bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of common and rare ophthalmic findings in adults attending a medical survey institute
Authors: Landau Prat Daphna , Kapelushnik Noa , Zloto Ofira , Leshno Ari , Klang Eyal , Sina Sigal , Segev Shlomo , Arazi Mattan , Soudry Shahar , Ben Simon Guy J.
Published: February 2024

Purpose

To examine the ophthalmic data from a large database of people attending a general medical survey institute, and to investigate ophthalmic findings of the eye and its adnexa, including differences in age and sex.

Methods

Retrospective analysis including medical data of all consecutive individuals whose ophthalmic data and the prevalences of ocular pathologies were extracted from a very large database of subjects examined at a single general medical survey institute.

Results

Data were derived from 184,589 visits of 3676 patients (mean age 52 years, 68% males). The prevalence of the following eye pathologies were extracted. Eyelids: blepharitis (n = 4885, 13.3%), dermatochalasis (n = 4666, 12.7%), ptosis (n = 677, 1.8%), ectropion (n = 73, 0.2%), and xanthelasma (n = 160, 0.4%). Anterior segment: pinguecula (n = 3368, 9.2%), pterygium (n = 852, 2.3%), and cataract or pseudophakia (n = 9381, 27.1%). Cataract type (percentage of all phakic patients): nuclear sclerosis (n = 8908, 24.2%), posterior subcapsular (n = 846, 2.3%), and capsular anterior (n = 781, 2.1%). Pseudophakia was recorded for 697 patients (4.6%), and posterior subcapsular opacification for 229 (0.6%) patients. Optic nerve head (ONH): peripapillary atrophy (n = 4947, 13.5%), tilted disc (n = 3344, 9.1%), temporal slope (n = 410, 1.1%), ONH notch (n = 61, 0.2%), myelinated nerve fiber layer (n = 94, 0.3%), ONH drusen (n = 37, 0.1%), optic pit (n = 3, 0.0%), and ON coloboma (n = 4, 0.0%). Most pathologies were more common in males except for ONH, and most pathologies demonstrated a higher prevalence with increasing age.

Conclusions

Normal ophthalmic data and the prevalences of ocular pathologies were extracted from a very large database of subjects seen at a single medical survey institute.
A note on Sen’s representation of the Gini coefficient: Revision and repercussions
Authors: Stark Oded
Published: February 2024

Sen (1973 and 1997) presents the Gini coefficient of income inequality in a population as follows. “In any pair-wise comparison the man with the lower income can be thought to be suffering from some depression on finding his income to be lower. Let this depression be proportional to the difference in income. The sum total of all such depressions in all possible pair-wise comparisons takes us to the Gini coefficient.” (This citation is from Sen 1973, p. 8.) Sen’s verbal account is accompanied by a formula (Sen 1997, p. 31, eq. 2.8.1), which is replicated in the text of this note as equation (1). The formula yields a coefficient bounded from above by a number smaller than 1. This creates a difficulty, because the “mission” of a measure of inequality defined on the unit interval is to accord 0 to perfect equality (maximal equality) and 1 to perfect inequality (maximal inequality). In this note we show that when the Gini coefficient is elicited from a neat measure of the aggregate income-related depression of the population that consists of the people who experience income-related depression, then the obtained Gini coefficient is “well behaved” in the sense that it is bounded from above by 1. We conjecture a reason for a drawback of Sen’s definition, and we present repercussions of the usage of the “well-behaved” Gini coefficient.
Backcrossing Modulates the Metabolic Profiles of Anthocyanin-Pigmented ‘Vitamaize’ Lines Derived from Elite Maize Lines
Authors: Peniche-Pavía Héctor Arturo , González-Rodríguez Tzitziki , Tiessen Axel , García-Lara Silvero , Winkler Robert
Published: February 2024

Vitamaize lines (VMLs) were created by backcrossing the pigmented aleurone trait into Centro Internacional de Mejoramiento de Maíz y Trigo (CIMMYT) maize lines (CMLs). This study evaluates metabolic differences between the VMLs and their original CMLs. Direct infusion mass spectrometry (DIMS) analyses, carotenoid profiling, total anthocyanins content (TAC) determination, and biochemical evaluation of the quality protein maize (QPM) endosperm trait allowed a comprehensive chemical characterization of the maize lines. DIMS data indicate higher hexoses and trigonelline content for most VMLs; the carotenoid profile revealed a decrease in β-cryptoxanthin to less than half of the original parent content for two VMLs but an augmentation for one VML. The pigmented aleurone VMLs did not inherit the complex QPM endosperm trait of the QPM CMLs. Except for anthocyanin accumulation, no other metabolites were consistently modified across all the backcross-generated maize lines with a pigmented aleurone trait. These findings suggest using genetic or metabolic markers rather than morphological or visual traits for future breeding programs.
Imprinting parental signals: a key driver of network status for new spinoff firms
Authors: Zarea Forough , Burgers J. Henri , Obschonka Martin , Davidsson Per
Published: February 2024

Although past research has firmly established the positive effects of network status for resource acquisition and success in entrepreneurial endeavors, we still have a fragmented, limited understanding of the actual drivers of network status emergence. Prior research has mainly focused on the post-founding phase, pointing to the importance of current employment–based and firm-level affiliations in new ventures for their future status formation. In this paper, we extend the attention to the pre-founding phase in a study of spinoffs. Building on imprinting and signaling theories, we theorize that coming from a highly reputable parent firm has a long-term positive impact on a spinoff’s subsequent status by signaling a young spinoff firm’s quality to external parties. We advance previous research by further theorizing that such imprinting is contingent on the level of knowledge relatedness between the parent and spinoff as well as on whether there exists a strategic alliance between them post-founding. In addition, we argue a positive three-way interaction among parent reputation, parent-spinoff knowledge relatedness, and the parent-spinoff strategic alliance. Our analysis of a comprehensive longitudinal sample of 162 Australian mining spinoffs (i.e., firms started by ex-employees of incumbent parent firms) and 3405 strategic alliances from 2001 to 2014 supports majority of our hypotheses.
LiDAR odometry survey: recent advancements and remaining challenges
Authors: Lee Dongjae , Jung Minwoo , Yang Wooseong , Kim Ayoung
Published: February 2024

Odometry is crucial for robot navigation, particularly in situations where global positioning methods like global positioning system are unavailable. The main goal of odometry is to predict the robot’s motion and accurately determine its current location. Various sensors, such as wheel encoder, inertial measurement unit (IMU), camera, radar, and Light Detection and Ranging (LiDAR), are used for odometry in robotics. LiDAR, in particular, has gained attention for its ability to provide rich three-dimensional (3D) data and immunity to light variations. This survey aims to examine advancements in LiDAR odometry thoroughly. We start by exploring LiDAR technology and then scrutinize LiDAR odometry works, categorizing them based on their sensor integration approaches. These approaches include methods relying solely on LiDAR, those combining LiDAR with IMU, strategies involving multiple LiDARs, and methods fusing LiDAR with other sensor modalities. In conclusion, we address existing challenges and outline potential future directions in LiDAR odometry. Additionally, we analyze public datasets and evaluation methods for LiDAR odometry. To our knowledge, this survey is the first comprehensive exploration of LiDAR odometry.
REMOVER-PITCh: microhomology-assisted long-range gene replacement with highly multiplexed CRISPR-Cas9
Authors: Matsuzaki Shu , Sakuma Tetsushi , Yamamoto Takashi
Published: February 2024

A variety of CRISPR-Cas9-based gene editing technologies have been developed, including gene insertion and gene replacement, and applied to the study and treatment of diseases. While numerous studies have been conducted to improve the efficiency of gene insertion and to expand the system in various ways, there have been relatively few reports on gene replacement technology; therefore, further improvements are still needed in this context. Here, we developed the REMOVER-PITCh system to establish an efficient long-range gene replacement method and demonstrated its utility at two genomic loci in human cultured cells. REMOVER-PITCh depends on microhomology-assisted gene insertion technology called PITCh with highly multiplexed CRISPR-Cas9. First, we achieved gene replacement of about 20-kb GUSB locus using this system. Second, by applying the previously established knock-in-enhancing platform, the LoAD system, along with REMOVER-PITCh, we achieved the replacement of a longer gene region of about 200 kb at the ARSB locus. Our REMOVER-PITCh system will make it possible to remove and incorporate a variety of sequences from and into the genome, respectively, which will facilitate the generation of various disease and humanized models.
Data-Driven Overlapping-Track Profile Modeling in Cold Spray Additive Manufacturing
Authors: Ikeuchi Daiki , Vargas-Uscategui Alejandro , Wu Xiaofeng , King Peter C.
Published: February 2024

Cold spray additive manufacturing is an emerging solid-state deposition process that enables large-scale components to be manufactured at high-production rates. Control over geometry is important for reducing the development and growth of defects during the 3D build process and improving the final dimensional accuracy and quality of components. To this end, a machine learning approach has recently gained interest in modeling additively manufactured geometry; however, such a data-driven modeling framework lacks the explicit consideration of a depositing surface and domain knowledge in cold spray additive manufacturing. Therefore, this study presents surface-aware data-driven modeling of an overlapping-track profile using a Gaussian Process Regression model. The proposed Gaussian Process modeling framework explicitly incorporated two relevant geometric features (i.e., surface type and polar length from the nozzle exit to the surface) and a widely adopted Gaussian superposing model as prior domain knowledge in the form of an explicit mean function. It was shown that the proposed model could provide better predictive performance than the Gaussian superposing model alone and the purely data-driven Gaussian Process model, providing consistent overlapping-track profile predictions at all overlapping ratios. By combining accurate prediction of track geometry with toolpath planning, it is anticipated that improved geometric control and product quality can be achieved in cold spray additive manufacturing.
From the Mind to the Spine: The Intersecting World of Alzheimer’s and Osteoporosis
Authors: Margetts Tyler J. , Wang Hannah S. , Karnik Sonali J. , Plotkin Lilian I. , Movila Alexandru , Oblak Adrian L. , Fehrenbacher Jill C. , Kacena Melissa A.
Published: February 2024

Purpose of Review

This comprehensive review delves into the intricate interplay between Alzheimer’s disease (AD) and osteoporosis, two prevalent conditions with significant implications for individuals’ quality of life. The purpose is to explore their bidirectional association, underpinned by common pathological processes such as aging, genetic factors, inflammation, and estrogen deficiency.

Recent Findings

Recent advances have shown promise in treating both Alzheimer’s disease (AD) and osteoporosis by targeting disease-specific proteins and bone metabolism regulators. Monoclonal antibodies against beta-amyloid and tau for AD, as well as RANKL and sclerostin for osteoporosis, have displayed therapeutic potential. Additionally, ongoing research has identified neuroinflammatory genes shared between AD and osteoporosis, offering insight into the interconnected inflammatory mechanisms. This knowledge opens avenues for innovative dual-purpose therapies that could address both conditions, potentially revolutionizing treatment approaches for AD and osteoporosis simultaneously.

This review underscores the potential for groundbreaking advancements in early diagnosis and treatment by unraveling the intricate connection between AD and bone health. It advocates for a holistic, patient-centered approach to medical care that considers both cognitive and bone health, ultimately aiming to enhance the overall well-being of individuals affected by these conditions. This review article is part of a series of multiple manuscripts designed to determine the utility of using artificial intelligence for writing scientific reviews.
Soziale Arbeit in Jordanien
Authors: Nashwan Ayat , Scherr Albert
Published: February 2024

Der Beitrag informiert über die Entwicklung, die Erfordernisse und die Schwierigkeiten der Sozialen Arbeit in Jordanien sowie die Studiengänge und den Arbeitsmarkt. Aufgezeigt wird, dass Soziale Arbeit unter Bedingungen eines nur schwach entwickelten Sozialstaats stattfindet und zu einem großen Teil im Kontext von internationalen, nationalen und lokalen Nichtregierungsorganisationen (NGOs), deren Angebote sich überwiegend an Geflüchtete richten. Aufgrund fehlender oder geringer rechtlicher Ansprüche auf sozialstaatliche Unterstützung erfolgt Hilfe überwiegend als eine zivilgesellschaftliche Wohltätigkeit unter Bedingungen knapper Mittel.
Assessing cytotoxicity and endoplasmic reticulum stress in human blood–brain barrier cells due to silver and copper oxide nanoparticles
Authors: Chojnacka-Puchta Luiza , Sawicka Dorota , Zapor Lidia , Miranowicz-Dzierzawska Katarzyna
Published: February 2024

In recent years, it has been generally accepted that metal-based nanoparticles (NPs) may induce stress in the endoplasmic reticulum (ER), a key organelle where protein folding occurs. We examined ER stress in immortalized human cerebral microvascular cells (hCMEC/D3) after exposure to silver-NPs (Ag-NPs)- and copper oxide-NPs (CuO-NPs) induced toxicity at < 10 nm and < 40 nm or < 50 nm diameters, respectively. In cytotoxicity assessments, cells were exposed to different CuO-NPs (5–400 µg/mL) or Ag-NPs (1–10 µg/mL) concentration ranges for 24 h and 72 h, and tetrazole salt reduction assays (EZ4U) were performed. Also, Ag-NP or CuO-NP effects on cell proliferation, apoptosis (caspase 3/7 assays), and ER stress and cell morphology were evaluated. In ER stress assessments, RNA-like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6), inositol-requiring enzyme 1 (IRE1a), and others stress factor mRNA levels were determined after 24 h treatment using Real-Time PCR. Increased stress sensors (IRE1a, PERK, and ATF6) mRNA levels were observed after exposure to Ag-NPs (< 10 and < 40 nm) or CuO-NPs (< 50 nm). We investigated the expression of tight junction (TJ) proteins (barrier junctions) and showed that both types of NP reduced of OCLN gene expression. Morphological changes were observed after Ag-NP or CuO-NP exposure using holotomographic microscopy. Our data suggest that Ag- and CuO-NPs should undergo future in vitro and in vivo toxicology studies, especially for downstream biomedical application and occupational risk assessments.
Network pharmacology and experimental validation to explore the molecular mechanisms of kidney and blood refreshing recipe for the treatment of intrauterine adhesions
Authors: Hu Renzhi , Xia Min , Weng Shuangya , Chen Zhi , Wang Zhen , Zou Xuemei , Zhang Yan , Chen Yiming , Tang Sisi
Published: February 2024

Kidney and blood refreshing recipe formula is usually used to effectively treat intrauterine adhesions (IUAs). However, little is known about the underlying mechanism of kidney and blood refreshing recipes. We investigated the pharmacological mechanism of Bushen Yixue recipe on IUA through pharmacological and experimental validation. By network pharmacological analysis, 183 active constituents of the kidney and blood refreshing recipe were screened out (retrieved from TCMSP and TCM-ID). According to Venn diagram analysis, there were 102 common targets of the kidney and blood refreshing recipe. PPI analysis of the above common targets showed that there were 102 nodes and 1678 edges. Subsequently, GO enrichment and KEGG pathway analyses were also performed, which resulted in 1582 biological processes, 111 molecular functions, 82 cell components, and 174 related pathways. The active component of the kidney and blood refreshing recipe was also determined by liquid mass spectrometry. Finally, a rat model of IUA was constructed and tested in vivo. After kidney and blood refreshing recipe treatment, HE staining, Masson staining and immunohistochemistry (TGF-β1, SDF-1, VEGF) were performed on the uterine tissues of rats. The results showed that fibrosis in the uterine tissue was inhibited. The kidney and blood refreshing recipe inhibits fibrosis by inhibiting the expression of genes typical of fibrosis.
Youth, Pornography, and Addiction: A Critical Review
Authors: Healy-Cullen Siobhán , Taylor Kris , Morison Tracy
Published: February 2024

Purpose of Review

In this article, we dig more deeply into the assumptions underpinning common-sense understandings about youth “exposure” to pornography and the ostensible “effects” of this exposure, specifically “pornography addiction”. We trace the emergence of the notion of “pornography addiction”, highlighting how cultural conditions have allowed for its realisation as a socially recognisable and intelligible narrative.

Recent Findings

Media effects research on the issue of youth “exposure” to pornography is not conclusive, nor is pornography addiction officially recognised as a diagnosable disorder. Moreover, an emerging body of multidisciplinary qualitative research, which, importantly, includes the perspectives and experiences of young people themselves, raises questions about some of the assumptions and conclusions of effects-focused research.

Despite inconclusive and contrasting findings, the social narrative of pornography addiction persists both within and beyond academe. We make sense of this persistence in relation to the broader problematisation of youth sexuality, which includes unease and moral objection to young people viewing pornography. It is important to recognise the broader socio-cultural systems supporting the cultural narrative of pornography addiction, and the social functions that this narrative serves, that is, the need for adult intervention into the sexual lives of youth.
Tribological properties of Al-GNP composites at elevated temperature
Authors: Poudel Sunil , Bajwa Rizwan , Xia Yongde , Khan Zakir , Zhang Yi , Zhu Yanqiu
Published: February 2024

Lighter and more powerful next generation vehicles and other rotary machinery demand bearings to operate in harsher conditions for higher efficiency, and the continuous development of advanced low-wear and friction materials is thus becoming even more important to meet these requirements. New aluminium composites reinforced with high performance lubricate phases such as graphene nanoplatelets (GNPs) are very promising and have been vigorously investigated. By maintaining a low coefficient of friction (COF) and offering great strength against wear due to their self-lubricating capability, the solid lubricant like GNPs protect the bearing surface from wear damage and prevent change in metallurgical properties during temperature fluctuations. This paper first studies the high-temperature tribological performance of aluminium matrix composites reinforced with GNP, consolidated via powder metallurgy, then elucidates their tribological mechanism. We report that the best tribological performance is achieved by the composite containing 2.0 wt% GNP, with an extraordinarily low COF of 0.09 and a specific wear rate of 3.5×10−2 mm3·N−1·m−1, which represent 75% and 40% reduction respectively, against the plain aluminium consolidated under identical conditions. The in-track and out-of-track Raman analysis have confirmed the role of GNPs in creating a tribofilm on the counterpart surface which contributed to the excellent performance.
The effects of ghrelin and LEAP-2 in energy homeostasis are modulated by thermoneutrality, high-fat diet and aging
Authors: Casado S. , Varela-Miguéns M. , de Oliveira Diz T. , Quintela-Vilariño C. , Nogueiras R. , Diéguez C. , Tovar S.
Published: February 2024

Purpose

Liver-expressed antimicrobial peptide 2 (LEAP-2) has been recently identified as the endogenous non-competitive allosteric antagonist of the growth hormone secretagogue receptor 1a (GHSR1a). In rodents, LEAP-2 blunts ghrelin-induced feeding and its plasma levels are modulated in response to nutritional status, being decreased upon fasting and increased in high-fat diet (HFD) fed mice. Clinical data support the regulation of circulating LEAP-2 by nutrient availability in humans. In this work, our primary objective was to examine the chronic effects of ghrelin and LEAP-2 administration on food intake, adiposity, and energy expenditure in young mice subjected to standard and HFD at both room temperature and at thermoneutrality. Furthermore, we aimed to assess the impact of these two hormones on aging mice.

Results

Our results indicate that LEAP-2 produces a significant decrease of body weight and adiposity, an increase in energy expenditure, and activation of the thermogenic program in white and brown adipose tissue depots. However, this effect is not maintained under HFD or under thermoneutral conditions and is only partially observed in aging mice.

Conclusion

In summary our studies describe the central effects of LEAP-2 within distinct experimental contexts, and contribute to the comprehension of LEAP-2's role in energy metabolism.
Surface Patterning of Metal Zinc Electrode with an In-Region Zincophilic Interface for High-Rate and Long-Cycle-Life Zinc Metal Anode
Authors: Wang Tian , Xi Qiao , Yao Kai , Liu Yuhang , Fu Hao , Kavarthapu Venkata Siva , Lee Jun Kyu , Tang Shaocong , Fattakhova-Rohlfing Dina , Ai Wei , Yu Jae Su
Published: February 2024

The undesirable dendrite growth induced by non-planar zinc (Zn) deposition and low Coulombic efficiency resulting from severe side reactions have been long-standing challenges for metallic Zn anodes and substantially impede the practical application of rechargeable aqueous Zn metal batteries (ZMBs). Herein, we present a strategy for achieving a high-rate and long-cycle-life Zn metal anode by patterning Zn foil surfaces and endowing a Zn-Indium (Zn-In) interface in the microchannels. The accumulation of electrons in the microchannel and the zincophilicity of the Zn-In interface promote preferential heteroepitaxial Zn deposition in the microchannel region and enhance the tolerance of the electrode at high current densities. Meanwhile, electron aggregation accelerates the dissolution of non-(002) plane Zn atoms on the array surface, thereby directing the subsequent homoepitaxial Zn deposition on the array surface. Consequently, the planar dendrite-free Zn deposition and long-term cycling stability are achieved (5,050 h at 10.0 mA cm−2 and 27,000 cycles at 20.0 mA cm−2). Furthermore, a Zn/I2 full cell assembled by pairing with such an anode can maintain good stability for 3,500 cycles at 5.0 C, demonstrating the application potential of the as-prepared ZnIn anode for high-performance aqueous ZMBs.
On semi-continuity and continuity of the smallest and largest minimizing point of real convex functions with applications in probability and statistics
Authors: Ferger Dietmar
Published: February 2024

We prove that the smallest minimizer $$\sigma (f)$$

σ
(
f
)

of a real convex function f is less than or equal to a real point x if and only if the right derivative of f at x is non-negative. Similarly, the largest minimizer $$\tau (f)$$

τ
(
f
)

is greater than or equal to x if and only if the left derivative of f at x is non-positive. From this simple result we deduce measurability and semi-continuity of the functionals $$\sigma $$
σ
and $$\tau $$
τ
. Furthermore, if f has a unique minimizing point, so that $$\sigma (f)=\tau (f)$$

σ
(
f
)
=
τ
(
f
)

, then the functional is continuous at f. With these analytical preparations we can apply Continuous Mapping Theorems to obtain several Argmin theorems for convex stochastic processes. The novelty here are statements about classical distributional convergence and almost sure convergence, if the limit process does not have a unique minimum point. This is possible by replacing the natural topology on $$\mathbb {R}$$
R
with the order topologies. Another new feature is that not only sequences but more generally nets of convex stochastic processes are allowed.
Revisiting the Classical Theory of Investment: An Empirical Assessment from the European Union
Authors: Boundi-Chraki Fahd , Perrotini-Hernández Ignacio
Published: February 2024

In alignment with classical investment theory, this study explores the enduring relationships and causal linkages among total private investment, profit rate, unit labour costs, and demand growth within the European Union throughout the period spanning from 1961 to 2019. The empirical approach adopted involves the use of advanced econometric techniques designed to address cross-sectional dependence and slope heterogeneity. As a first stage, we examine stationarity and cointegration by employing second-generation panel unit root and cointegration tests. Subsequently, we estimate long-run equations through estimators intended to control for cross-sectional dependence and slope heterogeneity. As a further step, we use the Dumitrescu-Hurlin procedure to examine potential bidirectional causality between the variables and detect whether there exists endogeneity in the data. Finally, we apply the dynamic common correlated effects estimator mean group with instrumental variables to control for the potential presence of endogeneity. The outcomes of the analysis underscore a positive association between private investment and the profit rate, unit labour costs, and demand growth, thus providing robust empirical support for the classical theory of investment.
Towards a digital twin of a holacratic organization: a point of view on Lyytinen et al. (2023)
Authors: Winkler Johannes , Kremser Waldemar
Published: February 2024

This point of view paper challenges and extends Lyytinen et al.’s (J Organ Des https://doi.org/10.1007/s41469-023-00151-z, 2023) conceptualization of Digital Twins of Organizations (DTOs) as highly complex models including multiple organizational facets like agency, conflict, and emergence. They argue that the journey to achieving a fully functional DTO is a long way. However, we suggest a more parsimonious approach, focusing on leveraging digital trace data on the four universal problems of organizing: task division, task allocation, provision of rewards, and provision of information. Using the specific context of a holacratic organization, we argue that some organizations already produce extensive digital traces that can be leveraged to construct a DTO that is fit-for-purpose. We propose that existing data-science methods like predictive models, matching algorithms, clustering algorithms, and association rule mining can be employed to transform these digital traces into actionable insights for decision-makers. This approach not only addresses the complexity concerns raised by Lyytinen et al. (J Organ Des https://doi.org/10.1007/s41469-023-00151-z, 2023) but also offers a near-term pathway for holacratic organizations to benefit from DTOs as decision-support tools.
Does Central Statistical Monitoring Improve Data Quality? An Analysis of 1,111 Sites in 159 Clinical Trials
Authors: de Viron Sylviane , Trotta Laura , Steijn William , Young Steve , Buyse Marc
Published: February 2024

Background

Central monitoring aims at improving the quality of clinical research by pro-actively identifying risks and remediating emerging issues in the conduct of a clinical trial that may have an adverse impact on patient safety and/or the reliability of trial results. This paper, focusing on statistical data monitoring (SDM), is the second of a series that attempts to quantify the impact of central monitoring in clinical trials.

Material and Methods

Quality improvement was assessed in studies using SDM from a single large central monitoring platform. The analysis focused on a total of 1111 sites that were identified as at-risk by the SDM tests and for which the study teams conducted a follow-up investigation. These sites were taken from 159 studies conducted by 23 different clinical development organizations (including both sponsor companies and contract research organizations). Two quality improvement metrics were assessed for each selected site, one based on a site data inconsistency score (DIS, overall -log10P-value of the site compared with all other sites) and the other based on the observed metric value associated with each risk signal.

Results

The SDM quality metrics showed improvement in 83% (95% CI, 80–85%) of the sites across therapeutic areas and study phases (primarily phases 2 and 3). In contrast, only 56% (95% CI, 41–70%) of sites showed improvement in 2 historical studies that did not use SDM during study conduct.

Conclusion

The results of this analysis provide clear quantitative evidence supporting the hypothesis that the use of SDM in central monitoring is leading to improved quality in clinical trial conduct and associated data across participating sites.
The study of angular distance distribution to the solar flares during different solar cycles
Authors: Mawad Ramy
Published: February 2024

The angular distance of the solar flares to the projective point of the center of the solar disk on the solar spherical surface has been studied by the heliographical or helioprojective coordinates, during the periods 1975–2021 for GOES events and 2002–2021 for RHESSI events, hereafter “distance.” It gives a specific distribution curvature. It has also been noted that when using the number of solar flare events in each satellite, GOES or RHESSI, or even using the sum of the flux (class) or importance parameter, it obtains the same result, which is that the shape of the distribution curve remains in its shape without any significant change. In addition, it has been shown that the distribution curve contains a specific number of peaks. These peaks have a specific distance from the center of the solar disk that is very similar to the projection of the solar interior layers on the solar disk. For this reason, the names of these four main peaks have been given as follows: (1) the core circle (0–15°): it is a projection of the solar core onto the solar disk, (2) radiative ring (15–45°), and (3) the convection ring (45–55°). The limb ring is 80–90°. This result makes us wonder why the number of events in the middle of the solar disk is few, and also small at the solar limb, while many in the other parts in the solar disk. This suggests that we need to understand the sun better than before, and it also suggests that solar flares are connected to each other through the solar interior layers, the extent of which may reach the convection zone or perhaps beyond that, or the opacity of the convection zone may be less than the currently estimated value.
Shapley value: from cooperative game to explainable artificial intelligence
Authors: Li Meng , Sun Hengyang , Huang Yanjun , Chen Hong
Published: February 2024

With the tremendous success of machine learning (ML), concerns about their black-box nature have grown. The issue of interpretability affects trust in ML systems and raises ethical concerns such as algorithmic bias. In recent years, the feature attribution explanation method based on Shapley value has become the mainstream explainable artificial intelligence approach for explaining ML models. This paper provides a comprehensive overview of Shapley value-based attribution methods. We begin by outlining the foundational theory of Shapley value rooted in cooperative game theory and discussing its desirable properties. To enhance comprehension and aid in identifying relevant algorithms, we propose a comprehensive classification framework for existing Shapley value-based feature attribution methods from three dimensions: Shapley value type, feature replacement method, and approximation method. Furthermore, we emphasize the practical application of the Shapley value at different stages of ML model development, encompassing pre-modeling, modeling, and post-modeling phases. Finally, this work summarizes the limitations associated with the Shapley value and discusses potential directions for future research.
Immigration, Security, and the Liberal State
Authors: Lahav Gallya , Messina Anthony M.
Published: February 2024

Contextualizing the regulation of human mobility in a new security framework, this book offers an original perspective on the dominant mode of politics and evolving norms shaping the immigration policies of contemporary liberal states. In doing so, the authors challenge existing paradigms that privilege economic and cultural factors over new security ones in explaining the critical institutional and normative changes in migration management, from the early post-WWII through the post-Cold War era. Drawing on evidence from multiple sources, including media and elite discourse, policy tracking, party manifesto data and public opinion across Europe and the US, the book exposes the restrictive nature of immigration politics and policies when immigration is framed as a security threat, and considers its implications for civil liberties. Informed by a rich breadth of scholarly sub-disciplines, the findings contribute both empirically and theoretically to the literatures on international migration, security and public opinion.
Wideband nonuniform metasurface antenna with stable gain
Authors: Han Guorui , Zheng Zijun , Su Jinrong , Yuan Hao , Zhang Wenmei
Published: February 2024

A novel wideband nonuniform metasurface antenna with stable gain is demonstrated. The nonuniform metasurface is composed of square patches and rings and is excited by a slot antenna. Based on characteristic mode analysis, two characteristic modes with same current direction are selected to achieve stable radiation performance in a wide frequency range. The wideband operation is achieved by assembling the resonant modes of the metasurface and slot antenna. The measured results show that the −10 dB impedance bandwidth of the proposed antenna is from 4.3 to 8.4 GHz (64.57%), and the 2 dB gain bandwidth is from 4.3 to 6.2 GHz (36.2%) with a peak gain value of 9.42 dBi. Moreover, broadside radiation performance is achieved.
Hydrothermal Plume Fallout, Mass Wasting, and Volcanic Eruptions Contribute to Sediments at Loki's Castle Vent Field, Mohns Ridge
Authors: Gartman A. , Payan D. , Au M. , Reeves E. P. , Jamieson J. W. , Gini C. , Roerdink D.
Published: February 2024

Sediments surrounding hydrothermal vents are important transition spaces between hydrothermal and pelagic environments. These sediments accumulate through diverse processes that include water column plume fallout, volcanic ash deposition, and mass wasting of hydrothermal chimneys and mounds superimposed upon background sedimentation which may originate from pelagic, terrestrial, and volcanic sources. In addition to being a sink for elements discharged from hydrothermal vents, elements may also be scavenged from seawater onto oxidized hydrothermal material. Preservation of these hydrothermal sediments may occur depending on the extent of oxidative and/or reductive dissolution processes after burial. Sediments remaining adjacent to active venting may also be hydrothermally altered after emplacement. To better understand these processes, here we evaluate sediment push cores collected from the Loki's Castle vent field at the intersection of the slow‐ultraslow spreading Mohns and Knipovich mid‐ocean ridges. All samples were collected within ∼225 m of current high‐temperature (299–316°C) “black smoker” fluid discharge. These sediment cores are highly heterogeneous and lack stratigraphic correlation, even for samples taken within meters of each other. Most sediment cores are dominated by either pelagic sediments or mass wasted hydrothermal material, with hydrothermal plume fallout contributing a low proportion of material, and only a single volcanic ash layer occurring in one of the 13 cores. Dominant hydrothermal minerals found include talc, goethite, pyrite, pyrrhotite, and sphalerite. We find that even after several thousand years, most mass wasted hydrothermal material remains minimally altered, with sedimentation rates indistinguishable from background rates within several hundred meters of the hydrothermal vent source.
Uranium Redox and Deposition Transitions Embedded in Deep‐Time Geochemical Models and Mineral Chemistry Networks
Authors: Moore E. K. , Li J. , Zhang A. , Hao J. , Morrison S. M. , Hummer D. R. , Yee N.
Published: February 2024

Uranium (U) is an important global energy resource and a redox sensitive trace element that reflects changing environmental conditions and geochemical cycling. The redox evolution of U mineral chemistry can be interrogated to understand the formation and distribution of U deposits and the redox processes involved in U geochemistry throughout Earth history. In this study, geochemical modeling using thermodynamic data, and mineral chemistry network analysis are used to investigate U geochemistry and deposition through time. The number of U6+ mineral localities surpasses the number of U4+ mineral localities in the Paleoproterozoic. Moreover, the number of sedimentary U6+ mineral localities increases earlier in the Phanerozoic than the number of U4+ sedimentary mineral localities, likely due to the necessity of sufficient sedimentary organic matter to reduce U6+–U4+. Indeed, modeling calculations indicate that increased oxidative weathering due to surface oxygenation limited U4+ uraninite (UO2) formation from weathered granite and basalt. Louvain network community detection shows that U6+ forms minerals with many more shared elements and redox states than U4+. The range of weighted Mineral Element Electronegativity Coefficient of Variation (wMEECV) values of U6+ minerals increases through time, particularly during the Phanerozoic. Conversely, the range of wMEECV values of U4+ minerals is consistent through time due to the relative abundance of uraninite, coffinite, and brannerite. The late oxidation and formation of U6+ minerals compared to S6+ minerals illustrates the importance of the development of land plants, organic matter deposition, and redox‐controlled U deposition from ground water in continental sediments during this time‐period.
Degassing of Mantle‐Derived Helium From Hot Springs Along the India‐Asia Continental Collision Settings: Origins, Migration Velocity and Flux
Authors: Hao Yinlei , Gong Qinghua , Kuang Xingxing , Feng Yuqing , Zhou Hui , Zheng Chunmiao
Published: February 2024

Mantle‐derived volatile degassing lacks quantitative evaluation in continental regions without active magmatism, such as the Tibetan Plateau. Ten new gas abundance and helium isotope data points combined with 286 hydrothermal volatile literature data points in India–Asia continental collision settings demonstrate widespread mantle‐derived volatiles across the thick (∼70 km) crust. The mantle‐derived 3He is best explained by direct mantle volatile input from subcontinental lithospheric mantle (1%–36.5%) or the asthenospheric wedge (1%–27.8%) instead of fossil residual magmatic fluids or Quaternary mantle‐derived melt intrusion into crustal depth. Mantle‐derived 3He is transported from the deep mantle to the surface at an upflow rate of 30–11,700 mm/year based on a newly developed steady‐state one‐dimensional flow model, corresponding to a mantle‐derived 3He flux of 17 to 1.5 × 107 atoms m−2 s−1 (81.7%–99.4% of the total 3He flux) and a mantle‐derived 4He flux from 2.0 × 106 to 1.8 × 1012 atoms m−2 s−1 (1.4%–36.5% of the total 4He flux). The mantle‐derived helium fluxes in the study area are comparable to those of other nonvolcanic hydrothermal systems in the tectonically active regions but lower than those of volcanic fields. The helium transit time ranges from 5.3 ka to 2.3 Ma, indicating that the spatial pattern of 3He/4He ratios in the India‐Asia continental collision settings can provide a snapshot of the state of the Indian mantle lithosphere between those revealed by potassic‐rich mafic rocks (25–8 Ma) and seismic methods (present).
How Did We Miss 20% of Greenland’s Ice Loss?
Authors: Cartier Kimberly
Published: February 2024

The ice loss was hidden in places existing monitoring methods can’t reach, such as hard-to-map fjords. Machine learning helped scientist revise mass loss estimates and uncover patterns in glacial retreat.
Acid sphingomyelinase as a pathological and therapeutic target in neurological disorders: focus on Alzheimer’s disease
Authors: Choi Byung Jo , Park Min Hee , Jin Hee Kyung , Bae Jae-sung
Published: February 2024

Over the past decade, numerous studies have highlighted the importance of acid sphingomyelinase (ASM) in disease treatment in humans. This enzyme functions primarily to generate ceramide, maintain the cellular membrane, and regulate cellular function. However, in the blood and brain of patients with neurological disorders, including major depression, ischemic stroke, amyotrophic lateral sclerosis, multiple sclerosis, and Alzheimer’s disease (AD), elevated ASM levels significantly suggest disease onset or progression. In these diseases, increased ASM is profoundly involved in neuronal death, abnormal autophagy, neuroinflammation, blood–brain barrier disruption, hippocampal neurogenesis loss, and immune cell dysfunction. Moreover, genetic and pharmacological inhibition of ASM can prevent or ameliorate various diseases. The therapeutic effects of ASM inhibition have prompted the urgent need to develop ASM inhibitors, and several ASM inhibitors have been identified. In this review, we summarize the current knowledge on the critical roles and mechanisms of ASM in brain cells and blood that are associated with different neuropathological features, especially those observed in AD. Furthermore, we elucidate the potential possibility and limitations of existing ASM-targeting drugs according to experimental studies in neurological disorder mouse models.
Major depressive disorder: hypothesis, mechanism, prevention and treatment
Authors: Cui Lulu , Li Shu , Wang Siman , Wu Xiafang , Liu Yingyu , Yu Weiyang , Wang Yijun , Tang Yong , Xia Maosheng , Li Baoman
Published: February 2024

Worldwide, the incidence of major depressive disorder (MDD) is increasing annually, resulting in greater economic and social burdens. Moreover, the pathological mechanisms of MDD and the mechanisms underlying the effects of pharmacological treatments for MDD are complex and unclear, and additional diagnostic and therapeutic strategies for MDD still are needed. The currently widely accepted theories of MDD pathogenesis include the neurotransmitter and receptor hypothesis, hypothalamic-pituitary-adrenal (HPA) axis hypothesis, cytokine hypothesis, neuroplasticity hypothesis and systemic influence hypothesis, but these hypothesis cannot completely explain the pathological mechanism of MDD. Even it is still hard to adopt only one hypothesis to completely reveal the pathogenesis of MDD, thus in recent years, great progress has been made in elucidating the roles of multiple organ interactions in the pathogenesis MDD and identifying novel therapeutic approaches and multitarget modulatory strategies, further revealing the disease features of MDD. Furthermore, some newly discovered potential pharmacological targets and newly studied antidepressants have attracted widespread attention, some reagents have even been approved for clinical treatment and some novel therapeutic methods such as phototherapy and acupuncture have been discovered to have effective improvement for the depressive symptoms. In this work, we comprehensively summarize the latest research on the pathogenesis and diagnosis of MDD, preventive approaches and therapeutic medicines, as well as the related clinical trials.
Neutrophil-to-lymphocyte ratio and all-cause mortality with and without myeloproliferative neoplasms—a Danish longitudinal study
Authors: Larsen Morten Kranker , Skov Vibe , Kjær Lasse , Eickhardt-Dalbøge Christina Schjellerup , Knudsen Trine Alma , Kristiansen Marie Hvelplund , Sørensen Anders Lindholm , Wienecke Troels , Andersen Morten , Ottesen Johnny T. , Gudmand-Høyer Johanne , Snyder Jordan Andrew , Andersen Mikkel Porsborg , Torp-Pedersen Christian , Poulsen Henrik Enghusen , Stiehl Thomas , Hasselbalch Hans Carl , Ellervik Christina
Published: February 2024

The neutrophil-to-lymphocyte ratio(NLR) is increased in chronic inflammation and myeloproliferative neoplasms (MPN). We hypothesize that NLR is associated with all-cause mortality and mortality by comorbidity burden in the general population and individuals with MPN. We included 835,430 individuals from The Danish General Suburban Population Study, general practitioners, and outpatient clinics. We investigated NLR on mortality stratified by prevalent and incident MPN, essential thrombocythemia (ET), polycythemia vera (PV), myelofibrosis (MF), comorbidity burden (CCI-score), and the Triple-A risk score using hazard ratio (HR) and 95% confidence interval (95%CI). NLR 1–1.9 was the reference level. During a median follow-up of 11.2 years, 197,802 deaths were recorded. All-cause mortality increased for a stepwise increasing NLR with a HR (95%CI) for NLR ≥ 6 of 2.06(2.03–2.09) for the whole population and 2.93(2.44–3.50) in prevalent MPN. ET, PV, and MF had a HR (95%CI) for NLR ≥ 2 of 2.14(1.71–2.69), 2.19(1.89–2.54), and 2.31(1.91–2.80). Results were similar for incident MPN. Mortality was higher for stepwise increasing NLR and CCI-score(pinteraction < 2×10–16), with a HR for NLR ≥ 6 of 2.23(2.17–2.29), 4.10(4.01–4.20), and 7.69(7.50–7.89), for CCI-score 0, 1–2, or ≥3. The Triple-A risk score demonstrated alignment with NLR. Increasing NLR and comorbidity burden were associated with lower survival in individuals without MPN but were even worse in prevalent and incident MPN, ET, PV, and MF.
Dental trainee motivations for the acquisition and use of postgraduate qualifications in medical education
Authors: Atkin Philip A. , Saini Kiran K.
Published: February 2024

Introduction Medical and dental education is increasingly professionalised. The expectation is that educators have appropriate training and qualifications. Entry to dental speciality training is highly competitive and applications are scored using defined criteria, including experience in education.

Material and methods We surveyed a group of junior trainees who had enrolled on postgraduate medical education courses to find out more about their motivations and use of their knowledge and qualifications. An online survey tool was used with anonymous participants who had been in junior training jobs in a university dental school, with 117 possible participants.

Results In total, 61% of respondents were enrolled in or had completed a postgraduate qualification in medical education, with 85% on a postgraduate certificate programme. Additionally, 77% were in the earliest part of general dental training, and 88% of programmes were distance-learning and cost £2,000 to £4,000. Motivations for enrolling included to ‘improve knowledge in medical education' and ‘increase my chances of progression through training'.

Discussion and conclusions We found the most common intrinsic reason to gain a qualification was to improve knowledge in medical education and the most common extrinsic reason was career progression. Scoring of applications into dental speciality training has changed, with points no longer awarded for completing a postgraduate qualification in medical education.