bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation and Verification of High-Fidelity Simulations of Thoracic Stent-Graft Implantation
Authors: Ramella Anna , Migliavacca Francesco , Rodriguez Matas Jose Felix , Heim Frederic , Dedola Francesca , Marconi Stefania , Conti Michele , Allievi Sara , Mandigers Tim J. , Bissacco Daniele , Domanin Maurizio , Trimarchi Santi , Luraghi Giulia
Published: July 2022

Thoracic Endovascular Aortic Repair (TEVAR) is the preferred treatment option for thoracic aortic pathologies and consists of inserting a self-expandable stent-graft into the pathological region to restore the lumen. Computational models play a significant role in procedural planning and must be reliable. For this reason, in this work, high-fidelity Finite Element (FE) simulations are developed to model thoracic stent-grafts. Experimental crimp/release tests are performed to calibrate stent-grafts material parameters. Stent pre-stress is included in the stent-graft model. A new methodology for replicating device insertion and deployment with explicit FE simulations is proposed. To validate this simulation, the stent-graft is experimentally released into a 3D rigid aortic phantom with physiological anatomy and inspected in a computed tomography (CT) scan at different time points during deployment with an ad-hoc set-up. A verification analysis of the adopted modeling features compared to the literature is performed. With the proposed methodology the error with respect to the CT is on average 0.92 ± 0.64%, while it is higher when literature models are adopted (on average 4.77 ± 1.83%). The presented FE tool is versatile and customizable for different commercial devices and applicable to patient-specific analyses.
On queueing-inventory-location problems
Authors: Daduna Hans
Published: July 2022

A network of queueing-inventory systems is considered where the inventories are replenished by a common central server. Travel times for transport of the items send out from the center and an adaptive dispatching regime to direct transportation towards the locations with queueing-inventory systems are incorporated in the model. The stationary distribution of the system is of product form and is explicitly given. An optimization procedure is developed to find for given locations of the queueing-inventory systems an optimal location for the replenishment center. Optimization is with respect to overall utilization of the resources measured in total throughput of the queueing-inventory systems.
Using artificial intelligence algorithms to predict self-reported problem gambling with account-based player data in an online casino setting
Authors: Auer Michael , Griffiths Mark D.
Published: July 2022

In recent years researchers have emphasized the importance of artificial intelligence (AI) algorithms as a tool to detect problem gambling online. AI algorithms require a training dataset to learn the patterns of a prespecified group. Problem gambling screens are one method for the collection of the necessary input data to train AI algorithms. The present study’s main aim was to identify the most significant behavioral patterns which predict self-reported problem gambling. In order to fulfil the aim, the study analyzed data from a sample of real-world online casino players and matched their self-report (subjective) responses concerning problem gambling with the participants’ actual (objective) gambling behavior. More specifically, the authors were given access to the raw data of 1,287 players from a European online gambling casino who answered questions on the Problem Gambling Severity Index (PGSI) between September 2021 and February 2022. Random forest and gradient boost machine algorithms were trained to predict self-reported problem gambling based on the independent variables (e.g., wagering, depositing, gambling frequency). The random forest model predicted self-reported problem gambling better than gradient boost. Moreover, problem gamblers showed a distinct pattern with respect to their gambling based on the player tracking data. More specifically, problem gamblers lost more money per gambling day, lost more money per gambling session, and deposited money more frequently per gambling session. Problem gamblers also tended to deplete their gambling accounts more frequently compared to non-problem gamblers. A subgroup of problem gamblers identified as being at greater harm (based on their response to PGSI items) showed even higher values with respect to the aforementioned gambling behaviors. The study showed that self-reported problem gambling can be predicted by AI algorithms with high accuracy based on player tracking data.
Extreme Physiology Extreme Tolerance to Hypoxia, Hypercapnia, and Pain in the Naked Mole-Rat
Authors: Park Thomas J. , Reznick Jane
Published: July 2022

Challenging environmental conditions can drive the evolution of extreme physiological traits. The naked mole-rat has evolved to survive and thrive in a low oxygen, high carbon dioxide environment that would be deadly to humans and most other mammals. The naked mole-rat’s lifestyle is unusual in that this species combines subterranean living and living in large, social groups of up to 300 + individuals. Many respiring animals in a closed environment can lead to depletion of oxygen (hypoxia) and accumulation of carbon dioxide (hypercapnia). Naked mole-rats display a variety of physiological traits that negate the adverse effects of living in this atmosphere. For hypoxia tolerance, naked mole-rats have a low resting metabolism, high affinity hemoglobin, intrinsic brain tolerance, the ability to use fructose for anaerobic glycolysis, and the ability to enter a low energy, suspended animation-like state. For hypercapnia tolerance, these animals have a mutation in a voltage gated sodium channel that effectively eliminates neuronal responses to tissue acidosis. In other mammals, acidosis from exposure to high concentrations of carbon dioxide induces pain and pulmonary edema. Understanding these mechanisms of extreme physiology is not only inherently interesting, but it may lead to biomedical breakthroughs in research on heart attacks, strokes, and pain pathologies.
Shifting Power in Practice: The Importance of Contextual and Experiential Evidence in Guiding MCH Decision Making
Authors: Powis Laura , Ramirez Grace Guerrero , Krisowaty Lynda , Kaufman Benjamin
Published: July 2022

Background

Evidence is central to all maternal and child health (MCH) decision-making processes, continuously interacting with and influencing our work. There is a growing emphasis in MCH on using evidence-based approaches when addressing public health challenges, but the field lacks a unified understanding of what constitutes evidence. MCH must operate from an expansive understanding of evidence that centers community voice and acknowledges the role of evidence prioritization in achieving equitable population-level outcomes.

Call to Action

What we consider valid evidence has immense implications for MCH practice, including whose work is deemed worthy of funding and replication. The authors advocate for shifting the field’s evidence paradigm from being primarily focused on research findings to also recognize the importance of community-rooted evidence. Contextual and experiential evidence, alongside research evidence, should be considered for two purposes: (1) to support the effectiveness of a given practice generally, and (2) to support that the practice will work in specific contexts.

Putting this shift into practice requires explicit power shifting – the MCH workforce must cede power to those who have been historically barred from participating in and guiding research. To facilitate this, MCH professionals must build skills in communication, equitable leadership, and change management.

Conclusion

The MCH workforce should position communities to set their own priorities and define, develop, and disseminate evidence representative of their priorities. Evidence co-creation is key to establishing and sustaining transformative relationships between community members and Title V programs, shifting power structures to build upon existing community leadership and assets.
Disparity in refuge: the plight of international students seeking health and education in the midst of the Ukrainian war
Authors: Awuah Wireko Andrew , Mehta Aashna , Yarlagadda Rohan , Ng Jyi Cheng , Abdul-Rahman Toufik
Published: July 2022

None
Liberalism and (how to avoid) paternalism
Authors: Gutmann Thomas
Published: July 2022

This article first presents a rough sketch of the core dynamics of the anti-paternalist liberal tradition (from Kant to Dworkin) centered around the notion of normative individualism and protecting the conditions of autonomy as a set of individual rights expressive of one’s sovereignty over oneself. Historically, the liberal tradition starts with a strong anti-paternalist momentum (Part I). Part II demonstrates that, within the theory of paternalism, a distinction has to be drawn between “personal autonomy” designating a family of ideal, gradual, and hence at least moderately perfectionist conceptions about what an autonomous person is, on the one hand, and what Feinberg calls “autonomy as a right”, on the other. It is shown that the anti-paternalist liberal tradition focuses only on “autonomy as a right”. In Part III, the text analyzes the so-called “argument from justice”, which claims that paternalistic and anti-paternalistic policies do have distributive effects of their own and might be a matter of distributive fairness. It discusses several options for understanding this claim and its relevance and criticizes most autonomy-enhancing approaches for blending out the dialectics of protection and tutelage.
The Importance of Being Attentive to Social Processes in School Bullying Research: Adopting a Constructivist Grounded Theory Approach
Authors: Forsberg Camilla
Published: July 2022

School bullying is a complex social phenomenon in need of further exploration regarding its connections to contextual aspects, group norms, and societal structures. This calls for research approaches that can get closer to participants’ experiences and the different social processes involved in school bullying. One such approach is the constructivist grounded theory (CGT) approach, which aims to be attentive to participants’ main concerns and social processes through both analysis and data collection. This approach comes as a theory-method package with its use of a symbolic interactionism perspective. In this paper, I will show how CGT as a theory-method package, as well as symbolic interactionism and sociology of childhood, has been helpful in my research on school bullying (focusing on social structures, norms, and processes). More specifically, I give different examples from the whole research process, e.g., maintaining a focus on participants’ main concerns, the coding process, being guided by sensitizing concepts, addressing issues of social justice and equity — and overall forming and maintaining a theoretically and ethically prepared researcher role. I also suggest that this approach is helpful in dealing with ethical and theoretical challenges when researching topics known to negatively affect people’s lives and wellbeing — and when the social context makes it difficult for participants to address victimizing structures, positions, and processes.
Fluid properties impact on energy separation in Ranque–Hilsch vortex tube
Authors: Alsaghir Ahmad , Hamdan Mohammad O. , Orhan Mehmet F.
Published: July 2022

This paper examines the energy separation in vortex tubes which is a passive device that can split a pressurized room temperature gas stream to hot and cold streams. The paper employs numerical simulations to investigate the impact of various working fluids such as helium, air, oxygen, nitrogen, and carbon dioxide on the energy separation in the vortex tube, using the SST $$k{-}\omega$$

k
-
ω

turbulence model with viscous heating. A three-dimensional numerical investigation is sued to examine the effect of a single fluid property on vortex tube performance, while keeping the rest of the fluid properties unchanged, which is impossible to achieve via experimental study. The numerical investigation examines the influence of molecular weight, heat capacity, thermal conductivity, and dynamic viscosity on energy separation. The results show that energy separation performance improves with lower molecular weight and heat capacity, and higher dynamic viscosity of the working fluids, while no impact of the thermal conductivity is observed. Out of five gases tested in this study, helium has yielded the maximum temperature separation, while carbon dioxide has yielded the lowest performance. Results show that viscous dissipation contributes to the temperature separation in vortex tube.
The impact of bison reintroduction on local economies
Authors: Li Liqing , Ando Amy W.
Published: July 2022

Bison is an important and iconic mammal in the U.S. that is being reintroduced in many places after being driven nearly to extinction. This paper provides a nationwide assessment of the local economic impacts of bison reintroduction so that rural communities can take economic well-being into account when considering decisions regarding future bison restorations. We estimate the causal impacts of bison herd establishment on county-level income, employment, and population growth using staggered difference-in-difference and the synthetic control approaches. The simple positive correlation between local per capita income and bison herds might lead planners to think that bison reintroduction is good for the local economy. However, none of the causal inference analyses find statistically significant effects of bison reintroduction.
Emergency Response to a Hospital Fire: A Report From the Field
Authors: Jamshidbeigi Yousef , Mohammadi Sara , Sahebi Ali
Published: July 2022

As the most important centers providing medical services during disasters and emergencies, hospitals have special structural complexities. Furthermore, the hospitals are exposed to many intrinsic and extrinsic hazards, including fire. On November 28, 2018, at 9:25am(local time), a fire started in Ayatollah Taleghani Hospital of Ilam, affiliated with Ilam University of Medical Sciences, Iran. Immediately, to save patients’ lives and prevent injuries to them, the horizontal and then vertical evacuation was performed to transfer patients to other hospitals by helping the support organizations. No physical injuries or deaths were reported in this incident. The results of this case study showed that hospitals should be sufficiently prepared to respond effectively to accidents and disasters, so it is needed to prepare and practice response programs and train hospital staff and managers.
Methods for determining the characteristics of weathered granite reservoirs: application to Binxian Uplift, Dongying Sag, Bohai Bay Basin
Authors: Li Xiaoke , Chen Gang , Liang Shangzi
Published: July 2022

With the discovery of high-productivity oilfields in granite buried hills, it is necessary to systematically investigate the types of granite weathered reservoirs at different depths and their spatial distribution. However, previously subdivided reservoirs have been assumed to exhibit the same vertical zoning in different structural parts, contradicting the fact that the degree of weathering varies with the topography. In addition, comprehensive and quantitative methods for classifying reservoir types are lacking. Taking the Binxian Uplift of the Dongying depression in Bohai Bay Basin as an example, we therefore established a comprehensive identification standard for dividing granite reservoirs using lithology division, logging curve statistics, a dual-medium matrix–fracture model and seismic facies identification. Subsequently, by combining logging and seismic methods, the vertical stacking types and distribution properties of weathered granite reservoirs in various structural positions were analysed. The reservoirs were divided vertically into three zones: regolith, dissolution and fracture. Quantitative logging response standards for the different reservoirs were established using acoustic, density, natural gamma and resistivity logging. In terms of the seismic response, the regolith, dissolution and fracture zone corresponded to high-, medium- and low-amplitude seismic facies, respectively. A dynamic double-layer structure of the reservoir was established, comprising a completely weathered layer and a semi-weathered layer. The reservoir division method proposed in this paper can be used in other areas, and the research results can help promote the exploration of granite buried hill reservoirs.
Cross-Cultural Dialogue and the German Theatre in St Petersburg
Authors: Melnikova Svetlana
Published: July 2022

This article explores the history of the German theatre in St Petersburg in the eighteenth and nineteenth centuries, a subject forgotten for a hundred years due to historical reasons. Svetlana Melnikova uses cross-cultural research methods, which, as she has discovered, appeared in Russian criticism concerning the arts as early as the nineteenth century. The ideas of Russian scholars turned out to be concordant with modern findings in cross-cultural dialogue and comparative research methods, because the process of establishing Russian culture was influenced by earlier cultures in a variety of ways. The German diaspora in the capital of the Russian Empire at the turn of the nineteenth century, and the artistic qualities of the German theatre (the activities of its managers, the company, the repertoire, theatre buildings, as well as the target audience) described in this article, are here presented as the expressive elements of intercultural communication that provide theatre history with a sense of actuality. The author introduces unique archive materials from the Russian State Historical Archive, as well as from publications preserved in Russia-focused departments of major Russian and German libraries. Examining these materials, she reconstructs the history of this rare phenomenon in the context of the mutual influence between German and Russian theatres. Svetlana Melnikova is Professor of Art at the St Petersburg State University of Film and Television. She is the author of six books, including Kotzebue in Russia (2005), and ninety-six articles on the history, theory, and practice of theatre in Russian and German.
The Sense of an Ending: Contemporary Visions of Medea
Authors: Fisher Sorgenfrei Carol
Published: July 2022

The story of Medea’s murder of her own children to gain revenge against their faithless father has been tackled from many angles by playwrights and directors from Euripides’ time to the present. In recent years, due to highly sensationalized, real-life cases of mothers murdering their children, it has become fodder for sociologists, criminologists, psychologists, and feminists. Many recent productions (both original plays and directorial approaches to Euripides’ original) have avoided tackling the difficult questions raised by Euripides’ ending, which demands an answer to the following question: how could the gods send down a dragon-drawn chariot to rescue a woman who murdered her own children? Many contemporary authors and directors prefer to eliminate Euripides’ ending in order to focus on more immediate issues, such as the psychological or social damage resulting from patriarchy, colonialism, and misogyny. After considering several such productions, this article analyzes three plays that directly tackle Euripides’ troubling ending: two original scripts, by Heiner Müller and Carol Fisher Sorgenfrei respectively; and a production of Euripides’ original by Japanese director Miyagi Satoshi. Carol Fisher Sorgenfrei is Professor Emerita of Theatre at UCLA. An expert on postwar Japanese and cross-cultural performance, she is also a translator, director, and playwright. The author of Unspeakable Acts: The Avant-Garde Theatre of Terayama Shūji and Postwar Japan (University of Hawaii Press, 2005) and co-author of Theatre Histories: An Introduction (third edition, Routledge, 2016), she has published over a hundred articles, chapters, and reviews. She is an Associate Editor of Asian Theatre Journal and a Fellow of the College of Fellows of the American Theatre.
New Amateurs and Tricksters: A manifesto for music and sound creation
Authors: Fox Simon
Published: July 2022

This article considers some of the potential advantages that creators without formal training – Barthes’s ‘amateurs’ – have employed in collaborative processes to make sound art and also considers ways in which the approach may open fresh forms of social engagement. Drawing on the author’s collaborative practice in sound creation, Maria Lind’s classification of types of collaboration is extended to develop the notion of a ‘quadruple’ variant. This is based on the relationship between human and non-human collaborators. The role of the ‘Trickster’ is developed as a means of supporting and facilitating amateurs operating in a radical context. I propose, and provide a manifesto for, a category of the ‘New Amateur’ who addresses social engagement in sound practices in at least two ways. First, via structural dependence on a notion of collaboration significantly expanded to include not only other humans but also materials, ideas and both non- and post-human entities. Second, by drawing upon the anarchist ethics and concepts of the Trickster to democratise artistic potential through collaborative and distributed authorship. Thus, the manifesto reflects a political dimension rooted in the everyday and reveals a route to social engagement via personal creative awakening. The New Amateur offers fresh possibilities in music and organised sound and engages via an unleashing of individual capability to mirror the ‘lines of flight’ pursued by John Cage, La Monte Young and Alan Kaprow. The mechanism initiated in this way locates individual creativity in the context of mutual aid. Social engagement is driven by individual creativity and the explosive awareness of the potential this awakens.
Cratering Experiments on Granular Targets With a Variety of Particle Sizes: Implications for Craters on Rubble‐Pile Asteroids
Authors: Yasui M. , Arakawa M. , Okawa H. , Hasegawa S.
Published: July 2022

We performed cratering experiments on targets composed of glass beads with a power‐law size distribution that simulated the surface of rubble‐pile asteroids, and we improved the previously studied reduction factor on the crater size scaling relationship including the armoring effect using the momentum transfer efficiency. Cratering experiments were conducted using light gas guns at Kobe University and ISAS/JAXA to control the impact velocity, , from 50 to 4,400 m s−1. Two kinds of mixed targets were prepared by mixing glass beads with diameters of 0.1, 1, 3, and 10 mm—one with the smallest diameter beads, and one without. The size ratio of the target bead to the projectile (diameter of 1–3 mm), , changed from 0.03 to 10. The crater size scaling relationships for the mixed targets were found to depend on the first contacted bead size. Notably, first contact with a 10 mm‐sized bead reduced the crater radius by 35% in maximum. The reduction factor due to this armoring effect on the crater size scaling relationship is written as follows: ; it decreased with the increase of the size ratio of the target bead to the projectile, while it increased with the increase of the impact velocity and approached unity. Our improved crater size scaling relationship that includes the reduction factor could be used to reconstruct the crater size frequency distribution on rubble‐pile asteroids such as Ryugu, and it may lead to a revision of the crater chronology of asteroids.
Observational Evidence for Multivariate Drought Hazard Amplifications Across Disparate Climate Regimes
Authors: Ganguli Poulomi , Majhi Avijit , Kumar Rohini
Published: July 2022

Drought poses significant challenges to global water security in a warming world. A global‐scale synthesis of the multivariate drought risk considering interdependencies between drought attributes across disparate climate regimes is still lacking. Leveraging precipitation and streamflow observations of 270 large catchments over the globe, we show that multivariate drought hazard amplifies significantly (at ∼65–76% of catchments) considering dependence between drought duration and severity. A signifying nature of this amplification (A) is the power‐law scaling with dependence metric ( where τ and λ are Kendall's correlation and the scaling exponent), revealing current approaches considering drought attributes as independent or linearly dependent will severely underestimate likelihood of extreme droughts. Furthermore, we find disparate responses in the multivariate imprints of meteorological to hydrological droughts across climate types, with strengths varying from large to modest in Tropics and Mid‐latitudes, which indicates weaker overlap between rain‐deficit and streamflow droughts. In contrast, a strong overlap in multivariate hazards of rain‐deficit and streamflow droughts is apparent across transitional Subtropics. Our study highlights the relevance of accounting for multivariate aspects of drought hazards to inform adaptation to water scarcity in a changing climate.
Wildfire Smoke Demonstrates Significant and Predictable Black Carbon Light Absorption Enhancements
Authors: Lee James E. , Gorkowski Kyle , Meyer Aaron G. , Benedict Katherine B. , Aiken Allison C. , Dubey Manvendra K.
Published: July 2022

Black carbon (BC) is estimated to have the second largest anthropogenic radiative forcing in earth‐systems models (ESMs), but there is significant uncertainty in its impact due to complex mixing with organics. Laboratory‐generated particles show that co‐mixed non‐absorbing material enhances absorption by BC by a factor of 2–3.5 as predicted by optical models. However, weak or no enhancements are often reported for field studies. The cause of lower‐than‐expected absorption is not well understood and implies a lower radiative impact of BC compared to how many ESMs currently treat aerosols. By analyzing BC aerosol particle‐by‐particle we reconcile observed and expected absorption for ambient smoke plumes varying in geographic origin, fuel types, burn conditions, atmospheric age and transport. Although particle‐by‐particle tracking is computationally prohibitive for sophisticated ESMs we show that realistic BC absorption is reliably estimated by bulk properties of the plume providing a suitable parameterization to constrain black carbon radiative forcing.
Thermophysical and Compositional Properties of Paleobedforms on Mars
Authors: Weintraub Aaron Robert , Edwards Christopher Scott , Chojnacki Matthew , Edgar Lauren A. , Fenton Lori K. , Piqueux Sylvain , Gullikson Amber L.
Published: July 2022

Bedforms on Earth and Mars are often preserved in the rock record in the form of sedimentary rock with distinct cross‐bedding. On rare occasions, the full‐surface geometry of a bedform can be preserved through burial and lithification. These features, known as paleobedforms, are found in a variety of geographic locations on Mars. Evidence in the morphology of paleobedforms, such as the retention of impact craters and steep erosional scarps, suggests that these features are well‐lithified and capable of withstanding prolonged weathering and erosion. Here, we present results from thermophysical and compositional analyses on a subset of the best preserved paleobedform candidate fields on Mars. Thermophysical modeling elucidates the changes these bedforms underwent from their unconsolidated, particulate nature to their currently observed properties. Certain paleobedforms have elevated thermal inertias (e.g., ∼300–500 J·m−2·s−1/2·K−1) when compared with modern bedforms (∼250 J·m−2·s−1/2·K−1), and modeling indicates that they have cement volumes of 0.8%–1.5% even as high as 30%. However, most paleobedform candidates have unexpectedly low thermal inertia when compared with modern dunes. Additionally, compositional analyses reveal a range of spectral characteristics within paleobedforms (e.g., primary and secondary alteration products). These features add to the already existing class of Martian surfaces in which thermal inertia does not seem to correspond to erodibility, cohesion, or mechanical strength. Studying paleobedforms with both raised and nonraised thermal inertia has provided new insights into lithification on Mars and constrained the environmental conditions leading to the formation of these enigmatic features.
Single-cell multiomics analysis reveals regulatory programs in clear cell renal cell carcinoma
Authors: Long Zhilin , Sun Chengfang , Tang Min , Wang Yin , Ma Jiayan , Yu Jichuan , Wei Jingchao , Ma Jianzhu , Wang Bohan , Xie Qi , Wen Jiaming
Published: July 2022

The clear cell renal cell carcinoma (ccRCC) microenvironment consists of many different cell types and structural components that play critical roles in cancer progression and drug resistance, but the cellular architecture and underlying gene regulatory features of ccRCC have not been fully characterized. Here, we applied single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) to generate transcriptional and epigenomic landscapes of ccRCC. We identified tumor cell-specific regulatory programs mediated by four key transcription factors (TFs) (HOXC5, VENTX, ISL1, and OTP), and these TFs have prognostic significance in The Cancer Genome Atlas (TCGA) database. Targeting these TFs via short hairpin RNAs (shRNAs) or small molecule inhibitors decreased tumor cell proliferation. We next performed an integrative analysis of chromatin accessibility and gene expression for CD8+ T cells and macrophages to reveal the different regulatory elements in their subgroups. Furthermore, we delineated the intercellular communications mediated by ligand–receptor interactions within the tumor microenvironment. Taken together, our multiomics approach further clarifies the cellular heterogeneity of ccRCC and identifies potential therapeutic targets.
Multifocal organoids reveal clonal associations between synchronous intestinal tumors with pervasive heterogeneous drug responses
Authors: Jeong Nahyun , Kim Soon-Chan , Park Ji Won , Park Seul Gi , Nam Ki-Hoan , Lee Ja Oh , Shin Young-Kyoung , Bae Jeong Mo , Jeong Seung-Yong , Kim Min Jung , Ku Ja-Lok
Published: July 2022

Multifocal colorectal cancer (CRC) comprises both clonally independent primary tumors caused by inherited predisposition and clonally related tumors mainly due to intraluminal spreading along an intact basement membrane. The distinction between these multifocal CRCs is essential because therapeutic strategies vary according to the clonal association of multiple tumor masses. Here, we report one unique case of synchronous intestinal cancer (SIC) with tumors occurring along the entire bowel tract, including the small intestine. We established six patient-derived organoids (PDOs), and patient-derived cell lines (PDCs) from each site of the SIC, which were subjected to extensive genomic, transcriptomic, and epigenomic sequencing. We also estimated the drug responses of each multifocal SIC to 25 clinically relevant therapeutic compounds to validate how the clinically actionable alternations between SICs were associated with drug sensitivity. Our data demonstrated distinct clonal associations across different organs, which were consistently supported by multi-omics analysis, as well as the accordant responses to various therapeutic compounds. Our results indicated the imminent drawback of a single tumor-based diagnosis of multifocal CRC and suggested the necessity of an in-depth molecular analysis of all tumor regions to avoid unexpected resistance to the currently available targeted therapies.
High sensitivity and broad linearity range pressure sensor based on hierarchical in-situ filling porous structure
Authors: Xu Jin , Li Huayang , Yin Yiming , Li Xin , Cao Jinwei , Feng Hanfang , Bao Wandi , Tan Hao , Xiao Fanyuan , Zhu Guang
Published: July 2022

Flexible piezoresistive pressure sensor with high sensitivity over a broad linearity range have been attracting tremendous attention for its applications in health monitoring, artificial intelligence, and human-machine interfaces. Herein, we report a hierarchical in-situ filling porous piezoresistive sensor (HPPS) by direct ink writing (DIW) printing and curing of carbon nanofibers (CNFs)/polydimethylsiloxane (PDMS) emulsion. Hierarchical geometry significantly increases the contact area, distributes stress to multilayered lattice and internal porous structure, resulting in a broad sensing range. Moreover, unlike conventional hollow porous structure, the CNFs networks in-situ filling porous structure generates more contact sites and conductive pathways during compression, thereby achieving high sensitivity and linearity over entire sensing range. Therefore, the optimized HPPS achieves high sensitivity (4.7 kPa−1) and linearity (coefficient of determination, R2 = 0.998) over a broad range (0.03–1000 kPa), together with remarkable response time and repeatability. Furthermore, the applications in diverse pressure scenarios and healthcare monitoring are demonstrated.
LRRK2 kinase activity regulates GCase level and enzymatic activity differently depending on cell type in Parkinson’s disease
Authors: Kedariti Maria , Frattini Emanuele , Baden Pascale , Cogo Susanna , Civiero Laura , Ziviani Elena , Zilio Gianluca , Bertoli Federico , Aureli Massimo , Kaganovich Alice , Cookson Mark R. , Stefanis Leonidas , Surface Matthew , Deleidi Michela , Di Fonzo Alessio , Alcalay Roy N. , Rideout Hardy , Greggio Elisa , Plotegher Nicoletta
Published: July 2022

Leucine-rich repeat kinase 2 (LRRK2) is a kinase involved in different cellular functions, including autophagy, endolysosomal pathways, and immune function. Mutations in LRRK2 cause autosomal-dominant forms of Parkinson’s disease (PD). Heterozygous mutations in GBA1, the gene encoding the lysosomal enzyme glucocerebrosidase (GCase), are the most common genetic risk factors for PD. Moreover, GCase function is altered in idiopathic PD and in other genetic forms of the disease. Recent work suggests that LRRK2 kinase activity can regulate GCase function. However, both a positive and a negative correlation have been described. To gain insights into the impact of LRRK2 on GCase, we performed a comprehensive analysis of GCase levels and activity in complementary LRRK2 models, including (i) LRRK2 G2019S knock in (GSKI) mice, (ii) peripheral blood mononuclear cell (PBMCs), plasma, and fibroblasts from PD patients carrying LRRK2 G2019S mutation, (iii) patient iPSCs-derived neurons; (iv) endogenous and overexpressed cell models. In some of these models we found a positive correlation between the activities of LRRK2 and GCase, which was further confirmed in cell lines with genetic and pharmacological manipulation of LRRK2 kinase activity. GCase protein level is reduced in GSKI brain tissues and in G2019S iPSCs-derived neurons, but increased in fibroblasts and PBMCs from patients, suggesting cell-type-specific effects. Overall, our study indicates that LRRK2 kinase activity affects both the levels and the catalytic activity of GCase in a cell-type-specific manner, with important implications in the context of therapeutic application of LRRK2 inhibitors in GBA1-linked and idiopathic PD.
Archaic chaperone–usher pili self-secrete into superelastic zigzag springs
Authors: Pakharukova Natalia , Malmi Henri , Tuittila Minna , Dahlberg Tobias , Ghosal Debnath , Chang Yi-Wei , Myint Si Lhyam , Paavilainen Sari , Knight Stefan David , Lamminmäki Urpo , Uhlin Bernt Eric , Andersson Magnus , Jensen Grant , Zavialov Anton V.
Published: July 2022

Adhesive pili assembled through the chaperone–usher pathway are hair-like appendages that mediate host tissue colonization and biofilm formation of Gram-negative bacteria1–3. Archaic chaperone–usher pathway pili, the most diverse and widespread chaperone–usher pathway adhesins, are promising vaccine and drug targets owing to their prevalence in the most troublesome multidrug-resistant pathogens1,4,5. However, their architecture and assembly–secretion process remain unknown. Here, we present the cryo-electron microscopy structure of the prototypical archaic Csu pilus that mediates biofilm formation of Acinetobacter baumannii—a notorious multidrug-resistant nosocomial pathogen. In contrast to the thick helical tubes of the classical type 1 and P pili, archaic pili assemble into an ultrathin zigzag architecture secured by an elegant clinch mechanism. The molecular clinch provides the pilus with high mechanical stability as well as superelasticity, a property observed for the first time, to our knowledge, in biomolecules, while enabling a more economical and faster pilus production. Furthermore, we demonstrate that clinch formation at the cell surface drives pilus secretion through the outer membrane. These findings suggest that clinch-formation inhibitors might represent a new strategy to fight multidrug-resistant bacterial infections.
Conditioned media of pancreatic cancer cells and pancreatic stellate cells induce myeloid-derived suppressor cells differentiation and lymphocytes suppression
Authors: Chong Yuen Ping , Peter Evelyn Priya , Lee Feon Jia Ming , Chan Chu Mun , Chai Shereen , Ling Lorni Poh Chou , Tan Eng Lai , Ng Sook Han , Masamune Atsushi , Ghafar Siti Aisyah Abd , Ismail Norsharina , Ho Ket Li
Published: July 2022

As pancreatic cancer cells (PCCs) and pancreatic stellate cells (PSCs) are the two major cell types that comprise the immunosuppressive tumor microenvironment of pancreatic cancer, we aimed to investigate the role of conditioned medium derived from PCCs and PSCs co-culture on the viability of lymphocytes. The conditioned medium (CM) collected from PCCs and/or PSCs was used to treat peripheral blood mononuclear cells (PBMCs) to determine CM ability in reducing lymphocytes population. A proteomic analysis has been done on the CM to investigate the differentially expressed protein (DEP) expressed by two PCC lines established from different stages of tumor. Subsequently, we investigated if the reduction of lymphocytes was directly caused by CM or indirectly via CM-induced MDSCs. This was achieved by isolating lymphocyte subtypes and treating them with CM and CM-induced MDSCs. Both PCCs and PSCs were important in suppressing lymphocytes, and the PCCs derived from a metastatic tumor appeared to have a stronger suppressive effect than the PCCs derived from a primary tumor. According to the proteomic profiles of CM, 416 secreted proteins were detected, and 13 DEPs were identified between PANC10.05 and SW1990. However, CM was found unable to reduce lymphocytes viability through a direct pathway. In contrast, CM that contains proteins secreted by PCC and/or PSC appear immunogenic as they increase the viability of lymphocytes subtypes. Lymphocyte subtype treated with CM-induced MDSCs showed reduced viability in T helper 1 (Th1), T helper 2 (Th2), and T regulatory (Treg) cells, but not in CD8+ T cells, and B cells. As a conclusion, the interplay between PCCs and PSCs is important as their co-culture displays a different trend in lymphocytes suppression, hence, their co-culture should be included in future studies to better mimic the tumor microenvironment.
A systematic review of healthcare provider-targeted mobile applications for non-communicable diseases in low- and middle-income countries
Authors: Geldsetzer Pascal , Flores Sergio , Wang Grace , Flores Blanca , Rogers Abu Bakarr , Bunker Aditi , Chang Andrew Y. , Tisdale Rebecca
Published: July 2022

Mobile health (mHealth) interventions hold promise for addressing the epidemic of noncommunicable diseases (NCDs) in low- and middle-income countries (LMICs) by assisting healthcare providers managing these disorders in low-resource settings. We aimed to systematically identify and assess provider-facing mHealth applications used to screen for, diagnose, or monitor NCDs in LMICs. In this systematic review, we searched the indexing databases of PubMed, Web of Science, and Cochrane Central for studies published between January 2007 and October 2019. We included studies of technologies that were: (i) mobile phone- or tablet-based, (ii) able to screen for, diagnose, or monitor an NCD of public health importance in LMICs, and (iii) targeting health professionals as users. We extracted disease type, intervention purpose, target population, study population, sample size, study methodology, technology stage, country of development, operating system, and cost. Our initial search retrieved 13,262 studies, 315 of which met inclusion criteria and were analyzed. Cardiology was the most common clinical domain of the technologies evaluated, with 89 publications. mHealth innovations were predominantly developed using Apple’s iOS operating system. Cost data were provided in only 50 studies, but most technologies for which this information was available cost less than 20 USD. Only 24 innovations targeted the ten NCDs responsible for the greatest number of disability-adjusted life years lost globally. Most publications evaluated products created in high-income countries. Reported mHealth technologies are well-developed, but their implementation in LMICs faces operating system incompatibility and a relative neglect of NCDs causing the greatest disease burden.
Effectiveness of automated alerting system compared to usual care for the management of sepsis
Authors: Zhang Zhongheng , Chen Lin , Xu Ping , Wang Qing , Zhang Jianjun , Chen Kun , Clements Casey M. , Celi Leo Anthony , Herasevich Vitaly , Hong Yucai
Published: July 2022

There is a large body of evidence showing that delayed initiation of sepsis bundle is associated with adverse clinical outcomes in patients with sepsis. However, it is controversial whether electronic automated alerts can help improve clinical outcomes of sepsis. Electronic databases are searched from inception to December 2021 for comparative effectiveness studies comparing automated alerts versus usual care for the management of sepsis. A total of 36 studies are eligible for analysis, including 6 randomized controlled trials and 30 non-randomized studies. There is significant heterogeneity in these studies concerning the study setting, design, and alerting methods. The Bayesian meta-analysis by using pooled effects of non-randomized studies as priors shows a beneficial effect of the alerting system (relative risk [RR]: 0.71; 95% credible interval: 0.62 to 0.81) in reducing mortality. The automated alerting system shows less beneficial effects in the intensive care unit (RR: 0.90; 95% CI: 0.73–1.11) than that in the emergency department (RR: 0.68; 95% CI: 0.51–0.90) and ward (RR: 0.71; 95% CI: 0.61–0.82). Furthermore, machine learning-based prediction methods can reduce mortality by a larger magnitude (RR: 0.56; 95% CI: 0.39–0.80) than rule-based methods (RR: 0.73; 95% CI: 0.63–0.85). The study shows a statistically significant beneficial effect of using the automated alerting system in the management of sepsis. Interestingly, machine learning monitoring systems coupled with better early interventions show promise, especially for patients outside of the intensive care unit.
Development of copper-catalyzed deaminative esterification using high-throughput experimentation
Authors: Shen Yuning , Mahjour Babak , Cernak Tim
Published: July 2022

Repurposing of amine and carboxylic acid building blocks provides an enormous opportunity to expand the accessible chemical space, because amine and acid feedstocks are typically low cost and available in high diversity. Herein, we report a copper-catalyzed deaminative esterification based on C–N activation of aryl amines via diazonium salt formation. The reaction was specifically designed to complement the popular amide coupling reaction. A chemoinformatic analysis of commercial building blocks demonstrates that by utilizing aryl amines, our method nearly doubles the available esterification chemical space compared to classic Fischer esterification with phenols. High-throughput experimentation in microliter reaction droplets was used to develop the reaction, along with classic scope studies, both of which demonstrated robust performance against hundreds of substrate pairs. Furthermore, we have demonstrated that this new esterification is suitable for late-stage diversification and for building-block repurposing to expand chemical space.
Single-gas and mixed-gas permeation of N2/CH4 in thermally-rearranged TR-PBO membranes and their 6FDA-bisAPAF polyimide precursor studied by molecular dynamics simulations
Authors: Tanis Ioannis , Brown David , Neyertz Sylvie , Vaidya Milind , Ballaguet Jean-Pierre , Duval Sebastien , Bahamdan Ahmad
Published: July 2022

High-performance polymers with polybenzoxazole (PBO) structures, formed via thermal rearrangement (TR) of aromatic polyimide precursors, have been developed for gas separation applications.
Correction: Cytocompatible, soft and thick brush-modified scaffolds with prolonged antibacterial effect to mitigate wound infections
Authors: Dhingra Shaifali , Gaur Vidit , Saini Varsha , Rana Kajal , Bhattacharya Jayanta , Loho Thomas , Ray Sudip , Bajaj Avinash , Saha Sampa
Published: July 2022

Correction for ‘Cytocompatible, soft and thick brush-modified scaffolds with prolonged antibacterial effect to mitigate wound infections’ by Shaifali Dhingra et al., Biomater. Sci., 2022, 10, 3856–3877, https://doi.org/10.1039/d2bm00245k.
Electro-deoxidation behavior of solid SeO2 in a low-temperature molten salt
Authors: Chang Cheng , Tu Jiguo , Chen Yunfei , Wang Mingyong , Jiao Shuqiang
Published: July 2022

The direct electro-deoxidation of solid SeO2 to Se was confirmed to be a two-step two-electron process in low-temperature NaCl–AlCl3 molten salt. And the morphology evolution of hexagonal Se products was revealed along with the change of potentials.
Amorphous-crystalline PdRu bimetallene for efficient hydrogen evolution electrocatalysis
Authors: Wang Hongjing , Wang Beibei , Yu Hongjie , Wang Peng , Deng Kai , Xu You , Wang Xin , Wang Ziqiang , Wang Liang
Published: July 2022

PdRu bimetallene has been synthesized for the hydrogen evolution reaction, and exhibits excellent catalytic activity with a small overpotential and Tafel slope.
Nitric oxide electrochemical reduction reaction on transition metal-doped MoSi2N4 monolayers
Authors: Tong Tianyue , Linghu Yaoyao , Wu Guangping , Wang Chao , Wu Chao
Published: July 2022

Among the considered 25 kinds of TM-MSN, Zr-MSN and Pt-MSN are theoretically proved to exhibit the most superior catalytic activity and selectivity for NH3 production with a limiting potential of 0 and −0.10 V.
Anion photoelectron spectroscopy and density functional theory study of TM2Sin− (TM = V, Cr; n = 14–20) clusters
Authors: Wang Kai , Yin Guang-Jia , Jia Ze-Zhao , Miao Lin , Moro Ramiro , von Issendorff Bernd , Ma Lei
Published: July 2022

We investigated the structural evolution and electronic properties of medium-sized silicon cluster anions doped with two transition metal atoms, TM2Sin− (TM = V, Cr; n = 14–20), by using mass-selective anion photoelectron spectroscopy combined with density functional theory (DFT) calculations.
Double Rydberg anions, Rydberg radicals and micro-solvated cations with ammonium–water kernels
Authors: Opoku Ernest , Pawłowski Filip , Ortiz Joseph Vincent
Published: July 2022

Optimized geometries and Dyson orbitals of electron detachment from double Rydberg NH4−–water complexes.
Predicted crystal structures of xenon and alkali metals under high pressures
Authors: Tian Yifan , Tse John S. , Liu Guangtao , Liu Hanyu
Published: July 2022

The pressure-induced reaction between xenon (Xe) and alkali metal elements and the formation mechanism of the resultant crystal structures have been investigated systematically.
Progress on transition metal catalyzed asymmetric hydroesterification, hydrocarboxylation, and hydroamidation reactions of olefins
Authors: Li Junhua , Shi Yian
Published: July 2022

This review provides a brief summary of the development of transition metal catalyzed asymmetric hydrocarboxylation, hydroesterification, and hydroamidation of olefins with CO and its surrogates.