bluuebunny/crossref_metadata_2025 huggingface dataset:
Music Therapy Increases Social and Emotional Well-Being in Persons With Dementia: A Randomized Clinical Crossover Trial Comparing Singing to Verbal Discussion
Authors: Reschke-Hernández Alaine E , Gfeller Kate , Oleson Jacob , Tranel Daniel
Published: May 2023

The number of people living with Alzheimer’s disease and related dementias (ADRD) is growing proportional to our aging population. Although music-based interventions may offer meaningful support to these individuals, most music therapy research lacks well-matched comparison conditions and specific intervention focus, which limits evaluation of intervention effectiveness and possible mechanisms. Here, we report a randomized clinical crossover trial in which we examined the impact of a singing-based music therapy intervention on feelings, emotions, and social engagement in 32 care facility residents with ADRD (aged 65–97 years), relative to an analogous nonmusic condition (verbal discussion). Both conditions were informed by the Clinical Practice Model for Persons with Dementia and occurred in a small group format, three times per week for two weeks (six 25-minute sessions), with a two-week washout at crossover. We followed National Institutes of Health Behavior Change Consortium strategies to enhance methodological rigor. We predicted that music therapy would improve feelings, positive emotions, and social engagement, significantly more so than the comparison condition. We used a linear mixed model approach to analysis. In support of our hypotheses, the music therapy intervention yielded significant positive effects on feelings, emotions, and social engagement, particularly for those with moderate dementia. Our study contributes empirical support for the use of music therapy to improve psychosocial well-being in this population. Results also highlight the importance of considering patient characteristics in intervention design and offer practical implications for music selection and implementation within interventions for persons with ADRD.
Republican Freedom and Committees of Safety: Notes on Historicization in Critical Security Studies
Authors: Bonacker Thorsten , Carl Horst , Langenohl Andreas , Marciniak Angela L
Published: May 2023

This paper discusses the historical case of committees of safety and their role in three republican revolutions in early modern western political history in order to conceptually contribute to the historicization of critical security studies. These committees were significant in amalgamating republican understandings of public freedom with demands for security from tyrannical oppression, thus highlighting the constitutive role of security considerations in the formation of republican polities and republican political constituencies. Yet, they also pointed to the seemingly self-defeating effects of those committees’ practices in situations perceived as revolutionary, which regularly involved clandestine, self-legitimating, and oppressive force against “enemies of the revolution” and potential internal opposition alike, and hence undermined normative notions of republican freedom. The paper introduces an analytical triad, consisting of definition of security situation, interpretative frame, and security repertoire, which allows analyzing historical situations of securitization in full complexity while at the same time allowing inter-comparability and the modeling of dynamic invocations of security by interdependent actors. Applied to the historical narrative, two interrelated conceptual consequences for a historicization of critical security studies are derived. First, prominent strands in critical security studies will profit from studying securitization as a politically constitutive, as opposed to a merely transformative, act, precisely as securitization crystallizes in historically specific, politically constitutive organizational forms, such as committees of safety. Second, the paper complicates accounts concerning the security/freedom nexus inherited from conceptual history, analyzing the entanglement of republicanism with security reasoning from the perspective of historically situated practices.
How Can We Know What We Think We Know about Cyber Operations?
Authors: Lilli Eugenio
Published: May 2023

Academic research on cyber operations is characterized by an exceptional paucity of work on sources and methods of information gathering and analysis. This lack of attention can arguably hinder the future development of this increasingly important area of research and weaken its potential impact on policymaking and the wider society. This article sets to redress this undesirable situation by addressing a number of critical questions: What obstacles make collecting information on cyber operations especially hard? What are the main sources of information available to the scholar of cyber international relations? Why should we rely critically on these sources? This article's second main contribution is to advance the adoption of a research technique for the study of cyber operations based on a combination of Triangulation and Problematization called TP technique. The article also provides three detailed examples of how this research technique can be used in practice to investigate specific scenarios concerning real-world cyber operations. The article ends with a discussion of the limitations of the proposed technique while also reaffirming the benefits deriving from its application to the study of cyber operations.
An elusive dark central mass in the globular cluster M4
Authors: Vitral Eduardo , Libralato Mattia , Kremer Kyle , Mamon Gary A , Bellini Andrea , Bedin Luigi R , Anderson Jay
Published: May 2023

Recent studies of nearby globular clusters have discovered excess dark mass in their cores, apparently in an extended distribution, and simulations indicate that this mass is composed mostly of white dwarfs (respectively stellar-mass black holes) in clusters that are core collapsed (respectively with a flatter core). We perform mass-anisotropy modelling of the closest globular cluster, M4, with intermediate slope for the inner stellar density. We use proper motion data from Gaia Early Data Release 3 (EDR3) and from observations by the Hubble Space Telescope. We extract the mass profile employing Bayesian Jeans modelling, and check our fits with realistic mock data. Our analyses return isotropic motions in the cluster core and tangential motions (β ≈ −0.4 ± 0.1) in the outskirts. We also robustly measure a dark central mass of roughly $800\pm 300 \, \rm M_\odot$ , but it is not possible to distinguish between a point-like source, such as an intermediate-mass black hole (IMBH), and a dark population of stellar remnants of extent ${\approx} 0.016\, {\rm pc} \simeq 3300\, {\rm au}$ . However, when removing a high-velocity star from the cluster centre, the same mass excess is found, but more extended (${\sim} 0.034\, {\rm pc} \approx 7000\, {\rm au}$ ). We use Monte Carlo N-body models of M4 to interpret the second outcome, and find that our excess mass is not sufficiently extended to be confidently associated with a dark population of remnants. Finally, we discuss the feasibility of these two scenarios (i.e. IMBH versus remnants), and propose new observations that could help to better grasp the complex dynamics in M4’s core.
A search for tryptophan in the gas of the IC 348 star cluster of the Perseus molecular cloud
Authors: Iglesias-Groth Susana
Published: May 2023

We have used spectra of the Spitzer Space Telescope to conduct a search for the aromatic amino acid tryptophan in the interstellar gas of the young star cluster IC 348. For all the strongest mid-infrared (mid-IR) laboratory bands of tryptophan, we have found counterpart emission lines in the observed spectrum which are consistent in wavelength and strength with the laboratory measurements. Assuming that the detected emission lines are due to tryptophan and using the measured fluxes, we estimate a tryptophan column density in the line of sight of the core of IC 348 in the range 109–1011 cm−2. The observed emission lines are also found in the combined spectrum of >30 interstellar locations obtained in diverse unrelated star-forming regions observed by Spitzer. This could be an indication that the molecule causing the emission is widespread in interstellar space. Future high spectral resolution mid-IR searches for proteinogenic amino acids in protostars, protoplanetary discs, and in the interstellar medium will be key to study an exogenous origin of meteoritic amino acids and to understand how the pre-biotic conditions for life were set in the early Earth.
On the distribution of the cold neutral medium in galaxy discs
Authors: Smith Rowan J , Tress Robin , Soler Juan D , Klessen Ralf S , Glover Simon C O , Hennebelle Patrick , Molinari Sergio , Mac Low Mordecai-Mark , Whitworth David
Published: May 2023

The cold neutral medium (CNM) is an important part of the galactic gas cycle and a precondition for the formation of molecular and star-forming gas, yet its distribution is still not fully understood. In this work, we present extremely high resolution simulations of spiral galaxies with time-dependent chemistry such that we can track the formation of the CNM, its distribution within the galaxy, and its correlation with star formation. We find no strong radial dependence between the CNM fraction and total neutral atomic hydrogen (H i) due to the decreasing interstellar radiation field counterbalancing the decreasing gas column density at larger galactic radii. However, the CNM fraction does increase in spiral arms where the CNM distribution is clumpy, rather than continuous, overlapping more closely with H2. The CNM does not extend out radially as far as H i, and the vertical scale height is smaller in the outer galaxy compared to H i with no flaring. The CNM column density scales with total mid-plane pressure and disappears from the gas phase below values of PT/kB = 1000 K cm−3. We find that the star formation rate density follows a similar scaling law with CNM column density to the total gas Kennicutt–Schmidt law. In the outer galaxy, we produce realistic vertical velocity dispersions in the H i purely from galactic dynamics, but our models do not predict CNM at the extremely large radii observed in H i absorption studies of the Milky Way. We suggest that extended spiral arms might produce isolated clumps of CNM at these radii.
What boost galaxy mergers in two massive galaxy protoclusters at z = 2.24?
Authors: Liu Shuang , Zheng Xian Zhong , Shi Dong Dong , Cai Zheng , Fan Xiaohui , Wang Xin , Yuan Qirong , Xu Haiguang , Pan Zhizheng , Liu Wenhao , Qin Jianbo , Zhang Yuheng , Wen Run
Published: May 2023

Characterizing the structural properties of galaxies in high-redshift protoclusters is key to our understanding of the environmental effects on galaxy evolution in the early stages of galaxy and structure formation. In this study, we assess the structural properties of 85 and 87 Hα emission-line candidates (HAEs) in the densest regions of two massive protoclusters, BOSS1244 and BOSS1542, respectively, using the Hubble Space Telescope (HST) H-band imaging data. Our results show a true pair fraction of 22 ± 5 (33 ± 6) per cent in BOSS1244 (BOSS1542), which yields a merger rate of 0.41 ± 0.09 (0.52 ± 0.04) Gyr−1 for massive HAEs with log (M*/M⊙) ≥ 10.3. This rate is 1.8 (2.8) times higher than that of the general fields at the same epoch. Our sample of HAEs exhibits half-light radii and Sérsic indices that cover a broader range than field star-forming galaxies. Additionally, about 15 per cent of the HAEs are as compact as the most massive (log (M*/M⊙) ≳ 11) spheroid-dominated population. These results suggest that the high galaxy density and cold dynamical state (i.e. velocity dispersion of <400 km s−1) are key factors that drive galaxy mergers and promote structural evolution in the two protoclusters. Our findings also indicate that both the local environment (on group scales) and the global environment play essential roles in shaping galaxy morphologies in protoclusters. This is evident in the systematic differences observed in the structural properties of galaxies between BOSS1244 and BOSS1542.
Iswarchandra Vidyasagar
Authors: Sen Amiya P.
Published: May 2023

Iswarchandra Bandopadhyay (b. 1820–d. 1891), commonly known as Pundit Iswarchandra Vidyasagar, was a prominent polymath of 19th-century Bengal, emblematic of the flowering of new ideas and values during that period. The Pundit felicitously combined the roles of an educator, creative writer, and social reformer in ways that were unique. The man was an exemplary student, highly meritorious and painstakingly diligent, notwithstanding the poverty and hardships he had to face in his early life. His prodigious scholarship earned him the title “Vidyasagar” (literally, the “ocean of learning”), conferred upon him by his teachers. Though groomed in the Sanskrit knowledge systems, Vidyasagar differed from the traditional Hindu scholar and teacher in two meaningful respects. First, he viewed his educational schemes as experiments in bridging indigenous knowledge and the European. This endeavor persuaded him to critique his own tradition and introduce innovative changes within existing courses of study. Second, he devoted much energy and attention to the production of a new genre of textbooks that simplified the processes of learning and employed a moral pedagogy, which he believed would help build character in young schoolboys. His primers for the study of the Bengali language are still in use in contemporary Bengal, more than a century after they were first produced. As a social reformer, Vidyasagar took up issues that were both daunting and deeply problematic. He was a pioneer in the field of female education and persuaded the government to pass a law enabling Hindu widows to marry. However, he was less successful with some related issues, such as prohibiting Hindu polygamy. All the same, his work demonstrates the importance of creating an enlightened public opinion, as well as the practical necessity for social legislation. Vidyasagar was also an accomplished writer and contributed to the modernization of the Bengali language. He wrote in elegant Bengali prose, freed of both older pedantic influences and vulgar colloquialism. In his own province, Vidyasagar is also still remembered as a great philanthropist and a compassionate soul, always ready to rescue those in distress, and often at the risk of incurring personal debts. In his mental constitution, he was an activist, pledged to improving everyday life in the world, and the traditional Hindu concerns with renunciation or afterlife utterly failed to move him. Sadly, Vidyasagar also remains the only iconic figure from renascent Bengal whose memory has been thoughtlessly tarnished by posterity. Both the political Left and the political Right in India have taken turns in publicly vandalizing his image without just cause.
Voting Technology and Election Administration in the United States
Authors: Alvarez R. Michael
Published: May 2023

Voting technologies and election administration have become a growth area for academic research. Before the 2000 US presidential election, a strong body of research in election science did not exist. However, in the decades since that close and contested presidential election, researchers from multiple academic disciplines have produced many excellent studies of election procedures, laws, administration, and technologies. This chapter provides an overview of the political science and political administration research literature on voting technologies and election administration in the United States.
Reliability–Contemporary Psychometric Conceptions
Authors: Raykov Tenko
Published: May 2023

Reliability is a major index of quality of behavioral measurement. Informally, reliability of a behavior measuring device—whether an item, question, scale, inventory, self-report, or test—reflects the repeatability of the results obtainable with it. The reliability index—often referred to as an index of reliability and defined as the (positive) square root of the reliability coefficient—is substantially less often used than the reliability coefficient in the behavioral sciences. This index represents the extent to which an observation, considered as a random variable, correlates with the associated true value it aims to evaluate. The reliability coefficient, which is at present nearly always employed in theoretical and empirical measurement-related discussions and treatments, can be thought of as the degree to which observed individual differences (of the units of analysis) are the result of true underlying individual differences.
The Arctic
Authors: Nicol Heather
Published: May 2023

Driven by the interests of explorers and scientists, polar geography emerged from the quest for territory, fame, and recognition. Until the second half of the twentieth century, “polar geography” was a field for physical geographers and until fairly recently, human geographers were more interested in the Arctic than Antarctic. The end of the Cold War and subsequent focus on Arctic environmental conservation, the looming specter of climate change, and the International Polar Year (2007–2008) were largely responsible for reinvigorating geographical research in the north and for advancing knowledge concerning both the North and South Poles. There was growing recognition of the environmental vulnerability of the Arctic region to global patterns of pollution, industrialization, and climate change. But there has also been considerable development in the study of Indigenous communities’ adaptation and resilience in the Arctic region, and a new and growing interest in traditional knowledge in light of climate change and its local impacts. Similarly, knowledge of the relationship between policy, governance, and sovereignty has grown, and has led to a resurgence of geopolitical assessments of the Arctic, as well as new research concerned with understanding the relationship between human security and economic development. At the same time, human security broadly defined has emerged as an important topic for geographical consideration. Over the past decade or so, polar geography—particularly that of the Arctic—has developed a renewed interest in environmental events as a consequence of climate change and globalization, but has also become a much more collaborative and interdisciplinary exercise as the roster of new publications derived from research on human development, and social resilience shows—see Arctic Resilience Report 2016 (cited under Environments and Climate Change: Books and Edited Volumes) and Human Development Report: Regional Processes and Global Linkages (Arctic Human Development Report Volume II) cited under General Overviews of the Arctic: Books and Edited Volumes. The citations below reflect this broad range, beginning with introductory, general, and seminal works on the geographies of the Arctic and following with a series of links to journals and collections of articles and websites organized by relevant topics and themes.
Josefa de Óbidos
Authors: Ripollés Carmen
Published: May 2023

Josefa de Ayala (b. Seville, 1630–d. Óbidos, 1684), commonly known as Josefa de Óbidos, is one of the few documented professional women artists of early modern Iberia, and arguably the most celebrated painter of the Portuguese baroque. She was the daughter of Baltazar Gomes Figueira, a Portuguese painter who was well known at the time for his still lifes and landscape backgrounds. Baltazar Gomes developed part of his career in Seville, where Josefa de Óbidos was born in 1630 (the painter Francisco Herrera the Elder was her godfather) and where she lived for an indeterminate number of years before 1646, when she signed and dated her first documented works, and only a few years after Portugal proclaimed its independence from Spain. Based in the Portuguese town of Óbidos from 1646 until her death in 1684, Josefa created engravings, small-format oil paintings on copper, large altarpieces for churches and monasteries, still lifes, portraits, and individual devotional paintings—an impressive variety of formats and subjects of which more than 100 works remain. Although she sometimes collaborated with her father, Josefa de Óbidos kept her own workshop after attaining the legal title of “donzela emancipada” (emancipated maidenba), which allowed for her independence. Her fame grew to mythical proportions during the eighteenth and nineteenth centuries, when a number of biographers stressed her feminine piety and celibate isolation—she never married. For much of the twentieth century, scholars built on these romantic notions, emphasizing the presumed folk provincialism, use of surface decoration, and sentimental naiveté of her work. They also placed undue weight on her still lifes (now considered a small portion of her oeuvre) and on the presumed mysticism of her works, exaggerating the isolated context of Óbidos—in reality, a town with important links to the court. From the 1970s, and thanks to the pioneering work of Vítor Serrão, Luís de Moura Sobral, and Joaquim Oliveira Caetano in Portugal, and Edward J. Sullivan in the United States, as well as the invaluable contribution of a number of exhibitions, Josefa de Óbidos’s career and work have undergone a profound reassessment through rigorous archival research and the introduction of new approaches taking into account gender, global connections, and material culture. The painter is now seen as a defining player of the Portuguese baroque who engaged with artistic, religious, and political concerns of utmost currency in the Portuguese culture of her day, making her one of the most characteristic, prolific, and original artists of early modern Portugal, although scholarship outside of Portugal is still limited.
Epidemiology of Gram-Negative Bloodstream Infections in the United States: Results From a Cohort of 24 Hospitals
Authors: Ince Dilek , Fiawoo Suiyini , Choudhury Rebecca , Cosgrove Sara E , Dobrzynski David , Gold Howard , Lee Jae Hyoung , Percival Kelly M , Shulder Stephanie , Sony Deepthi , Spivak Emily S , Tamma Pranita D , Nori Priya
Published: May 2023

Background

To address knowledge gaps in management of Gram-negative bloodstream infection, the Antibiotic Stewardship Implementation Collaborative was established consisting of programs from 24 academic and community hospitals across the United States.

Methods

A retrospective cohort study was conducted of unique adult patients with Gram-negative bloodstream infection hospitalized at participating hospitals from January to December 2019. Patient level and microbiologic data were collected via electronic medical record review with a standardized data collection form and data dictionary. Data analysis was largely descriptive. The Pearson χ2 test to compare categorical variables and the Wilcoxon rank sum test for continuous variables were used.

Results

In total, 4851 bacterial isolates from 3710 eligible unique patients were included in the cohort. Most common source of infection was the urinary tract (47.9%). Source control was achieved in 84% of cases. Escherichia coli (2471, 51.0%) was the most common Gram-negative organism recovered. Antibiogram combining isolates from all participating centers with species-level susceptibilities and source specific antibiograms for isolates from urinary, respiratory, and intraabdominal source were created. Northeast sites contributed the most extended spectrum beta-lactamase (ESBL) producing organisms (73%), but West sites had the highest percentage of ESBL producers of total isolates (16%). A statistically significant difference in percentage of ESBL-producing organisms in Whites vs. non-Whites (14.6 % and 9.5 %, respectively, P<0.01) was observed.

Conclusions

While the present study was conducted pre-pandemic, it highlights the need for stewardship data collaboratives to enhance our understanding of the antimicrobial resistance patterns.
Construction of regulatory network for alopecia areata progression and identification of immune monitoring genes based on multiple machine-learning algorithms
Authors: Xiong Jiachao , Chen Guodong , Liu Zhixiao , Wu Xuemei , Xu Sha , Xiong Jun , Ji Shizhao , Wu Minjuan
Published: May 2023

Objectives

Alopecia areata (AA) is an autoimmune-related non-cicatricial alopecia, with complete alopecia (AT) or generalized alopecia (AU) as severe forms of AA. However, there are limitations in early identification of AA, and intervention of AA patients who may progress to severe AA will help to improve the incidence rate and prognosis of severe AA.

Methods

We obtained two AA-related datasets from the gene expression omnibus database, identified the differentially expressed genes (DEGs), and identified the module genes most related to severe AA through weighted gene co-expression network analysis. Functional enrichment analysis, construction of a protein–protein interaction network and competing endogenous RNA network, and immune cell infiltration analysis were performed to clarify the underlying biological mechanisms of severe AA. Subsequently, pivotal immune monitoring genes (IMGs) were screened through multiple machine-learning algorithms, and the diagnostic effectiveness of the pivotal IMGs was validated by receiver operating characteristic.

Results

A total of 150 severe AA-related DEGs were identified; the upregulated DEGs were mainly enriched in immune response, while the downregulated DEGs were mainly enriched in pathways related to hair cycle and skin development. Four IMGs (LGR5, SHISA2, HOXC13, and S100A3) with good diagnostic efficiency were obtained. As an important gene of hair follicle stem cells stemness, we verified in vivo that LGR5 downregulation may be an important link leading to severe AA.

Conclusion

Our findings provide a comprehensive understanding of the pathogenesis and underlying biological processes in patients with AA, and identification of four potential IMGs, which is helpful for the early diagnosis of severe AA.
Effect of added calcium carbonate without and with benzoic acid on weanling pig growth performance, fecal dry matter, and blood Ca and P concentrations
Authors: Warner Alan J , DeRouchey Joel M , Tokach Mike D , Woodworth Jason C , Goodband Robert D , Gebhardt Jordan T
Published: May 2023

The objective of these studies was to determine the effects of increasing levels of calcium carbonate (CaCO3) with and without benzoic acid on weanling pig growth performance, fecal dry matter (DM), and blood Ca and P concentrations. In experiment 1, 695 pigs (DNA Line 200 × 400, initially 5.9 ± 0.02 kg) were used in a 28 d study. Pigs were weaned at approximately 21 d of age and randomly assigned to pens and then pens were allotted to one of five dietary treatments. Treatment diets were fed from weaning (day 0) to day 14, with a common diet fed from days 14 to 28. Dietary treatments were formulated to provide 0%, 0.45%, 0.90%, 1.35%, and 1.80% added CaCO3 at the expense of ground corn. From days 0 to 14 (treatment period), average daily gain (ADG) and G:F decreased (linear, P ≤ 0.01) as CaCO3 increased. From days 14 to 28 (common period) and for the overall experiment (days 0 to 28), there was no evidence of differences in growth performance between treatments. For fecal DM, there was a trend (quadratic, P = 0.091) where pigs fed with the highest CaCO3 diets had the greatest fecal DM. Experiment 2 used 360 pigs (DNA Line 200 × 400, initially 6.2 ± 0.03 kg) in a 38 d study. Upon arrival to the nursery facility, pigs were randomly assigned to pens and then pens were allotted to one of six dietary treatments. Dietary treatments were fed in three phases with treatment diets fed from days 0 to 10 and days 10 to 24, and a common phase 3 diet fed from days 24 to 38. Dietary treatments were formulated to provide 0.45%, 0.90%, and 1.35% added CaCO3 with or without 0.5% benzoic acid (VevoVitall, DSM Nutritional Products, Parsippany, NJ) added at the expense of ground corn. There was no evidence (P > 0.05) for any CaCO3 by benzoic acid interactions. For the experimental period (days 0 to 24), there was a tendency for benzoic acid to increase ADG (P = 0.056), average daily feed intake (ADFI; P = 0.071), and gain-to-feed ratio (G:F; linear, P = 0.014) as CaCO3 decreased. During the common period (days 24 to 38), pigs previously fed benzoic acid had increased (P = 0.045) ADG and marginally increased (P = 0.091) ADFI. For the overall study, pigs fed benzoic acid had increased ADG (P = 0.011) and ADFI (P = 0.030), marginally increased G:F (P = 0.096) and final body weight (P = 0.059). Serum Ca decreased (linear, P < 0.001) as CaCO3 decreased in the diet. These data show that decreasing the CaCO3 content in the nursery diet immediately after weaning may improve ADG and G:F. Dietary addition of benzoic acid may also provide beneficial effects on ADG and ADFI, regardless of dietary Ca level.
Terminology and Guidelines for Diagnostic Assay Development and Validation: Best Practices for Molecular Tests
Authors: Groth-Helms Deborah , Rivera Yazmín , Martin Frank N. , Arif Mohammad , Sharma Poonam , Castlebury Lisa A.
Published: May 2023

Effective use of diagnostic assays is essential for the early detection of plant pathogens and mitigation of potential disease impacts. Assay developers require a full understanding of the intended use of a test to address complicating factors that might be observed by an end user and limit the utility of the test and its scope of application in the field. The fitness of a test for a disease prevention application is determined by its performance characteristics, which are selected during assay design and defined during validation. This paper provides guidance to developers by standardizing the descriptions of key validation terms and concepts, including tiers that can be referenced in publications to better communicate the extent to which a test has been validated. These concepts are then applied in the broader context of a strategic approach to validation for various taxa and methods. The aim of this paper is to increase awareness of common pitfalls and gaps encountered during this process, with the goal of increased success in technology transfer. Recommendations are given for improving the efficiency and quality of test development through improved coordination among stakeholders.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Estrogen deficiency accelerates postmenopausal atherosclerosis by inducing endothelial cell ferroptosis through inhibiting NRF2/GPX4 pathway
Authors: Lv Ying , Zhang Shan , Weng Xiuzhu , Huang Jianxin , Zhao Honggang , Dai Xinyu , Bai Xiaoxuan , Bao Xiaoyi , Zhao Chen , Zeng Ming , Bai Yunshu , Hu Sining , Li Ji , Jia Haibo , Yu Bo
Published: May 2023

Oxidative stress and lipid metabolism disorder caused by estrogen deficiency are regarded as the main causes of postmenopausal atherosclerosis, but the underlying mechanisms remain still unclear. In this study, ovariectomized (OVX) female ApoE−/− mice fed with high‐fat diet were used to imitate postmenopausal atherosclerosis. The atherosclerosis progression was significantly accelerated in OVX mice, accompanied by the upregulation of ferroptosis indicators, including increased lipid peroxidation and iron deposition in the plaque and the plasma. While both estradiol (E2) and ferroptosis inhibitor ferrostatin‐1 alleviated atherosclerosis in OVX mice, with the inhibition of lipid peroxidation and iron deposition, as well as the upregulation of xCT and GPX4, especially in endothelial cells. We further investigated the effects of E2 on ferroptosis in endothelial cells induced by oxidized‐low‐density lipoprotein or ferroptosis inducer Erastin. It was found that E2 exhibited anti‐ferroptosis effect through antioxidative functions, including improving mitochondrial dysfunction and upregulating GPX4 expression. Mechanistically, NRF2 inhibition attenuated the effect of E2 against ferroptosis as well as the upregulation of GPX4. Our findings revealed that endothelial cell ferroptosis played a pivotal role in postmenopausal atherosclerosis progression, and the NRF2/GPX4 pathway activation contributed to the protection of E2 against endothelial cell ferroptosis.
Differential Structural Brain Changes Between Responders and Nonresponders After Physical Exercise Therapy for Chronic Nonspecific Neck Pain
Authors: de Zoete Rutger M. J. , Berryman Carolyn F. , Nijs Jo , Walls Angela , Jenkinson Mark
Published: May 2023

Objectives:

Physical exercise therapy is effective for some people with chronic nonspecific neck pain but not for others. Differences in exercise-induced pain-modulatory responses are likely driven by brain changes. We investigated structural brain differences at baseline and changes after an exercise intervention. The primary aim was to investigate changes in structural brain characteristics after physical exercise therapy for people with chronic nonspecific neck pain. The secondary aims were to investigate (1) baseline differences in structural brain characteristics between responders and nonresponders to exercise therapy, and (2) differential brain changes after exercise therapy between responders and nonresponders.

Materials and Methods:

This was a prospective longitudinal cohort study. Twenty-four participants (18 females, mean age 39.7 y) with chronic nonspecific neck pain were included. Responders were selected as those with ≥20% improvement in Neck Disability Index. Structural magnetic resonance imaging was obtained before and after an 8-week physical exercise intervention delivered by a physiotherapist. Freesurfer cluster-wise analyses were performed and supplemented with an analysis of pain-specific brain regions of interest.

Results:

Various changes in grey matter volume and thickness were found after the intervention, for example, frontal cortex volume decreased (cluster-weighted P value = 0.0002, 95% CI: 0.0000-0.0004). We found numerous differences between responders and nonresponders, most notably, after the exercise intervention bilateral insular volume decreased in responders, but increased in nonresponders (cluster-weighted P value ≤ 0.0002).

Discussion:

The brain changes found in this study may underpin clinically observed differential effects between responders and nonresponders to exercise therapy for people with chronic neck pain. Identification of these changes is an important step toward personalized treatment approaches.
Biologically Interpretable Deep Learning To Predict Response to Immunotherapy In Advanced Melanoma Using Mutations and Copy Number Variations
Authors: Zhang Liuchao , Cao Lei , Li Shuang , Wang Liuying , Song Yongzhen , Huang Yue , Xu Zhenyi , He Jia , Wang Meng , Li Kang
Published: May 2023

Only 30–40% of advanced melanoma patients respond effectively to immunotherapy in clinical practice, so it is necessary to accurately identify the response of patients to immunotherapy pre-clinically. Here, we develop KP-NET, a deep learning model that is sparse on KEGG pathways, and combine it with transfer- learning to accurately predict the response of advanced melanomas to immunotherapy using KEGG pathway-level information enriched from gene mutation and copy number variation data. The KP-NET demonstrates best performance with AUROC of 0.886 on testing set and 0.803 on an unseen evaluation set when predicting responders (CR/PR/SD with PFS ≥6 mo) versus non-responders (PD/SD with PFS <6 mo) in anti-CTLA-4 treated melanoma patients. The model also achieves an AUROC of 0.917 and 0.833 in predicting CR/PR versus PD, respectively. Meanwhile, the AUROC is 0.913 when predicting responders versus non-responders in anti-PD-1/PD-L1 melanomas. Moreover, the KP-NET reveals some genes and pathways associated with response to anti-CTLA-4 treatment, such as genes PIK3CA, AOX1 and CBLB, and ErbB signaling pathway, T cell receptor signaling pathway, et al. In conclusion, the KP-NET can accurately predict the response of melanomas to immunotherapy and screen related biomarkers pre-clinically, which can contribute to precision medicine of melanoma.
Greater Number of Plasma Exchanges Does Not Improve Outcome in Myasthenic Crisis
Authors: Hansen Michael , Neilson Lee , Parikh Melanie , Katirji Bashar
Published: May 2023

Objectives:

To determine the relationship between the number of plasma exchanges and clinical outcome in patients experiencing myasthenic crisis.

Methods:

We retrospectively reviewed all episodes of myasthenia gravis exacerbation/crisis who received plasmapheresis in patients admitted to a single-center tertiary care referral center from July 2008 to July 2017. We performed statistical analyses to determine whether the increased number of plasma exchanges improves the primary outcome (hospital length of stay) and the secondary outcome (disposition to home, skilled nursing facility, long-term acute care hospital, or death).

Results:

There is neither clinically observable nor statistically significant improvement in length of stay or disposition on discharge in patients who received 6 or greater sessions of plasmapheresis.

Conclusions:

This study provides class IV evidence that extending the number of plasma exchanges beyond 5 does not correlate with decreased hospital length of stay or improved discharge disposition in patients experiencing myasthenic crisis.
Clenbuterol Treatment Is Safe and Associated With Slowed Disease Progression in a Small Open-Label Trial in Patients With Amyotrophic Lateral Sclerosis
Authors: Li Xiaoyan , Koeberl Dwight D. , Lutz Michael W. , Bedlack Richard
Published: May 2023

Objective:

Clenbuterol, a beta-agonist, has plausible mechanisms for treating amyotrophic lateral sclerosis (ALS). In this highly inclusive open-label trial (NCT04245709), we aimed to study the safety and efficacy of clenbuterol in patients with ALS.

Methods:

All participants received clenbuterol starting at 40 μg daily and increased to 80 μg twice daily. Outcomes included safety, tolerability, ALS Functional Rating Score (ALSFRS-R) progression, forced vital capacity (FVC) progression, and myometry. ALSFRS-R and FVC slopes measured during treatment were compared with slopes before treatment (calculated by assuming ALSFRS-R was 48 and FVC was 100% at ALS onset).

Results:

The 25 participants had a mean age of 59, mean disease duration of 43 months, ALSFRS-R score at enrollment 34, and FVC at enrollment 77%. Forty-eight percent were female, 68% were taking riluzole, and none were taking edaravone. Two participants experienced severe adverse events, neither related to the study. Twenty-four participants experienced adverse events, most commonly tremors/jitters, cramps/spasms, insomnia, and stiffness/spasticity. Fourteen participants withdrew early from the trial, 13 due to adverse events. Patients who withdrew early were significantly older and more likely to be male. Per-protocol and intention-to-treat analyses showed meaningfully slower ALSFRS-R and FVC progression during treatment. Hand grip dynamometry and myometry changes were highly variable between participants; most declined slowly, but some showed improvements.

Conclusions:

Clenbuterol was safe but less tolerable at the doses we selected compared with an earlier Italian case series. Consistent with that series, our study suggested benefits on ALS progression. However, the latter result should be interpreted with caution as our study is limited by small sample size, large drop out, lack of randomization, and blinding and placebo controls. A larger, more traditional trial now seems warranted.
Frequency and Magnitude of Obstacles and Helpful Behavior Items in End-of-Life Care as Perceived by Nurses Working in Critical-Access Hospitals
Authors: Beckstrand Renea L. , Larsen Shalyn , Macintosh Janelle L. B. , Rasmussen Ryan , Luthy Karlen E. , Lyman Trissa M.
Published: May 2023

Background

Twenty percent of Americans live in rural areas where most of their health care is provided in critical-access hospitals (CAHs). It is unknown how frequently obstacle and helpful behavior items occur in end-of-life (EOL) care in CAHs.

Objectives

The aims of this study were to determine the frequency of occurrence scores of obstacle and helpful behavior items in providing EOL care in CAHs and to also determine which obstacles and helpful behaviors have the greatest or least impact on EOL care based on the magnitude scores.

Methods

A questionnaire was sent to nurses working in 39 CAHs in the United States. Nurse participants were asked to rate obstacle and helpful behavior items by size and frequency of occurrence. Data were analyzed to quantify the impact of obstacle and helpful behavior items on EOL care in CAHs by multiplying the mean size by the mean frequency of items to determine mean magnitude scores.

Results

Items with the highest and lowest frequency were determined. In addition, obstacle and helpful behavior item magnitude scores were calculated. Seven of the top 10 obstacles were related to patients' families. Seven of the top 10 helpful behaviors involved nurses ensuring families had positive experiences.

Conclusion

Nurses in CAHs perceived issues around patient family members as significant obstacles to EOL care. Nurses work to ensure that families have positive experiences. Visiting hour issues seemed to be irrelevant. The use of technology, such as telehealth, seemed to provide little benefit in EOL care in CAHs.
Evaluation of Training in Identifying and Responding to Suicide Risk by Staff of a Behavioral Health Managed Care Organization
Authors: Walker Marcie L. , Weems Lori A. , Hutchison Shari L. , Herschell Amy D. , Karpov Irina O. , MacDonald-Wilson Kim L.
Published: May 2023

Purpose of Study:

Gatekeeper training for individuals who may be in contact with someone contemplating suicide is a recommended suicide prevention strategy. This study assessed organizational-level gatekeeper training.

Primary Care Setting(s):

Gatekeeper training was conducted in a behavioral health managed care organization (BHMCO), which facilitates integrated behavioral and physical health services for 1.4 million Medicaid-enrolled Pennsylvanians.

Methodology and Sample:

Gatekeeper training was offered to BHMCO staff via a new training policy. Gatekeeper trainers were qualified BHMCO staff. Approximately half (47%) of trained staff served as care managers. Pre- and posttraining surveys were administered to assess self-reported confidence in ability to identify and assist individuals at risk for suicide. Post-training, staff responded to a hypothetical vignette involving suicide risk, which was evaluated for skills by gatekeeper trainers.

Results:

Eighty-two percent of staff completed training. Mean confidence scores improved significantly from pre- (η = 615) to posttraining (η = 556) (understanding = 3.41 vs. 4.11, respectively; knowledge = 3.47 vs. 4.04; identification = 3.30 vs. 3.94; respond = 3.30 vs. 4.04, p < .0001 for each). Intermediate and advanced skills to address suicide risk were demonstrated post-training in 68.6% and 17.2% of staff, respectively. More care managers versus other BHMCO staff demonstrated advanced skills (21.6% vs. 13.0%); however, both groups showed significant improvement pre- to post-training.

Implications for Case Management:

Care managers benefit from suicide prevention training and are uniquely positioned to serve as organizational leaders to successful population health initiatives to decrease suicide through training and education.
Build Trust and the Rest Will Get Done
Authors: Ferren Melora D.
Published: May 2023

In this column, Kathy Silard, MS, BSN, RN, FACHE, President and CEO of Stamford Health, shares leadership insights from a career path that started with neonatal ICU nursing and led to her current role as a healthcare system president and CEO.
Distinct trajectories of caregiver–toddler physiological attunement during routine vaccinations
Authors: Di Lorenzo-Klas Miranda G. , Waxman Jordana A. , Flora David B. , Schmidt Louis A. , Garfield Hartley , Flanders Dan , Weinberg Eitan , Savlov Deena , Pillai Riddell Rebecca R.
Published: May 2023

Introduction:

Toddlers rely on their caregivers for regulatory support when faced with pain-related distress. The caregiver's ability to support their toddler relies on their capacity to regulate their own distress and respond effectively to the child's need for support. The aim of the current study was to describe patterns of caregiver–toddler physiological co-regulatory patterns, also known as attunement, during routine vaccinations across the second year of life.

Methods:

Caregiver–toddler dyads (N = 189) were part of a longitudinal cohort observed at either 12-, 18-, or 24-month well-baby vaccinations. Parallel-process growth-mixture modeling was used to examine patterns of dyadic physiological co-regulatory responses, indexed by high-frequency heart rate variability (HF-HRV).

Results:

Three groups of dyads were discerned. The largest group (approximately 80%) demonstrated physiological attunement, with a stable and parallel regulatory pattern of HF-HRV from baseline to postneedle. The second group (7.9%) had parallel regulatory trajectories but with notably lower (ie, less regulated) HF-HRV values, which indicates independent regulatory responses (ie, a lack of attunement among dyad members). The third group (11.1%) showed diverging regulatory trajectories: Caregivers showed a stable regulatory trajectory, but toddlers demonstrated a steep decrease followed by an increase in HF-HRV values that surpassed their baseline levels by the third minute postneedle. Post hoc analyses with the HF-HRV groupings explored heart rate patterns and potential predictors.

Conclusions:

These findings elucidate potential adaptive and maladaptive co-regulatory parasympathetic patterns in an acute pain context.
Gluteal Fold: Cadaveric Dissection of the Superficial Fascial System in the Buttock and Anatomy-Based Gluteal Liposculpture
Authors: Si Loubin , Li Zhijin , Fu Lin , Zhang Mingzi , Tian Tong , Qi Zheng , Long Xiao , Wang Xiaojun , Wang Yang
Published: May 2023

Background:

The anatomy and formation mechanism of the gluteal fold (GF) remain unclear. Given that understanding the anatomy of the superficial fascial system (SFS) may facilitate the improvement of liposuction techniques, this study aimed to clarify and define the anatomical components of the GF.

Methods:

A total of 20 fresh female buttocks and thighs were dissected sagittally to observe the changes of the SFS along the GF and were dissected horizontally to observe the SFS on the upper, middle, and lower levels of the buttock.

Results:

Through these dissections, 2 patterns of the SFS in the GF region were identified. The retinaculum cutis (RC)-dominant SFS, named the fascial condensation zone, features an extremely dense and tough RC, originating from the bony structures (eg, the ischium) and radially anchored by the dermis. The fat-dominant SFS features a classic double-layered SFS structure. The RC-dominant SFS is mainly distributed at the medial GF, thus forming the depressed fold. It gradually disappears along the GF and the SFS becomes fat-dominant, making the fold increasingly less visible. At the lateral buttock, the SFS of the buttock and thigh reach an identical status in terms of morphologic features, showing a smooth curve between the buttock and the thigh instead of a fold. Thus, based on these findings, different liposuction methods were formulated to manage GF contouring.

Conclusions:

The SFS of the GF region shows a regional variation pattern. Topographic anatomy of the SFS in the GF region helps us understand GF contour deformities and provide an anatomical basis for surgical correction.