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Background Unicuspid aortic valve (UAV) represents a rare congenital anomaly characterized by two subtypes: acommissural unicuspid aortic valve and unicommissural unicuspid aortic valve. Acommissural UAV is often diagnosed and corrected during the neonatal period due to haemodynamic instability. Unicommissural UAV leads to aortic stenosis (AS) in early adulthood. The diagnostic challenge associated with UAV primarily stems from its eccentric orifice opening and valvular calcification, resulting in difficult visualization of the commissures and localization of the orifice plane. This case report aims to demonstrate the unique morphological features of UAV through a comprehensive analysis using multimodality imaging. Case summary A 61-year-old woman presented to the emergency department for recurrent episodes of dyspnoea. Severe AS was diagnosed on transthoracic echocardiography (TTE) by Doppler haemodynamic measurement. However, follow-up transesophageal echocardiography (TEE) and CT transcatheter aortic valve replacement showed moderate AS by planimetry. Following this, patient was monitored closely, but her dyspnoea kept worsening. Cardiovascular magnetic resonance (CMR) was performed due to persistent dyspnoea, identifying UAV with eccentric loophole orifice with unicommissural attachment and opposite free leaflet edge. The patient was managed medically. Discussion TTE is the test of choice for AS that defines valvular morphology by direct visualization and grades the severity by haemodynamic measurement. However, the accuracy of TTE can be limited by poor acoustic windows and heavy valvular calcification. TEE measures aortic valve area (AVA) by planimetry that requires accurate localization of the AV orifice plane. Similarly, it applies to multi-detector computed tomography (MDCT). While CMR is expensive and mainly available in tertiary centres, it can provide additional information when there is discordance. [ABSTRACT FROM AUTHOR]

Most traditional methods for solving partial differential equations (PDEs) require the costly solving of large linear systems. Neural operators (NOs) offer remarkable speed-ups over classical numerical PDE solvers. Here, we conduct the first exploration and comparison of NOs for three-dimensional topology optimization. Specifically, we propose replacing the PDE solver within the popular Solid Isotropic Material with Penalization (SIMP) algorithm, which is its main computational bottleneck. For this, the NO not only needs to solve the PDE with sufficient accuracy but also has the additional challenge of providing accurate gradients which are necessary for SIMP's density updates. To realize this, we do three things: (i) We introduce a novel loss term to promote gradient-consistency. (ii) We guarantee equivariance in our NOs to increase the physical correctness of predictions. (iii) We introduce a novel NO architecture called U-Net Fourier neural operator (U-Net FNO), which combines the multi-resolution properties of U-Nets with the Fourier neural operator (FNO)'s focus on local features in frequency space. In our experiments we demonstrate that the inclusion of the novel gradient loss term is necessary to obtain good results. Furthermore, enforcing group equivariance greatly improves the quality of predictions, especially on small training datasets. Finally, we show that in our experiments the U-Net FNO outperforms both a standard U-Net, as well as other FNO methods. [ABSTRACT FROM AUTHOR]

Imaging using cardiac computed tomography (CT) or magnetic resonance (MR) imaging has become an important option for anatomic and substrate delineation in complex atrial fibrillation (AF) and ventricular tachycardia (VT) ablation procedures. Computed tomography more common than MR has been used to detect procedure-associated complications such as oesophageal, cerebral, and vascular injury. This clinical consensus statement summarizes the current knowledge of CT and MR to facilitate electrophysiological procedures, the current value of real-time integration of imaging-derived anatomy, and substrate information during the procedure and the current role of CT and MR in diagnosing relevant procedure-related complications. Practical advice on potential advantages of one imaging modality over the other is discussed for patients with implanted cardiac rhythm devices as well as for planning, intraprocedural integration, and post-interventional management in AF and VT ablation patients. Establishing a team of electrophysiologists and cardiac imaging specialists working on specific details of imaging for complex ablation procedures is key. Cardiac magnetic resonance (CMR) can safely be performed in most patients with implanted active cardiac devices. Standard procedures for pre- and post-scanning management of the device and potential CMR-associated device malfunctions need to be in place. In VT patients, imaging—specifically MR—may help to determine scar location and mural distribution in patients with ischaemic and non-ischaemic cardiomyopathy beyond evaluating the underlying structural heart disease. Future directions in imaging may include the ability to register multiple imaging modalities and novel high-resolution modalities, but also refinements of imaging-guided ablation strategies are expected. [ABSTRACT FROM AUTHOR]

In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017. Seven years after the last consensus, an updated document was considered necessary to define a contemporary framework for selection and management of patients considered for or undergoing catheter or surgical AF ablation. This consensus is a joint effort from collaborating cardiac electrophysiology societies, namely the European Heart Rhythm Association, the Heart Rhythm Society, the Asia Pacific Heart Rhythm Society, and the Latin American Heart Rhythm Society. [ABSTRACT FROM AUTHOR]

Division of labor within a honey bee colony creates a codependence between bees performing different tasks. The most obvious example of this is between the reproductive queen and worker bees. Queen bees lay 1,000 or more eggs a day, while young worker bees tend and feed queens. Young workers and queens can be exposed to pesticides when foragers return to the hive with contaminated resources. Previous research has found negative effects of larval exposure to insect-growth disruptors (IGD) methoxyfenozide and pyriproxyfen, on adult responsiveness to artificial queen pheromone. The present work investigates potential physiological and molecular mechanisms underpinning this behavioral change by examining the development of hypopharyngeal glands and ovaries as well as the expression of genes related to reproduction and worker endocrine signaling in the brain and hypopharyngeal gland tissues. Though hypopharyngeal gland and ovary development were not altered by developmental exposure to IGDs, gene expression differed. Specifically, in the brain tissue, ilp1 was downregulated in bees exposed to pyriproxyfen during development, and Kr-h1 was downregulated in both methoxyfenozide- and pyriproxyfen-exposed bees. In the hypopharyngeal glands, Kr-h1 , EcR-A , EcR-B , and E75 were upregulated in honey bees exposed to methoxyfenozide compared to those in the pyriproxyfen or control treatments. Here we discuss these results and their potential implications for the health and performance of honey bee colonies. [ABSTRACT FROM AUTHOR]

With the widespread use of computer-aided technologies like CAD/CAM/CAPP in the product manufacturing process, a large amount of process data is constantly generated and data-driven process planning has shown promising potentials for effectively reusing the process knowledge. However, a lot of labeled data are needed to train a deep learning model for effectively extracting the embedded knowledge and experiences within these process data and the labeling of process data is quite expensive and time-consuming. This paper proposes a cost-effective process design intents extraction approach for process data by combining active learning (AL) and self-paced learning (SPL). First, the process design intents inference model based on Bi-LSTM is generated by using a few pre-labeled samples. Then, the prediction uncertainty of each unlabeled sample is calculated by using a Bayesian neural network, which can assist in the identification of high confidence samples in SPL and low confidence samples in AL. Finally, the low confidence samples with manual-labels and the high confidence samples with pseudo-labels are incorporated into the training data for retraining the process design intents inference model iteratively until the model attains optimal performance. The experiments demonstrate that our approach can substantially decrease the number of labeled samples required for model training and the design intents in the process data could be inferred effectively with dynamically undated training data. [ABSTRACT FROM AUTHOR]

Ubiquitination/ubiquitylation, one of the most fundamental post-translational modifications, regulates almost every critical cellular process in eukaryotes. Emerging evidence has shown that essential components of numerous biological processes undergo ubiquitination in mammalian cells upon exposure to diverse stresses, from exogenous factors to cellular reactions, causing a dazzling variety of functional consequences. Various forms of ubiquitin signals generated by ubiquitylation events in specific milieus, known as ubiquitin codes, constitute an intrinsic part of myriad cellular stress responses. These ubiquitination events, leading to proteolytic turnover of the substrates or just switch in functionality, initiate, regulate, or supervise multiple cellular stress-associated responses, supporting adaptation, homeostasis recovery, and survival of the stressed cells. In this review, we attempted to summarize the crucial roles of ubiquitination in response to different environmental and intracellular stresses, while discussing how stresses modulate the ubiquitin system. This review also updates the most recent advances in understanding ubiquitination machinery as well as different stress responses and discusses some important questions that may warrant future investigation. [ABSTRACT FROM AUTHOR]

The presence of reactive and strong pelvic floor muscle (PFM) activities is supposed to be associated with better urinary and sexual functions in female stress urinary incontinence (SUI). This study was to explore the association of baseline PFM activities, both volitional and reflex, with urinary and sexual functions in women with SUI but who had no experience of PFM training programs before. Secondary analysis of a prospectively maintained database identified 125 sexually active women with SUI who had met the eligibility criteria. All patients had undergone intravaginal digital examination and pelvic ultrasound to detect volitional and reflex PFM activities, respectively, and responded to questionnaire surveys, including short forms of the urogenital distress inventory, incontinence impact questionnaire-7, and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire. On pelvic ultrasound, an inward clitoral motion and an anorectal lift preceding or during coughing were regarded as the presence of reflex activities of the PFM. The relationship of volitional and reflex PFM activities with pelvic floor dysfunction relating questionnaires and urethral function on urodynamic studies was analyzed. Of the 125 women studied, 30 (24.0%) had volitional PFM contraction strength less than grade 2, 74 (59.2%) grade 2 to 3, and 21 (16.8%) greater than grade 3 based on the modified Oxford grading scale. During or preceding coughing, an inward clitoral motion was not observed on ultrasound in 9 (7.2%) women and an anorectal lift was not observed in 8 (6.4%) women. The strength of volitional PFM contraction and the presence or absence of anorectal lift reflex was not associated with urethral and sexual function. In contrast, the absence of reflex inward clitoral motion was significantly associated with lower maximum urethral closure pressure (P =.042) and higher scores of urogenital distress inventory-6 (P =.006) and incontinence impact questionnaire-7 (P =.029). Higher volitional PFM contraction strength was not associated with better sexual and urinary functions; however, loss of one reflex PFM activity was associated with poorer urinary function. To our knowledge, this is the first study that evaluates the association of baseline PFM activities with sexual and urinary functions in female SUI. Nevertheless, the cross-sectional design of this study cannot well support the cause-effect relationship Besides PFM physiotherapy for enhancing sexual and urinary functions in female SUI, additional treatment strategies such as neuromodulation should take into consideration for those who had absent reflex PFM activities. Yang E, Yang SH, Huang WC, et al. Association of Baseline Pelvic Floor Muscle Activities With Sexual and Urinary Functions In Female Stress Urinary Incontinence. J Sex Med 2021;18:1698–1704. [ABSTRACT FROM AUTHOR]

Aims Pericardial tamponade (PT) is the most frequent severe complication during electrophysiology (EP) procedures and requires immediate, co-ordinated, and effective treatment. However, multiple aspects of PT treatment are either not standardized or are under ongoing debate. Methods and results An online questionnaire consisting of 26 multiple-choice questions was sent out to the European Heart Rhythm (EHRA) Research Network and also distributed via social media outputs. The EHRA survey was conducted between May and June 2023. A total of 213 replies were received from European (87%) and non-European countries. Ninety per cent of all participants perform interventions in dedicated EP labs equipped with different ablation platforms. In case of PT, most participants use X-ray as the main imaging modality guiding pericardial puncture, predominantly aiming for an anterior puncture site. Sheaths of different sizes are introduced into the pericardial space (84.3%), followed by a pigtail catheter. Application of protamine is an established but variable step in the majority (84.6%). Novel oral anticoagulants (NOAC) antidotes are not used by 73.3% of participants, while 15.2% routinely apply them. Re-transfusion of aspirated blood is performed by 72.1% [before protamine administration (18.2%), after protamine administration (13.5%), if pericardial effusion cannot be controlled (40.4%)]. A total of 72.4% re-transfuse without blood filter systems. A decision for surgical intervention is mostly taken if bleeding continues despite all interventional measures. Conclusion The current survey demonstrates that the management of PT is heterogeneous among centres. The findings of this survey may help to guide operators in their treatment and decisions in the setting of PT. [ABSTRACT FROM AUTHOR]

Abstract. Akabare chili (Capsicum annuum) contributes to Nepalese rural livelihoods but suffers from low productivity due to various abiotic stresses including drought and heat. This study aimed to assess the physiological responses of Akabare chili landraces to heat and drought stress, individually and together, and to identify stress-tolerant genotypes in the early vegetative stage. Selected eight Akabare chili landraces and chili variety 'Jwala' were subjected to control (30/22 °C day/night) and heat stress (40/32 °C) conditions with irrigation, and drought stress (30/22 °C) and combined drought-heat stress conditions without irrigation for 7 days, followed by a 5-day recovery under control condition. Stress-tolerant landraces showed better performance compared to sensitive ones in terms of efficacy of PS II (F v / F m ), transpiration rate (E), net photosynthetic rate (P N), stomatal conductance (g s ), leaf temperature depression, water use efficiency (WUE) and the ratio of stomata pore area to stomata area under stress conditions, resulting in improved biomass. Although all genotypes performed statistically similar under control conditions, their responses F v / F m , P N, E , g s and WUE were significantly reduced under thermal stress, further reduced under drought stress, and severely declined under the combination of both. Total biomass exhibited a 57.48 % reduction due to combined stress, followed by drought (37.8 %) and heat (21.4 %) compared to the control. Among the landraces, C44 showed the most significant gain in biomass (35 %), followed by DKT77 (33.48 %), while the lowest gain percentage was observed for C64C and PPR77 during the recovery phase (29 %). The tolerant landraces also showed a higher percentage of leaf cooling, chlorophyll content and leaf relative water content with fewer stomata but broader openings of pores. The study identifies potential stress-tolerant Akabare chili landraces and discusses the stress-tolerant physiological mechanisms to develop resilient crop varieties in changing climates. [ABSTRACT FROM AUTHOR]

Color vision in insects is determined by signaling cascades, central to which are opsin proteins, resulting in sensitivity to light at different wavelengths. In certain insect groups, lineage-specific evolution of opsin genes, in terms of copy number, shifts in expression patterns, and functional amino acid substitutions, has resulted in changes in color vision with subsequent behavioral and niche adaptations. Lepidoptera are a fascinating model to address whether evolutionary change in opsin content and sequence evolution are associated with changes in vision phenotype. Until recently, the lack of high-quality genome data representing broad sampling across the lepidopteran phylogeny has greatly limited our ability to accurately address this question. Here, we annotate opsin genes in 219 lepidopteran genomes representing 33 families, reconstruct their evolutionary history, and analyze shifts in selective pressures and expression between genes and species. We discover 44 duplication events in opsin genes across ∼300 million years of lepidopteran evolution. While many duplication events are species or family specific, we find retention of an ancient long-wavelength-sensitive (LW) opsin duplication derived by retrotransposition within the speciose superfamily Noctuoidea (in the families Nolidae, Erebidae, and Noctuidae). This conserved LW retrogene shows life stage–specific expression suggesting visual sensitivities or other sensory functions specific to the early larval stage. This study provides a comprehensive order-wide view of opsin evolution across Lepidoptera, showcasing high rates of opsin duplications and changes in expression patterns. [ABSTRACT FROM AUTHOR]

Background Left ventricular outflow tract obstruction (LVOTO) sometimes presents with aortic stenosis (AS). Echocardiography is used to assess the diagnosis and severity of LVOTO or AS. However, LVOTO is one of the conditions that makes AS assessment difficult, and catheter pressure measurement is frequently useful in such cases. Case summary An 84-year-old female patient presented with New York Heart Association functional Class III dyspnoea. Transthoracic echocardiography revealed LVOTO caused by upper septal hypertrophy, mitral valve systolic anterior motion with moderate mitral regurgitation, and a highly calcified aortic valve, which suggested the possibility of severe AS. The continuous Doppler echocardiography revealed a late-systolic peaking dagger-shaped profile with a peak jet velocity of 5.6 m/s. Cardiac catheterization was performed to determine the contribution of AS or LVOTO to her symptoms. Catheter pressures were measured at the ascending aorta (using a coronary catheter) and the LV (using the Navvus RXi system). The initial mean pressure gradient between the apex of the LV, just below the aortic valve and aorta, was measured at 65 and 25 mmHg, respectively. The mean pressure gradient between the apex and the aorta decreased from 65 to 40 mmHg after a 50 mg disopyramide administration. Oral medication therapy effectively stabilized her symptom after catheterization. Discussion To the best of our knowledge, this is the first reported case of assessing the severity of LVOTO and AS using the Navvus RXi system. Catheter pressure measurement using the Navvus RXi system is a useful method of determining the severity of LVOTO and AS. [ABSTRACT FROM AUTHOR]

MADS-box transcription factors (TFs), among the first TFs extensively studied, exhibit a wide distribution across eukaryotes and play diverse functional roles. Varying by domain architecture, MADS-box TFs in land plants are categorized into Type I (M-type) and Type II (MIKC-type). Type I and II genes have been considered orthologous to the SRF and MEF2 genes in animals, respectively, presumably originating from a duplication before the divergence of eukaryotes. Here, we exploited the increasing availability of eukaryotic MADS-box sequences and reassessed their evolution. While supporting the ancient duplication giving rise to SRF- and MEF2-types, we found that Type I and II genes originated from the MEF2-type genes through another duplication in the most recent common ancestor (MRCA) of land plants. Protein structures predicted by AlphaFold2 and OmegaFold support our phylogenetic analyses, with plant Type I and II TFs resembling the MEF2-type structure, rather than SRFs. We hypothesize that the ancestral SRF-type TFs were lost in the MRCA of Archaeplastida (the kingdom Plantae sensu lato). The retained MEF2-type TFs acquired a Keratin-like domain and became MIKC-type before the divergence of Streptophyta. Subsequently in the MRCA of land plants, M-type TFs evolved from a duplicated MIKC-type precursor through loss of the Keratin-like domain, leading to the Type I clade. Both Type I and II TFs expanded and functionally differentiated in concert with the increasing complexity of land plant body architecture. The recruitment of these originally stress-responsive TFs into developmental programs, including those underlying reproduction, may have facilitated the adaptation to the terrestrial environment. [ABSTRACT FROM AUTHOR]

Aims Recurrence of arrhythmia after catheter ablation of atrial fibrillation (AF) in the form of atypical atrial flutter (AFL) is common among a significant number of patients and often requires redo ablation with limited success rates. Identifying patients at high risk of AFL after AF ablation could aid in patient selection and personalized ablation approach. The study aims to assess the relationship between pre-existing atrial cardiomyopathy and the occurrence of AFL following AF ablation. Methods and results We analysed a cohort of 1007 consecutive AF patients who underwent catheter ablation and were included in a prospective registry. Patients who did not have baseline cardiac magnetic resonance imaging and late gadolinium enhancement (LGE-CMR) or did not experience any recurrences were excluded. A total of 166 patients were included gathering 56 patients who underwent re-ablation due to AFL recurrences and 110 patients who underwent re-ablation due to AF recurrences (P = 0.11). A multiparametric assessment of atrial cardiomyopathy was based on basal LGE-CMR, including left atrial (LA) volume, LA sphericity, and global and segmental LA fibrosis using semiautomated post-processing software. Out of the initial cohort of 1007 patients, AFL and AF occurred in 56 and 110 patients, respectively. An age higher than 65 [odds ratio (OR) = 5.6, 95% confidence interval (CI): 2.2–14.4], the number of previous ablations (OR = 3.0, 95% CI: 1.2–7.8), and the management of ablation lines in the index procedure (OR = 2.5, 95% CI: 1.0–6.3) were independently associated with AFL occurrence. Furthermore, several characteristics assessed by LGE-CMR were identified as independent predictors of AFL recurrence after the index ablation for AF, such as enhanced LA sphericity (OR = 1.3, 95% CI: 1.1–1.6), LA global fibrosis (OR = 1.03, 95% CI: 1.01–1.07), and increased fibrosis in the lateral wall (OR = 1.03, 95% CI: 1.01–1.04). Conclusion Advanced atrial cardiomyopathy assessed by LGE-CMR, such as increased LA sphericity, global LA fibrosis, and fibrosis in the lateral wall, is independently associated with arrhythmia recurrence in the form of AFL following AF ablation. [ABSTRACT FROM AUTHOR]

The current design of aerodynamic shapes, like airfoils, involves computationally intensive simulations to explore the possible design space. Usually, such design relies on the prior definition of design parameters and places restrictions on synthesizing novel shapes. In this work, we propose a data-driven shape encoding and generating method, which automatically learns representations from existing airfoils and uses the learned representations to generate new airfoils.The representations are then used in the optimization of synthesized airfoil shapes based on their aerodynamic performance. Our model is built upon VAEGAN, a neural network that combines Variational Autoencoder with Generative Adversarial Network and is trained by the gradient-based technique. Our model can (1) encode the existing airfoil into a latent vector and reconstruct the airfoil from that, (2) generate novel airfoils by randomly sampling the latent vectors and mapping the vectors to the airfoil coordinate domain, and (3) synthesize airfoils with desired aerodynamic properties by optimizing learned features via a genetic algorithm. Our experiments show that the learned features encode shape information thoroughly and comprehensively without predefined design parameters. By interpolating/extrapolating feature vectors or sampling from Gaussian noises, the model can automatically synthesize novel airfoil shapes, some of which possess competitive or even better aerodynamic properties as compared to airfoils used for model training purposes. By optimizing shapes on the learned latent domain via a genetic algorithm, synthesized airfoils can evolve to target aerodynamic properties. This demonstrates an efficient learning-based airfoil design framework that encodes and optimizes the airfoil on the latent domain and synthesizes promising airfoil candidates for required aerodynamic performance. [ABSTRACT FROM AUTHOR]

Plankton phototrophy consumes CO2, increasing seawater pH, while heterotrophy does the converse. Elevation of pH (>8.5) during coastal blooms becomes increasingly deleterious for plankton. Mixoplankton, which can be important bloom-formers, engage in both photoautotrophy and phagoheterotrophy; in theory, this activity could create a relatively stable pH environment for plankton growth. Using a systems biology modelling approach, we explored whether different mixoplankton functional groups could modulate the environmental pH compared to the extreme activities of phototrophic phytoplankton and heterotrophic zooplankton. Activities by most mixoplankton groups do not stabilize seawater pH. Through access to additional nutrient streams from internal recycling with phagotrophy, mixoplankton phototrophy is enhanced, elevating pH; this is especially so for constitutive and plastidic specialist non-constitutive mixoplankton. Mixoplankton blooms can exceed the size of phytoplankton blooms; the synergisms of mixoplankton physiology, accessing nutrition via phagotrophy as well as from inorganic sources, enhance or augment primary production rather than depressing it. Ocean acidification will thus enable larger coastal mixoplankton blooms to form before basification becomes detrimental. The dynamics of such bloom developments will depend on whether the mixoplankton are consuming heterotrophs and/or phototrophs and how the plankton community succession evolves. [ABSTRACT FROM AUTHOR]

Species identification by fish otoliths is an effective and appropriate approach. However, the allometric growth of otoliths can cause discrimination confusion, particularly in juvenile otolith classification. In the Southern Ocean, Chionodraco rastrospinosus,Krefftichthys anderssoni,Electrona carlsbergi , and Pleuragramma antarcticum are frequently caught together in krill fishery as bycatch species. Furthermore, the otolith shape of these four species is relatively similar in juvenile fish, making the identification of fish species difficult. In this study, we tried and evaluated many commonly used machine learning techniques to solve this problem. Eventually, by introducing a triplet loss function (function used to reduce intraspecific variation and increase inter-specific variation), the discrimination confusion caused by the allometric growth of otoliths was reduced. The classification results show that the neural network model with the triplet loss function achieves the best classification accuracy of 96%. The proposed method can help improve otolith classification performance, especially under the context of limited sampling effort, which is of great importance for trophic ecology and the study of fish life history. [ABSTRACT FROM AUTHOR]

Epileptogenesis in infants with tuberous sclerosis complex (TSC) is a gradual and dynamic process, leading to early onset and difficult-to-treat seizures. Several cellular, molecular and pathophysiologic mechanisms, including mammalian target of rapamycin (mTOR) dysregulation, GABAergic dysfunction and abnormal connectivity, may play a role in this epileptogenic process and may also contribute to the associated developmental encephalopathy. Disease-specific antiseizure medications or drugs targeting the mTOR pathway have proved to be effective in TSC-associated epilepsy. Pre-symptomatic administration of vigabatrin, a GABAergic drug, delays seizure onset and reduces the risk of a subsequent epileptic encephalopathy, such as infantile spasms syndrome or Lennox–Gastaut syndrome. Everolimus, a rapamycin-derived mTOR inhibitor, reduces seizure frequency, especially in younger patients. This evidence suggests that everolimus should be considered early in the course of epilepsy. Future trials are needed to optimize the use of everolimus and determine whether earlier correction of mTOR dysregulation can prevent progression to developmental and epileptic encephalopathies or mitigate their severity in infants with TSC. Clinical trials of several other potential antiseizure drugs (cannabidiol and ganaxolone) that target contributing mechanisms are also underway. This review provides an overview of the different biological mechanisms occurring in parallel and interacting throughout the life course, even beyond the epileptogenic process, in individuals with TSC. These complexities highlight the challenges faced in preventing and treating TSC-related developmental and epileptic encephalopathy. [ABSTRACT FROM AUTHOR]

Mafic magmatic enclaves (MMEs) hosted in granitic plutons are ideal to investigate the role of mushes on magma mixing processes in crustal magma chambers. However, the petrographic evidence for mixing of magmas through infiltration and percolation in coexisting mushes and magmas is desired. Here, we describe complex zoning patterns of plagioclase in the MMEs hosted in the monzogranite of the Early Cretaceous Sanguliu pluton in East China to reveal a mush-facilitated magma mixing process. The MMEs appear as round to oval nodules about 10 to 20 cm in size and show diverse disequilibrium textures. Plagioclase in the MMEs can be identified as three populations (Plag1, Plag2, and Plag3) with distinct zoning patterns, anorthite contents (X An) and initial Sr isotopic ratios (87Sr/86Sri). Plag1 is antecryst displaying normal zoning with An42–67 in the core and An20–36 in the mantle. The core of Plag1 shows coarse sieve texture with high-frequency oscillation in the margin, and the mantle displays resorption surface and patchy zoning. Plag2 is also antecryst with An23–66 in the core and An21–35 in the mantle. However, its core can be further recognized as Core I inside and Core II outside with distinctly different An23–43 and An44–66, respectively, showing reverse zoning. In addition, Core I contains aligned biotite inclusions and Core II shows sieve texture, resorption surface and patchy zoning. Amphibole inclusions are sporadically enclosed within Core I of Plag2 (Amp1) and mantles of Plag1 and Plag2 (Amp2), but rarely observed in Core II of Plag2. Plag3 is anhedral grain in the matrix and shows core-rim texture with An20–37 in the core. The three plagioclase populations all exhibit angular rims with resembling An9–22. Plag1 core and Plag2 Core II have (87Sr/86Sr)i (0.70920 to 0.71092) similar to the bulk (87Sr/86Sr)i of the mafic dykes intruding the Sanguliu pluton, and likely crystallized from basaltic andesitic magmas. In contrast, the rims of Plag1, Plag2, and Plag3 overall have (87Sr/86Sr)i (0.71391 to 0.71583) nearly identical to the (87Sr/86Sr)i of host monzogranite and the plagioclase in the monzogranite, likely crystallized from granitic magmas. The mantles of Plag1 and Plag2 and the core of Plag3 have (87Sr/86Sr)i (0.71141 to 0.71390) overlapping the (87Sr/86Sr)i of the MMEs, and may have crystallized from mixed melts. Calculation results based on amphibole thermobarometers show that Amp1 crystallized at ~775 °C and ~ 16 km depth, whereas Amp2 and the amphibole in the matrix of the MMEs and monzogranite crystallized at 730 to 744 °C and 8 to 9 km depth. We thus propose that the chemical and textural complexity of the three plagioclase populations in the MMEs can be attributed to that the MMEs may have come from a mushy hybrid layer that was developed through a molten granitic body being recharged by upwelling basaltic andesitic magma. Core I of Plag2 may have nucleated and grown from andesitic magma that was evolved from the basaltic andesitic magma from which the core of Plag1 and Core II of Plag2 crystallized. The two types of antecrystic plagioclase then may have experienced resorption and disequilibrium growth in the hybrid layer, and finally rimmed with ambient, evolved interstitial melt within mushy MMEs. This study shows that complex zoning patterns and compositions of plagioclase populations in the MMEs hosted in granitic plutons have important bearings on mush-facilitated magma mixing processes. [ABSTRACT FROM AUTHOR]

The development of high-frequency devices and transducers in recent years has enabled the growth of the use of dermatologic ultrasound. Real-time monitoring of the anatomy of the face during the application of aesthetic injectables potentially prevents complications such as vascular occlusions. Injecting physicians starting out in the practice of ultrasound-guided injections are commonly faced with practical questions about its use. In this article, based on the experience with ultrasound-guided filler injections of 2 large clinical centers in 2 countries, the authors summarize the steps involved when setting out to use ultrasound to guide injectable aesthetic procedures, such as fillers and biostimulators. First, the authors discuss factors that guide the choice of equipment and ultrasound transducers to perform the procedures. Next, a detailed discussion on practical issues related to the procedure is provided. The authors then consider the positioning of operators and equipment in the treatment field. The authors conclude by suggesting 2 possible techniques to guide injectable procedures: (1) scan before injecting or (2) scan while injecting. [ABSTRACT FROM AUTHOR]

Nodule formation is a process of cellular immunity in insects and other arthropods with open circulatory systems. Based on histological observations, nodule formation occurs in 2 stages. The first stage occurs immediately after microbial inoculation and includes aggregate formation by granulocytes. The second stage occurs approximately 2–6 h later and involves the attachment of plasmatocytes to melanized aggregates produced during the first stage. The first stage response is thought to play a major role in the rapid capture of invading microorganisms. However, little is known regarding how granulocytes in the hemolymph form aggregates, or how the first stage of the immunological response protects against invading microorganisms. Since the late 1990s, our understanding of the molecules and immune pathways that contribute to nodule formation has improved. The first stage of nodule formation involves a hemocyte-induced response that is triggered by pathogen-associated molecular pattern (PAMP) recognition proteins in the hemolymph regulated by a serine proteinase cascade and cytokine (Spätzle) and Toll signaling pathways. Hemocyte agglutination proceeds through stepwise release of biogenic amine, 5-HT, and eicosanoids that act downstream of the Toll pathway. The first stage of nodule formation is closely linked to melanization and antimicrobial peptide (AMP) production, which is critical for insect humoral immunity. Nodule formation in response to artificial inoculation with millions of microorganisms has long been studied. It has recently been suggested that this system is the original natural immune system, and enables insects to respond to a single invading microorganism in the hemocoel. [ABSTRACT FROM AUTHOR]

Background Achieving viral suppression (VS) for persons living with HIV is key to reaching epidemic control. We assessed the prevalence of VS and the frequency of HIV drug resistance mutations (HIVDRM) among children and adolescents living with HIV (CALHIV) in the Southern Highland zone of Tanzania. Methods From 2019 to 2021, we enrolled CALHIV aged 1–19 years on ART for >6 months in a cross-sectional study. Participants had viral load (VL) testing; those with VL ≥ 1000 copies/mL underwent HIVDRM testing. VS (<1000 copies/mL) prevalence estimates were calculated and robust Poisson regression was used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for associations with potential predictors of VS. Results Of 707 participants, 595 had VS (PR: 0.84, 95% CI: 0.81–0.87). Use of an integrase strand transfer inhibitor-containing regimen (aPR 1.15, 95% CI: 0.99–1.34), age 5–9 years (aPR 1.16, 95% CI: 1.07–1.26), and seeking care at a referral center (aPR 1.12, 95% CI: 1.04–1.21) were associated with VS. Factors inversely associated with VS included having one (aPR 0.82, 95% CI: 0.72–0.92) or two or more (aPR 0.79, 95% CI: 0.66–0.94) referrals for adherence counselling, and self-reporting missing one to two (aPR 0.88, 95% CI: 0.78–0.99) or three or more (aPR 0.77, 95% CI: 0.63–0.92) doses of ART in the past month. Of 74 participants with PRRT and INT sequencing done, 60 (81.1%) had HIVDRMs at the following frequencies: 71.6%, 67.6%, 1.4%, and 4.1% for major NNRTI, NRTI, PI, and INSTI respectively. Conclusions Higher rates of VS were observed in this cohort, and HIVDRMs were common in those without VS. This evidence supports ART optimization using dolutegravir-based regimens. However, better strategies to improve adherence are needed. [ABSTRACT FROM AUTHOR]

Cleavage and polyadenylation of pre-mRNAs is a necessary step for gene expression and function. Majority of human genes exhibit multiple polyadenylation sites, which can be alternatively used to generate different mRNA isoforms from a single gene. Alternative polyadenylation (APA) of pre-mRNAs is important for the proteome and transcriptome landscape. APA is tightly regulated during development and contributes to tissue-specific gene regulation. Mis-regulation of APA is linked to a wide range of pathological conditions. APA-mediated gene regulation in the heart is emerging as a new area of research. Here, we will discuss the impact of APA on gene regulation during heart development and in cardiovascular diseases. First, we will briefly review how APA impacts gene regulation and discuss molecular mechanisms that control APA. Then, we will address APA regulation during heart development and its dysregulation in cardiovascular diseases. Finally, we will discuss pre-mRNA targeting strategies to correct aberrant APA patterns of essential genes for the treatment or prevention of cardiovascular diseases. The RNA field is blooming due to advancements in RNA-based technologies. RNA-based vaccines and therapies are becoming the new line of effective and safe approaches for the treatment and prevention of human diseases. Overall, this review will be influential for understanding gene regulation at the RNA level via APA in the heart and will help design RNA-based tools for the treatment of cardiovascular diseases in the future. [ABSTRACT FROM AUTHOR]

Motivation Sequence-based deep learning approaches have been shown to predict a multitude of functional genomic readouts, including regions of open chromatin and RNA expression of genes. However, a major limitation of current methods is that model interpretation relies on computationally demanding post hoc analyses, and even then, one can often not explain the internal mechanics of highly parameterized models. Here, we introduce a deep learning architecture called totally interpretable sequence-to-function model (tiSFM). tiSFM improves upon the performance of standard multilayer convolutional models while using fewer parameters. Additionally, while tiSFM is itself technically a multilayer neural network, internal model parameters are intrinsically interpretable in terms of relevant sequence motifs. Results We analyze published open chromatin measurements across hematopoietic lineage cell-types and demonstrate that tiSFM outperforms a state-of-the-art convolutional neural network model custom-tailored to this dataset. We also show that it correctly identifies context-specific activities of transcription factors with known roles in hematopoietic differentiation, including Pax5 and Ebf1 for B-cells, and Rorc for innate lymphoid cells. tiSFM's model parameters have biologically meaningful interpretations, and we show the utility of our approach on a complex task of predicting the change in epigenetic state as a function of developmental transition. Availability and implementation The source code, including scripts for the analysis of key findings, can be found at https://github.com/boooooogey/ATAConv , implemented in Python. [ABSTRACT FROM AUTHOR]

The sarcoplasmatic reticulum (SR) cardiac ryanodine receptor/calcium release channel RyR2 is an essential regulator of cardiac excitation–contraction coupling and intracellular calcium homeostasis. Mutations of the RYR2 are the cause of rare, potentially lethal inherited arrhythmia disorders. Catecholaminergic polymorphic ventricular tachycardia (CPVT) was first described more than 20 years ago and is the most common and most extensively studied cardiac ryanodinopathy. Over time, other distinct inherited arrhythmia syndromes have been related to abnormal RyR2 function. In addition to CPVT, there are at least two other distinct RYR2-ryanodinopathies that differ mechanistically and phenotypically from CPVT: RYR2 exon-3 deletion syndrome and the recently identified calcium release deficiency syndrome (CRDS). The pathophysiology of the different cardiac ryanodinopathies is characterized by complex mechanisms resulting in excessive spontaneous SR calcium release or SR calcium release deficiency. While the vast majority of CPVT cases are related to gain-of-function variants of the RyR2 protein, the recently identified CRDS is linked to RyR2 loss-of-function variants. The increasing number of these cardiac 'ryanodinopathies' reflects the complexity of RYR2-related cardiogenetic disorders and represents an ongoing challenge for clinicians. This state-of-the-art review summarizes our contemporary understanding of RYR2-related inherited arrhythmia disorders and provides a systematic and comprehensive description of the distinct cardiac ryanodinopathies discussing clinical aspects and molecular insights. Accurate identification of the underlying type of cardiac ryanodinopathy is essential for the clinical management of affected patients and their families. [ABSTRACT FROM AUTHOR]

Natural compounds in plants are often unevenly distributed, and determining the best sampling locations to obtain the most representative results is technically challenging. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) can provide the basis for formulating sampling guideline. For a succulent plant sample, ensuring the authenticity and in situ nature of the spatial distribution analysis results during MSI analysis also needs to be thoroughly considered. In this study, we developed a well-established and reliable MALDI-MSI method based on preservation methods, slice conditions, auxiliary matrices, and MALDI parameters to detect and visualize the spatial distribution of mescaline in situ in Lophophora williamsii. The MALDI-MSI results were validated using liquid chromatography–tandem mass spectrometry. Low-temperature storage at −80°C and drying of "bookmarks" were the appropriate storage methods for succulent plant samples and their flower samples, and cutting into 40 μm thick sections at −20°C using gelatin as the embedding medium is the appropriate sectioning method. The use of DCTB (trans-2-[3-(4-tert-butylphenyl)-2-methyl-2-propenylidene]malononitrile) as an auxiliary matrix and a laser intensity of 45 are favourable MALDI parameter conditions for mescaline analysis. The region of interest semi-quantitative analysis revealed that mescaline is concentrated in the epidermal tissues of L. williamsii as well as in the meristematic tissues of the crown. The study findings not only help to provide a basis for determining the best sampling locations for mescaline in L. williamsii , but they also provide a reference for the optimization of storage and preparation conditions for raw plant organs before MALDI detection. Key Points An accurate in situ MSI method for fresh water-rich succulent plants was obtained based on multi-parameter comparative experiments. Spatial imaging analysis of mescaline in Lophophora williamsii was performed using the above method. Based on the above results and previous results, a sampling proposal for forensic medicine practice is tentatively proposed. [ABSTRACT FROM AUTHOR]

A Bayesian feature allocation model (FAM) is presented for identifying cell subpopulations based on multiple samples of cell surface or intracellular marker expression level data obtained by cytometry by time of flight (CyTOF). Cell subpopulations are characterized by differences in marker expression patterns, and cells are clustered into subpopulations based on their observed expression levels. A model-based method is used to construct cell clusters within each sample by modeling subpopulations as latent features, using a finite Indian buffet process. Non-ignorable missing data due to technical artifacts in mass cytometry instruments are accounted for by defining a static missingship mechanism. In contrast with conventional cell clustering methods, which cluster observed marker expression levels separately for each sample, the FAM-based method can be applied simultaneously to multiple samples, and also identify important cell subpopulations likely to be otherwise missed. The proposed FAM-based method is applied to jointly analyse three CyTOF datasets to study natural killer (NK) cells. Because the subpopulations identified by the FAM may define novel NK cell subsets, this statistical analysis may provide useful information about the biology of NK cells and their potential role in cancer immunotherapy which may lead, in turn, to development of improved NK cell therapies. [ABSTRACT FROM AUTHOR]

Acetylation is one of the key post-translational protein modifications catalysed by the protein lysine acetyltransferases (KATs). KATs catalyse the transfer of acetyl groups to the epsilon-amino groups of lysine residues in histones and non-histone proteins. Because of its wide range of target proteins, KATs regulate many biological processes, and their aberrant activities may underlie several human diseases, including cancer, asthma, Chronic Obstructive Pulmonary Disease (COPD), and neurological disorders. Unlike most of the histone modifying enzymes, such as lysine methyltransferases, KATs do not possess any conserved domain like SET domain of lysine methyltransferases. However, almost all the major families of KATs are found to be transcriptional coactivators or adaptor proteins, with defined catalytic domains, called canonical KATs. Over the past two decades, a few proteins have been discovered to possess intrinsic KAT activity but are not classical coactivators. We would like to categorize them as non-canonical KATs (NC-KATs). These NC-KATs include general transcription factors TAFII250, mammalian TFIIIC complex, and mitochondrial protein GCN5L1, etc. This review focuses on our understanding, as well as controversies regarding non-canonical KATs, where we compare the structural and functional similarities and dissimilarities of non-canonical KATs with the canonical KATs. This review also highlights the potential role of NC-KATs in health and diseases. [ABSTRACT FROM AUTHOR]

Tintinnids play a pivotal role in the marine plankton ecosystem and are model organisms in plankton studies. However, the biogeographic distribution type and community variation of tintinnids from coastal to open waters in the western Pacific have never been studied before. In the present study, 42 surface tintinnid samples were collected from coastal water to the western Pacific warm pool. A total of 84 tintinnid species were identified. The Kuroshio intrusion has obvious influence on tintinnid distribution and community structure. Fifty-two tintinnid species with relatively high occurrence frequency were classified into neritic, transitional, Kuroshio, warm-pool and cosmopolitan species. We verified the existence of tintinnid transitional species and community in Mixed Water between Neritic and Kuroshio Waters (KW). Tintinnid species richness, abundance, Shannon-Wiener index and Pielou index were higher in the KW than in the Warm-pool Water. The community complexity and stability was highest in the KW. Our findings provide a profound understanding of planktonic biogeography and community variation from nearshore to open waters in tropical and subtropical oceans. [ABSTRACT FROM AUTHOR]

The most important design concern associated with wireless sensor networks is energy efficiency that mostly deals with routing and clustering techniques. The major aim of this study is to provide energy efficient cluster routing protocols for wireless sensor network. Initially, we used a Honey Badger Algorithm for cluster heads selection. Honey Badger Algorithm is used to choose the distance to the base station, residual energy, distance to its neighbors, node degree node and centrality with the optimal cluster head among all sensors. The routing between base stations and cluster heads is performed through Fuzzy Firebug Swarm Optimization algorithm. Hence, the fuzzy decision module automatically adjusts the search behavior of firebug swarm optimization. Fuzzy rules are used with the node degree, residual energy and distance to the base station to address the firebug swarm optimization algorithm's constraints during routing. Finally, cluster maintenance is done which is the major step to eliminate the failure nodes. This process assists to improve the network lifetime during data transmission by eliminating the faulty nodes and establish an efficient path between the source node and the base station. Wide experimentation is accomplished to assess the efficiency of the proposed protocol using different evaluation measures. The proposed methodology offers improved end-to-end delay, increased packet delivery ratio, higher throughput, low packet drop ratio and minimizes energy consumption when compared with the existing wireless sensor network routing protocols. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are single-stranded and covalently closed non-coding RNA molecules originated from RNA splicing. Their functions include regulatory potential over other RNA species, such as microRNAs, messenger RNAs and RNA binding proteins. For circRNA identification, several algorithms are available and can be classified in two major types: pseudo-reference-based and split-alignment-based approaches. In general, the data generated from circRNA transcriptome initiatives is deposited on public specific databases, which provide a large amount of information on different species and functional annotations. In this review, we describe the main computational resources for the identification and characterization of circRNAs, covering the algorithms and predictive tools to evaluate its potential role in a particular transcriptomics project, including the public repositories containing relevant data and information for circRNAs, recapitulating their characteristics, reliability and amount of data reported. [ABSTRACT FROM AUTHOR]

Objective To serve the over 1.82 million people of Korean descent who reside in the United States, we assembled a core and supplemental battery of culturally and linguistically appropriate neuropsychological measures for differential diagnosis of dementia for Korean-speaking patients. Method Test instruments in Korean were identified through systematic searches of PubMed and Google Scholar, US-based website searches in Korean, and in consultation with Korean-speaking cultural brokers, residing in the United States and Korea. Results A battery assessing cognitive domains and mood was assembled using core measures developed specifically for Korean-speaking individuals within the United States and supplemental English measures that can be administered using translated instructions and English normative data. The rationale for test selection and clinical utility, including strengths and limitations of the proposed measures, is presented. Additionally, a case illustration using the proposed battery is included. Conclusions Given the large and aging population of Korean-speaking residents in the United States, it is imperative to utilize appropriately designed and normed instruments to provide culturally competent assessments to better serve the Korean community. [ABSTRACT FROM AUTHOR]

Climate change has intensified the infection of tomato plants by pathogens such as Pseudomonas syringae pv. tomato (Pst). Rootstocks may increase plant tolerance to leaf phytopathogens. The aim of this study was to evaluate the effects of the tolerant Poncho Negro (R) tomato rootstock on physiological defence and the role of hydrogen sulfide (H2S) in susceptible Limachino (L) tomato plant responses to Pst attack. Ungrafted (L), self-grafted (L/L), and grafted (L/R) plants were infected with Pst. Rootstock increased the concentration of antioxidant compounds including ascorbate in the scion. Tolerant rootstock induced an increase of H2S in the scion, which correlated with enhanced expression of the SlAPX2 gene. A high accumulation of salicylic acid was observed in Pst -inoculated grafted L/L and L/R plants, but this was higher in L/R plants. The increase of H2S during Pst infection was associated with a reduction of ethylene in L/R plants. Our study indicates that the Poncho Negro rootstock reduced the symptoms of bacterial speck disease in the Limachino tomato plants, conferring tolerance to Pst infection. This study provides new knowledge about the impact of rootstock in the defence of tomato plants against leaf pathogens that could be used in sustainable management of tomato cultivation. [ABSTRACT FROM AUTHOR]