BackgroundArtificial intelligence (AI) and machine learning are transforming neurosurgical research and practice, yet the programming barrier has excluded most clinicians from building customized digital tools. Vibe coding - generating functional software through natural language instructions to large language models - has substantially lowered this barrier since its formalization in 2025. No study has examined its applications specifically within neurosurgery.MethodsA narrative review of the literature was conducted using PubMed, Google Scholar, and preprint repositories through April 2026, supplemented by the author's direct clinical experience developing vibe-coded tools in a tertiary neurosurgical unit.FindingsExisting literature on vibe coding in medicine is sparse and limited to non-surgical specialties; no prior publication addresses it in a neurosurgical context. Three practical domains of application are identified: (1) research data collection and multi-scale patient classification, illustrated by a personally developed integrated scoring tool for aneurysmal subarachnoid hemorrhage (Figure 1); (2) clinical workflow optimization including documentation and follow-up automation; and (3) educational tool development and literature engagement.ConclusionVibe coding represents an accessible paradigm enabling neurosurgical trainees to develop purpose-specific digital tools without programming expertise. The field lacks specialty-specific guidance on this approach. This review aims to address that gap and encourage adoption of vibe coding as a practical complement to institutional digital health infrastructure.
Flexible behavior requires the ability to modulate sensory processing based on task context, yet the circuit-level mechanisms supporting this capacity remain poorly understood. Here, we combine recurrent neural network modeling and neural recordings from mouse visual cortex to investigate how task context shapes sensory coding. Networks trained on an instruction-based discrimination task develop a disinhibitory interneuron-to-interneuron motif that dynamically gates task-relevant sensory information. Perturbation and lesion analyses show that this motif is necessary for task performance and for maintaining distinct sensory representations across contexts. We validate key predictions in mouse visual cortex, where interneuron activity patterns exhibit comparable task-dependent modulation. These results identify a biologically plausible circuit motif that supports flexible sensory processing and link recurrent connectivity structure to adaptive context integration in both artificial and biological systems.
Hospital-acquired complications (HACs) have recently been introduced in Australia as a quality-of-care metric. These use International Classification of Diseases (ICD) codes to identify potentially avoidable complications, including healthcare-associated infections. We sought to determine the positive predictive value (PPV) of the HAC algorithms in detecting hospital-acquired pneumonia (HAP) and healthcare-associated urinary tract infections (HA-UTI) using traditional surveillance as the standardised comparator. We conducted a retrospective analysis at Alfred Health. For both HAP and UTI, we selected 50 admitted episodes with ICD codes that satisfied the HAC definition. We applied standardised surveillance definitions to these episodes, based on European Centre for Disease Prevention and Control (ECDC) guidance. This involved a manual review of documentation and results by an Infection Prevention and Control Nurse Consultant. PPVs were calculated by comparing ICD-code diagnoses with surveillance-confirmed infections. The PPV for the HAP algorithm was 20% (95% CI: 11.0-33.2%). Among non-confirmed cases, 23% (9/40) had no radiological evidence of pneumonia, and 23% (9/40) had symptoms or consolidation on admission. Of the ten true HAP cases, 50% (5/10) were ventilator-associated. The PPV for the HA-UTI algorithm was 58% (95% CI: 44.2-70.6%), with 71% (15/21) of false positives due to asymptomatic bacteriuria. We found that current HAC algorithms based on ICD coding data did not reliably predict HAP and HA-UTI as defined by standardised surveillance. Given their use in healthcare funding, further validation and improvement of current algorithms should be explored.
To describe how experienced psychiatric nurses notice, interpret, and respond to adult inpatients whom they clinically judge to have childhood maltreatment-related attachment difficulties and to clarify the practical reasoning underlying these judgments. Eleven experienced psychiatric nurses from two private psychiatric hospitals in Japan were purposively sampled. Participant observation and semi-structured interviews focused on care of adults clinically understood to have childhood maltreatment-related attachment difficulties. Case identification relied on nurses' clinical judgment and routine team discussions or record information; no standardized attachment assessment or independent verification of childhood maltreatment history was used. Data were analyzed using the steps for coding and theorization (SCAT) method. SCAT generated 54 themes or concepts organized into 10 categories and 24 subcategories. Nurses noticed recurrent relational patterns, including distrust, checking behavior, dependency-aggression cycles, misinterpretation of staff intentions, self-harm, and distress around proximity, and adjusted their responses to stabilize the patient-nurse dyad, avoid re-traumatization, support emotional expression, and coordinate team care. Only a limited subset of subcategories was attachment-specific; many others reflected broader psychiatric nursing practices applied through an attachment-informed lens. A trauma-focused noticing process was visible in nurses' attention to nonverbal cues and early behavioral change. The findings describe situated clinical reasoning rather than a new diagnostic technique or intervention model. Experienced psychiatric nurses adapted everyday psychiatric nursing practices to relational patterns they understood as childhood maltreatment-related and attachment-relevant. The model may inform education, supervision, and future patient-inclusive research.
This study uncovered potential regulatory networks associated with cleistogamy in pigeonpea by analyzing interactions between lncRNAs, mRNAs, and miRNAs. Cleistogamy, a unique floral adaptation, is a valuable trait offering a unique reproductive advantage in self-pollinated species. In crops like pigeonpea, outcrossing significantly contributes to the deterioration of varietal purity, impacting the overall seed purity. Thus, as a primary effort to get molecular insights governing cleistogamy in pigeonpea, we performed RNA-seq analysis of unopened flower buds from three pigeonpea genotypes having different flower morphologies i.e., ICPL87154 (cleistogamous), ICPL87119 (chasmogamous), and UP26 (partially wrapped petals). Comparative analysis revealed differential gene expression patterns in the cleistogamous vs. chasmogamous combination. Comparative transcriptome profiling identified differential enrichment of biological pathways between the genotypes. Relative to the non-cleistogamous genotype, the cleistogamous genotype exhibited increased expression of genes involved in carbohydrate metabolism and ubiquitin-mediated proteolysis, whereas genes associated with hormone signaling and endocytosis showed reduced expression. To further delineate the regulation, LncRNAs were predicted from the assembled transcriptome, and a total of 25,307 transcripts were identified as lncRNAs based on length, exon number, and coding potential. Further interaction analysis revealed regulatory lncRNA-miRNA-mRNA networks, and expression validation of key networks uncovered some candidate genes, such as FT-interacting protein 1 (FTIP1) and auxin response factor 2A, that can be potentially involved in this trait. Upregulation of miRNAs miR156b, miR169g, and miR171g in the cleistogamous genotype suggests the post-transcriptional regulation of cleistogamy. Additionally, simple sequence repeats (SSRs) identified in differentially expressed genes and lncRNAs offer additional genomic resources pertaining to this trait. This study provides the first comprehensive identification of DEGs and DE-lncRNAs associated with cleistogamy in pigeonpea, laying the groundwork for further molecular dissection.
Prostate cancer (PCa) represents a hormone-dependent malignancy where androgen receptor (AR) signaling plays a central role in disease initiation, progression, and therapeutic resistance. Recent advances have revealed that long non-coding RNAs (lncRNAs) constitute a critical regulatory layer in prostate cancer, with implications for endocrine signaling pathways. lncRNAs orchestrate complex gene regulatory networks through diverse molecular mechanisms including chromatin remodeling, AR splice variant regulation, competitive endogenous RNA networks, translational control, and metabolic reprogramming. In castration-resistant prostate cancer, dysregulated lncRNAs contribute to resistance against androgen deprivation therapy and next-generation AR antagonists such as enzalutamide. This review synthesizes current knowledge on lncRNA biology in PCa, emphasizing lncRNA relationships with AR signaling and endocrine resistance mechanisms. We discuss key lncRNAs that modulate AR activity, metabolic adaptation, and lineage plasticity. Additionally, we examine structure-function relationships that enable rational therapeutic design, lncRNA roles in bone metastasis and neuroendocrine differentiation, and lncRNA clinical utility as biomarkers for disease progression and treatment stratification. Therapeutic strategies include antisense oligonucleotides, small-molecule inhibitors of lncRNA-protein interaction disruptors, and combination approaches with DNA-damaging agents and AR inhibitors. Understanding lncRNA-mediated endocrine regulation provides insights into prostate cancer biology and offers avenues for overcoming therapeutic resistance in advanced disease.
Single-cell RNA sequencing is increasingly applied to bacterial model species, but a dedicated technique for anaerobic microbiota members of the Bacteroidota phylum has been lacking. Here, working with Bacteroides thetaiotaomicron, we describe experimental steps for transcriptome stabilization, fluorescence-activated cell sorting (FACS) collection, and optimized lysis of single cells from this group of organisms. We detail procedures for reverse transcription of RNAs via the multiple annealing and dC-tailing-based quantitative single-cell RNA sequencing (MATQ-seq) protocol, sensitive Cas9-based depletion of ribosomal sequences, and cDNA library generation. For complete details on the use and execution of this protocol, please refer to Bornet et al.1.
Artificial intelligence (AI), particularly generative AI and large language models, is increasingly used for assessment-related tasks in medical education. Existing overviews often address AI in medical education broadly, limiting assessment-specific interpretation of functions, settings, learner stages, and responsible-AI reporting domains. This study aims to map the literature on AI for assessment and feedback in medical education, including publication trends, bibliometric structure, assessment functions, AI types, settings, learner stages, and reporting of validity, reliability, fairness, integrity, transparency, human oversight, implementation, and governance. We conducted a bibliometric mapping study incorporating structured thematic evidence-map coding. Web of Science Core Collection, Scopus, and PubMed were searched from January 1, 2015, to April 8, 2026. Document selection and main evidence-map coding were based primarily on titles, abstracts, and bibliographic metadata, with targeted ambiguity resolution. Because reporting domains may appear mainly in full-text sections, all 435 included records underwent full-text sensitivity analysis for the 8 reporting domains. Coding reliability was assessed by two coders using percent agreement and Cohen κ before adjudication. Exploratory subgroup analyses and an excluding-2026 partial-year sensitivity analysis were conducted. Searches identified 14,968 records; 435 were included after deduplication and selection. Overall, 399 (91.7%) records were indexed in the post-ChatGPT period. Generative AI was coded in 310 (71.3%) records, and large language models in 301 (69.2%) records. In the assessment-function umbrella analysis, learner performance evaluation accounted for 270 (62.1%) records, feedback for 93 (21.4%) records, assessment content generation for 65 (14.9%) records, and other or unclear functions for 7 (1.6%) records. The most common settings were board-style examinations (n=151, 34.7%) and written examinations (n=88, 20.2%); undergraduate medical education was the most represented learner stage (n=172, 39.5%). Full-text-confirmed reporting was most frequent for reliability (n=288, 66.2%) and implementation (n=231, 53.1%); intermediate for validity (n=158, 36.3%), fairness (n=132, 30.3%), and transparency (n=130, 29.9%); and less frequent for governance (n=57, 13.1%), human oversight (n=46, 10.6%), and integrity (n=26, 6%). Stage 1 κ values ranged from 0.785 to 0.895, and stage 2 κ values ranged from 0.809 to 0.880. Excluding 65 partial-year 2026 records did not change the overall interpretation. The indexed English-language literature on AI for assessment and feedback in medical education expanded rapidly in the post-ChatGPT period and was concentrated in generative AI, large language models, examination-oriented assessment, and undergraduate medical education. Future studies should complement examination benchmarking with authentic assessment contexts, distinguish assessment content generation from learner-facing evaluation and feedback, and report responsible assessment domains more consistently.
To explore aspects of professional identity formation in participants of a longitudinal pediatric program for final-year medical students in the US. Many institutions have specialty-specific courses focused on the transition to residency, typically at the end of medical school. This study examines professional identity formation among participants of a longitudinal fourth-year Pediatric Concentration. Authors used a case study design for this qualitative research study using semi-structured interview questions based on a conceptual model of professional identity formation. Authors used purposeful sampling to identify study participants who were randomly selected from former students who completed the program between 2019 and 2021. Three interviewers independently conducted interviews with individual program participants. Thematic analysis with coder reliability was utilized for data analysis; two investigators independently coded and performed inter-rater reliability (IRR) on three sets of questions from transcriptions. After ensuring acceptable IRR, investigators coded the remaining questions and subsequently identified themes and sub-themes. Eleven former students completed interviews. Following initial independent coding, IRR for three questions was 80%. After coding the 11 interviews, investigators determined that code saturation was achieved. They subsequently identified six main themes: career development, interpersonal connection, personal growth, positive role models, skill-building, and supportive learning environment. Two cross-cutting themes were recognized throughout the data: sense of belonging and gaining confidence toward starting residency. Participants in a longitudinal specialty-specific program in the final year of medical school experienced professional identity formation through a supportive learning environment fostering connection and personal growth while building skills, surrounded by positive role models. This community of practice cultivated a sense of belonging and helped participants gain confidence toward their residency and career. This longitudinal, specialty-specific approach to the final year of medical school may enhance professional identity formation for students entering all specialties and could facilitate transition to internship.
Acute lymphoblastic leukaemia (ALL) is characterized by uncontrolled proliferation of lymphoid progenitor cells. Advances in genomic and epigenomic profiling have enabled the identification of over 40 molecular subtypes defined by distinct genetic drivers, transcriptional programmes and regulatory alterations. These insights have refined the classification, particularly of B cell precursor ALL (B-ALL) and are increasingly informing risk stratification, therapeutic decision-making and disease monitoring. By contrast, the classification of T cell ALL (T-ALL) has historically relied on immunophenotypic criteria, but recent large-scale genomic studies have uncovered biologically defined subtypes driven by diverse coding and noncoding alterations. Many genomic lesions represent clinically actionable vulnerabilities, including kinase-activating alterations that have enabled the use of targeted therapies. However, treatment resistance remains a major challenge, arising through clonal evolution, acquisition of secondary mutations and adaptive transcriptional and epigenetic reprogramming. In this Review, we highlight recent advances in understanding of the biological basis of ALL, with a focus on recently identified genetic alterations, gene expression patterns, alterations in three-dimensional genome architecture and epigenetic regulation that drive ALL initiation, progression and therapeutic response. Furthermore, we discuss how genetic heterogeneity contributes to clinical variability and how integrating molecular and biological insights can improve risk stratification and therapeutic outcomes.
Context-dependent decision-making enables flexible behavior by allowing identical sensory inputs to guide different actions depending on memory, rules, or goals. Recent advances in large-scale neural recordings have shifted the focus from single-neuron tuning to population-level representations, revealing principles by which neural populations support such flexibility. Here, we review evidence of how context-dependent decisions are implemented by population coding mechanisms, including nonlinear mixed selectivity, task-dependent population geometry, shared representational subspaces, and structured across-neuron correlations. Nonlinear mixed selectivity expands representational dimensionality, allowing downstream readout of arbitrary combinations of task variables. Learning reshapes population geometry, and it may balance flexibility and generalization by promoting the reuse of shared representations when task components overlap. Structured correlations between neurons that share a projection target enhance transmission of context-dependent information to downstream circuits. These population-level coding mechanisms provide a conceptual framework for understanding how neural circuits integrate sensory and contextual information to guide behavior.
The King Ratsnake (Elaphe carinata), a widely distributed non-colubrine snake in East Asia, exhibits a remarkable capacity for broad-spectrum venom resistance, enabling it to prey on other snakes, including lethal viperid and elapid species. Despite its ecological and physiological significance, the genetic basis of this trait remains largely unknown. Here, we present a chromosome-level genome assembly of E. carinata, generated using PacBio HiFi long-read sequencing, Illumina short-read data, and RNA-seq-supported by a synteny-based scaffolding approach using the closely related Elaphe schrenckii. The 1.62 Gb assembly (contig N50 = 2.77 Mb, scaffold N50 = 143.07 Mb) achieves 97.3% BUSCO completeness, with over 90% of sequences anchored into 18 pseudochromosomes. Repetitive sequences account for 53.19% of the genome, with LINE elements being the most abundant. We annotated 19,750 protein-coding genes, of which 99.2% were functionally assigned using integrated evidence from homology, transcriptomics, and ab initio predictions. This high-quality genomic resource provides a foundation for exploring colubrid evolution, venom resistance mechanisms, and the development of novel antivenom therapies.
In 2021, a total of 82 million people used electronic cigarettes (e-cigarettes) globally. E-cigarette regulations around the globe vary widely from the product being banned in some jurisdictions to being completely unregulated in others. The Tobacco Pack Surveillance System (TPackSS) was initiated in 2012 to monitor tobacco packs available in 14 low- and middle-income countries with the greatest number of people who smoke. The aim of TPackSS is to assess compliance with country-specific tobacco packaging and labeling requirements and identify marketing features and appeals used on tobacco packaging. The objective of this study was to adapt and expand the previous TPackSS protocol to also include disposable e-cigarette devices and their accompanying products: e-cigarette liquids and pods or cartridges. E-cigarettes were added to TPackSS data collection in Indonesia in 2022 and in China in 2023. Collection took place in Jakarta, Medan, and Surabaya in Indonesia and Shanghai, Beijing, Chongqing, Guangzhou, Kunming, and Shenzhen in China. A total of 15 neighborhoods per city in Indonesia and 12 per city in China were visited. The TPackSS protocol developed for tobacco products in 2012 to 2013 was used as the foundation for the adapted protocol for e-cigarettes. The adaptation of the original TPackSS protocol followed an iterative process involving extensive discussions among the TPackSS study team, comprising researchers with expertise in tobacco control and 13 years of experience in tobacco product packaging surveillance. The study adapted the sampling frame and sampling strategy, pack collection procedures, photography guide, shipment and translation procedures, and codebook to account for the unique country contexts for e-cigarettes (eg, regulations, market for e-cigarettes, and retailer landscape) and the heterogeneity of e-cigarette packaging observed. These adaptations were based on the review of peer-reviewed literature, white papers, Euromonitor data, and consultation with researchers with expertise in e-cigarette marketing and with in-country public health professionals. Using Indonesia as a pilot country, the protocol was evaluated and further refined post implementation for use in China. The TPackSS study began in 2012 and was funded by Bloomberg Philanthropies. Data collection took place from September to October 2022 in Indonesia and April to May 2023 in China. Across Indonesia and China, 968 unique e-cigarette products were collected. TPackSS data collection, coding procedures, and study findings are publicly available for use on the TPackSS website. The protocols presented here, which were used in 2 countries with contrasting e-cigarette markets and regulatory requirements, can be adapted for use in other countries. Findings from use of this adapted protocol can inform policy by providing insights into the design features and marketing appeals of e-cigarette products available on the market, as well as compliance with health warning label requirements where applicable.
Prostate Cancer Antigen 3, a type of long non-coding RNA, exhibits outstanding specificity as a biomarker for the diagnosis of prostate cancer, offering a highly effective diagnostic indicator, whereas the currently used prostate specific antigen exhibits low specificity, leading to reduced accuracy in prostate cancer diagnosis. Herein, we designed a novel fluorescent sensing platform for targeted detection of PCA3, which integrates the non-specific trans-cleavage activity of the CRISPR/Cas12a with the remarkable fluorescence quenching effect of Gold Nanorods. The Cas12a recognizes and binds to specific sequences of PCA3, thereby activating nonspecific cleavage activity, which cleaves fluorescent reporter probes adsorbed on AuNRs, thus leading to the recovery of fluorescence signals and enabling sensitive detection. The proposed fluorescent sensor exhibits excellent accuracy and convenience for the detection of PCA3 in urine, and a detection limit as low as 1.65 pM was obtained. This sensing system has achieved effective detection of clinical samples of prostate cancer and is expected to provide significant assistance in the screening and therapeutic feedback of prostate cancer in clinical diagnosis.
In May of 2022, an aquarium-maintained broadnose sevengill shark (Notorynchus cepedianus) developed proliferative skin lesions that prompted pathologic and molecular investigation. Histopathologic examination revealed epidermal hyperplasia consisting of proliferation of spinous epithelial cells with mild dysplasia. Metagenomic sequencing identified a novel adomavirus with an 18,834 base pair circular double-stranded DNA genome. The virus, provisionally named broadnose sevengill shark adomavirus (7AdoV), contains two bidirectionally expressed protein-coding gene sets. Genomic annotation and structural predictions of proteins were used to contextualize 7AdoV phylogenetically and functionally. Transcriptomic analysis showed that expression of the structural late gene set was higher than the replicative early gene set at the time of diagnostic sampling. In situ hybridization using RNAscope technology localized transcripts of the adomavirus Wasp gene to epithelial cells of the hyperplastic epidermis. Infection by this novel adomavirus was associated with superficial and proliferative lesions that were self-limiting and resolved in this shark.
Recent advocacy efforts have resulted in 49 out of 50 U.S. states passing some form of dyslexia legislation. This legislation may serve as a starting point for educators, clinicians, and parents to advocate for universal oral language screening as well as dyslexia screening. The purpose of this exploratory study is to investigate the degree to which oral language skills are already included in existing policies. We used deductive and inductive coding procedures to identify key words related to oral language skills. We then performed document analysis on 156 legislative documents related to dyslexia to describe the following: (a) to what extent states include "language disorder" or other related terms in their descriptions of disorders encompassed by the legislation; (b) to what extent legislation includes keywords related to oral language; and (c) how language keywords are distributed across screening, intervention, preservice preparation, and professional development requirements. Two states include "language disorder" in the scope of dyslexia legislation. An additional eight states have legislation with terms that could encompass a language disorder. Out of the 49 states with dyslexia legislation, 29 include at least one language-related keyword. The most common language keywords found in such legislation were "comprehension" and "vocabulary." Keywords were mentioned across screening, intervention, preservice preparation, and professional development requirements. In many states, existing legislation lays the groundwork for implementing universal oral language skill screening. Further legislation dedicated to universal oral language screening is also necessary to ensure children with language disorders are identified early.
Understanding complex relations between neuronal activity and animal behavior is central question in neuroscience. Rapid advancements in Artificial Intelligence (AI) methods offer powerful tools to investigate highly non-linear mapping between motor cortex activity and body movements. Here, we developed a Generative Adversarial Network (GAN) that showed that detailed videos of behaving rats can be recreated from activity of just few selected neurons. This analysis also revealed that the predictability of behavior from neuronal activity (and vice versa) initially increases as a rat learns a new task. However, after the animal performance on the motor task achieves the required accuracy, then coupling between neuronal activity and behavior decreases, without degrading task performance. A plausible interpretation is that, as training progresses from Early to Mid training days, more neurons become engaged, forming a denser, broadly distributed representation, which then in the Late training days evolves into a sparse and more energy-efficient representation, with only a small subset of tuned neurons. Neuronal network simulations showed that such changes in coding strategy may be explained by neurons minimizing their energy use. Thus, our approach reveals a non-linear relationship between learning stages and neural-behavioral coupling, which is likely driven by energy efficiency.
Intervertebral disc degeneration (IDD) is the leading pathological cause of low back pain, while current clinical treatments are only palliative and cannot reverse the programmed cellular senescence driven by epigenetic dysregulation. This process is characterized by progressive loss of nucleus pulposus (NP) cell identity and establishment of a self-amplifying senescence-associated microenvironment. In this review, we synthesize recent advances elucidating how heterogeneous senescent cell populations and their secretory phenotype (SASP) orchestrate a destructive vicious cycle in IDD. We further dissect the synergistic interplay among DNA methylation, histone modifications, and non-coding RNAs that constitutes the "epigenetic aging clock" and drives premature cellular aging within the disc. Notably, we evaluate emerging therapeutic strategies aimed at clock reversal, including senolytic clearance of senescent cells, epigenetic remodeling using small-molecule inhibitors or CRISPR-dCas9 editing, and cellular reprogramming approaches ranging from iPSC differentiation to direct lineage conversion. We propose a synergistic "clear, prime, then seed" roadmap that sequentially combines these interventions for optimal regeneration. This work provides a systematic theoretical framework for the clinical translation of epigenetic-targeted therapy for IDD, and breaks through the cognitive limitation of traditional mechanical wear theory.
Low-dose ionizing radiation (LDIR, ≤100 mGy) is a public health concern due to its extensive use in diagnostic and therapeutic imaging. This study examined somatic variants (SV) among Korean industrial radiographers exposed to LDIR using whole-genome sequencing (WGS). WGS data from 65 workers (mean age 36.7 years) collected between 2016 and 2023 were analyzed. Participants had a mean employment duration of 12.7 years and an average cumulative radiation dose of 33.9 mSv from National Dose Registry records. SV were identified via the GATK Mutect2 single-sample workflow applied to peripheral blood-derived DNA and sequentially filtered using standard pipelines, including FilterMutectCalls, population frequency, recurrent artifacts, Funcotator annotation, and manual Integrative Genomics Viewer review. A total of 105 170 somatic variants were identified, with a median of 1744 variants per individual, approximately 98% of which were single nucleotide variants. Cumulative radiation dose showed a significant positive correlation with total SV burden (R=0.32, P=0.013), including both coding (R=0.34, P=0.008) and non-coding regions (R=0.31, P=0.015). Age, smoking, alcohol consumption, hypertension, and hyperlipidemia were not significantly associated with variant burden. These WGS-based findings provide preliminary insight into blood-derived SV patterns among occupationally exposed radiation workers. Given the small sample size, blood-only design, and absence of matched unexposed controls, the findings should be interpreted as hypothesis-generating and require validation in larger longitudinal studies with comprehensive exposure assessment.
We recently reported that GADD34, an integrated stress response (ISR)-associated protein expressed at low levels in many cell lines, functions as a novel HIV-1 restriction factor. To elucidate the mechanism underlying GADD34-mediated inhibition of HIV replication, we investigated the role of long non-coding RNAs (lncRNAs). Here, we identify and characterize a novel lncRNA, GRHAL1 (GADD34-regulated HIV accessory lncRNA-1), which is highly expressed in GADD34-knockout (GADD34-KO) cells relative to WT cells. GRHAL1 is expressed at low basal levels in Jurkat and MT-2 CD4+ T cell lines and in primary human CD4+ T cells and is upregulated following HIV-1 infection. T cell activation signals that promote HIV-1 replication also induced GRHAL1 expression; however, this induction was independent of IFN and ISR signalling. Transfection of in vitro - synthesized GRHAL1 significantly enhanced HIV-1 LTR-driven gene expression from both integrated and unintegrated promoters. GRHAL1 stimulated both Tat-independent and Tat-dependent LTR activation, with a more pronounced effect observed at suboptimal Tat levels, indicating functional synergy between GRHAL1 and Tat under limiting Tat conditions. Mutational analysis of the LTR demonstrated that GRHAL1-mediated activation requires an intact Tat-responsive TAR element and upstream Sp1-binding sites, linking GRHAL1 activity to Tat and Sp1 in transcriptional regulation. This synergy was further confirmed using a minimal HIV-1 promoter containing Sp1 sites and a TAR sequence. Moreover, GRHAL1 alone was sufficient to activate a heterologous promoter containing Sp1-binding elements. The Sp1-selective inhibitor mithramycin suppressed both Tat-independent LTR activation and the cooperative activation mediated by GRHAL1 and Tat. Electrophoretic mobility shift assays, RNA immunoprecipitation and RNA-pulldown experiments demonstrated that GRHAL1 directly interacts with Sp1 and that Tat enhances this interaction, suggesting that GRHAL1 modulates Sp1 activity through direct binding. In summary, we identify GRHAL1 as a novel HIV-1-induced lncRNA that regulates viral gene expression by interacting with Sp1 and synergizing with Tat to enhance HIV-1 transcription.