bluuebunny/crossref_metadata_2025 huggingface dataset:
Slurry erosion behavior of hydro-turbine steel treated cryogenically at different soaking periods
Authors: Kumar Munish , Sidhu Hazoor Singh , Sidhu Buta Singh
Published: October 2021

The influence of deep cryogenic treatment on the erosive wear performance of Stainless Steel-316L (SS-316L) used in hydropower plants is studied. For this purpose, several SS-316L samples were held at deep cryogenic temperatures (−196 °C) for different soaking periods (12, 24, 36 h). The erosive wear tests were conducted on a self-fabricated slurry erosion test rig and the same was evaluated by weighing the cumulative mass loss (CML) of samples for every 30 min post erosion. From experimental analysis, it was found that the erosive wear was found to be minimum and the hardness reaches to maximum value after 24 h of the soaking period which could be attributed to the significant microstructural changes such as the transformation of γ-austenite phase into (δ-ferrite+α′-martensite) along with precipitation of numerous carbides after deep cryogenic treatments.
Synthesis and characterization of magnesium melting fluxes
Authors: Patel Sonam M , Patel Mehul M , Rao Vandana J
Published: October 2021

Magnesium and its alloys are extremely susceptible to oxidation and fire due to their reactivity with oxygen. Therefore, special care should be taken while melting them. In this research, different types of fluxes were used to protect the molten magnesium from oxidation. These fluxes cover the molten magnesium surface and refine it. In this research, nine magnesium melting and refining fluxes were studied. Dow fluxes compositions were taken as a base to prepare five fluxes and another four fluxes were developed by varying the content of chlorides, fluorides, and oxide. The main purpose of this research is to increase the recovery of magnesium metal by melting in normal atmospheric conditions and develop a low-cost conventional melting practice. Decomposition behavior, mass change, and melting of these nine fluxes were studied by TG/DTA technique. After fusing, the surface morphology of these fluxes was studied by visual observation and scanning electron microscope. Magnesium was melted using these nine fluxes and for each flux, the weight loss of magnesium was calculated. From a thermal analysis study, it was confirmed that all the fluxes were fused before magnesium melting. Based on the flux layer which was generated during the melting and the weight loss analysis, flux 9 (250) was the best flux compared to other fluxes. The highest purity was obtained by using flux 2 with the highest tensile strength value.
Empirical performance of polycrystalline silicon pixel circuit components for monolithic, large-area photon counting arrays
Authors: Liang Albert K , Koniczek Martin , El-Mohri Youcef , Zhao Qihua , Antonuk Larry E
Published: October 2021

Photon counting detectors (PCDs) offer several advantages for medical x-ray imaging compared to conventional imagers. However, current PCDs, whose circuits are fabricated using crystalline silicon semiconductor material, are not well-suited for large-area imaging applications such as breast CT and kilovoltage cone-beam CT (kV CBCT) in radiotherapy. To address this challenge, prototype PCDs based on polycrystalline silicon (a semiconductor better suited for manufacture of large-area devices) were created and, in this paper, an empirical determination of the maximum count rate of individual pixel circuit components (amplifier, comparator, clock generator and counter) corresponding to those prototypes is reported. For each circuit component, test input pulses (which were generated so as to approximate those in a complete pixel circuit) were used to obtain output response waveforms from which count rate was determined. The maximum count rate (in units of counts per second, cps) for the amplifier was determined to be 20.8 kcps while that of the comparator, clock generator and counter components were determined to be 1.2 Mcps, 98 kcps and 4.9 Mcps, respectively. The comparator and counter components provide count rates beyond that required for breast CT (∼108 kcps at a pixel pitch of 330 μm) while those components as well as the clock generator exceed the rate required for kV CBCT in radiotherapy (∼72 kcps at a pitch of 400 μm). It is anticipated that new polycrystalline silicon circuit designs for the amplifier and clock generator could provide count rates sufficient for both applications.
Root pressure–volume curve traits capture rootstock drought tolerance
Authors: Bartlett M K , Sinclair G , Fontanesi G , Knipfer T , Walker M A , McElrone A J
Published: October 2021

Background and Aims

Living root tissues significantly constrain plant water uptake under drought, but we lack functional traits to feasibly screen diverse plants for variation in the drought responses of these tissues. Water stress causes roots to lose volume and turgor, which are crucial to root structure, hydraulics and growth. Thus, we hypothesized that root pressure–volume (p–v) curve traits, which quantify the effects of water potential on bulk root turgor and volume, would capture differences in rootstock drought tolerance.

Methods

We used a greenhouse experiment to evaluate relationships between root p–v curve traits and gas exchange, whole-plant hydraulic conductance and biomass under drought for eight grapevine rootstocks that varied widely in drought performance in field trials (101-14, 110R, 420A, 5C, 140-Ru, 1103P, Ramsey and Riparia Gloire), grafted to the same scion variety (Vitis vinifera ‘Chardonnay’).

Key Results

The traits varied significantly across rootstocks, and droughted vines significantly reduced root turgor loss point (πtlp), osmotic potential at full hydration (πo) and capacitance (C), indicating that roots became less susceptible to turgor loss and volumetric shrinkage. Rootstocks that retained a greater root volume (i.e. a lower C) also maintained more gas exchange under drought. The rootstocks that previous field trials have classified as drought tolerant exhibited significantly lower πtlp, πo and C values in well-watered conditions, but significantly higher πo and πtlp values under water stress, than the varieties classified as drought sensitive.

Conclusions

These findings suggest that acclimation in root p–v curve traits improves gas exchange in persistently dry conditions, potentially through impacts on root hydraulics or root to shoot chemical signalling. However, retaining turgor and volume in previously unstressed roots, as these roots deplete wet soil to moderately negative water potentials, could be more important to drought performance in the deep, highly heterogenous rooting zones which grapevines develop under field conditions.
Vertical Space Lift: Transcutaneous Lower Blepharoplasty, Subperiosteal Midface Lift, and Lower Face Lift: A Novel Technique of Buccal Fat Suspension to Medial Infraorbital Rim
Authors: Nural Hadi
Published: October 2021

Background

Despite traditional facelift and transtemporal endoscopic facelift techniques are used in treatment of mid face ptosis, they do not have a big impact on the midface area. Lower blepharoplasty techniques are effective to provide rejuvenation on nasojugal area, midface ptosis and tear trough deformity. Additionally, it is also possible to correct the lower face area and jowls with lower blepharoplasty.

Objectives

To define effect of vertical space lift in tear-trough, midcheek groove, midface, and lower face.

Methods

A retrospective study was carried out on 23 patients who had surgeries between January 2018 and January 2021. The buccal fat is suspended and anchored to the medial infra orbital rim with a superomedial vector and the midface flap anchored to the lower and lateral orbital rim with a superomedial and superolateral vector. The average follow-up period was 12 months.

Results

A high degree of satisfaction has been achieved in the feedback of questionnaires. Results showed that there is a significant improvement in nasojugal deformity, malar ptosis, mid-cheek grove, and jowls.

Conclusions

While transcutaneous lower blepharoplasty provides an opportunity for rejuvenation of the lower eyelid and midface area, vertical space lift allows the surgeon to work on the midface, lower face, and jowls area except the neck. Choosing appropriate technique according to area that needs to be corrected increases success rate.

Level of Evidence: 4
Optimizing viral genome subsampling by genetic diversity and temporal distribution (TARDiS) for phylogenetics
Authors: Marini Simone , Mavian Carla , Riva Alberto , Prosperi Mattia , Salemi Marco , Rife Magalis Brittany
Published: October 2021

TARDiS is a novel phylogenetic tool for optimal genetic subsampling. It optimizes both genetic diversity and temporal distribution through a genetic algorithm.

Availability and implementation

TARDiS, along with example datasets and a user manual, is available at https://github.com/smarini/tardis-phylogenetics
Hand and foot musculature of Sooglossoidea: synapomorphies, convergences and hind limb digging behaviour in anurans
Authors: Blotto Boris L , Biju S D , Pereyra Martín O , Araujo-Vieira Katyuscia , Faivovich Julián , Grant Taran
Published: October 2021

We describe the hand and foot musculature of the fossorial Indian purple frog, Nasikabatrachus sahyadrensis, and compare it to other members of Sooglossoidea: the Seychellean sooglossid genera Sechellophryne and Sooglossus. Due to the key phylogenetic position of Sooglossoidea, we compare its members with the diversity of Anura and define 52 characters from the hand and foot musculature, among which 26 are novel hypotheses of homology. We found several synapomorphies for Sooglossus, Sooglossidae, Nasikabatrachidae and Sooglossoidea. Additionally, we (1) propose synapomorphies for diverse anuran clades at different taxonomic levels, (2) re-evaluate the identity of some conflicting plantar and palmar muscles in the context of Batrachia and (3) discuss putative adaptations to hind limb digging behaviour resulting from morphological convergences. The lack of a clear pattern of convergences among hind limb digging species suggests the occurrence of a phenomenon of many-to-one mapping from form to function.
Molecular approaches reveal speciation between red- and blue-flowered plants in the MediterraneanLysimachia arvensisandL. monelli(Primulaceae)
Authors: Jiménez-López Francisco Javier , Viruel Juan , Arista Montserrat , Ortiz Pedro L , Talavera María
Published: October 2021

Flower colour has played a decisive role as an evolutionary force in many groups of plants by driving speciation. A well-known example of colour polymorphism is found across the Mediterranean populations of Lysimachia arvensis and L. monelli, in which blue- and red-flowered plants can be found. Previous studies recognized two lineages within L. arvensis differing in flower colour, but this variation has not yet been considered in a phylogenetic context. We have reconstructed the ancestral states of flower colour across Mediterranean Lysimachia spp. aiming at understanding its phylogenetic signal using the nuclear internal transcribed spacer (ITS) sequences and three plastid markers. All blue- and red-flowered specimens were nested in different clades in the ITS tree, thus supporting that L. arvensis and L. monelli are polyphyletic, whereas low phylogenetic resolution was found in plastid markers. Monophyly was reconstructed for blue-flowered L. arvensis and L. monelli samples, and similarly for red-flowered individuals of each species: (1) blue-flowered L. arvensis was reconstructed as sister to the strictly blue-flowered L. talaverae in a monophyletic clade sister to remaining Lysimachia; (2) red-flowered L. arvensis was resolved as sister to red-flowered L. monelli in a monophyletic clade; and (3) clade 2 was sister to blue-flowered L. monelli and the strictly blue-flowered L. foemina. Our results suggest that colour lineages in L. arvensis and L. monelli constitute different species, but flower colour did not promote the separation of these lineages. We propose a new name for blue-flowered L. arvensis (L. loeflingii) and a new combination for red-flowered L. monelli (L. collina), maintaining L. arvensis for red-flowered plants and L. monelli for blue-flowered plants.
Degeneration of basal and limbic networks is a core feature of behavioural variant frontotemporal dementia
Authors: Vuksanović Vesna , Staff Roger T , Morson Suzannah , Ahearn Trevor , Bracoud Luc , Murray Alison D , Bentham Peter , Kipps Christopher M , Harrington Charles R , Wischik Claude M
Published: October 2021

The behavioural variant of frontotemporal dementia is a clinical syndrome characterized by changes in behaviour, cognition and functional ability. Although atrophy in frontal and temporal regions would appear to be a defining feature, neuroimaging studies have identified volumetric differences distributed across large parts of the cortex, giving rise to a classification into distinct neuroanatomical subtypes. Here, we extended these neuroimaging studies to examine how distributed patterns of cortical atrophy map onto brain network hubs. We used baseline structural magnetic resonance imaging data collected from 213 behavioural variant of frontotemporal dementia patients meeting consensus diagnostic criteria and having definite evidence of frontal and/or temporal lobe atrophy from a global clinical trial conducted in 70 sites in Canada, United States of America, Australia, Asia and Europe. These were compared with data from 244 healthy elderly subjects from a well-characterized cohort study. We have used statistical methods of hierarchical agglomerative clustering of 68 regional cortical and subcortical volumes (34 in each hemisphere) to determine the reproducibility of previously described neuroanatomical subtypes in a global study. We have also attempted to link the structural findings to clinical features defined systematically using well-validated clinical scales (Addenbrooke’s Cognitive Examination Revised, the Mini-Mental Status Examination, the Frontotemporal Dementia Rating Scale and the Functional Assessment Questionnaire) and subscales derived from them. Whilst we can confirm that the subtypes are robust, they have limited value in explaining the clinical heterogeneity of the syndrome. We have found that a common pattern of degeneration affecting a small number of subcortical, limbic and frontal nodes within highly connected networks (most previously identified as rich club members or functional binding nodes) is shared by all the anatomical subtypes. Degeneration in these core regions is correlated with cognitive and functional impairment, but less so with behavioural impairment. These findings suggest that degeneration in highly connected basal, limbic and frontal networks is a core feature of the behavioural variant of frontotemporal dementia phenotype irrespective of neuroanatomical and clinical heterogeneity, and may underly the impairment of integration in cognition, function and behaviour responsible for the loss of insight that characterizes the syndrome.
Involvement of PD-L1-mediated tumor-intrinsic signaling and immune suppression in tumorigenic effect of α-tocopherol
Authors: Sun Zhenou , Yin Shutao , Zhao Chong , Fan Li hong , Hu Hongbo
Published: October 2021

Numerous studies have shown that the different isoforms vitamin E have distinct activity on carcinogenesis. α-Tocopherol (α-T), the most abundant vitamin E in certain types of food and animal tissues, has demonstrated a cancer-promoting effect in a number of human clinical trials and pre-clinical studies, whereas the γ- and δ- forms of Tocopherols and Tocotrienols have exhibited significant anticancer effect in various pre-clinical studies. However, the mechanisms underlying the tumorigenic effect of α-T have not yet been fully understood. In the present study, we found that α-T was able to activate programmed death-ligand 1 (PD-L1)-mediated tumor-intrinsic signaling and immune suppression via JAK/STAT3-dependent transcriptional and ERK-dependent post-transcriptional mechanism. In line with PD-L1 induction, α-T treatment increased cancer cell viability in vitro and promoted tumor growth in LLC xenograft mouse model. The findings of the present study for the first time provided evidence that PD-L1-mediated tumor-intrinsic and immune escape mechanism contributed to the tumorigenic effect of α-T.
Prediction errors for aversive events shape long-term memory formation through a distinct neural mechanism
Authors: Kalbe Felix , Schwabe Lars
Published: October 2021

Prediction errors (PEs) have been known for decades to guide associative learning, but their role in episodic memory formation has been discovered only recently. To identify the neural mechanisms underlying the impact of aversive PEs on long-term memory formation, we used functional magnetic resonance imaging, while participants saw a series of unique stimuli and estimated the probability that an aversive shock would follow. Our behavioral data showed that negative PEs (i.e., omission of an expected outcome) were associated with superior recognition of the predictive stimuli, whereas positive PEs (i.e., presentation of an unexpected outcome) impaired subsequent memory. While medial temporal lobe (MTL) activity during stimulus encoding was overall associated with enhanced memory, memory-enhancing effects of negative PEs were linked to even decreased MTL activation. Additional large-scale network analyses showed PE-related increases in crosstalk between the “salience network” and a frontoparietal network commonly implicated in memory formation for expectancy-congruent events. These effects could not be explained by mere changes in physiological arousal or the prediction itself. Our results suggest that the superior memory for events associated with negative aversive PEs is driven by a potentially distinct neural mechanism that might serve to set these memories apart from those with expected outcomes.
Genetic polymorphisms of matrix metalloproteinase-9, tissue inhibitor of matrix metalloproteinase-1 and development of postoperative atrial fibrillation in elderly patients
Authors: Rubanenko O , Shchukin Y , Rubanenko A
Published: October 2021

Purpose

The aim of the study was to assess the association of genetic polymorphisms of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) with atrial fibrillation development in elderly patients with coronary artery disease (CAD), undergoing coronary artery bypass graft (CABG) surgery.

Methods

Studied were 80 patients who underwent CABG. In all the patients routine laboratory and instrumental tests were performed. Patients also underwent genetic polymorphisms of MMP-9 A8202G and TIMP-1 C536T estimation with polymerase chain reaction. According to occurrence of postoperative atrial fibrillation (POAF) all the patients were divided into two groups: group 1 – patients without POAF (56 patients, 81.8% males, mean age 65.9±4.0 years), group 2 – patients with first detected episode of AF after CABG (24 patients, 87.5% males, mean age 67.7±5.4).

Results

In group 1 the II grade of stable angina was significantly more often than in patients of the 2 group (32.1% vs 12.5%, p=0.009). Patients of the 2 group had more long history of CAD (87.2±72.4 months vs 46.9±31.4 months, p=0.03), more often – NYHA III (45.8% vs 12.5%, p=0.01) and larger LA diameter (43.8±3.5 mm vs 37.5±3.9 mm, p<0.001) than the patients of the 1 group.

Genotype AA MMP-9 A8202G was found in 39.3% patients of the 1 group and in 16.7% patients of the 2 group (p=0.04), genotype AG – in 44.6% and 54.1% respectively (p=0.4), genotype GG – in 16.1% and 29.2% respectively (p=0.06). Genotype CC TIMP-1 C536T was found in 98.2% and 100% patients in 1 and 2 group respectively (p=0.72), genotype CT – in 1.8% patients of the 1 group.

According to results of multivariate regression analysis odds ratio of POAF development in patients with stable angina grade III was 1.8 (95% CI 0.5–7.5, p=0.4), NYHA III – 0.85 (95% CI 0.2–3.5, p=0.55), history of CAD more than 20 months – 1.8 (95% CI 1.2–8.1, p=0.03), LA diameter more than 39 mm - 4.2 (95% CI 1.6–9.5, p<0.0001), allele G MMP-9 A8202G – 2.6 (95% CI 1.2–7.5, p=0.03).

Conclusion

In elderly patients undergoing coronary artery bypass graft surgery left atrial diameter more than 39 mm, history of coronary artery disease more than 20 months and the presence of G allele of MMP-9 A820G are significantly associated with postoperative atrial fibrillation development.

Funding Acknowledgement

Type of funding sources: None.
Trends in all-cause mortality of atrial fibrillation in hospitalized patients in Sweden between 1995–2008
Authors: Sztaniszlav A , Magnuson A , Bryngelsson I L , Edvardsson N , Sztaniszlav K , Poci D
Published: October 2021

Introduction

Atrial fibrillation (AF) is the most common arrythmia. Both its incidence and prevalence increased significantly during the last decades. AF is associated with high morbidity and mortality.

Purpose

The aim of this study was to describe and evaluate the trends of all-cause mortality in patients first-ever hospitalized for AF, and the effect of age, sex, stroke risk, and education level on mortality over time.

Methods

In this observational retrospective cohort study, we enrolled the patients who were hospitalized primarily and for the first time because of AF between 1st January 1995 and 31st December 2004. In regard to the date of the index admission patients were divided into four cohorts and they were followed up to five years. Patients were compared with an age and sex matched control population. All data were collected from Swedish national registries. Kaplan-Meier plots and Cox regression with trend analysis were used for statistical evaluation.

Results

In total 64 489 AF patients (mean age 72±10.1 year) were included in this study. The control group comprised 116 893 individuals. 81.9% of the women and 58.5% of the men were older than 65 years of age. 65.5% of women and 58.5% of the men had a stroke risk of CHADS2-VA2Sc ≥2.

We found a significantly decreasing trend of the relative risk for all-cause mortality in AF patients over time: trend HR: 0.94 (95% CI: 0.92–0.96, p<0.001) in women and trend HR: 0.91 (95% CI: 0.89–0.93 p<0.001) in men. The mortality trends between AF patients and their controls did not show significant difference: trend HR: 0.99 (95% CI: 0.96–1.02, p=0.59) in women and trend HR: 1.00 (95% CI: 0.97–1.03, p=0.98) in men. The subpopulation analysis showed that the mortality risk remained unchanged over the time in women aged 18–69 years (trend HR: 0.91 – 95% CI: 0.82–1.02, p=0.099), in patients with low stroke risk (trend HR: 1.08 – 95% CI: 0.92–1.26, p=0.36 in women and trend HR: 0.95 – 95% CI: 0.87–1.05, p=0.30 in men) and in patients with post-secondary level of education (trend HR: 0.93 – 95% CI 0.83–1.04, p=0.23 in women and trend HR: 1.04 – 95% CI: 0.96–1.12, p=0.32 in men).

Conclusion

The all-cause mortality risk of the AF hospitalized patients was higher compared to control population and had a decreasing tendency during the time of the study. However, this trend is not significantly different from the control population. We found unchanged mortality trend in younger patients, in those with lower stroke risk, and in patients with higher education level.

Funding Acknowledgement

Type of funding sources: None.
Recovery of conduction following high power short duration approach in radiofrequency catheter ablation for atrial fibrillation: a single-center experience
Authors: Mohanty S , Trivedi C , Della Rocca D G , Gianni C , MacDonald B , Mayedo A , Burkhardt J D , Bassiouny M , Gallinghouse G J , Horton R , Al-Ahmad A , Di Biase L , Natale A
Published: October 2021

Introduction

High-power short-duration (HPSD) ablation is currently being adopted by many as the preferred procedural technique in atrial fibrillation (AF). However, the optimal duration of energy delivery to successfully create a durable lesion is not clear yet.

Purpose

We evaluated the association of electrical reconnection with lesion-duration in HPSD ablation.

Methods

Consecutive AF patients undergoing repeat procedure after a prior HPSD ablation with or without isolation of left atrial appendage (LAA) and coronary sinus (CS) were included in this analysis. HPSD ablation was defined as ablation with maximum temperature setting at 420C and power delivery at 45 W for 10–15 sec (5 seconds in the CS area and posterior wall near the esophagus). In some patients a mechanical esophageal deviation tool was used to deflect the esophagus away from the ablation site.

Results

A total of 2249 AF patients (with LAA and CS isolation: 1451; without LAA and CS isolation: 798) receiving redo ablation after a prior HPSD procedure were included in the analysis. At the prior procedure with the HPSD approach, mean duration of ablation was significantly shorter in the area facing the esophagus compared to elsewhere (5.2±1.5 vs 12.5±1.7 seconds, p<0.001). Application duration was reduced to <10 sec to avoid overheating and steam pops in 1221 (84%) patients receiving LAA and CS isolation.

At the redo, recovery of conduction was noted in the CS (592, 40.8%), LAA (493, 34%), and PV and left atrial posterior wall (LAPW) (310, 13.8%). Of the 310 patients with LAPW reconnection, 91% (n=282) had the conduction recovered in the area facing the esophagus.

In 73 patients, esophageal displacement device was used during the prior HPSD ablation. Average duration of ablation lesions in LAPW among those 73 patients was 9.2±2 seconds. PV-LAPW reconnection was observed in 3/73 (4.1%) patients.

Conclusion

HPSD ablation with lesion duration of <10 sec was associated with conduction recovery in the LAA, CS and the LAPW area facing esophagus.

Funding Acknowledgement

Type of funding sources: None.
Stent-Save a Life international survey on the practice of primary coronary angioplasty during the COVID-19 pandemic
Authors: Pereira H , On Behalf Of Stent Save A Life Initative S S L ,   Stent Save a Life
Published: October 2021

Aims

To evaluate the impact of the COVID-19 pandemic on patient admissions with acute coronary syndromes (ACS) and primary coronary angioplasty (PPCI) in countries participating in the Stent-Save a Life (SSL) global initiative.

Methods and results

We conducted a multicenter, observational survey to collect data on patient admissions for ACS, STEMI and PPCI in the SSL participating countries throughout a period during the COVID-19 outbreak (March and April 2020) compared with the equivalent period in 2019. From the 32 member countries of the SSL global initiative, 17 accepted to participate in the survey (3 from Africa, 5 from Asia, 6 from Europe and 3 from Latin America (LATAM)). We observed a global reduction of 27,5% and 20,0% in admissions with ACS and STEMI respectively. The decrease in PPCI was 26,7% (Figure 1). This trend was observed in all countries except two. In these two countries, the pandemic peaked later than in the other countries.

Conclusions

This survey shows that the COVID-19 outbreak was associated with a significant reduction of hospital admissions for ACS and STEMI as well as a reduction of PPCI, which can be explained by both patient and system related factors.

Funding Acknowledgement

Type of funding sources: None. Figure 1
The efficacy and safety of dual-pathway inhibition therapy among patients with peripheral arterial disease – a meta-analysis
Authors: Mapili J , Davin A S , Villanueva L M
Published: October 2021

Background and objectives

Peripheral artery disease (PAD) affects more than 200 million people worldwide and it is associated with an increased risk for cardiovascular morbidity and mortality. Current recommendations regarding the management of PAD have been controversial. Our meta-analysis investigated the efficacy of direct Xa inhibitor plus antiplatelet, also known as dual-pathway inhibition (DPI), on the individual components of major adverse cardiovascular events (stroke, myocardial infarction, and cardiovascular death) and major adverse limb events (amputation, restenosis, revascularization, and acute limb ischemia), the composite of MACE and MALE and its safety, in terms of bleeding, compared to antiplatelet therapy among patients with PAD.

Methodology

We performed a random-effects meta-analysis among patients with PAD comparing DPI to antiplatelet therapy. PubMed, EMBASE, CENTRAL, and ClinicalTrials.gov were searched from their dates of inception to August 2020 for Randomized Controlled Trials. Three studies met the inclusion criteria for final analysis. The selected studies were assessed for risk of bias using the Cochrane RoB2 tool and the overall quality of evidence was assessed using the GRADE approach.

Results

Among patients with PAD, DPI significantly reduces the risk of adverse limb events excluding amputation (RR 0.69, 95% CI 0.57–0.83) and composite MACE and MALE (RR 0.80, 95% CI 0.69–0.93) but significantly increases risk of major bleeding (RR 1.43, 95% CI 1.06–1.93) compared to antiplatelet therapy alone. Overall, DPI did not reduce myocardial infarction, stroke, cardiovascular death, or amputation, or increase the risk of fatal bleeding.

Conclusions

Among patients with PAD, DPI is more effective than antiplatelet therapy alone in preventing adverse limb events excluding amputation with an increased risk of major bleeding. We recommend the use of DPI among patients with PAD who are at a low risk of bleeding.

Funding Acknowledgement

Type of funding sources: None.
Association of rs3025058 polymorphism with the development of acute cerebrovascular event
Authors: Chernova A , Nikulina S , Nikulin D
Published: October 2021

Purpose

To study SNP rs3025058 association (5a/6a) with development of Acute Cerebrovascular Event in the patients with cardiovascular pathology and risk factors of its development who are representatives of the east Siberian population.

Material and methods

260 patients with Acute Cerebrovascular Event participated in a research (age [57.0; 51.0–62.0]) and 272 patients of control group (age [55.0; 51.0–62.0].). Among the patients who transferred Acute Cerebrovascular Event, 157 men and 103 women. The control group included 170 men and 102 women. Inspection of the main group included: collecting complaints, anamnesis, clinical examination, computer tomography of a brain, electrocardiography, echo, ultrasonic of arteries, daily monitoring of arterial blood pressure and cardiac rhythm, analysis of a coagulant system of blood. Patients of the main group had the following cardiovascular pathology and risk factors: arterial hypertension, supraventricular tachycardia, dislipidemiya, atherosclerosis brachiocephalic of arteries, disturbances of a system of a hemostasis. The control group is examined within the international HAPIEE project. The molecular and genetic research was conducted by PCR method in real time. Statistical processing of material was carried out with use of set of the Statistica for Windows 7.0, Excel and SPSS 22 application programs.

Results

In all analyzed groups and subgroups of patients statistically significant connection between a genotype of 5a/5a and an allele of 5a and in subgroup of women with Acute Cerebrovascular Event, subgroups of patients with AG and hypercoagulation of significant associations of polymorphism rs3025058 (5a/6a) with Acute Cerebrovascular Eventis not revealed.

Conclusion

A genotype 5a/5a and an allele 5a SNP rs3025058 (5a/6a) increase risk of development of an Acute Cerebrovascular Event in persons of the east Siberian population, including with such risk factors as atherosclerosis the brachiocephalic of arteries and a dislipidemiya.

Funding Acknowledgement

Type of funding sources: None.
Elucidating the role of Cavin1 in drug-induced long QT syndrome (diLQTS)
Authors: Al Sayed Z R , Pereira C , Jouve C , Hulot J.-S
Published: October 2021

Introduction

Several drugs can induce QT prolongation by altering cardiac ion currents, notably IKr. The cardiotoxic response to a drug is however extremely variable between individuals, ranging from no impact to life-threatening ventricular arrhythmias. The molecular mechanisms underlying this variability remain unclear. Previously, we reported higher expression levels of Cavin1, an essential protein for caveolae formation, in cardiomyocytes (CM) derived from patients with high susceptibility to develop sotalol-induced long QT.

Purpose

We aimed to explore whether Cavin1 could sway the cardiac repolarization response to drugs.

Method

We used induced pluripotent stem cells-derived CM (iPS-CM) from two subjects with the highest sensitivity (HS) to sotalol (ie, those with the highest increase in QTc) and two individuals with the lowest sensitivity to sotalol (LS) to perform molecular and electrophysiological investigations.

Results

At baseline, no differences in terms of repolarization durations, IKr amplitude, and ion channel expression were noted between the HS- and the LS-iPS-CM. However, the HS-iPS-CM displayed significant prolongation in action potential and field potential (FPD) durations after the application of 30 and 50μM of sotalol. They also displayed higher sensitivity to other drugs targeting hERG (E4031, vandetanib, and clarithromycin). Cavin1 mRNA and protein levels were increased by 2 fold in the HS-iPS-CM as compared to the LS-iPS-CM. Overexpressing Cavin1 in the LS-iPS-CM using adenovirus induced a higher sensitivity to sotalol as only 10μM was sufficient to induce 12% longer FPD. Consistently, the infection with Cavin1 increased the sensitivity of LS-CM to the other hERG blockers. In contrast, siRNA against Cavin1 reduced its expression by 60% in HS iPS-CM and switched their phenotype to a lower sensitivity to sotalol and the other hERG blockers. Interestingly, in line with the shortening of the FPD in LS-iPS-CM, overexpressing Cavin1 increased hERG expression in isolated membrane fraction from HEK cells stably expressing KCNH2. This suggests a role of Cavin1 in modulating hERG trafficking/recycling to the membrane and thereby the number of channels that can be blocked by drugs.

Conclusion

Altogether, this work identified Cavin1 as a novel modulator of cardiomyocyte response to hERG blockers and a potential risk factor for diLQT. Further understanding of its contribution may pave the way for personalized drug prescription to avoid undesirable cardiotoxicity.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Leducq
Implantable cardioverter-defibrillators and the older patient: the Dutch clinical practice
Authors: Yilmaz Dilek , Egorova Anastasia D , Schalij Martin J , van Erven Lieselot
Published: October 2021

Background and objective

Balance between benefit and burden of implantable cardioverter-defibrillator (ICD) therapy is more debatable in older patients, compared to younger patients. Of around 6000 yearly implanted ICDs in the Netherlands, 1:4 is received by patients ≥75 years. We aimed to evaluate the current clinical practice in the Netherlands for ICD implants and generator replacements, with a special focus on the older ICD patients.

Research design and methods

Cardiologists from all Dutch ICD implanting centres (n = 28) were interviewed. Questions aimed to evaluate outpatient care, pre-operative patient assessment, end-of-life-care counselling, evaluation of social and cognitive wellbeing, clinical evaluation of all patients prior to ICD replacement, and the consideration of the option to downgrade or not replace a device.

Results

Implanting cardiologists from all 28 implanting centres were approached for an interview. Response rate was 86%. Management appeared diverse. An age ≥80 years was consistently reported as incentive for more extensive patient evaluation. Patients were invited for counselling prior to device replacements in only the minority (46%) of hospitals. Downgrade or non-replacement was performed in rare cases. End-of-life care discussions were not standard procedure in 67% of the hospitals. Evaluation of social and cognitive wellbeing of patients was based solely on the general clinical impression of the physician in 83%, or not at all assessed in 8% of the centres.

Discussion and implication

A structured framework for care and evaluation of cognitive and/or physical limitations is currently absent in most hospitals. At time of ICD (re-)evaluation, several factors may be considered before deciding on (continuation of) ICD therapy: patient preferences and comorbidity, the need for pacemaker therapy, primary vs. secondary prevention, procedural risks, and patient preferences.
Genic Selection Within Prokaryotic Pangenomes
Authors: Douglas Gavin M , Shapiro B Jesse
Published: October 2021

Understanding the evolutionary forces shaping prokaryotic pangenome structure is a major goal of microbial evolution research. Recent work has highlighted that a substantial proportion of accessory genes appear to confer niche-specific adaptations. This work has primarily focused on selection acting at the level of individual cells. Herein, we discuss a lower level of selection that also contributes to pangenome variation: genic selection. This refers to cases where genetic elements, rather than individual cells, are the entities under selection. The clearest examples of this form of selection are selfish mobile genetic elements, which are those that have either a neutral or a deleterious effect on host fitness. We review the major classes of these and other mobile elements and discuss the characteristic features of such elements that could be under genic selection. We also discuss how genetic elements that are beneficial to hosts can also be under genic selection, a scenario that may be more prevalent but not widely appreciated, because disentangling the effects of selection at different levels (i.e., organisms vs. genes) is challenging. Nonetheless, an appreciation for the potential action and implications of genic selection is important to better understand the evolution of prokaryotic pangenomes.
Controls on surface wave overtone interference
Authors: Hariharan Anant , Dalton Colleen A , Babikoff Jordyn , Ekström Göran
Published: October 2021

Measurements of fundamental-mode (FM) surface waves along the minor arc are impacted by overtone interference. This interference is primarily due to major-arc overtones for Rayleigh waves and minor-arc overtones for Love waves. In both cases, interference contaminates measurements of phase and amplitude and can introduce bias in seismic images. Here, we use synthetic seismograms computed via normal mode summation to probe how interference can vary as a function of the surface wave group velocities, source mechanism and depth, which control the relative excitation of the FM and overtones, and period. By comparing seismograms that include all overtones to those that include only the FM, we can quantify the interference, i.e., how the presence of the overtones perturbs the FM phase and amplitude. We compare the strength of this interference to calculations of excitation of the overtones and FM. We show that these calculations explain well the varying strength of interference for different source mechanisms and depths. Notably, these calculations illuminate source depths where Love wave overtone excitation is quite low and therefore interference is unusually weak, and depths where Rayleigh wave FM excitation is low and therefore interference is unusually strong. Our analysis also reinforces the dependence of the interference on the FM and overtone group velocities. For Love waves, this results in weak minor-arc overtone interference at long periods and, for continental paths, short periods. For Rayleigh waves, the differing overtone and FM group velocities and the relative excitation of the overtones and FM explain rapid variations in the strength of Rayleigh wave major-arc overtone interference as a function of epicentral distance. We then show that real data are affected by the relative excitation of the FM and overtones. We find that errors in Rayleigh wave phase velocities determined at the EarthScope USArray stations are larger when the ratios of overtone to FM excitation are larger. We also find a dependence of phase velocity error on excitation ratio for Love waves, and we identify the presence of major-arc overtone interference in Love wave measurements. Our results highlight opportunities for more nuanced quality control of surface wave measurements. The relative excitation ratio of the overtones and FM may be a better criterion for event selection than source depth, allowing deeper events that well excite FMs to be included and shallower events with large overtone excitation to be excluded. This would allow the collection of more accurate measurements that will increase the precision of seismic images.
Slow slip events precursory to the 2014 Iquique Earthquake, revisited with long-base tilt and GPS records
Authors: Boudin F , Bernard P , Meneses G , Vigny Ch , Olcay M , Tassara C , Boy J P , Aissaoui E , Métois M , Satriano C , Esnoult M-F , Nercessian A , Vallée M , Vilotte J-P , Brunet Ch
Published: October 2021

The M= 8.1, 1 April 2014 Iquique earthquake, which broke part of the northern Chile seismic gap, was preceded by a strong foreshock sequence starting early January 2014. The reported analysis of the continuous records of the nearby GPS stations from the Integrated Plate Observatory Chile, North Chile array lead to contradictory results concerning the existence and location of slow slip events (SSEs) on the interplate contact. Resolving this controversy is an important issue, as although many SSEs are reported in subduction zones, only a few were found to be precursory to large earthquakes. Here we show that the records of a long base tiltmeter installed near Iquique, when corrected for coseismic steps, long-term drift, tidal signals and oceanic and atmospheric loading, show significant residual signals. These can be modelled with a sequence of four SSEs located close to Iquique. Their signature was already reported on some GPS stations, but their source was then characterized with a very low resolution in time and space, leading to contradicting models. With the tilt records, we can rule out the previously proposed models with a single large SSE closer to the main shock. Combining tilt with GPS records greatly improves the resolution of GPS alone, and one could locate their sources 100–180 km south–southeast to the main shock epicentre, with moment magnitudes between 5.8 and 6.2, at the edge of the main aftershock asperities. These moderate SSEs thus did not directly trigger the main shock, but contributed to trigger the main foreshock and the main aftershock. Only the sensitivity and resolution of the tiltmeter, added to the GPS records, allowed us to describe with unprecedented accuracy this precursory process as a cascade of cross-triggered, short-term aseismic slip events and earthquakes on the interplate contact. This three months of precursory activation appears to be the final acceleration burst of a weaker, longer term SSE which started mid-2013, already reported, with a moment release history which we could quantify. From the methodological point of view, our study takes advantage of an interesting complementarity of tilt and GPS measurements, due to their different dependence in distance to the source of strain, which turns out to be very efficient for resolving location and moment of strain sources, even when both instruments are close to each other. It finally demonstrates the efficient removal of sequences of small or even undetected coseismic steps from high resolution tilt record signal in order to retrieve the purely aseismic signal, a presently impossible task for high time resolution GPS records due to low signal to noise.
C/D box snoRNA SNORD113-6/AF357425 plays a dual role in integrin signalling and arterial fibroblast function via pre-mRNA processing and 2′O-ribose methylation
Authors: van Ingen Eva , van den Homberg Daphne A L , van der Bent M Leontien , Mei Hailiang , Papac-Milicevic Nikolina , Kremer Veerle , Boon Reinier A , Quax Paul H A , Wojta Johann , Nossent A Yaël
Published: October 2021

We have previously shown that C/D box small nucleolar RNAs (snoRNAs) transcribed from the DLK1-DIO3 locus on human chromosome 14 (14q32) are associated with cardiovascular disease. DLK1-DIO3 snoRNAs are ‘orphan snoRNAs’ that have no known targets. We aimed to identify RNA targets and elucidate the mechanism-of-action of human SNORD113-6 (AF357425 in mice). As AF357425-knockout cells were non-viable, we induced overexpression or inhibition of AF357425 in primary murine fibroblasts and performed RNA-Seq. We identified several pre-mRNAs with conserved AF357425/SNORD113-6 D′-seed binding sites in the last exon/3′ untranslated region (3′UTR), which directed pre-mRNA processing and splice-variant-specific protein expression. We also pulled down the snoRNA-associated methyltransferase fibrillarin from AF357425-High versus AF357425-Low fibroblast lysates, followed by RNA isolation, ribosomal RNA depletion and RNA-Seq. Identifying mostly mRNAs, we subjected these to PANTHER pathway analysis and observed enrichment for genes in the integrin pathway. We confirmed 2′O-ribose methylation in six integrin pathway mRNAs (MAP2K1, ITGB3, ITGA7, PARVB, NTN4 and FLNB). Methylation and mRNA expressions were decreased while mRNA degradation was increased under AF357425/SNORD113-6 inhibition in both murine and human primary fibroblasts, but effects on protein expression were more ambiguous. Integrin signalling is crucial for cell–cell and cell–matrix interactions, and correspondingly, we observed altered human primary arterial fibroblast function upon SNORD113-6 inhibition.
Quantifying bycatch risk factors for the Chinese distant water fishery
Authors: Xia Meng , Carruthers Tom , Kindong Richard , Dai Libin , Geng Zhe , Dai Xiaojie , Wu Feng
Published: October 2021

Mitigating bycatch of non-target fish species is a common objective in fisheries management that may be supported by the gathering of data from fishery observer programs and quantitative analysis of bycatch risk factors. We build three GLM models based on Chinese tuna longline fishery observer data in terms of analysis of total bycatch rate (TB rate), total bycatch ratio (TB ratio), and species-specific bycatch rate, respectively. The positive log-linear models assumed a Gaussian observation error model and a linear combination of categorical independent variables, including area, year, month, depth, and bycatch species. Results show that distributions of TB rate and TB ratio followed different trends and a latitudinal decrease was observed from both the northern and southern hemisphere of the equator. Comprehensively, the Pacific is a better place to fish compared to the Indian and Atlantic Oceans in terms of relatively lower TB rate and TB ratio. Fishing in open oceans can somehow avoid a high TB ratio than fishing in coastal waters. As a result, we recommend area 2SW, 2SE, 2 NW, 14SW, 14SE, and 14 NW as appropriate fishing ground for Albacore (Thunnus alalunga) while area 11N,  11S, 18SW, and 18SE to be appropriate fishing ground for fishing bigeye tuna (Thunnus obesus). Setting fishing gears deeper than 500 m would also help to get a low TB rate and TB ratio.