bluuebunny/crossref_metadata_2025_split huggingface dataset:
Harnessing cancer stem cell-derived exosomes to improve cancer therapy
Authors: Yang Jianqiang , Teng Yong 
Published: May 2023

AbstractCancer stem cells (CSCs) are the key “seeds” for tumor initiation and development, metastasis, and recurrence. Because of the function of CSCs in tumor development and progression, research in this field has intensified and CSCs are viewed as a new therapeutic target. Exosomes carrying a wide range of DNA, RNA, lipids, metabolites, and cytosolic and cell-surface proteins are released outside of the originating cells through the fusion of multivesicular endosomes or multivesicular bodies with the plasma membrane. It has become evident that CSC‐derived exosomes play a significant role in almost all “hallmarks” of cancer. For example, exosomes from CSCs can maintain a steady state of self-renewal in the tumor microenvironment and regulate microenvironmental cells or distant cells to help cancer cells escape immune surveillance and induce immune tolerance. However, the function and therapeutic value of CSC‐derived exosomes and the underlying molecular mechanisms are still largely undefined. To provide an overview of the possible role of CSC‐derived exosomes and targeting strategies, we summarize relevant research progress, highlight the potential impact of detecting or targeting CSC‐derived exosomes on cancer treatment, and discuss opportunities and challenges based on our experience and insights in this research area. A more thorough understanding of the characteristics and function of CSC‐derived exosomes may open new avenues to the development of new clinical diagnostic/prognostic tools and therapies to prevent tumor resistance and relapse.
Statistical analysis plans for two randomised controlled trials of the Narrative Experiences Online (NEON) Intervention: impact of receiving recorded mental health recovery narratives on quality of life in people experiencing psychosis (NEON) and people experiencing non-psychosis mental health problems (NEON-O)
Authors: Robinson Clare , Newby Chris , Rennick-Egglestone Stefan , Llewellyn-Beardsley Joy , Ng Fiona , Elliott Rachel A. , Slade Mike 
Published: May 2023

Abstract

Background
Mental health recovery narratives are a first-hand account of an individual’s recovery from mental health distress, access to narratives can aid recovery. The NEON Intervention is a web-application providing access to a managed collection of narratives. We present the statistical analysis plan for assessing the effectiveness of the NEON Intervention in improving quality of life at 1-year post-randomisation. We pay particular focus on the statistical challenges encountered due to the online nature of this trial.

Methods and design
The NEON Intervention is assessed in two trial populations, one for people with experience of psychosis in the last 5 years, and mental health distress in the last six months (NEON Trial) and one for people with experience of non-psychosis mental health problems (NEON-O Trial). Both NEON trials are two-arm randomised controlled superiority trials comparing the effectiveness of the NEON Intervention with usual care. The target sample size is 684 randomised participants for NEON and 994 for NEON-O. Participants were randomised centrally in a 1:1 ratio.

Results
The primary outcome is the mean score of subjective items on the Manchester Short Assessment of Quality-of-Life questionnaire (MANSA) at 52 weeks. Secondary outcomes are scores from the Herth Hope Index, Mental Health Confidence Scale, Meaning of Life questionnaire, CORE-10 questionnaire and Euroqol 5-Dimension 5-Level (EQ-5D-5L).

Conclusion
This manuscript is the statistical analysis plan (SAP) for the NEON trials. Any post hoc analysis, such as those requested by journal reviewers will be clearly labelled as such in the final trial reporting.
Trial registration
Both trials were prospectively registered. NEON Trial: ISRCTN11152837, registered on 13 August 2018. NEON-O Trial: ISRCTN63197153, registered on 9 January 2020.
Characteristics of ScleroID highlighting musculoskeletal and internal organ implications in patients afflicted with systemic sclerosis
Authors: Nagy Gabriella , Dobrota Rucsandra , Becker Mike Oliver , Minier Tünde , Varjú Cecília , Kumánovics Gábor , Distler Oliver , Czirják László 
Published: May 2023

Abstract
Background
Systemic sclerosis (SSc) is a multi-organ disease with impaired health-related quality of life (HRQoL). The EULAR SSc Impact of Disease (ScleroID) is a newly introduced SSc-specific patient-reported outcome to evaluate HRQoL in SSc.

Objective
To investigate the correlation between the ScleroID and the involvement of organ systems as well as disease activity/damage in a SSc cohort from a large tertiary care centre.

Patients and methods
The ScleroID and clinical characteristics including internal organ involvement and hand function were investigated in 160 consecutive patients with SSc (median age 46 (43;56) years; diffuse cutaneous SSc 55%).

Results
A strong correlation was found between the ScleroID and articular disease activity scores (DAS28-CRP, DAS28-ESR, CDAI, SDAI), a hand function performance test, the Hand Anatomy Index and muscle strength tests. Additionally, a strong significant correlation was discovered using instruments representing hand function and musculoskeletal disability including the Cochin Hand Function Scale, the Quick Questionnaire of the Disability of the Hands, Arms and the Shoulders and the Health Assessment Questionnaire Disability Index. A significant negative correlation was found between the ScleroID score and the 6-min walking test (6MWT) (rho − 0.444, p < 0.001). Clinically mild lung/heart disease did not show increased ScleroID values. The Mouth Handicap in the Scleroderma Scale and the University of California Los Angeles Scleroderma Clinical Trials Consortium gastrointestinal tract 2.0 also showed significant positive correlations to the ScleroID score (rho: 0.626, p < 0.001; rho: 0.646, p < 0.001, respectively). Patients experiencing oesophageal difficulties bore a significantly higher score compared to individuals with a normal functioning oesophagus (3.2/1.5;4.5/ vs. 2.2/1.0;3.2/, p = 0.011). Moreover, the ScleroID showed a significant positive correlation to the revised EUSTAR disease activity index and modified activity index.

Conclusion
In a large single-centre cohort, the previously described ScleroID-related findings were confirmed. Furthermore, several organ involvement-related functional and performance tests showed a good correlation to the ScleroID including the 6MWT and gastrointestinal-related complaints. Many aspects of musculoskeletal damage, overall disease activity, pain and fatigue were also well represented in the ScleroID, which efficiently reflects the impact of organ involvement, disease activity and functional damage.
Association between skeletal muscle mitochondrial dysfunction and insulin resistance in patients with rheumatoid arthritis: a case–control study
Authors: Moellering Douglas R. , Smith-Johnston Kelley , Kelley Christian , Sammy Melissa J. , Benedict Jason , Brock Guy , Johnson Jillian , Baskin Kedryn K. , Jarjour Wael N. , Belury Martha A. , Reiser Peter J. , Nagareddy Prabhakara R. , Hanaoka Beatriz Y. 
Published: May 2023

Abstract
Background
Insulin resistance affects a substantial proportion of patients with rheumatoid arthritis (RA). Skeletal muscle mitochondrial dysfunction results in the accumulation of lipid intermediates that interfere with insulin signaling. We therefore sought to determine if lower oxidative phosphorylation and muscle mitochondrial content are associated with insulin resistance in patients with RA.

Methods
This was a cross-sectional prospective study of RA patients. Matsuda index from the glucose tolerance test was used to estimate insulin sensitivity. Mitochondrial content was measured by citrate synthase (CS) activity in snap-frozen muscle samples. Mitochondrial function was measured by using high-resolution respirometry of permeabilized muscle fibers and electron transport chain complex IV enzyme kinetics in isolated mitochondrial subpopulations.

Results
RA participants demonstrated lower insulin sensitivity as measured by the Matsuda index compared to controls [median 3.95 IQR (2.33, 5.64) vs. 7.17 (5.83, 7.75), p = 0.02]. There was lower muscle mitochondrial content among RA vs. controls [median 60 mU/mg IQR (45, 80) vs. 79 mU/mg (65, 97), p = 0.03]. Notably, OxPhos normalized to mitochondrial content was higher among RA vs. controls [mean difference (95% CI) = 0.14 (0.02, 0.26), p = 0.03], indicating a possible compensatory mechanism for lower mitochondrial content or lipid overload. Among RA participants, the activity of muscle CS activity was not correlated with the Matsuda index (ρ =  − 0.05, p = 0.84), but it was positively correlated with self-reported (IPAQ) total MET-minutes/week (ρ = 0.44, p = 0.03) and Actigraph-measured time on physical activity (MET rate) (ρ = 0.47, p = 0.03).

Conclusions
Mitochondrial content and function were not associated with insulin sensitivity among participants with RA. However, our study demonstrates a significant association between muscle mitochondrial content and physical activity level, highlighting the potential for future exercise interventions that enhance mitochondrial efficiency in RA patients.
Mediterranean diet lowers all-cause and cardiovascular mortality for patients with metabolic syndrome
Authors: Fan Hongxuan , Wang Yongle , Ren Zhaoyu , Liu Xuchang , Zhao Jianqi , Yuan Yalin , Fei Xiaoning , Song Xiaosu , Wang Fengqin , Liang Bin 
Published: May 2023

AbstractA Mediterranean-style diet (MED) can promote people lengthen the span of life and avoid atherosclerotic cardiovascular disease (ASCVD) in primary prevention. Metabolic syndrome (MetS) can significantly reduce life expectancy and increase the risk of ASCVD. However, few studies have focused on the role of the Mediterranean diet in patients with MetS. Participants in the National Health and Nutrition Examination Survey (NHANES) with MetS (N = 8301) from 2007 to 2018 were examined. A 9-point evaluation scorewas used to measure the degree of adherence to the MED diet. In order to compare the various levels of adherence to the MED diet and the effects of the specific MED diet components on all-cause and cardiovascular mortality, Cox regression models were utilized. Among the 8301 participants with MetS, about 13.0% (1080 of 8301) died after a median follow-up of 6.3 years. In this study, participants with MetS with adherence to high-quality and moderate-quality Mediterranean diet were significantly associated with lower all-cause mortality as well as cardiovascular mortality during the follow-up period. Futhermore, in joint analysis of the Mediterranean diet and sedentary behavior or depression, we found that high-quality or moderate-quality Mediterranean diet could attenuate, even reverse the adverse effects of sedentary behavior and depression on all-cause and cardiovascular mortality in participants with MetS. Among the components of the MED diet, greater intakes of vegetables, legumes, nuts and high MUFA/SFA ratio were significantly associated with lower all-cause mortality and greater vegetables intake was significantly associated with lower cardiovascular mortality, while more red/processed meat intake was significantly associated with higher cardiovascular mortality in participants with MetS.
Chloroplast markers for the Malvaceae and the plastome of Henderson’s checkermallow (Sidalcea hendersonii S.Wats.), a rare plant from the Pacific Northwest
Authors: Percy Diana M. , Sveinsson Sæmundur , Ponomarev Andrew , Yang Ji Yong , Cronk Quentin C.B. 
Published: May 2023

Abstract
Objective
Sidalcea is a genus of flowering plants restricted to the west coast of North America, commonly known as checkermallows. Remarkably, of the ~ 30 recognized species, 16 are of conservation concern (vulnerable, imperilled or critically imperilled). To facilitate biological studies in this genus, and in the wider Malvaceae, we have sequenced the whole plastid genome of Sidalcea hendersonii. This will allow us both to check those regions already developed as general Malvaceae markers in a previous study, and to search for new regions.

Results
By comparing the Sidalcea genome to that of Althaea, we have identified a hypervariable circa 1 kb region in the short single copy region. This region shows promise for examining phylogeographic pattern, hybridization and haplotype diversity. Remarkably, considering the conservation of plastome architecture between Sidalcea and Althaea, the former has a 237 bp deletion in the otherwise highly conserved inverted repeat region. Newly designed primers provide a PCR assay to determine presence of this indel across the Malvaceae. Screening of previously designed chloroplast microsatellite markers indicates two markers with variation within S. hendersonii that would be useful in future population conservation genetics.
Plasma and cerebrospinal fluid cholesterol esterification is hampered in Alzheimer’s disease
Authors: Turri Marta , Conti Elisa , Pavanello Chiara , Gastoldi Francesco , Palumbo Marcella , Bernini Franco , Aprea Vittoria , Re Francesca , Barbiroli Alberto , Emide Davide , Galimberti Daniela , Tremolizzo Lucio , Zimetti Francesca , Calabresi Laura ,   AGAINST-AD Group, Andreoni Simona , Appollonio Ildebrando , Da Re Fulvio , Ferrarese Carlo , Karantzoulis Aristotelis , Negro Giulia , Pozzi Federico Emanuele , Remoli Giulia , Storti Benedetta , Zoia Chiara Paola 
Published: May 2023

Abstract

Objective
The purpose of this study was to evaluate cholesterol esterification and HDL subclasses in plasma and cerebrospinal fluid (CSF) of Alzheimer’s disease (AD) patients.

Methods
The study enrolled 70 AD patients and 74 cognitively normal controls comparable for age and sex. Lipoprotein profile, cholesterol esterification, and cholesterol efflux capacity (CEC) were evaluated in plasma and CSF.

Results
AD patients have normal plasma lipids but significantly reduced unesterified cholesterol and unesterified/total cholesterol ratio. Lecithin:cholesterol acyltransferase (LCAT) activity and cholesterol esterification rate (CER), two measures of the efficiency of the esterification process, were reduced by 29% and 16%, respectively, in the plasma of AD patients. Plasma HDL subclass distribution in AD patients was comparable to that of controls but the content of small discoidal preβ-HDL particles was significantly reduced. In agreement with the reduced preβ-HDL particles, cholesterol efflux capacity mediated by the transporters ABCA1 and ABCG1 was reduced in AD patients’ plasma. The CSF unesterified to total cholesterol ratio was increased in AD patients, and CSF CER and CEC from astrocytes were significantly reduced in AD patients. In the AD group, a significant positive correlation was observed between plasma unesterified cholesterol and unesterified/total cholesterol ratio with Aβ1-42 CSF content.

Conclusion
Taken together our data indicate that cholesterol esterification is hampered in plasma and CSF of AD patients and that plasma cholesterol esterification biomarkers (unesterified cholesterol and unesterified/total cholesterol ratio) are significantly associated to disease biomarkers (i.e., CSF Aβ1-42).
In the right place, at the right time: the integration of bacteria into the Plankton Ecology Group model
Authors: Park Hongjae , Shabarova Tanja , Salcher Michaela M. , Kosová Lenka , Rychtecký Pavel , Mukherjee Indranil , Šimek Karel , Porcal Petr , Seďa Jaromír , Znachor Petr , Kasalický Vojtěch 
Published: May 2023

Abstract
Background
Planktonic microbial communities have critical impacts on the pelagic food web and water quality status in freshwater ecosystems, yet no general model of bacterial community assembly linked to higher trophic levels and hydrodynamics has been assessed. In this study, we utilized a 2-year survey of planktonic communities from bacteria to zooplankton in three freshwater reservoirs to investigate their spatiotemporal dynamics.

Results
We observed site-specific occurrence and microdiversification of bacteria in lacustrine and riverine environments, as well as in deep hypolimnia. Moreover, we determined recurrent bacterial seasonal patterns driven by both biotic and abiotic conditions, which could be integrated into the well-known Plankton Ecology Group (PEG) model describing primarily the seasonalities of larger plankton groups. Importantly, bacteria with different ecological potentials showed finely coordinated successions affiliated with four seasonal phases, including the spring bloom dominated by fast-growing opportunists, the clear-water phase associated with oligotrophic ultramicrobacteria, the summer phase characterized by phytoplankton bloom-associated bacteria, and the fall/winter phase driven by decay-specialists.

Conclusions
Our findings elucidate the major principles driving the spatiotemporal microbial community distribution in freshwater ecosystems. We suggest an extension to the original PEG model by integrating new findings on recurrent bacterial seasonal trends.
Exposing new taxonomic variation with inflammation — a murine model-specific genome database for gut microbiome researchers
Authors: Leleiwi Ikaia , Rodriguez-Ramos Josué , Shaffer Michael , Sabag-Daigle Anice , Kokkinias Katherine , Flynn Rory M. , Daly Rebecca A. , Kop Linnea F. M. , Solden Lindsey M. , Ahmer Brian M. M. , Borton Mikayla A. , Wrighton Kelly C. 
Published: May 2023

Abstract
Background
The murine CBA/J mouse model widely supports immunology and enteric pathogen research. This model has illuminated Salmonella interactions with the gut microbiome since pathogen proliferation does not require disruptive pretreatment of the native microbiota, nor does it become systemic, thereby representing an analog to gastroenteritis disease progression in humans. Despite the value to broad research communities, microbiota in CBA/J mice are not represented in current murine microbiome genome catalogs.

Results
Here we present the first microbial and viral genomic catalog of the CBA/J murine gut microbiome. Using fecal microbial communities from untreated and Salmonella-infected, highly inflamed mice, we performed genomic reconstruction to determine the impacts on gut microbiome membership and functional potential. From high depth whole community sequencing (~ 42.4 Gbps/sample), we reconstructed 2281 bacterial and 4516 viral draft genomes. Salmonella challenge significantly altered gut membership in CBA/J mice, revealing 30 genera and 98 species that were conditionally rare and unsampled in non-inflamed mice. Additionally, inflamed communities were depleted in microbial genes that modulate host anti-inflammatory pathways and enriched in genes for respiratory energy generation. Our findings suggest decreases in butyrate concentrations during Salmonella infection corresponded to reductions in the relative abundance in members of the Alistipes. Strain-level comparison of CBA/J microbial genomes to prominent murine gut microbiome databases identified newly sampled lineages in this resource, while comparisons to human gut microbiomes extended the host relevance of dominant CBA/J inflammation-resistant strains.

Conclusions
This CBA/J microbiome database provides the first genomic sampling of relevant, uncultivated microorganisms within the gut from this widely used laboratory model. Using this resource, we curated a functional, strain-resolved view on how Salmonella remodels intact murine gut communities, advancing pathobiome understanding beyond inferences from prior amplicon-based approaches. Salmonella-induced inflammation suppressed Alistipes and other dominant members, while rarer commensals like Lactobacillus and Enterococcus endure. The rare and novel species sampled across this inflammation gradient advance the utility of this microbiome resource to benefit the broad research needs of the CBA/J scientific community, and those using murine models for understanding the impact of inflammation on the gut microbiome more generally.
Metagenomics reveals the habitat specificity of biosynthetic potential of secondary metabolites in global food fermentations
Authors: Du Rubing , Xiong Wu , Xu Lei , Xu Yan , Wu Qun 
Published: May 2023

Abstract

Background
Fermented foods are considered to be beneficial for human health. Secondary metabolites determined by biosynthetic gene clusters (BGCs) are precious bioactive compounds with various biological activities. However, the diversity and distribution of the biosynthetic potential of secondary metabolites in global food fermentations remain largely unknown. In this study, we performed a large-scale and comprehensive investigation for the BGCs in global food fermentations by metagenomics analysis.

Results
We recovered 653 bacterial metagenome-assembled genomes (MAGs) from 367 metagenomic sequencing datasets covering 15 general food fermentation types worldwide. In total, 2334 secondary metabolite BGCs, including 1003 novel BGCs, were identified in these MAGs. Bacillaceae, Streptococcaceae, Streptomycetaceae, Brevibacteriaceae and Lactobacillaceae contained high abundances of novel BGCs (≥ 60 novel BGCs). Among 2334 BGCs, 1655 were habitat-specific, originating from habitat-specific species (80.54%) and habitat-specific genotypes within multi-habitat species (19.46%) in different food fermentation types. Biological activity analysis suggested that 183 BGC-producing secondary metabolites exhibited high probabilities of antibacterial activity (> 80%). These 183 BGCs were distributed across all 15 food fermentation types, and cheese fermentation contained the most BGC number.

Conclusions
This study demonstrates that food fermentation systems are an untapped reservoir of BGCs and bioactive secondary metabolites, and it provides novel insights into the potential human health benefits of fermented foods.
An entomopathogenic fungus exploits its host humoral antibacterial immunity to minimize bacterial competition in the hemolymph
Authors: Wang Jia-Lin , Sun Jing , Song Ya-Jing , Zheng Huan-Huan , Wang Gui-Jie , Luo Wen-Xia , Li Li , Liu Xu-Sheng 
Published: May 2023

Abstract
Background
The insect hemolymph (blood-equivalent fluid), composed of a large number of hemocytes (blood cells) and a variety of soluble immune effectors, is hostile for pathogens including fungi. In order to survive in the insect hemocoel (body cavity), the entomopathogenic fungus (EPF) has evolved two classical coping strategies, namely evasion and suppression of the host immune reactions. However, it remains unclear whether EPF has other ways of coping with host immunity.

Results
In this study, we demonstrated that Metarhizium rileyi (an EPF) infection by injection of blastospores into the hemocoel enhanced the plasma antibacterial activity of cotton bollworm (Helicoverpa armigera), which was partially due to the enhanced expression of antimicrobial peptides (AMPs). The early stage of M. rileyi infection induced the translocation of gut bacteria into the hemocoel, where they were subsequently cleared due to the enhanced plasma antibacterial activity. Further, we showed that the enhanced plasma antibacterial activity and AMP expression were attributable to M. rileyi but not the invasive gut bacteria (opportunistic bacteria). Elevated ecdysone (major steroid hormone in insects) levels in the hemolymph at 48 h post-M. rileyi infection might contribute to the enhanced expression of AMPs. The fungus-elicited AMPs, such as cecropin 3 or lebocin, exhibited potent inhibitory activity against the opportunistic bacteria but not against hyphal bodies. In addition, the opportunistic bacteria competed with hyphal bodies for amino acid nutrients.

Conclusions
M. rileyi infection induced the translocation of gut bacteria, and then the fungi activated and exploited its host humoral antibacterial immunity to eliminate opportunistic bacteria, preventing them from competing for nutrients in the hemolymph. Unlike the classical strategies, EPF utilizes to evade or suppress host immunity, our findings reveal a novel strategy of interaction between EPF and host immunity.