Category: 8. Health

  • Purdue Maps Gene-Inserting Transpososome for Editing

    Purdue Maps Gene-Inserting Transpososome for Editing

    More than a decade ago, scientists harnessed a bacterial molecular machine that identifies and cuts specific sections of DNA, revolutionizing the ability to edit genes and accelerating research into treatments for all manner of diseases with a genetic link. But the technology known as CRISPR-Cas9 works by cutting DNA, not moving it. At Purdue University, researchers are investigating a similar molecular machine that moves so-called “jumping genes” into new locations in bacterial DNA, laying the groundwork for a more powerful gene-editing tool.

    The team, led by Leifu Chang, a Purdue associate professor of biological sciences, has produced high-resolution structural snapshots of the Tn7-like transpososome, a complex of nucleic acids and proteins that can accurately cut and paste an entire gene from one location to another in the genome of a cell. This structural information is analogous to an exploded parts diagram for an engine, showing all the parts in atomic-level detail and how they work together. In a pair of papers published in the journal Cell in 2023 and 2024, the team captured the structure of all the components needed to understand how the molecular machine recognizes a jumping gene and the location in the genome where it will insert that gene.

    “We’ve captured all the components that are really essential in this structure. This is a quite complicated process, requiring recognition of specific DNA in the gene and in the target and, while previous research has shown many partial structures, it’s important to see the whole picture,” said Chang, a member of the Purdue Institute for Cancer Research. “We’re providing a lot of information to understand how that process happens.”

    Chang’s research is part of Purdue’s presidential One Health initiative, which involves research at the intersection of human, animal and plant health and well-being.

    There are many similarities between the Tn7-like transpososome and the CRISPR system. CRISPR, which evolved as part of a bacterial defense system against known viral invaders, identifies and stores snippets of DNA from invaders between DNA brackets in a pattern called “clustered regularly interspersed short palindromic repeats,” hence CRISPR. Using the stored DNA as a template, the system generates an RNA mirror image of the viral DNA and surveils the cell looking for a match. When a match is made and an invader identified, a protein cuts the DNA of the viruses, blocking replication. The beauty of the system, from the standpoint of researchers, is that it uses RNA — a molecule easily synthesized in a lab — to identify and target DNA. By synthesizing an RNA snippet that searches for its own targets, researchers can use the system to snip DNA with precision.

    But while CRISPR is great at what it does in bacteria, Chang said, it’s not a one-stop gene editing tool in human cells. For starters, cutting DNA in humans triggers a DNA repair pathway that could undo the cut or unintentionally introduce a mutation as part of the repair. Also, once the DNA is cut, it might not be repaired in which case the cell would die. Researchers have devised various workarounds, but they aren’t yet efficient and only work in dividing cells, putting repairs to cells that don’t divide, like neurons, out of reach.

    By contrast, the transpososome is a complete package that includes the machinery for inserting genes. The transpososome facilitates the movement of transposons, or “jumping genes,” that can be copied and moved to different locations in the genome. Jumping genes make up about half of the genome in animal cells, including in humans, and are believed to increase genetic diversity.

    “In general, breaking DNA to achieve genome editing is not ideal,” Chang said. “The transposon system is a more efficient approach because the proteins insert DNA seamlessly, so that avoids the harmful consequence of breaking DNA.”

    Scientists who study the Tn7-like transpososome have discovered two pathways that it uses to find its target. The first uses a protein to directly recognize specific DNA sequences. The second is similar to CRISPR-Cas9, in that it uses a snippet of RNA as a guide to find the target. Chang, who is an expert in CRISPR-Cas systems, is interested in understanding how the CRISPR-type pathways work.

    The two Cell papers taken together present complete cryo-electron microscopy structures of essential components in atom-by-atom detail. The structures show the point at which DNA attaches to two proteins, which triggers formation of the entire transpososome complex, and initiate transposition. As the 2024 paper states, “The findings provide mechanistic insights into targeted DNA insertion by Tn7-like transposons with implications for improving the precision and efficiency of their genome-editing applications.”

    Chang said researchers are already trying to use the Tn7-like transpososome to edit animal cells but, so far, the process isn’t effective. While much work needs to be done to arrive at systems useful in nonbacterial cells, the full structural information he has provided will accelerate that work.

    References: 

    1. Wang S, Gabel C, Siddique R, Klose T, Chang L. Molecular mechanism for Tn7-like transposon recruitment by a type I-B CRISPR effector. Cell. 2023;186(19):4204-4215.e19. doi: 10.1016/j.cell.2023.07.010

    2. Wang S, Siddique R, Hall MC, Rice PA, Chang L. Structure of TnsABCD transpososome reveals mechanisms of targeted DNA transposition. Cell. 2024;187(24):6865-6881.e16. doi: 10.1016/j.cell.2024.09.023

    This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source. Our press release publishing policy can be accessed here.

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  • MIT Creates AI Tool to Improve Flu Vaccine Predictions – AI Business

    1. MIT Creates AI Tool to Improve Flu Vaccine Predictions  AI Business
    2. Influenza vaccine strain selection with an AI-based evolutionary and antigenicity model  Nature
    3. AI model predicts flu vaccine strains more accurately than WHO  News-Medical
    4. AI tool enhances flu vaccine strain selection  Medical Xpress
    5. MIT’s VaxSeer AI Aims to Revolutionize Flu Shot Selection, Outsmarting Viruses with Predictive Power  Hoodline

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  • Mapping Severe Child Nomophobia with Hierarchical Clustering and ROC

    Mapping Severe Child Nomophobia with Hierarchical Clustering and ROC

    Introduction

    Smartphones are ubiquitous in modern urban life, providing instant access to information, social networks, and diverse applications.1,2 This shift has fostered global connectivity, linking geographically distant individuals.3 However, alongside these benefits, excessive smartphone use is increasingly tied to adverse physical and mental health outcomes.4–6 One emerging concern is nomophobia— defined as the fear, anxiety, nervousness, or anguish experienced when being without a mobile phone or unable to use it.4,7–9 This construct encompasses four dimensions in adults: fear of not being able to communicate, fear of losing connectedness, fear of not being able to access information, and fear of giving up convenience.2,10 Nomophobia is now considered a potential public health challenge in our hyper-connected age.4,8,11 Prevalence estimates for nomophobia vary widely, from 6% to nearly 99%, reflecting diverse cultural contexts and methodological inconsistencies.8–15 Research has largely centered on older adolescents and university students, with some studies reporting mild, moderate, and severe nomophobia rates of 24%, 56%, and 17%, respectively.4,15–184,16–20 In contrast, research on younger children aged 9–13 is scarce.21 While two studies have included pre-adolescents within broader age ranges (10–19 years),22,23 their focus was not specifically on this developmentally distinct population. To date, only the study by López et al21 has specifically examined this age group using the validated Nomophobia Questionare for Children (NQC). This research gap is concerning given the evidence linking nomophobia to anxiety, stress, poor sleep and impaired school performance.4,10 Furthermore,24 nomophobia may induce a profound shift in developmental attachment,19 where the smartphone could supplant the role of parental figures, producing a qualitatively deeper impact in children. This dependency also disrupts school functioning by affecting attention and behaviour.

    This research gap is particularly relevant in Spain, where 69.6% of 10–15-year-olds regularly use smartphones.25 Urban children often gain access early, frequently with limited supervision, raising concerns about maladaptive habits.21,26–28 Given their developmental vulnerability, owing to immature executive functions and heightened sensitivity to social rewards, pre-adolescents may be especially susceptible to technology’s negative effects.26,27 Identifying severe nomophobia—beyond mild or moderate levels—could thus be key to prioritizing prevention and intervention efforts to mitigate disruptions in social functioning and academic achievement.This study builds on the pioneering work of López et al in 2023,21 which developed the NQC to assess nomopobia in children aged 9–13, by applying advanced classification techniques to establish severity thresholds. Unlike traditional percentile-based or arbitrary cutoffs, we employ hierarchical clustering and ROC analysis to empirically derive classifications. To address this, we examine nomophobia among Spanish children aged 9–13 in urban settings, where smartphone access is near-universal.8,21 Using hierarchical clustering and Receiver Operating Characteristic (ROC) analysis, we pursue two aims: (1) to estimate nomophobia severity in this cohort, and (2) to establish a conservative, data-driven cutoff for severe risk, validated against state anxiety and phone exposure duration. This binary threshold seeks to pinpoint a vulnerable minority—found to be ~5% in our sample, a prevalence that, while lower than in older groups, is clinically significant given the developmental risks and potential for early intervention—offering educators, parents, and clinicians a practical tool to detect when smartphone-related anxiety signals a need for support. This aligns with calls to curb problematic digital dependencies early.8

    Methods

    Study Design

    This cross-sectional, observational study employed an ex post facto design to identify and validate severity thresholds for nomophobia among Spanish children aged 9–13. The study utilized a quantitative approach combining hierarchical clustering and Receiver Operating Characteristic (ROC) analysis to empirically derive clinically meaningful cutoff scores.

    Setting and Participants

    The study was conducted in seven urban primary schools (Madrid, Valladolid, Ávila, cities with populations >50,000), López et al, 2023) between February and April 2024. The target population comprised all Spanish children aged 9–13 attending primary education in urban settings where smartphone exposure is widespread.

    Sampling Method

    We employed a two-stage convenience sampling approach. First, schools were selected based on geographic accessibility and administrative willingness to participate. Second, all students aged 9–13 within participating schools were invited to participate, yielding 1233 initial respondents.

    Inclusion Criteria

    (1) Age 9–13 years, (2) weekly smartphone use, (3) ability to complete questionnaires in Spanish, and (4) parental consent.

    Final Sample

    After excluding one participant with an invalid response pattern (all items scored ‘4’), the analytical sample comprised 1153 children. Table 1 presents detailed demographic characteristics.

    Table 1 Participant Demographics (N=1153)

    Sample Size Justification

    Post-hoc power analysis indicated favorable statistical power (>0.99) to detect the observed effect size (Cohen’s d = 2.87) between nomophobia severity clusters, confirming adequate sample size for the primary analyses.

    Measures

    Nomophobia Questionnaire for Children (NQC)

    1. The Spanish child-specific adaptation Nomophobia Questionnaire for Children (NQC) by21 was employed. This 32-item inventory captures psychological (emotional regulation and dependency), social (social connectivity), and biological (physiological and behavioral symptoms) elements of nomophobia (eg, “I get anxious if I can’t use my phone when I want”). Each item is scored on a 5-point Likert scale (1 = “Strongly disagree”, 5 = “Strongly agree”), yielding possible total scores between 32 and 160. Higher values indicate greater nomophobia severity. In the current sample, the NQC demonstrated excellent internal consistency (Cronbach’s alpha = 0.91), supporting its reliability for assessing nomophobia in Spanish children.

    Anxiety Assessment

    1. The State-Trait Anxiety Inventory for Children (STAIC) measured situational anxiety via its 20-item State Anxiety subscale, delivered online. Scores sum reverse-coded positive items (eg, “I feel calm”) and negative items (eg, “I feel nervous”), ranging from 20–60, with higher scores indicating greater anxiety. The STAIC showed good internal consistency in this study (Cronbach’s alpha = 0.847), confirming its adequacy for evaluating anxiety in this population.

    Demographic and Smartphone Usage Variables

    1. Age and sex were documented, along with children’s approximate daily smartphone usage (daily/weekend/weekdays) and years since first phone ownership to contextualize phone-exposure levels.

    Procedures

    This quantitative, cross-sectional study employed an ex post facto design. School directors were contacted to secure collaboration, highlighting nomophobia prevention through understanding children’s smartphone use. Data collection occurred from February to April 2024, with the research team visiting participating schools. Children completed questionnaires online via Google Forms in the classroom under supervision, ensuring standardized administration. Participants and parents were informed of the study’s aims, provided digital consent through the platform, and could withdraw without consequence. Data confidentiality and anonymity adhered to the Helsinki protocol. The study was approved by the Research Ethics Committee of Universidad San Pablo CEU (code 431/20/25).

    Data Collection

    Following ethics approval, school directors were contacted and provided with study information emphasizing nomophobia prevention benefits. Upon agreement, information sheets and consent forms were distributed to parents two weeks before data collection.

    Data collection occurred during regular school hours in computer laboratories. The research team administered questionnaires via Google Forms under standardized conditions. Team members remained present throughout the 20–30 minute session to clarify item wording without influencing responses. Children could withdraw at any time without consequence. All responses were anonymous, identified only by numerical codes.

    Statistical Analysis

    Analyses were conducted in R (version 4.4.2). Online responses were cleaned, excluding one outlier (NQC=128, all ‘4’s). Descriptive statistics (means, SDs, frequencies) summarized NQC and STAIC State Anxiety scores.

    1. Cluster-Based Identification of Severe-Risk Nomophobia.

    1. Hierarchical clustering used the agnes algorithm (R package cluster) with complete linkage and Euclidean distances on NQC scores. The optimal number of clusters was determined through:

    1. Visual inspection of the dendrogram for clear separation points.

    2. Silhouette analysis to assess cluster cohesion and separation (k=2: silhouette width=0.317).

    3. Elbow method examining within-cluster sum of squares across solutions.

    1. These methods converged on a two-cluster solution, labeled “Low-to-Moderate Nomophobia” (96.88%, n=1117) and “Severe Nomophobia” (3.12%, n=36) based on mean scores.

    2. ROC-Derived Cutoff Criterion

    1. A ROC analysis (using the pROC package) was performed to refine the classification boundaries. Cluster membership (Severe vs Low-to-Moderate Nomophobia) served as the reference, while the continuous NQC total score was the predictor.
    2. Multiple thresholds were examined, with the final cutoff chosen based on maximizing specificity and Youden’s index. This approach aimed to correctly flag only those likely to experience impactful nomophobia-related impairments. The cutoff (101.5) achieved AUC=0.993, sensitivity=0.889, and specificity=0.979, weighted by severe-cluster prevalence (3.12%), using the “closest.topleft” method.

    3. Inferential Statistics and Validity Checks

    • Between-Group Comparisons: Independent-samples t-tests compared STAIC State Anxiety between severe- vs low-to-moderate-nomophobia groups (NQC ≥ 101.5 vs < 101.5). Cohen’s d provided effect sizes for group differences.
    • Sex Differences: Additional t-tests assessed whether boys and girls differed in NQC total scores.
    • Correlational Analyses: Pearson’s correlations determined how NQC total scores related to STAIC State Anxiety, aligning with reports that nomophobia correlates with various anxiety indicators.
    • Statistical significance was set at p <.05 throughout.

    Ethical Considerations and Funding

    This study was a multi-center collaboration involving researchers from several institutions. To streamline the ethical review process, all procedures were submitted to the Research Ethics Committee of Universidad San Pablo CEU, which agreed to serve as the central approving body. The study adhered to the ethical standards of San Pablo CEU University Research Ethics Committee (CEINDO, approval code: 431/20/25) and complied with Spanish regulations for research involving minors. Each child’s anonymity and the right to withdraw were firmly upheld. No external grants supported this research, and the authors declare no conflicts of interest. The authors acknowledge the collaboration of participating schools, educators, families, and other administrative staff in enabling data collection. This study with file number 11172/2024, has received funding from the Call For Research Grants On Avila Topics (Gran Duque de Alba), 2024 (general modality and young researchers).

    Results

    Hierarchical Clustering

    Using complete-linkage hierarchical clustering on total Nomophobia Questionnaire for Children (NQC) scores, a two-cluster solution was visually identified from the dendrogram (Figure 1). One large cluster (“Low-to-Moderate Nomophobia”) and a much smaller, distinct cluster (“Severe Nomophobia”) emerged, suggesting a clear separation in nomophobia severity (Figure 1). Additionally, silhouette analysis (k=2: silhouette width=0.317) and the elbow method confirmed that two clusters were the best option for this cohort.

    Figure 1 Hierarchical clustering dendrogram of total Nomophobia Questionnaire for Children (NQC) scores. Two distinct clusters are evident, with most participants in the low‐to‐moderate group (blue) and a smaller subset in the severe group (Orange).

    Descriptive Statistics by Cluster

    Table 2 summarizes each cluster’s characteristics. The Low-to-Moderate Nomophobia cluster accounted for 96.88% of the sample (n = 1117), displaying a mean NQC score of 65.29 (SD = 17.28). By contrast, the Severe Nomophobia cluster comprised 3.12% (n = 36) with an elevated mean NQC score of 114.61 (SD = 12.71). A Welch’s t-test (t = −19.92, df ≈ 37, p <.001) indicated the difference between these two groups was highly significant and represented a large effect size (Cohen’s d = 2.95). The distribution of the NQC scores in both populations can be visualized in Figure 2.

    Table 2 Main Two Clusters Identified via Hierarchical Clustering on Total Nomophobia Questionnaire for Children (NQC) Scores

    Figure 2 Histogram illustrating the distribution of total NQC scores for the same sample. Blue bars represent the low‐to‐moderate scores, whereas Orange bars indicate severe scores (≥ 101.5). The dashed vertical line marks the empirically derived cutoff of 101.5.

    At the selected cutoff (101.5), false negatives (children with severe nomophobia incorrectly classified as low-risk) represent 11.1% of true severe cases, while false positives (children without severe nomophobia incorrectly flagged) represent 2.1% of true low-risk cases. This balance favors accurate identification of the most severe cases while avoiding over-pathologizing normal behavior.

    Receiver Operating Characteristic (ROC) Analysis

    To refine the severe-risk classification, membership in the “Severe Nomophobia” cluster served as the reference standard (“true” severe group) in an ROC analysis. The NQC total scores demonstrated strong discriminative capability (AUC = 0.993, 95% CI: [0.984, 0.999]; p <.001). An optimal cutoff point was identified at 101.5 using a closest.topleft approach that partially weighted cluster prevalence. This threshold achieved a sensitivity of 0.889 and specificity of 0.979 (Youden’s index ≈ 0.868), see Table 3. Overall, 56 participants (4.86% of the total sample) met or surpassed the 101.5 cutoff. High specificity was prioritized to ensure that only the most severe cases of nomophobia were flagged. Furthermore, total NQC scores differed significantly between the two groups (64.79 ± 16.92 vs 114.29 ± 11.03, p <0.001, Cohen’s d = 3.06), as illustrated in Figure 2.

    Table 3 Optimal Cutoff Value Identified for Classifying Participants into Severe vs Low-to-Moderate Nomophobia

    Validity Checks of the 101.5 Cutoff

    Subdimension Scores

    We examined whether children at or above the 101.5 cutoff (Severe Nomophobia) reported higher scores on each nomophobia subdimension (Psychological, Social, Physiological) compared to those below the cutoff (Low-to-Moderate Nomophobia). As shown in our continuous data (see Table 4), the Severe group exhibited significantly higher means in all three subdimensions (all ps <.001), with large effect sizes (Cohen’s d ranging from 1.96 to 2.84). These findings indicate that children meeting or exceeding the cutoff show heightened symptoms across psychological, social, and physiological domains.

    Table 4 Comparison of Dimension‐specific and Total Nomophobia Scores, as Well as State‐trait Anxiety Levels, Between Children Classified as Low‐to‐Moderate versus Severe Nomophobia (Cutoff > 101.5)

    Gender Differences

    We also compared the proportion of boys and girls in each group. Of 56 children above the cutoff, 4.21% were boys (n=23) and 5.45% were girls (n=33), with no significant difference (p=0.393, Cramer’s V = 0.03). Hence, gender did not appear to significantly influence nomophobia severity in our sample.

    Anxiety Associations

    Children in the Severe group showed higher STAIC State Anxiety scores (M=38.68, SD=5.64) than those below (M=36.83, SD=4.84; t=−2.36, p=0.019, Cohen’s d=0.38), indicating moderate elevation in situational anxiety. This further supports the idea that the 101.5 cutoff can differentiate participants with clinically relevant anxiety levels. The significant correlation between nomophobia severity and anxiety aligns with earlier findings.4,29,30

    Overall, these checks affirm that our 101.5 cutoff identifies children with elevated subdimension scores and higher anxiety, confirming its utility for distinguishing those most susceptible to severe nomophobia.

    Summary of Findings

    The combination of hierarchical clustering and ROC analysis singled out a small but distinctly severe-nomophobia group (3.12% by clustering, 4.86% by ROC) among children aged 9–13. Those meeting or surpassing the 101.5 cutoff scored considerably higher on measures of state anxiety, underscoring that even in a predominantly mild-to-moderate sample, a small subset may face serious psychological detriments. Absence of gender disparities suggests nomophobia risk is broadly similar for boys and girls at this age, at least in urban Spanish settings.

    Overall, these results highlight the practicality of a data-driven cutoff (NQC ≥ 101.5) for identifying children who might benefit from prompt intervention, thereby facilitating targeted prevention and support strategies during a pivotal phase of their developmental trajectory.

    Discussion

    This study provides a refined classification for nomophobia in a crucial but understudied demographic: pre-adolescent children. A key contribution of our work is its specific focus on nomophobia, rather than the broader construct of ‘smartphone addiction’. Nomophobia uniquely captures the affective dimension of digital dependency, including the anxiety and emotional distress tied to separation from the device—a concept closely linked to attachment theory.19 By concentrating on nomophobia, our research addresses a critical gap, as previous literature has not applied this specific framework to the 9–13 age group, thereby offering a more nuanced understanding of children’s emotional relationship with their smartphones.

    Our two-step approach—hierarchical clustering followed by ROC analysis—established a high-specificity cutoff (NQC ≥ 101.5) that identified a small subset (4.86%) of children facing severe risk. This data-driven method adds precision to prior literature, which often uses broad percentile-based or multi-tiered (mild/moderate/severe) classifications that can overeste intervention needs. Our finding of a ~5% prevalence for severe nomophobia is modest compared to rates in adolescents and university students, which can exceed 17%.4,15–18 However, this figure must be interpreted through a developmental lens, where its clinical significance is amplified. The 9-to-13-year-old period is a formative window for social and emotional maturation, where attachment patterns evolve and solidify. The emergence of severe nomophobia is particularly concerning at this stage, as it may signal a nascent, maladaptive attachment to the smartphone itself, potentially perturbing the development of secure interpersonal bonds. Therefore, even a 5% prevalence identifies a small but highly vulnerable subgroup for whom early monitoring and intervention are not just beneficial, but critical to fostering healthy emotional regulation and social development.The validity of our cutoff was strengthened by its association with external measures. The link between the severe nomophobia group and higher state anxiety (d=0.38) corroborates findings from numerous studies in other populations,4,29,30 reinforcing the view of nomophobia as a genuine anxiety-related construct.

    The absence of gender differences (4.66% boys vs 5.07% girls, p=0.671) suggests nomophobia severity in this age range is not sex-driven, possibly reflecting uniform smartphone exposure or environmental influences in urban settings. This result contrasts with previous studies in older cohorts that find higher nomophobia in females.16,17 This could indicate that at ages 9–13, smartphone integration into social life is more uniform between genders, with differences emerging later in adolescence.

    While dichotomizing a continuous psychological phenomenon inevitably loses information, clinical practice often requires binary decisions (intervene/monitor). For practitioners, this NQC ≥ 101.5 cutoff can be integrated into routine school-based mental health screenings as a first-line tool to identify children who may require a more thorough clinical assessment and targeted support, such as digital wellness workshops or individual counseling. However, the substantial variability within the low-to-moderate cluster (SD = 17.28) suggests a continuum of risk, and children scoring just below the threshold may still benefit from preventive attention.

    The study’s limitations include its cross-sectional design, which prevents tracking the evolution of nomophobia, and its urban focus, which may limit generalizability to rural contexts. Future studies could employ latent profile analysis to explore subgroups, particularly as children age into adolescence, where moderate nomophobia might warrant lighter intervention. Further exploration of environmental factors—such as parenting styles or school phone policies—could clarify risk pathways. Despite these limitations, the NQC ≥ 101.5 cutoff offers a practical tool for detecting urban Spanish children aged 9–13 most likely to benefit from early intervention, enhancing targeted prevention efforts. For practitioners, this NQC ≥ 101.5 cutoff can be integrated into routine school-based mental health screenings. School psychologists or counselors could use it as a first-line tool to identify children who may require a more thorough clinical assessment and targeted support strategies, such as digital wellness workshops or individual counseling.

    Conclusion

    Combining hierarchical clustering and ROC analysis, this study defined a conservative threshold (NQC ≥ 101.5) to identify severe nomophobia in urban Spanish children aged 9–13. Though only 4.86% exceeded this cutoff, their moderately higher State Anxiety (p=0.019, d=0.38) underscores the psychological stakes of severe smartphone-related fears. Unlike multi-tiered approaches, this binary cutoff isolates a small at-risk group for focused action, proving robust for this pre-adolescent cohort. Future research should not only validate this cutoff cross-culturally but also explore its utility in rural populations where smartphone access patterns may differ. Longitudinal studies are crucial to track whether children in the ‘severe’ group continue on this trajectory and to identify protective factors, such as specific parenting styles or school-based digital literacy programs, that could mitigate risk Ultimately, this benchmark provides a valuable tool for digital mental health surveillance in schools and health services, enabling early, tailored responses to curb maladaptive digital behaviors.

    Acknowledgments

    We would like to offer our most sincere thanks to the students who participated in this study, their parents, teachers and directors of the different centers, who have allowed us the data collection process.

    Disclosure

    The authors declare that they have no conflicts of interest to declare.

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    21. López S, González S, Chivite CM, Ramírez-Durán M, Jódar R, Sánchez-Martínez M. Diseño y validación de una escala para medir la nomofobia en niños de 9 a 13 años [Design and validation of a scale to measure nomophobia in children 9 to 13 years of age]. Aten Primaria. 2023;55(1):102528. doi:10.1016/j.aprim.2022.102528

    22. Galhardo A, Loureiro D, Massano-Cardoso I, Cunha M. Adaptation of the European Portuguese version of the Nomophobia Questionnaire for adolescents, factor structure and psychometric properties. Int J Ment Health Addict. 2022;10(5):1–18.

    23. Kazem AM, Emam MM, Alrajhi MN, Aldhafri SS, AlBarashdi HS, Al-Rashdi BA. Nomophobia in late childhood and early adolescence: the development and validation of a new interactive electronic nomophobia test. Trends Psychol = Temas EM Psicologia. 2021;29(3):543. doi:10.1007/s43076-021-00068-0

    24. Kara M, Baytemir K, Inceman-Kara F. Duration of daily smartphone usage as an antecedent of nomophobia: exploring multiple mediation of loneliness and anxiety. Behav Inf Technol. 2021;40(1):85–98. doi:10.1080/0144929X.2019.1673485

    25. INE. Encuesta sobre equipamiento y uso de tecnologías de información y comunicación en los hogares [Survey on equipment and use of information and communication technologies in households]. Madrid; 2024.

    26. Galhardo A, Loureiro D, Raimundo E, Massano-Cardoso I, Cunha M. Assessing nomophobia: validation study of the european portuguese version of the nomophobia questionnaire. Community Ment Health J. 2020;56(8):1521–1530. doi:10.1007/s10597-020-00600-z

    27. Hasebrink U, Livingstone S, Haddon L, Ólafsson K. Comparing Children’s Online Opportunities and Risks Across Europe: Cross-National Comparisons for EU Kids Online. London: EU Kids Online; 2009.

    28. Kabali HK, Irigoyen MM, Nunez-Davis R, et al. Exposure and use of mobile media devices by young children. Pediatrics. 2015;136(6):1044–1050. doi:10.1542/peds.2015-2151

    29. Kuscu TD, Gumustas F, Rodopman Arman A, Goksu M. The relationship between nomophobia and psychiatric symptoms in adolescents. Int J Psychiatry Clin Pract. 2021;25(1):56–61. doi:10.1080/13651501.2020.1819334

    30. Luo J, Bei DL, Gong J, Wang MC. Classification of nomophobia among Chinese college students: evidence from latent profile and ROC analysis. J Behav Addict. 2024;13(2):482–494. doi:10.1556/2006.2024.00013

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  • Weekly Rundown: First broad-spectrum antiviral shows promise against deadly diseases

    Weekly Rundown: First broad-spectrum antiviral shows promise against deadly diseases

    By targeting viral envelope glycans, sugar molecules conserved across multiple viral families, the team identified four lead compounds that blocked infection from seven high-risk viruses. 

    GEMINI

    Vertex-Enlaza autoimmune drugs, DNA-wrapped CRISPR, HHS staff demand Kennedy’s resignation, and more lead the news this week.

    First broad-spectrum antiviral shows promise against multiple deadly viruses

    Researchers at the CUNY Advanced Science Research Center’s Nanoscience Initiative have reported in Science Advances the development of synthetic carbohydrate receptors (SCRs) that could form the basis of the first broad-spectrum antiviral (BSA). By targeting viral envelope glycans, sugar molecules conserved across multiple viral families, the team identified four lead compounds that blocked infection from seven high-risk viruses, including Ebola, Marburg, Nipah, Hendra, and both SARS coronaviruses. In animal studies, one SCR compound protected 90 percent of mice infected with SARS-CoV-2, compared to zero percent survival in controls. This novel mechanism of action, distinct from traditional antivirals that are limited to narrow viral targets, has far-reaching implications: If translated into the clinic, SCR-based drugs could provide a deployable first line of defense against future pandemics and open new avenues for therapeutic development in infectious diseases. – Andrea Corona

    Vertex offers Enlaza Therapeutics up to $2B in new partnership

    Vertex Pharmaceuticals has teamed up with Enlaza Therapeutics to use their War-Lock platform, which aims to develop first-in-class covalent biologics. Enlaza’s technology builds small format drug conjugates and T-cell engagers to target cancer, and will now be used to target autoimmune diseases during the four-year partnership. With an initial payment and equity investment of $45 million and up to $2 billion in future milestone payments, Enlaza will continue to lead all research activities up until drug candidate nomination. “By partnering with Vertex, a proven leader in bringing first-in-class and/or best-in-class medicines to patients, we gain a valued partner to help unlock the potential of covalent protein drugs, opening new markets and accelerating development of differentiated biologics with best-in-class potential,” said Sergio Duron, CEO of Enlaza. – Allison Whitten

    DNA-wrapped nanoparticles triple CRISPR’s efficiency

    Northwestern University scientists and collaborators at Flashpoint Therapeutics have developed a new nanostructure that could dramatically improve the safety and effectiveness of CRISPR gene editing. The technology, called lipid nanoparticle spherical nucleic acids (LNP-SNAs), packages the full CRISPR toolkit — Cas9 enzymes, guide RNA, and a DNA repair template — inside a lipid nanoparticle wrapped in a dense DNA shell. This DNA coating not only shields the cargo but also helps direct it to specific cells and tissues, overcoming a major hurdle in gene-editing delivery. Published in Proceedings of the National Academy of Sciences, the study showed that LNP-SNAs entered cells up to three times more efficiently, caused less toxicity, boosted gene-editing efficiency threefold, and increased precise DNA repair rates by over 60 percent compared to current lipid nanoparticles. “With CRISPR and other modalities, we intend to apply our platform to creating life-saving treatments for a wide range of diseases,” said Barry Labinger, CEO of Flashpoint Therapeutics. – Bree Foster 

    Over 1,000 HHS employees ask for secretary Kennedy’s resignation amid health policy concerns

    More than 1,000 current and former US Department of Health and Human Services (HHS) workers have signed a letter demanding Secretary Robert F. Kennedy Jr.’s resignation, citing actions they say endanger public health and undermine scientific integrity. The signatories highlight Kennedy’s firing of CDC leaders, appointment of politically-driven figures with controversial stances on vaccines, refusal to consult top experts, and rescinding of COVID-19 vaccine emergency authorizations without transparent data. HHS staff warn that his policies and public statements compromise evidence-based guidance, put the workforce at risk, and threaten the nation’s health. The letter calls on the President and Congress to appoint a science-informed, independent leader and urges partner organizations to join in restoring public trust in health policy.  – Andrea Corona

    Biological sex influences cognitive and functional outcomes in mental disorders

    New research highlights the role of sex in shaping the onset, symptoms, and outcomes of serious mental illnesses such as bipolar disorder and schizophrenia. A study published in Acta Psychiatrica Scandinavica analyzed 1,516 participants and found that females with schizophrenia were older than males at first outpatient treatment, while males with schizophrenia reported the highest rates of illicit drug use. These findings complement results from the DiAPAson study, published in Social Psychiatry and Psychiatric Epidemiology in March 2025, which examined sex differences in schizophrenia spectrum disorders among 619 Italian patients. The study also found that males tend to experience earlier onset, more severe negative symptoms, and higher antipsychotic use, while females displayed stronger interpersonal functioning and more affective symptoms. Using machine learning, researchers identified distinct male and female phenotypes, reinforcing the need for tailored treatment approaches. Together, the studies highlight that sex-sensitive strategies are vital for improving clinical outcomes, promoting healthier lifestyles and addressing comorbidities in patients with serious  mental health conditions. – Bree Foster

    Novartis invests in alpha-synuclein drug to treat Parkinson’s again

    After their prior alpha-synuclein inhibitor with UCB failed to treat Parkinson’s disease in a Phase 2a trial last year, Novartis is trying again with an investment up to $200 million in Arrowhead Pharmaceuticals’ RNAi therapy, ARO-SNCA. Just like before, Arrowhead’s therapy aims to inhibit alpha-synuclein, the protein that misfolds and builds up to form Lewy bodies within dopaminergic neurons. But unlike the previous small molecule drug, ARO-SCNA works by silencing the gene responsible for producing the alpha-synuclein protein. “We see Arrowhead’s TRiM™ technology as having great potential to achieve the type of widespread and effective delivery in key brain structures that will be necessary to see the full benefit of RNA medicines in neurodegeneration,” said Fiona Marshall, President of Biomedical Research at Novartis. Novartis will receive an exclusive worldwide license to the ARO-SCNA, which is still in the preclinical stage. – Allison Whitten

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  • Gaps in Low-Dose Aspirin Use for Preeclampsia Prevention: Insights and

    Gaps in Low-Dose Aspirin Use for Preeclampsia Prevention: Insights and

    Introduction

    Preeclampsia is a hypertensive disorder of pregnancy that typically develops after 20 weeks of gestation and contributes substantially to maternal and perinatal morbidity and mortality. Its pathophysiology involves abnormal placentation, endothelial dysfunction, and immune system dysregulation.1–4 Low-dose aspirin (LDA) prophylaxis has been shown to reduce the incidence of preterm preeclampsia by up to 62% in high-risk populations when initiated between 12 and 16 weeks of gestation at a dose of 150 mg.5 The proposed mechanisms of this treatment include inhibition of thromboxane synthesis, improved placental blood flow, decreased platelet aggregation, and modulation of inflammatory pathways.6,7 The American College of Obstetricians and Gynecologists (ACOG) and other leading organizations recommend LDA for pregnant women at high risk for preeclampsia.5,6

    The Israeli Society of Maternal Fetal Medicine adopted elements of the ACOG guidelines,8 recommending LDA prophylaxis for women with major risk factors such as chronic hypertension and pregestational diabetes, and twin pregnancies, thus aligning these guidelines with local clinical practice.9–11 Nonetheless, there is ongoing debate in Israel regarding the extent to which the broader ACOG criteria, including moderate-risk factors, should be implemented in routine clinical practice.9 The Israeli guidelines primarily emphasize major risk factors. However, it remains unclear whether some clinicians also consider moderate-risk factors, which would lead to potential variations in the application of LDA prophylaxis.12 This debate reflects differing interpretations of the evidence and highlights the need for a deeper understanding of current practices across healthcare providers.

    Our medical center, a tertiary university-affiliated hospital in Israel’s periphery, serves a diverse population of over 600,000 individuals, including both Jewish and Arab communities. In this retrospective study, we sought to assess adherence to LDA prophylaxis guidelines, comparing prescribing practices based on two distinct sets of criteria: the local Israeli guidelines and the broader ACOG recommendations. This study specifically addressed the extent to which pregnant women who met either the Israeli or ACOG criteria for LDA were actually prescribed treatment, and identified the characteristics of those who were not treated within a diverse Israeli population. By identifying characteristics of pregnant women who were not prescribed LDA despite meeting either set of criteria, this study aimed to highlight gaps in guideline implementation and support efforts to optimize preventive care practices for preeclampsia. Although previous studies have documented suboptimal adherence to aspirin prophylaxis, our goal was to examine these patterns in a diverse Israeli population and to explore barriers to implementation. Moreover, the specific impact of guideline differences is less well understood and may help explain real-world variability in clinical practice.

    Methodology

    In a retrospective study conducted at Galilee Medical Center, we included all the live births occurring between March 2020 and April 2024. The primary outcome of this study was the rate of LDA prescription among pregnant women who met the eligibility criteria for treatment according to Israeli and ACOG guidelines. Eligibility for LDA prophylaxis was assessed using two approaches: local Israeli guidelines9–11 and the ACOG Committee Opinion No. 743: “Low-Dose Aspirin Use in Pregnancy”.8

    The Israeli guidelines emphasize high-risk factors, including a history of preeclampsia, especially when accompanied by an adverse outcome. Other high-risk factors include: chronic hypertension, type 1 or type 2 diabetes, renal disease, autoimmune diseases such as systemic lupus erythematosus and antiphospholipid syndrome,9 advanced maternal age (≥45 years),10 and multifetal gestation with additional risk factors. The latter include high BMI (≥35kg/m2), maternal age ≥40 years, nulliparity, in vitro fertilization (IVF), and personal history factors such as low birth weight, small for gestational age, previous adverse pregnancy outcome, and >10-year pregnancy interval.11

    The ACOG criteria recommend LDA prophylaxis for women with one high-risk factor or at least two moderate-risk factors.8 High-risk factors include: a history of preeclampsia, multifetal gestation, chronic hypertension, type 1 or 2 diabetes, renal disease, and an autoimmune disease, such as systemic lupus erythematosus or antiphospholipid syndrome. The moderate risk factors included: nulliparity, obesity (body mass index >30 kg/m2), age 35 years or older, and personal history factors. The latter include: low birth weight, small for gestational age, a previous adverse pregnancy outcome, >10-year pregnancy interval, and IVF. Given the retrospective study design, certain risk factors were inconsistently or inadequately recorded in the prenatal records. Consequently, variables such as a family history of preeclampsia in a first-degree relative, low socioeconomic status, and black race were not considered.

    Women who met the eligibility criteria and had a prescription for LDA prophylaxis were classified as having been prescribed “appropriate prophylaxis”. Women who met the criteria for prophylactic treatment but did not have evidence of an LDA prescription were categorized as having “missed prophylaxis”. Prescription status was based on documentation in the prenatal and hospital records; data on whether the medication was actually dispensed or taken were not available.

    In addition to assessing the prescription of LDA prophylaxis, we collected data on the incidence of preeclampsia and severe preeclampsia, as documented in the medical records at the time of delivery. These outcomes were recorded to provide information on the frequency of hypertensive complications within the study cohort. We did not collect data on additional maternal or neonatal outcomes, as this was beyond the scope of our study, which was primarily focused on evaluating prescription patterns in relation to guideline-based prophylaxis. Major fetal anomalies were identified using ICD-10 codes and confirmed by manual chart review; and women were excluded from the analysis if the anomaly was likely to impact pregnancy management or outcomes. Missing data were defined as the absence of essential clinical variables needed to determine eligibility for LDA or document prescription status.

    Documentation of low-dose aspirin prophylaxis was based on provider records and reflects prescriptions or recommendations, not confirmed patient intake. Pharmacy or patient-reported data were unavailable.

    Qualitative variables are displayed as frequencies and percentages. Categorical variables were assessed using Pearson’s chi-squared test or Fisher’s exact test, with statistical significance defined by a two-tailed p-value of <0.05. To evaluate the relation between specific preeclampsia risk factors and the likelihood that LDA was prescribed, a multinomial logistic regression was applied. The rationale for this analysis was to assess the degree to which the presence of specific clinical risk factors, which were included in the definition of eligibility for LDA, were associated with actual prescription. This enabled evaluating real-world adherence to guideline-based recommendations and identifying factors most strongly linked with implementation. The results are presented as odds ratios (OR) or adjusted odds ratios (aOR) with 95% confidence intervals (CI). All the statistical analyses were performed using SPSS software, version 27.0 (IBM Corp., Armonk, NY, USA).

    Results

    During the study period, 19,620 women delivered at Galilee Medical Center. After 782 were excluded due to severe fetal anomalies or incomplete data, a total of 18,838 women were included in the analysis.

    The Utilization of LDA Prophylaxis According to Israeli Guidelines

    A total of 1,160 women were classified as eligible for aspirin prophylaxis according to the Israeli guidelines. Of these, 511 (44.1%) received aspirin as recommended. Conversely, among the 17,678 women who were not eligible, 829 (4.7%) received aspirin despite not meeting the criteria.

    Among the women with the highest prescription rates for aspirin prophylaxis, 79.0% (94/119) of those with a history of preeclampsia were prescribed aspirin, followed by 66.3% (67/101) of those with pre-gestational diabetes. In contrast, the lowest prescription rates were observed among women with autoimmune diseases (41.3%, 64/155) and chronic hypertension (30.3%, 148/489). Figure 1 illustrates the rates of LDA prophylaxis across various risk factors according to Israeli guidelines.

    Figure 1 Prescription rates of low-dose aspirin among 1,160 pregnant women eligible under Israeli guidelines. Blue bars represent the percentages of women with each risk factor who were prescribed low-dose aspirin; Orange bars represent those not prescribed. The percentages shown on each bar reflect the proportions that received versus did not receive a prescription.

    Abbreviations: PET, preeclampsia; DM, diabetes mellitus; HTN, hypertension; IVF, in vitro fertilization.

    The prescription rate of LDA varied by the number of risk factors. The rate was 40.7% (395/971) among women with one risk factor, and increased to 61.9% (99/160) for two risk factors and 55.6% (15/27) for three risk factors. The prescription rates did not differ significantly between eligible Arab and Jewish women: 45.2% (325/719) vs 42.6% (179/420), p=0.422.

    In a multivariate regression analysis, a history of preeclampsia was significantly associated with a LDA prescription, with an OR of 7.15 (95% CI: 4.201–12.150, p<0.001). Similarly, pre-gestational diabetes was significantly associated, with an OR of 3.80 (95% CI: 2.263–6.393, p<0.001). Conversely, chronic hypertension, renal disease, autoimmune disease, and multifetal gestation combined with IVF were not significantly associated with LDA prophylaxis prescriptions (Table 1).

    Table 1 Independent Relations Between Specific Risk Factors and Low-Dose Aspirin Prophylaxis Among 1,160 Women Eligible for Treatment According to Israeli Guidelines. Adjusted Odds Ratios with 95% Confidence Intervals and p Values are Shown

    LDA Prophylaxis Prescription According to ACOG Guidelines

    Of the total cohort, 2,559 women (13.6%) were eligible for LDA prophylaxis based on ACOG criteria. Among them, 715 (27.9%) received appropriate prescriptions. Of the 16,279 women who did not meet ACOG criteria, 625 (3.8%) were prescribed LDA. Prescription rates were highest among women with a history of preeclampsia (79.0%, 94/119) and type 1 or 2 diabetes mellitus (66.3%, 67/101). Lower rates were observed among those with chronic hypertension (30.3%, 148/489), obesity (26.8%, 114/425), and advanced maternal age (25.5%, 306/1,199) (Figure 2). Table 2 demonstrates LDA prophylaxis rates across various combinations of high- and moderate-risk factors. The prescription rate was 54% (95/177) among women with one high- and two moderate-risk factors, and increased to 61% (23/38) among those with one high- and three moderate-risk factors. Among women with two high-risk factors and no moderate-risk factors, the prescription rate was 57% (30/53). Women with no high-risk factors but multiple moderate-risk factors were significantly less likely to be prescribed LDA than were women with at least one high-risk factor (OR: 0.16, 95% CI: 0.131–0.198, p<0.001).

    Table 2 Prescription Rates of Low-Dose Aspirin Prophylaxis Among 2,559 Women Eligible for Treatment According to American College of Obstetricians and Gynecologists Criteria, Stratified by the Number of High- and Moderate-Risk Factors. The Data are Presented as the Number That Received a Prescription Relative to the Total Number in Each Subgroup, with the Corresponding Percentage in Parentheses

    Figure 2 Prescription rates of low-dose aspirin among 2,559 pregnant women eligible under the American College of Obstetricians and Gynecologists guidelines, stratified by combinations of high- and moderate-risk factors. Blue bars represent the percentages of women with each risk factor combination who received a prescription; Orange bars represent those who did not. The percentages shown on each bar reflect the proportions within each subgroup.

    Abbreviations: PET, preeclampsia; DM, diabetes mellitus; HTN, hypertension; BMI, body mass index; IVF, in vitro fertilization.

    Higher proportions of Arab than Jewish women had at least one high-risk factor for preeclampsia (57% vs 43%, p<0.001), and two or more high-risk factors (7.4% vs 4.2%, p<0.001). This difference likely explains the higher prescription rate of LDA prophylaxis among Arab than Jewish women: 31.2% (441/1,412) vs 24.5% 266/1,086, p<0.001).

    Table 3 illustrates the independent relations between specific risk factors and LDA prophylaxis prescriptions. High-risk factors, including autoimmune disease, renal disease, multifetal gestation, a history of preeclampsia, chronic hypertension, and type 1 or 2 diabetes were all significantly associated with increased LDA prophylaxis prescriptions during pregnancy (p<0.05 for all). However, some moderate risk factors, namely nulliparity, personal history factors, and IVF were not significantly associated with LDA prophylaxis prescriptions.

    Table 3 Independent Associations Between Specific High- and Moderate-Risk Factors and Prescription Rates of Low-Dose Aspirin Among 2,559 Women Eligible for Treatment According to American College of Obstetricians and Gynecologists Criteria. The Data Include the Number of Women Who Received or Did Not Receive Low-Dose Aspirin, Adjusted Odds Ratios (aOR), 95% Confidence Intervals, and p Values for Each Factor

    Preeclampsia occurred in 144 out of 715 women (20.1%) who were prescribed LDA prophylaxis compared to 110 out of 1844 women (6.0%) who were not prescribed. The OR was 3.975 (95% CI: 3.048–5.185, p<0.01). Severe preeclampsia was observed in 23 of 715 women (3.2%) in the LDA group, compared to 22 of 1844 women (1.2%) in the non-aspirin group. The OR was 2.753 (95% CI: 1.524–4.971, p=0.001). No association was found of LDA prophylaxis with preeclampsia or with severe preeclampsia before 32 weeks of gestation.

    Discussion

    We report a low prescribing rate of LDA prophylaxis among women who met the criteria delineated in existing guidelines. High-risk factors were significantly associated with an increased likelihood of receiving LDA during pregnancy. However, women with multiple moderate risk factors but not a high-risk factor were 84% less likely than those with a high-risk factor to be prescribed LDA (OR=0.16, 95% CI 0.13–0.2, p<0.001).

    Aspirin, or acetylsalicylic acid, is well established for its anti-inflammatory and antithrombotic properties. At low doses, it irreversibly inhibits the COX-1 enzyme, reducing thromboxane A2 production, which is a potent vasoconstrictor, and promotes platelet aggregation.10 This mechanism is believed to improve placental blood flow and decrease the risk of hypertensive disorders in pregnancy, particularly preeclampsia.11 Despite the incomplete understanding of the precise pathways by which LDA prevents preeclampsia, it remains a key intervention for women at high risk. In 2018, the ACOG, in collaboration with the Society for Maternal-Fetal Medicine, recommended daily LDA for women at high risk of preeclampsia, starting between 12 and 28 weeks of gestation, ideally before 16 weeks, and continuing until delivery. Additionally, LDA is recommended for women with multiple moderate-risk factors, such as advanced maternal age or nulliparity.8 The Israeli Society of Maternal Fetal Medicine partially adopted these guidelines, emphasizing LDA prophylaxis for women with major risk factors, such as chronic hypertension and pregestational diabetes, while incorporating some elements related to moderate-risk factors.9–11 As LDA should ideally be started at 12 to 16 weeks of gestation, it is often prescribed by general obstetricians in the community, who are typically the first to treat pregnant women. This highlights the need for targeted educational initiatives for these providers to enhance adherence to prophylaxis guidelines.

    Our findings align with reports from other countries, of low prescribing and use of LDA prophylaxis despite guidelines.12–15 For example, a US study by Krishnamurti et al revealed that 27.4% of women at high risk for preeclampsia had no mention of LDA in their medical records, and among those with documented recommendations, 36.7% were unaware of the need for LDA.14 These findings highlight significant gaps in both risk identification and communication between healthcare providers and patients. Our finding that women with moderate-risk factors compared to those with high-risk were less likely to be prescribed LDA, corroborates other reports, and raises an opportunity for intervention in this subgroup.16,17 Moreover, our study showed that Arab women were more commonly prescribed LDA, reflecting their higher prevalence of risk factors for preeclampsia. This suggests that specific subpopulations, such as Arab women, may benefit from focused efforts to prevent preeclampsia. Although there is ongoing debate in Israel regarding the criteria that should guide aspirin prophylaxis, our findings suggest that suboptimal prescribing persists regardless of whether the narrower Israeli or the broader ACOG criteria are applied. This indicates that prescription rates may be less dictated by the choice of criteria, and more by gaps in implementation. Understanding that both approaches yielded similarly low prescribing rates supports the need for system-level interventions—such as provider education, clearer risk assessment protocols, and early identification strategies—regardless of the guideline that is ultimately followed.

    An intriguing finding in our study was the higher incidence of preeclampsia among women who received LDA. This may be due to selection bias, by which women at higher risk were more likely to be prescribed LDA. Other factors, such as inappropriate dosing or non-adherence, could have also contributed. Reverse causality should also be considered. Specifically, subtle early signs of evolving disease, such as mildly rising blood pressure, may have prompted clinicians to initiate aspirin treatment even within the recommended gestational window. Additionally, unmeasured confounders may have influenced both the decision to prescribe LDA and the actual risk of developing preeclampsia. Adherence to LDA was not assessed in our study, which may have limited its protective effect. Although current guidelines recommend initiating LDA ideally between 12 and 16 weeks of gestation, it remains acceptable to begin treatment as late as 28 weeks. However, in our cohort, precise data regarding the actual timing of initiation were unavailable, and such variability may have influenced the observed outcomes. Moreover, information on the type of provider (eg, community obstetrician versus maternal-fetal medicine specialist) and care delivery model was not available, though these factors may also influence prescribing behavior and contribute to practice variation.

    Notably, the method currently used in Israel to identify candidates for aspirin prophylaxis—based solely on clinical risk factors—may not be optimal. Prescription that is based solely on clinical risk factors—such as maternal age, parity, BMI, and medical or obstetric history is limited in its ability to identify women at risk for preeclampsia.and the detection of preterm preeclampsia is about 60%.11 In contrast, incorporating biochemical and biophysical markers, including mean arterial pressure, uterine artery Doppler, PAPP-A, and PlGF, significantly improves prediction. This combined approach, as applied in the ASPRE trial, enables earlier and more accurate identification of high-risk women, this yielding targeted aspirin use and achieving a substantially greater reduction in preeclampsia incidence.5 However, in Israel, this screening algorithm is not currently implemented in routine clinical practice, and risk assessment remains primarily based on clinical criteria. It is important to note that our study was not designed to evaluate the effectiveness of LDA in preventing preeclampsia; therefore, these findings should be interpreted with caution and warrant further investigation.

    The strengths of our study include the large sample size and the real-world clinical setting, which support the robustness and clinical relevance of our findings. The large cohort enabled examining current LDA prescribing practices across diverse patient populations. Furthermore, our assessment of prescription rate according to both Israeli and ACOG guidelines provided a unique opportunity to evaluate differences in prescribing practices based on national and international recommendations. Stratifying LDA use by risk categories helped identify potential gaps in prophylaxis, particularly in moderate-risk groups, in which adherence to guidelines may be more variable. Although the regression model included risk factors already defined by the guidelines, it was applied to assess whether these factors were indeed associated with real-world prescription, thus highlighting potential gaps in implementation. Potential misclassification bias, unmeasured confounders, and lack of dose validation are limitations that must be considered due to the retrospective study design. Moreover, incomplete or missing information, especially regarding certain risk factors that were not consistently recorded in medical charts should also be considered. This limitation may have introduced selection or information bias, particularly in identifying all the women eligible for LDA prophylaxis. These include incomplete or missing information, especially regarding certain risk factors that were not consistently recorded in medical charts. The single-center design also limits the generalizability of our findings, as the prescribing practices and patient demographics at our institution may not reflect those in other regions or healthcare settings. Additionally, we were unable to assess adherence to aspirin therapy, as direct confirmation of intake (eg, pharmacy dispensing data or patient self-report) was not available. Our data therefore reflect prescribing behavior rather than confirmed use, which may result in either over- or under-estimation of actual adherence. This limitation should be considered when interpreting the identified gaps in clinical practice. Moreover, data on the exact dose were unavailable, although doses in Israel range between 75 and 150 mg. As explained above, we did not collect data on obstetric or neonatal outcomes, other than on incidences of preeclampsia. Regardless, our ability to draw conclusions about the clinical effectiveness of aspirin prophylaxis is limited by the low prescription rate of aspirin and the likely bias in provider decision-making regarding whom to treat.

    This study may be viewed as a real-world audit of aspirin prescribing practices in a tertiary Israeli center. While suboptimal adherence to LDA guidelines has been documented elsewhere, our findings contextualize this issue within a local healthcare system that incorporates both national and international recommendations. By identifying population-specific patterns and potential barriers to implementation, such as ambiguity in criteria and lack of provider awareness, this work contributes insight to the global conversation on preeclampsia prevention. To enhance adherence to LDA guidelines, we recommend integrating standardized risk assessment tools into early prenatal visits, supported by decision aids or electronic alerts within clinical software. Educational initiatives targeting community-based providers—who are most often responsible for initiating LDA—could improve early identification and prescription. Additionally, national efforts to harmonize guideline implementation and to consider inclusion of biochemical or Doppler markers, as in the ASPRE model,11 may further refine risk stratification and improve prophylaxis.

    In conclusion, the rate of LDA prophylaxis for preeclampsia prevention in our population was low. Our findings underscore the need for a more structured approach to identifying and managing women at risk for preeclampsia. The low adherence to LDA guidelines indicates gaps in clinical practice, which could be addressed through provider education, systematic risk assessment tools, and clearer treatment protocols. Future efforts should focus on refining risk assessment, improving physician awareness of LDA recommendations, and ensuring early initiation of prophylaxis within the critical gestational window.

    Abbreviations

    LDA, low-dose aspirin; ACOG, The American College of Obstetricians and Gynecologists; IVF, in vitro fertilization.

    Data Sharing Statement

    Data may be obtained from the corresponding author (I.S) upon reasonable request.

    Ethics Approval and Consent to Participate

    Our study was performed in compliance with the Declaration of Helsinki. The protocol of the study was approved by the local Institutional Review Board (Helsinki Committee) of the Galilee Medical Center, Nahariya, Israel (number of approval NHR-23-186). The need for written informed consent was waived because of the retrospective study design. All the data were anonymized to ensure patient confidentiality.

    Author Contributions

    All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

    Funding

    There is no funding to report.

    Disclosure

    The authors report no conflicts of interest in this work.

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    8. ACOG Committee Opinion No. 743 summary: low-dose aspirin use during pregnancy. obstet gynecol. 2018;132(1)254–256. doi:10.1097/AOG.0000000000002709

    9. Available from: chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://cdn.mednet.co.il/2019/10/Ne125_bloodPressurePregnancy.pdf. Accessed September 01, 2025.

    10. Atallah A, Lecarpentier E, Goffinet F, Doret-Dion M, Gaucherand P, Tsatsaris V. Aspirin for prevention of preeclampsia. Drugs. 2017;77(17):1819–1831. doi:10.1007/s40265-017-0823-0

    11. Rolnik DL, Nicolaides KH, Poon LC. Prevention of preeclampsia with aspirin. Am. J Obstet Gynecol. 2022;226(2S):S1108–S1119. doi:10.1016/j.ajog.2020.08.045

    12. Ayyash M, Goyert G, Pitts D, et al. Provider adherence to aspirin prophylaxis prescription guidelines for preeclampsia. Pregnancy Hypertension. 2023;34:1–4. doi:10.1016/j.preghy.2023.09.002

    13. Olson DN, Russell T, Ranzini AC. Assessment of adherence to aspirin for preeclampsia prophylaxis and reasons for nonadherence. Am. J Obstet Gynecol MFM. 2022;4(5):100663. doi:10.1016/j.ajogmf.2022.100663

    14. Krishnamurti T, Davis AL, Rodriguez S, Hayani L, Bernard M, Simhan HN. Use of a smartphone app to explore potential underuse of prophylactic aspirin for preeclampsia. JAMA Netw Open. 2021;4(10):e2130804. PMID: 34714341; PMCID: PMC8556626. doi:10.1001/jamanetworkopen.2021.30804

    15. Lewkowitz AK, Rouse DJ. Miscommunication about low-dose aspirin for preeclampsia prevention-further support for universal prophylaxis. JAMA Netw Open. 2021;4(10):e2130960. PMID: 34714349. doi:10.1001/jamanetworkopen.2021.30960

    16. Phelps AJD, Holmgren C. Relationship between risk factor profile and prescription of low-dose aspirin for preeclampsia prevention. Arch Gynecol Obstet. 2023;308(4):1279–1286. doi:10.1007/s00404-022-06773-0

    17. Sium AF, Gudu W, Tolu LB, Birara M, Bekele D. Missed opportunity for aspirin prophylaxis for preeclampsia prevention: a cross-sectional study from Sub-Saharan Africa. AJOG Glob Rep. 2023;4(1):100295. doi:10.1016/j.xagr.2023.100295

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  • Immune-Evasive Islets Show Promise in Type 1 Diabetes Trial – Medscape

    1. Immune-Evasive Islets Show Promise in Type 1 Diabetes Trial  Medscape
    2. First FDA-approved islet transplant at UI Health ends insulin dependence  News-Medical
    3. After decades, UI Health-developed diabetes therapy leaves realm of experimental  Crain’s Chicago Business
    4. New Cell Transplant Treatment Offers Hope for Type 1 Diabetics  Goodnet | Gateway to doing good
    5. Type 1 Diabetes Patient’s Insulin Production Restored with New Cell Transplant Therapy  Scientific American

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  • Who Benefits From Chemoradiotherapy in Early-Stage OPSCC ? – Medscape

    1. Who Benefits From Chemoradiotherapy in Early-Stage OPSCC ?  Medscape
    2. New Throat Cancer Treatments Aim To Reduce Deaths and Preserve Function in 2025 and Beyond  Memorial Sloan Kettering Cancer Center
    3. DART Therapy Exhibits Greater Tolerability in Oropharyngeal SCC  CancerNetwork
    4. Shorter, less intense radiation-chemo regimen effective for HPV-linked oropharyngeal cancer, Mayo study shows  southfloridahospitalnews.com

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  • Breast cancer surgeon warns ‘breast cancer doesn’t always come with lump’: Nipple discharge, swelling can be signs

    Breast cancer surgeon warns ‘breast cancer doesn’t always come with lump’: Nipple discharge, swelling can be signs

    Breast cancer is the most common cancer in women worldwide and the most common cancer diagnosed in American women, per the Breast Cancer Research Foundation. Per the report, it is a leading cause of cancer death in less developed countries and the second leading cause of cancer death in American women. Meanwhile, as per the ICMR- National Cancer Registry Programme (NCRP) data, the estimated number of incidence of cancer cases in India for 2025 is 15,69,793.

    Limiting alcohol and processed foods and increasing daily movement is a great place to start if you want to lower breast cancer risk. (Freepik)

    Also Read | AIIMS gastroenterologist shares 8 powerful ways to lower cancer risk: Limit meat, maintain weight, choose healthy oils

    Therefore, educating oneself about this type of cancer, especially for women, is essential. In an Instagram post shared on July 11, Dr Lauren Ramsey, breast cancer surgeon, MD, shared some key facts that every woman should know:

    4 facts about breast cancer

    Captioned, “Advice I would give you as a breast cancer surgeon if I wasn’t afraid of hurting your feelings,” the breast cancer surgeon highlighted these 4 important details:

    1. The breast cancer surgeon pointed out that only about 5-10 percent of breast cancers are linked to inherited mutations like BRCA. However, you should still get regular screenings even if you don’t have a family history.

    2. The surgeon highlighted that breast cancer doesn’t always come with a lump. In fact, skin changes, nipple discharge, swelling, or subtle pain can be signs too. “Know what’s normal for you,” she advised.

    3. “Dense breast tissue makes breast cancer harder to detect,” the breast cancer surgeon warned. “It’s common and normal, but it may require additional imaging. Ask if your breast density is noted on your mammogram,” she added.

    According to Radiologyinfo.org, mammography is specialised medical imaging that uses a low-dose X-ray system to see inside the breasts. It aids in the early detection and diagnosis of breast diseases in women.

    4. Lastly, she highlighted that the lifestyle changes people talk about really do make a difference. She suggested limiting alcohol and processed foods and increasing daily movement is a great place to start.

    Lifestyle changes to lower breast cancer risk

    Per PubMed Central, diet, physical activity, smoking, alcohol use, and vitamin and mineral use are key factors influencing the risk of breast cancer among women. Since breast cancer has a high rate of mortality and morbidity among women, it is logical to try to find ways to decrease the risk of developing breast cancer using easy, effective, and economical lifestyle changes.

    Note to readers: This report is based on user-generated content from social media. HT.com has not independently verified the claims and does not endorse them.

    This article is for informational purposes only and not a substitute for professional medical advice.

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  • Clinical Significance, Differential Diagnosis and Initial Management of Hematuria in Emergency and Outpatient Settings

    Clinical Significance, Differential Diagnosis and Initial Management of Hematuria in Emergency and Outpatient Settings


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  • Early signs of kidney problems that most people ignore

    Early signs of kidney problems that most people ignore

    Kidney ailments like Chronic Kidney Disease (CKD), once seen largely as diseases of the elderly, are now rising at alarmingly rates among younger people. The surge is driven by increasing cases of diabetes and hypertension, compounded by sedentary lifestyles, unhealthy diets, and growing obesity.

    This shift highlights the urgent need for increased awareness, early detection, and preventive measures to tackle the growing burden of kidney disease in India. Routine screening, lifestyle changes, and better health education—particularly among the youth—are critical to curbing the rise in kidney-related problems.

    Are you at risk of kidney disease? Here are the key signs and symptoms to watch for:

    Trouble sleeping: When kidneys don’t filter properly, toxins build up in the blood, making it harder to sleep. People with kidney disease are also more likely to experience sleep apnea.

    Frequent urination: Damaged kidney filters can cause an increased urge to urinate, particularly at night. While this may also signal a urinary infection or, in men, an enlarged prostate, any noticeable change in frequency should be discussed with a healthcare professional.

    Low energy: When toxins build up in the blood, they can cause fatigue, weakness, and difficulty concentrating. Kidney disease can also lead to anaemia, which further contributes to tiredness.

    Blood in urine: Healthy kidneys prevent blood cells from leaking into urine. When the filters are damaged, blood may appear, signalling possible kidney disease, stones, tumours, or infection. Any such sign should be checked by a doctor immediately.

    Puffiness around eyes: Protein leaking into urine, instead of staying in the body, may cause swelling or puffiness around the eyes—a possible sign of kidney damage.

    Swollen ankles and feet: When kidneys don’t function properly, sodium retention can cause swelling. This symptom may also be linked to heart disease, liver disease, or chronic vein problems in the legs.

    Muscle cramping: Kidney dysfunction can disrupt electrolyte balance—like low calcium or high phosphorus—triggering muscle cramps.

    When to See a Doctor?

    Consult a doctor if you notice any signs of kidney disease. Early detection is key to preventing progression to kidney failure. Those at higher risk may be advised to undergo regular urine and blood tests for timely monitoring.

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