Miracle-dz/UniFAR-FTUs huggingface dataset:
Conserved Molecular Players Involved in Human Nose Morphogenesis Underlie Evolution of the Exaggerated Snout Phenotype in Cichlids

Abstract Instances of repeated evolution of novel phenotypes can shed light on the conserved molecular mechanisms underlying morphological diversity. A rare example of an exaggerated soft tissue phenotype is the formation of a snout flap in fishes. This tissue flap develops from the upper lip and has evolved in one cichlid genus from Lake Malawi and one genus from Lake Tanganyika. To investigate the molecular basis of snout flap convergence, we used mRNA sequencing to compare two species with snout flap to their close relatives without snout flaps from each lake. Our analysis identified 201 genes that were repeatedly differentially expressed between species with and without snout flap in both lakes, suggesting shared pathways, even though the flaps serve different functions. Shared expressed genes are involved in proline and hydroxyproline metabolism, which have been linked to human skin and facial deformities. Additionally, we found enrichment for transcription factor binding sites at upstream regulatory sequences of differentially expressed genes. Among the enriched transcription factors were members of the FOX transcription factor family, especially foxf1 and foxa2, which showed an increased expression in the flapped snout. Both of these factors are linked to nose morphogenesis in mammals. We also found ap4 (tfap4), a transcription factor showing reduced expression in the flapped snout with an unknown role in craniofacial soft tissue development. As genes involved in cichlid snout flap development are associated with human midline facial dysmorphologies, our findings hint at the conservation of genes involved in midline patterning across distant evolutionary lineages of vertebrates, although further functional studies are required to confirm this.
The impact of SWI/SNF and NuRD inactivation on gene expression is tightly coupled with levels of RNA polymerase II occupancy at promoters

SWI/SNF and NuRD are protein complexes that antagonistically regulate DNA accessibility. However, repression of their activities often leads to unanticipated changes in target gene expression (paradoxical), highlighting our incomplete understanding of their activities. Here we show that SWI/SNF and NuRD are in a tug-of-war to regulate PRC2 occupancy at lowly expressed and bivalent genes in mouse embryonic stem cells (mESCs). In contrast, at promoters of average or highly expressed genes, SWI/SNF and NuRD antagonistically modulate RNA polymerase II (Pol II) release kinetics, arguably owing to accompanying alterations in H3.3 and H2A.Z levels at promoter-flanking nucleosomes, leading to paradoxical changes in gene expression. Owing to this mechanism, the relative activities of the two remodelers potentiate gene promoters toward Pol II–dependent open or PRC2-dependent closed chromatin states. Our results highlight RNA Pol II occupancy as the key parameter in determining the direction of gene expression changes in response to SWI/SNF and NuRD inactivation at gene promoters in mESCs.
Social Network Influences on Adolescent E-cigarette Use

Abstract Background: Determine if individual adolescent vaping is associated with the vaping behavior of their school-based friendships; whether that association stems from peer influence or peer selection; and whether it varies by age. Methods: Two wave longitudinal survey of 1,208 students in one Midwestern US school district. Students were asked if they ever vaped and to name their seven closest friends within the school district. A roster of all eligible students was pre-loaded into the survey to facilitate network data collection. Terms for network exposure, the proportion of vaping friends; and selection, the number of new friends who vape, were created. Logistic regression and Stochastic Actor Oriented Models were used to test both influence and selection effects. Results: A cross-sectional logistic regression model indicated that friend vaping was associated with individual vaping (AOR = 4.96, p < 0.01); and lagged logistic models indicated that increased friend vaping was associated with individual vaping initiation (AOR = 1.72, p < 0.05). Selecting new friends who vape was also associated with becoming a vaper (AOR = 1.25, p < 0.01). Both influence and selection were present for those less than 14 years old. Conclusions: This is the first study to use social network analysis to show that adolescents who vape or initiate vaping are more likely to do so if their friends vape, and/or they make new friends who vape. Prevention and cessation programs should address the role of friend influence and selection on e-cigarette use; particularly at younger ages.
Methods for the estimation of the tissue motion using digitized ultrasound echo signals

Tissue motion estimation in ultrasound images plays a central role in many modern signal processing applications, including tissue characterization, strain and velocity imaging, and tissue viscoelasticity imaging. Therefore, the performance of tissue motion estimation is of significant importance. Also, its computational cost determines if it can be implemented in real-time so that it can be used clinically. This thesis presents several efficient methods for accurate estimation of tissue motion using digitized ultrasound echo signals. First, sample tracking algorithms are presented as a new class of motion estimators. These algorithms are based on the tracking of individual samples using a continuous representation of the reference echo signal. Simulations and experimental results on tissue mimicking phantoms show that sample tracking algorithms significantly outperform common algorithms in terms of accuracy, precision, sensitivity, and resolution. However, their performance degrades in the presence of noise. To improve the performance of motion estimation in multi-dimensions, pattern matching interpolation techniques are studied and new interpolation techniques are presented. Simulation and experimental results show that, with small computational overhead, the proposed interpolation techniques significantly improve the accuracy and the precision of motion estimation in both 2D and 3D. Employing these techniques, real-time 2D motion tracking software is developed. Furthermore, the performance of the proposed 2D estimators is compared with that of 2D tracking using angular compounding. The results show that the proposed interpolation methods bring the performance of pattern matching techniques close to that of 2D compound tracking. Finally, angular compounding is combined with custom pulse sequencing and delay cancellation techniques to develop a system that estimates the motion vectors at very high frame rates (> 500Hz) in real-time. The application of the system in the study of the propagation of mechanical waves for tissue characterization is also presented.
Research on the real and complex multimodal wavelet packet subbands and its application in image classification

Compared with unimodal wavelet packet subbands, multimodal subbands have strong texture discriminatory power. The existence of mulitimodal subbands in dual-tree complex wavelet packet transform is proved. Similar to the multimodal subbands in real wavelet packet transform, there are shift-modal subbands in complex transform to capture the periodicities running through the texture images. Furthermore, the stability of multimodal subbands in real transform is investigated through a classification experiment. It is concluded that, to the textures with small and very regular periodicities, stable multimodal subbands can be obtained.
Multilayer brain networks can identify the epileptogenic zone and seizure dynamics

Seizure generation, propagation, and termination occur through spatiotemporal brain networks. In this paper, we demonstrate the significance of large-scale brain interactions in high-frequency (80–200Hz) for the identification of the epileptogenic zone (EZ) and seizure evolution. To incorporate the continuity of neural dynamics, here we have modeled brain connectivity constructed from stereoelectroencephalography (SEEG) data during seizures using multilayer networks. After introducing a new measure of brain connectivity for temporal networks, named multilayer eigenvector centrality (mlEVC), we applied a consensus hierarchical clustering on the developed model to identify the EZ as a cluster of nodes with distinctive brain connectivity in the ictal period. Our algorithm could successfully predict electrodes inside the resected volume as EZ for 88% of participants, who all were seizure-free for at least 12 months after surgery. Our findings illustrated significant and unique desynchronization between EZ and the rest of the brain in the early to mid-seizure. We showed that aging and the duration of epilepsy intensify this desynchronization, which can be the outcome of abnormal neuroplasticity. Additionally, we illustrated that seizures evolve with various network topologies, confirming the existence of different epileptogenic networks in each patient. Our findings suggest not only the importance of early intervention in epilepsy but possible factors that correlate with disease severity. Moreover, by analyzing the propagation patterns of different seizures, we demonstrate the necessity of collecting sufficient data for identifying epileptogenic networks.
Abnormal noise detector for gear units

An abnormal noise detector for use in evaluating the quality of automotive gear units or the like is disclosed. The present invention employs a microphone which picks up the noise produced by a gear unit being tested and an adjustable bandpass filter connected to the microphone which passes only those signals from the microphone having a desired frequency, the desired frequency being a function of the rate of rotation of the gear unit. The bandpass filter is controlled by a proportional amplifier responsive to the rate of rotation of the gear unit which at any rate of rotation of the gear unit causes the bandpass filter to pass only the desired frequency. The filtered output from the bandpass filter is applied to an X-Y recorder which automatically plots the sound pressure of the noise having the desired frequency as a function of the rate of rotation of the gear unit or as a function of the desired frequency.
Pearls for practice from the 2022 joint task force drug allergy practice parameter

Purpose of review To review updated recommendations in the 2022 Drug Allergy Practice Parameters for the evaluation and management of drug hypersensitivity reactions. Recent findings Adverse drug reactions have become increasingly prominent with the advent of new and emerging pharmacologic therapies. Hypersensitivity reactions encompass a significant proportion of adverse drug reactions and negatively impact both the individual patient and overall health system. Reactions are heterogeneous in presentation and may be immediate (onset of symptoms ≤6 h) or delayed (onset of symptoms >6 h to months) after drug exposure. The 2022 Drug Allergy Practice Parameter provides consensus-based statements for evaluation of hypersensitivity reactions to antibiotics, NSAIDs, cancer chemotherapies, immune checkpoint inhibitors, biologics, and excipients. In general, the guideline highlights the importance of patient history in elucidating the phenotype and severity of the index reaction. Drug challenge remains the gold standard for diagnosis and is increasingly favored over skin testing in patients with nonsevere, nonanaphylactic drug reaction histories. Summary The 2022 Drug Allergy Practice Parameter provides an updated framework for physicians to reference in clinical practice when managing patients with drug hypersensitivity reactions.
7-Deazaguanines in DNA: functional and structural elucidation of a DNA modification system

Abstract The modified nucleosides 2′-deoxy-7-cyano- and 2′-deoxy-7-amido-7-deazaguanosine (dPreQ0 and dADG, respectively) recently discovered in DNA are the products of the bacterial queuosine tRNA modification pathway and the dpd gene cluster, the latter of which encodes proteins that comprise the elaborate Dpd restriction–modification system present in diverse bacteria. Recent genetic studies implicated the dpdA, dpdB and dpdC genes as encoding proteins necessary for DNA modification, with dpdD–dpdK contributing to the restriction phenotype. Here we report the in vitro reconstitution of the Dpd modification machinery from Salmonella enterica serovar Montevideo, the elucidation of the roles of each protein and the X-ray crystal structure of DpdA supported by small-angle X-ray scattering analysis of DpdA and DpdB, the former bound to DNA. While the homology of DpdA with the tRNA-dependent tRNA-guanine transglycosylase enzymes (TGT) in the queuosine pathway suggested a similar transglycosylase activity responsible for the exchange of a guanine base in the DNA for 7-cyano-7-deazaguanine (preQ0), we demonstrate an unexpected ATPase activity in DpdB necessary for insertion of preQ0 into DNA, and identify several catalytically essential active site residues in DpdA involved in the transglycosylation reaction. Further, we identify a modification site for DpdA activity and demonstrate that DpdC functions independently of DpdA/B in converting preQ0-modified DNA to ADG-modified DNA.
The intellectual base and global trends in contrast-induced acute kidney injury: a bibliometric analysis

Abstract Contrast-induced acute kidney injury (CI-AKI) has become the third leading cause of hospital-acquired kidney injury. A comprehensive analysis of the current state of research in the field of CI-AKI will help to reveal trends and hot topics in the field. To date, there are no published bibliometric analyses related to CI-AKI studies. Here, we analyze the relevant literature since the emergence of the concept and provide valuable insights. The literature was collected from the Web of Science Core Collection. The data were analyzed visually using CiteSpace and VOSviewer software. We collected a total of 4775 papers, with the United States and Guangdong Acad Med Sci as the major publishing powers in terms of country/region and institution. J AM COLL CARDIOL was the journal with the most published and cocited articles. Cluster analysis showed that clinical trials are the current research hotspot. The areas of risk assessment, prevention strategies, risk factors, and vascular lesions have been popular in recent years. Research on the mechanism of injury in CI-AKI will be the focus of future research, which will be crucial to reduce the clinical incidence of CI-AKI. In summary, this study provides a comprehensive analysis of the development process in the field of CI-AKI and discusses future research directions based on the analysis of objective data from many studies on CI-AKI.
MRI‐based synthetic CT in the detection of knee osteoarthritis: Comparison with CT

Magnetic resonance Imaging is the gold standard for assessment of soft tissues; however, X‐ray‐based techniques are required for evaluating bone‐related pathologies. This study evaluated the performance of synthetic computed tomography (sCT), a novel MRI‐based bone visualization technique, compared with CT, for the scoring of knee osteoarthritis. sCT images were generated from the 3T T1‐weighted gradient‐echo MR images using a trained machine learning algorithm. Two readers scored the severity of osteoarthritis in tibiofemoral and patellofemoral joints according to OACT, which enables the evaluation of osteoarthritis, from its characteristics of joint space narrowing, osteophytes, cysts and sclerosis in CT (and sCT) images. Cohen's κ was used to assess the interreader agreement for each modality, and intermodality agreement of CT‐ and sCT‐based scores for each reader. We also compared the confidence level of readers for grading CT and sCT images using confidence scores collected during grading. Inter‐reader agreement for tibiofemoral and patellofemoral joints were almost‐perfect for both modalities (κ = 0.83–0.88). The intermodality agreement of osteoarthritis scores between CT and sCT was substantial to almost‐perfect for tibiofemoral (κ = 0.63 and 0.84 for the two readers) and patellofemoral joints (κ = 0.78 and 0.81 for the two readers). The analysis of diagnosis confidence scores showed comparable visual quality of the two modalities, where both are showing acceptable confidence levels for scoring OA. In conclusion, in this single‐center study, sCT and CT were comparable for the scoring of knee OA.
Parental experiences of eczema advice in online parenting forums: a qualitative interview study

Background Parents of children with eczema are increasingly turning to online parenting forums for advice about how to manage it. Little is known about how parents make sense of advice about eczema treatments in online forums, and how it affects their management of childhood eczema. Aim To explore how parents of children with eczema make sense of and act on advice about eczema treatments exchanged in online parenting forums. Design & setting Qualitative interviews with parents of children with eczema from the UK. Method Fifteen parents were recruited through online advertisements and snowball sampling. Semi-structured interviews were carried out face to face or by telephone, and analysed inductively using reflexive thematic analysis. Results When seeking advice from online parenting forums about eczema treatments, parents described appraising the credibility of advice and considering the potential suitability of treatments that were recommended in the forum. Parents proceeded to make sense of online advice through either reading advice and not engaging in online discussions, or actively engaging in online discussions to direct topics and seek most relevant advice. Parents discussed advice received online in subsequent consultations with their GP and requested prescriptions of recommended treatments. Some parents described trying new treatments without consulting their GP. Conclusion Understanding how parents appraise, make sense of, and act on online advice could support healthcare professionals to disseminate advice appropriately, ask additional questions, and signpost parents to reliable online resources.
Sociodemographic and environmental factors associated with dengue, Zika, and chikungunya among adolescents from two Brazilian capitals

Among the emerging and reemerging arboviral diseases, Zika, dengue and chikungunya deserve special attention due to their wide geographical distribution and clinical severity. The three arboviruses are transmitted by the same vector and can present similar clinical syndromes, bringing challenges to their identification and register. Demographic characteristics and individual and contextual social factors have been associated with the three arboviral diseases. However, little is known about such associations among adolescents, whose relationships with the social environment are different from those of adult populations, implying potentially different places, types, and degrees of exposure to the vector, particularly in the school context. This study aims to identify sociodemographic and environmental risk factors for the occurrence of Zika, dengue, and chikungunya in a cohort of adolescents from the Study of Cardiovascular Risks in Adolescents—ERICA—in the cities of Rio de Janeiro/RJ and Fortaleza/CE, from January 2015 to March 2019. Cases were defined as adolescents with laboratory or clinical-epidemiological diagnosis of Zika, dengue, or chikungunya, notified and registered in the Information System for Notifiable Diseases (SINAN). The cases were identified by linkage between the databases of the ERICA cohort and of SINAN. Multilevel Cox regression was employed to estimate hazard ratios (HR) as measures of association and respective 95% confidence intervals (95%CI). In comparison with adolescents living in lower socioeconomic conditions, the risk of becoming ill due to any of the three studied arboviral diseases was lower among those living in better socioeconomic conditions (HR = 0.43; 95%CI: 0.19–0.99; p = 0.047) and in the adolescents who attended school in the afternoon period (HR = 0.17; 95%CI: 0.06–0.47; p<0.001). When compared to areas whose Building Infestation Index (BII) for Aedes aegypti was considered satisfactory, a BII in the school region classified as “alert” and “risk” was associated with a higher risk of arboviral diseases (HR = 1.62, 95%CI: 0.98–2.70; p = 0.062; HR = 3.72, 95%CI: 1.27–10.9; p = 0.017, respectively). These findings indicate that living in less favored socioeconomic conditions, attending school in the morning, and having a high BII for Ae. aegypti in school’s region can contribute to an increased risk of infection by Zika, dengue, or chikungunya in adolescents. The identification of residential or school areas based on those variables can contribute to the implementation of control measures in population groups and priority locations.
First-in-human phase I study of the OX40 agonist GSK3174998 with or without pembrolizumab in patients with selected advanced solid tumors (ENGAGE-1)

Background The phase I first-in-human study ENGAGE-1 evaluated the humanized IgG1 OX40 agonistic monoclonal antibody GSK3174998 alone (Part 1 (P1)) or in combination with pembrolizumab (Part 2 (P2)) in patients with advanced solid tumors. Methods GSK3174998 (0.003–10 mg/kg) ± pembrolizumab (200 mg) was administered intravenously every 3 weeks using a continuous reassessment method for dose escalation. Primary objectives were safety and tolerability; secondary objectives included pharmacokinetics, immunogenicity, pharmacodynamics, and clinical activity. Results 138 patients were enrolled (45 (P1) and 96 (P2, including 3 crossovers)). Treatment-related adverse events occurred in 51% (P1) and 64% (P2) of patients, fatigue being the most common (11% and 24%, respectively). No dose-toxicity relationship was observed, and maximum-tolerated dose was not reached. Dose-limiting toxicities (P2) included Grade 3 (G3) pleural effusion and G1 myocarditis with G3 increased troponin. GSK3174998 ≥0.3 mg/kg demonstrated pharmacokinetic linearity and >80% receptor occupancy on circulating T cells; 0.3 mg/kg was selected for further evaluation. Limited clinical activity was observed for GSK3174998 (P1: disease control rate (DCR) ≥24 weeks 9%) and was not greater than that expected for pembrolizumab alone (P2: overall response rate 8%, DCR ≥24 weeks 28%). Multiplexed immunofluorescence data from paired biopsies suggested that increased infiltration of natural killer (NK)/natural killer T (NKT) cells and decreased regulatory T cells (Tregs) in the tumor microenvironment may contribute to clinical responses: CD16+CD56–CD134+ NK /NKT cells and CD3+CD4+FOXP3+CD134+ Tregs exhibited the largest magnitude of change on treatment, whereas CD3+CD8+granzyme B+PD-1+CD134+ cytotoxic T cells were the least variable. Tumor gene expression profiling revealed an upregulation of inflammatory responses, T-cell proliferation, and NK cell function on treatment with some inflammatory cytokines upregulated in peripheral blood. However, target engagement, evidenced by pharmacologic activity in peripheral blood and tumor tissue, did not correlate with clinical efficacy. The low number of responses precluded identifying a robust biomarker signature predictive of response. Conclusions GSK3174998±pembrolizumab was well tolerated over the dose range tested and demonstrated target engagement. Limited clinical activity does not support further development of GSK3174998±pembrolizumab in advanced cancers. Trial registration number NCT02528357.