We report a case of left ventricular apical thrombus induce embolic stroke in patient with stress cardiomyopathy. In this case, although we initiated anticoagulant treatment after finding apical thrombus on time, stroke occurred. However, favorable clinical results were achieved with prompt percutaneous mechanical thrombectomy after early suspicion and accurate diagnosis. This case emphasized the need for a follow-up echocardiography during SCMP recovery period to evaluate possible complications such as LV thrombus.

Background Acute dyspnea (AD) is one of the main reasons for admission to the Emergency Department (ED). In the last years integrated ultrasound examination (IUE) of lung, heart and inferior vena cava be-come an extension of clinical examination for a fast differential diagnosis. The aim of present study is to assess the feasibility and diagnostic accuracy of diastolic function evaluation for diagnosing acute heart failure (aHF) in patients with acute dyspnea. Methods We included 113 patients presenting to the ED of CTO Hospital in Naples (Italy) for AD. All pa-tients underwent IUE of lung-heart-IVC with a portable ultrasound device. Left ventricle diastolic function was assessed using pulse wave doppler at the tips of the mitral valve and E wave velocity and E/A ratio were recorded. The FINAL diagnosis determined by two expert reviewers: acute HF or non-acute HF (non-aHF). We used 2 × 2 contingency tables to analyze sensitivity, specificity, positive predictive and negative predictive value of ultrasound parameters for the diagnosis of AD, comparing with the FINAL diagnosis. Results Lung ultrasound (LUS) showed high sensitivity, good specificity and accuracy in identification of patients with HF. However the highest accuracy was obtained by diastolic function parameters. The E/A ratio, detected in patients in sinus rhythm, showed the highest diagnostic performance with an AUC for aHF of 0.913. Conclusion In patients presenting with AD E/A ratio is easy to obtain in a fast ultrasound protocol and showed an excellent accuracy for diagnosis of acute HF.

Background: Pulmonary hypertension is a significant yet rare disease that can have many long-term consequences, including death. Cardiac catheterization is the gold standard for measuring pulmonary artery mean pressures (PAMP), but is invasive and risks potentially serious complications. This study aimed to create a semi-quantitative, non-invasive measure of PAMP using septal positioning. Methods: This study was a retrospective study of patients with and without pulmonary hypertension who had a transthoracic echocardiogram and cardiac catheterization. Patients undergoing atrial septal defect closure represented controls. Two blinded readers calculated the “Echocardiographically-Derived Septal Positional Angle (EDSPA)” which was compared to corresponding catheterization data including mean pulmonary artery pressures. Results: A total of 159 children were included, of which 151 had useable echocardiographic data. 40 children were identified as having pulmonary hypertension while 111 children had an atrial septal defect. Patient age ranged from a minimum of 54 days and maximum of 19 years [mean 7.1 years (SD=5.30)]. Inter-observer variability between two readers [Pearson correlation coefficient of 0.939 (p <0.001)] and intra-observer variability were low [intraclass correlation coefficient (ICC) of 0.95 and 0.96 for each observer respectively]. An EDSPA of ≤39° predicted a PAMP>20 mmHg (as measured by cardiac catheterization) with a 76% sensitivity and 76% specificity (AUC 0.846). Conclusions: EDSPA is a useful, non-invasive, and reproducible echocardiographic measure of PAMP that is easy to perform. With a sensitivity and specificity near 80%, it has significant utility in screening for pulmonary hypertension and determining which patients should undergo further invasive diagnostic testing.

Different versions of Restriction-site Associated DNA sequencing (RADseq) have become powerful and popular tools in molecular ecology. Although RADseq datasets are regarded as representative of the nuclear genome, reduced representation genomic libraries may also sample the organellar (mitochondrial and, in case of plants, plastid) DNA. Extraction of organellar loci from RADseq data can provide additional insights into the phylogenetics of the study group which comes at no additional sequencing effort. Cytoplasmic genetic variance can help better understand the evolutionary history by uncovering past hybridization and identifying the maternal (or, rarely, the paternal) lineage due to rapid lineage sorting. We developed a pipeline in bash that is based on existing bioinformatic tools to automatically mine and genotype organellar loci contained RADseq libraries. The utility of our pipeline is tested on eight, publicly available datasets spanning different phylogenetic levels (i.e. from family-level phylogenies to phylogeography) and RADseq methods (sdRAD, ddRAD, ezRAD, GBS) for genotyping both mitochondrial and plastid loci, which were subject to phylogenetic tree reconstruction. In all cases, organellar phylogenies adequately supplemented the original studies either by corroborating the large-scale picture based on RADseq or by bringing additional evidence on past or contemporary hybridization. RADseq methods designed to achieve a larger horizontal coverage (i.e. ddRAD, ezRAD) evidently yielded longer organellar alignments, but sdRAD and GBS still provided useful polymorphic loci found in the cytoplasmic DNA. Our newly developed pipeline for the above purpose can be run under a Unix-line operating system and is freely accessible at https://github.com/laczkol/RADOrgMiner

The molecular characterisation of complex behaviours is a challenging task as a range of different factors are often involved to produce the observed phenotype. An established approach is to look at the overall levels of expression of brain genes – known as ‘neurogenomics’ – to select the best candidates that associate with patterns of interest. This approach has relied so far on a set of powerful statistical tools capable to provide a snapshot of the expression of many thousands of genes that are present in an organism’s genome. However, traditional neurogenomic analyses have some well-known limitations; above all, the limited number of biological replicates compared to the number of genes tested – often referred to as “curse of dimensionality”. Here we implemented a new Machine Learning (ML) approach that can be used as a complement to established methods of transcriptomic analyses. We tested three types of ML models for their performance in the identification of genes associated with honeybee waggle dance. We then intersected the results of these analyses with traditional outputs of differential gene expression analyses and identified two promising candidates for the neural regulation of the waggle dance: the G-protein coupled receptor boss and hnRNP A1, a gene involved in alternative splicing. Overall, our study demonstrates the application of Machine Learning to analyse transcriptomics data and identify genes underlying social behaviour. This approach has great potential for application to a wide range of different scenarios in evolutionary ecology, when investigating the genomic basis for complex phenotypic traits.

Porcine Circovirus type 2d (PCV2d) is becoming the predominant PCV genotype and considerably affects the global pig industry. Nevertheless, currently no commercial PCV2d vaccine is available. Preventing and controlling the disease caused by PCV2d is therefore based on other genotype-based vaccines. However, their production platforms are laborious, limited in expression level and relatively expensive for veterinary applications. To address these challenges, we have developed a simple and cost-efficient platform for a novel PCV2d vaccine production platform, using fed-batch E. coli fermentation followed by cell disruption and filtration, and a single purification step via cation exchange chromatography. The process was developed at bench scale and then pilot scale where the PCV2d subunit protein yield was approximately 0.8 g/L fermentation volume in a short production time. Moreover, we have successfully implemented this production process at two different sites, in Southeast Asia and Europe. This demonstrates transferability and the high potential for successful industrial production.

Sophorolipids (SLs) are regarded as one of the most promising biosurfactants. However, high production costs are the main obstacle to extended SLs application. Semi-continuous fermentation, which is based on in-situ separation, is a promising technology for achieving high SLs productivity. In this study, the sedimentation mechanism of SLs was analyzed. The formation of a hydrophobic mixture of SLs and rapeseed oil was a key factor in sedimentation. And the hydrophobicity and density of the mixture determined SLs sedimentation rate. On this basis, ultrasonic enhanced sedimentation technology (UEST) was introduced, by which the sedimentation rates were increased by 46.9% to 485.4% with different ratio of rapeseed oil to SLs. UEST-assisted real-time in-situ separation and semi-continuous fermentation were performed. SLs productivity and yield were 2.15 g/L/h and 0.58 g/g, respectively, simultaneously the loss ratio of cells, glucose, and rapeseed oil were significantly reduced. This study provides the new horizon for optimization of the SLs fermentation process.

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a genetic arrhythmia syndrome characterized by adrenergically-triggered ventricular arrhythmias, syncope, and sudden cardiac death. Several small studies suggest that atrial arrhythmias (AAs) are common in patients with CPVT. Objective: To determine the incidence and type of AAs observed within a large, single-center cohort of CPVT cases as well as the efficacy and durability of AA-directed management. Methods: In this retrospective study, the electronic medical record of 129 patients (52% female; average age at diagnosis 20.8  15.3 years) with CPVT (95% with a putative CPVT1-causative RYR2 variant) between 01/2000 and 09/2019 were reviewed for electrocardiographic evidence of AAs. Clinical features and efficacy of pharmacologic and ablation therapy were assessed. Results: Overall, 10/129 (7.8%) CPVT patients, all RYR2 variant-positive, had evidence of an AA (atrial fibrillation/flutter in 6, atrial tachycardia in 3, and supraventricular tachycardia in 1). The median age at AA diagnosis was 23 (14.2-35.5) years. 8/10 of patients experienced symptoms attributed to their AA, including inappropriate shocks. All patients were trialed on anti-arrhythmics, including -blockers, and/or flecainide. Owing to drug failure (1/10), drug intolerance (1/10), or patient preference (2/10); 4/10 patients received an ablation. Over a median follow-up of 23.5 (4.5-63) months, no AA recurrences were observed. Conclusion: Compared to prior studies, the incidence of AAs in this large, single-center referral cohort of CPVT patients was substantially lower (7.8% vs. 26%-35%). Although larger multi-center studies are needed to confirm, this study suggests that ablation is efficacious and durable in CPVT-associated AAs.

The decline in cardio-respiratory function is rising among COVID-19 survivors amid the pandemic. Cardiopulmonary rehabilitation is known to be clinically effective but no studies show data to substantiate its application. The simultaneous treatment improved cardiopulmonary clinical indicators in our patient yielding enhanced functional restoration to enable independent community participation.

We examine above-threshold ionization spectra of model atomic hydrogen in short infrared laser pulses by solving the one-electron time-dependent Schr\“odinger equation in momentum space. To bypass the difficulty of solving the time-dependent Schr\”odinger equation with the interacting nonlocal Coulomb potential, we have recently formulated an alternative \emph{ab initio} approach [Ongonwou et al. Annals of Physics {\bf 375}, 471 (2016)], which is relied on the expansion of the atomic wavefunction and the interacting nonlocal Coulomb potential on a discrete basis set of Coulomb Sturmians in momentum space. As far as short infrared laser pulses are concerned, we have numerically evaluated the photoelectron momentum distributions, angular distributions and bound states populations. The results obtained from our accurate new computationally method are compared against predictions of other time-dependent calculations in the literature. This new theoretical model shows its sensitivity to the carrier-envelope phase of the laser pulse and captures the left-right dependence of the emitted photoelectrons momentum and angular distributions. More precisely, short pulses manifest significant dependence of the differential ionization probability on carrier-envelope phase of the laser pulse and broken forward-backward symmetry in the angular distributions.

We use variance minimization and Monte Carlo integration to calculate the relativistic one-electron atomic (Z=92) wavefunctions (both the 2-component and 4-component forms) for the 1S1/2, 2S1/2, 2P1/2, 2P3/2, 3S1/2, 3P1/2, 3P3/2, 3D3/2 and 3D5/2 states. With these wavefunctions we then evaluate the energy, a variety of simple properties and the decay rates for a number of E1, M1, E2 and M2 transitions. Our results are in excellent agreement with those in the literature.

Abstract Background: This study aimed to describe the clinical characteristics, pathogeny and bronchoscopic findings of 34 children with bronchitis obliterans after severe pneumonia. Methods: Thirty-four children diagnosed with bronchitis obliterans were retrospectively studied at the Children’s Hospital of Chongqing Medical University in China between January, 2014 and October, 2020. The clinical manifestations, pathogeny, lung computed tomography imaging and bronchoscopic findings of the 34 children were reported. Results: In children with bronchitis obliterans, repeated coughing, fever, wheezing, tachypnea, and lung rales were common clinical manifestations. Mycoplasma pneumoniae (M. pneumoniae) was the most common etiologic agent, followed by adenovirus. The CT scan images included uneven lung inflation(12/34), lung consolidation( 27/34), pulmonary atelectasis(23/34), and pleural effusion(22/34). All children underwent flexible bronchoscopy, and major types of airway findings were identified: mucosal congestion, luminal longitudinal folds, mucosal erosion or necrosis, hyperplastic changes, sputum emboli, bronchiectasis and obliterative-like lesions. Conclusion: In conclusion, severe M. pneumoniae pneumonia and adenovirus pneumonia appeared to have a higher risk of development of bronchitis obliterans. Bronchoscopy can be used as the main criterion for the diagnosis of bronchitis obliterans. Bronchoscopy interventional treatment is an effective measure to quickly recanalize the occluded lumen, but there is a risk of recurrence after treatment. Children with severe pneumonia should undergo regular follow-up and bronchoscopy to detect possible lumen occlusion in time.

Genomic studies may generate massive amounts of data, bringing interpretation challenges. Efforts for the differentiation of benign and pathogenic variants gain importance. In this article, we used segregation analysis and other molecular data to reclassify to benign or likely benign several rare clinically curated variants of autosomal dominant inheritance from a cohort of 500 Brazilian patients with rare diseases. This study included only symptomatic patients who had undergone molecular investigation with exome sequencing for suspected diseases of genetic etiology. Variants clinically suspected as the causative etiology and harbored by genes associated with highly-penetrant conditions of autosomal dominant inheritance underwent Sanger confirmation in the proband and inheritance pattern determination because a “de novo” event was expected. Among all 327 variants studied, 321 variants were inherited from asymptomatic parents. Considering segregation analysis, we have reclassified 51 rare variants as benign (n=51) and 211 as likely benign (n=211). In our study, the inheritance of a highly penetrant variant expected to be de novo for pathogenicity assumption was considered as a non-segregation and, therefore, a key step for benign or likely benign classification. Studies like ours may help to identify rare benign variants and improve the correct interpretation of genetic findings.

Many genomic variants are currently classified, but many more are extremely rare, have minimal associated patient data, and are classified as variants uncertain significance (VUS). Accumulating patient data such as family history and de novo status can help classify variants. Understanding potential timelines for data accumulation and variant classification can inform reporting, diagnosis, and treatment decisions. We modeled future clinical data observations with different strategies for sharing and aggregating clinical evidence for variants across multiple sequencing centers over time. Models illustrate how long it takes for variants to be classified when evidence is or is not shared between clinical laboratories and compared to when only variant interpretations are shared. When sequencing centers share evidence the probability of classifying a one in 100,000 pathogenic variant increases from less than 25% to nearly 80% after one year and to nearly 100% with 5 years of observations. Extremely rare variants have a low likelihood of classification using clinical data even with optimal data sharing. Sharing clinical evidence between laboratories will lead to faster and more certain classifications. Modeling can effectively illustrate the likelihood of variant classification under current classification frameworks and may help define realistic provider and patient expectations.

Despite all the importance of dams, dam failure, always threatens downstream areas by both natural and man-made sources and caused great human and financial losses. Vulnerability analysis is one of the main assessments to achieve a risk map and help policymakers reduce the losses and consequences of the failure. Therefore, this study aims to develop a new integrated hybrid model based on the security vulnerability assessment (SVA) and hydraulic analysis of flood and Source-Pathway-Receptor–Consequences (SPRC) approach. For SVA forms, data were collected by questionnaires survey, and for flood mapping, the open-source software, HEC-RAS was used. Geographical Information System (GIS) was applied to a combination of layers based on the SPRC approach. Five different scenarios were modeled to obtain the flood map due to a dam break. Then, the output data from the HEC-RAS software were transferred to the GIS software to be merged with other data achieved from the survey based on the SVA approach. Finally, the risk map for a case study was developed by this new hybrid approach. The results of the modeling showed that the highest vulnerability was achieved by residential areas and the lowest vulnerability is achieved by agricultural land due to floods by the dam failure.

This study aimed at investigating the variation of heat transfer and velocity changes of the fluid flow along the vertical line on a surface drawn from both sides. In the beginning, the several parameters such as Prandtl number and viscoelastic effect evaluated for heat transfer and fluid velocity by variation Iteration method. The results were compared with the numerical method. The second part of the description relates to the use RSM method in the Design Expert software. In this paper by using the RSM method, optimized the fluid velocity and heat transfer passing from the stretching sheet. By increasing the Prandtl number, the convection heat transfer 43 % increased ratio the minimum Prandtl number. In accordance with balanced modes for Prandtl number and viscoelastic parameter and wall temperature, the best optimization occurred for fluid velocity and fluid temperature with f=0.67 and θ=0.606. The results of variation iteration method are accurate for the nonlinear solution. As the value of k increases, the value of fluid velocity indicates an increase and by increase Prandtl number, the value of Temperature decreases.

Fabricating a bonded magnet with a near-net shape in suitable thermoplastic polymer binders is of paramount importance in the development of cost-effective energy technologies. In this work, anisotropic Sm2Fe17N3 (Sm-Fe-N) bonded magnets are additively printed using Sm-Fe-N anisotropic magnetic particles in a polymeric binder polyamide-12 (PA12). The anisotropic bonded permanent magnets are fabricated by Big Area Additive Manufacturing followed by post-aligned in a magnetic field. Optimal post-alignment results in an enhanced remanence of ~ 0.68 T in PA12 reflected in a parallel-oriented (aligned) measured direction. The maximum energy product achieved for the additively printed anisotropic bonded magnet of Sm-Fe-N in PA12 polymer is 78.8 KJ m-3. Our results show advanced processing flexibility of additive manufacturing for the development of Sm-Fe-N bonded magnets in polymer media designed for applications with no critical rare earth magnets.

Human activities affect the structure, dynamics, and energy flow of aquatic ecosystems. River damming, a common anthropic impact in Brazil, changes solar incidence, water flow, and temperature of waterbodies, thereby affecting their fauna. Due to their high sensitivity to environmental changes, the Odonata may be indicators of these impacts. We sampled two ecologically distinct sites, (1) a quasi-pristine forested area; and (2) a nearby human-impacted reservoir landscape, to evaluate the effects of damming on odonate community structure. The species composition of quasi-pristine communities was more heterogeneous and differed almost completely (indicating high turnover) from that of the reservoir-area communities. The capacity of the reservoir to maintain local fauna was almost nil. The communities in the changed landscape had the highest local diversity, which is related to the high occurrence of widespread generalist South American species. We also tested two recently proposed bioindication ratio tools based on the abundance of high-level taxonomic categories; both effectively demonstrated the extent of the impacts of damming. The best performing ratios were Coenagrionidae/other Zygoptera richness ratio, Zygoptera/Anisoptera abundance ratio, and Libellulidae/other Anisoptera richness ratio. The reservoir landscape promotes biotic homogenization. However, the water supply system entails the preservation of part of the native habitat in its surrounding areas, consequently maintaining local biodiversity in quasi-pristine environments.

From 2003 onwards, three pandemics have been caused by coronaviruses: severe acute respiratory syndrome coronavirus (SARS-CoV); middle east respiratory syndrome coronavirus (MERS-CoV); and, most recently, SARS-CoV-2. Notably, all three were transmitted from animals to humans. This would suggest that animals are potential sources of epidemics for humans. The emerging porcine delta-coronavirus was reported to infect children. This is a red flag that marks the ability of PDCoV to break barriers of cross-species transmission to humans. Therefore, we conducted molecular genetic analysis of global clade PDCoV to characterize spatio-temporal patterns of viral diffusion and genetic diversity. PDCoV was classified into three major lineages, according to distribution and phylogenetic analysis of PDCoV. It can be determined that PDCoV originated in Asia—most likely in Southeast Asia—through inference of migration rate and transmission routes. We also selected six special spike amino acid sequences to align and analyze to find seven significant mutation sites. The accumulation of these mutations may enhance dynamic movements, accelerating spike protein membrane fusion events and transmission. Altogether, our study offers a novel insight into the diversification, evolution, and interspecies transmission and origin of PDCoV and emphasizes the need to study the zoonotic potential of the PDCoV and comprehensive surveillance and enhanced biosecurity precautions for PDCoV.

Heart Transplantation in the Current Era: Thinking Outside the Box of Normal Donor CriteriaNicholas R. Hess MD1, Arman Kilic MD2

Background: Childhood acute lymphoblastic leukemia (ALL) treatment requires numerous lumbar punctures (LPs) with intrathecal (IT) chemotherapy to prevent and treat central nervous system disease. Historically, LPs in this setting are performed using propofol sedation. At our institution, LPs are often alternatively performed under nitrous oxide (N2O). To date, there have been no large scale assessments comparing these sedation methods for this purpose. Procedures: Retrospective cohort study of patients aged 0-31 years with ALL treated between 1/1/2013-12/31/2018 at the Children’s Minnesota Cancer and Blood Disorders Center, including all therapeutic LPs performed in the clinic setting under either propofol or N2O. Results: Among 215 patients and 2677 therapeutic LPs, 56.6% (n = 1515) occurred under N2O with 43.3% (n = 93) of patients using exclusively N2O with all LPs. The incidence of traumatic LPs (RBC ≥ 10 cells/µL) were similar between both treatments (27.3% vs 30.2). Successful IT chemotherapy delivery (99.7% N2O vs 99.8% propofol) did not differ between sedation types. Experiencing a traumatic LP under N2O was associated with a sedation switch for the subsequent LP (aOR 2.40, p=0.002) while older age (aOR 1.08, p<0.0001) and higher BMI percentile (aOR 1.01, p=0.009) were associated with increased likelihood for undergoing a traumatic LP. Conclusion: N2O is an effective sedation option for therapeutic LPs in children with ALL with noninferiority to propofol in terms of IT chemotherapy administration and traumatic LP incidence. For many patients, N2O can effectively replace propofol during LP procedures, which has important safety and quality-of-life implications.

Introduction. The search for risk factors for high-dose methotrexate (MTX)–induced nephrotoxicity in children with acute lymphoblastic leukemia (ALL) has been complex in the context of resource-limited countries where serum levels of MTX are not always available. Objective. To analyze the demographic, clinical, and biochemical factors associated with MTX-induced nephrotoxicity in children with ALL. Methodology. Case-control study in children with ALL from a General Hospital in Mexico over a four-year period (2016-2020). Kidney damage was defined with KDIGO criteria and the following variables were analyzed: sex, age, weight, height, creatinine, urea, transaminases, hematic cytometry, vomiting, mucositis, dermatitis, and number of MTX applications. Results: One hundred and eight children were studied, 22 females (38%) and 36 males (62%), ages 1 to14 years. The incidence of nephrotoxicity was 5.8% in 238 events of MTX administration. The children in the group with nephrotoxicity were older (average age 9.5 vs 5, p = 0.036), had higher baseline creatinine (0.5 mg/dL vs 0.4 mg/dL p = 0.006), and had lower baseline hemoglobin (10.1 g/dL vs 11.3 g/dL, p = 0.034). Mucositis was associated with nephrotoxicity with OR 13 95% CI 4-42, p <0.001. A cut-off value for creatinine of 0.44 mg/dL (AUC of 68%) and an age of 8 years (AUC of 64%) were identified for risk of nephrotoxicity. Conclusions: The incidence of MTX nephrotoxicity in children with ALL was 5.8%, with a high association with mucositis. The risk is greater for children older than 8 years and baseline creatinine higher than 0.44 mg/dL.

LCH is an aberrant monoclonal proliferation of dendritic cells, ranging from a self-limiting local condition to a rapidly progressive multisystemic disease. Pathogenic cells expressed, in almost 70% of cases, an activation of the MAPK/ERK signaling pathway, in particular BRAF V600E mutation. We report on a newborn with multisystemic disease diagnosed in life-threatening medical conditions, who was successfully treated with the early association of BRAF inhibitor Vemurafenib to chemotherapy. After 12 months, Vemurafenib was discontinued, without any signs of relapse. This case indicates that early combination of target therapy with standard treatment may induce rapid response and prolonged disease remission.

Clinical Letters to the Editor