFR, internalized and degraded in the lysosomal pathway at low nM concentrations of bispecific VHHs. This directed degradation in non-target cells may provide a clearance platform for the removal of viruses and other unwanted agents from the circulation, including toxins, and may thus provide a novel method for curing.

Abstract Controlled human malaria infection (CHMI) using cryopreserved non-attenuated Plasmodium falciparum sporozoites (PfSPZ) offers a unique opportunity to investigate naturally acquired immunity (NAI). By analyzing blood samples from 5 malaria-naïve European and 20 African adults with lifelong exposure to malaria, before, 5, and 11 days after direct venous inoculation (DVI) with SanariaR PfSPZ Challenge, we assessed the immunological patterns associated with control of microscopic and submicroscopic parasitemia. All (5/5) European individuals developed parasitemia as defined by thick blood smear (TBS), but 40% (8/20) of the African individuals controlled their parasitemia, and therefore remained thick blood smear-negative (TBS− Africans). In the TBS− Africans, we observed higher baseline frequencies of CD4+ T cells producing interferon-gamma (IFNγ) that significantly decreased 5 days after PfSPZ DVI. The TBS− Africans, which represent individuals with either very strong and rapid blood-stage immunity or with immunity to liver stages, were stratified into subjects with sub-microscopic parasitemia (TBS-PCR+) or those with possibly sterilizing immunity (TBS−PCR−). Higher frequencies of IFNγ+TNF+CD8+ γδ T cells at baseline, which later decreased within five days after PfSPZ DVI, were associated with those who remained TBS−PCR−. These findings suggest that naturally acquired immunity is characterized by different cell types that show varying strengths of malaria parasite control. While the high frequencies of antigen responsive IFNγ+CD4+ T cells in peripheral blood keep the blood-stage parasites to a sub-microscopic level, it is the IFNγ+TNF+CD8+ γδ T cells that are associated with either immunity to the liver-stage, or rapid elimination of blood-stage parasites.

Abstract GTP-cyclohydrolase deficiency in dopa-responsive dystonia (DRD) patients impairs the biosynthesis of dopamine, but also of serotonin. The high prevalence of non-motor symptoms suggests involvement of the serotonergic pathway. Our study aimed to investigate the serotonergic system in vivo in the brain of`DRD patients and correlate this to (non-)motor symptoms. Dynamic [11C]DASB PET scans, a marker of serotonin transporter availability, were performed. Ten DRD, 14 cervical dystonia patients and 12 controls were included. Univariate- and network-analysis did not show differences in binding between DRD patients compared to controls. Sleep disturbances were correlated with binding in the dorsal raphe nucleus (all participants: r s = 0.45, p = 0.04; patients: rs = 0.64, p = 0.05) and participants with a psychiatric disorder had a lower binding in the hippocampus (all participants: p = 0.00; patients: p = 0.06). Post-hoc analysis with correction for psychiatric co-morbidity showed a significant difference in binding in the hippocampus between DRD patients and controls (p = 0.00). This suggests that psychiatric symptoms might mask the altered serotonergic metabolism in DRD patients, but definite conclusions are difficult as psychiatry is considered part of the phenotype. We hypothesize that an imbalance between different neurotransmitter systems is responsible for the non-motor symptoms, and further research investigating multiple neurotransmitters and psychiatry in DRD is necessary.

Abstract Head-and-neck squamous cell carcinomas (HNSCCs) are relatively common in patients with Fanconi anemia (FA), a hereditary chromosomal instability disorder. Standard chemo-radiation therapy is not tolerated in FA due to an overall somatic hypersensitivity to such treatment. The question is how to find a suitable alternative treatment. We used whole-exome and whole genome mRNA sequencing to identify major genomic and transcriptomic events associated with FA-HNSCC. CRISPR-engineered FA-knockout models were used to validate a number of top hits that were likely to be druggable. We identified deletion of 18q21.2 and amplification of 11q22.2 as prevailing copy-number alterations in FA HNSCCs, the latter of which was associated with strong overexpression of the cancer-related genes YAP1, BIRC2, BIRC3 (at 11q22.1-2). We then found the drug AZD5582, a known small molecule inhibitor of BIRC2-3, to selectively kill FA tumor cells that overexpressed BIRC2-3. This occurred at drug concentrations that did not affect the viability of untransformed FA cells. Our data indicate that 11q22.2 amplifications are relatively common oncogenic events in FA-HNSCCs, as holds for non FA-HNSCC. Therefore, chemotherapeutic inhibition of overexpressed BIRC2-3 may provide the basis for an approach to develop a clinically realistic treatment of FA-HNSCCs that carry 11q22.2 amplifications.

Abstract Protein arginine methyltransferase 3 (PRMT3) is a co-activator of liver X receptor capable of selectively modulating hepatic triglyceride synthesis. Here we investigated whether pharmacological PRMT3 inhibition can diminish the hepatic steatosis extent and lower plasma lipid levels and atherosclerosis susceptibility. Hereto, male hyperlipidemic low-density lipoprotein receptor knockout mice were fed an atherogenic Western-type diet and injected 3 times per week intraperitoneally with PRMT3 inhibitor SGC707 or solvent control. Three weeks into the study, SGC707-treated mice developed severe pruritus and scratching-associated skin lesions, leading to early study termination. SGC707-treated mice exhibited 50% lower liver triglyceride stores as well as 32% lower plasma triglyceride levels. Atherosclerotic lesions were virtually absent in all experimental mice. Plasma metabolite analysis revealed that levels of taurine-conjugated bile acids were ~ threefold increased (P

Abstract Globally increasing levels of artificial light at night (ALAN) are associated with shifting rhythms of behaviour in many wild species. However, it is unclear whether changes in behavioural timing are paralleled by consistent shifts in the molecular clock and its associated physiological pathways. Inconsistent shifts between behavioural and molecular rhythms, and between different tissues and physiological systems, disrupt the circadian system, which coordinates all major body functions. We therefore compared behavioural, transcriptional and metabolomic responses of captive great tits (Parus major) to three ALAN intensities or to dark nights, recording activity and sampling brain, liver, spleen and blood at mid-day and midnight. ALAN advanced wake-up time, and this shift was paralleled by advanced expression of the clock gene BMAL1 in all tissues, suggesting close links between behaviour and clock gene expression across tissues. However, further analysis of gene expression and metabolites revealed that clock shifts were inconsistent across physiological systems. Untargeted metabolomic profiling showed that only 9.7% of the 755 analysed metabolites followed the behavioural shift. This high level of desynchronization indicates that ALAN disrupted the circadian system on a deep, easily overlooked level. Thus, circadian disruption could be a key mediator of health impacts of ALAN on wild animals.

Abstract Knowledge on characteristics of people that seek help for tinnitus is scarce. The primary objective of this study was to describe differences in characteristics between people with tinnitus that seek help compared to those who do not seek help. Next, we described differences in characteristics between those with and without tinnitus. In this cross-sectional study, we sent a questionnaire on characteristics in different domains; demographic, tinnitus-specific, general- and psychological health, auditory and noise- and substance behaviour. We assessed if participants had sought help or planned to seek help for tinnitus. Tinnitus distress was defined with the Tinnitus Functional Index. Differences between groups (help seeking: yes/no, tinnitus: yes/no) were described. 932 people took part in our survey. Two hundred and sixteen participants were defined as having tinnitus (23.2%). Seventy-three of those sought or planned to seek help. A constant tinnitus pattern, a varying tinnitus loudness, and hearing loss, were described more frequently in help seekers. Help seekers reported higher TFI scores. Differences between help seekers and people not seeking help were mainly identified in tinnitus- and audiological characteristics. These outcomes might function as a foundation to explore the heterogeneity in tinnitus patients.

Abstract Carriage of Neisseria meningitidis is an accepted endpoint in monitoring meningococcal vaccines effects. We have assessed N. meningitidis and vaccine-type genogroup carriage prevalence in college students at the time of MenACWY vaccine introduction in the Netherlands, and evaluated the feasibility of saliva sampling for the surveillance of carriage. For this, paired saliva and oropharyngeal samples collected from 299 students were cultured for meningococcus. The DNA extracted from all bacterial growth was subjected to qPCRs quantifying meningococcal and genogroup-specific genes presence. Samples negative by culture yet positive for qPCR were cultured again for meningococcus. Altogether 74 (25%) of students were identified as meningococcal carrier by any method. Sixty-one students (20%) were identified as carriers with qPCR. The difference between number of qPCR-positive oropharyngeal (n = 59) and saliva (n = 52) samples was not significant (McNemar’s test, p = 0.07). Meningococci were cultured from 72 students (24%), with a significantly higher (p

Abstract In retinoblastoma, accurate segmentation of ocular structure and tumor tissue is important when working towards personalized treatment. This retrospective study serves to evaluate the performance of multi-view convolutional neural networks (MV-CNNs) for automated eye and tumor segmentation on MRI in retinoblastoma patients. Forty retinoblastoma and 20 healthy-eyes from 30 patients were included in a train/test (N = 29 retinoblastoma-, 17 healthy-eyes) and independent validation (N = 11 retinoblastoma-, 3 healthy-eyes) set. Imaging was done using 3.0 T Fast Imaging Employing Steady-state Acquisition (FIESTA), T2-weighted and contrast-enhanced T1-weighted sequences. Sclera, vitreous humour, lens, retinal detachment and tumor were manually delineated on FIESTA images to serve as a reference standard. Volumetric and spatial performance were assessed by calculating intra-class correlation (ICC) and dice similarity coefficient (DSC). Additionally, the effects of multi-scale, sequences and data augmentation were explored. Optimal performance was obtained by using a three-level pyramid MV-CNN with FIESTA, T2 and T1c sequences and data augmentation. Eye and tumor volumetric ICC were 0.997 and 0.996, respectively. Median [Interquartile range] DSC for eye, sclera, vitreous, lens, retinal detachment and tumor were 0.965 [0.950–0.975], 0.847 [0.782–0.893], 0.975 [0.930–0.986], 0.909 [0.847–0.951], 0.828 [0.458–0.962] and 0.914 [0.852–0.958], respectively. MV-CNN can be used to obtain accurate ocular structure and tumor segmentations in retinoblastoma.

Abstract The WMI and WLI inbred rats were generated from the stress-prone, and not yet fully inbred, Wistar Kyoto (WKY) strain. These were selected using bi-directional selection for immobility in the forced swim test and were then sib-mated for over 38 generations. Despite the low level of genetic diversity among WKY progenitors, the WMI substrain is significantly more vulnerable to stress relative to the counter-selected WLI strain. Here we quantify numbers and classes of genomic sequence variants distinguishing these substrains with the long term goal of uncovering functional and behavioral polymorphism that modulate sensitivity to stress and depression-like phenotypes. DNA from WLI and WMI was sequenced using Illumina xTen, IonTorrent, and 10X Chromium linked-read platforms to obtain a combined coverage of ~ 100X for each strain. We identified 4,296 high quality homozygous SNPs and indels between the WMI and WLI. We detected high impact variants in genes previously implicated in depression (e.g. Gnat2), depression-like behavior (e.g. Prlr, Nlrp1a), other psychiatric disease (e.g. Pou6f2, Kdm5a, Reep3, Wdfy3), and responses to psychological stressors (e.g. Pigr). High coverage sequencing data confirm that the two substrains are nearly coisogenic. Nonetheless, the small number of sequence variants contributes to numerous well characterized differences including depression-like behavior, stress reactivity, and addiction related phenotypes. These selected substrains are an ideal resource for forward and reverse genetic studies using a reduced complexity cross.

Abstract The use of Augmented Reality (AR) in anatomical education has been promoted by numerous authors. Next to financial and ethical advantages, AR has been described to decrease cognitive load while increasing student motivation and engagement. Despite these advantages, the effects of AR on learning outcome varies in different studies and an overview and aggregated outcome on learning anatomy is lacking. Therefore, a meta-analysis on the effect of AR vs. traditional anatomical teaching methods on learning outcome was performed. Systematic database searches were conducted by two independent investigators using predefined inclusion and exclusion criteria. This yielded five papers for meta-analysis totaling 508 participants; 240 participants in the AR-groups and 268 participants in the control groups. (306 females/202 males). Meta-analysis showed no significant difference in anatomic test scores between the AR group and the control group (− 0.765 percentage-points (%-points); P = 0.732). Sub analysis on the use of AR vs. the use of traditional 2D teaching methods showed a significant disadvantage when using AR (− 5.685%-points; P = 0.024). Meta-regression analysis showed no significant co-relation between mean difference in test results and spatial abilities (as assessed by the mental rotations test scores). Student motivation and/or engagement could not be included since studies used different assessment tools. This meta-analysis showed that insufficient evidence is present to conclude AR significantly impacts learning outcome and that outcomes are significantly impacted by students’ spatial abilities. However, only few papers were suitable for meta-analysis, indicating that there is a need for more well-designed, randomized-controlled trials on AR in anatomy education research.

Abstract Olfactory sensing is generally organized into groups of similarly sensing olfactory receptor neurons converging into their corresponding glomerulus, which is thought to behave as a uniform functional unit. It is however unclear to which degree axons within a glomerulus show identical activity, how many converge into a glomerulus, and to answer these questions, how it is possible to visually separate them in live imaging. Here we investigate activity of olfactory receptor neurons and their axon terminals throughout olfactory glomeruli using electrophysiological recordings and rapid 4D calcium imaging. While single olfactory receptor neurons responsive to the same odor stimulus show a diversity of responses in terms of sensitivity and spontaneous firing rate on the level of the somata, their pre-synaptic calcium activity in the glomerulus is homogeneous. In addition, we could not observe the correlated spontaneous calcium activity that is found on the post-synaptic side throughout mitral cell dendrites and has been used in activity correlation imaging. However, it is possible to induce spatio-temporal presynaptic response inhomogeneities by applying trains of olfactory stimuli with varying amino acid concentrations. Automated region-of-interest detection and correlation analysis then visually distinguishes at least two axon subgroups per glomerulus that differ in odor sensitivity.

Abstract This study explored a germplasm collection consisting of 112 Luffa acutangula (ridge gourd) accessions, mainly from Thailand. A total of 2834 SNPs were used to establish population structure and underlying genetic diversity while exploring the fruit characteristics together with genetic information which would help in the selection of parental lines for a breeding program. The study found that the average polymorphism information content value of 0.288 which indicates a moderate genetic diversity for this L. acutangula germplasm. STRUCTURE analysis (ΔK at K = 6) allowed us to group the accessions into six subpopulations that corresponded well with the unrooted phylogenetic tree and principal coordinate analyses. When plotted, the STRUCTURE bars to the area of collection, we observed an admixed genotype from surrounding accessions and a geneflow confirmed by the value of F ST = 0.137. AMOVA based on STRUCTURE clustering showed a low 12.83% variation between subpopulations that correspond well with the negative inbreeding coefficient value (F IS = − 0.092) and low total fixation index (F IT = 0.057). There were distinguishing fruit shapes and length characteristics in specific accessions for each subpopulation. The genetic diversity and different fruit shapes in the L. acutangula germplasm could benefit the ridge gourd breeding programs to meet the demands and needs of consumers, farmers, and vegetable exporters such as increasing the yield of fruit by the fruit width but not by the fruit length to solve the problem of fruit breakage during exportation.

Abstract Neuroanatomy as a subject is important to learn, because a good understanding of neuroanatomy supports the establishment of a correct diagnosis in neurological patients. However, rapid changes in curricula reduced time assigned to study (neuro)anatomy. Therefore, it is important to find alternative teaching methods to study the complex three-dimensional structure of the brain. The aim of this manuscript was to explore the effectiveness of Virtual Reality (VR) in comparison with Radiological Data (RaD) as suitable learning methods to build knowledge and increase motivation for learning neuroanatomy. Forty-seven students (mean age of 19.47 ± 0.54 years; 43 females; 4 males) were included; 23 students comprised the VR group. Both methods showed to improve knowledge significantly, the improvement between groups was not different. The RaD group showed to have a significantly higher score on expectancy than students in the VR group. Task value scores regarding finding a task interesting, useful and fun were found to be significantly different in favor of the VR group. Consequently, significant higher Motivation scores were found in the VR group. Motivation and expectancy, however, did not moderate learning results, whereas task value impacted the results in favour of the VR group. This study concludes that VR and RaD are effective and diverting methods to learn neuroanatomy, with VR being more motivating than RaD. Future research should investigate motivation and task value when using VR over a longer period of time.

Abstract Chordomas are rare slow growing, malignant bone tumors of the axial skeleton with no approved medical treatment. As the majority of chordomas express cMET and its ligand, HGF, and crosstalks between EGFR and MET-signaling exist, we aimed to explore cMET activity in chordoma cell lines and clinical samples. We investigated nine chordoma patients and four chordoma cell lines for cMET expression. Two clival and two sacral chordoma cell lines were tested for chromosomal abnormalities of the MET gene locus; we studied the influence of HGF on the autocrine secretion and migration behavior, as well as protein expression and phosphorylation. Two MET/ALK inhibitors were investigated for their effects on cell viability, cell cycle, cyclin alterations, apoptosis, and downstream signaling pathways. Moderate and strong expression of membrane and cytoplasmic cMET in chordoma patients and cell lines used, as well as concentration-dependent increase in phospho cMET expression after HGF stimulation in all four chordoma cell lines was shown. U-CH2, MUG-Chor1, and UM-Chor1 are polysomic for MET. Chordoma cell lines secreted EGF, VEGF, IL-6, and MMP9 upon HGF-stimulation. Sacral cell lines showed a distinct HGF-induced migration. Both inhibitors dose-dependently inhibited cell growth, induce apoptosis and cell-cycle arrest, and suppress downstream pathways. Heterogeneous responses obtained in our in vitro setting indicate that cMET inhibitors alone or in combination with other drugs might particularly benefit patients with sacral chordomas.

Abstract Finding novel biomarkers for human pathologies and predicting clinical outcomes for patients is challenging. This stems from the heterogeneous response of individuals to disease and is reflected in the inter-individual variability of gene expression responses that obscures differential gene expression analysis. Here, we developed an alternative approach that could be applied to dissect the disease-associated molecular changes. We define gene ensemble noise as a measure that represents a variance for a collection of genes encoding for either members of known biological pathways or subunits of annotated protein complexes and calculated within an individual. The gene ensemble noise allows for the holistic identification and interpretation of gene expression disbalance on the level of gene networks and systems. By comparing gene expression data from COVID-19, H1N1, and sepsis patients we identified common disturbances in a number of pathways and protein complexes relevant to the sepsis pathology. Among others, these include the mitochondrial respiratory chain complex I and peroxisomes. This suggests a Warburg effect and oxidative stress as common hallmarks of the immune host–pathogen response. Finally, we showed that gene ensemble noise could successfully be applied for the prediction of clinical outcome namely, the mortality of patients. Thus, we conclude that gene ensemble noise represents a promising approach for the investigation of molecular mechanisms of pathology through a prism of alterations in the coherent expression of gene circuits.

Abstract Ecologists study how populations are regulated, while scientists studying biological pest control apply population regulation processes to reduce numbers of harmful organisms: an organism (a natural enemy) is used to reduce the population density of another organism (a pest). Finding an effective biological control agent among the tens to hundreds of natural enemies of a pest is a daunting task. Evaluation criteria help in a first selection to remove clearly ineffective or risky species from the list of candidates. Next, we propose to use an aggregate evaluation criterion, the pest kill rate, to compare the pest population reduction capacity of species not eliminated during the first selection. The pest kill rate is the average daily lifetime killing of the pest by the natural enemy under consideration. Pest kill rates of six species of predators and seven species of parasitoids of Tuta absoluta were calculated and compared. Several natural enemies had pest kill rates that were too low to be able to theoretically reduce the pest population below crop damaging densities. Other species showed a high pest reduction capacity and their potential for practical application can now be tested under commercial crop production conditions.

Abstract Dual-energy CT (DECT) material decomposition techniques may better detect edema within cerebral infarcts than conventional non-contrast CT (NCCT). This study compared if Virtual Ischemia Maps (VIM) derived from non-contrast DECT of patients with acute ischemic stroke due to large-vessel occlusion (AIS-LVO) are superior to NCCT for ischemic core estimation, compared against reference-standard DWI-MRI. Only patients whose baseline ischemic core was most likely to remain stable on follow-up MRI were included, defined as those with excellent post-thrombectomy revascularization or no perfusion mismatch. Twenty-four consecutive AIS-LVO patients with baseline non-contrast DECT, CT perfusion (CTP), and DWI-MRI were analyzed. The primary outcome measure was agreement between volumetric manually segmented VIM, NCCT, and automatically segmented CTP estimates of the ischemic core relative to manually segmented DWI volumes. Volume agreement was assessed using Bland–Altman plots and comparison of CT to DWI volume ratios. DWI volumes were better approximated by VIM than NCCT (VIM/DWI ratio 0.68 ± 0.35 vs. NCCT/DWI ratio 0.34 ± 0.35; P

Abstract Measurement of intracranial aneurysm wall motion may refine the current rupture risk estimation. A golden standard for measuring aneurysm pulsation is lacking. The aim is to evaluate magnitudes of aneurysm pulsation as published in current literature. Embase and PubMed were searched for publications containing quantitative measures of cardiac-cycle related cerebral aneurysm pulsation (no date or language restrictions). Eleven studies were included, covering 197 unruptured and untreated cerebral aneurysms. Quantitative pulsation measurements were extracted from the studies. Characteristics of the study population and aneurysms were taken into account, as well as the imaging modality, scanning technique and data processing methods used. A meta-analysis was performed of studies with similar methodologies and individual IA measures and locations. The magnitude of the absolute volume pulsations varied between 14 ± 9 mm3 and 106 ± 123 mm3 and the mean relative volume change varied between 5 and 36%. The meta-analysis revealed a positive correlation between size and absolute volume change. The relative volume change in Basilar artery aneurysms seems smaller. No authors were contacted for original study data and articles only describing visual pulsations were excluded. The variation in methodologies impedes an accurate estimation of the magnitude of IA pulsations. Validation of aneurysm pulsation measurement is crucial prior to clinical studies evaluating IA pulsatility in relation to IA rupture risk. Prerequisite is a reliable and robust imaging method with high spatial and temporal resolution and standardization of the image analysis methods.

Materials scientists increasingly employ machine or statistical learning (SL) techniques to accelerate materials discovery and design. Such pursuits benefit from pooling training data across, and thus being able to generalize predictions over, k-nary compounds of diverse chemistries and structures. This work presents a SL framework that addresses challenges in materials science applications, where datasets are diverse but of modest size, and extreme values are often of interest. Our advances include the application of power or Hölder means to construct descriptors that generalize over chemistry and crystal structure, and the incorporation of multivariate local regression within a gradient boosting framework. The approach is demonstrated by developing SL models to predict bulk and shear moduli (K and G, respectively) for polycrystalline inorganic compounds, using 1,940 compounds from a growing database of calculated elastic moduli for metals, semiconductors and insulators. The usefulness of the models is illustrated by screening for superhard materials.