bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbiome-derived metabolites in early to mid-pregnancy and risk of gestational diabetes: a metabolome-wide association study
Authors: Susarla Sita Manasa , Fiehn Oliver , Thiele Ines , Ngo Amanda L. , Barupal Dinesh K. , Chehab Rana F. , Ferrara Assiamira , Zhu Yeyi 
Published: October 2024

Abstract

Background

Pre-diagnostic disturbances in the microbiome-derived metabolome have been associated with an increased risk of diabetes in non-pregnant populations. However, the roles of microbiome-derived metabolites, the end-products of microbial metabolism, in gestational diabetes (GDM) remain understudied. We examined the prospective association of microbiome-derived metabolites in early to mid-pregnancy with GDM risk in a diverse population.

Methods
We conducted a prospective discovery and validation study, including a case–control sample of 91 GDM and 180 non-GDM individuals within the multi-racial/ethnic The Pregnancy Environment and Lifestyle Study (PETALS) as the discovery set, a random sample from the PETALS (42 GDM, 372 non-GDM) as validation set 1, and a case–control sample (35 GDM, 70 non-GDM) from the Gestational Weight Gain and Optimal Wellness randomized controlled trial as validation set 2. We measured untargeted fasting serum metabolomics at gestational weeks (GW) 10–13 and 16–19 by gas chromatography/time-of-flight mass spectrometry (TOF–MS), liquid chromatography (LC)/quadrupole TOF–MS, and hydrophilic interaction LC/quadrupole TOF–MS. GDM was diagnosed using the 3-h, 100-g oral glucose tolerance test according to the Carpenter-Coustan criteria around GW 24–28.

Results
Among 1362 annotated compounds, we identified 140 of gut microbiome metabolism origin. Multivariate enrichment analysis illustrated that carbocyclic acids and branched-chain amino acid clusters at GW 10–13 and the unsaturated fatty acids cluster at GW 16–19 were positively associated with GDM risk (FDR < 0.05). At GW 10–13, the prediction model that combined conventional risk factors and LASSO-selected microbiome-derived metabolites significantly outperformed the model with only conventional risk factors including fasting glucose (discovery AUC: 0.884 vs. 0.691; validation 1: 0.945 vs. 0.731; validation 2: 0.987 vs. 0.717; all P < 0.01). At GW 16–19, similar results were observed (discovery AUC: 0.802 vs. 0.691, P < 0.01; validation 1: 0.826 vs. 0.780; P = 0.10).

Conclusions
Dysbiosis in microbiome-derived metabolites is present early in pregnancy among individuals progressing to GDM.
A field comparison study of two vaccine protocols against Erysipelothrix rhusiopathiae in two types of swine breeds in Spain
Authors: Sanchez-Tarifa E. , Alonso C. , Perez I. , García L. A. , Fernández-Fontelo A. , Gómez-Duran O. , García-Morante B. , García–Vázquez Francisco A. , Hernández-Caravaca I. 
Published: October 2024

AbstractErysipelas still causes large economic losses to pig industry. Maternal immunity is critical to prevent erysipelas in young animals, thus, intensive vaccination protocols or practices focused on the improvement of the maternally derived immunity could provide substantial benefits. The present study evaluates potential changes in antibodies levels in sows and their offspring using two types of tests (commercial ELISA, Ingenasa or rSpaA415 ELISA) when two different vaccination programs (before farrowing or after farrowing) against Erysipelothrix rhusiopathiae were applied to sows from Iberian (A) or conventional Large White-Landrace (B) pig farms. The results showed a statistical correlation between titers found in sows and their one-week old piglets in both tests. The overall mean of (log) antibody titers in farm B measured by the commercial ELISA test was significantly higher in pre-farrowing vaccinated sows compared to the post-farrowing vaccine protocol (p = 0.0278). Additionally, using the rSpaA415 ELISA test, the overall mean of (log) antibody titers was significantly higher in pre-farrowing sows (p = 0.0056) compared to sows following post-farrowing vaccine protocol (p = 0.0003) or non- vaccinated sows. None of the above-mentioned differences were found in farm A. The overall mean of (log) antibody titers in piglets from the pre-farrowing vaccination protocol was significantly higher than piglets from the post-farrowing vaccination protocol in farm A (p = 0.0059; rSpaA415 ELISA) and farm B (p = 0.0168 and p = 0.0098 for the commercial and rSpaA415 ELISA data, respectively). Additionally, higher proportion of piglets from pre-farrowing vaccinated sows remained seropositive during the post-weaning period (days 42 to 84) compared to piglets from non-vaccinated or post-farrowing vaccinated groups in both farms A and B.
Secretome from estrogen-responding human placenta-derived mesenchymal stem cells rescues ovarian function and circadian rhythm in mice with cyclophosphamide-induced primary ovarian insufficiency
Authors: Le Duy-Cuong , Ngo Mai-Huong T. , Kuo Yung-Che , Chen Shu-Hwa , Lin Chung-Yen , Ling Thai-Yen , Pham Quoc Thao Trang , Au Heng-Kien , Myung Jihwan , Huang Yen-Hua 
Published: October 2024

Abstract
Background
Primary ovarian insufficiency (POI) is an early decline in ovarian function that leads to ovarian failure. Conventional treatments for POI are inadequate, and treatments based on mesenchymal stem cells (MSCs) have emerged as an option. However, the lack of consideration of the estrogen niche in ovarian tissue significantly reduces the therapeutic efficacy, with an unclear mechanism in the MSCs in POI treatment. Furthermore, the disruption of circadian rhythm associated with POI has not been previously addressed.

Methods
Conditioned medium (CM) and estradiol-conditioned medium (E2-CM) were generated from estrogen receptor positive MSCs (ER+pcMSCs). Chemotherapy-induced POI models were established using C57BL/6 mice (in vivo) and KGN cells (in vitro) treated with cyclophosphamide (CTX) or 4-hydroperoxycyclophosphamide (4-OOH-CP). Gene/protein expressions were detected using RT-qPCR, Western blotting, and immunohistochemistry assays. Locomotor activity was monitored for behavioral circadian rhythmicity. Cytokine arrays and miRNA analysis were conducted to analyze potential factors within CM/E2-CM.

Results
The secretome of ER+pcMSCs (CM and E2-CM) significantly reduced the CTX-induced defects in ovarian folliculogenesis and circadian rhythm. CM/E2-CM also reduced granulosa cell apoptosis and rescued angiogenesis in POI ovarian tissues. E2-CM had a more favorable effect than the CM. Notably, ER+pcMSC secretome restored CTX-induced circadian rhythm defects, including the gene expressions associated with the ovarian circadian clock (e.g., Rora, E4bp4, Rev-erbα, Per2 and Dbp) and locomotor activity. Additionally, the cytokine array analysis revealed a significant increase in cytokines and growth factors associated with immunomodulation and angiogenesis, including angiogenin. Neutralizing the angiogenin in CM/E2-CM significantly reduced its ability to promote HUVEC tube formation in vitro. Exosomal miRNA analysis revealed the miRNAs involved in targeting the genes associated with POI rescue (PTEN and PDCD4), apoptosis (caspase-3, BIM), estrogen synthesis (CYP19A1), ovarian clock regulation (E4BP4, REV-ERBα) and fibrosis (COL1A1).

Conclusion
This study is the first to demonstrate that, in considering the estrogen niche in ovarian tissue, an estrogen-priming ER+pcMSC secretome achieved ovarian regeneration and restored the circadian rhythm in a CTX-induced POI mouse model. The potential factors involved include angiogenin and exosomal miRNAs in the ER+pcMSC secretome. These findings offer insights into potential stem cell therapies for chemotherapy-induced POI and circadian rhythm disruption.
miR-210 is essential to retinal homeostasis in fruit flies and mice
Authors: Colaianni Davide , Virga Federico , Tisi Annamaria , Stefanelli Chiara , Zaccagnini Germana , Cusumano Paola , Sales Gabriele , Preda Mihai Bogdan , Martelli Fabio , Taverna Daniela , Mazzone Massimiliano , Bertolucci Cristiano , Maccarone Rita , De Pittà Cristiano 
Published: October 2024

Abstract
Background
miR-210 is one of the most evolutionarily conserved microRNAs. It is known to be involved in several physiological and pathological processes, including response to hypoxia, angiogenesis, cardiovascular diseases and cancer. Recently, new roles of this microRNA are emerging in the context of eye and visual system homeostasis. Recent studies in Drosophila melanogaster unveiled that the absence of miR-210 leads to a progressive retinal degeneration characterized by the accumulation of lipid droplets and disruptions in lipid metabolism. However, the possible conservation of miR-210 knock-out effect in the mammalian retina has yet to be explored.

Results
We further investigated lipid anabolism and catabolism in miR-210 knock-out (KO) flies, uncovering significant alterations in gene expression within these pathways. Additionally, we characterized the retinal morphology of flies overexpressing (OE) miR-210, which was not affected by the increased levels of the microRNA. For the first time, we also characterized the retinal morphology of miR-210 KO and OE mice. Similar to flies, miR-210 OE did not affect retinal homeostasis, whereas miR-210 KO mice exhibited photoreceptor degeneration. To explore other potential parallels between miR-210 KO models in flies and mice, we examined lipid metabolism, circadian behaviour, and retinal transcriptome in mice, but found no similarities. Specifically, RNA-seq confirmed the lack of involvement of lipid metabolism in the mice’s pathological phenotype, revealing that the differentially expressed genes were predominantly associated with chloride channel activity and extracellular matrix homeostasis. Simultaneously, transcriptome analysis of miR-210 KO fly brains indicated that the observed alterations extend beyond the eye and may be linked to neuronal deficiencies in signal detection and transduction.

Conclusions
We provide the first morphological characterization of the retina of miR-210 KO and OE mice, investigating the role of this microRNA in mammalian retinal physiology and exploring potential parallels with phenotypes observed in fly models. Although the lack of similarities in lipid metabolism, circadian behaviour, and retinal transcriptome in mice suggests divergent mechanisms of retinal degeneration between the two species, transcriptome analysis of miR-210 KO fly brains indicates the potential existence of a shared upstream mechanism contributing to retinal degeneration in both flies and mammals.
An outbreak of blaKPC−4- and blaVIM−1-producing Klebsiella pneumoniae and Klebsiella variicola at a single hospital in South Korea
Authors: Chu Jiyon , Choi Jaeki , Ji Seul Ki , Park Chulmin , Jung Seung-Hyun , Park Sun Hee , Lee Dong-Gun 
Published: October 2024

Abstract
Background
The dissemination of Klebsiella spp. producing multiple carbapenemases has been increasingly recognized. Between July 2019 and August 2021, ten patients were found to carry Klebsiella spp. co-harboring blaKPC−4 and blaVIM−1 across multiple wards at a Korean hospital, and one isolate was recovered from a hand-washing sink, more than a year after the outbreak. This study aimed to investigate the outbreak and conduct a genomic study of these isolates.

Methods
Whole-genome sequencing, including long-read sequencing, was performed to analyze plasmid structures and mobile genetic elements (MGEs). Bioinformatics analyses were performed to trace clonal transmission chains and horizontal gene transfer.

Results
The findings suggested that the inter-ward spread of Klebsiella spp. seemed to be facilitated by healthcare worker contact or patient movement. Of the nine isolates collected (eight clinical and one environmental), seven (including the environmental isolate) were identified as K. pneumoniae (ST3680) and two were K. variicola (single-locus variant of ST5252). These isolates showed high genetic relatedness within their species and harbored the IncHI5B plasmid carrying both blaKPC−4 and blaVIM−1 (pKPCVIM.1). On this plasmid, blaVIM−1 was located in the Class 1 integron associated with IS1326::IS1353 (In2), and Tn4401b carrying blaKPC−4 was inserted into IS1326::IS1353, creating a novel MGE construct (In2_blaVIM−1-Tn4401b_blaKPC−4).

Conclusion
The hospital-wide spread of blaKPC−4 and blaVIM−1 was facilitated by clonal spread and horizontal plasmid transfer. The persistence of this strain in the hospital sink suggests a potential reservoir of the strain. Understanding the transmission mechanisms of persistent pathogens is important for improving infection control strategies in hospitals.
Bibliometric and visual analysis of sustainable preservation of heritage gardens
Authors: Liu Kun , Xian Zheng , Yang Ruochen , Takeda Shiro , Cui Jingshu , Sun Fuhao , Zhang Siyu , Zhang Junhua , Zhao Caijun , Liu Bing 
Published: October 2024

Abstract
Heritage gardens represent the cultural heritage pride of many nations, and their sustainable preservation has garnered widespread academic attention globally. Despite numerous qualitative reviews, a comprehensive quantitative analysis of heritage garden preservation literature from 2004 to 2024 is lacking. This study examines the dynamic evolution of heritage garden conservation (2004–2024) through bibliometric analysis, focusing on Research Activity and Impact, Cooperation Networks, and Knowledge Structure and Thematic Evolution. To achieve this goal, this study conducted a bibliometric analysis using the Web of Science Core Collection database. Initially, 1,540 documents were retrieved. After excluding irrelevant categories and conducting a manual review of titles, abstracts, and keywords to ensure relevance, 774 articles were selected for analysis. The analysis utilized bibliometric software tools such as VOS viewer, CiteSpace, and Biblioshiny. The results initially reveal that the period from 2010 to 2021 marked a significant increase in publication volume within the field of heritage gardens, although only 2.4% of the papers were reviews. Landscape Urban Planning and Geoheritage emerged as the most influential journals, based on their high local citation counts within the field. Additionally, collaboration networks indicated that scholars from the United States and China published the most papers, with Canadian scholars’ works having significant impact. Influenced by the evolving concepts of technology, politics, and cultural heritage, the analysis of knowledge structure and theme evolution identified ecosystem services, user perceptions, and cultural landscape impacts as recent hot topics. Future research on the sustainable preservation of heritage gardens should focus more on balancing urban development, incorporating sustainable management, and digital restoration through quantitative methods. In summary, this study offers insights into the global evolution of heritage garden preservation from 2004 to 2024, providing a valuable resource for future research and policy-making.
Individual placement and support (IPS): duration of employment support and equity of access and outcome in routine clinical practice
Authors: Rinaldi Miles , Perkins Rachel , Baxter Robert , Dorrington Paul , Saville Kat 
Published: October 2024

Aims and method
To explore the duration of support, reach, effectiveness and equity in access to and outcome of individual placement and support (IPS) in routine clinical practice. A retrospective analysis of routine cross-sectional administrative data was performed for people using the IPS service (N = 539).

Results
A total of 46.2% gained or retained employment, or were supported in education. The median time to gaining employment was 132 days (4.3 months). Further, 84.7% did not require time-unlimited in-work support, and received in-work support for a median of 146 days (4.8 months). There was a significant overrepresentation of people from Black and minority ethnic communities accessing IPS, but no significant differences in outcomes by diagnosis, ethnicity, age or gender.

Clinical implications
Most people using IPS services do not appear to need time-unlimited in-work support. Community teams with integrated IPS employment specialists can be optimistic when addressing people's recovery goals of gaining and retaining employment.
Arterial Stiffness Associated With Long-term Major Adverse Cardiac Events in Patients With Primary Aldosteronism
Authors: Wu Vin-Cent , Chu Wen-Kai , Yang Po-Lung , Lin Yen-Hung , Wang Shuo-Meng , Chueh Jeff S 
Published: October 2024

Abstract

Context
As a novel parameter for risk prediction, artery stiffness may hold promise in refining risk assessment strategies, guiding therapeutic interventions, and ultimately improving cardiovascular outcomes in patients with primary aldosteronism (PA).

Objective and Methods
To investigate the correlation between brachial-ankle pulse wave velocity (baPWV), an indicator of arterial stiffness, and the occurrence of major adverse cardiovascular events (MACEs) in patients with PA under a primary prevention design.

Results
Among the 830 patients included in the final analysis, 113 (13.6%) developed incident MACEs over a median follow-up period of 5.8 years, with a crude rate of 23.2 per 1000 person-years. Multivariable Cox proportional hazards analyses revealed that baPWV was an independent risk factor for incident MACEs, with an adjusted hazard ratio (HR) of 1.01 (P = .028). The generalized additive model identified a cut-off value of 2000 cm/s for baPWV, which was independently associated with incident MACEs, with a HR of 1.81 (P = .024), while accounting for mortality as a competing risk. Subgroup analyses revealed that PA patients who were mineralocorticoid receptor antagonist users and had high baPWV had a significantly higher risk of incident MACEs (HR = 3.34; P &lt; .001), whereas the risk was not significant in patients who underwent adrenalectomy (P = .062). Furthermore, the addition of baPWV to the cardiovascular Framingham risk score significantly improved the category-free net reclassification index (0.308, P &lt; .001).

Conclusions
Our study found that 13.6% of patients with PA developed MACEs after a median follow-up of 5.8 years. Our findings highlight the potential utility of baPWV as a tool for risk stratification in patients with PA in primary prevention, whereas adrenalectomy appears to mitigate this risk regardless of baPWV. The measurement of baPWV could be a valuable addition to hypertension screening programs for primary prevention, providing additional predictive information for the potential occurrence of MACEs.
Predicting Futile Recanalization After Endovascular Thrombectomy for Patients With Stroke With Large Cores: The SNAP Score
Authors: Matsukawa Hidetoshi , Chen Huanwen , Elawady Sameh Samir , Cunningham Conor , Uchida Kazutaka , Sowlat Mohammad-Mahdi , Maier Ilko , Jabbour Pascal , Kim Joon-Tae , Wolfe Stacey Quintero , Rai Ansaar , Starke Robert M. , Psychogios Marios-Nikos , Samaniego Edgar A. , Arthur Adam , Yoshimura Shinichi , Cuellar Hugo , Grossberg Jonathan A. , Alawieh Ali , Romano Daniele G. , Tanweer Omar , Mascitelli Justin , Fragata Isabel , Polifka Adam , Osbun Joshua , Crosa Roberto , Matouk Charles , Park Min S. , Levitt Michael R. , Brinjikji Waleed , Moss Mark , Williamson Richard , Navia Pedro , Kan Peter , De Leacy Reade , Chowdhry Shakeel , Ezzeldin Mohamad , Spiotta Alejandro M. ,   for the Stroke Thrombectomy and Aneurysm Registry (STAR) Collaborators
Published: October 2024

BACKGROUND AND OBJECTIVES:
We aimed to develop and validate a prediction score for futile recanalization (FR) for large vessel occlusion (LVO) presenting low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) for patients who underwent endovascular thrombectomy (EVT).

METHODS:
Patients with anterior circulation LVO with low ASPECTS (<6) who underwent successful EVT (modified treatment in cerebral ischemia score ≥2b) from Stroke Thrombectomy and Aneurysm Registry were retrospectively analyzed. FR was defined as 90-day modified Rankin Scale (mRS) scores ≥4 despite successful EVT. Multivariable logistic regression was used to identify independent predictors of FR, and they were used to create a clinical score. The performance of the score was assessed by receiver operating characteristic curve analyses.

RESULTS:
Of 219 patients, 170 and 49 patients were randomly assigned to the training and validation cohort, respectively. Independent predictors of FR identified in the training cohort were used to construct the SNAP score: site of occlusion (middle cerebral artery = 0, internal carotid artery = 1), National Institutes of Health Stroke Scale score at admission (≤10 = 0, 10 to 19 = 1, ≥20 = 2), age (<75 = 0, ≥75 = 2), and prestroke mRS score (0-3). Receiver operating characteristic curve analyses of the SNAP score in the training and validation cohorts showed areas under the curve of 0.79 (95% CI 0.72-0.86) and 0.79 (95% CI 0.65-0.92) for predicting FR, respectively. A SNAP score ≥5 had a positive predictive value of 92.1% [95% CI 78.8%-97.3%] for FR.

CONCLUSION:
The SNAP score may be useful in predicting FR after EVT in low-ASPECTS patients with LVO. It can provide patients, family members, and physicians with reliable outcome expectations among patients with acute ischemic stroke with large infarcts.
The production and utility of evidence synthesis during the COVID-19 pandemic in Canada: perspectives of evidence synthesis producers
Authors: Corrin Tricia , Cairney Paul , Kennedy Eric B. 
Published: October 2024

Background:
COVID-19 accentuated an evergreen dilemma in evidence-informed policy making: the imperative to synthesise the best available evidence with limited time to produce high quality synthesis. The pandemic prompted the adaptation of evidence synthesis practices to match the urgency of the crisis, and heightened demand by policy makers, while maintaining a focus on quality. This study documents the response to these challenges from the perspectives of those who produced evidence syntheses in Canada.

Methods:
A qualitative phenomenological study was conducted between October 2022 and January 2023. Data collection included interviews with 22 participants within 19 organisations across seven provinces. A thematic analysis was performed and reported narratively.

Results:
Evidence synthesis producers in Canada adapted in response to the demands of different types of requests during the pandemic. Participants described several key challenges in responding to end-users, in which a lack of knowledge of evidence synthesis processes and products prompted difficult questions and unrealistic expectations. They responded to the needs of evidence synthesis requestors by creating custom syntheses, utilising rapid review methodologies, emphasising limitations and incorporating recommendations into syntheses.

Discussion and conclusion:
The evidence synthesis field was able to adapt to pandemic challenges in valuable ways. Still, this experience accentuates disconnects between producers and users, including differing views on the purpose, methods, limitations and implementation of synthesis findings.