bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics, pharmacodynamics and safety profile of the dual orexin receptor antagonist vornorexant/TS‐142 in healthy Japanese participants following single/multiple dosing: Randomized, double‐blind, placebo‐controlled phase‐1 studies
Authors: Kambe Daiji , Hasegawa Sayaka , Imadera Yumiko , Mano Yoko , Matsushita Isao , Konno Yoshihiro , Ogo Hiroki , Uchimura Naohisa , Uchiyama Makoto 
Published: August 2023

AbstractThe pharmacokinetics, pharmacodynamics and safety profile of vornorexant were investigated in healthy Japanese participants in three double‐blind studies: a single ascending dose of 1–30 mg (Study 101; n = 6) and multiple ascending doses of 10–30 mg (Study 102; n = 6). Study 202 consisted of two steps: an open‐label, 20 mg repeated‐dose in non‐elderly individuals (Step 1; n = 12) and a double‐blind, 20 mg repeated‐dose in elderly individuals (Step 2; n = 8/3 for vornorexant/placebo). Vornorexant was rapidly absorbed and eliminated under fasting conditions, with a time to maximum plasma concentration of 0.500–3.00 h (range) and elimination half‐life of 1.32–3.25 h. The area under the plasma concentration‐time curve (AUC) of vornorexant increased proportionally with dose increments. Sleepiness‐related pharmacodynamic outcome changes (Karolinska sleepiness scale, digit symbol substitution test and psychomotor vigilance task) were generally increased with dose increments at 1 and 4 h post‐dose, whereas no consistent dose‐related changes were detected the next morning. Food intake did not affect the maximum observed plasma concentration of vornorexant but increased the AUC0–inf. Exposure in elderly individuals was generally comparable to that in non‐elderly individuals. Altogether, vornorexant may have a favourable profile for insomnia treatment, including rapid onset of action and minimal next‐day residual effects.
A novel alpha‐amylase inhibitor‐based spirooxindole‐pyrrolidine‐clubbed thiochromene‐pyrzaole pharmacophores: Unveiling the [3+2] cycloaddition reaction by molecular electron density theory
Authors: Islam Mohammad Shahidul , Al‐Majid Abdullah Mohammed , Haukka Matti , Parveen Zahida , Ravaiz Nabeela , Wadood Abdul , Rehman Ashfaq Ur , Ríos‐Gutiérrez Mar , Domingo Luis R. , Barakat Assem 
Published: August 2023

AbstractA novel spirooxindole‐pyrrolidine clubbed thiochromene and pyrazole motifs were synthesized by [3+2] cycloaddition (32CA) reactions in one step process starting from the ethylene‐based thiochromene and pyrazole scaffolds with the secondary amino‐acids and substituted isatins in high yield. The 32CA reaction of AY 10 with ethylene derivative 6 has also been studied with Molecular Electron Density Theory. The high nucleophilic character of AY 10, N = 4.39 eV, allows explaining that the most favorable TS‐on is 13.9 kcal mol−1 below the separated reagent. This 32CA, which takes place through a non‐concerted one‐step mechanism, presents a total ortho regio‐ and endo stereoselectivity, which is controlled by the formation of two intramolecular H…O hydrogen bonds. The design of spirooxindole‐pyrrolidines engrafted thiochromene and pyrazole was tested for alpha‐amylase inhibition and show a high efficacy in nanoscale range of reactivity. The key interaction between the most active hybrids and the receptor was studied by molecular docking. The physiochemical properties of the designed spirooxindole‐pyrrolidines were carried out by in silico ADMET prediction. The newly synthesized most potent hybrid could be considered as a lead compound for drug discovery development for type 2 diabetes mellitus (T2DM).
Distressing testing: A propensity score analysis of high‐stakes exam failure and mental health
Authors: Beck Kathryn Christine , Røhr Helene Lie , Reme Bjørn‐Atle , Flatø Martin 
Published: August 2023

AbstractThis study used rich individual‐level registry data covering the entire Norwegian population to identify students aged 17–21 who either failed a high‐stakes exit exam or who received the lowest passing grade from 2006 to 2018. Propensity score matching on high‐quality observed characteristics was utilized to allow meaningful comparisons (N = 18,052, 64% boys). Results showed a 21% increase in odds of receiving a psychological diagnosis among students who failed the exam. Adolescents were at 57% reduced odds of graduating and 44% reduction in odds of enrolling in tertiary education 5 years following the exam. Results suggest that failing a high‐stakes exam is associated with mental health issues and therefore may impact adolescents more broadly than captured in educational outcomes.
A variant in the LDL receptor‐related protein encoding gene LRP4 underlying polydactyly and phalangeal synostosis in a family of Pakistani origin
Authors: Khan Hammal , Ullah Kifayat , Jan Abid , Ali Hamid , Ullah Imran , Ahmad Wasim 
Published: August 2023

AbstractA family of Pakistani origin, segregating polydactyly, and phalangeal synostosis in an autosomal dominant manner, has been investigated and presented in the present report. Whole‐exome sequencing (WES), followed by segregation analysis using Sanger sequencing, revealed a heterozygous missense variant [c.G1696A, p.(Gly566Ser)] in the LRP4 gene located on human chromosome 11p11.2. Homology protein modeling revealed the mutant Ser566 generated new interactions with at least four other amino acids and disrupted protein folding and function. Our findings demonstrated the first direct evidence of involvement of LRP4 in causing polydactyly and phalangeal synostosis in the same family. This study highlighted the importance of inclusion of LRP4 gene in screening individuals presenting polydactyly in hands and feet, and phalangeal synostosis in the same family.
Quadratic‐Attraction Subdivision
Authors: Karčiauskas K. , Peters J. 
Published: August 2023

AbstractThe idea of improving multi‐sided piecewise polynomial surfaces, by explicitly prescribing their behavior at a central surface point, allows for decoupling shape finding from enforcing local smoothness constraints. Quadratic‐Attraction Subdivision determines the completion of a quadratic expansion at the central point to attract a differentiable subdivision surface towards bounded curvature, with good shape also in‐the‐large.
A Shape Modulus for Fractal Geometry Generation
Authors: Schor A.L. , Kim Theodore 
Published: August 2023

AbstractWe present an efficient new method for computing Mandelbrot‐like fractals (Julia sets) that approximate a user‐defined shape. Our algorithm is orders of magnitude faster than previous methods, as it entirely sidesteps the need for a time‐consuming numerical optimization. It is also more robust, succeeding on shapes where previous approaches failed. The key to our approach is a versor‐modulus analysis of fractals that allows us to formulate a novel shape modulus function that directly controls the broad shape of a Julia set, while keeping fine‐grained fractal details intact. Our formulation contains flexible artistic controls that allow users to seamlessly add fractal detail to desired spatial regions, while transitioning back to the original shape in others. No previous approach allows Mandelbrot‐like details to be “painted” onto meshes.
Poisson Manifold Reconstruction — Beyond Co‐dimension One
Authors: Kohlbrenner M. , Lee S. , Alexa M. , Kazhdan M. 
Published: August 2023

AbstractScreened Poisson Surface Reconstruction creates 2D surfaces from sets of oriented points in 3D (and can be extended to co‐dimension one surfaces in arbitrary dimensions). In this work we generalize the technique to manifolds of co‐dimension larger than one. The reconstruction problem consists of finding a vector‐valued function whose zero set approximates the input points. We argue that the right extension of screened Poisson Surface Reconstruction is based on exterior products: the orientation of the point samples is encoded as the exterior product of the local normal frame. The goal is to find a set of scalar functions such that the exterior product of their gradients matches the exterior products prescribed by the input points. We show that this setup reduces to the standard formulation for co‐dimension 1, and leads to more challenging multi‐quadratic optimization problems in higher co‐dimension. We explicitly treat the case of co‐dimension 2, i.e., curves in 3D and 2D surfaces in 4D. We show that the resulting bi‐quadratic problem can be relaxed to a set of quadratic problems in two variables and that the solution can be made effective and efficient by leveraging a hierarchical approach.
Cross‐Shape Attention for Part Segmentation of 3D Point Clouds
Authors: Loizou Marios , Garg Siddhant , Petrov Dmitry , Averkiou Melinos , Kalogerakis Evangelos 
Published: August 2023

AbstractWe present a deep learning method that propagates point‐wise feature representations across shapes within a collection for the purpose of 3D shape segmentation. We propose a cross‐shape attention mechanism to enable interactions between a shape's point‐wise features and those of other shapes. The mechanism assesses both the degree of interaction between points and also mediates feature propagation across shapes, improving the accuracy and consistency of the resulting point‐wise feature representations for shape segmentation. Our method also proposes a shape retrieval measure to select suitable shapes for cross‐shape attention operations for each test shape. Our experiments demonstrate that our approach yields state‐of‐the‐art results in the popular PartNet dataset.
Factored Neural Representation for Scene Understanding
Authors: Wong Yu‐Shiang , Mitra Niloy J. 
Published: August 2023

AbstractA long‐standing goal in scene understanding is to obtain interpretable and editable representations that can be directly constructed from a raw monocular RGB‐D video, without requiring specialized hardware setup or priors. The problem is significantly more challenging in the presence of multiple moving and/or deforming objects. Traditional methods have approached the setup with a mix of simplifications, scene priors, pretrained templates, or known deformation models. The advent of neural representations, especially neural implicit representations and radiance fields, opens the possibility of end‐to‐end optimization to collectively capture geometry, appearance, and object motion. However, current approaches produce global scene encoding, assume multiview capture with limited or no motion in the scenes, and do not facilitate easy manipulation beyond novel view synthesis. In this work, we introduce a factored neural scene representation that can directly be learned from a monocular RGB‐D video to produce object‐level neural presentations with an explicit encoding of object movement(e.g., rigid trajectory)and/or deformations(e.g., nonrigid movement). We evaluate ours against a set of neural approaches on both synthetic and real data to demonstrate that the representation is efficient, interpretable, and editable(e.g., change object trajectory).Code and data are available at:http://geometry.cs.ucl.ac.uk/projects/2023/factorednerf/.
3D Keypoint Estimation Using Implicit Representation Learning
Authors: Zhu Xiangyu , Du Dong , Huang Haibin , Ma Chongyang , Han Xiaoguang 
Published: August 2023

AbstractIn this paper, we tackle the challenging problem of 3D keypoint estimation of general objects using a novel implicit representation. Previous works have demonstrated promising results for keypoint prediction through direct coordinate regression or heatmap‐based inference. However, these methods are commonly studied for specific subjects, such as human bodies and faces, which possess fixed keypoint structures. They also suffer in several practical scenarios where explicit or complete geometry is not given, including images and partial point clouds. Inspired by the recent success of advanced implicit representation in reconstruction tasks, we explore the idea of using an implicit field to represent keypoints. Specifically, our key idea is employing spheres to represent 3D keypoints, thereby enabling the learnability of the corresponding signed distance field. Explicit key‐points can be extracted subsequently by our algorithm based on the Hough transform. Quantitative and qualitative evaluations also show the superiority of our representation in terms of prediction accuracy.
MAP2K1‐mutated melanocytic tumors have reproducible histopathologic features and share similarities with melanocytic tumors with BRAFV600E mutations
Authors: Alomari Ahmed K. , Harms Paul W. , Andea Aleodor A. , Warren Simon J. 
Published: August 2023

AbstractBackgroundMelanocytic tumors driven by MAP2K1 in‐frame deletions are among the most recently described class of melanocytic neoplasms. The reported range of diagnoses and associated genomic aberrations in these neoplasms is wide and includes melanomas, deep penetrating melanocytomas, and pigmented epithelioid melanocytoma. However, little is known about the characteristics of these tumors, especially in the absence of well‐known second molecular “hits.” Moreover, despite their frequent spitzoid cytomorphology, their potential categorization among the Spitz tumors is debatable.Materials and MethodsWe conducted a retrospective search through our molecular archives to identify sequenced melanocytic tumors with MAP2K1 in‐frame deletions. We reviewed the clinical and histomorphological features of these tumors and compared them to similar neoplasms reported to date. In addition, we performed single‐nucleotide polymorphism (SNP) array testing to identify structural chromosomal aberrations.ResultsOf 27 sequenced tumors, 6 (22%) showed a pathogenic MAP2K1 in‐frame deletion (with or without insertion) and were included in this series. Five (83%) were females with lesions involving the upper limb. Histopathologically, all neoplasms were compounded with plaque‐like or wedge‐shaped silhouettes, spitzoid cytomorphology, and impaired cytologic maturation. All cases showed background actinic damage with sclerotic stroma replacing solar elastosis, variable pagetoid scatter, and occasional dermal mitotic figures (range 1–2/mm2). Five cases (83%) had a small component of nevic‐looking melanocytes. Biologically, these tumors likely fall within the spectrum of unusual nevi. Five cases (83%) had a relatively high mutational burden and four (67%) showed an ultraviolet radiation signature. Four cases (67%) showed in‐frame deletion involving the p.I103_K104del locus while two cases (33%) showed in‐frame deletion involving the p.Q58_E62del locus. SNP array testing showed structural abnormalities ranging from 1 to 5 per case. Five of these cases showed a gain of chromosome 15 spanning the MAP2K1 gene locus.Discussion and ConclusionMelanocytic tumors with MAP2K1 in‐frame deletion could represent another spectrum of melanocytic tumors with close genotypic–phenotypic correlation. They are largely characterized by a spectrum that encompasses desmoplastic Spitz nevus as shown in our series and Spitz and Clark nevus as shown by others. Evolutionary, they share many similarities with tumors with BRAF V600E mutations, suggesting they are better classified along the conventional pathway rather than the Spitz pathway despite the frequent spitzoid morphology.
Publications on the diagnostic accuracy of dermatopathology tests: A cross‐sectional quality analysis
Authors: Knez Nora , Kroflin Karla , Fraga Garth R. 
Published: August 2023

AbstractBackgroundAncillary diagnostic tests are frequent in dermatopathology practice. Publications on their accuracy influence their utilization. The transparency and completeness of these publications are unknown.MethodsWe performed a cross‐sectional study on diagnostic accuracy studies in dermatopathology published between 2020 and 2022 for compliance with Standards for Reporting of Diagnostic Accuracy Studies (STARD) and the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS‐2).Results14.67 ± 3.02 STARD items were reported in 62 publications (range, 9.5–23.5 out of the recommended total of 30). More items were reported in high‐impact factor journals (16.01 vs. 13.32, p = 0.0002) and journals that endorsed STARD in their author instructions (17.22 vs. 14.11, p = 0.0039). Less than 10% of publications reported quantifiable hypotheses, sample size calculations, flow diagrams, or study registrations. The risk of bias by our analysis of QUADAS‐2 criteria was high or uncertain for index test interpretation (36/62, 58%) and patient selection (44/62, 71%).ConclusionsPublications on dermatopathology tests are exploratory studies without prespecified hypotheses or study designs. They do not meet the criteria for transparent reporting. We suggest that medical journal leadership should consider updating their instructions with more explicit guidance on recommended manuscript elements.
Nodular amyloidosis presenting like a primary scarring alopecia
Authors: Gulotta Anthony P. , Collins Joshua M. , England Janessa R. , Lew Jeffrey L. , Lee Christine M. 
Published: August 2023

AbstractNodular amyloidosis (NA) is a rare type of primary localized cutaneous amyloidosis in which light chain amyloid deposits in the skin without concurrent systemic involvement. We report a challenging case of NA on the scalp, mimicking primary scarring alopecia, in a relatively young and healthy 36‐year‐old man. In addition to a nonspecific clinical appearance with a broad differential, NA can be a difficult diagnosis because it may require ancillary testing, such as liquid chromatography–tandem mass spectrometry to type the amyloid protein, and hematology–oncology workup to exclude systemic disease. Pathologists can highlight the importance of systemic evaluation in their reports to ensure patients receive appropriate management.
Post‐initiation predictors of discontinuation of the sodium‐glucose cotransporter‐2 inhibitors: A comparative cohort study from the United Kingdom
Authors: Alkabbani Wajd , Shah Baiju R. , Zongo Arsène , Eurich Dean T. , Alsabbagh Mhd Wasem , Gamble John‐Michael 
Published: August 2023

AbstractAimsTo assess post‐initiation predictors of discontinuation of sodium‐glucose cotransporter‐2 (SGLT2) inhibitors compared to dipeptidyl‐peptidase‐4 (DPP‐4) inhibitors in the United Kingdom.Materials and MethodsWe conducted a comparative population‐based retrospective cohort study using primary care data from the UK Clinical Practice Research Datalink (CPRD) with linked data to hospital and death records. We included new metformin users who initiated either SGLT2 inhibitors or DPP‐4 inhibitors between January 2013 and October 2019. The main outcome was treatment discontinuation, defined as the first 90‐day gap after the estimated treatment end date. We used a series of extended Cox models to assess which time‐dependent predictors were associated with treatment discontinuation. To test if the hazard ratio of discontinuation for each predictor was statistically different between SGLT2 and DPP‐4 inhibitors, an exposure‐predictor interaction term was added to each model.ResultsThere were 2550 new users of SGLT2 inhibitors and 8195 new users of DPP‐4 inhibitors. Approximately 69% of SGLT2 inhibitor and 74% of DPP‐4 inhibitor users had discontinued treatment by the end of follow‐up. Occurrence of fractures after treatment initiation was a significant predictor of discontinuation of SGLT2 inhibitors (hazard ratio [HR] 4.13, 95% confidence interval [CI] 2.12‐8.06) but not DPP‐4 inhibitors (HR 0.93, 95% CI 0.79‐1.11). The rate of treatment discontinuation was significantly higher for those with low estimated glomerular filtration rate and minimal contact with the healthcare system. Efficacy endpoints, such as heart failure and glycated haemoglobin level, were not associated with treatment discontinuation.ConclusionsOur findings reflect some discrepancy between the available evidence and prescribing behaviour for SGLT2 inhibitors.
Assessing and developing critical‐thinking skills in higher education
Authors: Van Damme Dirk , Zahner Doris , Cortellini Olivia , Dawber Teresa , Rotholz Kelly 
Published: August 2023

AbstractGeneric skills such as critical thinking, problem solving, and communication are essential for students' success in higher education and their careers. This article presents findings from an international study of students' (n ≈ 120,000) generic skills from six countries using a performance‐based assessment. Results indicate that higher education students, on average, gain generic skills between entry and exit. However, learning gain is less marked than could be expected and varies significantly among country samples. Various background variables such as gender, ethnicity, parental level of education, and primary language are also explored. The authors conclude that it is feasible to reliably and validly measure generic skills in a cross‐cultural context and that assessment of these skills is an essential component of best practices in higher education.
Valuing adolescent students' street smarts to foster critical thinking
Authors: Davies Maree , Xie Yan , Girard Patrick 
Published: August 2023

AbstractThe New Zealand Ministry of Education has included an increase in the expectations of critical thinking for secondary students across curricula. However, New Zealand has a history of inequitable opportunities for minority students to learn critical thinking. This article presents a framework designed for adolescent learners to make critical thinking equitable and accessible through valuing student experiences or Street Smarts. A mixed methods study trialled the critical thinking talk model Street Smarts. There were 33 teacher participants and 824 student participants (average age 15 years). Students identified ethnically as New Zealand European (46.1%), 17.1% as Asian, 10.6% as Pasifika, 5.2% as Māori, and 4.3% as other; and as undisclosed ethnicity (16.7%). Descriptive statistics of all the critical thinking indicators showed that Providing a statement of evidence was the most frequently observed indicator in both 2018 and 2019, followed by Building points and Uptake questions. The deeper cognitive features of High‐level questioning, Recognising power structures in society and developing Situated awareness were observed in classes with high academic ability and far less so in several classes of mixed academic ability and low academic ability. However, where teachers had allowed the opportunity for students identified in the low academic ability group to share their stories and experiences of the controversy, these students demonstrated deeper cognitive features in their discussions. We conclude that more time and opportunity should be given to adolescent students, particularly minority students and students in low ability classes, to share their narratives and stories before discussing controversial topics.