bluuebunny/crossref_metadata_2025 huggingface dataset:
An outer approximation algorithm for generating the Edgeworth–Pareto hull of multi-objective mixed-integer linear programming problems
Authors: Bökler Fritz , Parragh Sophie N. , Sinnl Markus , Tricoire Fabien
Published: January 2024

In this paper, we present an outer approximation algorithm for computing the Edgeworth–Pareto hull of multi-objective mixed-integer linear programming problems (MOMILPs). It produces the extreme points (i.e., the vertices) as well as the facets of the Edgeworth–Pareto hull. We note that these extreme points are the extreme supported non-dominated points of a MOMILP. We also show how to extend the concept of geometric duality for multi-objective linear programming problems to the Edgeworth–Pareto hull of MOMILPs and use this extension to develop the algorithm. The algorithm relies on a novel oracle that solves single-objective weighted-sum problems and we show that the required number of oracle calls is polynomial in the number of facets of the convex hull of the extreme supported non-dominated points in the case of MOMILPs. Thus, for MOMILPs for which the weighted-sum problem is solvable in polynomial time, the facets can be computed with incremental-polynomial delay—a result that was formerly only known for the computation of extreme supported non-dominated points. Our algorithm can be an attractive option to compute lower bound sets within multi-objective branch-and-bound algorithms for solving MOMILPs. This is for several reasons as (i) the algorithm starts from a trivial valid lower bound set then iteratively improves it, thus at any iteration of the algorithm a lower bound set is available; (ii) the algorithm also produces efficient solutions (i.e., solutions in the decision space); (iii) in any iteration of the algorithm, a relaxation of the MOMILP can be solved, and the obtained points and facets still provide a valid lower bound set. Moreover, for the special case of multi-objective linear programming problems, the algorithm solves the problem to global optimality. A computational study on a set of benchmark instances from the literature is provided.
In vitro evaluation of the reductive carbonyl idarubicin metabolism to evaluate inhibitors of the formation of cardiotoxic idarubicinol via carbonyl and aldo–keto reductases
Authors: Bajraktari-Sylejmani Gzona , Oster Julia Sophie , Burhenne Jürgen , Haefeli Walter Emil , Sauter Max , Weiss Johanna
Published: January 2024

The most important dose-limiting factor of the anthracycline idarubicin is the high risk of cardiotoxicity, in which the secondary alcohol metabolite idarubicinol plays an important role. It is not yet clear which enzymes are most important for the formation of idarubicinol and which inhibitors might be suitable to suppress this metabolic step and thus would be promising concomitant drugs to reduce idarubicin-associated cardiotoxicity. We, therefore, established and validated a mass spectrometry method for intracellular quantification of idarubicin and idarubicinol and investigated idarubicinol formation in different cell lines and its inhibition by known inhibitors of the aldo–keto reductases AKR1A1, AKR1B1, and AKR1C3 and the carbonyl reductases CBR1/3. The enzyme expression pattern differed among the cell lines with dominant expression of CBR1/3 in HEK293 and MCF-7 and very high expression of AKR1C3 in HepG2 cells. In HEK293 and MCF-7 cells, menadione was the most potent inhibitor (IC50 = 1.6 and 9.8 µM), while in HepG2 cells, ranirestat was most potent (IC50 = 0.4 µM), suggesting that ranirestat is not a selective AKR1B1 inhibitor, but also an AKR1C3 inhibitor. Over-expression of AKR1C3 verified the importance of AKR1C3 for idarubicinol formation and showed that ranirestat is also a potent inhibitor of this enzyme. Taken together, our study underlines the importance of AKR1C3 and CBR1 for the reduction of idarubicin and identifies potent inhibitors of metabolic formation of the cardiotoxic idarubicinol, which should now be tested in vivo to evaluate whether such combinations can increase the cardiac safety of idarubicin therapies while preserving its efficacy.
Human colorectal cancer: upregulation of the adaptor protein Rai in TILs leads to cell dysfunction by sustaining GSK-3 activation and PD-1 expression
Authors: Montecchi Tommaso , Nannini Giulia , De Tommaso Domiziana , Cassioli Chiara , Coppola Federica , Ringressi Maria Novella , Carraro Fabio , Naldini Antonella , Taddei Antonio , Marotta Giuseppe , Amedei Amedeo , Baldari Cosima T. , Ulivieri Cristina
Published: January 2024

Background

The immunosuppressive tumor microenvironment (TME) of colorectal cancer (CRC) is a major hurdle for immune checkpoint inhibitor-based therapies. Hence characterization of the signaling pathways driving T cell exhaustion within TME is a critical need for the discovery of novel therapeutic targets and the development of effective therapies. We previously showed that (i) the adaptor protein Rai is a negative regulator of T cell receptor signaling and T helper 1 (Th1)/Th17 cell differentiation; and (ii) Rai deficiency is implicated in the hyperactive phenotype of T cells in autoimmune diseases.

Methods

The expression level of Rai was measured by qRT-PCR in paired peripheral blood T cells and T cells infiltrating tumor tissue and the normal adjacent tissue in CRC patients. The impact of hypoxia-inducible factor (HIF)-1α on Rai expression was evaluated in T cells exposed to hypoxia and by performing chromatin immunoprecipitation assays and RNA interference assays. The mechanism by which upregulation of Rai in T cells promotes T cell exhaustion were evaluated by flow cytometric, qRT-PCR and western blot analyses.

Results

We show that Rai is a novel HIF-1α-responsive gene that is upregulated in tumor infiltrating lymphocytes of CRC patients compared to patient-matched circulating T cells. Rai upregulation in T cells promoted Programmed cell Death protein (PD)-1 expression and impaired antigen-dependent degranulation of CD8+ T cells by inhibiting phospho-inactivation of glycogen synthase kinase (GSK)-3, a central regulator of PD-1 expression and T cell-mediated anti-tumor immunity.

Conclusions

Our data identify Rai as a hitherto unknown regulator of the TME-induced exhausted phenotype of human T cells.
Interval cancer in the Córdoba Breast Tomosynthesis Screening Trial (CBTST): comparison of digital breast tomosynthesis plus digital mammography to digital mammography alone
Authors: Pulido-Carmona Cristina , Romero-Martín Sara , Raya-Povedano José Luis , Cara-García María , Font-Ugalde Pilar , Elías-Cabot Esperanza , Pedrosa-Garriguet Margarita , Álvarez-Benito Marina
Published: January 2024

Purpose

This work aims to compare the interval cancer rate and interval cancer characteristics between women screened with digital breast tomosynthesis (DBT) + digital mammography (DM) and those screened with DM alone.

Methods

The interval cancer rate and interval cancer characteristics of the study population included in the Córdoba Breast Tomosynthesis Screening Trial (CBTST) were compared to a contemporary control population screened with DM. The tumour characteristics of screen-detected and interval cancers were also compared. Contingency tables were used to compare interval cancer rates. The chi-square test and Fisher’s exact test were used to compare the qualitative characteristics of the cancers whereas Student’s t test and the Mann–Whitney U test were used to analyse quantitative features.

Results

A total of 16,068 screening exams with DBT + DM were conducted within the CBTST (mean age 57.59 ± 5.9 [SD]) between January 2015 and December 2016 (study population). In parallel, 23,787 women (mean age 58.89 ± 5.9 standard deviation [SD]) were screened with DM (control population). The interval cancer rate was lower in the study population than in the control population (15 [0.93‰; 95% confidence interval (CI): 0.73, 1.14] vs 43 [1.8‰; 95% CI: 1.58, 2.04] respectively; p = 0.045). The difference in rate was more marked in women with dense breasts (0.95‰ in the study population vs 3.17‰ in the control population; p = 0.031). Interval cancers were smaller in the study population than in the control population (p = 0.031).

Conclusions

The interval cancer rate was lower in women screened with DBT + DM compared to those screened with DM alone. These differences were more pronounced in women with dense breasts.

Clinical relevance statement

Women screened using tomosynthesis and digital mammography had a lower rate of interval cancer than women screened with digital mammography, with the greatest difference in the interval cancer rate observed in women with dense breasts.

Key Points

• The interval cancer rate was lower in the study population (digital breast tomosynthesis [DBT] + digital mammography [DM]) than in the control population (DM).

• The difference in interval cancer rates was more pronounced in women with dense breasts.

• Interval cancers were smaller in the study population (DBT + DM) than in the control population (DM).
SAL3D: a model for saliency prediction in 3D meshes
Authors: Martin Daniel , Fandos Andres , Masia Belen , Serrano Ana
Published: January 2024

Advances in virtual and augmented reality have increased the demand for immersive and engaging 3D experiences. To create such experiences, it is crucial to understand visual attention in 3D environments, which is typically modeled by means of saliency maps. While attention in 2D images and traditional media has been widely studied, there is still much to explore in 3D settings. In this work, we propose a deep learning-based model for predicting saliency when viewing 3D objects, which is a first step toward understanding and predicting attention in 3D environments. Previous approaches rely solely on low-level geometric cues or unnatural conditions, however, our model is trained on a dataset of real viewing data that we have manually captured, which indeed reflects actual human viewing behavior. Our approach outperforms existing state-of-the-art methods and closely approximates the ground-truth data. Our results demonstrate the effectiveness of our approach in predicting attention in 3D objects, which can pave the way for creating more immersive and engaging 3D experiences.
Associations of dietary choline and betaine with all-cause mortality: a prospective study in a large Swedish cohort
Authors: Karlsson Therese , Winkvist Anna , Strid Anna , Lindahl Bernt , Johansson Ingegerd
Published: January 2024

Purpose

Investigate the association between choline and betaine intake and all-cause mortality in a large Swedish cohort.

Methods

Women (52,246) and men (50,485) attending the Västerbotten Intervention Programme 1990–2016 were included. Cox proportional hazard regression models adjusted for energy intake, age, BMI, smoking, education, and physical activity were used to estimate mortality risk according to betaine, total choline, phosphatidylcholine, glycerophosphocholine, phosphocholine, sphingomyelin, and free choline intakes [continuous (per 50 mg increase) and in quintiles].

Results

During a median follow-up of 16 years, 3088 and 4214 deaths were registered in women and men, respectively. Total choline intake was not associated with all-cause mortality in women (HR 1.01; 95% CI 0.97, 1.06; P = 0.61) or men (HR 1.01; 95% CI 0.98, 1.04; P = 0.54). Betaine intake was associated with decreased risk of all-cause mortality in women (HR 0.95; 95% CI 0.91, 0.98; P < 0.01) but not in men. Intake of free choline was negatively associated with risk of all-cause mortality in women (HR 0.98; 95% CI 0.96, 1.00; P = 0.01). No other associations were found between intake of the different choline compounds and all-cause mortality. In women aged ≥ 55 years, phosphatidylcholine intake was positively associated with all-cause mortality. In men with higher folate intake, total choline intake was positively associated with all-cause mortality.

Conclusion

Overall, our results do not support that intake of total choline is associated with all-cause mortality. However, some associations were modified by age and with higher folate intake dependent on sex. Higher intake of betaine was associated with lower risk of all-cause mortality in women.
Effects of a single phosphate-enriched test meal on inflammasome activity and postprandial inflammatory markers in healthy subjects
Authors: Nier Anika , Ulrich Christof , Volk Christin , Wolffgang Marie-Charlotte , Brandsch Corinna , Wensch-Dorendorf Monika , Girndt Matthias , Stangl Gabriele I.
Published: January 2024

Purpose

The consumption of highly processed food is often associated with a high intake of inorganic phosphate. Hyperphosphatemia is accompanied by an inflammatory status in patients with chronic kidney disease. However, the immune response to high phosphorus intake in healthy individuals is largely unknown. Therefore, the aim of the present study was to evaluate the effect of a single phosphate-enriched meal on inflammasome activity and plasma levels of inflammatory markers.

Methods

The analysis included 28 participants who received a single dose of either 700 mg phosphorus or a placebo with a test meal. At baseline, 4 and 8 h post-meal, plasma interleukin (IL)-6, IL-1β, IL-10, c-reactive protein (CRP), soluble IL-6 receptor (sIL-6R) and glycoprotein 130 (sgp130) levels were determined. At baseline and 4 h post-meal, peripheral blood mononuclear cells were isolated to assess inflammasome activity. Subsequently, the effect of phosphate with or without glucose on IL-6 and IL-1β gene expression and secretion in U937 monocytes was examined.

Results

While both groups showed a marked postprandial increase in IL-6 plasma levels, neither plasma levels of IL-6, IL-1β, CRP, IL-10, sIL-6R, and sgp130 nor inflammasome activity were affected by phosphate compared to placebo. In U937 cells, there was also no effect of phosphate on IL-6 expression, but the addition of glucose increased it. Phosphate, however, reduced the IL-1β secretion of these cells.

Conclusion

Postprandial inflammatory markers were not affected by dietary phosphate. However, IL-6 plasma levels were markedly increased post-meal, which appears to be a metabolic rather than a pro-inflammatory phenomenon.

Trial registration number

ClinicalTrials.gov, NCT03771924, date of registration: 11th December 2018, retrospectively registered.
Cortical matrix remodeling as a hallmark of relapsing–remitting neuroinflammation in MR elastography and quantitative MRI
Authors: Silva Rafaela V. , Morr Anna S. , Herthum Helge , Koch Stefan P. , Mueller Susanne , Batzdorf Clara S. , Bertalan Gergely , Meyer Tom , Tzschätzsch Heiko , Kühl Anja A. , Boehm-Sturm Philipp , Braun Jürgen , Scheel Michael , Paul Friedemann , Infante-Duarte Carmen , Sack Ingolf
Published: January 2024

Multiple sclerosis (MS) is a chronic neuroinflammatory disease that involves both white and gray matter. Although gray matter damage is a major contributor to disability in MS patients, conventional clinical magnetic resonance imaging (MRI) fails to accurately detect gray matter pathology and establish a clear correlation with clinical symptoms. Using magnetic resonance elastography (MRE), we previously reported global brain softening in MS and experimental autoimmune encephalomyelitis (EAE). However, it needs to be established if changes of the spatiotemporal patterns of brain tissue mechanics constitute a marker of neuroinflammation. Here, we use advanced multifrequency MRE with tomoelastography postprocessing to investigate longitudinal and regional inflammation-induced tissue changes in EAE and in a small group of MS patients. Surprisingly, we found reversible softening in synchrony with the EAE disease course predominantly in the cortex of the mouse brain. This cortical softening was associated neither with a shift of tissue water compartments as quantified by T2-mapping and diffusion-weighted MRI, nor with leukocyte infiltration as seen by histopathology. Instead, cortical softening correlated with transient structural remodeling of perineuronal nets (PNNs), which involved abnormal chondroitin sulfate expression and microgliosis. These mechanisms also appear to be critical in humans with MS, where tomoelastography for the first time demonstrated marked cortical softening. Taken together, our study shows that neuroinflammation (i) critically affects the integrity of PNNs in cortical brain tissue, in a reversible process that correlates with disease disability in EAE, (ii) reduces the mechanical integrity of brain tissue rather than leading to water accumulation, and (iii) shows similar spatial patterns in humans and mice. These results raise the prospect of leveraging MRE and quantitative MRI for MS staging and monitoring treatment in affected patients.
Validating the virtual: a deep dive into ultrasound simulator metrics in otorhinolaryngology
Authors: Risgaard Anne Line , Andersen Iben Bang , Friis Mikkel Lønborg , Tolsgaard Martin Grønnebæk , Danstrup Christian Sander
Published: January 2024

Purpose

This study aimed to assess the validity of simulation-based assessment of ultrasound skills for thyroid ultrasound.

Methods

The study collected validity evidence for simulation-based ultrasound assessment of thyroid ultrasound skills. Experts (n = 8) and novices (n = 21) completed a test containing two tasks and four cases on a virtual reality ultrasound simulator (U/S Mentor's Neck Ultrasound Module). Validity evidence was collected and structured according to Messick’s validity framework. The assessments being evaluated included built-in simulator metrics and expert-based evaluations using the Objective Structured Assessment of Ultrasound Skills (OSAUS) scale.

Results

Out of 64 built-in simulator metrics, 9 (14.1%) exhibited validity evidence. The internal consistency of these metrics was strong (Cronbach’s α = 0.805) with high test–retest reliability (intraclass correlation coefficient = 0.911). Novices achieved an average score of 41.9% (SD = 24.3) of the maximum, contrasting with experts at 81.9% (SD = 16.7). Time comparisons indicated minor differences between experts (median: 359 s) and novices (median: 376.5 s). All OSAUS items differed significantly between the two groups. The correlation between correctly entered clinical findings and the OSAUS scores was 0.748 (p < 0.001). The correlation between correctly entered clinical findings and the metric scores was 0.801 (p < 0.001).

Conclusion

While simulation-based training is promising, only 14% of built-in simulator metrics could discriminate between novices and ultrasound experts. Already-established competency frameworks such as OSAUS provided strong validity evidence for the assessment of otorhinolaryngology ultrasound competence.
15 weeks of soccer training increases left ventricular mass and improves indices of left ventricular diastolic function in previously sedentary, mildly hypertensive, middle-aged women
Authors: Sjúrðarson Tórur , Kyhl Kasper , Nordsborg Nikolai B. , Kollslíð Rudi , Andersen Lars Juel , Krustrup Peter , Mohr Magni
Published: January 2024

Purpose

To investigate the impact of soccer training on cardiac adaptations in mildly hypertensive middle-aged women.

Methods

Hypertensive premenopausal women (n = 41; age (mean ± SD): 44 ± 7 years; height: 166 ± 6 cm; weight: 78.6 ± 11.6 kg; body fat: 43.3 ± 5.2%) were randomized to soccer training (SOC, n = 21) or control (CON, n = 20). SOC performed three weekly training sessions for 15 weeks, whereas CON had no training or lifestyle changes during the same period. Cardiac structure and function were assessed by echocardiography pre-intervention and post-intervention.

Results

Soccer training increased (P = 0.001) left ventricular mass index by 10% [95% CI 4; 15], while no changes occurred in CON (time × group interaction, P = 0.005). In addition, only SOC demonstrated a within-group increase (P = 0.01) of 8% [95% CI 2; 14] in left ventricular septum diameter. For markers of right ventricular remodelling, a within-group increase (P = 0.02) occurred for tricuspid annulus plane systolic excursion of 8% [95% CI 1; 14] in SOC only. Left atrial diameter index increased (P < 0.001) by 6% [95% CI 3; 10] after SOC, while it was unaffected in CON (time × group interaction, P = 0.02). For makers of diastolic function, SOC demonstrated a within-group increase (P = 0.02) in the average early diastolic mitral annulus velocity of 10% [95% CI 2; 19]. In addition, a reduction (P < 0.001) in mitral valve A velocity of − 19% [95% CI − 29; − 10] was observed following soccer training, which manifested in increased (P < 0.001) mitral valve E/A ratio of 34% [95% CI 16; 53] in SOC. No within-group changes were apparent in CON.

Conclusion

In sedentary, mildly hypertensive, middle-aged women, 15 weeks of soccer training increases left ventricular mass and left atrial diameter and improves indices of left ventricular diastolic function.
Adverse childhood events and mental health problems in cancer survivors: a systematic review
Authors: Hinnen Chris , von Haeseler Emma , Tijssens Frederiek , Mols Floortje
Published: January 2024

Purpose

The purpose of this study was to systematically review the literature on the association between adverse childhood events (ACEs) and mental health problems in cancer survivors.

Methods

This review was conducted in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Four databases (PubMed, PsychINFO, Web of Science, and Cochrane) were searched on 27–08-2023.

Results

Of the 1413 references yielded by the literature search, 25 papers met inclusion criteria and were reviewed. Most studies were performed in the USA, most included breast cancer survivors, and the number of included participants ranged between 20 and 1343. ACEs were relatively prevalent, with self-report rates ranging between 40 and 95%. Having been exposed to ACEs was a risk factor for heightened levels of emotional distress, anxiety, depressive symptoms, and fatigue during cancer treatment. Results varied depending on the variables included, and per subscale, but were consistent across different cultures and heterogenous patient groups.

Conclusion

The association between ACE and mental health outcomes was significant in most studies. In order to improve treatment for this vulnerable population, it may be necessary to screen for ACEs before cancer treatment and adjust treatment, for example, by means of trauma-informed care (TIC), which recognizes and responds to the impact of trauma on individuals seeking healthcare.
Effects of the tetravanadate [V4O12]4− anion on the structural, magnetic, and biological properties of copper/phenanthroline complexes
Authors: Sánchez-Lara Eduardo , Favela Roberto , Tzian Kitze , Monroy-Torres Brian , Romo-Pérez Adriana , Ramírez-Apan María Teresa , Flores-Alamo Marcos , Rodríguez-Diéguez Antonio , Cepeda Javier , Castillo Ivan
Published: January 2024

The aim to access linked tetravanadate [V4O12]4− anion with mixed copper(II) complexes, using α-amino acids and phenanthroline-derived ligands, resulted in the formation of four copper(II) complexes [Cu(dmb)(Gly)(OH2)]2[Cu(dmb)(Gly)]2[V4O12]·9H2O (1) [Cu(dmb)(Lys)]2[V4O12]·8H2O (2), [Cu(dmp)2][V4O12]·C2H5OH·11H2O (3), and [Cu(dmp)(Gly)Cl]·2H2O (4), where dmb = 4,4′-dimethioxy-2,2′-bipyridine; Gly = glycine; Lys = lysine; and dmp = 2,9-dimethyl-1,10-phenanthroline. The [V4O12]4− anion is functionalized with mixed copper(II) units in 1 and 2; while in 3, it acts as a counterion of two [Cu(dmp)]2+ units. Compound 4 crystallized as a unit that did not incorporate the vanadium cluster. All compounds present magnetic couplings arising from Cu⋯O/Cu⋯Cu bridges. Stability studies of water-soluble 3 and 4 by UV–Vis spectroscopy in cell culture medium confirmed the robustness of 3, while 4 appears to undergo ligand scrambling over time, resulting partially in the stable species [Cu(dmp)2]+ that was also identified by electrospray ionization mass spectrometry at m/z = 479. The in vitro cytotoxicity activity of 3 and 4 was determined in six cancer cell lines; the healthy cell line COS-7 was also included for comparative purposes. MCF-7 cells were more sensitive to compound 3 with an IC50 value of 12 ± 1.2 nmol. The tested compounds did not show lipid peroxidation in the TBARS assay, ruling out a mechanism of action via reactive oxygen species formation. Both compounds inhibited cell migration at 5 µM in wound-healing assays using MCF-7, PC-3, and SKLU-1 cell lines, opening a new window to study the anti-metastatic effect of mixed vanadium–copper(II) systems.

Graphical abstract
Children and young people’s reported contact with professional services for mental health concerns: a secondary data analysis
Authors: Mathews Frances , Ford Tamsin Jane , White Simon , Ukoumunne Obioha Chukwunyere , Newlove-Delgado Tamsin
Published: January 2024

Children and young people’s mental health services have been under increasing pressure following COVID-19. Understanding, for which channels help is sought from, will highlight services needing support. This study aims to explore the professional services that parents of children, and young people get help from when they have a concern for the child’s/their mental health. Secondary analysis of data is taken from Mental Health of Children and Young People in England Survey, 2017. 7608 reports of mental health-related contact with professional services from parents of 5–16 year-olds and self-reports from young people aged 17–19 were available. Service contact was reported by Diagnostic and Statistical Manual of Mental Disorders (DSM-V) diagnosis, age, gender and ethnicity. Less than two-thirds of children and young people with a DSM-V diagnosis (63.5% (95% CI 58.6–68.1) aged 5–10, and 64.0% (95% CI 59.4–68.4) aged 11–16) reported contact with any professional services. The figure was lower for those aged 17–19; 50.1% (95% CI 42.8–58.2), p = 0.005. Children and young people aged 5–16 from Black (11.7%; 95% CI 2.4–41.4), Asian (55.1%; 95% CI 34.7–73.9) and Mixed (46.0%; 95% CI 32.4–60.3) ethnic groups reported less contact with professional services compared to those from the White group (66.9%; 95% CI 63.5–70.2). Patterns of service access during the three main educational stages aid with understanding service need during childhood. These lower levels of reported service access for young people aged 17–19 with a DSM-V diagnosis and those in ethnic minority groups demand further investigation.
Human-in-the-loop latent space learning for biblio-record-based literature management
Authors: Watanabe Shingo , Ito Hiroyoshi , Matsubara Masaki , Morishima Atsuyuki
Published: January 2024

Every researcher must conduct a literature review, and the document management needs of researchers working on various research topics vary. However, there are two major challenges. First, traditional methods such as the tree hierarchy of document folders and tag-based management are no longer effective with the enormous volume of publications. Second, although their bibliographic information is available to everyone, many papers can only be accessed through paid services. This study attempts to develop an interactive tool for personal literature management based solely on their bibliographic records. To make such a tool possible, we developed a principled “human-in-the-loop latent space learning” method that estimates the management criteria of each researcher based on his or her feedback to calculate the positions of documents in a two-dimensional space on the screen. As a set of bibliographic records forms a graph, our model is naturally designed as a graph-based encoder–decoder model that connects the graph and the space. In addition, we also devised an active learning framework using uncertainty sampling for it. The challenge here is to define the uncertainty in a problem setting. Experiments with ten researchers from the humanities, science, and engineering domains show that the proposed framework provides superior results to a typical graph convolutional encoder–decoder model. In addition, we found that our active learning framework was effective in selecting good samples.
Virtual non-contrast series of photon-counting detector computed tomography angiography for aortic valve calcium scoring
Authors: Risch Franka , Harmel Eva , Rippel Katharina , Wein Bastian , Raake Philip , Girdauskas Evaldas , Elvinger Sébastien , Owais Tamer , Scheurig-Muenkler Christian , Kroencke Thomas , Schwarz Florian , Braun Franziska , Decker Josua A.
Published: January 2024

The aim of our study was to evaluate two different virtual non-contrast (VNC) algorithms applied to photon counting detector (PCD)-CT data in terms of noise, effectiveness of contrast media subtraction and aortic valve calcium (AVC) scoring compared to reference true non-contrast (TNC)-based results. Consecutive patients underwent TAVR planning examination comprising a TNC scan, followed by a CTA of the heart. VNC series were reconstructed using a conventional (VNCconv) and a calcium-preserving (VNCpc) algorithm. Noise was analyzed by means of the standard deviation of CT-values within the left ventricle. To assess the effectiveness of contrast media removal, heart volumes were segmented and the proportion of their histograms > 130HU was taken. AVC was measured by Agatston and volume score. 41 patients were included. Comparable noise levels to TNC were achieved with all VNC reconstructions. Contrast media was effectively virtually removed (proportions > 130HU from 81% to < 1%). Median calcium scores derived from VNCconv underestimated TNC-based scores (up to 74%). Results with smallest absolute difference to TNC were obtained with VNCpc reconstructions (0.4 mm, Br36, QIR 4), but with persistent significant underestimation (median 29%). Both VNC algorithms showed near-perfect (r²>0.9) correlation with TNC. Thin-slice VNC reconstructions provide equivalent noise levels to standard thick-slice TNC series and effective virtual removal of iodinated contrast. AVC scoring was feasible on both VNC series, showing near-perfect correlation, but with significant underestimation. VNCpc with 0.4 mm slices and Br36 kernel at QIR 4 gave the most comparable results and, with further advances, could be a promising replacement for additional TNC.
Epidemiology of gastroenteropancreatic neuroendocrine neoplasms: a review and protocol presentation for bridging tumor registry data with the Italian association for neuroendocrine tumors (Itanet) national database
Authors: Panzuto Francesco , Partelli Stefano , Campana Davide , de Braud Filippo , Spada Francesca , Cives Mauro , Tafuto Salvatore , Bertuzzi Alexia , Gelsomino Fabio , Bergamo Francesca , Marcucci Stefano , Mastrangelo Laura , Massironi Sara , Appetecchia Marialuisa , Filice Angelina , Badalamenti Giuseppe , Bartolomei Mirco , Amoroso Vito , Landoni Luca , Rodriquenz Maria Grazia , Valente Monica , Colao Annamaria , Isidori Andrea , Fanciulli Giuseppe , Bollina Roberto , Ciola Michele , Butturini Giovanni , Marconcini Riccardo , Arvat Emanuela , Cinieri Saverio , Berardi Rossana , Baldari Sergio , Riccardi Ferdinando , Spoto Chiara , Giuffrida Dario , Gattuso Domenico , Ferone Diego , Rinzivillo Maria , Bertani Emilio , Versari Annibale , Zerbi Alessandro , Lamberti Giuseppe , Lauricella Eleonora , Pusceddu Sara , Fazio Nicola , Dell’Unto Elisabetta , Marini Marco , Falconi Massimo
Published: January 2024

Neuroendocrine neoplasms (NENs) are rare tumors with diverse clinical behaviors. Large databases like the Surveillance, Epidemiology, and End Results (SEER) program and national NEN registries have provided significant epidemiological knowledge, but they have limitations given the recent advancements in NEN diagnostics and treatments. For instance, newer imaging techniques and therapies have revolutionized NEN management, rendering older data less representative. Additionally, crucial parameters, like the Ki67 index, are missing from many databases. Acknowledging these gaps, the Italian Association for Neuroendocrine Tumors (Itanet) initiated a national multicenter prospective database in 2019, aiming to gather data on newly-diagnosed gastroenteropancreatic neuroendocrine (GEP) NENs. This observational study, coordinated by Itanet, includes patients from 37 Italian centers. The database, which is rigorously maintained and updated, focuses on diverse parameters including age, diagnostic techniques, tumor stage, treatments, and survival metrics. As of October 2023, data from 1,600 patients have been recorded, with an anticipation of reaching 3600 by the end of 2025. This study aims at understanding the epidemiology, clinical attributes, and treatment strategies for GEP-NENs in Italy, and to introduce the Itanet database project. Once comprehensive follow-up data will be acquired, the goal will be to discern predictors of treatment outcomes and disease prognosis. The Itanet database will offer an unparalleled, updated perspective on GEP-NENs, addressing the limitations of older databases and aiding in optimizing patient care.

Study registration

This protocol was registered in clinicaltriasl.gov (NCT04282083).
Cerebellar Asymmetry of Motivational Direction: Anger-Dependent Effects of Cerebellar Transcranial Direct Current Stimulation on Aggression in Healthy Volunteers
Authors: Kruithof Eline S. , Klaus Jana , Schutter Dennis J. L. G.
Published: January 2024

It has recently been theorized that the frontal asymmetry of approach- and avoidance-related motivation is mirrored in the posterolateral cerebellum. Accordingly, left-to-right dominant cerebellar activity is associated with avoidance-related motivation, whereas right-to-left dominant cerebellar activity is associated with approach-related motivation. The aim of this study was to examine the cerebellar asymmetry of motivational direction in approach-related behavior in the context of aggression. In this randomized double-blind sham-controlled crossover study, thirty healthy right-handed adult volunteers received 2 mA active or sham left cathodal-right anodal transcranial direct current stimulation (tDCS) to the cerebellum on two separate occasions while engaging in the Point Subtraction Aggression Paradigm (PSAP) task to measure aggressive behavior. Self-reported state anger was assessed before, halfway and immediately after the task, and heart rate and heart rate variability (HRV) were measured during the task. No main effects of tDCS on aggressive behavior, heart rate and HRV were found. Higher state anger before and during the PSAP task was associated with increased aggressive behavior in the active compared to sham tDCS condition. Aggressive behavior was positively correlated with heart rate during active tDCS, while an inverse association was observed during sham tDCS. Results provide support for the cerebellar asymmetry of motivational direction in approach-related behavior and illustrate the importance of affective state-dependency in tDCS-related effects.
Transient Decrease in Sperm Motility after Plateletpheresis
Authors: von Ostau Nicola E. , Martynov Aleksandr , Schreiber Janina , Wiesehöfer Marc , Hadaschik Boris A. , Temme Christian , Stang Andreas , Dankert Jaroslaw T. , Wiesehöfer Caroline , Wennemuth Gunther
Published: January 2024

Although people are constantly exposed to phthalates little is known about the extent to which PAEs affect sperm. Most studies do not address changes at the single-cell level. Our study concentrated on the examination of donors who were assumed to have been exposed to high levels of phthalate under plateletpheresis. We used Computer-Assisted-Sperm-Analysis to study the association between the most potent phthalate, di-2-ethylhexyl phthalate, and a decrease in sperm motility. In an exploratory in vivo study, we investigated whether plateletpheresis of donors led to an increase in the concentration of active metabolites of DEHP in seminal plasma and whether this had an effect on sperm motility. PAE metabolites and sperm motility parameters of ejaculate donors were analyzed at a single-cell level before and after plateletpheresis. We found an increase in PAE metabolite concentration in the seminal plasma, associated with a decrease in flagellar beat frequency after plateletpheresis. Follow-up analysis showed that this was a transient effect of plateletpheresis in terms of a PAE concentration increase in seminal plasma and a decrease in sperm motility. This study shows that plateletpheresis results in high levels of phthalate exposure and that these are associated with a transient and reversible decrease in sperm motility.
Two-Step Parameter Estimation for Read Feature Models
Authors: Erhard Florian
Published: January 2024

Over the last two decades, the field of molecular biology has witnessed a revolution due to the development of next generation sequencing (NGS) technologies. NGS enables researchers to routinely generate huge amounts of data that can be used to pursue a large variety of questions in diverse biological systems. The development of these techniques has propelled the emergence of a sub-discipline within computational biology that is concerned with developing methods and statistical models to derive quantitative information from the complex and often indirect data that are generated by NGS. Often, NGS analysis results in particular patterns per biological entity that can be exploited to estimate quantitative parameters of biological interest. Here, I define read feature models (RFMs) as a general framework for such data. RFMs entail global, genome-wide parameters as well as parameters per biological entity, suggesting a two-step procedure for parameter estimation. I describe the analysis of metabolic RNA labeling data as an example of an RFM and analyze and discuss the merits and shortcomings of the two-step estimation.
Impact of differential torsional rotor cant on the flight characteristics of a passenger-grade quadrotor
Authors: Atci Kagan , Jusko Tim , Štrbac Alexander , Guner Feyyaz
Published: January 2024

At the Institute of Flight Systems at DLR, studies have been performed to understand the flight characteristics of novel eVTOL configurations. As part of these studies, previously conducted handling qualities assessments on a two-passenger generic quadrotor configuration had revealed major deficiencies about its yaw axis. Based on this result, the quadrotor model has been modified by differential torsional canting to improve its yaw characteristics. This paper analyzes the resulting impacts of such modification on the flight performance, dynamic stability and handling qualities. A piloted simulator test campaign was conducted to assess predicted and assigned handling qualities levels in compliance with the quantitative and qualitative performance standards of ADS-33E. The results show an improvement in midterm yaw response at the expense of increase in total required power. The pilot ratings and comments confirm the improvement on the yaw response upon the flown MTEs.
Decade Milestone Advancement of Defect-Engineered g-C3N4 for Solar Catalytic Applications
Authors: Hou Shaoqi , Gao Xiaochun , Lv Xingyue , Zhao Yilin , Yin Xitao , Liu Ying , Fang Juan , Yu Xingxing , Ma Xiaoguang , Ma Tianyi , Su Dawei
Published: January 2024

Over the past decade, graphitic carbon nitride (g-C3N4) has emerged as a universal photocatalyst toward various sustainable carbo-neutral technologies. Despite solar applications discrepancy, g-C3N4 is still confronted with a general fatal issue of insufficient supply of thermodynamically active photocarriers due to its inferior solar harvesting ability and sluggish charge transfer dynamics. Fortunately, this could be significantly alleviated by the “all-in-one” defect engineering strategy, which enables a simultaneous amelioration of both textural uniqueness and intrinsic electronic band structures. To this end, we have summarized an unprecedently comprehensive discussion on defect controls including the vacancy/non-metallic dopant creation with optimized electronic band structure and electronic density, metallic doping with ultra-active coordinated environment (M–Nx, M–C2N2, M–O bonding), functional group grafting with optimized band structure, and promoted crystallinity with extended conjugation π system with weakened interlayered van der Waals interaction. Among them, the defect states induced by various defect types such as N vacancy, P/S/halogen dopants, and cyano group in boosting solar harvesting and accelerating photocarrier transfer have also been emphasized. More importantly, the shallow defect traps identified by femtosecond transient absorption spectra (fs-TAS) have also been highlighted. It is believed that this review would pave the way for future readers with a unique insight into a more precise defective g-C3N4 “customization”, motivating more profound thinking and flourishing research outputs on g-C3N4-based photocatalysis.
Emissions from the Construction Sector in the United Kingdom
Authors: Desouza Carl , Marsh Daniel , Beevers Sean , Molden Nick , Green David
Published: January 2024

The UK national atmospheric emissions inventory estimates of construction industry emissions use a top-down approach, based on fuel consumption and employment. It estimates that the sector is the 2nd largest emitter of PM2.5 (14%) and 4th largest emitter of NOX (7%). In this study, we have adopted a bottom-up approach to assess emissions of NOX from the sector and show that emissions are 39% higher than the existing estimates. By developing a novel fleet turnover model to predict the population and emission standard of construction machinery up to 2025, we demonstrate a significant shift in the quantity and types of machines used. The overall uncertainty of the model was calculated to be 55%. Applying the estimated uncertainties to the model, in 2018, the non-road mobile machinery fleet in the UK emitted 36.6 ± 10.0 kilo-tonnes of NOX, whilst the NAEI estimated 33.2 kilo-tonnes for the same sector. For the subsequent years 2019 and 2020, the NAEI estimate was within the model’s uncertainty prediction—28.0 kilo-tonnes compared with 32.7 ± 8.9 kilo-tonnes for 2019 and 23.2 kilo-tonnes compared with 29.5 ± 8.1 kilo-tonnes for 2020. Overall, the size of the non-road mobile machinery fleet in the UK is predicted to reduce by 4% in 2025 compared to 2018. Furthermore, the introduction of Stages IV and V emission regulations for new machines will lead to a 58% reduction in fleet NOX emissions over the same period. These emission regulations are targeted at the larger, more polluting machines, with smaller machines not required to meet tighter emissions standards under Stage V. As a result, mini-excavators are the most common machines and consequently become the dominant source of NOX emissions from the fleet, contributing 55% in 2025. Therefore, tighter emissions regulations, or the uptake of battery power in the form of electrification, for these small machines would yield significant emissions reductions.

Graphical Abstract
Anthony V. Bouza and the Founding of Evidence-Based Policing
Authors: Sherman Lawrence W.
Published: January 2024

Anthony V. Bouza (1928–2023) was a founding father of evidence-based policing. The first police chief to authorize a randomized controlled trial (RCTs) of arrest, he turned the Minneapolis Police Department (MPD) into a “crime lab’’ for what works in policing. In his 9 years as Chief, he sponsored the first RCTs done anywhere on such key topics as hot spot patrols, problem-oriented policing, neighborhood watch, and arrests for misdemeanor domestic assault. He also sponsored the first digital analysis of repeat call addresses, which found that 5% of the street addresses produced 64% of the calls for service (New York Times, Minneapolis study places origins of 911 calls, 1987). Taken together, these research projects formed a critical mass of knowledge for describing evidence-based policing as a framework for police reform (Sherman, Evidence-Based Policing, 1998).
FDrisk: development of a validated risk assessment tool for Fabry disease utilizing electronic health record data
Authors: Lobel Caryn J. , Laney Dawn A. , Yang Jingjing , Jacob David , Rickheim Amy , Ogg Carol Z. , Clynes Diana , Dronen Jessica
Published: January 2024

Purpose

Fabry disease (FD) is a rare, X-linked, lysosomal storage disease characterized by great variability in clinical presentation and progressive multisystemic organ damage. Lack of awareness of FD and frequent misdiagnoses cause long diagnostic delays. To address the urgent need for earlier diagnosis, we created an online, risk-assessment scoring tool, the FDrisk, for predicting an individual’s risk for FD and prompting diagnostic testing and clinical evaluation.

Methods

Utilizing electronic health records, data were collected retrospectively from randomly selected, deidentified patients with FD treated at the Emory Lysosomal Storage Disease Center. Deidentified, negative controls were randomly selected from the Fabry Disease Diagnostic Testing and Education project database, a program within the American Association of Kidney Patients Center for Patient Education and Research. Diagnosis of FD was documented by evidence of a pathogenic variant inGLAand/or an abnormal level of leukocyte α-Gal A. Thirty characteristic clinical features of FD were initially identified and subsequently curated into 16 clinical covariates used as predictors for the risk of FD. An overall prediction model and two sex-specific prediction models were built. Two-hundred and sixty samples (130 cases, 130 controls) were used to train the risk prediction models. One-hundred and ninety-seven independent samples (30 cases, 167 controls) were used for testing model performance. Prediction accuracy was evaluated using a threshold of 0.5 to determine a predicted case vs. control.

Results

The overall risk prediction model demonstrated 80% sensitivity, 83.8% specificity, and positive predictive value of 47.1%. The male model demonstrated 75% sensitivity, 95.8% specificity, and positive predictive value of 75%. The female model demonstrated 83.3% sensitivity, 81.3% specificity, and positive predictive value of 45.5%. Patients with risk scores at or above 50% are categorized as “at risk” for FD and should be sent for diagnostic testing.

Conclusion

We have developed a statistical risk prediction model, the FDrisk, a validated, clinician-friendly, online, risk-assessment scoring tool for predicting an individual’s risk for FD and prompting diagnostic testing and clinical evaluation. As an easily accessible, user-friendly scoring tool, we believe implementing the FDrisk will significantly decrease the time to diagnosis and allow earlier initiation of FD-specific therapy.
Supervised machine learning algorithms for predicting student dropout and academic success: a comparative study
Authors: Villar Alice , de Andrade Carolina Robledo Velini
Published: January 2024

Utilizing a dataset sourced from a higher education institution, this study aims to assess the efficacy of diverse machine learning algorithms in predicting student dropout and academic success. Our focus was on algorithms capable of effectively handling imbalanced data. To tackle class imbalance, we employed the SMOTE resampling technique. We applied a range of algorithms, including Decision Tree (DT), Support Vector Machine (SVM), Random Forest (RF), as well as boosting algorithms such as Gradient Boosting (GB), Extreme Gradient Boosting (XGBoost), CatBoost (CB), and Light Gradient Boosting Machine (LB). To enhance the models' performance, we conducted hyperparameter tuning using Optuna. Additionally, we employed the Isolation Forest (IF) method to identify outliers or anomalies within the dataset. Notably, our findings indicate that boosting algorithms, particularly LightGBM and CatBoost with Optuna, outperformed traditional classification methods. Our study's generalizability to other contexts is constrained due to its reliance on a single dataset, with inherent limitations. Nevertheless, this research provides valuable insights into the effectiveness of various machine learning algorithms for predicting student dropout and academic success. By benchmarking these algorithms, our project offers guidance to both researchers and practitioners in their choice of suitable approaches for similar predictive tasks.