ClusTrast: a short read de novo transcript isoform assembler guided by clustered contigs

Motivation: Transcriptome assembly from RNA sequencing data in species without a reliable reference genome has to be performed de novo, but studies have shown that de novo methods often have inadequate reconstruction ability of transcript isoforms. This impedes the study of alternative splicing, in particular for lowly expressed isoforms. Result: We present the de novo transcript isoform assembler ClusTrast, which clusters a set of guiding contigs by similarity, aligns short reads to the guiding contigs, and assembles each clustered set of short reads individually. We tested ClusTrast on datasets from six eukaryotic species, and showed that ClusTrast reconstructed more expressed known isoforms than any of the other tested de novo assemblers, at a moderate reduction in precision. An appreciable fraction were reconstructed to at least 95% of their length. We suggest that ClusTrast will be useful for studying alternative splicing in the absence of a reference genome. Availability and implementation: The code and usage instructions are available at https://github.com/karljohanw/clustrast.

SGLT-2 inhibitors and cardiorenal outcomes in patients with or without type 2 diabetes: a meta-analysis of 11 CVOTs

Background It has been suggested that sodium–glucose cotransporter 2 (SGLT-2) inhibitors reduce the cardiorenal risk in patients with type 2 diabetes (T2D). The purpose of this study is to provide an update of all large cardiovascular outcome trials (CVOTs) with SGLT-2 inhibitors to assess their cardiorenal efficacy in patients with and without T2D. Methods An electronic search up to 30 September 2021 was conducted in PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov. to determine eligible trials. We included CVOTs comparing any SGLT-2 inhibitor with placebo, reporting desired cardiovascular or renal outcomes and with a follow-up duration of at least 6 months. Results Eleven CVOTs, with data from five SGLT-2 inhibitors (empagliflozin, canagliflozin, dapagliflozin, ertugliflozin and sotagliflozin) and 77,541 participants, were included. In the overall analysis, the risk of the composite CV mortality or hospitalization for heart failure (HF) was reduced by 23% (HR = 0.77, 95% CI 0.73–0.82, P < 0.001) compared with placebo, with not significant heterogeneity (I2 = 26%, P = 0.20), and irrespective of the presence of T2D (P for interaction = 0.81) and age (> 65 vs ≤ 65 years, P for interaction = 0.78). The risk of CV mortality, total mortality and hospitalization for HF was significantly reduced by 16%, 13%, and 32%, respectively; similarly, the risk of the composite renal outcome was reduced by 35% (HR = 0.65, 95% CI 0.56–0.75), with moderate heterogeneity (I2 = 32%). In the analysis of 6 CVOTs reporting the data, the risk of major cardiovascular events (MACE) was reduced by 12%, with low heterogeneity (I2 = 21.2%, P = 0.19) and irrespective of the presence of established CV disease at baseline (P for interaction = 0.46). Conclusions Therapy with SGLT-2 inhibitors in patients with cardiometabolic and renal diseases results in a sustained to moderate reduction of the composite CV death or hospitalization for HF, robust reduction of HF and renal outcomes, moderate reduction of CV mortality, total mortality and MACE.

A Prospective, Randomised, Controlled, Split-Face Clinical Trial to Assess the Safety and the Efficacy of Cold Atmospheric Plasma in the Treatment of Acne Vulgaris

The increase in antibiotic resistance requires effective non-antibiotic therapies for acne. Cold atmospheric plasma (CAP) inactivates bacteria and improves wound healing, but its effect on acne has not been investigated. The objective of this controlled split-face study was to assess safety and efficacy of CAP in moderate acne. One side of the face received 8–10 treatments with cold helium plasma within 4–6 weeks; follow-up was two and four weeks thereafter. Acne lesions were counted, followed by global acne severity ratings. Of the 34 patients included, 29 completed the study. No serious adverse events occurred. The two facial sides did not significantly differ in the number of inflammatory and non-inflammatory lesions. An interaction effect of number and type of treatment was found for inflammatory lesions. Lesion reduction after 10 treatments was significantly higher on the treated than on the untreated side. Percentage of patients reporting improved aesthetics was higher for the treated than for the untreated side after treatment completion (79% vs. 45%) and at the two- (72% vs. 45%) and four-week follow-up (79% vs. 52%). In conclusion, CAP was safe with excellent tolerability, showed moderate reduction in acne lesions and led to higher patient-based ratings of aesthetics than non-treatment.

The influence of wood processing waste on the technical and energy characteristics of the Maikuben coal-based mixed fuels

The manuscript presents the results of experimental studies of the energy and technical characteristics of mixed fuels based on lignite from the Maikuben basin of the Republic of Kazakhstan and wood processing waste, pine sawdust from the Tomsk LPC. The addition of wood biomass to coal is found to result in a significant reduction in the ash content of the mixed fuel (by 73.1 %) with a wood fraction equal to 50 % and a moderate reduction in calorific value (by 8.2 %) with the same concentration of biomass in the mixed fuel.

Low voltage in limb leads in arrhythmogenic cardiomyopathy

Low voltage in limb leads characterizes left ventricular involvement in arrhythmogenic cardiomyopathy. A large collective of patients with arrhythmogenic cardiomyopathy including 438 patients (268 males, mean age 46.8±11.6 years) were analyzed. Method Low voltage in limb leads were analyzed in typical patients with arrhythmogenic cardiomyopathy. Several other ECG features such a slow voltage in precordial leads, epsilon waves, right precordial T wave inversions, QRS fragmentation, typical appearance in lead aVR, amplitude of T wave inversion in special right ventricular leads, and developing complete right bundle branch block. Results Low voltage in limb leads was found in 60 patients (15%). Two patients represented with low voltage in limb leads and T wave inversions in inferolateral leads charactizing arrhythmogenic left ventricular leads with moderate reduction of left ventricular function with a large aneurysm of the apex. The other patients presented with sustained RBBB-VT. In 38 patients low voltage in limb leads and typical ECG findings of arrhythmogenic cardiomyopathy were found. These patients had arrhythmogenic biventricular cardiomyopathy of moderate reduction of left ventricular function and typical arrhythmias. Low voltage in limb and precordial leads was found in 14 patients with two cardiac deaths due to therapy-resistant heart failure. In 6 cases low voltage in limb and precordial leads and developing complete right bundle branch block were found. Four patients were tranplanted, two cases died due to heart failure. These 20 patients characterize advances, end-stage disease arrhythmogenic cardiomyopathy. Conclusion Standard ECG can differentiate between arrhythogenic left ventricular, arrhythmogenic biventricular, and arrhythmogenic advanced end-stage cardiomyopathy FUNDunding Acknowledgement Type of funding sources: None.

Atrial Fibrillation in Heart Failure Is Associated with High Levels of Circulating microRNA-199a-5p and 22–5p and a Defective Regulation of Intracellular Calcium and Cell-to-Cell Communication

MicroRNAs (miRNAs) participate in atrial remodeling and atrial fibrillation (AF) promotion. We determined the circulating miRNA profile in patients with AF and heart failure with reduced ejection fraction (HFrEF), and its potential role in promoting the arrhythmia. In plasma of 98 patients with HFrEF (49 with AF and 49 in sinus rhythm, SR), differential miRNA expression was determined by high-throughput microarray analysis followed by replication of selected candidates. Validated miRNAs were determined in human atrial samples, and potential arrhythmogenic mechanisms studied in HL-1 cells. Circulating miR-199a-5p and miR-22-5p were significantly increased in HFrEF patients with AF versus those with HFrEF in SR. Both miRNAs, but particularly miR-199a-5p, were increased in atrial samples of patients with AF. Overexpression of both miRNAs in HL-1 cells resulted in decreased protein levels of L-type Ca2+ channel, NCX and connexin-40, leading to lower basal intracellular Ca2+ levels, fewer inward currents, a moderate reduction in Ca2+ buffering post-caffeine exposure, and a deficient cell-to-cell communication. In conclusion, circulating miR-199a-5p and miR-22-5p are higher in HFrEF patients with AF, with similar findings in human atrial samples of AF patients. Cells exposed to both miRNAs exhibited altered Ca2+ handling and defective cell-to-cell communication, both findings being potential arrhythmogenic mechanisms.

Larval development of the Caribbean king crab Maguimithrax spinosissimus (Lamarck, 1818), the largest brachyuran in the western Atlantic (Crustacea: Decapoda: Majoidea)

The complete larval development of the spider crab Maguimithrax spinosissimus (Lamarck, 1818) is re-described and illustrated in detail from laboratory-reared material. The development consisted of the typical pattern reported for the Majoidea, two zoeal stages and one megalopa. The complete larval development from hatching to first crab lasted 5–6 days at temperatures that ranged between 24–28 °C. Both zoeal stages of M. spinosissimus exhibited moderate reduction in the number of setae in the maxilla and maxillipeds, from the first to the second zoeal stage, when compared with other closely related species. Maguimithrax spinosissimus can be easily distinguished from other species belonging to the closely related genus Mithrax by the (i) setation of the endopod of the maxillule, maxilla and second maxilliped in both zoeal stages; (ii) setation of the scaphognathite of the maxilla in the first zoeal stage; (iii) setation of the basis of maxilliped I in the second zoeal stage and megalopa; (iv) morphology of the antennule and antenna in the second zoeal stage; and (v) setation of the antennule, coxal endite of maxilla, and exopod of second maxilliped in the megalopa. All these characters support the recent generic status of Maguimithrax within the Mithracidae. Additional morphological details, not available previously, are provided. This study will provide support for conservation strategies in this species.

The Efficacy of Heat Acclimatization Pre-World Cup in Female Soccer Players

The efficacy of a 14-day field-based heat acclimatization (HA) training camp in 16 international female soccer players was investigated over three phases: phase 1: 8 days moderate HA (22. 1°C); phase 2: 6 days high HA (34.5°C); and phase 3: 11 days of post-HA (18.2°C), with heart rate (HR), training load, core temp (Tc), and perceptual ratings recorded throughout. The changes from baseline (day−16) in (i) plasma volume (PV), (ii) HR during a submaximal running test (HRex) and HR recovery (HRR), and (iii) pre-to-post phase 2 (days 8–13) in a 4v4 small-sided soccer game (4V4SSG) performance were assessed. Due to high variability, PV non-significantly increased by 7.4% ± 3.6% [standardized effect (SE) = 0.63; p = 0.130] from the start of phase 1 to the end of phase 2. Resting Tc dropped significantly [p &lt; 0.001 by −0.47 ± 0.29°C (SE = −2.45)], from day 1 to day 14. Submaximal running HRR increased over phase 2 (HRR; SE = 0.53) after having decreased significantly from baseline (p = 0.03). While not significant (p &gt; 0.05), the greatest HR improvements from baseline were delayed, occurring 11 days into phase 3 (HRex, SE = −0.42; HRR, SE = 0.37). The 4v4SSG revealed a moderate reduction in HRex (SE = −0.32; p = 0.007) and a large increase in HRR (SE = 1.27; p &lt; 0.001) from pre-to-post phase 2. Field-based HA can induce physiological changes beneficial to soccer performance in temperate and hot conditions in elite females, and the submaximal running test appears to show HRex responses induced by HA up to 2 weeks following heat exposure.

Mechanism of Producing Metallic Nanoparticles, with an Emphasis on Silver and Gold Nanoparticles, Using Bottom-Up Methods

Bottom-up nanoparticle (NP) formation is assumed to begin with the reduction of the precursor metallic ions to form zero-valent atoms. Studies in which this assumption was made are reviewed. The standard reduction potential for the formation of aqueous metallic atoms—E0(Mn+aq/M0aq)—is significantly lower than the usual standard reduction potential for reducing metallic ions Mn+ in aqueous solution to a metal in solid state. E0(Mn+aq/M0solid). E0(Mn+aq/M0aq) values are negative for many typical metals, including Ag and Au, for which E0(Mn+aq/M0solid) is positive. Therefore, many common moderate reduction agents that do not have significantly high negative reduction standard potentials (e.g., hydrogen, carbon monoxide, citrate, hydroxylamine, formaldehyde, ascorbate, squartic acid, and BH4−), and cannot reduce the metallic cations to zero-valent atoms, indicating that the mechanism of NP production should be reconsidered. Both AgNP and AuNP formations were found to be multi-step processes that begin with the formation of clusters constructed from a skeleton of M+-M+ (M = Ag or Au) bonds that is followed by the reduction of a cation M+ in the cluster to M0, to form Mn0 via the formation of NPs. The plausibility of M+-M+ formation is reviewed. Studies that suggest a revised mechanism for the formation of AgNPs and AuNPs are also reviewed.

Impact of cardiovascular health status on the association between changes in physical activity and major cardiovascular events and mortality among 88,320 adults: outcomes of the Lifelines Cohort Study

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Lifelines Biobank initiative received funding from the Dutch Ministry of Health, Welfare and Sport, the Dutch Ministry of Economic Affairs, the University Medical Center Groningen [UMCG], University Groningen and the Northern Provinces of the Netherlands. The work of T.M.H.E is supported by the Netherlands Heart Foundation [Senior E-Dekker grant #2017T051]. Background. Regular physical activity (PA) improves health. Many observational studies investigated the association between PA and health at a single time-point, but PA might change over time. Purpose. To examine the association between change in PA and major adverse cardiovascular events (MACE) and all-cause mortality, and to investigate the impact of cardiovascular health status at baseline on these outcomes. Methods. This study used data from the Lifelines Cohort Study (N = 88,320). Self-reported PA volumes were presented as Metabolic Equivalent of Task (MET) min/week. Change in PA was calculated by subtracting MET-min/week at the first assessment from the second assessment (median interval: 4 yrs), and 5 groups were created; large reduction (&lt; -1500), moderate reduction (-1500 to -250), no change (-250 to 250), moderate improvement (-250 to 250) and large improvement (&gt;1500). The outcome was a combination of MACE and all-cause mortality. Results. During a median follow-up of 7 years, 667 events occurred among healthy individuals (43 ± 12 yrs, 1% of 69,818) and 599 in individuals with CVRF (55 ± 11 yrs, 3% of 18,502). Adjusted for confounders and baseline PA, healthy individuals with a large reduction in PA had a greater risk of incident MACE and mortality (Table). In CVRF, moderate to large improvements in PA were associated with reductions in adverse outcomes. Risk estimates became stronger in individuals with lower baseline PA (&lt;2000 MET-min/week), Table). Conclusions. Maintaining PA in healthy individuals and increasing PA in individuals with CVRF over time is important to prevent MACE and mortality. The impact of changes in PA was stronger for individuals with lower baseline PA. Table. Change of PA, MACE and mortality. Changes in PA Healthy CVRF Large reduction 1.40 [1.02;1.93] 1.27 [0.95;1.70] Moderate reduction 1.22 [0.89;1.68] 0.97 [0.72;1.30] No changes Ref Ref Moderate improvement 1.04 [0.74;1.44] 0.65 [0.47;0.91] Large improvement 0.96 [0.71;1.31] 0.69 [0.51; 0.94] Individuals with lower baseline PA Large reduction 2.24 [0.96;5.21] 2.85 [1.44;5.63] Moderate reduction 1.77 [1.10;2.84] 1.33 [0.89;1.98] No changes Ref Ref Moderate improvement 1.16 [0.73;1.83] 0.49 [0.31;0.76] Large improvement 0.77 [0.48;1.23] 0.58 [0.39;0.86]