Queuosine (Q) is a modification of the wobble base in tRNAs that decode NAC codons. It is ubiquitous in bacteria, including many pathogens. Streptococcus mutans is an early colonizer of dental plaque biofilm and a key player in dental caries. Using a combination of genetic and physiological approaches, the predicted Q synthesis and salvage pathways were validated in this organism. These experiments confirmed that S. mutans can synthesize Q de novo through similar pathways found in Bacillus subtilis and Escherichia coli. However, S. mutans has a distinct salvage pathway compared to these model organisms, as it uses a transporter belonging to the Energy Coupling Factor (ECF) family controlled by a preQ 1-dependent riboswitch. Furthermore, Q levels in this oral pathogen depended heavily on the media composition, suggesting that micronutrients can affect Q-mediated translation efficiency.

Title: Papillary muscle free strain- promising parameter to predict sudden cardiac death in hypertrophic cardiomyopathy?Author:Dr Aslannif Roslan (MBBS, MRCP)Institut Jantung Negara,50400 Kuala Lumpur,MalaysiaE-mail: Elysess1@gmail.comCorresponding author:Dr Aslannif Roslan (MBBS, MRCP)Institut Jantung Negara,50400 Kuala Lumpur,MalaysiaE-mail:Elysess1@gmail.comHypertrophic Cardiomyopathy (HCM) generally have a good prognosis. In the long follow-up study over 5 decades annual overall HCM-related mortality was 1.3%/y (0.7% first decade to 1.8% in second and third decades). The sudden cardiac death (SCD) mortality rate was also low (0.1%/y first decade to 0.44% in second and third decades)1. SCD is the most feared HCM complication and the only effective treatment for this is Implantable Cardioverter Defibrillator (ICD) that is responsible for >10-fold decrease in HCM related mortality2. In 2014,the European Society of Cardiology (ESC) come out with risk score comprising 7 variables but this risk score have low sensitivity3,4. This led to the search for additional risk factors such as percentage of late gadolinium enhancement (LGE) in the left ventricle, presence of apical aneurysm and left ventricle ejection fraction <50% .The American Society of Cardiology/American Heart Association (ACC/AHA) incorporate this for their guidelines in 20205.Eventhough this guidelines have high sensitivity, it have low ability to identify low risk patients which can lead to inappropriate ICD implantation4. The ongoing challenge is to identify the small yet significant group of patients who are at risk of sudden cardiac death, heart failure, and death resulting from heart failure.Neither the 2014 nor the 2020 SCD risk calculators/predictors, nor even the latest 2022 ESC guidelines, have incorporated the relatively new echocardiography technique of speckle-tracking strain measurements. This technique is non-doppler oriented, angle independent and have been shown to be highly reproducible with high sensitivity and specificity6. These techniques can measure Global longitudinal strain (GLS), left atrial reservoir (LArS), conduit (LAcS) and booster (LAbS) strain and right ventricle global (RVGLS) and free wall strain (RVFWS). The most studied of these is Global Longitudinal Strain (GLS) and a recent study showed GLS have the highest accuracy to predict fatal arrhythmia and accurate ICD indication compare to all the other echocardiographic parameters that was previously considered important like diastolic left atrial (LA) diameter, left ventricular wall thickness and ejection fraction7.This is consistent with another study of large cohort of 427 HCM patients showing independent association between GLS and all cause mortality, heart transplantation, aborted SCD, and appropriate ICD therapy8. Furthermore, the latest meta-analysis of 13 studies with 2441 HCM patients showed significant correlation between impaired GLS and major adverse cardiovascular outcomes (MACE). The same correlation was also found with LA strain. A recent meta-analysis in 2023 shows significant association between all aspect of LA strain (reservoir, conduit and booster) with MACE as well as development of new atrial fibrillation (AF)9. This is not only true with echocardiography derived strain. In a Cardiac MRI (CMR) strain study published in 2024, the combination of left ventricle circumferential strain and left atrial reservoir strain model shows high diagnostic value of SCD with staggeringly high area under the curve (AUC) of 0.9510. All of these studies show how powerful is strain study in HCM SCD prognosis and it is natural to then look at papillary muscle (PM) strain as this structure is frequently abnormal in HCM11.It is widely known that papillary muscle abnormalities are part of HCM phenotypes, in addition to elongated mitral valve leaflets and hypertrophied muscle with excessive contractility (the sine qua non of HCM)11. Abnormal papillary muscle morphology is independently associated with increase left ventricular outflow tract (LVOT) obstruction with anteroapically displaced PM and double bifid PM patients having higher resting LVOT gradients than control independent of septal thickness, use of rate control medications and resting heart rate12. The variations of papillary muscle abnormalities are anterior and apical displacement of the PM usually involving ALPM, bifid PM characterized by the presence of more than one muscle head (If both PM involved it is called double bifid morphology), accessory PM that extend from the LV apex and inserted to basal myocardium without insertion into the mitral leaflets and anomalous insertion of the PM itself12,13,14.In HCM, the PM are frequently hypertrophied, with a mass measuring roughly twice the healthy controls. HCM patients also tend to have larger number of PM (2.5 muscles vs 2.1 in control) with half of the patients demonstrating multiple (3 or 4) PM15.In this issue of Echocardiography Atilla Koyuncu et al look at 79 patients with HCM that were divided into low/intermediate-risk (n=57, ESC risk score <6 points) and high risk (n=22, ESC risk score ≥6 points) groups based on the ESC risk calculator. Their mean follow-up duration is 6.2 years. They specifically look for PM abnormalities and measured anterolateral papillary muscle (ALPM) and posteromedial papillary muscle (PMPM) free strain in addition to other conventional 2-dimensional echocardiographic parameters and GLS. They enrolled all HCM phenotypic groups with or without obstruction and they exclude patients with hypertension, valvular heart diseases, hepatic/renal failure or inflammatory diseases. Of note, they did not perform left atrium (LA) or right ventricle (RV) strain. Papillary muscle strain is a relatively new tool and the measurements of ALPM strain is done in apical 4 chamber view and measurement for PMPM strain is done in apical 3 chamber view. The majority of patients have sigmoid or reverse curvature phenotype (70.9%). Interestingly 5 patients (6.3%) had anteriorly displaced papillary muscles, 7(8.8%) had bifid ALPM, 5(6.3%) had bifid PMPM and 2 patients have both bifid ALPM and PMPM (double bifid morphology).They found that the high SCD-risk group had greater wall thickness, interventricular septum thickness, posterior wall thickness and left ventricle mass index and lower GLS, ALPM (-16.88 ± 4.41% vs. -14.34 ± 3.68%, p = .028) and PMPM (-18.48 ± 6.31% vs. -15.28 ± 6.88%, p = .042) free strain. Furthermore, the SCD risk score was positively correlated with GLS, ALPM (r=0.658, p<0.001) and PMPM (r=0.600, p<0.001) strain. Also important is the fact that patient who have papillary muscle abnormalities had significantly worse ALPM and PMPM free strain. Finally, in multivariate analysis, LVMI, presence of syncope, worse GLS and ALPM-free strain were predictors of death. In terms of PM free strain value in normal healthy populations, one study done in 2016 shows between -32.5% to -48% for ALPM and -34.5% to -39.5% for PMPM but for the moment at least there are no guidelines for normal values16.What is the relevance of this paper for our understanding of HCM? It introduces an additional parameter that is easy to measure and reproducible alongside GLS and LA strain, aiding in the prediction of SCD. Although the technique is new and the sample size is limited, further studies with larger populations are necessary to establish its predictive value for SCD, similar to GLS. As strain measurements are generally robust and reproducible, papillary muscle strain has the potential to replace traditional parameters like left atrial dimension, wall thickness, and ejection fraction. Moreover, this paper highlights the importance of considering papillary muscle involvement in HCM, drawing attention to abnormalities such as bifid papillary muscles and anterior displacement during strain measurement. Ultimately, by integrating papillary muscle free strain with GLS, RV, and LA strain, we can enhance our ability to predict sudden cardiac death and ensure more appropriate ICD implantation. For clinicians focused on managing HCM, these are exciting times, and this paper provides valuable insights into the field.Maurizi N, Olivotto I, Maron M, et al. Lifetime clinical course of hypertrophic cardiomyopathy: Outcome of the historical Florence cohort over five decades. JACC Adv. 2023;2(4). doi:10.1016/j.jacadv.2023.100337Maron MS, Rowin EJ, Maron BJ. The paradigm of sudden death prevention in hypertrophic cardiomyopathy. Am J Cardiol. 2024;212S:S64-S76. doi:10.1016/j.amjcard.2023.10.076Zeppenfeld K, Tfelt-Hansen J, de Riva M, et al. 2022 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J. 2022;26:ehac262. doi:10.1093/eurheartj/ehac262Monda E, Limongelli G. Integrated sudden cardiac death risk prediction model for patients with hypertrophic cardiomyopathy. Circulation. 2023;147(4):281-283. doi:10.1161/CIRCULATIONAHA.122.063019Ommen SR, Mital S, Burke MA, et al. 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2020;142:e558–e631. doi:10.1161/CIR.0000000000000937Shirani J, Pick R, Roberts WC, Maron BJ. Morphology and significance of the left ventricular collagen network in young patients with hypertrophic cardiomyopathy and sudden cardiac death. J Am Coll Cardiol. 2000;35(1):36-44. doi:10.1016/s0735-1097(99)00492-1Nikoo MH, Zarrabi M, Moaref A, Razeghian-Jahromi I. Global longitudinal strain may be the one that appropriately identifies candidates for ICD implantation. Cardiol Res Pract. 2024;2024:2214072. doi:10.1155/2024/2214072Hiemstra YL, Debonnaire P, Bootsma M, et al. Global longitudinal strain and left atrial volume index provide incremental prognostic value in patients with hypertrophic cardiomyopathy. Circ Cardiovasc Imaging. 2017;10(7): e005706. doi:10.1161/CIRCIMAGING.116.005706Hussain K, Nso N, Tsourdinis G, et al. A systematic review and meta-analysis of left atrial strain in hypertrophic cardiomyopathy and its prognostic utility. Curr Probl Cardiol. 2024;49(1 Pt C):102146. doi:10.1016/j.cpcardiol.2023.102146Zhu X, Shi Y, Lian J, et al. Left atrial and left ventricular strain in feature-tracking cardiac magnetic resonance for predicting patients at high risk of sudden cardiac death in hypertrophic cardiomyopathy. Quant Imaging Med Surg. 2024;14(5):3544-3556. doi:10.21037/qims-23-1615Sherrid MV, Adams DH. The mitral valve in hypertrophic cardiomyopathy: Other side of the outflow tract. J Am Coll Cardiol. 2020;76(19):2248-2251. doi:10.1016/j.jacc.2020.09.580Kwon DH, Setser RM, Thamilarasan M, et al. Abnormal papillary muscle morphology is independently associated with increased left ventricular outflow tract obstruction in hypertrophic cardiomyopathy. Heart. 2008;94(10):1295-1301. doi:10.1136/hrt.2007.118018Klues HG, Maron BJ, Dollar AL, Roberts WC. Diversity of structural mitral valve alterations in hypertrophic cardiomyopathy. Circulation. 1992;85(5):1651-1660. doi:10.1161/01.cir.85.5.1651Gruner C, Chan RH, Crean A, et al. Significance of left ventricular apical-basal muscle bundle identified by cardiovascular magnetic resonance imaging in patients with hypertrophic cardiomyopathy. Eur Heart J. 2014;Rajiah P, Fulton NL, Bolen M. Magnetic resonance imaging of the papillary muscles of the left ventricle: Normal anatomy, variants, and abnormalities. Insights Imaging. 2019;10(1):83. doi:10.1186/s13244-019-0761-3Kılıcgedik A, Kahveci G, Gurbuz AS, et al. Papillary muscle free strain in patients with severe degenerative and functional mitral regurgitation. Arq Bras Cardiol. 2017;108(4):339-346. doi:10.5935/abc.20170035

The study of species environmental niches underpins numerous questions in ecology and evolutionary and has increasing relevance in a rapidly changing world. Environmental niches, characterized from observations of organisms, inform about a species’ specialization in multivariate environment space and help assess their exposure and sensitivity to a changing climate. Environmental niches are also the central concept behind the species distribution models (SDMs) which assess and predict the geographic variation in environmental suitability. Despite the clear role of past evolutionary processes in driving contemporary biodiversity distribution, the assessment of multivariate or n-dimensional (where n is the number of environmental axes) niches in a phylogenetic framework has remained limited and constrained by restrictive assumptions. This hampers important existing and emerging applications, such as assessments of niche conservatism, estimates of species’ adaptive potential under changing climates, and prediction of niches in less-studied parts of the tree of life. Here we introduce a framework that extends SDMs to estimate n-dimensional environmental niches jointly with underlying evolutionary processes. Specifically, we fit the relationship between niche distance and phylogenetic distance as a latent Gaussian Process across all species in a clade. We demonstrate mathematically how the parameters of the Gaussian Process can be linked to existing traditional evolutionary models. Simulations indicate that the approach successfully recovers evolutionary parameters. Applied to two clades of hummingbirds, the presented joint framework uncovers the relationships among species’ niches in phylogenetic space and supports the quantification and hypothesis testing of niche evolution. A key advantage of the presented framework is its joint estimation of the evolutionary process alongside niches directly from species observations with uncertainty propagated to evolutionary model parameters. The proposed approach has the potential to increase the robustness of inference about niche evolution and improve understanding of how the processes of niche formation and evolution interact.

Body size determines mobility and fitness of insects in various ways. Yet, especially in parasitoid species, drivers of body size are poorly understood, as they can be influenced by complex interactions between parasitoid behaviour, the environment, and their hosts. We measured the body size of 393 individuals of four parasitoid species sampled with trap nests for cavity-nesting bees and wasps in the Southern Black Forest, Germany. We related the body size of the parasitoids to the size of 15 host species and the diameters of their nests along four environmental gradients (canopy cover, structural complexity, herb cover and deadwood diameter). Host identity, nest diameter, and to a lesser extent, size differences within host species, were primary drivers of parasitoid body size, albeit parasitoid species differed in their responses. For instance, when the host Trypoxylon figulus doubled in size, Nematopodius debilis (parasitizing the host directly) increased by 37% in size, while Trichrysis cyanea (parasitizing food resources) increased by only 8%. Across host-parasitoid species combinations, there was only a weak positive relationship between the size of parasitoids and their hosts. In addition, we did not observe size variations in hosts and parasitoids across environmental gradients. Our findings highlight the primary factors influencing parasitoid size, with host identity and nest diameter emerging as influential factors within and between species, though not uniformly across all species. In contrast, the relationship between parasitoid and host size and environmental gradients were less influential. Considering the environmental variables that directly affect body size, such as microhabitat conditions and biotic interactions, may further clarify the dynamics shaping variation in parasitoid size.

Background. Drug shortages are an increasing and worldwide problem. Oral antibiotics are one of the most used medicines worldwide and have recently been affected by drug shortages. Despite this, little is known about the impact of antibiotic shortages on clinical and prescribing practices. Aim. To explore the impact of oral antibiotic shortages on national antibiotic utilisation. Methods. A longitudinal study of oral antibiotic shortages and antibiotic utilisation was conducted using Australian reimbursement and regulatory data from January 2022 to December 2023. All nationally reimbursed oral antibiotics were included in the study. The number and duration of reported antibiotic shortages per product were determined for each active ingredient. The clinical impact was assessed using national utilisation in Defined Daily Doses per 100,000 inhabitants. Changes in trends were analysed using Joinpoint regression. Results. Shortages were reported for eighteen of the twenty-one (86%) oral antibiotics reimbursed in Australia. No clear relation between the number and duration of shortages was observed for most antibiotics. Changes in utilisation coinciding with shortages were observed for eight active ingredients. For cefaclor (-20% decrease in utilisation) and roxithromycin (-26% decrease), the impact of shortages is most clearly reflected by decreases in utilisation. For the other six, either minor or mixed changes in utilisation were observed. Conclusions. Antibiotic shortages were common in Australia during 2022 and 2023. The impact of shortages appears complex with various factors most likely influencing impact. Australia’s healthcare professionals seem successful in mitigating the effects of shortages on drug utilisation.

FTO/ZnO/Ag-x films (where x = 0, 2, 4, 6, 8 wt.% dopant) were made by sol-gel/spin-coating technique and precursor zinc acetate dehydrate at room temperature. The samples were synthesized at 500°C calcination temperature for 2 hours. The optical (E g was determined by UV-visible spectroscopy), structural (crystallite size was obtained by X-Ray Diffraction analysis), and geometrical (surface morphology was confirmed by Field Emission Scanning Electron Microscopy) properties of synthesized samples were characterized. By UV-Vis spectra, it was revealed the transmittance reduction corresponding to the absorbance increase in the visible region indicates the merit interaction of silver with ZnO and the photocatalytic properties of the prepared films. These results were closely associated with the extinction coefficient curves. Moreover, it was demonstrated that decreasing optical band-gap (3.24 eV → 2.92 eV) by increased silver-doping, signifying the emergence of the Localized Surface Plasmon Resonance effect within the visible spectrum. This, in turn, extends the photocatalytic activity. The crystalline structure of the samples was investigated through three analytic methods: Scherrer, Williamson-Hall, and Rietveld. The results confirmed that the prepared samples had a hexagonal wurtzite phase of ZnO and body-centered-cubic Ag that formed continuous layers of polycrystalline mixtures of solids onto single-crystalline FTO substrate. Using the FESEM images and watershed algorithm, the granular structure of films statistically was examined in terms of circularity, roundness, and solidity parameters as well as the Feret’s diameter. The analysis obtained for the parameters above was found to correlate with the XRD pattern. Thus, the introduced structure could be applied in water-splitting H2 production photocatalysis applications.

Endothelial to mesenchymal transition (EndMT) serves as a crucial source of myofibroblasts and exerts a significant impact on fibrosis diseases through an unidentified underlying mechanism. Sirtuin6 (Sirt6) is widely involved in the physiology and pathology of cardiovascular diseases. However, the role of Sirt6 on the EndMT in viral myocarditis (VMC) remains unclear. This study aimed to investigate the effect of Sirt6 on the EndMT in coxsackievirus B3 (CVB3)-infected mouse cardiac endothelial cells (MCECs). Firstly, the occurrence of EndMT was confirmed in CVB3-induced MCECs, and a down-regulation of Sirt6 expression was observed during this process. To further explore the impact of Sirt6 on EndMT, the expression of Sirt6 in MCECs was manipulated using lentiviral transfection. The results showed that Sirt6 over-expression led to a up-regulation in the endothelial marker ve-Cadherin and a concomitant down-regulation in the mesenchymal marker α-Sma, partially reversing the EndMT caused by CVB3 stimulation or Sirt6 deficiency. Flow cytometry and western blot were used to detect apoptosis, and the results indicated that Sirt6 over-expression might reduce apoptosis through the Caspase-3 pathway. Subsequently, proteomic analysis was conducted based on MCECs with Sirt6 knockdown. The results suggested that Sirt6 deficiency was closely associated with apoptosis, biological oxidation, and energy metabolism. Further detection of oxidative stress and autophagy levels in MCECs revealed that CVB3 stimulation led to enhanced oxidative stress and reduced autophagy. This condition was exacerbated by lack of Sirt6 but partially mitigated by its over-expression. These findings suggested that Sirt6 might inhibit the EndMT by ameliorating oxidative stress and autophagy in CVB3-induced MCECs.

The global biodiversity loss is causing abrupt shifts in the structure and functioning of ecosystems with severe ecological and socio-economic consequences. Therefore, improving our understanding of ecosystem dynamics and regime shifts, as well as the stabilizing role of biodiversity across multiple scales is needed. Here we investigate the temporal dynamics and stability of marine ecosystems using high-resolution monitoring data on fish species composition, abundances and traits throughout European Seas. More specifically, we quantify and compare the direction and magnitude of community change at multiple spatial scales and levels of biological organization. Our results show less variability in community trajectories at larger spatial scales and higher levels of biological organization. The main underlying processes providing stability are statistical averaging arising from a larger pool of species, while at smaller spatial scales stability also emerge from functional complementarity channeled through the distribution of species traits within functional groups.

Oncolytic viruses are emerging as promising cancer therapeutic agents, with several poxviruses, including vaccinia virus (VACV) and myxoma virus, showing significant potential in preclinical and clinical trials. Modified vaccinia virus Ankara (MVA), a laboratory-derived VACV strain approved by the FDA for mpox and smallpox vaccination, has been shown to be incapable of replicating in human cells unless zinc finger antiviral protein (ZAP) is repressed. Notably, ZAP deficiency is prevalent in various cancer types. We hypothesized that MVA could selectively target and replicate in ZAP-deficient cancer cells. Our study examined MVA’s replication across multiple cancer cell lines with varying ZAP expression levels, revealing that MVA replicates more efficiently in cells with lower ZAP expression. Additionally, we assessed MVA’s oncolytic potential using a xenograft mouse model, where cancer cells were transplanted into immunodeficient mice. The data demonstrated that MVA significantly reduced tumors with lower ZAP expression without causing morbidity in nude mice. These findings suggest that MVA holds promise for further development as a targeted therapy for ZAP-deficient cancers.

Paper and pulp mills generate large volumes of wastewater containing lignin-derived compounds that are challenging to degrade using conventional wastewater treatment methods. This study presents a novel biofilm-based process for enhanced lignin removal in wastewater using the fungus Neurospora discreta, which is capable of degrading lignin effectively and forming strong biofilms on the air-liquid interface under specific conditions. The process was optimised using the Taguchi statistical design of experiments approach, evaluating three factors - pH, copper sulphate, and trace elements, at three levels. The experimental data was analysed against three responses: lignin degradation efficiency, and the activities of two ligninolytic enzymes, polyphenol oxidase, and versatile peroxidase. Results indicated that wastewater pH was the most significant parameter affecting lignin degradation efficiency and enzyme activities. Over 70% lignin degradation was achieved at pH 5 and 6 with copper sulphate concentrations above 4 mg L-1, while the degradation efficiency dropped drastically to as low as 45% at pH 7. Reversed-phase High-Performance Liquid Chromatography analysis demonstrated the effects of the three factors on the polar and non-polar components of lignin in the wastewater, revealing a clear decrease in all peak areas after treatment. Additionally, the relationships between biofilm properties including porosity, water retention value, polysaccharide and protein content, and lignin removal efficiency were demonstrated. This study also reports for the first time, the presence of versatile peroxidase, a ligninolytic enzyme, in Neurospora spp.

not-yet-known not-yet-known not-yet-known unknown Background: IgE-mediated fish allergy has long been considered an umbrella term due to the high cross-reactivity of parvalbumin, the major fish allergen. Yet, clinical tolerance to certain fish highlights allergenicity differences. In this study, we sought to construct a fish allergenicity ladder and identify fish parvalbumin epitopes to improve the diagnosis of fish allergy. Methods: Reported clinical history and the serum-specific IgE (sIgE) responses of 200 fish allergic patients were collected and analyzed, while the relative parvalbumin content in different fish were measured for the construction of fish allergenicity ladder. Double-blind placebo-controlled food challenge (DBPCFC) and open challenge against salmon, grass carp and grouper were performed in 58 selected patients for validation of the ladder. Epitope mapping was performed by peptide array against parvalbumins of salmon (both β-1 and β-2), cod, grouper, and grass carp with sera from fish allergic (n=11), partial fish tolerant (n=12), and complete fish tolerant (n=5) patients diagnosed based on oral food challenge outcome. Results: The distribution pattern of clinical, sIgE and molecular data and their strong positive correlation led to the construction of a 4-step fish allergenicity ladder comprising: step 1 of the least allergenic fishes (tuna, halibut, salmon), steps 2 (cod) and 3 (herring and grouper) of moderately allergenic fishes to step 4 of highly allergenic fishes (catfish, grass carp and tilapia). Epitope mapping revealed one epitope from grouper parvalbumin (AA64-78) for diagnosing general fish allergy and one epitopic region from salmon parvalbumin (AA19-33) as biomarker of specific fish tolerance. Only epitope-specific IgE differentiated these patients but not sIgE to fish extract or parvalbumin. Conclusion: The fish ladder and epitopes discovery can precisely differentiate fish-allergic and tolerant subjects and guide fish reintroduction by stepping up the ladder, which innovate fish allergy care in the next millennium.

not-yet-known not-yet-known not-yet-known unknown There is a paucity of literature describing equine lipoid pneumonia (LP) caused by inadvertent intra-pulmonary administration of liquid paraffin (mineral oil). This case report improves our understanding of LP by describing; 1) the first reported return of a horse to racing after LP, 2) the likely benefits of prolonged dexamethasone administration, 3) the detailed short- and long-term pulmonary and systemic responses to intra-pulmonary liquid paraffin, and 4) the prolonged pulmonary retention of liquid paraffin.

This paper introduces Feedback-Based Validation Learning (FBVL), a groundbreaking mechanism that reimagines the role of validation datasets in deep learning frameworks. Unlike conventional methods that utilize validation datasets for performance evaluation post-training, FBVL integrates these datasets into the training process itself. It employs real-time feedback to optimize the model’s weight adjustments, leading to enhanced prediction accuracy and overall model performance. Importantly, FBVL preserves the integrity of the validation process by using prediction outcomes on the validation dataset to guide training adjustments, without directly accessing the dataset. Our empirical study, conducted using the Iris dataset, highlights the transformative potential of FBVL. The Iris dataset, comprising 150 samples from three species of Iris flowers, each characterized by four features, served as an ideal testbed for demonstrating FBVL’s effectiveness. The implementation of FBVL led to substantial performance improvements, surpassing the accuracy of the best result by approximately 7.14% and achieving a reduction in loss greater than the other by approximately 49.18%. When FBVL was applied to the Multimodal EmotionLines Dataset (MELD), it showcased its wide applicability across various datasets and domains. The model achieved a test set Accuracy of 70.08%, surpassing the best reported accuracy by approximately 3.12%. These remarkable results underscore FBVL’s ability to optimize performance on established datasets and its capacity to minimize loss. Using our method FBVL, we achieved a test set f1_score micro of 70.07%, which is higher than the best reported value for f1_score micro of 67.59%. These findings position FBVL as a powerful tool set to redefine neural network training paradigms, heralding a new era of efficiency and accuracy in deep learning and artificial intelligence research.

not-yet-known not-yet-known not-yet-known unknown A variable gain amplifier (VGA) is an essential building block used in the automatic gain control (AGC) loop to provide a continuous, adjustable gain for the signal strength. To maintain the stability and consistency of the AGC loop, it is necessary to ensure that the gain of the VGA has an accurate dB-linear characteristic. This tutorial provides a detailed overview of the development of dB-linear VGAs based on differential pair structures over recent years. We categorise various VGA cells based on differential pair structures, analyse their operating principles, and explain the key features of each topology. Based on observation and extraction of the dB-linear implementation schemes used by these VGAs, we summarise three basic methods for achieving dB-linear gain control. We also discuss specific methods for realising the exponential function, using a true exponential and a mathematical approximation, and present the different types of approximation functions adopted in the works described here. Considerations in regard to the tuning range, gain error, bandwidth, linearity, process-temperature robustness, and circuit simplicity are also discussed. Finally, we draw comparisons and give perspectives for future dB-linear VGAs.

Power electronic converters are widely used in every domain for any type of power conversion. The working horse of the power conversion is a switching device. The selection of the switching device for the design is based on achieving maximum efficiency of the converter. The design or selection of the device is thus started with a model to calculate the power loss at different operating conditions. The model can be developed in many ways including the parameters from the device datasheet or the operating behavior in the complete switching cycle. The model would include determination of values of parasitic elements for power loss analysis. Thus, by developing model, power loss with higher accuracy can be predicted for device selection to achieve the maximum possible efficiency.

Power electronics plays a major role in development and advancement of electric vehicles as it enables efficient energy conversion, optimal power management, maximizes the utilization of clean energy and reduces the reliance on fossil fuels. So, by leveraging power electronic technology, electric vehicles can achieve higher energy efficiency, reduced emissions and can contribute to a more sustainable and greener future of transportation which is the need of hour. One of the key components in the electric vehicle is power electronic converter which converts electrical energy between different forms and for controlling the voltage and current levels. Power electronic converters enable efficient power flow, control the speed and torque of electric motor, and facilitate regenerative braking. The first step to design a power converter is the selection of switching device which is based on the power loss analysis of the converter. The detailed study is to determine power loss with higher accuracy by considering parasitic elements and dependence factors like junction temperature, gate-source voltage, etc.

In the rapidly evolving landscape of energy storage technologies, sodium-ion batteries (SIBs) have emerged as promising alternatives to conventional lithium-ion batteries. SIBs exhibit moderate to high specific energy ranging from approximately 70 to 170 Wh/kg, ensuring suitability for diverse applications. Furthermore, with their abundance of raw materials and potential for lower costs, sodium-ion batteries are attracting significant interest from researchers, manufacturers, and investors. This heightened interest is evidenced by the exponential growth in the number of patents filed for SIBs over the past decade, totalling 131,026 patents. This surge in patent filings underscores the growth pattern of SIBs as promising alternatives in the energy storage landscape. In this dynamic environment, securing and maintaining a robust patent portfolio is imperative for companies and innovators to establish a competitive edge, enabling them to capitalize on the increasing market demand. This article examines the strategies involved in building, protecting, and managing a robust patent portfolio as well as provides intellectual property challenges and patent filing opportunities in SIB technologies.

We revisit multi-slit diffraction with a scaling of space and time to exploit an equivalence of wave packets describing quantum free and harmonic oscillator (HO) motion. We introduce a co-moving frame of space and time coordinates to define an effective, time-independent, HO potential that confines and directs initially displaced wave packets along the classical phase space of the oscillator. $N$-slit diffraction in the lab frame from the slits to a distant detector and the familiar spreading of the propagating wave front is then described as the propagation of HO wave packets over just a quarter cycle of the oscillator and confined to the HO potential well. This connection with the co-moving frame suggests a simplified time of flight experiment wherein the arrival time distribution of diffracted particles hitting a \emph{single point detector} in the lab frame images in the co-moving frame as the \emph{full} diffraction pattern from grating to detector.

IntroductionPsoriasis is a chronic, immune-mediated, inflammatory skin disease resulting from genetic and environmental factors [1], which is characterized by the aberrant proliferation of keratinocytes and excessive infiltration of immune cells [2]. The IL-23/IL-17 axis is recognized to be the key driver of psoriasis pathogenesis, activating complex interactions between the innate and adaptive immune systems [3]. Biological therapy that blocks IL-17A from activating keratinocytes presents an extraordinary therapeutic effect on psoriasis patients [3, 4]. Although the majority of psoriasis patients can achieve complete skin clearance with anti-IL-17A biological therapy, the symptoms of psoriasis eventually recur in 20 to 24 weeks in most cases [5, 6]. Indeed, psoriasis is one of the most extensively studied skin diseases, but its pathogenesis and recurrence have not been completely elucidated. Therefore, further insight into the molecular mechanism and therapeutic targets of psoriasis is urgently needed.Currently, increasing evidence has indicated that long non-coding RNAs (lncRNAs), a group of non-coding RNAs with a length over 200 nucleotides, are involved in the pathogenesis of hyperproliferative cutaneous diseases, including psoriasis [7, 8]. Extensive research has demonstrated that lncRNAs are differentially expressed in psoriatic skin compared with healthy skin, indicating the important role of the non-coding region in the progression of psoriasis [9-11]. Several lncRNAs involved in psoriasis have been reported to be associated with the differentiation and proliferation of keratinocytes and serve as potential therapeutic targets [12-14]. More recently, our RNA‐seq analysis demonstrated that numerous differentially expressed lncRNAs (DE lncRNAs) play a crucial role in gene expression and regulation [10, 15]. Unexpectedly, further investigations suggested that the dysregulation of lncRNAs was involved in biological processes, such as the inflammatory response, cell proliferation, and cell differentiation [16-19]. The diverse functional repertoire of lncRNAs reveals their potential as therapeutic targets [20]. Thus, targeting lncRNAs is a promising approach for the treatment of psoriasis.In this study, we identified the location, assessed the expression, and characterized the biological function of the lncRNA GAS6-AS2 in psoriasis. We showed that GAS6-AS2 is downregulated in psoriatic skin and negatively correlated with the severity of psoriasis. Furthermore, our analysis found that GAS6-AS2 is involved in the cell cycle of keratinocytes. Of note, GAS6-AS2 knockdown activated the NF-kB signaling pathway in keratinocytes. Therefore, our results allow us to further investigate whether GAS6-AS2 can serve as a potential therapeutic biomarker in psoriasis.

Objectives. Impulsivity is a common reaction following interpersonal trauma (IPT) experiences, such as physical and sexual assault. Research suggests emotion dysregulation (ED) explains the link between IPT and impulsivity. To advance this research, we assessed the indirect effects of ED on associations between physical/sexual assault endorsement and the five impulsivity facets (negative urgency, positive urgency, lack of premeditation, lack of perseverance, sensation seeking). Methods. A sample of 176 participants seeking treatment at a community mental health center [M age = 34.79; women = 52.8%] completed the scales on traumatic experiences, ED, and the five impulsivity facets. Five simple mediation models were conducted to examine the hypothesized indirect effects on each impulsivity facet. Results. Results revealed significant indirect effects of ED in associations between IPT endorsement and negative urgency (B=2.17, SE=0.58, 95% CI [1.09, 3.35]), positive urgency ( B=1.87, SE=0.59, 95% CI [0.84, 3.16]), lack of premeditation ( B=1.92, SE=0.58, 95% CI [0.89, 3.18]), lack of perseverance ( B=1.67, SE=0.49, 95% CI [0.79, 2.73]), and sensation seeking ( B=0.83, SE=0.36, 95% CI [0.20, 1.62]). Conclusion. ED explained the relationship between IPT endorsement and each of the five facets of impulsivity. IPT survivors may experience more ED, which may increase impulsivity. Findings help identify underlying factors that relate to survivors’ level of impulsivity following IPT experiences, as well as suggest trauma treatments targeting ED may be effective in reducing post-trauma impulsivity for these individuals.

OBJECTIVE: To investigate how serum uric acid (SUA) influences the reproductive outcomes among women with polycystic ovary syndrome (PCOS) undergoing freeze-all strategy. DESIGN: Retrospective cohort study. Setting: Reproductive center in a tertiary hospital in China. Population: 1115 women aged 20-40 years with PCOS were included. Method: The entire population was categorized into four groups based on SUA quartiles, logistic regression analysis was conducted to determine odds ratios (ORs) for reproductive and pregnancy complications, adjusting for potential confounders. Main Outcome Measures: Primary outcome was live birth, defined as the gestational age ≥28 weeks or weighing ≥ 1000 grams. RESULTS: In quartiles of SUA levels, there was no significant difference in the live birth rate from the lowest quartile (Q1: 57.9%) to the highest (Q4: 56.6%) (adjusted OR 1.08, 95% CI, 0.74-1.57, P=0.58). Similarly, SUA showed no significant effect on biochemical and clinical pregnancy rate, or miscarriage rate (p>0.05). Women in quartile 4 had added the risk of gestational diabetes mellitus (GDM) (adjusted OR 3.87, 95% CI 1.77-8.47), gestational hypertension (GH) (adjusted OR 3.82, 95% CI 1.16-12.58) compared with quartile 1. Women in quartile 4 also had an increased probability of preterm birth and low birth weight（adjusted OR 2.24, 95% CI 0.90-5.59；adjusted OR 3.58, 95% CI 0.88-14.56, respectively). CONCLUSION: No significant correlation was found between SUA and live birth in women with PCOS undergoing freeze-all strategy. However, elevated SUA increased the risk of GH, GDM and tended to increase the risk of preterm labor and LBWI.

Restoration efforts are urgently needed for the conservation of coral reefs. The application of probiotics has recently gained attention due to the positive results in laboratory trials. In situ validation of the beneficial effects of coral probiotics is the natural next step for the development of coral microbiome manipulation research and application. Here, we present the Coral Probiotics Village (CPV) as the first underwater laboratory using an integrated and holistic approach to test innovative solutions to rehabilitate coral reefs, with a main focus on the use of microbial-based therapies. The pillars of this initiative include the establishment of a reproducible platform for sustained environmental data observations, pioneering research, including in situ coral microbiome stewardship, technology development, restoration efforts, disease outbreaks and invasive species surveillance, outreach and education. We also suggest the use of the CPV as a model that can be replicated worldwide.

Hemifacial microsomia, resulting from aberrant development of branchial arches, presents with craniofacial malformations including mandibular hypoplasia. The treatment requires both soft tissue augmentation and skeletal correction. The case involved a 25-year-old man with right hemifacial microsomia who underwent skeletal reconstruction with vascularized scapula bone grafting and soft tissue reconstruction with a

The escalating frequency and sophistication of cyberattacks targeting digital payment systems present a significant challenge to the security of financial transactions globally [1] [2]. In response to this growing threat, this research investigates the development of an advanced tokenization framework designed to enhance the security, scalability, and interoperability of digital payment infrastructures. Tokenization, a process that replaces sensitive payment information with unique, non-sensitive tokens, has emerged as a pivotal technology in mitigating the risks associated with data breaches and fraud.This study aims to push the boundaries of current tokenization methods by integrating cutting-edge encryption techniques, including quantum-resistant algorithms, with Blockchain technology to establish a decentralized, immutable ledger for transaction records. Additionally, Artificial Intelligence (AI) and machine learning are leveraged to create a dynamic, context-sensitive tokenization system capable of real-time fraud detection and prevention.The research will address several key objectives: enhancing the robustness of tokenization systems against emerging cyber threats, ensuring the system’s ability to handle high transaction volumes across various sectors, and facilitating seamless integration with existing and future digital payment platforms. By focusing on these objectives, the study seeks to create a tokenization solution that not only secures digital transactions but also promotes wider adoption of digital payment technologies by ensuring consumer trust and confidence.The findings of this research are expected to have profound implications for the security of digital payments, contributing to the resilience of financial systems and supporting the ongoing evolution of the global fintech landscape. The research outcomes will provide critical insights and practical solutions that can be applied to enhance the security of digital payment systems, ensuring their sustainability and reliability in the face of evolving cyber threats.