bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cognitive Impairment and Social Determinants of Health Among Indigenous Women
Authors: Roh Soonhee , Lee Yeon-Shim , Moon Heehyul , Steele Joel S , Warne Donald K , Lee Jung-Ah 
Published: June 2024

Abstract

Background and Objectives
Cognitive impairment and Alzheimer’s disease and related dementias (ADRD) pose significant challenges for Indigenous populations, necessitating urgent research. Limited evidence suggests that high rates of ADRD among Indigenous peoples are associated with social determinants of health (SDOH), such as education, income, health literacy, religion, and social engagement.

Research Design and Methods
Collaborating with a Northern Plains tribe, participants were recruited 123 self-identified Indigenous women aged 40–70 through a comprehensive recruitment strategy. Employing the SDOH framework, the research assessed cognitive impairment and Alzheimer’s disease knowledge (ADK), utilizing the Ascertain Dementia 8 and Alzheimer’s disease knowledge scales (ADK-30). The investigation examined the relationships between selected SDOH variables and cognitive impairment status.

Results
More than half of the participants showed signs of cognitive impairment, which correlated with lower income and education levels. Increased knowledge about Alzheimer’s disease, particularly in terms of treatment management and its life impact subscales, was associated with lower odds of cognitive impairment. Conversely, higher levels of depressive symptoms and participation in religious activities were linked to increased odds of cognitive impairment.

Discussion and Implications
The findings underscore the importance of culturally grounded tools and SDOH frameworks tailored to Indigenous contexts in addressing ADRD disparities. Future research should integrate historical and cultural factors to advance health equity within Indigenous communities, ultimately mitigating the impact of ADRD and promoting overall well-being.
Market landscape and insurer–provider integration: the case of ambulatory surgery centers
Authors: Zhao Xiaoxi , Richards Michael R , Damberg Cheryl L , Whaley Christopher M 
Published: June 2024

Abstract
Insurer–provider integration is a new form of vertical integration, with increasing prominence in health care markets. While there are potential benefits from tighter alignment between providers and payers, risks of perverse impacts on health care markets loom large. Yet, little is known about this new wave of consolidation, which limits options for policy or regulatory responses. We focus on a dominant insurer's acquisitions of ambulatory surgery centers (ASCs) to document the growth and geographic spread of these ownership events. We found that a diverse swathe of the United States has experienced an insurer-led ASC takeover. The acquisitions are also more frequently in areas where the insurer holds a higher enrollee market share at baseline, although a linear prediction of the likelihood of ASC acquisition shows a more nuanced picture.
Introgression of the Gamete Recognition Molecule, Bindin, in the Sea Urchin Diadema
Authors: Lessios H A 
Published: June 2024

Synopsis
Hybridization is important in evolution, because it is a necessary (though not sufficient) step in the introgression of potentially adaptive variation between species. Bindin is a gamete recognition protein in echinoids and asteroids, capable of blocking cross-fertilization between species to varying degrees. Four species of the sea urchin genus Diadema are broadly sympatric in the Indo-Pacific: D. paucispinum, D. savignyi, D. clarki, and D. setosum. Data from three published studies, one of identification of hybrids through allozymes, one of the phylogeography of mitochondrial DNA, and one of the phylogeny of bindin, were combined to assess the degree of bindin introgression between these four species. I analyzed sequences of the ATPase 8 and ATPase 6 mitochondrial genes and of bindin, sampled throughout the species ranges, with an isolation–migration algorithm, IMa3. IMa3 uses a coalescent approach to produce Bayesian estimates of effective population sizes and gene flow between populations. The results showed that bindin alleles coalesce completely within the species bounds of D. clarki and of D. setosum. The sister species D. paucispinum and D. savignyi, however, were estimated as having exchanged a bindin allele at an average of every one to two-and-a-half generations since they speciated from each other. As the allozyme study detected nine hybrids between three of these species in Okinawa (most of them between D. setosum and D. savignyi) in a single sample, hybrids between these species are produced, but bindin does not introgress. Therefore, bindin must not be efficient in blocking heterospecific fertilizations. Complete, or almost complete, reproductive isolation between species of Diadema must result from low hybrid fitness.
Cumulus: a federated electronic health record-based learning system powered by Fast Healthcare Interoperability Resources and artificial intelligence
Authors: McMurry Andrew J , Gottlieb Daniel I , Miller Timothy A , Jones James R , Atreja Ashish , Crago Jennifer , Desai Pankaja M , Dixon Brian E , Garber Matthew , Ignatov Vladimir , Kirchner Lyndsey A , Payne Philip R O , Saldanha Anil J , Shankar Prabhu R V , Solad Yauheni V , Sprouse Elizabeth A , Terry Michael , Wilcox Adam B , Mandl Kenneth D 
Published: June 2024

Abstract

Objective
To address challenges in large-scale electronic health record (EHR) data exchange, we sought to develop, deploy, and test an open source, cloud-hosted app “listener” that accesses standardized data across the SMART/HL7 Bulk FHIR Access application programming interface (API).

Methods
We advance a model for scalable, federated, data sharing and learning. Cumulus software is designed to address key technology and policy desiderata including local utility, control, and administrative simplicity as well as privacy preservation during robust data sharing, and artificial intelligence (AI) for processing unstructured text.

Results
Cumulus relies on containerized, cloud-hosted software, installed within a healthcare organization’s security envelope. Cumulus accesses EHR data via the Bulk FHIR interface and streamlines automated processing and sharing. The modular design enables use of the latest AI and natural language processing tools and supports provider autonomy and administrative simplicity. In an initial test, Cumulus was deployed across 5 healthcare systems each partnered with public health. Cumulus output is patient counts which were aggregated into a table stratifying variables of interest to enable population health studies. All code is available open source. A policy stipulating that only aggregate data leave the institution greatly facilitated data sharing agreements.

Discussion and Conclusion
Cumulus addresses barriers to data sharing based on (1) federally required support for standard APIs, (2) increasing use of cloud computing, and (3) advances in AI. There is potential for scalability to support learning across myriad network configurations and use cases.
Milk microbiome in the first month of lactation and at weaning from ewes supplemented with zinc pre- and postpartum
Authors: Knuth Ryan M , Page Chad M , Stewart Whitney C , Hummel Gwendolynn L , Woodruff Kelly L , Whaley Jaelyn R , Springer Alexis L , Austin Kathleen J , Murphy Thomas W , Bisha Bledar , Cunningham-Hollinger Hannah C 
Published: June 2024

Abstract
Mastitis is an important disease with economic and welfare implications in both clinical and subclinical states. The aim of this research was to sequence the hypervariable V4 region of the 16S rRNA gene to describe the microbial diversity and taxonomy of milk from clinically healthy ewes (Rambouillet, WF = 9; Hampshire, BF = 5). Experimental ewes represented a subset of a larger study assessing the impacts of divergent dietary zinc (Zn) concentrations [1 × National Academics of Sciences, Engineering, and Medicine (NASEM) recommendations = CON or 3 × NASEM recommendations = ZnTRT] throughout late gestation and lactation. Milk was collected at four periods during early lactation (18 to 24 h, 7 d, 14 d, and 21 d postpartum) and at weaning (84 ± 14 d postpartum). Somatic cell counts (SCC) were quantified, averaged, and classed (low: &lt; 500 × 103; medium: 500 × 103 – 100 × 104; high: &gt; 100 × 104 cells/mL). Milk samples (n = 67) were sequenced to identify bacteria and archaea; the most abundant phyla were Actinobacteria, Bacteroidetes, Cyanobacteria, Euryarchaeota, Firmicutes, Fusobacteria, Lentisphaerae, Proteobacteria, Spirochaetes, Tenericutes, Saccharibacteria TM7, and Verrucomicrobia. Mastitis pathogens were among the most relatively abundant genera, including Staphylococcus, Mannheimia, Corynebacterium, and Pseudomonas. Effects of breed, dietary Zn concentration, SCC class, and their two-way interactions on milk microbiome diversity and taxonomy were assessed within early lactation (using a repeated measures model) and weaning samples. Alpha-diversity metrics included Pielou’s evenness, Faith’s phylogenetic diversity, and Shannon’s entropy indices. The main and interactive effects between Zn treatment, breed, SCC class, and period were variable in early lactation and not evident in weaning samples. Milk from BF ewes had increased Faith’s phylogenetic diversity and Shannon’s entropy, and differed in unweighted UniFrac composition (P ≤ 0.10). Milk from CON ewes had a reduced rate of composition change through early lactation (P = 0.02) indicating greater microbiome stability than ZnTRT ewe milk. These results support that milk is not sterile, and breed, dietary Zn concentration, and SCC class variably affect the milk microbiome. Findings from the current study provide important foundational insights into the effects of increased dietary Zn supplementation on longitudinal changes in the milk microbiome and associations with mammary gland health and mastitis.
Fractures in women with type 2 diabetes are associated with marked deficits in cortical parameters and trabecular plates
Authors: Agarwal Sanchita , Germosen Carmen , Rosillo Isabella , Bucovsky Mariana , Colon Ivelisse , Kil Nayoung , Wang Zexi , Dinescu Andreea , Guo Xiang-Dong Edward , Walker Marcella 
Published: June 2024

Abstract
The basis for increased fracture risk in type 2 diabetes (T2DM) is not well understood. In this multi-ethnic, population-based study (n = 565), we investigated bone microstructure, trabecular plate/rod morphology, and mineralization in women with T2DM (n = 175) with and without fracture using a second-generation HRpQCT and individual trabecula segmentation and mineralization (ITS; ITM). Covariate-adjusted aBMD was 3.0%-6.5% higher at all sites (all p&lt;.005) in T2DM vs controls. By HRpQCT, T2DM had higher covariate-adjusted trabecular vBMD (5.3%-6.4%) and number (3.8%-5.1%) and greater cortical area at the radius and tibia. Covariate-adjusted cortical porosity was 10.0% higher at the tibia only in T2DM vs controls, but failure load did not differ. Among women with T2DM, those with adult atraumatic fracture (n = 59) had 5.2%-8.5% lower adjusted aBMD at all sites by DXA compared with those without fracture (n = 103). By HRpQCT, those with fracture had lower adjusted total vBMD and smaller cortical area (10.2%-16.1%), lower cortical thickness (10.5-15.8%) and lower cortical vBMD associated with 18.1 and 17.2% lower failure load at the radius and tibia, respectively (all p&lt;.05); plate volume and thickness were 5.7% and 4.7% lower, respectively, (p&lt;.05) while rod volume fraction was 12.8% higher in the fracture group at the tibia only. Sodium glucose cotransporter 2 inhibitor users (SGLT2i; n = 19), tended to have lower radial rod tissue mineral density by ITS (p=.06). GLP1 agonist users (n = 19) had trabecular deficits at both sites and higher cortical porosity and larger pores at the distal tibia. In summary, T2DM is associated with increased cortical porosity while those with T2DM and fracture have more marked cortical deficits and fewer trabecular plates associated with lower failure load.
Introducing the SPS Agreement
Authors: Gruszczynski Lukasz 
Published: June 2024

Abstract
This chapter introduces the Agreement on the Application of Sanitary and Phytosanitary Measures (the SPS Agreement). According to the agreement’s preamble, the agreement is conceived as an elaboration of the original General Agreement on Tariffs and Trade (GATT) exception. Sanitary and phytosanitary measures are those which apply to protect human, animal, plant life or health, or to prevent other damage within the territory of an importing Member.
In the above context, the chapter examines the scope of the SPS Agreement’s application, and its relationship to other parts of the WTO package, in particular the GATT and the Agreement on Technical Barriers to Trade. The chapter concludes by introducing the idea of Member autonomy in determining the appropriate level of SPS protection pursued. Later chapters will consider the extent to which this so-called right has, in practice, been undermined by the pronouncements of the WTO dispute settlement bodies.
Science and SPS
Authors: Gruszczynski Lukasz 
Published: June 2024

Abstract
This chapter discusses the science-based provisions of the Agreement on the Application of Sanitary and Phytosanitary Measures (the SPS Agreement), including the core obligation in Article 2.2 and the closely related obligations in Articles 5.1 (requirement of risk assessment). The usage of science as a benchmark in the agreement marks a radical departure from the predominantly discrimination-based approach of the General Agreement on Tariffs and Trade (GATT). It includes a careful discussion of the panel’s and AB’s reading of these obligations. It considers the nature of the scientific thresholds constructed by the dispute settlement bodies and, building upon Chapter 1, it considers the extent to which Members really do retain autonomy in defining their own ‘appropriate level of protection’.
The SPS Agreement and Developing Countries
Authors: Gruszczynski Lukasz 
Published: June 2024

Abstract
This chapter discusses of the developing country dimension of the Agreement on the Application of Sanitary and Phytosanitary Measures (the SPS Agreement). In this context, it elaborates on the key concepts of special and differential (S&D) treatment and technical assistance as well as related proposals for reform. The chapter also considers private standards as a challenge for developing countries. It then looks into the contrast between the high politics of systemic reform and the concrete achievements secured in the less high-profile world of the Committee governance.
Determination method for binary fractions using the integrated spectrum
Authors: Zhang F , Li L , Han Z , Wang X 
Published: June 2024

ABSTRACT
We need to resolve the individual stars for binary-fraction determinations of stellar systems. Therefore, it is not possible to obtain the binary fractions for dense or distant stellar systems. We propose a method to determine the binary fraction of a dense or distant stellar system: this method is first to determine the binary-fraction variation for any two adjacent regions and then to add up those binary-fraction variations along the radial direction to obtain the binary fraction for a stellar system. The binary-fraction variation is derived using 10 binary-fraction-sensitive spectral absorption feature indices (SAFIs) and the binary-fraction variation calibrations in terms of these SAFIs. Using this method, we first present the binary-fraction variations for 21 Galactic globular clusters (GCs). By comparison, we find that they agree well with the binary fractions based on the main-sequence fiducial line method from previous studies. This verifies that the above-mentioned method is feasible. Next, we present the binary-fraction variations of 13 Galactic GCs. We give the relationships between the binary fraction and various parameters, and find that the binary fraction is negatively correlated with NHB and NRR, the binary fraction of some studies is not strongly correlated with NBS, and the number of GCs with large binary fraction is greater for the extreme blue horizontal branch population ratio. Finally, if we want to obtain a more accurate binary fraction, we suggest that spectroscopic and photometric observations are conducted at an appropriate area interval for a stellar system.
High-throughput neural stem cell-based drug screening identifies S6K1 inhibition as a selective vulnerability in sonic hedgehog-medulloblastoma
Authors: Zhou Leilei , van Bree Niek , Boutin Lola , Ryu Jinhye , Moussaud Simon , Liu Mingzhi , Otrocka Magdalena , Olsson Magnus , Falk Anna , Wilhelm Margareta 
Published: June 2024

Abstract

Background
Medulloblastoma (MB) is one of the most common malignant brain tumors in children. Current treatments have increased overall survival but can lead to devastating side effects and late complications in survivors, emphasizing the need for new, improved targeted therapies that specifically eliminate tumor cells while sparing the normally developing brain.

Methods
Here, we used a sonic hedgehog (SHH)-MB model based on a patient-derived neuroepithelial stem cell system for an unbiased high-throughput screen with a library of 172 compounds with known targets. Compounds were evaluated in both healthy neural stem cells (NSCs) and tumor cells derived from the same patient. Based on the difference of cell viability and drug sensitivity score between normal cells and tumor cells, hit compounds were selected and further validated in vitro and in vivo.

Results
We identified PF4708671 (S6K1 inhibitor) as a potential agent that selectively targets SHH-driven MB tumor cells while sparing NSCs and differentiated neurons. Subsequent validation studies confirmed that PF4708671 inhibited the growth of SHH-MB tumor cells both in vitro and in vivo, and that knockdown of S6K1 resulted in reduced tumor formation.

Conclusions
Overall, our results suggest that inhibition of S6K1 specifically affects tumor growth, whereas it has less effect on non-tumor cells. Our data also show that the NES cell platform can be used to identify potentially effective new therapies and targets for SHH-MB.
Epigenetically rewiring metabolic genes via SIRT6 orchestrates MSC fate determination
Authors: Liao Xueyang , Li Feifei , Yu Fanyuan , Ye Ling 
Published: June 2024

Abstract
SIRT6 owns versatile types of enzymatic activities as a multitasking protein, including ribosyltransferase and deacetylase. To investigate the epigenetic regulations of SIRT6 on MSC fate determination via histone deacetylation, we used allosteric small molecules specifically controlling its histone 3 deacetylation activities. Results showed that enhanced deacetylation of SIRT6 promoted the ossific lineage commitment of MSC and finally achieved anabolic effects on hard tissues. Mechanistically, H3K9ac and H3K56ac, governed by SIRT6, in MSC orchestrated the transcriptions of crucial metabolic genes, mediating MSC fate determination. Most importantly, our data evidenced that modulating the epigenetic regulations of SIRT6, specifically via enhancing its deacetylation of H3K9ac and H3K56ac, was a promising choice to treat bone loss diseases and promote dentin regeneration. In this study, we revealed the specific roles of SIRT6’s histone modification in MSC fate determination. These findings endow us with insights on SIRT6 and the promising therapeutic choices through SIRT6’s epigenetic functions for hard tissues regeneration.
Disaggregation of canopy photosynthesis among tree species in a mixed broadleaf forest
Authors: Stojanović Marko , Jocher Georg , Kowalska Natalia , Szatniewska Justyna , Zavadilová Ina , Urban Otmar , Čáslavský Josef , Horáček Petr , Acosta Manuel , Pavelka Marian , Marshall John D 
Published: June 2024

Abstract
Carbon dioxide sequestration from the atmosphere is commonly assessed using the eddy covariance method. Its net flux signal can be decomposed into gross primary production and ecosystem respiration components, but these have seldom been tested against independent methods. In addition, eddy covariance lacks the ability to partition carbon sequestration among individual trees or species within mixed forests. Therefore, we compared gross primary production from eddy covariance versus an independent method based on sap flow and water-use efficiency, as measured by the tissue heat balance method and δ13C of phloem contents, respectively. The latter measurements were conducted on individual trees throughout a growing season in a mixed broadleaf forest dominated by three tree species, namely English oak, narrow-leaved ash and common hornbeam (Quercus robur L., Fraxinus angustifolia Vahl, and Carpinus betulus L., respectively). In this context, we applied an alternative ecophysiological method aimed at verifying the accuracy of a state-of-the-art eddy covariance system while also offering a solution to the partitioning problem. We observed strong agreement in the ecosystem gross primary production estimates (R2 = 0.56; P &lt; 0.0001), with correlation being especially high and nearly on the 1:1 line in the period before the end of July (R2 = 0.85; P &lt; 0.0001). After this period, the estimates of gross primary production began to diverge. Possible reasons for the divergence are discussed, focusing especially on phenology and the limitation of the isotopic data. English oak showed the highest per-tree daily photosynthetic rates among tree species, but the smaller, more abundant common hornbeam contributed most to the stand-level summation, especially early in the spring. These findings provide a rigorous test of the methods and the species-level photosynthesis offers avenues for enhancing forest management aimed at carbon sequestration.
DDB2 promotes melanoma cell growth by transcriptionally regulating the expression of KMT2A and predicts a poor prognosis
Authors: Zhang Changlin , Li Weizhao , Liu Lixiang , Li Miao , Sun Haohui , Zhang Chi , Zhong Li , Huang Jiajia , Li Tian 
Published: June 2024

AbstractIdentification of potential key targets of melanoma, a fatal skin malignancy, is critical to the development of new cancer therapies. Lysine methyltransferase 2A (KMT2A) promotes melanoma growth by activating the human telomerase reverse transcriptase (hTERT) signaling pathway; however, the exact mechanism remains elusive. This study aimed to reveal new molecular targets that regulate KMT2A expression and melanoma growth. Using biotin–streptavidin–agarose pull‐down and proteomics, we identified Damage‐specific DNA‐binding protein 2 (DDB2) as a KMT2A promoter‐binding protein in melanoma cells and validated its role as a regulator of KMT2A/hTERT signaling. DDB2 knockdown inhibited the expression of KMT2A and hTERT and inhibited the growth of melanoma cells in vitro. Conversely, overexpression of DDB2 activated the expression of KMT2A and promoted the growth of melanoma cells. Additionally, we demonstrated that DDB2 expression was higher in tumor tissues of patients with melanoma than in corresponding normal tissues and was positively correlated with KMT2A expression. Kaplan–Meier analysis showed a poor prognosis in patients with high levels of DDB2 and KMT2A. Overall, our data suggest that DDB2 promotes melanoma cell growth through the transcriptional regulation of KMT2A expression and predicts poor prognosis. Therefore, targeting DDB2 may regulate the effects of KMT2A on melanoma growth and progression, providing a new potential therapeutic strategy for melanoma.