bluuebunny/crossref_metadata_2025 huggingface dataset:
Study of the mechanisms of change in hydride phases in zirconium beryllide during its linear heating
Authors: Kulsartov Timur , Zaurbekova Zhanna , Kenzhin Yergazy , Kenzhina Inesh , Bochkov Vadim , Askerbekov Saulet , Ponkratov Yuriy , Yelishenkov Alexandr , Udartsev Sergey
Published: October 2024

Beryllides have a number of unique properties that make them promising for use in various fields of industry and energy. Since some of the beryllides have the potential to dissolve large amounts of hydrogen (in some cases forming hydride phases), there is some interest in evaluating their possible applications in hydrogen technologies. This paper presents the results of studies of changes in the phase composition of the zirconium beryllide deuteride compound during its linear heating. The studies were carried out using a complex method including thermal gravimetrical analysis (TGA), differential scanning calorimetry (DSC) and mass spectrometry. Based on the results of the experiments, a number of parameters were obtained characterizing the transitions of deuteride from the phase of the Orthorhombic I

mma
crystal structure of deuteride ZrBe2D into the Orthorhombic C

mcm
crystal structure of deuteride ZrBe2D0.67, as well as the decomposition parameters of Orthorhombic C

mcm
crystal structure of ZrBe2D0.67. The energies of endothermic reactions of the corresponding transitions and decompositions of deuteride phases were estimated, and the activation energy of the interaction of water vapor with the surface of zirconium beryllide samples was also estimated.
The effect of complex extra-furnace treatment of metal melts on the formation of non-metallic inclusions in large-sized ingots
Authors: Issagulov Aristotel , Kovalev Pavel , Melnik Sergey , Kulikov Vitaliy , Kvon Svetlana , Arinova Saniya
Published: October 2024

The article presents the results of studying non-metallic inclusions (NI) after extra-furnace treatment of the 13Cr9Mo2Co1NiVNbNB steel melt to produce large-sized ingots. The objects of the study were laboratory samples (the first batch), and samples obtained after melting in industrial furnace, followed by modification and double vacuuming (the second batch). Previously, using the Fact Sage software, modeling of the NI formation processes was carried out. The data were obtained on the possible NI composition and amount in this steel. The composition, the contamination index, parameters of NI in samples have been studied. It was established that in the samples of the first batch, the main part of the NI consisted of chromium- and manganese-containing oxides, which occupy more than 94% of the total area of the NI. In the samples of the second batch, the main part of the NI was represented by aluminum containing systems. It was shown that the average size of NI in the samples after extra-furnace treatment differs slightly (5%–12%), however, the contamination index in industrial samples after vacuum treatment and especially after modification and repeated vacuum treatment was reduced by more than 10 times. The results obtained allow to recommend vacuum treatment and complex modification with calcium and boron as measures to prevent the formation of NI and to improve metallurgical quality when smelting large ingots using complex alloy steels.
Spring water discharge and metal enrichment in urban soils
Authors: Mullins Angela R , Bain Daniel J
Published: October 2024

Urban centers have inherited a unique mix of persistent contamination that impacts interactions among urban soil and groundwater systems. In particular, the potential for urban groundwater to transport contaminants from surface sources through the subsurface environment and ultimately to soils is not well understood. Studies have focused on specific ‘natural’ mechanisms driving distribution of metals in urban soils. However, very few studies have examined the accumulation of contamination in soils at groundwater discharge locations (springs) and the potential for groundwater to redistribute urban legacy contaminants far from the source. Soil transects straddling four groundwater springs in Pittsburgh, Pennsylvania were sampled to evaluate patterns resulting from contaminated groundwater discharge on urban soils. Metal concentrations were measured in pore water and compared with concentrations observed in total digestions and exchangeable extractions (acetic acid) of the soil. Across the springs Co, Cr, Ni, and V (metals often used in steel alloys) were elevated downslope, suggesting contaminated groundwater discharge enriches trace metals in these locations. These processes create unexpected biogeochemical patterns on the landscape and have the potential to create hotspots of soil metal contamination at predictable points across the urban landscape.
Heat impacts on an aging society: a spatio-temporal analysis of heatstroke deaths in Japan
Authors: Zeng Ming , Baptista Emerson Augusto , Kakinuma Kaoru
Published: October 2024

Climate change, especially through heatwaves, significantly affects human health and is a growing global concern. Concurrently, population aging is occurring worldwide, with many countries experiencing an increase in their elderly populations. As the elderly are particularly susceptible to extreme temperatures and unevenly distributed due to internal migration of younger populations, a spatio-temporal analysis integrating temperature changes and demographic data is essential. This study focuses on Japan, a super-aged society where over 25% of the total population is 65 years or older. We examined the effects of climate and the proportion of the elderly population on heatstroke deaths through spatio-temporal analysis within a Bayesian framework. We estimated the annual relative risk of heatstroke-related deaths at the prefecture level from 2008 to 2019. The results indicate a strong spatial autocorrelation in heatstroke deaths across Japan. The spatio-temporal interaction model was the best-performing, showing that regional and temporal variations significantly impact heatstroke mortality. In this model, a one-degree increase in temperature anomaly was linked to a 0.35 (95% CI 0.25 to 0.46) times higher odds of heatstroke deaths, while a 1% increase in the population aged 65 years or older was associated with 4.85 (95% CI 0.92 to 8.65) times higher odds. We found that not only metropolitan areas but also rural areas, such as the Tohoku and Shikoku regions, face a high risk of heatstroke, emphasizing the need to address the challenges in rural communities. Our study highlights the necessity of integrating temperature changes and demographic data in a spatio-temporal context for heatstroke risk assessment. It demonstrates the profound effects of temperature anomalies and the proportion of the elderly population on heatstroke mortality. This research framework could be applicable to other countries experiencing aging and heatwave issues, aiding in the development of targeted public health interventions.
6G networks for the operating room of the future
Authors: Jurosch Franziska , Kröger Nicolai , Kolb Sven , Mehmeti Fidan , Martens Eimo , Speidel Stefanie , Kellerer Wolfgang , Wilhelm Dirk , Fuchtmann Jonas
Published: October 2024

Technical setups in today’s operating rooms (ORs) are becoming increasingly complex, especially with the integration of applications which rely on the fusion of multiple information sources. While manufacturers have already started to make use of such approaches, the quest for fully integrated ORs becoming standard is still ongoing. We describe a variety of state-of-the-art projects that envision an OR of the future in order to identify missing building blocks. While these initial implementations of sensor fused ORs have shown to be promising, all current proposals lack a scalable networking backbone that serves the needs of future applications. We therefore discuss how the coming 6G standard’s envisioned advancements can provide a flexible and intelligent platform to enable the fully integrated OR of the future.
Risk assessment of transmission towers based on variable weight theory and matter-element extension model
Authors: Gao Haihang , Wang Minzhen , Wang Zhigang , Zhang Jiyao , Zheng Yu , Zhang Qi
Published: October 2024

The risk assessment of transmission towers is a critical approach to ensuring the safe and stable operation of power grids. In response to the increasingly frequent and severe impacts of seasonal permafrost on transmission towers in permafrost regions, this paper proposes a novel risk assessment method based on Variable Weight Theory and the Matter-Element Extension Model. By incorporating key influencing factors—such as the number of freeze–thaw cycles, soil moisture content, temperature fluctuations, soil dry density, melting settlement coefficient, and porosity ratio—an indicator system tailored to risk assessment in seasonal permafrost regions is established. Utilizing the Matter-Element Extension Model, this approach applies Variable Weight Theory to integrate both the best-worst method and the entropy weight method for calculating subjective and objective indicator weights. The risk level of the towers is then determined by their proximity to risk thresholds. Finally, a case study involving transmission towers in a specific region of a province in China is presented, where the assessment results are compared with the actual conditions to validate the rationality and effectiveness of the proposed method.
Cooperating with the Courts
Authors: Newbery Samantha
Published: October 2024

This chapter’s account of supergrasses and assisting offenders demonstrates that arrest is not always the end of a terrorist informer’s contribution to counter-terrorism. They can take on a new role after arrest by providing evidence that can help support court cases. Their provision of evidence through the supergrass system in use in Northern Ireland in the 1980s proved tricky, as many of the convictions obtained this way were later overturned. More recent attempts, in the form of ‘assisting offenders’ provided for by the Serious Organised Crime and Police Act (SOCPA) 2005, look more promising. The best-known examples of supergrasses are Raymond Gilmour of the IRA and INLA and Christopher Black of the IRA, both of whom are examined in this chapter, as is the best-known example of an assisting offender, Gary Haggarty of the UVF.
The Murder of Patrick Finucane
Authors: Newbery Samantha
Published: October 2024

Chapter 11 evaluates the range of types of investigation that have so far been held into the murder of solicitor Patrick Finucane and the involvement of informers and, therefore, the involvement of the security and intelligence agencies in that murder. This chapter adopts a chronological approach, analysing the role of intelligence relative to other factors that explain the decisions made regarding investigations. Although far from the only factor influencing decisions made by campaigners and government, the role of informers and the intelligence they provided runs throughout these decisions. The chapter addresses the murder investigation and the de Silva Review, as well as the views of the Finucane family, successive governments, and the courts, on whether there should be a public inquiry.
Behavioral and Psychosocial Dynamics in Diabetes Management: A Path Analysis to Examine the Influence of Acculturation in Arab Immigrant Communities
Authors: Alzubaidi Hamzah , Oliveira Vitor H , Saidawi Ward , Aljobowry Raya , Shaw Jonathan E , Samorinha Catarina
Published: October 2024

Background

Type 2 diabetes mellitus (T2DM) prevalence is rising globally. Arab immigrants with T2DM, one of the least studied ethnic minorities, have a higher diabetes prevalence and more prominent management-related challenges compared with mainstream host societies. Acculturation’s impact on self-care activities and diabetes distress (DD) is understudied globally.

Purpose

To examine how acculturation affects self-care practices and DD in first-generation Arab immigrants with T2DM and how health literacy, illness perceptions, and self-efficacy mediate these associations.

Methods

This multicenter cross-sectional study was conducted in Victoria, Australia. Eligible patients were invited while waiting for their appointments. The questionnaire included validated tools to assess DD, self-care activities, health literacy, self-efficacy, and acculturation. We tested mediation hypothesis using path analysis, with a maximum likelihood estimation to calculate total, direct, and indirect effects and bias-corrected accelerated 95% CI.

Results

Overall, 382 Arab immigrants with T2DM participated, with an average age of 57.9 years (SD = 8.0). Half were males, most had low education, and were married. Participants lived in Australia for a mean of 19.1 years (SD = 8.3) and had diabetes for 7.1 years (SD =4.7). Higher acculturation was directly associated with decreased DD. Illness perceptions (p = .002) and self-efficacy (p = .001) mediated the association of acculturation with self-care activities, while health literacy did not. Additionally, self-efficacy fully mediated the relationship between acculturation and DD (p = .001).

Conclusions

This research provided valuable insights into the complex interplay between acculturation, diabetes management, and psychosocial factors. Interventions targeting self-efficacy and illness perceptions may improve self-care activities and reduce DD among Arab immigrants with T2DM.
Halophytic succulence is a driver of the leaf non-structural carbohydrate contents in plants in the arid and hyper-arid deserts of northwestern China
Authors: Wang Lilong , Li Yuqiang , Wang Xuyang , Duan Yulong , Zheng Chengzhuo
Published: October 2024

Background and Aims

Non-structural carbohydrates (NSC), primarily sugars and starch, play a crucial role in plant metabolic processes and the ability of a plant to tolerate and recover from drought stress. Despite their importance, our understanding of NSC characteristics in the leaves of plants that thrive in hyper-arid and saline environments remains limited.

Methods

To investigate the variations in leaf NSC across different species and spatial scales and to explore their possible causes, we collected 488 leaf samples from 49 native plant species at 115 sites in the desert area of northwestern China. The contents of soluble sugars (SS), starch and total NSC were then determined.

Key Results

The average contents of SS, starch and total NSC were 26.99, 60.28 and 87.27 mg g−1, respectively, which are much lower than those reported for Chinese forest plants and global terrestrial plants. Herbaceous and woody plants had similar NSC levels. In contrast, succulent halophytes, a key component of desert flora, showed significantly lower leaf SS and total NSC contents than non-succulent plants. We observed a strong negative correlation between leaf succulence and SS content, suggesting a role of halophytic succulence in driving multispecies NSC pools. Environmental factors explained a minor portion of the spatial variation in leaf NSC, possibly owing to the narrow climatic variation in the study area, and soil properties, particularly soil salinity, emerged as more significant contributors.

Conclusions

Our findings increase the understanding of plant adaptation to drought and salt stress, emphasizing the crucial role of halophytic succulence in shaping the intricate dynamics of leaf NSC across diverse plant species in arid and hyper-arid environments.
Ecology, Pathology, and the Life of Paper
Authors: Gagné John
Published: October 2024

This essay charts the way that ideas of nature, life and disease generated new approaches to Europe’s documentary culture between roughly 1650 and 1950. Training its focus on the medium of paper, specifically the essay, reveals conceptual intersections between caretakers of libraries and archives and naturalists or physicians whose focus was the entomology or bacteriology. The recognition of the fundamentally organic nature of books (animal, vegetable, mineral, in a Linnaean sense) invited fresh vocabularies and practices of care and preservation. The essay first explores how book lovers—often encouraged by learned societies or state agencies in the eighteenth century—campaigned against insects whose habitat lay between the covers of precious tomes. It then traces how nineteenth-century microscopy and bacteriology informed notions of sickness or ‘pathology’ in books. It ends by describing the efforts to remediate these impairments in the twentieth century: to deploy chemistry and medicine as therapies for bringing imperilled papers back to health.
MetaDegron: multimodal feature-integrated protein language model for predicting E3 ligase targeted degrons
Authors: Zheng Mengqiu , Lin Shaofeng , Chen Kunqi , Hu Ruifeng , Wang Liming , Zhao Zhongming , Xu Haodong
Published: October 2024

Protein degradation through the ubiquitin proteasome system at the spatial and temporal regulation is essential for many cellular processes. E3 ligases and degradation signals (degrons), the sequences they recognize in the target proteins, are key parts of the ubiquitin-mediated proteolysis, and their interactions determine the degradation specificity and maintain cellular homeostasis. To date, only a limited number of targeted degron instances have been identified, and their properties are not yet fully characterized. To tackle on this challenge, here we develop a novel deep-learning framework, namely MetaDegron, for predicting E3 ligase targeted degron by integrating the protein language model and comprehensive featurization strategies. Through extensive evaluations using benchmark datasets and comparison with existing method, such as Degpred, we demonstrate the superior performance of MetaDegron. Among functional features, MetaDegron allows batch prediction of targeted degrons of 21 E3 ligases, and provides functional annotations and visualization of multiple degron-related structural and physicochemical features. MetaDegron is freely available at http://modinfor.com/MetaDegron/. We anticipate that MetaDegron will serve as a useful tool for the clinical and translational community to elucidate the mechanisms of regulation of protein homeostasis, cancer research, and drug development.
Biologically-informed killer cell immunoglobulin-like receptor gene annotation tool
Authors: Ford Michael K B , Hari Ananth , Zhou Qinghui , Numanagić Ibrahim , Sahinalp S Cenk
Published: October 2024

Natural killer (NK) cells are essential components of the innate immune system, with their activity significantly regulated by Killer cell Immunoglobulin-like Receptors (KIRs). The diversity and structural complexity of KIR genes present significant challenges for accurate genotyping, essential for understanding NK cell functions and their implications in health and disease. Traditional genotyping methods struggle with the variable nature of KIR genes, leading to inaccuracies that can impede immunogenetic research. These challenges extend to high-quality phased assemblies, which have been recently popularized by the Human Pangenome Consortium. This article introduces BAKIR (Biologically informed Annotator for KIR locus), a tailored computational tool designed to overcome the challenges of KIR genotyping and annotation on high-quality, phased genome assemblies. BAKIR aims to enhance the accuracy of KIR gene annotations by structuring its annotation pipeline around identifying key functional mutations, thereby improving the identification and subsequent relevance of gene and allele calls. It uses a multi-stage mapping, alignment, and variant calling process to ensure high-precision gene and allele identification, while also maintaining high recall for sequences that are significantly mutated or truncated relative to the known allele database. BAKIR has been evaluated on a subset of the HPRC assemblies, where BAKIR was able to improve many of the associated annotations and call novel variants. BAKIR is freely available on GitHub, offering ease of access and use through multiple installation methods, including pip, conda, and singularity container, and is equipped with a user-friendly command-line interface, thereby promoting its adoption in the scientific community.

Availability and implementation

BAKIR is available at github.com/algo-cancer/bakir
OpenDock: a pytorch-based open-source framework for protein–ligand docking and modelling
Authors: Hu Qiuyue , Wang Zechen , Meng Jintao , Li Weifeng , Guo Jingjing , Mu Yuguang , Wang Sheng , Zheng Liangzhen , Wei Yanjie
Published: October 2024

Motivation

Molecular docking is an invaluable computational tool with broad applications in computer-aided drug design and enzyme engineering. However, current molecular docking tools are typically implemented in languages such as C++ for calculation speed, which lack flexibility and user-friendliness for further development. Moreover, validating the effectiveness of external scoring functions for molecular docking and screening within these frameworks is challenging, and implementing more efficient sampling strategies is not straightforward.

Results

To address these limitations, we have developed an open-source molecular docking framework, OpenDock, based on Python and PyTorch. This framework supports the integration of multiple scoring functions; some can be utilized during molecular docking and pose optimization, while others can be used for post-processing scoring. In terms of sampling, the current version of this framework supports simulated annealing and Monte Carlo optimization. Additionally, it can be extended to include methods such as genetic algorithms and particle swarm optimization for sampling docking poses and protein side chain orientations. Distance constraints are also implemented to enable covalent docking, restricted docking or distance map constraints guided pose sampling. Overall, this framework serves as a valuable tool in drug design and enzyme engineering, offering significant flexibility for most protein–ligand modelling tasks.

Availability and implementation

OpenDock is publicly available at: https://github.com/guyuehuo/opendock.
BIMSA: accelerating long sequence alignment using processing-in-memory
Authors: Alonso-Marín Alejandro , Fernandez Ivan , Aguado-Puig Quim , Gómez-Luna Juan , Marco-Sola Santiago , Mutlu Onur , Moreto Miquel
Published: October 2024

Motivation

Recent advances in sequencing technologies have stressed the critical role of sequence analysis algorithms and tools in genomics and healthcare research. In particular, sequence alignment is a fundamental building block in many sequence analysis pipelines and is frequently a performance bottleneck both in terms of execution time and memory usage. Classical sequence alignment algorithms are based on dynamic programming and often require quadratic time and memory with respect to the sequence length. As a result, classical sequence alignment algorithms fail to scale with increasing sequence lengths and quickly become memory-bound due to data-movement penalties.

Results

Processing-In-Memory (PIM) is an emerging architectural paradigm that seeks to accelerate memory-bound algorithms by bringing computation closer to the data to mitigate data-movement penalties. This work presents BIMSA (Bidirectional In-Memory Sequence Alignment), a PIM design and implementation for the state-of-the-art sequence alignment algorithm BiWFA (Bidirectional Wavefront Alignment), incorporating new hardware-aware optimizations for a production-ready PIM architecture (UPMEM). BIMSA supports aligning sequences up to 100K bases, exceeding the limitations of state-of-the-art PIM implementations. First, BIMSA achieves speedups up to 22.24× (11.95× on average) compared to state-of-the-art PIM-enabled implementations of sequence alignment algorithms. Second, achieves speedups up to 5.84× (2.83× on average) compared to the highest-performance multicore CPU implementation of BiWFA. Third, BIMSA exhibits linear scalability with the number of compute units in memory, enabling further performance improvements with upcoming PIM architectures equipped with more compute units and achieving speedups up to 9.56× (4.7× on average).

Availability and implementation

Code and documentation are publicly available at https://github.com/AlejandroAMarin/BIMSA.
PONYTA: prioritization of phenotype-related genes from mouse KO events using PU learning on a biological network
Authors: Kim Jun Hyeong , Koo Bonil , Kim Sun
Published: October 2024

Motivation

Transcriptome data from gene knock-out (KO) experiments in mice provide crucial insights into the intricate interactions between genotype and phenotype. Differentially expressed gene (DEG) analysis and network propagation (NP) are well-established methods for analysing transcriptome data. To determine genes related to phenotype changes from a KO experiment, we need to choose a cutoff value for the corresponding criterion based on the specific method. Using a rigorous cutoff value for DEG analysis and NP is likely to select mostly positive genes related to the phenotype, but many will be rejected as false negatives. On the other hand, using a loose cutoff value for either method is prone to include a number of genes that are not phenotype-related, which are false positives. Thus, the research problem at hand is how to deal with the trade-off between false negatives and false positives.

Results

We propose a novel framework called PONYTA for gene prioritization via positive-unlabeled (PU) learning on biological networks. Beginning with the selection of true phenotype-related genes using a rigorous cutoff value for DEG analysis and NP, we address the issue of handling false negatives by rescuing them through PU learning. Evaluations on transcriptome data from multiple studies show that our approach has superior gene prioritization ability compared to benchmark models. Therefore, PONYTA effectively prioritizes genes related to phenotypes derived from gene KO events and guides in vitro and in vivo gene KO experiments for increased efficiency.

Availability and implementation

The source code of PONYTA is available at https://github.com/Jun-Hyeong-Kim/PONYTA.
Heterogeneity-aware integrative regression for ancestry-specific association studies
Authors: Molstad Aaron J , Cai Yanwei , Reiner Alexander P , Kooperberg Charles , Sun Wei , Hsu Li
Published: October 2024

Ancestry-specific proteome-wide association studies (PWAS) based on genetically predicted protein expression can reveal complex disease etiology specific to certain ancestral groups. These studies require ancestry-specific models for protein expression as a function of SNP genotypes. In order to improve protein expression prediction in ancestral populations historically underrepresented in genomic studies, we propose a new penalized maximum likelihood estimator for fitting ancestry-specific joint protein quantitative trait loci models. Our estimator borrows information across ancestral groups, while simultaneously allowing for heterogeneous error variances and regression coefficients. We propose an alternative parameterization of our model that makes the objective function convex and the penalty scale invariant. To improve computational efficiency, we propose an approximate version of our method and study its theoretical properties. Our method provides a substantial improvement in protein expression prediction accuracy in individuals of African ancestry, and in a downstream PWAS analysis, leads to the discovery of multiple associations between protein expression and blood lipid traits in the African ancestry population.
Functional generalized canonical correlation analysis for studying multiple longitudinal variables
Authors: Sort Lucas , Le Brusquet Laurent , Tenenhaus Arthur
Published: October 2024

In this paper, we introduce functional generalized canonical correlation analysis, a new framework for exploring associations between multiple random processes observed jointly. The framework is based on the multiblock regularized generalized canonical correlation analysis framework. It is robust to sparsely and irregularly observed data, making it applicable in many settings. We establish the monotonic property of the solving procedure and introduce a Bayesian approach for estimating canonical components. We propose an extension of the framework that allows the integration of a univariate or multivariate response into the analysis, paving the way for predictive applications. We evaluate the method’s efficiency in simulation studies and present a use case on a longitudinal dataset.
Case-crossover designs and overdispersion with application to air pollution epidemiology
Authors: Perreault Samuel , Dong Gracia Y , Stringer Alex , Shin Hwashin , Brown Patrick E
Published: October 2024

Over the last three decades, case-crossover designs have found many applications in health sciences, especially in air pollution epidemiology. They are typically used, in combination with partial likelihood techniques, to define a conditional logistic model for the responses, usually health outcomes, conditional on the exposures. Despite the fact that conditional logistic models have been shown equivalent, in typical air pollution epidemiology setups, to specific instances of the well-known Poisson time series model, it is often claimed that they cannot allow for overdispersion. This paper clarifies the relationship between case-crossover designs, the models that ensue from their use, and overdispersion. In particular, we propose to relax the assumption of independence between individuals traditionally made in case-crossover analyses, in order to explicitly introduce overdispersion in the conditional logistic model. As we show, the resulting overdispersed conditional logistic model coincides with the overdispersed, conditional Poisson model, in the sense that their likelihoods are simple re-expressions of one another. We further provide the technical details of a Bayesian implementation of the proposed case-crossover model, which we use to demonstrate, by means of a large simulation study, that standard case-crossover models can lead to dramatically underestimated coverage probabilities, while the proposed models do not. We also perform an illustrative analysis of the association between air pollution and morbidity in Toronto, Canada, which shows that the proposed models are more robust than standard ones to outliers such as those associated with public holidays.
Primary cutaneous T-cell lymphoma not otherwise specified reveals a novel RAB27A variant in Griscelli syndrome type 2
Authors: Blanchard Gabriela , Atallah Isis , Blanchard Maël , Fehrenbacher Birgit , Schaller Martin , Riccio Orbicia , Ballerini Claudia , Candotti Fabio , Guenova Emmanuella
Published: October 2024

Griscelli syndrome type 2 (GS2) is a rare, autosomal recessive disorder that typically emerges during childhood. It manifests with partial albinism, silvery hair, immunodeficiency and haemophagocytic lymphohistiocytosis predisposition (HLH). Our findings suggest that lymphoproliferative disorders, including cutaneous lymphomas, should be considered part of the dermatological spectrum of GS2. While GS2 has previously been diagnosed in adults presenting with HLH, our observations indicate that HLH is not an inevitable outcome, even in patients who survive into their fifth decade of life.
Recovering nested structures in networks: an evaluation of hierarchical clustering techniques
Authors: Gera Imre , London András
Published: October 2024

In this article, we present various algorithms to partition the nodes of a network into groups that show the property of nestedness. Since perfect nestedness is a rare phenomenon, we consider the task from a data mining perspective, and we search for groups having high-level of nestedness. We utilize both agglomerative and divisive hierarchical clustering procedures and compare them on several benchmark and real-life networks. Furthermore, we propose different metrics derived from the results of our algorithms. We show that average-linkage and complete-linkage clustering can recover the largest fully nested clusters, and that the cluster size-weighted mean nestedness was a more stable metric for measuring clustering performance. Our proposed algorithms allow us to create multiple resolution views of nestedness-based clustering of networks, extending the field of graph-based data mining.
Michael Wirth’s Kunstbüchlein: Books of Arts and Weapons Magic in a Sorcery Trial from Seventeenth-Century Germany
Authors: Rowlands Alison
Published: October 2024

How did men and magical objects interact in the early modern period, and with what consequences? This article seeks to answer these questions through a close reading of the trial for sorcery of an urban artisan named Michael Wirth, who was accused in 1663 of murdering his neighbour by magical means. The article foregrounds the role that Wirth’s Kunstbüchlein (books of arts) played in his practice of magic (in his case, a type of weapons magic aimed at ensuring his accuracy in musket-shooting) and in his acquisition of a reputation for malevolent sorcery in the eyes of some of his neighbours. In so doing, it analyses the competing claims made by different trial protagonists about Wirth’s relationship with, and use of, his books of arts, and explores how the books themselves participated in these meaning-making processes. The article furthers our understanding of the practice of weapons magic and the use of books of arts by urban artisans in the seventeenth century. It also contributes to ongoing debates about the gendering and material culture of magic in early modern Germany, and about the agency of human and non-human actors in networks of social practices.
Reducing Ageism and Ableism With Brief Videos Providing Education About Aging and Disabilities and Exposure to Positive Intergenerational Contact
Authors: Monahan Caitlin , Levy Sheri R , Lytle Ashley
Published: October 2024

Background and Objectives

Older adults living with a disability (LWD) face both ageism and ableism, but there are few interventions to address this significant and growing social problem.

Research Design and Methods

Drawing on the Positive Education about Aging and Contact Experiences model, 3 online studies involved participants randomly assigned to watch 4 brief online videos providing education about aging and disability and exposure to positive contact between younger adults and older adults/older adults LWD (experimental condition) or videos about interior design (control condition). Studies 1 (community sample) and 2 (university sample) included an immediate posttest whereas Study 3 (2 university samples) additionally included a pretest and delayed posttest.

Results

Experimental condition (vs control) participants reported greater agreement with older adults LWD as contributors to society (immediate posttest in Studies 1 and 2; immediate and delayed posttest in Study 3), lesser (greater) endorsement of negative (positive) stereotypes of older adults and older adults LWD, lesser agreement with older adults LWD as burdensome, lesser intergenerational tension with older adults (immediate posttest in Study 2; immediate and delayed posttest in Study 3), and greater openness to careers working with older adults and older adults LWD (immediate and delayed posttest in Study 3).

Discussion and Implications

Brief online interventions that involve education about aging and disabilities as well as exposure to positive intergenerational contact can be an effective means of reducing ableism and ageism toward older adults and older adults LWD.
(Re)constructing global health security and universal health coverage: norm contestation and interaction
Authors: Lal Arush , Parkhurst Justin , Wenham Clare
Published: October 2024

To effectively tackle public health challenges, policy-makers increasingly advocate for aligning global health security (GHS) and universal health coverage (UHC), two influential norms driving international health cooperation. However, despite operating within overlapping spheres of governance, the normative histories linking GHS and UHC remain relatively unexplored in the literature. This article examines how GHS and UHC have been (re)constructed—from distinct policy sectors to synergistic norm regimes—through repeated contestation and interaction. Utilizing the ‘norm life-cycle’ framework to trace development across three stages (emergence, tipping-point/cascade and internalization), this study discursively analyses key texts from major crises and international agreements spanning several decades to unpack how norms and their underlying discourses and core functions have influenced each other as they evolved. The findings illustrate that GHS and UHC norms would be better understood as dynamic ‘processes’ rather than static concepts. The article concludes that GHS and UHC norms have shaped each other more significantly than previous scholarship suggests, characterizing them as continuously evolving, closely interlinked and increasingly integrated. This work contributes not only to the broader scholarship on international norms theory, but also offers pragmatic implications for navigating normative development where multiple norms compete for influence amid ever-shifting priorities.
Hitting the High-dimensional notes: an ODE for SGD learning dynamics on GLMs and multi-index models
Authors: Collins-Woodfin Elizabeth , Paquette Courtney , Paquette Elliot , Seroussi Inbar
Published: October 2024

We analyze the dynamics of streaming stochastic gradient descent (SGD) in the high-dimensional limit when applied to generalized linear models and multi-index models (e.g. logistic regression, phase retrieval) with general data-covariance. In particular, we demonstrate a deterministic equivalent of SGD in the form of a system of ordinary differential equations that describes a wide class of statistics, such as the risk and other measures of sub-optimality. This equivalence holds with overwhelming probability when the model parameter count grows proportionally to the number of data. This framework allows us to obtain learning rate thresholds for the stability of SGD as well as convergence guarantees. In addition to the deterministic equivalent, we introduce an SDE with a simplified diffusion coefficient (homogenized SGD), which allows us to analyze the dynamics of general statistics of SGD iterates. Finally, we illustrate this theory on some standard examples and show numerical simulations, which give an excellent match to the theory.
Randomized phase III study comparing re-irradiation stereotactic body radiotherapy and conventional radiotherapy for painful spinal metastases: Japan Clinical Oncology Group study JCOG2211 (RESCORE study)
Authors: Kita Ryosuke , Ito Kei , Machida Ryunosuke , Sekino Yuta , Nakamura Naoki , Nakajima Yujiro , Saito Tetsuo , Imano Nobuki , Fukuda Haruhiko , Ito Yoshinori , Mizowaki Takashi ,   Japan Clinical Oncology Group Radiation Therapy Study Group
Published: October 2024

Bone metastases are often associated with pain and can occur in various types of cancer, significantly affecting patients’ quality of life. Despite the high response rates to initial conventional radiotherapy in patients with painful spinal metastases, recurrence and inadequate response still occur. Thus, the development of a highly effective strategy for pain recurrence is crucial to improving the quality of life in patients with advanced metastatic cancer. This randomized phase III trial aims to confirm the superiority of re-irradiation with stereotactic body radiotherapy (24 Gy in 2 fractions) over conventional radiotherapy (8 Gy in a single fraction) in achieving a complete pain response at 12 weeks in patients with previously irradiated painful spinal metastases. A total of 158 patients from 33 hospitals will be enrolled in Japan over 3.5 years. This trial has been registered in the Japan Registry of Clinical Trials as jRCTs1030240172 (https://jrct.niph.go.jp/latest-detail/jRCT1030240172).
Basophils induce protumorigenic cytokines from A549 lung adenocarcinoma via mechanisms requiring IgE, galectin-3, and IL-3 priming
Authors: Schroeder John T , Ehrlich Laurent , Bieneman Anja P
Published: October 2024

Galectin-3 (Gal-3) is implicated in innate immune cell activation in a host of diseases/conditions. We identified a unique response whereby human basophils secrete interleukin (IL)-4/IL-13 when cocultured with A549 cells—lung adenocarcinoma. While displaying parameters consistent with standard IgE-dependent activation, these Gal-3–dependent responses occurred in the absence of specific IgE/allergens and required cell-to-cell contact. We now hypothesize that this mode of activation also impacts A549 function. Our findings show that cytokines are induced in basophil/A549 cocultures that are not detected when either cell is cultured alone, in particular IL-6. As previously shown for IL-4/IL-13, IL-6 production also required cell-to-cell contact and was dependent on A549-Gal-3, as clones deficient of this lectin induced less cytokine. Using culture-derived basophils (CDBAs), we demonstrate that the IL-6 response and production of another tumorigenic factor, vascular endothelial growth factor A (VEGF-A), are induced in CDBA/A549 cocultures but only after passively sensitizing CDBAs with IgE, in a manner similar to IL-4/IL-13. However, IgE-dependent activation of basophils/CDBAs cultured alone failed to induce IL-6/VEGF. Importantly, IL-3–primed basophils, even those fixed with paraformaldehyde, readily induced IL-6/VEGF-A in cocultures, thus verifying that these cytokines are derived from A549. Overall, these results suggest a complex mechanism whereby Gal-3/IgE interactions between IL-3–primed basophils and A549 have the potential to modulate cytokine production by both cells. With Gal-3 implicated not only in many diseases ranging from asthma to cancer, but also in normal physiological conditions, such as wound healing, these findings are predicted to provide insight into the molecular mechanisms by which this lectin (and IgE) functions in these processes.
The WEIRD Trio: The Cultural Gap between Physicians, Learners, and Patients in Pluralistic Societies
Authors: Liao Lester
Published: October 2024

Physicians are shaped by sociological and philosophical factors that often differ from those of their patients. This is of particular concern in pluralistic societies when navigating ethical disagreements because physicians often misunderstand or even dismiss patient perspectives as being irrational. This paper examines these factors and why many physicians approach ethics as they do while elucidating various patient perspectives and demonstrating how they make sense when considered from a different cultural worldview. Many physicians are trained in contexts that are WEIRD: Western, educated, industrialized, rich, and democratic. These sociological characteristics tend to go hand in hand with the trio of individualism, secularism, and existentialism. These then shape an approach to ethics that focuses on the individual patient, makes no reference to the divine, and focuses on a patient’s personal desires. This contrasts significantly with many patients who are collectivistic or religious, and then make rational decisions based on other values. The social fact of pluralism implores physicians to temper confidence in their own cultures while considering others to promote mutual understanding and improved care. This paper concludes with a discussion of how bridges can be built across cultures without sliding into relativism, beginning with recognizing and communicating our shared moral intuitions.
Impact of chemotherapy on patients with mismatch repair deficient advanced endometrial carcinomas—a meta-analysis
Authors: Tjokrowidjaja Angelina , Kok Peey-Sei , Antill Yoland C , Scott Clare L , Mileshkin Linda R , Friedlander Michael L , Lee Chee K
Published: October 2024

Background

Chemo-immunotherapy is standard of care for women with recurrent or advanced mismatch repair deficient endometrial carcinoma. However, it is uncertain whether patients with mismatch repair deficient advanced or recurrent endometrial carcinoma derive less benefit from chemotherapy than those with mismatch repair proficient endometrial carcinoma.

Methods

We performed a meta-analysis of randomized controlled trials (RCTs) in advanced or recurrent endometrial carcinoma to determine the difference in the benefit of chemotherapy in mismatch repair deficient vs mismatch repair proficient endometrial carcinoma. Data on chemotherapy outcomes including objective response rate, progression-free survival (PFS), and overall survival were retrieved. We pooled these data using the inverse variance method and examined subgroup difference by mismatch repair status. We also compared differences in PFS and overall survival outcomes by creating individual patient data from the Kaplan–Meier curves of trial publications for sensitivity analyses.

Results

A total of 5 RCTs with 1137 participants (mismatch repair deficient, 26%; mismatch repair proficient, 74%) were included. All participants were treated with carboplatin-based chemotherapy. There was no difference between the mismatch repair deficient and mismatch repair proficient subgroups for objective response rate (66.5% vs 64.0%; P = .20 for subgroup difference), PFS (hazard ratio [HR] = 0.93, 95% confidence interval [CI] = 0.77 to 1.12; P = .44; median PFS = 7.6 vs 9.5 months) or overall survival (HR = 1.03, 95% CI = 0.73 to 1.44; P = .88; median overall survival = not reached vs 28.6 months).

Conclusions

Objective response rate, PFS, and overall survival were similar among those with mismatch repair deficient vs mismatch repair proficient endometrial cancer treated with front-line, platinum-doublet chemotherapy in RCTs. These findings reinforce the importance of combining chemotherapy together with immune checkpoint inhibitors until the results of trials comparing immune checkpoint therapy alone with combination therapy are available.
Rare finding of ectopic pancreas in a cholecystectomy specimen: case report and literature review
Authors: Baz Carolina , Nudotor Richard , Buseey Ian , Stitely Kevin
Published: October 2024

Ectopic pancreatic tissue (EPT) is a rare condition in which pancreatic tissue is situated outside its normal position. It is commonly found in the stomach and small bowel, typically asymptomatic, and is usually discovered incidentally during histopathological analysis. Although fewer than 40 cases of ectopic pancreatic tissue in the gallbladder have been reported, its significance relies on the risk of malignant transformation, highlighting the need for a thorough pathological study. This case report describes the presence of EPT in the gallbladder incidentally found during the pathological examination following a laparoscopic cholecystectomy of a 37-year-old female due to chronic cholecystitis.
A rare finding of pulmonary nodules in a middle ear neuroendocrine tumor: a case report and review of the literature
Authors: Alharbi Nader , Alotaibi Ghadah , Alabood Saleh , AlSulaiman Ibrahim , Bakry Essa
Published: October 2024

Neuroendocrine tumors (NETs) are usually found in the gastrointestinal tract and pancreas; however, they are rare in the middle ear. The presentation of vague symptoms, such as tinnitus and conductive hearing loss, complicates the diagnosis. We present a 46-year-old male with a history of right ear discharge and a previous canal wall-down mastoidectomy, suspected to have cholesteatoma recurrence. Imaging and surgery demonstrated a well-differentiated G1 NET in the middle ear. Postoperative metastatic workup revealed few pulmonary nodules needing ongoing observation. Middle-ear NETs are difficult to diagnose due to their rarity. This case underscores the importance of histological and immunohistochemical evaluation and the need for systemic assessment to rule out metastasis due to pulmonary nodules. We contribute to the limited literature highlighting the need to include NETs in the differential of middle ear masses and the usefulness of interdisciplinary teamwork.