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1.
Methods Mol Biol ; 2847: 33-43, 2025.
Artículo en Inglés | MEDLINE | ID: mdl-39312135

RESUMEN

In silico design of artificial riboswitches is a challenging and intriguing task. Since experimental approaches such as in vitro selection are time-consuming processes, computational tools that guide riboswitch design are desirable to accelerate the design process. In this chapter, we describe the usage of the MODENA web server to design ON riboswitches on the basis of a multi-objective genetic algorithm and RNA secondary structure prediction.


Asunto(s)
Algoritmos , Biología Computacional , Conformación de Ácido Nucleico , Riboswitch , Programas Informáticos , Biología Computacional/métodos
2.
JMIR Pediatr Parent ; 7: e54051, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39231431

RESUMEN

BACKGROUND: Web-based self-help (WASH) has been found to be effective in the treatment of child externalizing behavior disorders. However, research on the associations of caregivers' use of WASH and symptom changes of child externalizing behaviors is lacking. OBJECTIVE: This study examined the longitudinal and reciprocal associations between the use of WASH by caregivers of children with externalizing behavior disorders and their children's externalizing behavior symptoms. METHODS: Longitudinal data of 276 families from 2 intervention conditions of a randomized controlled trial (either unguided or supported by a therapist over the phone) were analyzed. Caregiver- and clinician-rated child externalizing behavior symptoms were assessed before (T1), in the middle (T2), and after the 6-month WASH intervention (T3). Additionally, 2 indicators of the caregivers' use of the WASH intervention were considered: number of log-ins (frequency) and the percentage of completed material (intensity). Associations of caregivers' use during early (T1-T2) and late (T2-T3) treatment with child externalizing behavior symptoms were analyzed using path analyses (structural equation modeling). RESULTS: Frequency and intensity of use were higher during the first 3 months than during the next 3 months of the intervention period. The number of log-ins at early treatment was significantly but weakly associated with caregiver-reported child externalizing behavior symptoms in the long term (T3). Moreover, caregiver-reported child externalizing severity at T2 predicted the number of log-ins in the late treatment. The results were not replicated when considering the percentage of completed material as a measure of use or when considering clinician ratings of child externalizing behavior symptoms. CONCLUSIONS: The findings provide the first, albeit weak, evidence for longitudinal associations between caregivers' use of WASH and improvements in caregiver-rated child externalizing behavior symptoms. However, as the associations were rather weak and could not be replicated across different rater perspectives and operationalizations of use, further research is needed to better understand these relations and their interplay with other putative influence factors (eg, quality of the implementation of the interventions, changes in parenting behaviors). TRIAL REGISTRATION: German Clinical Trials Register DRKS00013456; https://www.drks.de/DRKS00013456. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12888-020-2481-0.

3.
J Sch Psychol ; 106: 101357, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39251313

RESUMEN

Many studies have indicated an alarming prevalence of anxiety among Chinese adolescents, highlighting the critical need for prevention protocols. DNA-V (Discoverer, Noticer, Advisor-Values model) is an adapted version of Acceptance and Commitment Therapy designed to prevent mental health problems in adolescents. This study investigated the effects and underlying mechanisms of DNA-V. The DNA-V prevention program was culturally adapted and optimized in both content and form specifically for Chinese adolescents, with the aim of reducing anxiety levels. A total of 139 participants (59 females) from six eighth-grade classes at an average middle school in Beijing were randomly assigned to one of three groups consisting of the DNA-V face-to-face group (two classes), the DNA-V web-based group (two classes), or the active control group (two classes). Adolescents' anxiety and cognitive fusion were measured before (Time 1), immediately after (Time 2), and 2 months after (Time 3) the program using the Chinese Secondary School Students Anxiety Scale (CSSSAS) and Cognitive Fusion Questionnaire (CFQ). Results showed that in the DNA-V face-to-face group, the anxiety score at Time 3 was significantly lower than the scores at Time 1 (p < .001, Cohen's drm = 0.56) and Time 2 (p = .043, Cohen's drm = 0.24). The cognitive fusion score at Time 3 was significantly lower than the scores at Time 1 (p = .001, Cohen's drm = 0.51) and Time 2 (p = .003, Cohen's drm = 0.37). The results of the study suggest that the DNA-V prevention program could serve as an effective tool for reducing anxiety in adolescents.


Asunto(s)
Ansiedad , Humanos , Adolescente , Femenino , Masculino , Ansiedad/psicología , China , Estudiantes/psicología , Terapia Cognitivo-Conductual/métodos , Pueblos del Este de Asia
4.
Sci Rep ; 14(1): 21048, 2024 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-39251684

RESUMEN

Controlled sediment flushing operations (CSFOs) allow to recover reservoirs storage loss while rebalancing the sediment flux interrupted by dams but, at the same time, may cause unacceptable ecological impact. In this study, we investigated the responses of the food web of an upland stream to a CSFO, focusing on the effects of fine sediment deposition detected in three different mesohabitats, i.e., a pool, a riffle, and a step-pool. The field campaign lasted two years and included repeated measurements of fine sediment deposits, and sampling of periphyton, benthic macroinvertebrates and fishes. A moderate and patchy deposition occurred due to the CSFO with short and medium-term ecological impact on the lower trophic levels of the food web, which may affect the whole ecosystem functioning. The monitoring of all available mesohabitats in the investigated stream allowed to detect variations in the ecological response to CSFO, providing a more adequate assessment of the impact. As expected, sedimentation was larger in the pool but, in contrast to our hypotheses, the impact was lower and the recovery was longer for the benthic organisms inhabiting the riffle. In the case of fishes, no lethal impact of both brown trout and bullhead was recorded in the short term but the occurrence of longer lasting effects could not be excluded. To date, this is one of the few studies dealing with a detailed integrative assessment of the downstream impact of sediment management from reservoir on both abiotic and biotic components of stream ecosystem.


Asunto(s)
Biota , Ecosistema , Sedimentos Geológicos , Ríos , Sedimentos Geológicos/análisis , Animales , Ríos/química , Peces/fisiología , Cadena Alimentaria , Monitoreo del Ambiente/métodos
5.
Ecol Evol ; 14(9): e70071, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39318529

RESUMEN

The relationship between phytophagous insects and plants is a central aspect of food webs and ecosystem functioning. The introduction of new species into an environment can have significant impacts on the food web of a native ecosystem. In many cases, there is a lack of knowledge on the biology and feeding behavior of invasive species prior their introduction and in the invaded regions. Gut content analyses of insects have provided valuable information on the host spectrum of insects. However, current approaches are time-consuming and costly. Here, we describe a new molecular gut content analysis (GCA) approach using the Oxford Nanopore (ONT) Flongle sequencing platform to characterize the plant DNA present in the gut of the highly polyphagous insect species Halyomorpha halys. We demonstrate that this technique efficiently amplifies and correctly identifies plant DNA in a mock community. We performed a feeding experiment to determine the sensitivity of this approach and to assess how long the plant DNA can be detected. All plants used in the feeding experiment were correctly identified and detected after 56 days. Surprisingly, we also detected various plant genera that were not included in the feeding experiment and thus were likely ingested months before the experiment. Our study suggests that the GCA using the ONT Flongle sequencing platform represents a rapid and cost-efficient diagnosis of the dietary preferences, host range, and the diversity of consumed plant species of pest insects with high precision.

6.
PNAS Nexus ; 3(9): pgae400, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39319324

RESUMEN

Large language models (LLMs) are a potential substitute for human-generated data and knowledge resources. This substitution, however, can present a significant problem for the training data needed to develop future models if it leads to a reduction of human-generated content. In this work, we document a reduction in activity on Stack Overflow coinciding with the release of ChatGPT, a popular LLM. To test whether this reduction in activity is specific to the introduction of this LLM, we use counterfactuals involving similar human-generated knowledge resources that should not be affected by the introduction of ChatGPT to such extent. Within 6 months of ChatGPT's release, activity on Stack Overflow decreased by 25% relative to its Russian and Chinese counterparts, where access to ChatGPT is limited, and to similar forums for mathematics, where ChatGPT is less capable. We interpret this estimate as a lower bound of the true impact of ChatGPT on Stack Overflow. The decline is larger for posts related to the most widely used programming languages. We find no significant change in post quality, measured by peer feedback, and observe similar decreases in content creation by more and less experienced users alike. Thus, LLMs are not only displacing duplicate, low-quality, or beginner-level content. Our findings suggest that the rapid adoption of LLMs reduces the production of public data needed to train them, with significant consequences.

7.
J Med Syst ; 48(1): 92, 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39322812

RESUMEN

Diabetes mellitus is called as the "pandemic of the era" due to its rising prevalence. Since it is a disease that affects all spheres of life, it has an impact on the quality of life of individuals. This systematic review aims to examine the effect of web-based diabetes training programmes prepared for individuals with type 2 diabetes mellitus on their quality of life. The PRISMA-P (Preferred Reporting Items for Systematic Review and Meta Analysis Protocols) flowchart was used in the literature search stage. A comprehensive search was performed through the [MeSH] keywords (Web-based Intervention, Randomised Controlled Trial, HRQOL, Type 2 Diabetes) until May 8, 2024 in databases of PubMed, Web of Science, Science Direct, Medline, CINAHL, EBSCO host, Cochrane Library, and Google Scholar. Zotero software program was used to identify duplications of the obtained studies. Seven randomised controlled studies were included in the review. It was found that, most of the studies that were included in review showed that quality of life did not cause any significant difference in the level of quality of life; whereas, improvement was observed in quality-of-life levels in all of the experimental groups. Also, studies conducted for 1.5 to 3 months showed that web-based training was effective in improving the quality of life. Consequently, it is recommended that web-based trainings be long enough to prevent patients from dropping out of training, with possibility of an online individual interview, and follow-up periods of 1.5 to 3 months in order to achieve effective results. PROSPERO Number: CRD42024530777.


Asunto(s)
Diabetes Mellitus Tipo 2 , Calidad de Vida , Humanos , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/psicología , Educación del Paciente como Asunto/métodos , Educación del Paciente como Asunto/organización & administración , Internet , Ensayos Clínicos Controlados Aleatorios como Asunto , Autocuidado , Intervención basada en la Internet
8.
JMIR Pediatr Parent ; 7: e56816, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39287603

RESUMEN

Background: Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disorder with no cure. Most children are prescribed several medications aimed at controlling disease activity, managing symptoms, and reducing pain. Physical activity is also encouraged to retain musculoskeletal function. The primary determinants of treatment success are maintaining long-term adherence, ongoing monitoring by a pediatric rheumatologist, and involvement of an interdisciplinary team. To support these goals, a new digital intervention was developed, InteractiveClinics, which aimed to prompt children to take their medications, report pain levels, and increase their physical activity. Objective: This study aims to evaluate the usability of InteractiveClinics among children with JIA. Methods: As part of this pediatric cross-sectional study, 12 children were asked to wear a smartwatch for 2 weeks, which was synchronized to the InteractiveClinics phone app and web-based platform. Personalized notifications were sent daily to the watch and phone, to prompt and record medication adherence and pain level assessment. Physical activity was automatically recorded by the watch. At the end of the study, all children and parents completed a postintervention survey. Written comments were also encouraged to gain further feedback. Descriptive statistics were used to summarize the survey results, and all qualitative data underwent thematic analysis. Results: Twelve children aged 10 to 18 years (mean 14.2, SD 3.1 years; female: n=8, 66.7%) and 1 parent for each child (n=12; female: n=8, 66.7%) were enrolled in the study. Based on the highest and lowest agreement areas of the survey, most children and parents liked the smartwatch and web-based platform; they found it easy to learn and simple to use. They were also satisfied with the pain and physical activity module. However, usability and acceptability barriers that hindered uptake were identified in the phone app and medication module. Children required a unique in-app experience, and their suggestive improvements included more personalization within the app; simplification by removing all links not relevant to antirheumatic medications; flexibility in response times; improved conferment through gamification; additional comment fields for the input of more data, such as medication side effects or pain-related symptoms; more detailed graphical illustrations of the physical activity module, including a breakdown of metrics; and importantly, interconnections between modules, because medication adherence, pain levels, and physical activity can each influence the other. They were, overall, improving usefulness for children and parents. Conclusions: The usability of InteractiveClinics was positive. Children and parents liked the watch and web-based platform and were satisfied with the pain and physical activity module. However, children wanted a unique in-app experience through more personalization, simplification, flexibility, conferment, comment fields, graphical illustrations, a breakdown of metrics, and interconnections. Certainly, inclusions are needed to promote user adoption and advancement of new validated digital health interventions in pediatric rheumatology, to support the delivery of integrated care.

9.
Environ Pollut ; 362: 124993, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39303937

RESUMEN

In order to understand the transfer of macroelements and toxic metals in the terrestrial food web, barn swallows, terrestrial frogs, and insects were collected from farmlands in the Leizhou Peninsula, and analyzed for macroelements carbon (C), nitrogen (N), phosphorus (P), and sulfur (S) and trace metals nickel (Ni), zinc (Zn), selenium (Se), copper (Cu), chromium (Cr), cadmium (Cd), lead (Pb), and mercury (Hg). The multi-element ecological stoichiometry was discussed to trace the food web flow of nutrients and toxicants. The percentage contents of C, N, P, and S were 35.43-59.91%, 6.89-12.11%, 0.49-4.66%, and 0.44-2.19%, respectively. The concentrations of Ni, Zn, Se, Cu, Cr, Cd, Pb, and Hg were 0.163-116 mg/kg, 38.7-227 mg/kg, 0.0453-3.82 mg/kg, 3.11-141 mg/kg, not detected-79.6 mg/kg, 0.0203-0.358 mg/kg, 0.148-4.57 mg/kg, and 0.00159-1.46 mg/kg, respectively. Organisms at high trophic levels had higher contents of N, P, and S, and lower contents of C. Significant correlations were observed between δ15N and ratios of C: N, C: P, C: S, N: P, N: S, and S: P, indicating selective transfer of biogenic elements for predators in the terrestrial food web. Most metals including Ni, Zn, Se, Cu, Cr, Pb, and Hg had biomagnification factors and trophic magnification factors higher than 1, because the whole body of organisms rather than tissues were used. The negative correlations between the detoxification ratios of Se: X (each toxic metal) and metal concentrations suggest potential adverse effect of metals on terrestrial organisms.

10.
EClinicalMedicine ; 76: 102834, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39328810

RESUMEN

Background: It is estimated that ∼60% of people with Alzheimer's disease (AD) are undetected or undiagnosed, with higher rates of underdiagnosis in low-to middle-income areas with limited medical resources. To promote health equity, we have developed a web-based tool that utilizes easy-to-collect clinical data to enhance AD detection rate in primary care settings. Methods: This study was leveraged on the data collected from participants of the Australian Imaging, Biomarker & Lifestyle (AIBL) study and the Religious Orders Study and Memory and Aging Project (ROSMAP). The study included three phases: (1) constructing and evaluating a model on retrospective cohort data (1407 AIBL participants), (2) performing simulated trials to assess model accuracy (30 AIBL participants) and missing data tolerability (30 AIBL participants), and (3) external evaluation using a non-Australian dataset (500 ROSMAP participants). The auto-score machine learning algorithm was employed to develop the Florey Dementia Risk Score (FDRS). All the simulated trials and evaluation were performed using a web-based FDRS tool. Findings: FDRS achieved an area under the curve (AUC) of approximately 0.82 [95% CI, 0.75-0.88], with a sensitivity of 0.74 [0.60-0.86] and a specificity of 0.73 [0.70-0.79]. The accuracy of the simulated pilot trial for 30 AIBL participants with complete record was 87% (26/30 correct), while it only slightly decreased (80.0-83.3%, depending on imputation methods) for another 30 AIBL participants with one or two missing data. FDRS achieved an AUC of 0.82 [0.77-0.86] of 500 ROSMAP participants. Interpretation: The FDRS tool offers a potential low-cost solution to AD screening in primary care. The present study warrants future trials of FDRS for optimization and to confirm its generalizability across a more diverse population, especially people in low-income countries. Funding: National Health and Medical Research Council, Australia (GNT2007912) and Alzheimer's Association, USA (23AARF-1020292).

11.
Gigascience ; 132024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-39320317

RESUMEN

BACKGROUND: Antimicrobial resistance is a serious threat to global health. Due to the stagnant antibiotic discovery pipeline, bacteriophages (phages) have been proposed as an alternative therapy for the treatment of infections caused by multidrug-resistant pathogens. Genomic features play an important role in phage pharmacology. However, our knowledge of phage genomics is sparse, and the use of existing bioinformatic pipelines and tools requires considerable bioinformatic expertise. These challenges have substantially limited the clinical translation of phage therapy. FINDINGS: We have developed PhageGE (Phage Genome Explorer), a user-friendly graphical interface application for the interactive analysis of phage genomes. PhageGE enables users to perform key analyses, including phylogenetic analysis, visualization of phylogenetic trees, prediction of phage life cycle, and comparative analysis of phage genome annotations. The new R Shiny web server, PhageGE, integrates existing R packages and combines them with several newly developed functions to facilitate these analyses. Additionally, the web server provides interactive visualization capabilities and allows users to directly export publication-quality images. CONCLUSIONS: PhageGE is a valuable tool that simplifies the analysis of phage genome data and may expedite the development and clinical translation of phage therapy. PhageGE is publicly available at https://jason-zhao.shinyapps.io/PhageGE_Update/.


Asunto(s)
Bacteriófagos , Genoma Viral , Programas Informáticos , Bacteriófagos/genética , Genómica/métodos , Biología Computacional/métodos , Internet , Filogenia
12.
Water Res ; 267: 122487, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39321727

RESUMEN

Biofilms, essential for material circulation and energy flow in aquatic ecosystems, markedly enrich heavy metals in water environments. However, the impact of these accumulated metals on organisms feeding on biofilms remains poorly unknown. This study involved a year-long seasonal survey along the Bijiang River, located next to Asia's largest lead (Pb)-zinc (Zn) mine, conducted to investigate the role of biofilms in nutrient and metal transfer in food webs. In total, 355 biotic and abiotic samples, including water, biofilms, and aquatic biota, were analyzed for the presence of eight heavy metals (arsenic [As], cadmium, chromium, copper, Pb, nickel, Zn, and iron) as well as stable carbon (δ13C) and nitrogen (δ15N) isotopes. Wide ranges of δ13C and δ15N values indicated diverse dietary carbon sources and trophic positions in the Bijiang River (maximum trophic level: 4.28). A Bayesian mixing model revealed that periphytic biofilms were the dominant basal carbon source, especially in spring, whereas in summer, consumers exploited more diverse food sources, possibly because feeding on spring biofilms enhanced predator feeding efficiency. Metals tended to be biodiluted along food chains owing to their higher concentrations in biofilms and benthic organisms as well as their chemical forms. Although diet did not significantly affect heavy metal accumulation in fish, those relying on biofilms as the main carbon source showed significantly higher As (p = 0.048) and Pb (p = 0.007) levels compared with those relying on C4 plants. Overall, this study highlights the critical role of periphytic biofilms in nutrient and metal dynamics in aquatic food webs.

13.
Protein Sci ; 33(10): e5147, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39276018

RESUMEN

Alzheimer's disease (AD) is one of the most common forms of dementia and neurodegenerative diseases, characterized by the formation of neuritic plaques and neurofibrillary tangles. Many different proteins participate in this complicated pathogenic mechanism, and missense mutations can alter the folding and functions of these proteins, significantly increasing the risk of AD. However, many methods to identify AD-causing variants did not consider the effect of mutations from the perspective of a protein three-dimensional environment. Here, we present a machine learning-based analysis to classify the AD-causing mutations from their benign counterparts in 21 AD-related proteins leveraging both sequence- and structure-based features. Using computational tools to estimate the effect of mutations on protein stability, we first observed a bias of the pathogenic mutations with significant destabilizing effects on family AD-related proteins. Combining this insight, we built a generic predictive model, and improved the performance by tuning the sample weights in the training process. Our final model achieved the performance on area under the receiver operating characteristic curve up to 0.95 in the blind test and 0.70 in an independent clinical validation, outperforming all the state-of-the-art methods. Feature interpretation indicated that the hydrophobic environment and polar interaction contacts were crucial to the decision on pathogenic phenotypes of missense mutations. Finally, we presented a user-friendly web server, AlzDiscovery, for researchers to browse the predicted phenotypes of all possible missense mutations on these 21 AD-related proteins. Our study will be a valuable resource for AD screening and the development of personalized treatment.


Asunto(s)
Enfermedad de Alzheimer , Mutación Missense , Enfermedad de Alzheimer/genética , Humanos , Aprendizaje Automático , Biología Computacional/métodos , Programas Informáticos , Conformación Proteica
14.
bioRxiv ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39282403

RESUMEN

The advent of cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET), coupled with computational modeling, has enabled the creation of integrative 3D models of viruses, bacteria, and cellular organelles. These models, composed of thousands of macromolecules and billions of atoms, have historically posed significant challenges for manipulation and visualization without specialized molecular graphics tools and hardware. With the recent advancements in GPU rendering power and web browser capabilities, it is now feasible to render interactively large molecular scenes directly on the web. In this work, we introduce Mesoscale Explorer, a web application built using the Mol* framework, dedicated to the visualization of large-scale molecular models ranging from viruses to cell organelles. Mesoscale Explorer provides unprecedented access and insight into the molecular fabric of life, enhancing perception, streamlining exploration, and simplifying visualization of diverse data types, showcasing the intricate details of these models with unparalleled clarity.

15.
J Stroke Cerebrovasc Dis ; 33(11): 108010, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39277066

RESUMEN

BACKGROUND: Carotid web is a thin shelf-like fibrointimal membrane arising from the posterior or posterolateral wall of the carotid bulb. Webs cause stroke, especially in younger adults with high risk of recurrence. METHODS: To report the first case of de-novo formation of an asymptomatic carotid web and describe longitudinal clinical-angiographic follow-up. RESULTS: A previously healthy 50-year-old White female presented with acute vestibular syndrome. Brain MRI showed no brain infarction. An arch-to-vertex CT angiogram showed normal posterior circulation, however, the left internal carotid artery bulb had a thin shelf-like projection into the lumen arising from the posterior wall of the artery - an incidental carotid web. A CT angiogram performed seven years earlier showed normal carotid arteries. The three-year angiographic follow-up showed an unchanged angiographic appearance of the carotid web. The patient preferred staying on aspirin and suffered no retinal or cerebral ischemic event during the 5-year clinic follow-up. CONCLUSION: Our case suggests de novo (acquired) formation of a carotid web in an adult. This challenges the prevailing theory that carotid web is a congenital/developmental lesion.

16.
Quant Imaging Med Surg ; 14(9): 6386-6396, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39281137

RESUMEN

Background: Congenital duodenal obstruction (CDO) is commonly detected antenatally through the presence of the "double bubble" sign on prenatal ultrasound, denoting dilatation of the stomach and duodenum. Subsequent postnatal ultrasonography plays a pivotal role in determining the causes of obstruction, thereby informing surgical strategies and neonatal management. The aim of this study was to investigate the diagnostic accuracy of postnatal ultrasonography in comparison to that of prenatal ultrasound and surgical findings in a cohort of 43 patients with fetal double bubble sign. Methods: A total of 43 patients, comprising 24 males and 19 females, who exhibited double bubble sign on prenatal ultrasound were subjected to postnatal ultrasound assessment at a tertiary care facility during the 2018-2023 period. The accuracy of both pre-and postnatal ultrasonography in the identification and diagnosis of CDO, as well as its underlying causes, was compared to that of the established gold standard of surgical findings. Results: The accuracy rates for prenatal and postnatal ultrasonic diagnosis of CDO were 97.7% (42/43) and 100% (42/42), respectively. In terms of etiological diagnosis, prenatal and postnatal ultrasound correctly identified the causes of obstruction in 45.2% (19/42) and 81.0% (34/42) of cases, respectively, as confirmed by surgical intervention. Conclusions: The presence of the prenatal double bubble sign serves as a highly reliable indicator for CDO. Additionally, postnatal ultrasonography proved to be a valuable tool in refining the diagnosis and determining the underlying causes of obstruction in neonates.

17.
Mol Ther Nucleic Acids ; 35(3): 102303, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39281703

RESUMEN

Mature microRNAs (miRNAs) are short, single-stranded RNAs that bind to target mRNAs and induce translational repression and gene silencing. Many miRNAs discovered in animals have been implicated in diseases and have recently been pursued as therapeutic targets. However, conventional pharmacological screening for candidate small-molecule drugs can be time-consuming and labor-intensive. Therefore, developing a computational program to assist mature miRNA-targeted drug discovery in silico is desirable. Our previous work (https://doi.org/10.1002/advs.201903451) revealed that the unique functional loops formed during Argonaute-mediated miRNA-mRNA interactions have stable structural characteristics and may serve as potential targets for small-molecule drug discovery. Developing drugs specifically targeting disease-related mature miRNAs and their target mRNAs would avoid affecting unrelated ones. Here, we present SMTRI, a convolutional neural network-based approach for efficiently predicting small molecules that target RNA secondary structural motifs formed by interactions between miRNAs and their target mRNAs. Measured on three additional testing sets, SMTRI outperformed state-of-the-art algorithms by 12.9%-30.3% in AUC and 2.0%-18.4% in accuracy. Moreover, four case studies on the published experimentally validated RNA-targeted small molecules also revealed the reliability of SMTRI.

18.
PeerJ ; 12: e17912, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39282123

RESUMEN

The increasing frequency and intensity of heatwaves driven by climate change significantly impact microbial communities in freshwater habitats, particularly eukaryotic microorganisms. Heterotrophic nanoflagellates are important bacterivorous grazers and play a crucial role in aquatic food webs, influencing the morphological and taxonomic structure of bacterial communities. This study investigates the responses of three flagellate taxa to heatwave conditions through single-strain and mixed culture experiments, highlighting the impact of both biotic and abiotic factors on functional redundancy between morphologically similar protist species under thermal stress. Our results indicate that temperature can significantly impact growth and community composition. However, density-dependent factors also had a significant impact. In sum, stabilizing effects due to functional redundancy may be pronounced as long as density-dependent factors play a minor role and can be overshadowed when flagellate abundances increase.


Asunto(s)
Agua Dulce , Agua Dulce/parasitología , Cambio Climático , Calor/efectos adversos , Ecosistema
20.
Ecotoxicol Environ Saf ; 285: 117032, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39299214

RESUMEN

Contamination of aquatic food webs with nanomaterials poses a significant ecological and human health challenge. Ingestion of nanomaterials alongside food disrupts digestion and impairs physiological processes, with potential consequences for organism fitness and survival. Complex interactions between nanomaterials and biota further exacerbate the issue, influencing life-history strategies and ecosystem dynamics. Accumulation of nanomaterials within autotrophic and detritus-based food webs raises concerns about biomagnification, especially for top-level consumers and seafood-dependent human populations. Understanding the extent and impact of nanomaterial contamination on aquatic biota is crucial for effective mitigation strategies. To address this challenge, we conducted a comprehensive study evaluating the bioaccumulation effects of graphene oxide (GO), a commonly used nanomaterial, within an aquatic food chain. Using a gnotobiotic freshwater microcosm, we investigated the effects of micro- and nano-scale GO sheets on key organisms: green algae (Chlorella vulgaris), brine shrimp (Artemia salina), and zebrafish (Danio rerio). Two feeding regimes, direct ingestion and trophic transfer, were employed to assess GO uptake and transfer within the food web. Direct exposure involved individual organisms being exposed to either nano- or micro-scale GO sheets, while trophic transfer involved a sequential exposure pathway: algae exposed to GO sheets, artemias feeding on the algae, and zebrafish consuming the artemias. Our study provides critical insights into nanomaterial contamination in aquatic ecosystems. Physicochemical properties of GO sheets, including ζ-potential and dispersion, were influenced by salt culture media, resulting in aggregation under salt conditions. Microscopic imaging confirmed the bioaccumulation of GO sheets within organisms, indicating prolonged exposure and potential long-term effects. Notably, biodistribution analysis in zebrafish demonstrated the penetration of nano-sized GO into the intestinal wall, signifying direct interaction with vital organs. Exposure to GO resulted in increased zebrafish mortality and impaired reproductive performance, particularly through trophic transfer. These findings emphasize the urgent need to address nanomaterial contamination in aquatic food webs to protect ecosystem components and human consumers. Our study highlights the importance of developing effective mitigation strategies to preserve the integrity of aquatic ecosystems, ensure resource sustainability, and safeguard human well-being. In conclusion, our study provides crucial insights into the impact of nanomaterial pollution on aquatic biota. By recognizing the challenges posed by nanomaterial contamination and implementing targeted interventions, we can mitigate the adverse effects, preserving the integrity of aquatic ecosystems and safeguarding human health.

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