Leukemia represents the most prevalent malignancy in children, constituting 30% of childhood cancer cases, with acute lymphoblastic leukemia (ALL) being particularly heterogeneous. This paper explores the role of alternative splicing in leukemia, highlighting its significance in cancer development and progression. Aberrant splicing is often driven by mutations in splicing-factor genes, which can lead to the production of variant proteins that contribute to oncogenesis. The spliceosome, a complex of small nuclear RNAs and proteins, facilitates RNA splicing, a process critical for generating diverse mRNA and protein products from single genes. Mutations in splicing factors, such as U2AF1, SF3B1, SRSF2, ZRSR2, and HNRNPH1, are frequently observed across various hematological malignancies and are associated with poor prognosis and treatment resistance. This research underscores the necessity of understanding the mechanisms of RNA splicing dysregulation in order to develop targeted therapies to correct these aberrant processes, thereby improving outcomes for patients with leukemia and related disorders.
Introduction The differential ratio of nonsynonymous to synonymous nucleotide substitutions (dN/dS) is a common measure of the rate of structural evolution in proteincoding genes. In addition, we recently suggested that the proportion of transposable elements in gene promoters that host functional genomic sites serves as a marker of the rate of regulatory evolution of genes. Such functional genomic regions may include transcription factor binding sites and modified histone binding loci. Methods Here, we constructed a model of the human interactome based on 600,136 documented molecular interactions and investigated the overall relationship between the number of interactions of each protein and the rate of structural and regulatory evolution of the corresponding genes. Results By evaluating a total of 4,505 human genes and 1,936 molecular pathways we found a general correlation between structural and regulatory evolution rate metrics (Spearman 0.08–0.16 and 0.25–0.37 for gene and pathway levels, respectively, p < 0.01). Further exploration revealed in the established human interactome model lack of correlation between the rate of gene regulatory evolution and the number of protein interactions on gene level, and weak negative correlation (∼0.15) on pathway level. We also found a statistically significant negative correlation between the rate of gene structural evolution and the number of protein interactions (Spearman −0.11 and −0.3 for gene and pathway levels, respectively, p < 0.01). Discussion Our result suggests stronger structural rather than regulatory conservation of genes whose protein products have multiple interaction partners.
Abstract Background Transactional sex, which includes exchanging sex for material goods, services, or money, is a key HIV risk factor. Risk patterns associated with transactional sex among men who have sex with men (MSM) in Sweden, where buying sexual services is illegal, have not been examined earlier. This study aims to assess whether transactional sex (both buying and selling), country of birth, and migration-related factors (described by country of origin) are associated with self-reported HIV status among MSM in Sweden. Methods We analyzed secondary data from the 2017 European MSM Internet Survey (EMIS-2017), including participants reporting to live in Sweden (n = 4443). Using multivariate logistic regression analysis, we aimed to understand factors related to involvement in transactional sex and risk of HIV acquisition. Results Among the respondents, 5.4% reported living with HIV, with 8.8% of foreign-born MSM and 4.8% of Swedish-born MSM. The multivariable analysis showed that both selling and buying sex in the past five years increased the odds of reporting a positive HIV serostatus among all participants. Stratifying by transactional sex exposure and country of birth showed an HIV prevalence increase for all groups. Foreign-born selling or buying sex ever in the last five years had the highest prevalence of all groups (ranging from 17.8 to 19.1%). Other factors associated with a positive HIV status were age, outness, sex with a woman in the past twelve months, and condom use. Conclusions The relatively high reported HIV prevalence supports the need for HIV prevention, including the scale-up of access to pre-exposure prophylaxis to foreign-born MSM. A transparent discussion about risk factors and socioeconomic structures contributing to risk behaviors, including transactional sex, is needed. Key messages • Engaging in transactional sex increases the HIV risk among MSM in Sweden, particularly among foreign-born MSM. • HIV prevention needs to address the socioeconomic factors contributing to risky behaviors, such as transactional sex.
PurposeThe purpose of this study is to empirically examine the indirect effect of big data analytics capability (BDAC) on performance through innovativeness and risk-taking among small and medium-sized enterprises (SMEs) by considering the moderating role of absorptive capacity (ACAP).Design/methodology/approachThis study utilized a quantitative method through a survey questionnaire. The hypotheses were tested with a sample size of 202 surveys completed by SME owners. Partial least squares structural equation modeling (PLS-SEM) was administered to analyze data via the SmartPLS 4.0 software.FindingsThe analysis revealed that BDAC had an indirect effect on performance through innovativeness and risk-taking. ACAP strengthened the relationship between risk-taking and performance and also enhanced the link between BDAC and performance. Interestingly, ACAP weakened the connection between innovativeness and performance.Practical implicationsFrom a practical standpoint, our study offers valuable insights for entrepreneurs in the process of implementing BDAC. The mediating roles of innovativeness and risk-taking underscore their potential as drivers of SME performance. Also, it is crucial for managers to leverage lower-order capabilities (BDAC) to build higher-order organizational capabilities (innovativeness and risk-taking) and improve performance. Finally, managers are advised to utilize ACAP to identify external opportunities that contribute to performance.Originality/valueThe current study leverages the resource-based view (RBV) to provide new insights into the significance of innovativeness and risk-taking as key drivers to harness the benefits of BDAC for improving the performance of SMEs. Moreover, this study presents evidence of the moderating role of ACAP in the above relationships.
There is little knowledge about within- and between-referee variation (WBRV) in cardiovascular responses (CVR) and locomotor game demands (LMD). Thus, the primary aim of this study was to assess the WBRV of CVR and LMD in male basketball referees during elite international games in preparation [e.g., warm-up (WU) and re-warm-up (R-WU)] and active game phases. The secondary aim was to explore quarter-by-quarter differences in CVR and LMD. Thirty-five international male referees took part in this study (age, 40.4 ± 5.4 years; body height, 184.9 ± 5.7 cm; body weight, 85.1 ± 7.5 kg; BMI, 24.0 ± 1.7 kg × m−2; fat%, 18.8 ± 4.7% and VO2max, 50.4 ± 2.2 L × kg−1 × min−1. In total, 76 games (e.g., 228 officiating cases) were analyzed during the FIBA elite men’s competition. They officiated 4.5 games on average (range 3–9 games). Each referee used the Polar Team Pro system to measure CVR [e.g., heart rate (HR), time spent in different HR intensity categories] and LMD (e.g., distance covered, maximal and average velocity, and number of accelerations). Results showed that the referees had bigger WBRV during the active and preparation (e.g., W-U than R-WU) phase when variables of higher CVR and LMD intensity were observed (e.g., time spent at higher HR zones, distance covered in higher speed zones). The WBRV, CVR, and LMD were higher during WU than R-WU. Moreover, the referees had a lower CVR and LMD in the second half. In conclusion, the referees should establish and follow consistently a game-to-game preparation routine and attempt to spread their on-court preparation time equally within the crew. A half-time preparation routine should be improved to re-establish a sufficient activation level similar to that achieved in pre-game preparation.
Mathematics, along with reading and writing, is a core academic subject in the school curriculum. The development of mathematical skills is influenced by various cognitive factors, with executive functions (EF) playing a central role. EF, which encompasses working memory, inhibitory control, and cognitive flexibility, is critical for supporting complex cognitive processes required for problem-solving and mathematical reasoning. Research consistently shows that children with stronger EF tend to achieve better academic outcomes, including in mathematics. The goal of the present study was to examine the relationships between the global EF and its three core components - working memory, inhibitory control, and cognitive flexibility - and their impact on mathematics achievement. The sample for this study consisted of 180 children, aged 8-11 years (mean age: 9.6, SD: 1.0 year; 83 girls, 97 boys). EF was assessed using the Yellow-Red test, while mathematics achievement was evaluated based on teachers' evaluations of the child's mathematics performance. The results indicated a statistically significant effect of global EF and its three components on mathematics achievement. Given the potential malleability of EFs, we conclude with recommendations for strategies to enhance EF development at an early school age.
The ability to access physiologically driven signals, such as surface temperature, photochemical reflectance index (PRI), and sun-induced chlorophyll fluorescence (SIF), through remote sensing (RS) are exciting developments for vegetation studies. Accessing this ecophysiological information requires considering processes operating at scales from the top-of-the-canopy to the photosystems, adding complexity compared to reflectance index-based approaches. To investigate the maturity and knowledge of the growing RS community in this area, COST Action CA17134 SENSECO organized a Spatial Scaling Challenge (SSC). Challenge participants were asked to retrieve four key ecophysiological variables for a field each of maize and wheat from a simulated field campaign: leaf area index (LAI), leaf chlorophyll content ( C ab ), maximum carboxylation rate ( V cmax,25 ), and non-photochemical quenching (NPQ). The simulated campaign data included hyper-spectral optical, thermal and SIF imagery, together with ground sampling of the four variables. Non-parametric methods that combined multiple spectral domains and field measurements were used most often, thereby indirectly performing the top-of-the-canopy to photosystem scaling. LAI and C ab were reliably retrieved in most cases, whereas V cmax,25 and NPQ were less accurately estimated and demanded information ancillary to RS imagery. The factors considered least by participants were the biophysical and physiological canopy vertical profiles, the spatial mismatch between RS sensors, the temporal mismatch between field sampling and RS acquisition, and measurement uncertainty. Furthermore, few participants developed NPQ maps into stress maps or provided a deeper analysis of their parameter retrievals. The SSC shows that, despite advances in statistical and physically based models, the vegetation RS community should improve how field and RS data are integrated and scaled in space and time. We expect this work will guide new-comers and support robust advances in this research field.
The future of space exploration lies in cooperative autonomous systems. Ensuring their high-integrity remains a challenge. The Robust Software Engineering group at NASA Ames Research Center has been developing the Troupe project to explore the challenges with developing and assuring high-integrity of cooperative autonomous robotic systems. In particular, Troupe aims to develop a swarm of autonomous rovers capable of mapping unknown terrain, and assure their high-integrity using the advanced V&V tools developed in the group. In this paper, we present the evolution of the design of Troupe. We focus on the lessons learned in developing and assuring the rover swarm using core Flight System (cFS). In particular, we discuss the benefits and challenges in applying model-based development to develop the rover swarm.
Bluetooth’s LE Audio, particularly broadcast audio, is at the forefront of becoming the de facto standard for immersive audio applications in public venues. Nevertheless, the security of the transmitted audio data is solely based on a passkey (Broadcast_Code) shared between all (including possibly malicious) receiver devices, leaving many envisaged applications vulnerable to impersonation as well as denial-of-service attacks. In order to address these vulnerabilities, we present BACON, a novel Bluetooth core specification-compliant mechanism for the authentication of Broadcast Isochronous Groups (BIGs). Authenticated BIGs are able to provide data authenticity for broadcast isochronous streams as well as control subevents used to disseminate control information to all receiver devices in the communication range. With BACON, we are the first to outline a mechanism that protects against attacks on broadcast audio applications while being small enough to fit on resource-constrained devices thanks to the underlying protocol’s lightweight symmetric cryptography.
In the last ten years, social networks have appeared as main opinion-sharing and discussionenabling resources. At the same time, the development of machine learning (ML) and natural language processing (NLP) technologies has allowed for new approaches to analyzing the huge quantities of data created by users. This research uses data loading, class imbalance handling, text preprocessing and tokenization, sentiment analysis, and model assessment techniques to analyze the sentiment of the tweets. Using metrics like accuracy, precision, recall, and F1 score the study reveals that SVM and Logistic Regression are the most suitable machine-learning models for this purpose. SVM attained an accuracy of 90% for training and 77% for testing while Logistic Regression showed 83% for training and 78% for testing.
Background and Objectives: The primary objective of this study is to assess the effectiveness of 18F-FDG–PET–CT in preoperative staging of cervical cancer, focusing on determining surgical operability and exploring the correlation between its quantitative parameters and clinicopathological characteristics. Materials and Methods: This retrospective study included 62 cervical cancer patients treated at the Department of Gynecology, Clinic for Operative Oncology at the Institute of Oncology Vojvodina between January 2016 and January 2020, where preoperative clinical examinations and 18F-FDG–PET–CT were performed to assess the extent of cancer, followed by intraoperative and pathohistological examinations of surgically removed specimens to provide a comprehensive evaluation. Results: The mean tumor size measured by 18F-FDG–PET–CT was slightly greater than that obtained through clinical examination (26.4 mm vs. 26.0 mm), with a strong linear correlation (r = 0.678, p < 0.001) observed between the two measurement methods. The overall prediction accuracy of 18F-FDG–PET–CT for primary tumors is 88.7% (55/62) [sensitivity 86.8%, specificity 100.0%, PPV 100.0%, NPV 56.2%] and for intraoperative examination is 88.7% (55/62) [sensitivity 98.1%, specificity 33.3%, PPV 89.7%, NPV 75.0%]. The agreement with histopathological examination was good for 18F-FDG–PET–CT and moderate for intraoperative examination for primary tumors. Regarding lymph nodes, the overall prediction accuracy of 18F-FDG–PET–CT is 82.2% (51/62) [sensitivity 53.8%, specificity 89.8%, PPV 58.3%, NPV 88.8%] and for intraoperative examination 66.1% (41/62) [sensitivity 76.9%, specificity 63.3%, PPV 35.7%, NPV 91.2%]. The agreement with histopathological examination was moderate for 18F-FDG–PET–CT and poor for intraoperative examination for lymph node metastasis, highlighting that the overall accuracy of 18F-FDG–PET–CT (82.1%) was significantly higher than that of intraoperative examination (66.1%) (p = 0.002). Conclusions: In conclusion, 18F-FDG–PET–CT provides high accuracy in detecting primary tumors and superior predictive value for lymph node metastases compared to intraoperative examination, highlighting the importance of incorporating this imaging modality into the preoperative evaluation process to enhance diagnostic precision and inform treatment decisions.
The purpose of this paper is to explore how New York City is perceived as a tourist destination. The quantitative research method offered a structured approach to collecting data, allowing for the analysis and quantification of participant responses. The convenience sample consisted of 108 respondents. The aim of this study is to analyze the factors influencing both the attraction to and deterrence from visiting New York City as a tourist destination, as well as to gauge overall perceptions of the city among potential visitors. Through a comprehensive survey, key motivators such as iconic monuments, a vibrant cultural scene, and accessibility were identified as primary draws for tourists. Respondents expressed strong support for experiencing attractions like the Statue of Liberty and Broadway shows, highlighting the significance of cultural richness and unique architectural features. Conversely, the study also revealed significant barriers to visitation. The high cost of accommodation emerged as the most prominent deterrent, underscoring economic accessibility as a critical factor in tourism decision-making. Other concerns included congestion, security issues, and limited public transport options, which may dissuade potential visitors from traveling to the city. In terms of overall impressions, the results showed that a vast majority of respondents view New York City as an iconic and glamorous location with a diverse cultural landscape. Most participants expressed a willingness to recommend the city to friends and family, although a notable percentage exhibited reservations. Furthermore, the analysis emphasized the importance of affordable options for activities and attractions, suggesting that enhancing economic accessibility could positively influence visitation rates. Overall, the findings provide valuable insights for tourism agencies and local authorities. By addressing key concerns and highlighting the city's unique offerings, strategies can be developed to enhance New York City's appeal and accessibility, ultimately boosting its status as a leading tourist destination.
African swine fever virus (ASFV) is the etiological agent of African swine fever, a highly contagious hemorrhagic disease affecting both wild boars and domestic pigs with lethality rates up to 100%. Until now, the most effective measure to prevent an outbreak of ASFV was early detection. In this situation, whole genome sequencing (WGS) allows the gathering of detailed information about the identity and epidemiology of the virus. However, due to the large genome size and complex genome ends, WGS is challenging. Current WGS workflows require either elaborate enrichment methods or are based on tiled PCR approaches, which are susceptible to genetic differences between ASFV strains. To overcome this, we developed a novel approach for WGS of ASFV, using the Phi29 DNA polymerase-based multiple displacement amplification in combination with only seven primers. Furthermore, we applied an alkaline-based DNA denaturation step to significantly increase the number of viral reads, which resolves the near-full genome of ASFV. This novel isothermal WGS approach can be used in authorized laboratories for the genomic epidemiological analysis of ASFV outbreaks caused by different genotypes.
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