bluuebunny/crossref_metadata_2025 huggingface dataset:
Leaf carbon isotope tracks the facilitation pattern of legume shrubs shaped by water availability and species replacement along a large elevation gradient in Trans-Himalayas
Authors: Ale Rita , Zhang Lin , Bahadur Raskoti Bhakta , Cui Guangshuai , Pugnaire Francisco I , Luo Tianxiang
Published: August 2023

Background and Aims

Understanding patterns and mechanisms of nurse plant facilitation is important to predict the resilience of arid/semi-arid ecosystems to climate change. We investigate whether water availability and nurse species turnover interact to shape the facilitation pattern of widespread legume shrubs along a large elevation gradient. We also investigate whether leaf δ13C of nurse plants can track the facilitation pattern.

Methods

We measured the relative interaction index (RII) of the number of species within and outside the canopy of two widespread legume shrub species (Caragana gerardiana and Caragana versicolor) alternatively distributed along a large elevation gradient in the Trans-Himalayas. We also assessed the proportional increase of species richness (ISR) at the community level using the paired plot data. To determine site-specific water availability, we measured the leaf δ13C of nurse shrubs and calculated the Thornthwaite moisture index (MI) for each elevation site.

Key Results

Elevational variations in RII, ISR and δ13C were mainly explained by the MI when the effects of soil nitrogen and plant traits (leaf nitrogen and shrub size) were controlled. Variations in RII and ISR across the two nurse species were explained better by δ13C than by smoothly changing climatic factors along elevation. At the transition zone between the upper limit of C. gerardiana (4100 m) and the lower limit of C. versicolor (4200 m), RII and ISR were much higher in C. versicolor than in C. gerardiana under a similar MI. Such an abrupt increase in facilitation induced by nurse species replacement was well tracked by the variation of δ13C.

Conclusions

Water availability and nurse species replacement are crucial to shaping facilitation patterns by legume shrubs along a large elevation gradient in dry mountainous regions, such as the Trans-Himalayas. Turnover in nurse species under global change might significantly alter the pattern of nurse plant facilitation associated with water availability, which can be well tracked by leaf δ13C.
Differentially methylated genomic regions of lettuce seeds relate to divergence across morphologically distinct horticultural types
Authors: Simko Ivan
Published: August 2023

Heritable cytosine methylation plays a role in shaping plant phenotypes; however, no information is available about DNA methylation in cultivated lettuce (Lactuca sativa), one of the most important leafy vegetables. Whole-genome bisulfite sequencing (WGBS) performed on seeds of 95 accessions from eight morphologically distinct horticultural types (Batavia, butterhead, iceberg, Latin, leaf, oilseed, romaine and stem) revealed a high level of methylation in lettuce genome with an average methylation of 90.6 % in the CG context, 72.9 % in the CHG context and 7.5 % in the CHH context. Although WGBS did not show substantial differences in overall methylation levels across eight horticultural types, 350 differentially methylated regions (DMR) were identified. Majority of the 41 pivotal DMR overlapped with genomic features predicted or confirmed to be involved in plant growth and development. These results provide the first insight into lettuce DNA methylation and indicate a potential role for heritable variation in cytosine methylation in lettuce morphology. The results reveal that differences in methylation profiles of morphologically distinct horticultural types are already detectable in seeds. Identified DMR can be a focus of the future functional studies.
Joint embedding of biological networks for cross-species functional alignment
Authors: Li Lechuan , Dannenfelser Ruth , Zhu Yu , Hejduk Nathaniel , Segarra Santiago , Yao Vicky
Published: August 2023

Motivation

Model organisms are widely used to better understand the molecular causes of human disease. While sequence similarity greatly aids this cross-species transfer, sequence similarity does not imply functional similarity, and thus, several current approaches incorporate protein–protein interactions to help map findings between species. Existing transfer methods either formulate the alignment problem as a matching problem which pits network features against known orthology, or more recently, as a joint embedding problem.

Results

We propose a novel state-of-the-art joint embedding solution: Embeddings to Network Alignment (ETNA). ETNA generates individual network embeddings based on network topological structure and then uses a Natural Language Processing-inspired cross-training approach to align the two embeddings using sequence-based orthologs. The final embedding preserves both within and between species gene functional relationships, and we demonstrate that it captures both pairwise and group functional relevance. In addition, ETNA’s embeddings can be used to transfer genetic interactions across species and identify phenotypic alignments, laying the groundwork for potential opportunities for drug repurposing and translational studies.

Availability and implementation

https://github.com/ylaboratory/ETNA
Ganoderma from Cuba: an approach to some species based on morphology and phylogenetic analyses
Authors: Cabarroi-Hernández Milay , Decock Cony , Welti Stéphane , Amalfi Mario , Rosa Villalobos-Arámbula Alma , Aliaga-Ramos Daniela , Morera Guillermo , Macedo-Pérez Sandi Emilia , Almarales Castro Abel , Guzmán-Dávalos Laura
Published: August 2023

Ganoderma is a genus of wood-decaying polypores fungi with several species, in which morphological delimitation has been challenging due to its large plasticity. Knowledge of the taxonomic diversity of Ganoderma in Cuba remains incomplete. Here, we identified some species, mainly laccate, of Ganoderma present in Cuba based on morphological and phylogenetic data and investigated their relationships with other species. Type specimens, recently collected materials, herbarium specimens and in vitro cultures were studied to delimit morphological species. The phylogenetic affinities of ten species were inferred based on multilocus (ITS rDNA, rpb2, tef1-α) DNA sequences to delimit phylogenetic species. In this work, 14 species of Ganoderma were recognized in Cuba, of which G. amazonense, G. curtisii, G. dussii and G. multiplicatum are reported for the first time. Ganoderma rodriguezii sp. nov. is described as a novel species. We confirmed G. amazonense is a non-laccate species although it is phylogenetically affine to laccate species. An identification key for studied species, nomenclatural information, updated descriptions and geographical distributions are presented. The lectotypification in second step of ﻿G. perzonatum, ﻿G. pulverulentum and ﻿G. zonatum was made here. To correctly interpret G. perzonatum, recent collections, including live strains from the type locality, are described. We confirm G. lucidum is not present in Cuba, despite previous records from the country.
Dazzle: surface patterns that impede interception
Authors: Scott-Samuel Nicholas E , Caro Tim , Matchette Samuel R , Cuthill Innes C
Published: August 2023

‘Dazzle coloration’ describes a wide variety of high-contrast patterns allegedly providing protection against attack during motion. Previous research falls into three broad groups. First, studies using humans demonstrate that certain surface patterns can cause significant misperceptions in controlled laboratory conditions, although the effects are inconsistent in both direction and magnitude. Second, experiments on target capture or tracking also show effects that are strongly dependent upon the test paradigm. It has not been established that these laboratory findings generalize to other species, or to the real world. Third, mainly comparative studies build a case for longitudinal striping being involved in escape strategies in some squamate reptiles. We suggest that: (1) the concept of dazzle conflates a description of appearance with presumed function; (2) some effects attributed to dazzle have not been distinguished clearly from other mechanisms of protective coloration; and (3) confusion persists over the evidence necessary to attribute a dazzle function to markings. We refine the definition of dazzle to exclude appearance: d﻿azzle is coloration that interferes with target interception, as a result of misperception of its speed, trajectory and/or range. Our review clarifies discussion of dazzle, and sets out a coherent and practical framework for future research.
Demographic imbalance in the hybrid zone led to asymmetric gene flow between two closely related geckos, Gekko hokouensis and Gekko yakuensis (Squamata: Gekkonidae)
Authors: Okamoto Kota , Tominaga Atsushi , Toda Mamoru
Published: August 2023

Introgressive hybridization caused by invasive species may lead to the extinction of pure native species, but a theoretical model of the invasion process with hybridization (the neutral demographic model) suggests that introgression occurs mainly from native to invasive species. Clarifying the direction of introgression is important to evaluate the impact of hybridization on native species. In southern Japan, a widely disseminated gecko, Gekko hokouensis, and a local gecko, Gekko yakuensis, have formed mosaic hybrid zones. Given the presumed invasiveness of Gekko hokouensis, the neutral demographic model predicts that introgression would mainly occur in the direction to Gekko hokouensis, whereas possible asymmetric assortative mating suggested by a previous study predicts the opposite direction of introgression. Our investigations using microsatellite markers and mitochondrial DNA for the gecko assemblages in 12 localities and comparisons with allozyme data collected 18 years ago indicated that Gekko hokouensis expanded its range and tended to have replaced hybrids and Gekko yakuensis. Introgression was skewed towards Gekko hokouensis, but interspecific mating between the parental species was reciprocal. These results suggest that their hybridization progress follows the neutral demographic model and that the higher population growth rate of Gekko hokouensis is the major cause of species replacement, although we cannot rule out the possibility that asymmetric assortative mating also influences the later stages of species replacement.
Incomplete lineage sorting explains the low performance of DNA barcoding in a radiation of four species of Western European grasshoppers (Orthoptera: Acrididae: Chorthippus)
Authors: Nabholz Benoit
Published: August 2023

DNA barcoding often fails to identify species despite its undisputed advantages. Hybridization, sample contamination, incomplete lineage sorting and nuclear copies of mitochondrial genes (NUMTs) are often put forward as explanations but have seldomly been tested. Here I used available RNA-sequencing data to explore this issue in four Chorthippus grasshopper species. I was able to exclude NUMTs, contamination and recent hybridization as probable causes of the low barcoding performance. Using a phylogenetic method, I estimated the nuclear and mitochondrial mutation rates as 1.31 × 10−9–2.27 × 10−9 and 8.1 × 10−9–1.4 × 10−8 mutations/site/year, respectively. These grasshoppers therefore did not exhibit a particularly low mitochondrial mutation rate compared to other insect species. Using coalescence simulation, I was able to show that two simple demographic scenarios, with a divergence period of 1–3 Myr, provided a good fit to the mitochondrial genealogies in three of the four target species. Interestingly, the mitochondrial genealogy of Chorthippus mollis was inconsistent with a neutral evolution pattern, suggesting that it had undergone adaptive selection.
Professional Burnout as a Mediator in the Relationship Between Pandemic-Related Stress and Social Care Workers’ Mental Health
Authors: Swords Lorraine , Spratt Trevor , Hanlon Holly
Published: August 2023

Understanding pathways between social care workers’ Coronavirus disease-2019 (COVID-19)-related stress and poorer mental health outcomes can inform employers’ efforts to support the well-being of staff. The present study engaged 103 workers at an Irish Non-Government Organisation providing child and family support services. In the initial months following the cessation of pandemic restrictions in 2022, they completed an anonymous online survey that included questions about their experiences of COVID-19, their professional quality of life and their mental health. The aim was to explore the direct effect of COVID-related stress on workers’ mental health, and the indirect effect through the mediators of compassion satisfaction and the compassion fatigue components of burnout and secondary traumatic stress. The results indicated that greater levels of pandemic stress are significantly and directly related to both increased burnout and poorer mental health, and that burnout also partially mediates the relationship between pandemic stress and poorer mental health. This study adds to a growing body of work concerned to better understand the social care workers’ pandemic experiences, and results are discussed in terms of apprising employers of the need for timely and effective staff supports.
Toxic effects of mutant huntingtin in axons are mediated by its proline-rich domain
Authors: Brady Scott T , Mesnard-Hoaglin Nichole A , Mays Sarah , Priego Mercedes , Dziechciowska Joanna , Morris Sarah , Kang Minsu , Tsai Ming Ying , Purks Jennifer L , Klein Alison , Gaona Angelica , Melloni Alexandra , Connors Theresa , Hyman Bradley , Song Yuyu , Morfini Gerardo A
Published: August 2023

Huntington’s disease results from expansion of a polyglutamine tract (polyQ) in mutant huntingtin (mHTT) protein, but mechanisms underlying polyQ expansion-mediated toxic gain-of-mHTT function remain elusive.

Here, deletion and antibody-based experiments revealed that a proline-rich domain (PRD) adjacent to the polyQ tract is necessary for mHTT to inhibit fast axonal transport and promote axonal pathology in cultured mammalian neurons. Further, polypeptides corresponding to subregions of the PRD sufficed to elicit the toxic effect on fast axonal transport, which was mediated by c-Jun N-terminal kinases (JNKs) and involved PRD binding to one or more SH3-domain containing proteins. Collectively, these data suggested a mechanism whereby polyQ tract expansion in mHTT promotes aberrant PRD exposure and interactions of this domain with SH3 domain-containing proteins including some involved in activation of JNKs. In support, biochemical and immunohistochemical experiments linked aberrant PRD exposure to increased JNK activation in striatal tissues of the zQ175 mouse model and from post-mortem Huntington’s disease patients.

Together, these findings support a critical role of PRD on mHTT toxicity, suggesting a novel framework for the potential development of therapies aimed to halt or reduce axonal pathology in Huntington’s disease.
Review of the role of the endogenous opioid and melanocortin systems in the restless legs syndrome
Authors: Walters Arthur S , Li Yuqing , Koo Brian B , Ondo William G , Weinstock Leonard B , Champion David , Afrin Lawrence B , Karroum Elias G , Bagai Kanika , Spruyt Karen
Published: August 2023

Restless legs syndrome (RLS) is responsive to opioid, dopaminergic and iron-based treatments. Receptor blocker studies in RLS patients suggest that the therapeutic efficacy of opioids is specific to the opioid receptor and mediated indirectly through the dopaminergic system. An RLS autopsy study reveals decreases in endogenous opioids, β-endorphin and perhaps Met-enkephalin in the thalamus of RLS patients. A total opioid receptor knock-out (mu, delta and kappa) and a mu-opioid receptor knock-out mouse model of RLS show circadian motor changes akin to RLS and, although both models show sensory changes, the mu-opioid receptor knock mouse shows circadian sensory changes closest to those seen in idiopathic RLS. Both models show changes in striatal dopamine, anaemia and low serum iron. However, only in the total receptor knock-out mouse do we see the decreases in serum ferritin that are normally found in RLS. There are also decreases in serum iron when wild-type mice are administered a mu-opioid receptor blocker. In addition, the mu-opioid receptor knock-out mouse also shows increases in striatal zinc paralleling similar changes in RLS. Adrenocorticotropic hormone and α-melanocyte stimulating hormone are derived from pro-opiomelanocortin as is β-endorphin. However, they cause RLS-like symptoms and periodic limb movements when injected intraventricularly into rats. These results collectively suggest that an endogenous opioid deficiency is pathogenetic to RLS and that an altered melanocortin system may be causal to RLS as well.
Emotional self-body odors do not influence the access to visual awareness by emotional faces
Authors: Rocha Marta , Grave Joana , Korb Sebastian , Parma Valentina , Semin Gün R , Soares Sandra C
Published: August 2023

A growing body of research suggests that emotional chemosignals in others’ body odor (BO), particularly those sampled during fearful states, enhance emotional face perception in conscious and preconscious stages. For instance, emotional faces access visual awareness faster when presented with others’ fear BOs. However, the effect of these emotional signals in self-BO, that is, one’s own BO, is still neglected in the literature. In the present work, we sought to determine whether emotional self-BOs modify the access to visual awareness of emotional faces. Thirty-eight women underwent a breaking-Continuous Flash Suppression task in which they were asked to detect fearful, happy, and neutral faces, as quickly and accurately as possible, while being exposed to their fear, happiness, and neutral self-BOs. Self-BOs were previously collected and later delivered via an olfactometer, using an event-related design. Results showed a main effect of emotional faces, with happy faces being detected significantly faster than fearful and neutral faces. However, our hypothesis that fear self-BOs would lead to faster emotional face detection was not confirmed, as no effect of emotional self-BOs was found—this was confirmed with Bayesian analysis. Although caution is warranted when interpreting these results, our findings suggest that emotional face perception is not modulated by emotional self-BOs, contrasting with the literature on others’ BOs. Further research is needed to understand the role of self-BOs in visual processing and emotion perception.
Clinical and Genomic Characterization of a Cohort of Patients With Klebsiella pneumoniae Bloodstream Infection
Authors: Roach David J , Sridhar Sushmita , Oliver Elizabeth , Rao Sowmya R , Slater Damien M , Hwang Wontae , Hutt Vater Kian , Dinesh Anupama , Qadri Firdausi , Chisti Mohammod J , Pierce Virginia M , Turbett Sarah E , Bhattacharyya Roby P , Worby Colin J , Earl Ashlee M , LaRocque Regina C , Harris Jason B
Published: August 2023

Background

The clinical and microbial factors associated with Klebsiella pneumoniae bloodstream infections (BSIs) are not well characterized. Prior studies have focused on highly resistant or hypervirulent isolates, limiting our understanding of K. pneumoniae strains that commonly cause BSI. We performed a record review and whole-genome sequencing to investigate the clinical characteristics, bacterial diversity, determinants of antimicrobial resistance, and risk factors for in-hospital death in a cohort of patients with K. pneumoniae BSI.

Methods

We identified 562 patients at Massachusetts General Hospital with K. pneumoniae BSIs between 2016 and 2022. We collected data on comorbid conditions, infection source, clinical outcomes, and antibiotic resistance and performed whole-genome sequencing on 108 sequential BSI isolates from 2021 to 2022.

Results

Intra-abdominal infection was the most common source of infection accounting for 34% of all BSIs. A respiratory tract source accounted for 6% of BSIs but was associated with a higher in-hospital mortality rate (adjusted odds ratio, 5.4 [95% confidence interval, 2.2–12.8]; P < .001 for comparison with other sources). Resistance to the first antibiotic prescribed was also associated with a higher risk of death (adjusted odds ratio, 5.2 [95% confidence interval, 2.2–12.4]; P < .001). BSI isolates were genetically diverse, and no clusters of epidemiologically and genetically linked cases were observed. Virulence factors associated with invasiveness were observed at a low prevalence, although an unexpected association between O-antigen type and the source of infection was found.

Conclusions

These observations demonstrate the versatility of K. pneumoniae as an opportunistic pathogen and highlight the need for new approaches for surveillance and the rapid identification of patients with invasive antimicrobial-resistant K. pneumoniae infection.
Clinical and pathological characteristics in elderly patients with IgA nephropathy
Authors: Zhang Yongji , Li Qianqian , Shi Sufang , Liu Lijun , Lv Jicheng , Zhu Li , Zhang Hong
Published: August 2023

Background

Immunoglobulin A nephropathy (IgAN) is the most common cause of primary glomerulonephritis, with highly variable manifestations. Although the peak incidence of IgAN is in young adults, the diagnosis among elderly people is increasing. Here we explored the effect of aging on IgAN features, as well as cellular senescence in the kidney of IgAN.

Methods

A total of 910 patients with IgAN were enrolled, which contained 182 individuals in each age stage (aged ≥60, 50–59, 40–49, 30–39 and 20–29 years). Clinical and pathological manifestations at the time of renal biopsy were compared. Additionally, 38 patients with IgAN (19 aged over or equal to 60 years and 19 aged below 60 years) were randomly selected for p16INK4a staining by immunohistochemistry. The percentage of p16INK4a-positive cells in glomeruli, renal tubule and interstitium were separately quantified.

Results

Compared with young IgAN patients, elderly patients presented with higher levels of circulating IgA, uric acid and proteinuria, but lower estimated glomerular filtration rates (eGFR), as well as lower red blood cell counts, platelet counts and lymphocyte counts. Moreover, elderly IgAN patients showed higher incidence of hypertension, and lower incidence of prodromic infection. Regarding histological lesions in the kidney, young IgAN patients had higher degree of IgA and C3 deposits, while elderly IgAN patients had more severe Oxford-E lesions, but less severe Oxford-S lesions. The percentage of glomerular and tubular p16INK4a-positive cells in elderly patients showed an increasing trend, but statistical significance was not reached. The percentage of p16INK4a-positive nuclei in renal interstitium was positively associated with T score, while increased percentage of p16INK4a-positive nuclei in renal tubule was associated with eGFR and 24-h urinary protein level.

Conclusion

In our IgAN cohort, elderly IgAN patients presented with some aging-related features, and both aging- and IgAN-induced pathological injury contributed to the kidney lesions in patients with IgAN.
Low Occurrence of Colectomy With Long-Term (up to 4 Years) Golimumab Treatment in Patients With Moderate-to-Severe Active Ulcerative Colitis: Data From the PURSUIT Maintenance and Long-Term Extension Studies
Authors: Weinstein Cindy L J , Meehan Alan G , Govoni Marinella , Lin Jianxin , Reinisch Walter
Published: August 2023

Background

This analysis evaluated the incidence of all-cause colectomies (total or partial) among patients with moderate-to-severe active ulcerative colitis (UC) in the golimumab (GLM) Program of Ulcerative Colitis Utilizing an Investigational Treatment (PURSUIT)-maintenance (-M) and long-term extension (-LTE) studies.

Methods

Eligible PURSUIT-M trial participants completed a 6-week GLM induction trial without requiring colectomy. Responders to GLM induction were randomized 1:1:1 to GLM 50 mg, GLM 100 mg, or placebo (PBO) maintenance for up to 1 year, administered every 4 weeks (q4w). Nonresponders to GLM or PBO induction received GLM 100 mg; responders to PBO induction received PBO (each administered q4w for up to 1 year). Participants who completed PURSUIT-M were eligible to continue their treatment in the 3-year PURSUIT-LTE study.

Results

A total of 60 (4.9%) colectomies were reported among the 1228 patients who enrolled in the 1-year PURSUIT-M study, which included 672 participants who continued into the 3-year PURSUIT-LTE LTE study (of which 666 were treated). The colectomy rate during the 3-year extension was lower than that observed during the maintenance phase of the study (9/666 [1.4%] compared to 51/1228 [4.2%]). The majority (43/60 [71.7%]) of the reported colectomies occurred in patients who had not responded to induction therapy and who tended to have had more severe disease characteristics at baseline.

Conclusions

This retrospective evaluation of colectomy data from the PURSUIT-M and -LTE studies in patients with moderate-to-severe active UC demonstrated a low (<5%) occurrence of colectomy with long-term (up to 4 years) GLM treatment. PURSUIT-M (NCT00488631; EudraCT, 2006-003399-37).
Superior predictive value of transmural over endoscopic severity for colectomy risk in ulcerative colitis: a multicentre prospective cohort study
Authors: Piazza O Sed Nicole , Noviello Daniele , Filippi Elisabetta , Conforti Francesco , Furfaro Federica , Fraquelli Mirella , Costantino Andrea , Danese Silvio , Vecchi Maurizio , Fiorino Gionata , Allocca Mariangela , Caprioli Flavio
Published: August 2023

Background and Aims

Endoscopic activity is associated with an increased risk of surgery in patients with ulcerative colitis [UC]. Transmural activity, as defined by Milan Ultrasound Criteria [MUC] > 6.2, reliably detects endoscopic activity in patients with UC. The present study aimed to assess in UC patients whether transmural severity is a better predictor of colectomy as compared to endoscopy.

Methods

Consecutive adult UC patients were recruited in two IBD Referral Centres and underwent colonoscopy and intestinal ultrasound in a blinded fashion. The need for colectomy was assessed at follow-up. Univariable and multivariable logistic and Cox regression analyses were performed. Receiver operating characteristic [ROC] analysis was used to compare MUC baseline values and Mayo Endoscopic Scores [MES] in predicting colectomy risk.

Results

Overall, 141 patients were enrolled, and 13 underwent colectomy in the follow-up period. Both MES (hazard ratio [HR]: 3.15, 95% confidence interval [CI]: 1.18–8.37, p = 0.02) and MUC [HR: 1.48, 95% CI: 1.19–1.76, p < 0.001] were associated with colectomy risk, but only MUC was independently associated with this event on multivariable analysis [HR: 1.46, 95% CI: 1.06–2.02, p = 0.02]. MUC was the only independent variable associated with colectomy risk in patients with clinically active disease (odds ratio [OR]: 1.53 [1.03–2.27], p = 0.03). MUC demonstrated higher accuracy than MES (area under ROC curve [AUROC] 0.83, 95% CI: 0.75–0.92 vs 0.71, 95% CI: 0.62–0.80) and better performance for predicting colectomy [p = 0.02]. The optimal MUC score cut-off value for predicting colectomy, as assessed by the Youden index, was 7.7.

Conclusions

A superior predictive value was found for transmural vs endoscopic severity for colectomy risk in UC patients.
Safety of cangrelor and transition to oral P2Y12 inhibitors in patients undergoing percutaneous coronary intervention: the ARCANGELO study
Authors: De Luca Leonardo , Calabrò Paolo , Capranzano Piera , Di Mario Carlo , Chirillo Fabio , Rolfo Cristina , Menozzi Alberto , Menichelli Maurizio , Bolognese Leonardo , Musumeci Giuseppe
Published: August 2023

Aims

Cangrelor is the only intravenous P2Y12 inhibitor available. Safety, efficacy, and transitioning from cangrelor to oral P2Y12 inhibitors were recorded in patients with acute coronary syndrome (ACS). The ARCANGELO study aims to assess the safety of cangrelor on bleeding and the effects of the transition to oral P2Y12 inhibitors in a real-world setting according to the European Medical Agency’s requirement.

Methods and results

Adult patients with ACS undergoing percutaneous coronary intervention (PCI) receiving cangrelor were included in the study. Patients were followed for 30 days. Incidence of bleeding events, major adverse cardiac events, and transition strategy to oral P2Y12 were recorded. Among 1004 ACS patients undergoing PCI, 995 (99.1%) were eligible for the analysis; 597 (60.0%) of them had ST-segment elevation myocardial infarction. A total of 925 (93.1%) patients underwent PCI by radial catheter access, and 972 (97.2%) received drug-eluting stents. All eligible patients received bolus and cangrelor infusion between 2 and 4 h in 95% of the cases. A total of 730 patients (73.4%) received ticagrelor, 127 (12.8%) prasugrel, and 138 (13.9%) clopidogrel as transition therapy. Bleeding, according to Bleeding Academic Research Consortium (BARC) criteria, within 30 days post-PCI occurred in 5.2% of patients (95% confidence interval: 3.9–6.8%); 0.5% experienced a moderate (BARC 3), and all others mild (BARC 1–2) bleeding events. Major adverse cardiac events occurred in 14 (1.4%) patients, principally all-cause mortality (n = 6 patients) and myocardial infarction (n = 7 patients).

Conclusion

The use of cangrelor in ACS patients undergoing PCI and the transition strategy to P2Y12 inhibitors are confirmed as safe and effective in daily practice.
Aortic flow is associated with aging and exercise capacity
Authors: Zhao Xiaodan , Garg Pankaj , Assadi Hosamadin , Tan Ru-San , Chai Ping , Yeo Tee Joo , Matthews Gareth , Mehmood Zia , Leng Shuang , Bryant Jennifer Ann , Teo Lynette L S , Ong Ching Ching , Yip James W , Tan Ju Le , van der Geest Rob J , Zhong Liang
Published: August 2023

Aims

Increased blood flow eccentricity in the aorta has been associated with aortic (AO) pathology, however, its association with exercise capacity has not been investigated. This study aimed to assess the relationships between flow eccentricity parameters derived from 2-dimensional (2D) phase-contrast (PC) cardiovascular magnetic resonance (CMR) imaging and aging and cardiopulmonary exercise test (CPET) in a cohort of healthy subjects.

Methods and Results

One hundred and sixty-nine healthy subjects (age 44 ± 13 years, M/F: 96/73) free of cardiovascular disease were recruited in a prospective study (NCT03217240) and underwent CMR, including 2D PC at an orthogonal plane just above the sinotubular junction, and CPET (cycle ergometer) within one week. The following AO flow parameters were derived: AO forward and backward flow indexed to body surface area (FFi, BFi), average flow displacement during systole (FDsavg), late systole (FDlsavg), diastole (FDdavg), systolic retrograde flow (SRF), systolic flow reversal ratio (sFRR), and pulse wave velocity (PWV). Exercise capacity was assessed by peak oxygen uptake (PVO2) from CPET. The mean values of FDsavg, FDlsavg, FDdavg, SRF, sFRR, and PWV were 17 ± 6%, 19 ± 8%, 29 ± 7%, 4.4 ± 4.2 mL, 5.9 ± 5.1%, and 4.3 ± 1.6 m/s, respectively. They all increased with age (r = 0.623, 0.628, 0.353, 0.590, 0.649, 0.598, all P < 0.0001), and decreased with PVO2 (r = −0.302, −0.270, −0.253, −0.149, −0.219, −0.161, all P < 0.05). A stepwise multivariable linear regression analysis using left ventricular ejection fraction (LVEF), FFi, and FDsavg showed an area under the curve of 0.769 in differentiating healthy subjects with high-risk exercise capacity (PVO2 ≤ 14 mL/kg/min).

Conclusion

AO flow haemodynamics change with aging and predict exercise capacity.

Registration

NCT03217240
Prognostic implication of liver fibrosis scores in patients with non-ischemic dilated cardiomyopathy
Authors: Liu Yupeng , Song Jingjing , Wang Wenyao , Tang Yi-Da
Published: August 2023

Aims

Liver fibrosis was associated with adverse outcomes in various cardiovascular diseases. The current risk stratification of non-ischemic dilated cardiomyopathy (NIDCM) still largely depends on the left ventricular ejection fraction (LVEF). At present, the relationship between liver fibrosis and prognosis in patients with NIDCM remains blank.

Methods and results

A total of 433 NIDCM patients were analysed in this study. Liver fibrosis was assessed by three liver fibrosis scores (LFS), including aspartate aminotransferase to platelet ratio index (APRI), aspartate aminotransferase/alanine aminotransferase ratio (AST/ALT ratio), and gamma-glutamyltransferase to platelet ratio (GPR). The primary endpoint was defined as all-cause mortality or heart transplantation (ACM/HTx). During a median follow-up period of 1.7 years, 140 ACM/HTx events occurred. Positive associations were observed between LFS and ACM/HTx. Patients with elevated APRI, AST/ALT ratio, and GPR scores exhibited increased ACM/HTx (all P < 0.05). Intermediate-to-high APRI [hazard ratio (HR) 1.66, 95%CI 1.06–2.61, P = 0.027], AST/ALT ratio (HR 1.59, 95%CI 1.07–2.36, P = 0.021), and GPR (HR 1.64, 95%CI 1.11–2.42, P = 0.013) were independently associated with increased risk of ACM/HTx, even after adjusting for LVEF and other covariates. The positive relationship remains consistent across different subgroups, including those with diabetes and obesity.

Conclusions

Elevated liver fibrosis scores were associated with a worse outcome beyond LVEF in patients with NIDCM, which may provide additional prognostic value in the management of NIDCM.
Prevalence and determinants of dilated ascending aorta in a Swedish population: a case–control study
Authors: Swahn Eva , Lekedal Hanna , Engvall Jan , Nyström Fredrik H , Jonasson Lena
Published: August 2023

Aims

Dilation of the ascending aorta (AA) is often asymptomatic until a life-threatening dissection or rupture occurs. An overall increase in the use of thoracic imaging has enabled early and sometimes incidental identification of AA dilation. Still, the prevalence and determinants of AA dilation remain to be clarified. The aim was to identify and characterize persons with AA dilation in a middle-aged Swedish population.

Methods and results

We used the Swedish CardioPulmonary BioImage Study Linköping (n = 5058, age 50–65 years) to identify cases with AA diameter ≥ 40 mm on coronary computed tomography angiography (CCTA) or chest computed tomography. Age- and gender-matched individuals with AA diameter < 40 mm served as controls. Echocardiography, blood pressure (BP) measurements (office and home), pulse wave velocity (PWV), coronary artery calcification (CAC), CCTA-detected coronary atherosclerosis, and carotid ultrasound were used to characterize these subjects. We identified 70 cases (mean AA diameter 44 mm, 77% men) and matched these to 146 controls (mean AA diameter 34 mm). Bicuspid aortic valve and aortic valve dysfunction were more common in cases than in controls (8% vs. 0% and 39% vs. 11%, respectively). Both office and home BP levels were significantly higher among cases. Also, high PWV (>10 m/s) levels were more common in cases (33% vs. 17%). Neither CAC scores nor prevalence or burden of atherosclerosis in coronary and carotid arteries differed between groups.

Conclusion

The prevalence of dilated AA was 1.4% and showed positive associations with male gender, aortic valve pathology, and diastolic BP, though not with subclinical atherosclerosis.
Revascularization of low-surgical risk patients with disease of the left main coronary artery: a fresh look at the evidence
Authors: Baigent Colin , Sádaba Rafael
Published: August 2023

This editorial refers to ‘2022 joint ESC/EACTS review of the 2018 guideline recommendations on the revascularization of left main coronary artery disease in patients at low surgical risk and anatomy suitable for PCI or CABG’, by R.A.
Bone changes post-sleeve gastrectomy in relation to body mass and hormonal changes
Authors: Kaur Snimarjot , Nimmala Supritha , Singhal Vibha , Mitchell Deborah M , Pedreira Clarissa C , Lauze Meghan , Lee Hang , Stanford Fatima Cody , Bouxsein Mary L , Bredella Miriam A , Misra Madhusmita
Published: August 2023

Objective

To determine mechanisms contributing to impaired bone health in youth 24 months following sleeve gastrectomy (SG).

Design

Twenty-four-month longitudinal observational study.

Methods

Participants included 23 youth undergoing SG and 30 non-surgical controls (NS) 13-25 years old with moderate-to-severe obesity. Subjects underwent fasting labs for bone turnover markers (N-terminal propeptide of type 1 procollagen, C-telopeptide (CTX)), sex hormones, sex hormone binding globulin (SHBG), and enteric peptides, DXA for areal bone mineral density (aBMD) and body composition, high-resolution peripheral quantitative CT for volumetric BMD (vBMD) at the distal radius and tibia, and microfinite element analysis for strength estimates.

Results

Groups did not differ for mean age or BMI z-scores. Over 24 months, compared to NS, SG had greater reductions in BMI z-scores, and spine, hip, and femoral neck aBMD Z-scores (P ≤ .012), greater increases in serum CTX and SHBG (P ≤ .039), and greater decreases in estrone and ghrelin (P ≤ .021). Among females, estrone and free androgen index (FAI) decreased (P ≤ .022) in SG vs NS groups. After controlling for age and sex, decreases in BMI and lean mass were associated with decreases in total hip and femoral neck aBMD Z-scores, and decreases in radial total and trabecular vBMD and failure load, and tibial total and trabecular vBMD. Among females, after controlling for age, decreases in estrone were associated with decreases in spine aBMD Z-scores and radial total and trabecular vBMD, and decrease in FAI with decreases in radial failure load.

Conclusion

Reductions in BMI, lean mass, and sex steroids over 24 months post-SG are associated with bone loss and could be targeted for preventative or therapeutic interventions.

Clinical trial registration number: The study is registered in ClinicalTrials.gov (NCT02557438).
2022 Joint ESC/EACTS review of the 2018 guideline recommendations on the revascularization of left main coronary artery disease in patients at low surgical risk and anatomy suitable for PCI or CABG
Authors: Byrne Robert A , Fremes Stephen , Capodanno Davide , Czerny Martin , Doenst Torsten , Emberson Jonathan R , Falk Volkmar , Gaudino Mario , McMurray John J V , Mehran Roxana , Milojevic Milan , Sousa Uva Miguel
Published: August 2023

In October 2021, the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) jointly agreed to establish a Task Force (TF) to review recommendations of the 2018 ESC/EACTS Guidelines on myocardial revascularization as they apply to patients with left main (LM) disease with low-to-intermediate SYNTAX score (0–32). This followed the withdrawal of support by the EACTS in 2019 for the recommendations about the management of LM disease of the previous guideline. The TF was asked to review all new relevant data since the 2018 guidelines including updated aggregated data from the four randomized trials comparing percutaneous coronary intervention (PCI) with drug-eluting stents vs. coronary artery bypass grafting (CABG) in patients with LM disease. This document represents a summary of the work of the TF; suggested updated recommendations for the choice of revascularization modality in patients undergoing myocardial revascularization for LM disease are included. In stable patients with an indication for revascularization for LM disease, with coronary anatomy suitable for both procedures and a low predicted surgical mortality, the TF concludes that both treatment options are clinically reasonable based on patient preference, available expertise, and local operator volumes. The suggested recommendations for revascularization with CABG are Class I, Level of Evidence A. The recommendations for PCI are Class IIa, Level of Evidence A. The TF recognized several important gaps in knowledge related to revascularization in patients with LM disease and recognizes that aggregated data from the four randomized trials were still only large enough to exclude large differences in mortality.
Dipeptidyl peptidase 3 plasma levels predict cardiogenic shock and mortality in acute coronary syndromes
Authors: Wenzl Florian A , Bruno Francesco , Kraler Simon , Klingenberg Roland , Akhmedov Alexander , Ministrini Stefano , Santos Karine , Godly Konstantin , Godly Julia , Niederseer David , Manka Robert , Bergmann Andreas , Camici Giovanni G , von Eckardstein Arnold , Stähli Barbara , Muller Olivier , Roffi Marco , Räber Lorenz , Lüscher Thomas F
Published: August 2023

Background and Aims

Dipeptidyl peptidase 3 (DPP3) is a protease involved in the degradation of angiotensin II which disturbs peripheral blood pressure regulation and compromises left ventricular function. This study examined the relationship of circulating DPP3 (cDPP3) with cardiogenic shock (CS) and mortality in patients presenting with acute coronary syndromes (ACS).

Methods

Plasma cDPP3 levels were assessed at baseline and 12–24 h after presentation in patients with ACS prospectively enrolled into the multi-centre SPUM-ACS study (n = 4787).

Results

Circulating DPP3 levels were associated with in-hospital CS when accounting for established risk factors including the ORBI risk score [per log-2 increase, hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.05–1.82, P = .021]. High cDPP3 was an independent predictor of mortality at 30 days (HR 1.87, 95% CI 1.36–2.58, P < .001) and at one year (HR 1.61, 95% CI 1.28–2.02, P < .001) after adjustment for established risk factors and the GRACE 2.0 score. Compared to values within the normal range, persistently elevated cDPP3 levels at 12–24 h were associated with 13.4-fold increased 30-day mortality risk (HR 13.42, 95% CI 4.86–37.09, P < .001) and 5.8-fold increased 1-year mortality risk (HR 5.79, 95% CI 2.70–12.42, P < .001). Results were consistent across various patient subgroups.

Conclusions

This study identifies cDPP3 as a novel marker of CS and increased mortality in patients with ACS. Circulating DPP3 offers prognostic information beyond established risk factors and improves early risk assessment.
Significance of lipids, lipoproteins, and apolipoproteins during the first 14–16 months of life
Authors: Taageby Nielsen Sofie , Mohr Lytsen Rikke , Strandkjær Nina , Juul Rasmussen Ida , Sillesen Anne-Sophie , Vøgg R Ottilia B , Axelsson Raja Anna , Nordestgaard Børge G , Kamstrup Pia R , Iversen Kasper , Bundgaard Henning , Tybjærg-Hansen Anne , Frikke-Schmidt Ruth
Published: August 2023

Background and Aims

The aims of this study were to investigate lipid parameters during the first 14–16 months of life, to identify influential factors, and to test whether high concentrations at birth predict high concentrations at 2- and 14–16 months.

Methods

The Copenhagen Baby Heart Study, including 13,354 umbilical cord blood samples and parallel venous blood samples from children and parents at birth (n = 444), 2 months (n = 364), and 14–16 months (n = 168), was used.

Results

Concentrations of lipids, lipoproteins, and apolipoproteins in umbilical cord blood samples correlated highly with venous blood samples from newborns. Concentrations of low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (HDL) cholesterol, apolipoprotein B, and lipoprotein(a) increased stepwise from birth to 2 months to 14–16 months. Linear mixed models showed that concentrations of LDL cholesterol, non-HDL cholesterol, and lipoprotein(a) above the 80th percentile at birth were associated with significantly higher concentrations at 2 and 14–16 months. Finally, lipid concentrations differed according to sex, gestational age, birth weight, breastfeeding, and parental lipid concentrations.

Conclusions

Lipid parameters changed during the first 14–16 months of life, and sex, gestational age, birth weight, breastfeeding, and high parental concentrations influenced concentrations. Children with high concentrations of atherogenic lipid traits at birth had higher concentrations at 2 and 14–16 months. These findings increase our knowledge of how lipid traits develop over the first 14–16 months of life and may help in deciding the optimal child age for universal familial hypercholesterolaemia screening.
Heart failure medical therapy prior to mitral transcatheter edge-to-edge repair: the STS/ACC Transcatheter Valve Therapy Registry
Authors: Varshney Anubodh S , Shah Miloni , Vemulapalli Sreekanth , Kosinski Andrzej , Bhatt Ankeet S , Sandhu Alexander T , Hirji Sameer , DeFilippis Ersilia M , Shah Pinak B , Fiuzat Mona , O’Gara Patrick T , Bhatt Deepak L , Kaneko Tsuyoshi , Givertz Michael M , Vaduganathan Muthiah
Published: August 2023

Background and Aims

Guideline-directed medical therapy (GDMT) is recommended before mitral valve transcatheter edge-to-edge repair (MTEER) in patients with heart failure (HF) and severe functional mitral regurgitation (FMR). Whether MTEER is being performed on the background of optimal GDMT in clinical practice is unknown.

Methods

Patients with left ventricular ejection fraction (LVEF) < 50% who underwent MTEER for FMR from 23 July 2019 to 31 March 2022 in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry were identified. Pre-procedure GDMT utilization was assessed. Cox proportional hazards models were constructed to evaluate associations between pre-MTEER therapy (no/single, double, or triple therapy) and risk of 1-year mortality or HF hospitalization (HFH).

Results

Among 4199 patients across 449 sites, beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, mineralocorticoid receptor antagonists, and angiotensin receptor–neprilysin inhibitors were used in 85.1%, 44.4%, 28.6%, and 19.9% before MTEER, respectively. Triple therapy was prescribed for 19.2%, double therapy for 38.2%, single therapy for 36.0%, and 6.5% were on no GDMT. Significant centre-level variation in the proportion of patients on pre-intervention triple therapy was observed (0%–61%; adjusted median odds ratio 1.48 [95% confidence interval (CI) 1.25–3.88]; P < .001). In patients eligible for 1-year follow-up (n = 2014; 341 sites), the composite rate of 1-year mortality or HFH was lowest in patients prescribed triple therapy (23.0%) compared with double (24.8%), single (35.7%), and no (41.1%) therapy (P < .01 comparing across groups). Associations persisted after accounting for relevant clinical characteristics, with lower risk in patients prescribed triple therapy [adjusted hazard ratio (aHR) 0.73, 95% CI .55–.97] and double therapy (aHR 0.69, 95% CI .56–.86) before MTEER compared with no/single therapy.

Conclusions

Under one-fifth of patients with LVEF <50% who underwent MTEER for FMR in this US nationwide registry were prescribed comprehensive GDMT, with substantial variation across sites. Compared with no/single therapy, triple and double therapy before MTEER were independently associated with reduced risk of mortality or HFH 1 year after intervention.