bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perceived discrimination and refraining from seeking physician’s care in Sweden: an intersectional analysis of individual heterogeneity and discriminatory accuracy (AIHDA)
Authors: Hassan Mariam , Öberg Johan , Wemrell Maria , Vicente Raquel Perez , Lindström Martin , Merlo Juan 
Published: October 2024

Abstract
Background
Discrimination may further impede access to medical care for individuals in socially disadvantaged positions. Sociodemographic information and perceived discrimination intersect and define multiple contexts or strata that condition the risk of refraining from seeking physician’s care. By applying analysis of individual heterogeneity and discriminatory accuracy (AIHDA) we aimed to improve the mapping of risk by considering both strata average risk differences and the accuracy of such strata risks for distinguishing between individuals who did or did not refrain from seeking physician’s care.

Methods
We analysed nine annual National Public Health Surveys (2004, 2007–2014) in Sweden including 73,815 participants. We investigated the risk of refraining from seeking physician’s care across 64 intersectional strata defined by sex, education, age, country of birth, and perceived discrimination. We calculated strata-specific prevalences and prevalence ratios (PR) with 95% confidence intervals (CI), and the area under the receiver operating characteristic curve (AUC) to evaluate the discriminatory accuracy (DA).

Results
Discriminated foreign-born women aged 35–49 with a low educational level show a six times higher risk (PR = 6.07, 95% CI 5.05–7.30) than non-discriminated native men with a high educational level aged 35–49. However, the DA of the intersectional strata was small (AUC = 0.64). Overall, discrimination increased the absolute risk of refraining from seeking physician’s care, over and above age, sex, and educational level.

Conclusions
AIHDA disclosed complex intersectional inequalities in the average risk of refraining from seeking physician’s care. This risk was rather high in some strata, which is relevant from an individual perspective. However, from a population perspective, the low DA of the intersectional strata suggests that potential interventions to reduce such inequalities should be universal but tailored to the specific contextual characteristics of the strata. Discrimination impairs access to healthcare.
Pharmacological targeting of P300/CBP reveals EWS::FLI1-mediated senescence evasion in Ewing sarcoma
Authors: Wei Erdong , Mitanoska Ana , O’Brien Quinn , Porter Kendall , Molina MacKenzie , Ahsan Haseeb , Jung Usuk , Mills Lauren , Kyba Michael , Bosnakovski Darko 
Published: October 2024

AbstractEwing sarcoma (ES) poses a significant therapeutic challenge due to the difficulty in targeting its main oncodriver, EWS::FLI1. We show that pharmacological targeting of the EWS::FLI1 transcriptional complex via inhibition of P300/CBP drives a global transcriptional outcome similar to direct knockdown of EWS::FLI1, and furthermore yields prognostic risk factors for ES patient outcome. We find that EWS::FLI1 upregulates LMNB1 via repetitive GGAA motif recognition and acetylation codes in ES cells and EWS::FLI1-permissive mesenchymal stem cells, which when reversed by P300 inhibition leads to senescence of ES cells. P300-inhibited senescent ES cells can then be eliminated by senolytics targeting the PI3K signaling pathway. The vulnerability of ES cells to this combination therapy suggests an appealing synergistic strategy for future therapeutic exploration.
Proteomic analysis and experimental validation reveal the blood–brain barrier protective of Huanshaodan in the treatment of SAMP8 mouse model of Alzheimer’s disease
Authors: Su Yunfang , Liu Ningning , Wang Pan , Shang Congcong , Sun Ruiqin , Ma Jinlian , Li Zhonghua , Ma Huifen , Sun Yiran , Zhang Zijuan , Song Junying , Xie Zhishen , Xu Jiangyan , Zhang Zhenqiang 
Published: October 2024

Abstract
Background
Huanshaodan (HSD) is a Chinese Herbal Compound which has a definite clinical effect on Alzheimer’s disease (AD), however, the underlying mechanism remains unclear. The aim of this study is to preliminarily reveal the mechanism of HSD in the treatment of AD model of SAMP8 mice.

Methods
Chemical composition of HSD and its drug-containing serum were identified by Q-Orbitrap high resolution liquid mass spectrometry. Six-month-old SAMP8 mice were treated with HSD and Donepezil hydrochloride by gavage for 2 months, and Wogonin for 28 days. Behavioral test was performed to test the learning and memory ability of mice. Immunofluorescence (IF) or Western-blot methods were used to detect the levels of pSer404-tau and β-amyloid (Aβ) in the brain of mice. Hematoxylin–eosin (H&E) staining and Transmission electron microscopy (TEM) assay was applied to observe the pathological changes of neurons. Proteomic technology was carried out to analyze and identify the protein network of HSD interventions in AD. Then the pathological process of the revealed AD-related differential proteins was investigated by IF, Q-PCR, Western-blot, Fluorescence in situ hybridization (FISH) and 16S rRNA sequencing methods.

Results
The results showed that HSD and Wogonin, one of the components in its drug-containing serum, can effectively improve the cognitive impairments of SAMP8 mice, protect hippocampal neurons and synapses, and reduce the expression of pSer404-tau and Aβ. HSD and Wogonin reduced the levels of fibrinogen β chain (FGB) and γ chain (FGG), the potential therapeutic targets revealed by proteomics analysis, reduced the colocalization of FGB and FGG with Aβ, ionized calcium binding adaptor molecule 1 (Iba-1), glial fibrillary acidic protein (GFAP), increased level of and myelin basic protein (MBP). Meanwhile, HSD and Wogonin increased ZO-1 and Occludin levels, improved brain microvascular injury, and reduced levels of bacteria/bacterial DNA and lipopolysaccharide (LPS) in the brain of mice. In addition, 16S rRNA sequencing indicated that HSD regulated the structure of intestinal microbiota of mice.

Conclusion
The effects of HSD on AD may be achieved by inhibiting the levels of fibrinogen and the interactions on glia cells in the brain, and by modulating the structure of intestinal microbiota and improving the blood–brain barrier function.
Development of a new paradigm model for deciphering action mechanism of Danhong injection using a combination of isothermal shift assay and database interrogation
Authors: Wang Tianxiang , Yang Changmei , Tang Yuxiang , Wen Ke , Ma Yuxin , Chen Yuling , Li Zhiqiang , Zhao Yujiao , Zhu Songbiao , Meng Xianbin , Du Sijing , Miao Zelong , Wei Wei , Deng Haiteng 
Published: October 2024

Abstract
Background
Identification of active components of traditional Chinese Medicine (TCM) and their respective targets is important for understanding the mechanisms underlying TCM efficacy. However, there are still no effective technical methods to achieve this.

Methods
Herein, we have established a method for rapidly identifying targets of a specific TCM and interrogating the targets with their corresponding active components based on Isothermal Shift Assay (iTSA) and database interrogation.

Results
We optimized iTSA workflow and identified 110 targets for Danhong injection (DHI) which is used as an effective remedy for cardiovascular and cerebrovascular diseases. Moreover, we identified the targets of the nine major ingredients found in DHI. Database interrogation found that the potential targets for DHI, in which we verified that ADK as the target for salvianolic acid A and ALDH1B1 as the target for protocatechualdehyde in DHI, respectively.

Conclusion
Overall, we established a novel paradigm model for the identification of targets and their respective ingredients in DHI, which facilitates the discovery of drug candidates and targets for improving disease management and contributes to revealing the underlying mechanisms of TCM and fostering TCM development and modernization.

Graphical Abstract
Differences in seasonal dynamics and pyrethroid resistance development among Anopheles Hyrcanus group species
Authors: Lee Do Eun , Han Jeong Heum , Lee Gang Chan , Choi Junhyeong , Kwun Wonyong , Lee Si Hyeock , Kim Ju Hyeon 
Published: October 2024

Abstract
Background
The Anopheles Hyrcanus group, which transmits Plasmodium vivax, consists of six confirmed species in South Korea. An epidemiological study revealed differences in the seasonal occurrence patterns of each species. Pyrethroid resistance in An. sinensis dates back to the early 2000s, whereas information on pyrethroid resistance in other species is lacking despite their greater significance in malaria epidemiology.

Methods
Anopheles mosquitoes were collected from two malaria-endemic regions in South Korea for 2 years and their knockdown resistance (kdr) mutations were genotyped. The larval susceptibility to λ-cyhalothrin was compared in six Anopheles species and its seasonal changes in three species were investigated. The full-length sequences of the voltage-sensitive sodium channel (VSSC) were compared across six species to evaluate potential target-site insensitivity. The contribution of the kdr mutation to phenotypic resistance was confirmed by comparing median lethal time (LT50) to λ-cyhalothrin between populations of Anopheles belenrae with distinct genotypes.

Results
The composition and seasonal occurrence of rare species (Anopheles kleini, Anopheles lestri, and Anopheles sineroides) varied considerably, whereas An. sinensis occurs continuously throughout the season. A kdr mutation in the form of heterozygous allele was newly identified in An. belenrae, An. lesteri, An. pullus, and An. sineroides. The baseline susceptibility to λ-cyhalothrin was the highest in An. belenrae, followed by An. lesteri, An. sineroides, An. kleini, An. pullus, and An. sinensis, with median lethal concentration (LC50) values ranging from 6.0- to 73.5-fold higher than that of An. belenrae. The susceptibility of An. sinensis and An. pullus varied by season, whereas that of An. belenrae remained stable. The kdr-heterozygous An. belenare population exhibited 5.1 times higher LT50 than that of the susceptible population. Species-specific VSSC sequence differences were observed among the six species.

Conclusions
Our findings suggest that the status and extent of pyrethroid resistance vary among Anopheles Hyrcanus group species. While An. sinensis, the predominant species, developed a considerable level of pyrethroid resistance through kdr mutation, the resistance levels of other species appeared to be less pronounced. Large-scale monitoring is crucial to fully understand species-specific seasonal occurrence and resistance status for effective management strategies, considering the ongoing impact of climate change on their vectorial capacity.

Graphical Abstract
The goat pan-genome reveals patterns of gene loss during domestication
Authors: Liu Jiaxin , Shi Yilong , Mo Dongxin , Luo Lingyun , Xu Songsong , Lv Fenghua 
Published: October 2024

Abstract
Background
Unveiling genetic diversity features and understanding the genetic mechanisms of diverse goat phenotypes are pivotal in facilitating the preservation and utilization of these genetic resources. However, the total genetic diversity within a species can’t be captured by the reference genome of a single individual. The pan-genome is a collection of all the DNA sequences that occur in a species, and it is expected to capture the total genomic diversity of the specific species.

Results
We constructed a goat pan-genome using map-to-pan assemble based on 813 individuals, including 723 domestic goats and 90 samples from their wild relatives, which presented a broad regional and global representation. In total, 146 Mb sequences and 974 genes were identified as absent from the reference genome (ARS1.2; GCF_001704415.2). We identified 3,190 novel single nucleotide polymorphisms (SNPs) using the pan-genome analysis. These novel SNPs could properly reveal the population structure of domestic goats and their wild relatives. Presence/absence variation (PAV) analysis revealed gene loss and intense negative selection during domestication and improvement.

Conclusions
Our research highlights the importance of the goat pan-genome in capturing the missing genetic variations. It reveals the changes in genomic architecture during goat domestication and improvement, such as gene loss. This improves our understanding of the evolutionary and breeding history of goats.
Metaproteogenomics resolution of a high-CO2 aquifer community reveals a complex cellular adaptation of groundwater Gracilibacteria to a host-dependent lifestyle
Authors: Figueroa-Gonzalez Perla Abigail , Bornemann Till L. V. , Hinzke Tjorven , Maaß Sandra , Trautwein-Schult Anke , Starke Joern , Moore Carrie J. , Esser Sarah P. , Plewka Julia , Hesse Tobias , Schmidt Torsten C. , Schreiber Ulrich , Bor Batbileg , Becher Dörte , Probst Alexander J. 
Published: October 2024

Abstract
Background
Bacteria of the candidate phyla radiation (CPR), constituting about 25% of the bacterial biodiversity, are characterized by small cell size and patchy genomes without complete key metabolic pathways, suggesting a symbiotic lifestyle. Gracilibacteria (BD1-5), which are part of the CPR branch, possess alternate coded genomes and have not yet been cultivated. The lifestyle of Gracilibacteria, their temporal dynamics, and activity in natural ecosystems, particularly in groundwater, has remained largely unexplored. Here, we aimed to investigate Gracilibacteria activity in situ and to discern their lifestyle based on expressed genes, using the metaproteogenome of Gracilibacteria as a function of time in the cold-water geyser Wallender Born in the Volcanic Eifel region in Germany.

Results
We coupled genome-resolved metagenomics and metaproteomics to investigate a cold-water geyser microbial community enriched in Gracilibacteria across a 12-day time-series. Groundwater was collected and sequentially filtered to fraction CPR and other bacteria. Based on 725 Gbps of metagenomic data, 1129 different ribosomal protein S3 marker genes, and 751 high-quality genomes (123 population genomes after dereplication), we identified dominant bacteria belonging to Gallionellales and Gracilibacteria along with keystone microbes, which were low in genomic abundance but substantially contributing to proteomic abundance. Seven high-quality Gracilibacteria genomes showed typical limitations, such as limited amino acid or nucleotide synthesis, in their central metabolism but no co-occurrence with potential hosts. The genomes of these Gracilibacteria were encoded for a high number of proteins involved in cell to cell interaction, supporting the previously surmised host-dependent lifestyle, e.g., type IV and type II secretion system subunits, transporters, and features related to cell motility, which were also detected on protein level.

Conclusions
We here identified microbial keystone taxa in a high-CO2 aquifer, and revealed microbial dynamics of Gracilibacteria. Although Gracilibacteria in this ecosystem did not appear to target specific organisms in this ecosystem due to lack of co-occurrence despite enrichment on 0.2-µm filter fraction, we provide proteomic evidence for the complex machinery behind the host-dependent lifestyle of groundwater Gracilibacteria.
Ozone therapy mitigates parthanatos after ischemic stroke
Authors: Li Jiahui , Liu Xiaolei , Wang Zengze , Xie Pengyun , Zhu Min , Zhong Hanhui , Luo Sirui , Tang Jing , Mo Guixi 
Published: October 2024

Abstract
Background
Stroke is a leading cause of death worldwide, with oxidative stress and calcium overload playing significant roles in the pathophysiology of the disease. Ozone, renowned for its potent antioxidant properties, is commonly employed as an adjuvant therapy in clinical settings. Nevertheless, it remains unclear whether ozone therapy on parthanatos in cerebral ischemia–reperfusion injury (CIRI). This study aims to investigate the impact of ozone therapy on reducing parthanatos during CIRI and to elucidate the underlying mechanism.

Methods
Hydrogen peroxide (H2O2) was utilized to mimic the generation of reactive oxygen species (ROS) in SH-SY5Y cell reperfusion injury in vitro, and an in vivo ischemic stroke model was established. Ozone saline was introduced for co-culture or intravenously administered to mice. Apoptosis and oxidative stress were assessed using flow cytometry and immunofluorescence. Western blotting was utilized to examine the expression of parthanatos signature proteins. The mechanism by which ozone inhibits parthanatos was elucidated through inhibiting PPARg or Nrf2 activity.

Results
The findings demonstrated that ozone mitigated H2O2-induced parthanatos by either upregulating nuclear factor erythroid 2-related factor 2 (Nrf2) or activating peroxisome proliferator-activated receptorg (PPARg). Furthermore, through the use of calcium chelators and ROS inhibitors, it was discovered that ROS directly induced parthanatos and facilitated intracellular calcium elevation. Notably, a malignant feedback loop between ROS and calcium was identified, further amplifying the induction of parthanatos. Ozone therapy exhibited its efficacy by increasing PPARg activity or enhancing the Nrf2 translation, thereby inhibiting ROS production induced by H2O2. Concurrently, our study demonstrated that ozone treatment markedly inhibited parthanatos in stroke-afflicted mice. Additionally, ozone therapy demonstrated significant neuroprotective effects on cortical neurons, effectively suppressing parthanatos.

Conclusions
These findings contribute valuable insights into the potential of ozone therapy as a therapeutic strategy for reducing parthanatos during CIRI, highlighting its impact on key molecular pathways associated with oxidative stress and calcium regulation.
Planning for complex inferior vena cava filter retrievals: the implementation and effectiveness of 3D printed models
Authors: Lee Joonhyuk , Rybicki Frank J. , Ravi Prashanth , Chadalavada Seetharam C. 
Published: October 2024

Abstract
Background
Inferior vena cava filter (IVC) retrieval is most often routine but can be challenging with high morbidity in complex cases, especially those with an extended dwelling time. While risk of morbidity in complex retrievals is decreased with advanced filter retrieval techniques, deciding when and which to use these requires detailed pre-procedural planning. The purpose of our study was to evaluate patient-specific 3D printed anatomic IVC filter models for aiding complex IVC filter retrievals.

Methods
All IVC filter retrieval patients between June 2021 and September 2022 at one academic medical hospital were prospectively screened. Nine met criteria for complex retrieval, and their CT images were used to 3D print patient-specific IVC and filter models. Models were used in pre-procedural planning and clinical utility was assessed using the Anatomic Model Utility Likert Questionnaire and estimations of the procedural and fluoroscopy time saved.

Results
The usage of 3D printed models in pre-procedural planning had high clinical utility based on the Likert questionnaire (Anatomic Model Utility Points 366.7 ± 103.1). Using a model significantly increased confidence in planning (p = 0.03) and modified the treatment plan in seven cases. It also led to cost-efficient use of resources in the procedure suite with estimated reduction in procedure and fluoroscopy time of 29.0 [20.3] (p = 0.003) and 10.2 [6.7] (p = 0.002) minutes, respectively.

Conclusion
3D printed anatomic models for patients who require complex IVC filter retrieval demonstrated Likert-based high clinical utility and led to estimated reductions of procedural and fluoroscopy time.
Physical, functional and bioactive properties of microencapsulated powders from banana pseudostem and inflorescence extracts
Authors: Gayathry K. S. , John Jenny Ann 
Published: October 2024

AbstractApplication of agricultural by-products in the functional food and beverage industry is currently gaining prominence. Banana (Musa spp) is a popular tropical fruit with global production of 124.97 million tonnes. The banana production industry contributes to large amount of solid waste/ banana by-products, such as, pseudostem and inflorescence. Palayankodan (Musa × paradisiaca Mysore AAB group), Nendran (Musa × paradisiaca AAB group) and Njalipoovan (Musa × paradisiaca AB group) are three popular and common cultivars in Kerala, a state in South India. The present study was aimed to extract the potential bioactive compounds from the pseudostem and inflorescence of the above-mentioned cultivars and to standardise the process of microencapsulation using spray drying. Ultrasonication assisted extraction using ethanol as solvent was carried out. The extract and wall material parameters were standardised for microencapsulation. The encapsulated powders were analysed for encapsulation yield, retention efficiency, physical properties, phytochemical composition, antioxidant potential and anti-diabetic activity. The encapsulation yields and retention efficiencies of the encapsulated powders were found to be approximately 75 and 70.51%, respectively. Results revealed that the powders exhibited lower bulk density, good solubility and reconstitutability. Scanning electron microscopy was also conducted to reveal the particle morphology. All the powders exhibited smooth, spherical shape, with no pores. The phenolic and flavonoid contents of the encapsulated pseudostem and inflorescence extract powders ranged from 2.75 to 3.13 mg GAE/ g of powder and 34.83 to 46.67 mg QE/g of powder, respectively. The present study also reported the in vitro bioactive properties, in terms of antioxidant and anti-diabetic activities of the encapsulated powders. The HPLC analysis of the microencapsulated powders revealed the presence of gallic acid, protocatechuic acid, trans cinnamic acid, trans ferulic acid, epicatechin and syringic acid. It is clear from the study that the encapsulated powders from banana by-products have a great potential to be utilised by the functional food industry.
Graphical Abstract