bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of active-duty military service on neonatal birth outcomes: a systematic review
Authors: Morris Kirsten A L , McKee M
Published: April 2024

Introduction

Increasing numbers of women serve in the armed forces in countries worldwide. Stress experienced during pregnancy is associated with adverse birth outcomes including preterm delivery (PTD) and low birth weight (LBW). Several characteristics of military employment and lifestyle can increase stress acting on active-duty servicewomen (ADSW) and hence may increase the risk of adverse neonatal outcomes. This paper reviews the prevalence of PTD, preterm labour (PTL), LBW and stillbirth in babies born to ADSW in the armed forces.

Methods

This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. Medline, EMBASE, Web of Science, Global Health and CINAHL Plus databases were searched from inception to July 2021 (November 2023, EMBASE) using subject heading and keyword searches for English language journal articles on babies born to ADSW in any military branch and any country. The Joanna Briggs Institute prevalence critical appraisal tool assessed risk of bias in included papers. Studies were paired with a comparator non-active-duty population to generate a prevalence ratio as the effect measure. A narrative synthesis was conducted.

Results

21 observational studies fulfilled the eligibility criteria. They were all conducted in the US military, involved a total of 650 628 participants, and were published between 1979 and 2023. Their results indicate increased LBW in ADSW compared with non-service women. There was insufficient evidence to conclude or rule out whether ADSW have increased rates of PTD or PTL.

Conclusions

ADSW may be at increased risk of having an LBW baby. However, caution is needed if seeking to generalise the findings beyond the US context. This review highlights a growing need for female-specific research in other armed forces and, specifically, into reproductive health. Such research is necessary to inform military maternity pathways and policies in ways that safeguard mothers and their babies while enhancing military readiness.
The Bayes factor surface for searches for new physics
Authors: Fowlie Andrew
Published: April 2024

The Bayes factor surface is a new way to present results from experimental searches for new physics. Searches are regularly expressed in terms of phenomenological parameters – such as the mass and cross-section of a weakly interacting massive particle. Bayes factor surfaces indicate the strength of evidence for or against models relative to the background only model in terms of the phenomenological parameters that they predict. They provide a clear and direct measure of evidence, may be easily reinterpreted, but do not depend on choices of prior or parameterization. We demonstrate the Bayes factor surface with examples from dark matter, cosmology, and collider physics.
Research on the Application of Decision Tree and Correlation Analysis Algorithm in College Students’ Physical Fitness Analysis
Authors: Fan Jingang , Yang Yan , Liu Jiabao
Published: April 2024

With the advent of the big data era, data-driven decision-making and analysis are increasingly valued in various fields. Especially in the field of education, how to use big data technology to better understand student needs, optimize the education process, and improve education quality has become an important research topic. This paper will explore the application of decision trees and related analysis algorithms in the analysis of college students’ physical fitness, in order to provide scientific basis for improving the physical health level of college students. This paper studies the application of DT (decision tree) and correlation analysis algorithm in the analysis of college students’ physical fitness. In this paper, the method of big data and DM (data mining) is proposed to extract the rules contained in the data information, so as to directly provide auxiliary decision-making for physical fitness test and analysis. The research results show that through training the training set, a good classification accuracy rate is achieved, and through optimizing the depth, the accuracy rate can reach more than 85.033%. Using DM technology as a carrier, this paper digs into the rules behind the new knowledge of college students’ physical fitness, and digs out the previously unknown, implied and potentially useful information and knowledge.
Reproducing property of bounded linear operators and kernel regularized least square regressions
Authors: Sheng Baohuai
Published: April 2024

We consider bounded linear operators from the view of functional reproducing property. For some bounded linear operators associated with orthogonal polynomials we define an inner product space associated with a kernel constructed with orthogonal polynomials, show that it is a functional reproducing kernel Hilbert space (FRKHS) associated with these bounded linear operators and give decay rate for the best FRKHS approximation with a [Formula: see text]-functional associated with the FRKHS. On this basis, we provide a learning rate for kernel regularized regression whose hypothesis space is the defined FRKHS. As applications, we define some concrete FRKHSs associated with polynomial operators such as the Bernstein–Durrmeyer operators, the de la Vallée Poussin operators on both the unit sphere [Formula: see text] and the unit ball [Formula: see text]. We show that these polynomial operators have reproducing property with respect to the corresponding concrete FRKHSs and show the learning rate for the kernel regularized regression. In short, we provide a way of constructing FRKHS operators with Fourier multipliers and show a learning framework from the view of operator approximation.
Flexible Minimalist Self-Tracking to Support Individual Reflection
Authors: Barker-Canler Matthew , Gooch Daniel , Van Der Linden Janet , Petre Marian
Published: April 2024

Self-tracking technology can help users develop new knowledge about themselves, supporting their health and general wellbeing. Most of these devices inform users about their lives by autonomously generating data about highly constrained topics. Recent research has started to explore more flexible, manual self-tracking systems, which allow users to express themselves through their data and learn by engaging with their experiences in-the-moment. This article describes a field trial using the Chromatize app, designed to explore the value of minimalism and flexibility — including in data histories — in personal tracking systems. Our data indicate that low-burden experience logging systems which focus on the creation of symbolically-rich, self-defined data can support self-awareness, reflection and regulation at opportune moments. The analysis also contributes a formulation of reflection in the context of self-tracking technologies that is more meaningful than the loose use of ‘reflection’ used in much of the literature.
“We’re Not That Gullible!” Revealing Dark Pattern Mental Models of 11-12-Year-Old Scottish Children
Authors: Renaud Karen , Sengul Cigdem , Coopamootoo Kovila , Clift Bryan , Taylor Jacqui , Springett Mark , Morrison Ben
Published: April 2024

Deceptive techniques known as dark patterns specifically target online users. Children are particularly vulnerable as they might lack the skills to recognise and resist these deceptive attempts. To be effective, interventions to forewarn and forearm should build on a comprehensive understanding of children’s existing mental models. To this end, we carried out a study with 11- to 12-year-old Scottish children to reveal their mental models of dark patterns. They were acutely aware of online deception, referring to deployers as being ‘up to no good.’ Yet, they were overly vigilant and construed worst-case outcomes, with even a benign warning triggering suspicion. We recommend that rather than focusing on specific instances of dark patterns in awareness raising, interventions should prioritise improving children’s understanding of the characteristics of, and the motivations behind, deceptive online techniques. By so doing, we can help them to develop a more robust defence against these deceptive practices.
A Dynamic Threat Prevention Framework for Autonomous Vehicle Networks based on Ruin-theoretic Security Risk Assessment
Authors: Anwar Anika , Halabi Talal , Zulkernine Mohammad
Published: April 2024

In recent years, Autonomous Vehicle Networks (AVNs) have gained significant attention for their potential to make transportation safer and more efficient. These networks rely on Vehicle-to-Vehicle (V2V) communication to exchange critical information, such as location, speed, and driving intentions. However, V2V communication also introduces security vulnerabilities that can be exploited to compromise the safety and privacy of drivers and passengers. Malicious or selfish drivers can potentially intercept, modify, and manipulate V2V communication, causing confusion among vehicles or stealing sensitive data. Therefore, to identify and mitigate security threats that could jeopardize V2V communication in AVNs, the implementation of a threat prevention framework is imperative. This article presents a threat prevention framework that assesses security risks dynamically to facilitate secure message forwarding in V2V communication. First, we propose a dynamic risk assessment technique that utilizes the Probability-Impact-Exposure-Recovery metrics approach to evaluate the level of security threats posed to V2V communication and ultimately generate a risk score. Second, we develop a security decay assessment method that utilizes ruin theory to continuously monitor security risk within the AVNs. Third, we design a risk-aware message forwarding protocol based on coalitional game theory to facilitate secure V2V communication. Our experiments using the simulator Veins demonstrate the efficiency and scalability of the proposed framework in preventing potential damage caused by common security threats and enhancing the security of the Automated Highway System.
Backbone Index and GNN Models for Skyline Path Query Evaluation over Multi-cost Road Networks
Authors: Gong Qixu , Chen Huiying , Cao Huiping , Liu Jiefei
Published: April 2024

Skyline path queries (SPQs) extend skyline queries to multi-dimensional networks, such as multi-cost road networks (MCRNs). Such queries return a set of non-dominated paths between two given network nodes. Despite the existence of extensive works on evaluating different SPQ variants, SPQ evaluation is still very inefficient due to the nonexistence of efficient index structures to support such queries. Existing index building approaches for supporting shortest-path query execution, when directly extended to support SPQs, use an unreasonable amount of space and time to build, making them impractical for processing large graphs. In this article, we propose a novel index structure,
backbone index
, and a corresponding index construction method that condenses an initial MCRN to multiple smaller summarized graphs with different granularity. We present efficient approaches to find approximate solutions to SPQs by utilizing the backbone index structure. Furthermore, considering making good use of historical query and query results, we propose two models,
S
kyline
P
ath
G
raph
N
eural
N
etwork (SP-GNN) and
T
ransfer SP-GNN (TSP-GNN), to support effective SPQ processing. Our extensive experiments on real-world large road networks show that the backbone index can support finding meaningful approximate SPQ solutions efficiently. The backbone index can be constructed in a reasonable time, which dramatically outperforms the construction of other types of indexes for road networks. As far as we know, this is the first compact index structure that can support efficient approximate SPQ evaluation on large MCRNs. The results on the SP-GNN and TSP-GNN models also show that both models can help get approximate SPQ answers efficiently.
A Scenario-Based DVFS-Aware Hybrid Application Mapping Methodology for MPSoCs
Authors: Spieck Jan , Wildermann Stefan , Teich Jürgen
Published: April 2024

Sound techniques for mapping soft real-time applications to resources are indispensable for meeting the application deadlines and minimizing objectives such as energy consumption, particularly on heterogeneous MPSoC architectures. For applications with input-dependent workload variations, static mappings are not able to sufficiently cope with the run-time variation, which can lead to deadline misses or unnecessary energy consumption. As a remedy, hybrid application mapping (HAM) techniques combine a design-time optimization with run-time management that adapts the mappings dynamically to the changes of the arriving input. This paper focuses on scenario-based HAM techniques. Here, the application input space is systematically clustered such that data inside the same scenario exhibit similar characteristics concerning workload when being processed under the same operating points. This static clustering of the input space into data scenarios has proven to be a good abstraction layer for simplifying the design and employment of high-quality run-time managers. However, existing state-of-the-art scenario-based HAM approaches neglect or underutilize the synergistic interplay between mapping selection and the usage of dynamic voltage/frequency scaling (DVFS) when adapting to workload variation. By combining mapping and DVFS selection, variations in the input can be either compensated by a complete re-mapping of the application, evoking a potential high reconfiguration overhead or by just changing the DVFS settings of the resources, offering a low-overhead adaptation alternative and thus significantly reducing the necessary overhead compared to DVFS-agnostic HAM. Furthermore, DVFS enables a fine-grained adaptation of a mapped application to the input data variation, e.g., by slowing down tasks with no impact on the end-to-end latency for the current input using low-frequency DVFS settings. It is shown that this combined approach can save even more energy than a pure mapping adaptation scheme, especially in the presence of data scenarios. In particular, scenario-based design operates as a catalyst for eliciting the synergies between a combined DVFS and mapping optimization and the peculiarities inside a data scenario, i.e., exploiting the commonalities inside a data scenario by perfectly tailored DVFS settings and task mapping. In this scope, this paper proposes two supplementary scenario-based DVFS-aware HAM approaches that consistently outperform existing state-of-the-art mapping approaches in terms of the number of deadline misses and energy consumption as we demonstrate in an empirical study on the basis of four different applications and three different architectures. It is also shown that these benefits still apply to target architectures with increasing mapping migration overheads, thwarting frequent mapping reconfigurations.
MRI in the Evaluation of Cryptogenic Stroke and Embolic Stroke of Undetermined Source
Authors: Xiao Jiayu , Poblete Roy A. , Lerner Alexander , Nguyen Peggy L. , Song Jae W. , Sanossian Nerses , Wilcox Alison G. , Song Shlee S. , Lyden Patrick D. , Saver Jeffrey L. , Wasserman Bruce A. , Fan Zhaoyang
Published: April 2024

MRI is a valuable modality for the etiologic work up in patients with cryptogenic stroke and embolic stroke of undetermined source.
Planetary Health and Radiology: Why We Should Care and What We Can Do
Authors: McKee Hayley , Brown Maura J. , Kim Helen H. R. , Doo Florence X. , Panet Hayley , Rockall Andrea G. , Omary Reed A. , Hanneman Kate
Published: April 2024

Immediate action is needed to sustain planetary health by implementing mitigation strategies to reduce greenhouse gas emissions in radiology and adaptation strategies that build resiliency to the effects of climate change.
Fabrication of Highly Sensitive Electrochemical Sensor Based on Chromium-Doped Ferrite Nanoparticles: Hybrid Graphene Nanosheets for the First Voltammetric Determination of Asenapine Maleate in Formulations and Human Plasma
Authors: Gado Mohamed S. , El-Desoky Hanaa S. , Abdel-Galeil Mohamed M.
Published: April 2024

Ferrite nanoparticles are interesting materials given their unique physical and chemical properties and wide applications. A novel electrochemical sensor based on a series of chromium-nano-ferrites {Fe3+[Fe2+Fe3+
(1-x)Cr3+

x
]O4; x (0.0–1.0} was fabricated for determination of Asenapine maleate (ASE.M). X-ray diffraction revealed the formation of crystallite nano-particles of lattice constant of (8.299–8.345 Å) with a single phase of cubic inverse spinel structures. Particle size and specific surface area were (9.10–27.60 nm) and (60–175 m2g−1) using Transmission electron microscopy and Brunnauer-Emmett-Teller (BET) analysis, respectively. Among this Cr
x
Fe(3−x)O4 series, (CrFe2O4; x = 1) was appeared to get the smallest particles size and highest BET surface area. The charge transfer resistance (RCT) of (2220, 1680, 765, and 490 Ω) were achieved for Cr
x
Fe(3−x)O4 NPs/CPE (x = 0.0, 0.4, 0.8, and 1.0), respectively. CrFe2O4 performance was then improved via incorporation of 2D-graphene atomic crystals in a new ferrite-graphene nanocomposite of [0.25%(w/w) CrFe2O4 NPs: 7%(w/w) graphene nanosheets]. The feasibility of this sensor is achieved for determination of ASE.M in brand Saphris® and local Asenapine pharmaceutical products. In addition, a wide linear concentration range of (6.5 × 10−9–1.0 × 10−6 M) with LOD value of 8.88 × 10−10 M were achieved in human plasma.
Charge-Traps, Thermal Stability and Water-Uptakes of CaSiO3/EP and SiO2/EP Nanocomposites from Molecular Simulations and First-Principles Calculations
Authors: Zhang Yanyan , Sun Weifeng
Published: April 2024

Various analytical methods were employed to elucidate the effects of filling nano-calcium-silicate or nano-silica on the electronic property, water-uptake, and thermal stability of an amine-crosslinked epoxy (EP) polymer. Molecular-mixture models consisting of a nanofiller or several calcium ions and EP crosslinked macro-molecules were used to simulate local regions of nanofiller/matrix interface or ion-infiltrated matrix, calculating their density of electron-states by first-principles method to determine whether and how the nanofillers introduce charge traps into EP matrix. Calcium cations on nanofiller surface dissociate away from coordinating with silicon-oxygen tetrahedron and infiltrate into void spaces in EP matrix, leaving a larger free volume at filler/matrix interface than in matrix. Calcium cations dissolved in EP matrix are adsorbed in the low electrostatic potential region or coordinate with carbonyl groups in EP matrix and thus introduce a miniband of deep electron traps at energy levels >1 eV lower than conduction band minimum of the amine-crosslinked EP polymer. Even at room temperature, thermal vibrations can break coordinate bonds between calcium cations and silicon-oxygen framework on calcium-silicate nanofiller surface and make considerable calcium ions infiltrating void spaces within EP matrix, leading to comprehensive improvements of cohesive energy, thermal stability, and charge trapping ability in the calcium-silicate/EP nanocomposite.
CD4+T and CD8+T Cells in Uterus Exhibit Both Selective Dysfunction and Residency Signatures
Authors: Kang Shuangpeng , Jin Shuiping , Mao Xueying , He BinSheng , Wu Changyou
Published: April 2024

Unlike T cells in other tissues, uterine T cells must balance strong immune defense against pathogens with tolerance to semiallogeneic fetus. Our previous study fully elucidated the characteristics of γδT cells in nonpregnant uterus and the mechanism modulated by estrogen. However, comprehensive knowledge of the immunological properties of αβT (including CD4+T cells and CD8+T) cells in nonpregnancy uterus has not been acquired. In this study, we fully compared the immunological properties of αβT cells between uterus and blood using mouse and human sample. It showed that most of CD4+T cells and CD8+T cells in murine uterus and human endometrium were tissue resident memory T cells which highly expressed tissue residence markers CD69 and/or CD103. In addition, both CD4+T cells and CD8+T cells in uterus highly expressed inhibitory molecular PD‐1 and cytokine IFN‐γ. Uterine CD4+T cells highly expressed IL‐17 and modulated by transcription factor pSTAT3. Moreover, we compared the similarities and differences between human and murine uterine T cell phenotype. Together, uterine CD4+T cells and CD8+ cells exhibited a unique mixed signature of T cell dysfunction, activation, and effector function which enabled them to balance strong immune defense against pathogens with tolerance to fetus. Our study fully elucidated the unique immunologic properties of uterine CD4+T and CD8+T cells and provided a base for further investigation of functions.
Effect of NPS and Zinc Fertilizer Rates on Growth and Yield of Onion (Allium cepa L.) at Shewa Robit, North Shewa, Ethiopia
Authors: Muluneh Kelem , Tesfa Tiru , Desta Bizuayehu
Published: April 2024

Onions, a crucial bulb crop cultivated globally, including in Ethiopia, face significant production challenges. These constraints encompass poor soil fertility, inappropriate fertilizer usage, limited availability of improved varieties, disease and insect pests, and the high costs associated with commercial fertilizers. Among these limitations, improper fertilizer application amounts and types play a pivotal role in restricting onion production. To address this, a field experiment was conducted during the 2020-2021 cropping season in the Shewa Robit district of the North Shewa zone. The study assessed the impact of NPS and Zn fertilizer rates on onion growth and yield. The treatments included four NPS fertilizer rates (0, 121, 242, and 363 kg/ha) and four levels of ZnSO4 (0, 0.25, 0.5, and 0.75% w/v). The experiment was laid out as a randomized complete block design in a factorial arrangement and replicated three times. The results demonstrated that the interaction effect of NPS and Zn fertilizers significantly influenced various onion parameters, including days to maturity, plant height, leaf length, marketable bulb yield, unmarketable bulb yield, and total bulb yield. The application of NPS at a rate of 242 kg/ha and 0.75% ZnSO4 led to the highest plant height (65.20 cm), leaf length (51.93 cm), marketable bulb yield (34.87 t/ha), and total bulb yield (35.04 t/ha). In addition, this treatment combination yielded the highest net benefit (908,628.89 ETB/ha) with an acceptable MRR (313.64%) compared to other treatments. Hence, it can be recommended for economical production of onion in the study area and areas with similar agroecologies.
The Relationship between Personality Profiles and the Esthetic Perception of Orthodontic Appliances
Authors: Pascoal Selma , Gonçalves Maria , Salvador Pietro , Azevedo Rui , Leite Manuela , Pinho Teresa
Published: April 2024

Introduction. In orthodontics, patients’ esthetic expectations involve the final esthetic result as well as the treatment’s appliance choice. Personality traits can influence patients’ perception, treatment modality selection, expectations, compliance, and satisfaction with the treatment outcome, although there are very few studies on this interconnection between personality and orthodontic appliances. Objective. The aim of this study is to evaluate the relationship between personality traits and the esthetic perception of different orthodontic appliances. Materials and Methods. The online questionnaire is composed of three parts: (1) sociodemographic variables; (2) questions on the esthetic perception of different orthodontic appliances; (3) general personality assessment via the NEO‐FFI. A total of 461 questionnaires were accepted. Results. There were statistically significant differences between laypeople and professionals related to assessing smiles and the need for orthodontic treatment. Laypeople identified a statistically significant relationship between personality traits and orthodontic appliances, in which esthetic perception is associated with high traits of agreeableness and openness. Neuroticism is most associated with orthodontic treatment with fixed appliances, which are the most conventional. Conclusions. Professionals tend to have a more critical judgment than laypeople as far as esthetics is concerned. Personality traits play an important role in esthetic perception and may influence orthodontic treatment.
Appendectomy and Risk of Prostate Cancer in the Health Professionals Follow-up Study
Authors: Zhang Yiwen , Feng Xiaotong , Giovannucci Edward L.
Published: April 2024

Background:

Appendectomy is a common surgical procedure to treat appendicitis. Limited studies have examined its association with prostate cancer, with one large cohort study suggesting a significantly increased risk of overall and advanced prostate cancer, especially among younger men.

Methods:

A total of 49,104 men in the Health Professionals Follow-up Study were followed from 1986 to 2016. Cox proportional hazards models were applied to evaluate the association between self-reported history of appendectomy and risk of overall and subtype-specific prostate cancer, adjusted for multiple risk factors.

Results:

During 30 years of follow-up, we documented 7,253 overall prostate cancer cases, including 579 advanced and 1,092 lethal events. Compared to men without appendectomy, those who reported at baseline having had appendectomy were not at higher risk of overall [HR, 1.01; 95% confidence interval (CI), 0.95–1.07], advanced (HR, 0.99; 95% CI, 0.81–1.23), or lethal (HR, 1.04; 95% CI, 0.89–1.20) prostate cancer. The association remained null when stratified by age.

Conclusions:

We found no evidence of an association between appendectomy and the risk of overall and clinically important prostate cancer.

Impact:

We showed that appendectomy was not associated with overall or advanced prostate cancer after adjusting for multiple risk factors in a large population of men with 30 years of follow-up.
Genomic Profiling to Contextualize the Results of Intervention for Smoldering Multiple Myeloma
Authors: Kazandjian Dickran , Diamond Benjamin , Papadimitriou Marios , Hill Elizabeth , Sklavenitis-Pistofidis Romanos , Ziccheddu Bachisio , Blaney Patrick , Chojnacka Monika , Durante Michael , Maclachlan Kylee , Young Ryan , Usmani Saad , Davies Faith , Getz Gad , Ghobrial Irene , Korde Neha , Morgan Gareth , Maura Francesco , Landgren Ola
Published: April 2024

Purpose:

Early intervention for high-risk smoldering multiple myeloma (HR-SMM) achieves deep and prolonged responses. It is unclear if beneficial outcomes are due to the treatment of less complex, susceptible disease or inaccuracy in clinical definition of cases entered.

Experimental Design:

In this study, we interrogated whole-genome and whole-exome sequencing for 54 patients across two HR-SMM interventional studies (NCT01572480 and NCT02279394).

Results:

We reveal that the genomic landscape of treated HR-SMM is generally simple as compared with newly diagnosed multiple myeloma counterparts with less inactivation of tumor suppressor genes, RAS pathway mutations, MYC disruption, and APOBEC contribution. The absence of these events parallels that of indolent precursor conditions, possibly explaining overall excellent outcomes. However, some patients harboring genomic complexity fail to sustain response and experience resistant, progressive disease. Overall, clinical risk scores do not effectively discriminate between genomically indolent and aggressive disease.

Conclusions:

Genomic profiling can contextualize the advantage of early intervention in SMM and guide personalization of therapy.

See related commentary by Weinhold and Rasche, p. 4263
Hematopoietic Clonal Evolution Goes Spatial
Authors: Austin Rebecca , Aifantis Iannis
Published: April 2024

The spatial distribution of cells carrying clonal hematopoiesis mutations in the bone marrow and the potential role of interactions with the microenvironment are largely unknown. This study takes clonal evolution to the spatial level by describing a novel technique examining the spatial location of mutated clones in the bone marrow and the first evidence that mutated hematopoietic clones are spatially constrained and have heterogenous locations within millimeters of distance.

See related article by Young et al., p. 153 (10).
Long-Term Healthcare Resource Utilization and Costs among Patients with Myasthenia Gravis: A Swedish Nationwide Population-Based Study
Authors: Cai Qian , Batista Alberto E. , Börsum Jakob , Zhang Qiaoyi , Isheden Gabriel , Kunovszki Peter , Gandhi Kavita , Heerlein Kristin , Brauner Susanna
Published: April 2024

Introduction: Healthcare costs and societal impact of myasthenia gravis (MG), a potentially life-threatening rare, chronic neuromuscular disease, are sparsely studied. We assessed healthcare resource utilization (HCRU) and associated costs among patients with newly diagnosed (ND) and preexisting (PE) MG in Sweden. Methods: This observational, retrospective cohort study used data from four linkable Swedish nationwide population-based registries. Adult MG patients receiving pharmacological treatment for MG and having ≥24-month follow-up during the period January 1, 2010, to December 31, 2017, were included. Results: A total of 1,275 patients were included in the analysis, of which 554 patients were categorized into the ND MG group and 721 into the PE MG group. Mean (±SD) age was 61.3 (±17.4) years, and 52.3% were female. In the first year post-diagnosis, ND patients had significantly higher utilization of acetylcholinesterase inhibitors (96.0% vs. 83.9%), corticosteroids (59.6% vs. 45.8%), thymectomy (12.1% vs. 0.7%), and plasma exchange (3.8% vs. 0.6%); had higher all-cause (70.9% vs. 35.8%) and MG-related (62.5% vs. 18.4%) hospitalization rates with 11 more hospitalization days (all p < 0.01) and an increased risk of hospitalization (odds ratio [95% CI] = 4.4 [3.43, 5.64]) than PE MG. In year 1 post-diagnosis, ND MG patients incurred EUR 7,302 (p < 0.01) higher total all-cause costs than PE MG, of which 84% were estimated to be MG-related and the majority (86%) were related to inpatient care. These results remained significant also after controlling for baseline demographics and comorbidities (p < 0.01). In year 2 post-diagnosis, the all-cause medical costs decreased by ∼55% for ND MG from year 1 and were comparable with PE MG. Conclusion: In this population-based study, MG patients required significantly more healthcare resources in year 1 post-diagnosis than PE MG primarily due to more pharmacological treatments, thymectomies, and associated hospitalizations. These findings highlight the need to better understand potential factors including disease characteristics associated with increased health resource use and costs and need for more efficacious treatments early in the disease course.
Erythroid Predominance in Bone Marrow Biopsies of Acute Myeloid Leukemia Patients after Decitabine Treatment Correlates with Mutation Profile and Complete Remission
Authors: Tiso Francesca , Hebeda Konnie M. , Langemeijer Saskia M.C. , de Graaf Aniek O. , Martens Joost H.A. , Koorenhof-Scheele Thessa N. , Knops Ruth , Kroeze Leonie I. , van der Reijden Bert A. , Jansen Joop H.
Published: April 2024

Introduction: Acute myeloid leukemia (AML) patients may receive hypomethylating agents such as decitabine (DAC) as part of their treatment. Not all patients respond to this therapy, and if they do, the clinical response may occur only after 3–6 courses of treatment. Hence, early biomarkers predicting response would be very useful. Methods: We retrospectively analyzed a cohort of 22 AML patients who were treated with DAC. Histology of the bone marrow biopsy, pathogenic mutations, and methylation status were related to the treatment response. Results: In 8/22 (36%) patients, an erythroid dominant response (EDR) pattern, defined as a ratio of myeloid cells/erythroid cells <1, was observed. In the remaining 14 cases, a myeloid predominance was preserved during treatment. No difference in the hypomethylating effect of DAC treatment was observed in patients with and without EDR, as global 5-methylcytosine levels dropped similarly in both groups. Mutational analysis by NGS using a panel of commonly mutated genes in AML showed that patients with an early EDR harbored on average less mutations, with U2AF1 mutations occurring more frequently, whereas RUNX1 mutations were underrepresented compared to non-EDR cases. Interestingly, the development of an EDR correlated with complete remission (7/8 cases with an EDR vs. only 2/14 cases without an EDR). Conclusion: We conclude that early histological bone marrow examination for the development of an EDR may be helpful to predict response in AML patients during treatment with DAC.
Transcriptomic Profiling of Lactotroph Pituitary Neuroendocrine Tumors via RNA Sequencing and Ingenuity Pathway Analysis
Authors: Hattori Yujiro , Tahara Shigeyuki , Ozawa Hitoshi , Morita Akio , Ishii Hirotaka
Published: April 2024

Introduction: Lactotroph pituitary neuroendocrine tumors (PitNETs) are common pituitary tumors, but their underlying molecular mechanisms remain unclear. This study aimed to investigate the transcriptomic landscape of lactotroph PitNETs and identify potential molecular mechanisms and therapeutic targets through RNA sequencing and ingenuity pathway analysis (IPA). Methods: Lactotroph PitNET tissues from five surgical cases without dopamine agonist treatment underwent RNA sequencing. Normal pituitary tissues from 3 patients served as controls. Differentially expressed genes (DEGs) were identified, and the functional pathways and gene networks were explored by IPA. Results: Transcriptome analysis revealed that lactotroph PitNETs had gene expression patterns that were distinct from normal pituitary tissues. We identified 1,172 upregulated DEGs, including nine long intergenic noncoding RNAs (lincRNAs) belonging to the top 30 DEGs. IPA of the upregulated DEGs showed that the estrogen receptor signaling, oxidative phosphorylation signaling, and EIF signaling were activated. In gene network analysis, key upstream regulators, such as EGR1, PRKACA, PITX2, CREB1, and JUND, may play critical roles in lactotroph PitNETs. Conclusion: This study provides a comprehensive transcriptomic profile of lactotroph PitNETs and highlights the potential involvement of lincRNAs and specific signaling pathways in tumor pathogenesis. The identified upstream regulators may be potential therapeutic targets for future investigations.
Sobre a posição taxonômica de Dorcasia e Trigonephrus (Gastropoda, Pulmonata)
Authors: Leme José Luiz Moreira
Published: April 2024

.
Desenvolvimento pós-embrionário De Isocheles Sawayai Forest e Saint Laurent. 1967 (Decapoda, Diogenidae), em laboratório
Authors: Negreiros-Fransozo Maria Lucia , Hebling Nilton José
Published: April 2024

.
Abstract 4183: Gender Difference in the Relationship Between Socioeconomic Deprivation and Fatal Compared to Non-fatal Myocardial Infarction
Authors: Jhund Pardeep , Macintyre Kate , McMurray John
Published: April 2024

Introduction: Although socioeconomic deprivation (SED) has been identified as an important risk factor for myocardial infarction (MI), it is not clear whether it predicts outcome after adjustment for traditional risk factors. The relative importance of SED as a predictor of fatal versus non-fatal outcomes and in men versus women is also uncertain.

Hypothesis: We hypothesized that SED is an independent predictor of both first hospitalization for MI and MI death (and equally so in men and women).

Methods: We examined outcomes in 15,378 men and women initially surveyed between 1972–76 in Renfrew and Paisley, Scotland, and followed until 3/31/2004. Hazards ratios (HR) for a first admission with a MI (as principal diagnosis) and death from MI were calculated using Cox Regression. All analyses were adjusted for age, body mass index, systolic and diastolic blood pressure, cholesterol, smoking, ECG ischemia, and a history of diabetes, angina or stroke. Deprivation was defined using the seven category Carstairs deprivation index. Deprivation categories (depcat) 6 and 7 (the most deprived depcats) were combined to increase power due to small numbers of individuals in group 7. Log rank tests were used to compare the overall trend across depcats.

Results: During >=28 years follow-up, 1873 men and women had a first MI hospitalization and 2370 a MI death. Compared to the most affluent (depcat 1), the risk of MI death in men and women combined in depcat 6/7 was 37% higher (hazard ratio (HR) 1.37 (P=0.001)), trend P<0.0001. The HR for men alone in depcat 6/7 versus depcat 1 was 1.35 (P=0.018) and similarly 1.38 for women alone (P=0.027). For men and women in depcat 6/7 (compared to depcat 1), the HR for a first MI hospitalization was 1.34 (P= 0.007), P<0.0001. The HR was 1.1 for men (P=0.5) and 1.74 for women (P=0.002).

Conclusion: SED is associated with an increased risk of MI death which is of similar magnitude in men and women, even after accounting for “traditional” risk factors. By contrast, SED is associated with a smaller risk of 1st hospitalization for MI in men than women. This explanation for this gender difference is uncertain but may represent a differential effect of SED on survival to hospital admission in men and women.
Abstract 4184: Gender Difference in Utilization of Secondary Preventive Measures in Patients with CAD
Authors: Cho Leslie , Huang Julie , Brennan Danielle , Hazen Stanley L
Published: April 2024

Background
: Previous studies have suggested that women with cardiovascular disease may receive less aggressive care compared to men. Using a cardiology database from a tertiary referral center, we sought to determine if treatment difference still persist in the current era.

Methods
: 2462 patients who were referred for secondary prevention to Preventive Cardiology Clinic at The Cleveland Clinic between 1997 to 2004 were analyzed. The primary objective was to analyze utilization of effective secondary preventive therapies as stated by ACC/AHA guideline such as ASA, statin, B- blocker, or ACE inhibitor use between gender. Multivariate logistic regression analysis was performed to assess the independent effect of gender on all cause mortality.

Results
: Women were older (62.2 ± 11.1 vs. 59.4 ± 11.0, p<0.001) and more likely to be hypertensive (68.1% vs. 56.1%, p<0.001) than their male counterparts. However, they had similar rates of diabetes, smoking, and peripheral vascular disease. Overall, women were more likely to present with statistically higher baseline CRP (6.1 vs. 4.9 p<0.001), LDL (135 vs. 116, p<0.001), HDL (52 vs. 41, p<0.001), total cholesterol (238 vs. 202, p<0.001) than their male counterparts. Women were less likely to be on antiplatelet therapy (76.6 % vs. 85.0%, p<0.001) and statins or any lipid lowering therapy (62.6% vs. 67.1%, p=0.04) compared to men on presentation. There was a trend toward higher all-cause mortality in women compared to men (21.5% vs. 17.8%, p=0.09) at 7 years.

Conclusion
: Even in the current era, women continue to receive less aggressive care compared to men. More efforts should be made to bridge the treatment gap between men and women.
Abstract 4204: Osteoprotegerin Levels and Risk of Future Cardiovascular Events in Apparently Healthy Men and Women: the Prospective EPIC-Norfolk Population Study 1993–2003
Authors: Semb Anne Grete , Ueland T , Aukrust P , Kuivenhoven J- A , Wareham N J , Bingham S A , Day N E , Luben R , Gullestad L , Pedersen T , Kastele J J , Boekholdt S M , Khaw K- T
Published: April 2024

Introduction:
The identification of osteoprotegerin (OPG) as a novel cardiovascular risk marker suggests an association between mediators of bone homeostasis and cardiovascular disease. OPG is a member of the tumour necrosis factor (TNF) superfamily, and functions as a soluble decoy receptor for RANKL. There is no epidemiological evidence that OPG levels predict future coronary events in healthy individuals. It was therefore our objective to study the prospective relationship between plasma levels of OPG and the risk of future CAD in such a population.

Methods and Results:
A nested case-control study among participants of the European prospective Investigation into Cancer and Nutrition (EPIC-Norfolk) study, a prospective population study of 25 663 men and women between 45 and 79 years of which 988 apparently healthy individuals developed coronary artery disease (CAD) were matched by sex and age with 1812 healthy controls which did not develop CAD. Baseline OPG was higher in cases than in controls [6957 pg/ml (5778 – 8727)
vs.
6602 pg/ml (5434–8242) (p<0.005) median and interquartile range], and significantly higher in women than men in both cases and controls. Using OPG quartiles based on the distribution among controls, baseline OPG levels were independently correlated with fatal and non fatal coronary events and the risk increased continuously (p for linearity= 0.008 men, p=0.01 women), also when adjusted for age, smoking, diabetes, body mass index, LDL, HDL, systolic blood pressure, this strong relationship still existed. When adjusted for log (CRP) as well, the OR in the highest OPG quartile was 2.17(0.86–5.49)(95% CI)(p=0.04) for women and 2.78 (1.45–5.32)(p<0.001) for men.

Conclusion:
Among apparently healthy men and women, an elevated level of OPG is associated with increased risk of future fatal and non fatal CAD.
Abstract 587: Impaired Renal Function is not only related to Decreased Cardiac Output but also to Increased Venous Pressure in Patients with Cardiac Dysfunction
Authors: Damman Kevin , Smilde Tom D , Voors Adriaan A , van der Bij Wim , Navis Gerjan , van Veldhuisen Dirk J , Hillege Hans L
Published: April 2024

Introduction:
Glomerular filtration rate (GFR) is an important prognostic variable in chronic heart failure (CHF). CHF is associated with increased venous congestion and decreased cardiac output. The latter results in decreased renal blood flow (RBF). While the relationship between RBF and GFR is well established, little is known about the relationship between venous congestion and GFR.

Hypothesis:
We assessed the hypothesis that venous congestion plays a significant contributing role in determining renal function in patients with cardiac dysfunction.

Methods:
We studied 51 patients (30% male, mean age 40 ± 11 years), with cardiac dysfunction due to pulmonary hypertension. Right heart catheterisation was done to investigate right atrial pressure (RAP), mean pulmonary artery pressure, pulmonary vascular resistance (PVR) and cardiac index. GFR and RBF were measured by iothalamate and hippuran clearances, respectively.

Results.
Mean age was 40 ± 11 years and 69% of patients was female. Mean GFR was 73 ± 19 ml/min/1.73m
2
with a mean cardiac index of 2.1 ± 0.7 l/min/m
2
. In univariate analysis, RBF, RAP, cardiac index and PVR were related to GFR. In multivariate analysis, RBF ( r = 0.664, p < 0.001) and RAP (r = − 0.367, p < 0.020) were independently associated with GFR, accounting for 61% of the variability in GFR. Especially in patients with lower values of RBF, increased RAP was an important determinant of GFR (Figure

).

Conclusion.
RBF remains the most important factor associated with GFR in patients with cardiac dysfunction. However, especially in patients with low RBF, venous congestion indicated by an increased RAP plays a significant role in predicting GFR.
2009 Sol Sherry Distinguished Lecture in Thrombosis—Hemostasis and Thrombosis—Two Sides of the Same Coin?
Authors: Mackman Nigel
Published: April 2024

Blood coagulation is essential for life. The clotting cascade is divided into extrinsic (tissue factor and factor VIIa), intrinsic (factors XIIa, XIa, IXa, and FVIIIa), and common (factor Xa, factor Va, and thrombin) pathways that generate cross-linked fibrin. Hemostasis is a physiological process that prevents excess bleeding after vessel injury. Under normal conditions, all coagulation factors, except tissue factor, reside in the blood. Tissue factor is expressed in the vessel wall and activates the clotting system after injury. Thrombosis is a pathological process that leads to occlusion of blood vessels. Thrombosis can be triggered by rupture of an atherosclerotic plaque or by tissue factor–positive microparticles in the blood. Mice lacking components of the extrinsic or common pathways do not survive, which indicates that these pathways are essential for hemostasis. In contrast, mice lacking either factor XI or factor XII have no hemostatic defects, which suggests that these factors are not required for hemostasis. Mice deficient in either factor VIII or IX survive but exsanguinate after tail transection, consistent with a role in amplification of the cascade.

Surprisingly, mice lacking either factor XII or factor XI were protected in thrombosis models demonstrating a role in thrombosis. These results reveal mechanistic differences between hemostasis and thrombosis. At present, the identity of the activators of the intrinsic pathway has not been defined but may include extracellular RNA released from damaged cells and polyphosphate secreted from activated platelets. A better understanding of the different pathways may lead to the development of novel antithrombotic drugs.

These designations were based on the “ex vivo” activation of coagulation. An “extrinsic” factor called tissue thromboplastin (also known as factor III or tissue factor) initiated clotting via the extrinsic pathway, and this reaction formed the basis of the prothrombin time assay. In contrast, addition of blood to a negatively charged surface, such as kaolin, activated the clotting cascade via the intrinsic pathway. This is called the activated partial thromboplastin time and is driven by factor XIIa (also known as Hageman factor). However, individuals deficient in factor XII, such as John Hageman, were not bleeders. This suggested that factor XIIa was not required for in vivo clotting. In 1991, Gailani and Broze found that thrombin could activate factor XI and factor XII was largely removed from diagrams of the clotting cascade. Studies on mice lacking different clotting factors demonstrated essential roles in hemostasis for components of the extrinsic and common pathways.