bluuebunny/crossref_metadata_2025 huggingface dataset:
iSFun: an R package for integrative dimension reduction analysis
Authors: Fang Kuangnan , Ren Rui , Zhang Qingzhao , Ma Shuangge
Published: April 2022

In the analysis of high-dimensional omics data, dimension reduction techniques—including principal component analysis (PCA), partial least squares (PLS) and canonical correlation analysis (CCA)—have been extensively used. When there are multiple datasets generated by independent studies with compatible designs, integrative analysis has been developed and shown to outperform meta-analysis, other multidatasets analysis, and individual-data analysis. To facilitate integrative dimension reduction analysis in daily practice, we develop the R package iSFun, which can comprehensively conduct integrative sparse PCA, PLS and CCA, as well as meta-analysis and stacked analysis. The package can conduct analysis under the homogeneity and heterogeneity models and with the magnitude- and sign-based contrasted penalties. As a ‘byproduct’, this article is the first to develop integrative analysis built on the CCA technique, further expanding the scope of integrative analysis.

Availability and implementation

The package is available at https://CRAN.R-project.org/package=iSFun.

Supplementary information

Supplementary materials are available at Bioinformatics online.
Underground metabolism as a rich reservoir for pathway engineering
Authors: Kovács Szabolcs Cselgő , Szappanos Balázs , Tengölics Roland , Notebaart Richard A , Papp Balázs
Published: April 2022

Motivation

Bioproduction of value-added compounds is frequently achieved by utilizing enzymes from other species. However, expression of such heterologous enzymes can be detrimental due to unexpected interactions within the host cell. Recently, an alternative strategy emerged, which relies on recruiting side activities of host enzymes to establish new biosynthetic pathways. Although such low-level ‘underground’ enzyme activities are prevalent, it remains poorly explored whether they may serve as an important reservoir for pathway engineering.

Results

Here, we use genome-scale modeling to estimate the theoretical potential of underground reactions for engineering novel biosynthetic pathways in Escherichia coli. We found that biochemical reactions contributed by underground enzyme activities often enhance the in silico production of compounds with industrial importance, including several cases where underground activities are indispensable for production. Most of these new capabilities can be achieved by the addition of one or two underground reactions to the native network, suggesting that only a few side activities need to be enhanced during implementation. Remarkably, we find that the contribution of underground reactions to the production of value-added compounds is comparable to that of heterologous reactions, underscoring their biotechnological potential. Taken together, our genome-wide study demonstrates that exploiting underground enzyme activities could be a promising addition to the toolbox of industrial strain development.

Availability and implementation

The data and scripts underlying this article are available on GitHub at https://github.com/pappb/Kovacs-et-al-Underground-metabolism.

Supplementary information

Supplementary data are available at Bioinformatics online.
Climate change negatively affects Amazonian social wasps
Authors: Dejean Alain , Corbara Bruno , Azémar Frédéric , Petitclerc Frédéric , Burban Benoit , Talaga Stanislas , Compin Arthur
Published: April 2022

The impact of climate change is intensifying in Amazonia through, among other causes, the higher frequency of both severe droughts and floods due to El Niño and La Niña events as well as an Atlantic influence. Over a 25-year period (1997–2021) we examined in French Guiana the impact of different climatic parameters on the most frequent social wasp, Polybia bistriata (Polistinae). As it commonly nests on Clusia grandiflora (Clusiaceae), its nests are easily found. Heavy rainfall, particularly during the 1999–2000 La Niña episode, negatively affected this social wasp species as the percentage of Clusia sheltering an active P. bistriata nest decreased from ≈ 40% during the pre-2000 period to zero in 2021. We conclude that extreme wet seasons related to climate change translated into the decline of this species and likely were detrimental to many other polistine wasps of north-eastern Amazonia.
Body size is not correlated with the evolution of male coloration in darters (Percidae: Etheostomatinae)
Authors: Ciccotto Patrick J , Mendelson Tamra C
Published: April 2022

Coloration and body size are among the many morphological traits that vary among fish lineages. Elaborate coloration and body size covary in other animal groups, but relationships between these two morphological characteristics have not been rigorously examined in fishes. We formally test for correlations between coloration and body size in darters (Percidae: Etheostomatinae), a group of North American freshwater fishes that vary in the presence of male coloration and maximum body size. Although uncorrected analyses indicate a significant correlation between colour traits and body size in darters, phylogenetically corrected logistic regression models and ANOVAs revealed no significant correlations, suggesting body size does not act as a constraint on elaborate coloration or vice versa. These results are discussed in an ecological and behavioural context.
Compression following treatment of superficial venous incompetence: systematic review
Authors: Mohamed Abduraheem H , Thadani Simran , Mohamed Sundus Hussein , Sidapra Misha , Smith George , Chetter Ian , Carradice Daniel
Published: April 2022

Background

International guidelines recommend postprocedural compression when treating symptomatic superficial venous incompetence (SVI). This updated review of RCTs investigated the requirement for postprocedural compression and how it can be applied optimally.

Methods

The National Institute for Health and Care Excellence’s Healthcare Databases Advanced Search engine was used to identify all English-language RCTs of compression following treatment for SVI. Outcomes of interest included postprocedural pain, venous thromboembolism, health-related quality of life (HRQoL), and anatomical occlusion.

Results

A total of 18 studies were included comprising some 2584 treated limbs. Compression was compared with no compression in four studies, nine studies compared different durations of compression, and a further five compared different types of compression. A 1–2-week period of compression was associated with a mean reduction of 11 (95 per cent c.i. 8 to 13) points in pain score on a 100-mm visual analogue scale compared with a shorter duration (P < 0.001). This was associated with improved HRQoL and patient satisfaction. Longer durations of compression did not add further benefit. There was low-quality evidence suggesting that 35-mmHg compression with eccentric thigh compression achieved lower pain scores than lower interface pressures. There were no significant differences in venous thromboembolism rates or technical success in any group, including no compression.

Conclusion

Postprocedural compression of 1–2 weeks after SVI treatment is associated with reduced pain compared with a shorter duration. The optimal interface pressure and type of compression, and the impact on venous thromboembolism risk, remain to be determined.
Adverse events following robotic surgery: population-based analysis
Authors: Muaddi Hala , Stukel Therese A , de Mestral Charles , Nathens Avery , Pautler Stephen E , Shayegan Bobby , Hanna Waël C , Schlachta Christopher , Breau Rodney H , Hopkins Laura , Jackson Timothy , Karanicolas Paul J
Published: April 2022

Background

Robotic surgery was integrated into some healthcare systems despite there being few well designed, real-world studies on safety or benefit. This study compared the safety of robotic with laparoscopic, thoracoscopic, and open approaches in common robotic procedures.

Methods

This was a population-based, retrospective study of all adults who underwent prostatectomy, hysterectomy, pulmonary lobectomy, or partial nephrectomy in Ontario, Canada, between 2008 and 2018. The primary outcome was 90-day total adverse events using propensity score overlap weights, and secondary outcomes were minor or major morbidity/adverse events.

Results

Data on 24 741 prostatectomy, 75 473 hysterectomy, 18 252 pulmonary lobectomy, and 6608 partial nephrectomy operations were included. Relative risks for total adverse events in robotic compared with open surgery were 0.80 (95 per cent c.i. 0.74 to 0.87) for radical prostatectomy, 0.44 (0.37 to 0.52) for hysterectomy, 0.53 (0.44 to 0.65) for pulmonary lobectomy, and 0.72 (0.54 to 0.97) for partial nephrectomy. Relative risks for total adverse events in robotic surgery compared with a laparoscopic/thoracoscopic approach were 0.94 (0.77 to 1.15), 1.00 (0.82 to 1.23), 1.01 (0.84 to 1.21), and 1.23 (0.82 to 1.84) respectively.

Conclusion

The robotic approach is associated with fewer adverse events than an open approach but similar to a laparoscopic/thoracoscopic approach. The benefit of the robotic approach is related to the minimally-invasive approach rather than the platform itself.
Influence of patient sex on outcomes after pancreatic surgery: multicentre study
Authors: Damanakis Alexander I , Toader Justus , Wahler Isabell , Plum Patrick , Quaas Alexander , Ernst Angela , Popp Felix , Gebauer Florian , Bruns Christiane
Published: April 2022

Background

Recent findings support the hypothesis of sex-related differences in inflammatory and immunological responses to trauma. The aim of this study was to address sex-specific aspects in patients who underwent pancreatic surgery.

Methods

This retrospective study used data from the German StuDoQ registry. Patients who underwent pancreatic surgery between 2010 and 2020 were stratified according to procedure (pancreatic head resection, distal pancreatectomy (DP), total pancreatectomy (TP)). Each cohort underwent propensity score matching (PSM) with the co-variables BMI, ASA, age, coronary heart disease (CHD), diabetes, hypertension with medication, and histology to level the distribution of co-morbidities between men and women. The main outcomes were morbidity and mortality.

Results

The total cohort consisted of 10 224 patients (45.3 per cent women). Men had higher ASA grades, and more often had CHD, diabetes, and hypertension with medication. Women had fewer overall complications (57.3 versus 60.1 per cent; P = 0.005) and a lower mortality rate (3.4 versus 4.9 per cent; P < 0.001). Rates of pancreatic surgery-specific complications, such as clinically relevant postoperative pancreatic fistula (POPF) (grade B/C: 14 versus 17 per cent; P < 0.001), delayed gastric emptying (grade B/C: 7.8 versus 9.2 per cent; P = 0.014), and postpancreatectomy haemorrhage (grade B/C: 7.1 versus 9.0 per cent; P < 0.001), were also lower in women. After PSM, 8358 patients were analysed. In the pancreatic head resection cohort (5318 patients), women had fewer complications (58.6 versus 61.4 per cent; P = 0.044), a lower in-hospital mortality rate (3.6 versus 6.1 per cent; P < 0.001), and less often had clinically relevant POPF (11.6 versus 16.2 per cent; P < 0.001). After DP, the clinically relevant POPF rate was lower in women (22.5 versus 27.3 per cent; P = 0.012). In the TP cohort, men more often developed intra-abdominal abscess requiring drainage (5.0 versus 2.3 per cent; P = 0.050).

Conclusion

Women had favourable outcomes after pancreatic surgery.
Green Multiplex Chromatographic Determination of Nine Penicillin Antibiotics Residues in Industrial Air Dust and Wastewater Environmental Samples
Authors: El-Kimary Eman I , Korany Mohammed A , Issa Ahmed E , Basuny Mohamed G
Published: April 2022

Determination of penicillin residues in different industrial effluents including wastewater and air samples is important to prevent exposure to residual amounts of penicillin and the development of antibiotic resistance. A green high performance liquid chromatography (HPLC) method coupled with diode array detection has been developed and validated for multiplex determination of nine penicillin antibiotics in the industrial air dust and wastewater environmental samples of penicillin facility in addition to the monitoring of facility surface cleaning. Separation was performed on C18 column with gradient elution of methanol and phosphate buffer (pH 4) at a flow rate of 1.5 mL min-1 and ultra violet (UV) detection at 220 nm. Low limits of detection were achieved (0.1–0.3 μg mL-1) indicating good sensitivity of the proposed. The method was applied for ensuring the efficiency of cleaning validation after worst-case selection. Recovery studies of the studied penicillins from fortified stainless steel and polycarbonate surfaces and swabs were between 91.91 and 100.22% with relative standard deviation 0.11–1.79%. The presence of any of the studied penicillins in wastewater samples from penicillin plant drainage was checked. Also, total air dust concentration (mg m–3) and % of penicillin active material residues in air dust were calculated from the area of the exposed group in suspension, tablet and vial production lines. The proposed method can be recommended for routine analysis of air and wastewater environmental samples for the detection of penicillin antibiotics at low levels as well as monitoring of facility surface cleaning with high accuracy and precision.
Precision Vaccine Adjuvants for Older Adults: A Scoping Review
Authors: Nanishi Etsuro , Angelidou Asimenia , Rotman Chloe , Dowling David J , Levy Ofer , Ozonoff Al
Published: April 2022

Older adults, defined as those ≥60 years of age, are a growing population vulnerable to infections including severe acute respiratory syndrome coronavirus 2. Although immunization is a key to protecting this population, immunosenescence can impair responses to vaccines. Adjuvants can increase the immunogenicity of vaccine antigens but have not been systematically compared in older adults. We conducted a scoping review to assess the comparative effectiveness of adjuvants in aged populations. Adjuvants AS01, MF59, AS03, and CpG-oligodeoxynucleotide, included in licensed vaccines, are effective in older human adults. A growing menu of investigational adjuvants, such as Matrix-M and CpG plus alum, showed promising results in early phase clinical trials and preclinical studies. Most studies assessed only 1 or 2 adjuvants and no study has directly compared >3 adjuvants among older adults. Enhanced preclinical approaches enabling direct comparison of multiple adjuvants including human in vitro modeling and age-specific animal models may derisk and accelerate vaccine development for older adults.
Legal Enforcement of the National Emissions Trading Scheme and the Environmental Protection Tax in China: Heavy Hand or Light Touch?
Authors: Geroe Steven , Zhang Hao
Published: April 2022

This article evaluates the severity of legal enforcement measures for the 2021 National Carbon Emissions Trading Management (Trial) Measures (ETS Trial Measures) and the Environment Protection Tax (EPT) as a potential model or basis for carbon taxation. While the focus is on the content of specific regulatory provisions, evidence of enforcement action forms part of their evaluation. The ETS Trial Measures are compared to the enforcement provisions in Chinese regional emission-trading scheme (ETS) pilots, the 2019 and 2020 opinion solicitation drafts (OSDs), and the March 2021 OSD for a proposed State Council regulation, drawing on the scholarly literature and interviews in the specialist Chinese government and professional and research institutions. The current ETS enforcement measures are weaker and less comprehensive than those in some pilots and in all of the OSDs. Adopting measures recommended by interviewees as effective in the pilots could augment their stringency. The EPT has a stronger basis for enforcement through existing taxation and environmental laws. While its enforcement has been backed by an increasingly centralized environmental governance system, design elements that allow regional flexibility in implementation and inconsistent enforcement have reduced its effectiveness. These outcomes may be influenced by trade-offs between central government objectives and subnational economic and industrial priorities and resistance by powerful commercial interests. These limiting factors can be addressed by effective regulatory implementation, successful trading, and combining stringent penalties with measures that have a lighter touch, such as capacity building, leading to deepening acceptance by all stakeholders.
Guiding Covid policy: cost-benefit analysis and beyond
Authors: Aldred Jonathan
Published: April 2022

Cost-benefit analysis (CBA) is inappropriate as an aid to Covid policy-making because the plural, incommensurable values at stake are not all amenable to monetary measurement. CBA for Covid policy is also undermined by pervasive uncertainty and ignorance, and has some troubling distributional implications. However, non-consequentialist alternatives to CBA tend towards implausibly absolutist prohibitions on risk imposition. Arguments for setting aside consequentialism for special circumstances (the precautionary principle, or a medical rule of rescue) are also problematic when applied to Covid policy. A broad consequentialist approach to policy guidance is defended, one which does not demand commensuration on a common monetary scale. Despite the absence of commensuration, policy guidance is still possible.
From WEDA to EDTA to ERA: 60 years of supporting European nephrology and counting
Authors: Wanner Christoph
Published: April 2022

Nephrology has evolved from treating kidney failure, first with dialysis and then with kidney transplantation, to identifying and treating early stages of kidney disease and eventually to prevent kidney disease from occurring. Similarly, the name of the European scientific society caring for people with kidney disease has evolved from the West European Dialysis Society Association to the European Dialysis and Transplant Association to the European Renal Association. These name changes reflect a deeper change in the mission of the society to the current mission of leading European nephrology by promoting kidney health for all, improving kidney care for patients, and strengthen the kidney community and the vision of a Europe where kidney health is prioritized, kidney health is accessible and the kidney community is thriving. We now review the major changes in the society over the years and present its current structure and focus as we face the largest projected increase to date in the global burden of kidney diseases.
The hidden diabetic kidney disease in a university hospital-based population: a real-world data analysis
Authors: Marques María , López-Sánchez Paula , Tornero Fernando , Gargantilla Pedro , Maroto Alba , Ortiz Alberto , Portolés José
Published: April 2022

Background

Correct identification of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) patients is crucial to implement therapeutic interventions that may prevent disease progression.

Methods

We compared the real prevalence of DKD in T2DM patients according to actual serum and urine laboratory data with the presence of the diagnostic terms DKD and/or CKD on the electronic medical records (EMRs) using a natural language processing tool (SAVANA Manager). All patients ˃18 years of age and diagnosed with T2DM were selected. DKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or a urinary albumin:creatinine ratio (UACR) >30 mg/g or a urinary protein:creatinine ratio (UPCR) >0.3 g/g after excluding acute kidney injury.

Results

A total of 15 304 T2DM patients identified on EMRs were eligible to enter the study. A total of 4526 (29.6%) T2DM patients had DKD according to lab criteria. However, the terms CKD or DKD were only present in 33.1% and 7.5%, representing a hidden prevalence of CKD and DKD of 66.9% and 92.5%, respectively. Less severe kidney disease (lower UACR or UPCR, higher eGFR values), female sex and lack of insulin prescription were associated with the absence of DKD or CKD terms in the EMRs (P < .001)

Conclusions

The prevalence of DKD among T2DM patients defined by lab data is significantly higher than that reported on hospital EMRs. This could imply underdiagnosis of DKD, especially in patients with the least severe disease who may benefit the most from optimized therapy.
Increase in the global burden of chronic kidney disease: might it be attributable to air pollution?
Authors: Copur Sidar , Ucku Duygu , Kanbay Mehmet
Published: April 2022

Air pollution is an emerging etiology of chronic kidney disease (CKD). Evidence regarding this causative relationship has been shown by several studies. Recently, Lin et al. conducted the first community-based study investigating the association between CKD prevalence and air pollutant levels utilizing a Fuzzy Logic Interference model. Despite the study's limitations, the results correlate with the previous meta-analysis and observational studies. Higher fine particular matter (PM2.5) levels are associated with the increased global burden of CKD and may also influence the unequal distribution of burden in low-to-middle income countries. Despite growing evidence of the association of air pollution with CKD risk, the underlying pathophysiology has yet to be fully understood. Future studies investigating the pathophysiology and efficiency of the potential therapeutic and preventive measures against air pollution-related kidney injury are required to reduce the CKD burden.
Network psychometrics and cognitive network science open new ways for understanding math anxiety as a complex system
Authors: Stella Massimo
Published: April 2022

Math anxiety is a clinical pathology impairing cognitive processing in math-related contexts. Originally thought to affect only inexperienced, low-achieving students, recent investigations show how math anxiety is vastly diffused even among high-performing learners. This review of data-informed studies outlines math anxiety as a complex system that: (i) cripples well-being, self-confidence and information processing on both conscious and subconscious levels, (ii) can be transmitted by social interactions, like a pathogen, and worsened by distorted perceptions, (iii) affects roughly 20$\%$ of students in 63 out of 64 worldwide educational systems but correlates weakly with academic performance and (iv) poses a concrete threat to students’ well-being, computational literacy and career prospects in science. These patterns underline the crucial need to go beyond performance for estimating math anxiety. Recent advances in network psychometrics and cognitive network science provide ideal frameworks for detecting, interpreting and intervening upon such clinical condition. Merging education research, psychology and data science, the approaches reviewed here reconstruct psychological constructs as complex systems, represented either as multivariate correlation models (e.g. graph exploratory analysis) or as cognitive networks of semantic/emotional associations (e.g. free association networks or forma mentis networks). Not only can these interconnected networks detect otherwise hidden levels of math anxiety but—more crucially—they can unveil the specific layout of interacting factors, for example, key sources and targets, behind math anxiety in a given cohort. As discussed here, these network approaches open concrete ways for unveiling students’ perceptions, emotions and mental well-being, and can enable future powerful data-informed interventions untangling math anxiety.
Petroleum-derived naphthenic acids disrupt hormone-dependent sexual behaviours in male Western clawed frogs
Authors: Zhang Wo Su , Farmer Elizabeth J , Muhanzi Daniella , Trudeau Vance L
Published: April 2022

Naphthenic acids (NAs), the carboxylic acids found in petroleum, are of emerging concern as they contaminate coastlines after oil spills, leech into freshwater ecosystems of oil sands areas and have wide industrial applications. They are acutely toxic in fish and tadpoles and may be endocrine disruptors at sublethal levels. We characterized androgen-dependent courtship behaviours and their disruption by NAs in male Western clawed frogs, Silurana tropicalis. Courtship primarily consists of males producing low trills and achieving amplexus, a mating position where a male clasps a female. Adult males were exposed for 5 days to 20 mg/l NA and injected with human chorionic gonadotropin to induce calling. The duration of calling activity was significantly reduced by NA exposure. Other acoustic parameters such as dominant frequency, click rate and trill length were not affected. Vocalization and amplexus were both inhibited after NA exposure and restored after 2 weeks of recovery in clean water. To determine possible disruption at the level of the testes, the effects of NA exposure on gene expression of key players in steroidogenesis was determined. Exposure to NAs decreased srd5a on average by ~ 25%. The enzyme 5α-reductase, encoded by srd5a, converts testosterone to its more bioactive form 5α-dihydrotestosterone (DHT), so NAs may be affecting this steroidogenic step. However, the observed upregulation of lhr, star and cyp17a1 suggests that NA-exposed males may be attempting to counteract the reduced potential to produce DHT. Yet, these NA-exposed frogs have dramatically reduced calling duration, so the observed upregulation of star and cyp17a1 is decoupled from the vocalizations. Calling duration and the ability of males to amplex females is reversibly disrupted by NA exposure, implying that environmental reduction and removal of NAs may help improve habitability of contaminated ecosystems.
Physiological performance of native and invasive crayfish species in a changing environment: insights from Dynamic Energy Budget models
Authors: Marn Nina , Hudina Sandra , Haberle Ines , Dobrović Ana , Klanjšček Tin
Published: April 2022

Crayfish are keystone species important for maintaining healthy freshwater ecosystems. Crayfish species native to Europe, such as Astacus astacus and Austropotamobius torrentium, are facing decline and are increasingly endangered by changing climate and invasions of non-native crayfish, such as Pacifastacus leniusculus and Procambarus virginalis. The success of these invasions largely depends on differences in ontogeny between the native species and the invaders and how changes in the environment will affect the ontogeny. Dynamic Energy Budget (DEB) models can be used to investigate such differences because the models capture dependence of metabolism, and therefore ontogeny, on environmental conditions. We develop DEB models for all four species and investigate key elements of ontogeny and metabolism affecting interspecific competition. We then use the DEB models to predict individual growth and reproduction in current and new conditions that are expected to arise from climate change. Although observations suggest that P. leniusculus poses the major threat to native species, our analysis identifies P. virginalis, in spite of its smaller size, as the superior competitor by a large margin—at least when considering metabolism and ontogeny. Our simulations show that climate change is set to increase the competitive edge of P. virginalis even further. Given the prospects of P. virginalis dominance, especially when considering that it is able to withstand and spread at least some crayfish plague strains that severely affect native species, additional research into P. virginalis is necessary.
WHAT REMAINS OF THE CAMBRIDGE CRITIQUE? ON PROFESSOR SCHEFOLD’S THESES
Authors: Petri Fabio
Published: April 2022

Professor Bertram Schefold’s recent papers on capital theory and the Cambridge critique argue that the very low likelihood of reswitching and reverse capital deepening that appears to emerge from empirical input–output tables is confirmed by theoretical results; these results, he concludes, largely rehabilitate traditional neoclassical views on capital and show that the Sraffian critics’ insistence on reverse capital deepening as a fundamental criticism of neoclassical theory is misplaced. The present paper raises doubts about these arguments. In particular, Professor Schefold does not give adequate consideration to the ‘supply-side’ problems with the measurability and the given endowment of the traditional notion of capital as a single factor. On the empirical evidence based on input–output tables, I agree with Professor Kurz that it suffers from very serious weaknesses. The more recent argument for an extremely low likelihood of double switching, advanced in Schefold (2016, 2018), appears criticisable too. Some weaknesses are also found in the recent argument jointly with Professor Götz Kersting on the ‘poverty of production functions.’
What Remains of the Cambridge Critique? A New Proposal
Authors: Schefold Bertram
Published: April 2022

The debate on capital theory is no more about the historical formation of neoclassical ideas in their original, most abstract form, but about the tools—certainly influenced by those ideas—which are used in teaching applied economics. One focus still is on the economy’s aggregate production function, almost 70 years after Joan Robinson attacked this concept. It has turned out that reswitching—once the most effective argument against the production function—is rare, and that an approximate surrogate production function can be constructed, using random matrices. This seems to weaken the critique, but a new one has emerged, which shows that the number of effective techniques on the wage curve is small and that the possibilities of substitution between capital and labour are quite restricted in the relevant range.
Mechanisms, therapeutic implications, and methodological challenges of gut microbiota and cardiovascular diseases: a position paper by the ESC Working Group on Coronary Pathophysiology and Microcirculation
Authors: Tousoulis Dimitris , Guzik Tomasz , Padro Teresa , Duncker Dirk J , De Luca Giuseppe , Eringa Etto , Vavlukis Marija , Antonopoulos Alexios S , Katsimichas Themistoklis , Cenko Edina , Djordjevic-Dikic Ana , Fleming Ingrid , Manfrini Olivia , Trifunovic Danijela , Antoniades Charalambos , Crea Filippo
Published: April 2022

The human gut microbiota is the microbial ecosystem in the small and large intestines of humans. It has been naturally preserved and evolved to play an important role in the function of the gastrointestinal tract and the physiology of its host, protecting from pathogen colonization, and participating in vitamin synthesis, the functions of the immune system, as well as glucose homeostasis and lipid metabolism, among others. Mounting evidence from animal and human studies indicates that the composition and metabolic profiles of the gut microbiota are linked to the pathogenesis of cardiovascular disease, particularly arterial hypertension, atherosclerosis, and heart failure. In this review article, we provide an overview of the function of the human gut microbiota, summarize, and critically address the evidence linking compositional and functional alterations of the gut microbiota with atherosclerosis and coronary artery disease and discuss the potential of strategies for therapeutically targeting the gut microbiota through various interventions.
Activating P2Y1 receptors improves function in arteries with repressed autophagy
Authors: Cho Jae Min , Park Seul-Ki , Kwon Oh Sung , Taylor La Salle David , Cerbie James , Fermoyle Caitlin C , Morgan David , Nelson Ashley , Bledsoe Amber , Bharath Leena P , Tandar Megan , Kunapuli Satya P , Richardson Russell S , Anandh Babu Pon Velayutham , Mookherjee Sohom , Kishore Bellamkonda K , Wang Fei , Yang Tianxin , Boudina Sihem , Trinity Joel D , Symons John David
Published: April 2022

Aim

The importance of endothelial cell (EC) autophagy to vascular homeostasis in the context of health and disease is evolving. Earlier, we reported that intact EC autophagy is requisite to maintain shear-stress-induced nitric oxide (NO) generation via glycolysis-dependent purinergic signalling to endothelial NO synthase (eNOS). Here, we illustrate the translational and functional significance of these findings.

Methods and results

First, we assessed translational relevance using older male humans and mice that exhibit blunted EC autophagy and impaired arterial function vs. adult controls. Active hyperaemia evoked by rhythmic handgrip exercise-elevated radial artery shear-rate similarly from baseline in adult and older subjects for 60 min. Compared with baseline, indexes of autophagy initiation, p-eNOSS1177 activation, and NO generation, occurred in radial artery ECs obtained from adult but not older volunteers. Regarding mice, indexes of autophagy and p-eNOSS1177 activation were robust in ECs from adult but not older animals that completed 60-min treadmill-running. Furthermore, 20 dyne • cm2 laminar shear stress × 45-min increased autophagic flux, glycolysis, ATP production, and p-eNOSS1177 in primary arterial ECs obtained from adult but not older mice. Concerning functional relevance, we next questioned whether the inability to initiate EC autophagy, glycolysis, and p-eNOSS1177  in vitro precipitates arterial dysfunction ex vivo. Compromised intraluminal flow-mediated vasodilation displayed by arteries from older vs. adult mice was recapitulated in vessels from adult mice by (i) NO synthase inhibition; (ii) acute autophagy impairment using 3-methyladenine (3-MA); (iii) EC Atg3 depletion (iecAtg3KO mice); (iv) purinergic 2Y1-receptor (P2Y1-R) blockade; and (v) germline depletion of P2Y1-Rs. Importantly, P2Y1-R activation using 2-methylthio-ADP (2-Me-ADP) improved vasodilatory capacity in arteries from (i) adult mice treated with 3-MA; (ii) adult iecAtg3KO mice; and (iii) older animals with repressed EC autophagy.

Conclusions

Arterial dysfunction concurrent with pharmacological, genetic, and age-associated EC autophagy compromise is improved by activating P2Y1-Rs.
Association of peripheral venous pressure with adverse post-discharge outcomes in patients with acute heart failure: a prospective cohort study
Authors: Nagao Kazuya , Maruichi-Kawakami Shiori , Aida Kenji , Matsuto Kenichi , Imamoto Kazumasa , Tamura Akinori , Takazaki Tadashi , Nakatsu Taro , Tanaka Masaru , Nakayama Shogo , Morimoto Takeshi , Kimura Takeshi , Inada Tsukasa
Published: April 2022

Aims

Congestion is the major cause of hospitalization for heart failure (HF). Traditional bedside assessment of congestion is limited by insufficient accuracy. Peripheral venous pressure (PVP) has recently been shown to accurately predict central venous congestion. We examined the association between PVP before discharge and post-discharge outcomes in hospitalized patients with acute HF.

Methods and results

Bedside PVP measurement at the forearm vein and traditional clinical examination were performed in 239 patients. The association with the primary composite endpoint of cardiovascular death or HF hospitalization and the incremental prognostic value beyond the established HF risk score was examined. The PVP correlated with peripheral oedema, jugular venous pressure, and inferior vena cava diameter, but not with brain-type natriuretic peptide. The 1-year incidence of the primary outcome measure in the first, second, and third tertiles of PVP was 21.4, 29.9, and 40.7%, respectively (log-rank P = 0.017). The adjusted hazard ratio of PVP per 1 mmHg increase for the 1-year outcome was 1.08 [95% confidence interval (1.03–1.14), P = 0.004]. When added onto the Meta-Analysis Global Group in Chronic HF risk score, PVP significantly increased the area under the receiver-operating characteristic curve for predicting the outcome [from 0.63 (0.56–0.71) to 0.70 (0.62–0.77), P = 0.02), while traditional assessments did not. The addition of PVP also yielded significant net reclassification improvement [0.46 (0.19–0.74), P < 0.001].

Conclusion

The PVP at discharge correlated with prognosis. The results warrant further investigation to evaluate the clinical application of PVP measurement in the care of HF.

Trial registration number

UMIN000034279
Myocardial bridging is significantly associated to myocardial infarction with non-obstructive coronary arteries
Authors: Matta Anthony , Nader Vanessa , Canitrot Ronan , Delmas Clement , Bouisset Frederic , Lhermusier Thibault , Blanco Stephanie , Campelo-Parada Francisco , Elbaz Meyer , Carrie Didier , Galinier Michel , Roncalli Jerome
Published: April 2022

Background

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a common disorder characterized by the presence of clinical criteria for acute myocardial infarction in the absence of obstructive coronary artery disease on angiography. We aim to investigate the relationship between myocardial bridging (MB) and MINOCA.

Methods and results

An observational retrospective study was conducted on 15 036 patients who had been referred for coronary angiography and who fulfilled the Fourth Universal Definition of Myocardial Infarction. The study population was divided into ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) patients, from which we defined two main groups: the MINOCA group and the coronary artery disease (CAD) group. Statistical analyses were carried out by using SPSS, version 20. The prevalence of angiographic MB among the groups was significantly greater in the MINOCA group (2.9% vs. 0.8%). MINOCA accounted for 14.5% of spontaneous myocardial infarction, and the clinical presentation was more frequently NSTEMI rather than STEMI (84.3% vs. 15.7%). After adjusting for confounders, multivariate analyses showed a positive association between MB and MINOCA [odds ratio = 3.28, 95% CI (2.34; 4.61) P < 0.001]. Cardiovascular risk factors were less common in the MINOCA population, which was younger and more often female.

Conclusion

MB is a risk factor for MINOCA. Because MB prevalence differed significantly between the controls (CAD group) and cases (MINOCA group), which were positively associated to MB, it seems likely that MB would be a potential cause of MINOCA. Investigations for MB in MINOCA cases and especially in NSTEMI patients seem necessary.
Comparison of non-invasive assessment for pulmonary vascular indices by two-dimensional echocardiography and cardiac computed tomography angiography with conventional catheter angiocardiography in unrepaired Tetralogy of Fallot physiology patients weighing more than 10 kg: a retrospective analysis
Authors: Kumar Amarendu , Sahu Ankit Kumar , Goel Pravin K , Jain Neeraj , Garg Naveen , Khanna Roopali , Kumar Sudeep , Tewari Satyendra , Kapoor Aditya
Published: April 2022

Aims

Assessment of pulmonary vascular dimensions (PVDs) in Tetralogy of Fallot (TOF) is an integral part of planning transcatheter and surgical interventions. We sought to examine the reliability and correlation of echocardiography (ECHO) and computed tomography angiography (CTA) measurements with those obtained by cardiac catheterization and angiography (CCA).

Methods and results

Tetralogy of Fallot physiology patients undergoing ECHO, CTA, and CCA within a month prior to surgical correction during 2018–2020 were retrospectively enrolled. Indexed diameter of pulmonary annulus (iPAnn), indexed right pulmonary artery (iRPA), indexed left pulmonary artery (iLPA) and indexed descending aorta (iDA) were measured using ECHO and CTA followed by derivation of Nakata index (NI), McGoon’s ratio (MGR), ratio of predicted peak right ventricular (RV) and left ventricular (LV) pressures (pRV/pLV) and Z-scores. Comparison with CCA-derived measurements was made and correlational equations were subsequently deduced. Pulmonary vascular dimensions for 54 patients with mean age of 15.5 ± 9.3 years (range: 3–34 years) were analysed. Computed tomography angiography and CCA measurements for iPAnn, iRPA, NI, MGR, pRV/pLV, and Z-score were comparable with each other while ECHO parameters were significantly lower than CCA. However, iLPA diameter was significantly underestimated by ECHO and overestimated by CTA. Correlational analysis showed stronger correlation between CTA- and CCA-derived PVD as against ECHO measurements except for iDA, pRV/pLV, and Z-score.

Conclusions

For unrepaired TOF physiology patients weighing more than 10 kg, CTA-acquired PVD are reliable and comparable with CCA except for DA for which ECHO is non-inferior. Non-invasive modalities though are inferior to CCA for LPA sizing. Utilizing derived equations, precise estimation of PVD can be carried out using non-invasive tools.
Impact of distal aortic perfusion on ‘segmental steal’ depleting spinal cord blood flow—a quantitative experimental approach
Authors: Haunschild Josephina , von Aspern Konstantin , Herajärvi Johanna , Dietze Zara , Naumann Jörg , Ossmann Susann , Misfeld Martin , Borger Michael A , Etz Christian D
Published: April 2022

OBJECTIVES

Aortic steal is an underestimated risk factor for intraoperative spinal cord ischaemia. A negative effect on spinal cord perfusion in thoraco-abdominal aneurysm repair has been suspected if blood drains away from the cord initiated by a reversal of the arterial pressure gradient. The amount of blood and pressure loss via back-bleeding of segmental arteries and the impact of distal aortic perfusion (DaP) have not been analysed yet. The aim of our study was to quantify ‘segmental steal’ in vivo during simulated thoraco-abdominal aneurysm repair and to determine the impact of DaP on steal and spinal cord perfusion.

METHODS

Ten juvenile pigs were put on cardiopulmonary bypass with DaP and visceral arteries were ligated. ‘Segmental steal’ was quantified by draining against gravity with/without DaP. Blood volume of ‘segmental steal’ was quantified and microspheres were injected for Post mortem spinal cord perfusion analysis. ‘Segmental steal’ was quantified with/without DaP—and with stopped DaP.

RESULTS

Quantification revealed a significantly higher steal on cardiopulmonary bypass with DaP with a mean difference of 24(11) ml/min. In all spinal cord segments, blood flow was diminished during steal drainage on DaP, compared to ‘no steal’. The least perfused region was the low thoracic to upper lumbar segment.

CONCLUSIONS

‘Segmental steal’ is a relevant threat to spinal cord perfusion—even with the utilization of DaP—diminishing spinal cord perfusion. The blood volume lost by back-bleeding of segmental arteries is not to be underestimated and occlusion of segmental arteries should be considered in thoraco-abdominal aneurysm repair.
High cholesterol absorption is associated with increased cardiovascular risk in haemodialysis patients: insights from the AURORA study
Authors: Silbernagel Günther , Duarte Kévin , Sadiku Samir , Fauler Günter , März Winfried , Schmieder Roland E , Jardine Alan G , Massy Ziad A , Girerd Nicolas , Fellström Bengt , Rossignol Patrick , Scharnagl Hubert , Zannad Faiez
Published: April 2022

Aims

Statin treatment did not reduce the risk of cardiovascular events in haemodialysis patients in the 4D and AURORA trials. Post hoc analyses in the 4D study suggested that high cholesterol absorption was associated with increased cardiovascular risk and that atorvastatin would reduce cardiovascular risk in haemodialysis patients with low cholesterol absorption but not in those with high cholesterol absorption.

Methods and results

AURORA is a randomized, double-blind, placebo-controlled, multi-centre trial in haemodialysis patients. The participants were randomly assigned to receive either rosuvastatin, 10 mg daily, or a matching placebo. There was a follow-up for cardiovascular death with a median duration of 3.9 years. The cholestanol and lathosterol to cholesterol ratios were used to estimate cholesterol absorption and synthesis, respectively. Measurement of non-cholesterol sterols was available in 2332 participants of the 2733 patients included in the primary analysis of the AURORA study. A total of 598 participants died from cardiovascular diseases. The 3rd vs. the 1st tertile of the cholestanol-to-cholesterol ratio was significantly associated with increased risk of cardiovascular death [hazard ratio, HR (95% confidence interval, CI) = 1.36 (1.11–1.65)] in univariate (P = 0.002) and multivariate models (P = 0.034). In contrast, the 3rd vs. the 1st tertile of the lathosterol-to-cholesterol ratio was significantly associated with decreased risk of cardiovascular death [HR (95% CI) = 0.81 (0.67–0.99)] in univariate (P = 0.041) and multivariate (P = 0.019) models. There was no significant interaction between the cholestanol and lathosterol to cholesterol tertiles and treatment group in predicting cardiovascular death.

Conclusion

The present data from the AURORA study confirm that high cholesterol absorption is associated with increased cardiovascular risk in haemodialysis patients. Assessment of the individual cholesterol absorption rate to guide initiation of statin treatment is not supported by the findings in the AURORA study.
A 2-item version of the Japanese Consultation and Relational Empathy measure: a pilot study using secondary analysis of a cross-sectional survey in primary care
Authors: Takahashi Noriyuki , Matsuhisa Takaharu , Takahashi Kunihiko , Aomatsu Muneyoshi , Mercer Stewart W , Ban Nobutaro
Published: April 2022

Background

The Consultation and Relational Empathy (CARE) measure is a patient-reported measure of physician empathy which is widely used internationally. The Japanese version of the CARE measure has very high internal reliability, suggesting that a shorter version may have adequate validity and reliability.

Objective

To investigate a valid shorter version of the Japanese CARE measure.

Methods

We conducted a pilot study using secondary analysis of previous data obtained from 9 general practitioners and 252 patients and used to develop the Japanese CARE measure. All 1,023 possible combinations of the Japanese CARE items (n = 1–10) were candidates for the short measure. The internal consistency (Cronbach’s alpha) and the correlations between candidate short questionnaires and the original questionnaire were calculated. After selecting the most valid short questionnaire, inter-rater reliability was determined using generalizability theory, and construct validity (Spearman’s rho) was determined using patient satisfaction.

Results

Two items were selected for a pilot shorter version: item 6 “Showing care and compassion” and item 9 “Helping you to take control.” These showed high internal consistency and correlations with the 10-item measure (Cronbach’s alpha = 0.920, correlation = 0.979). Forty-five questionnaires per doctor allowed us to reliably differentiate between practitioners. The construct validity for the pilot short measure was high (Spearman’s rho 0.706, P < 0.001).

Conclusion

We generated a pilot 2-item version of the Japanese CARE measure. This pilot 2-item version provides a basis for future validation studies of short CARE measures in other languages.