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We report the 8,451-nt coding-complete genome sequence of a divergent black queen cell virus strain (BQCV-Ro). This strain was identified via retrospective analyses of metagenomic virome data of Apis mellifera samples from Europe. The genome assembly is supported by extensive read mapping, with 100% horizontal coverage and a mean sequencing depth of ~338,171×. and shares 94.3% identity with the BQCV Yeongdeok isolate.
Examine neonatologists' perspectives on disclosing rapid genomic sequencing (rGS) results, including the barriers and facilitators they perceive. Neonatologists from 10 NICUs participating in the Virtual Genome Center (VIGOR) study were surveyed after each rGS disclosure and interviewed regarding their experience after 2 or more disclosures. Quantitative results were compared by result type, and qualitative results were iteratively coded for themes. 93% of neonatologists felt comfortable disclosing rGS results regardless of result type. Neonatologists utilized multiple resources to prepare for disclosures, including the VIGOR Clinical Interpretive Report, medical literature, and local genetics experts. They preferred to have a geneticist present during disclosure when possible. Neonatologists were motivated to participate in disclosures to help families and leverage existing trust. Neonatologists are important to the rGS disclosure experience, but a joint effort with genetics experts may be the ideal model to successfully expand access. NCT05205356/clinicaltrials.gov .
Barriers to initiating and maintaining HIV care continue to impede efforts to "End the HIV Epidemic" in the United States, particularly among members of Black sexual and gender minoritized (BSGM) groups in the US South. Evidence-informed social network-based interventions may improve engagement in HIV care services among BSGM; however, understanding and addressing context-specific barriers and facilitators to HIV service use are critical for intervention effectiveness. We explored barriers to HIV care engagement to inform the adaptation of a social network strategy to increase participation in HIV prevention and care services in Charlotte, NC. We interviewed BSGM with HIV who were in treatment, local health department officials, clinicians, and community-based organization leaders and held four focus groups (FGs) with HIV public health services staff. Transcripts were iteratively coded and analyzed thematically. We identified two themes across all FGs and in-depth interviews (IDIs). Two additional themes were identified specifically from IDIs with BSGM. Across data sources, participants described multi-level stigma, competing priorities, and logistical hurdles that impede BSGM engagement in HIV care. BSGM with HIV indicated that supportive social networks enhanced HIV treatment adherence and described how their personal agency and self-efficacy evolved after receiving an HIV diagnosis. Interventions to improve HIV care engagement among BSGM with HIV must address inequities, leverage social support networks, and enhance self-efficacy.
ARL15, coding for a small GTPase, was identified as a non-HLA susceptibility gene in rheumatoid arthritis (RA) through a GWAS in a North Indian cohort, with serum adiponectin and ARL15 levels higher in RA patients with the associated genotype. This study aimed to delineate the functional role of ARL15 in RA pathobiology. Differential transcriptomics in both ex vivo RA synovial fibroblasts and in vitro MH7A cells using a gene knockdown (KD) approach and standard analyses pipeline were performed to obtain insights into ARL15's role. In RASF, ARL15 KD led to downregulation of COMP-an extracellular matrix stabilizer linked to severe RA-alongside upregulation of adiponectin and IFN response genes like IFI6 and USP18. Furthermore, upregulation of NPTX1 and MX1, previously associated with disease modulation and treatment response, was observed. Downregulation of CTGF, CD248, and PTX3 suggested involvement of ARL15 in inflammation and RA-associated cardiovascular risk. Conversely, ARL15 KD in MH7A cells displayed distinct signatures with upregulated cytokines (IL1A, IL8, CXCLs) and downregulated inflammatory regulators (DOCK2, TLR4, TGFB2), reflecting an inflammatory bias distinct from patient-derived RASF. The dual-system approach, despite its divergent differential expression, underscores the multifaceted role of ARL15 in regulating connective tissue architecture, inflammation, and immune response. Limitations of immortalized cell models in capturing patient heterogeneity and disease complexity are apparent, but the key findings position ARL15 as a promising therapeutic target, warranting further investigation in RA animal models and genomic medicine. Taken together, this work provides a compelling rationale to pursue ARL15 targeted interventions in RA management.
Collecting reliable sexual behaviour data remains a major challenge in conservative, low-literacy contexts such as The Gambia, where stigma, privacy concerns, and social desirability bias influence responses. The Prevalence of Human Papillomavirus, Antimicrobial resistance, and Sexually transmitted infection Estimation (PHASE) survey sought to address this challenge by introducing Audio Computer-Assisted Self-Interviewing (ACASI) for the first time in The Gambia. This paper documents the design, development, and piloting of the ACASI tool, highlighting key lessons for similar settings in sub-Saharan Africa.A Community Advisory Board (CAB) was central to the tool's development, ensuring cultural sensitivity, acceptability, and linguistic accuracy. CAB members guided the drafting and adaptation of sexual behaviour questions, advised on culturally relevant response categories, and reviewed translations into four local languages (Mandinka, Serahule, Fula, Wolof). They also oversaw the design of non-threatening, familiar images to accompany response options and ensured accurate, context-appropriate audio recordings. Technical implementation was achieved using the SurveyCTO platform, allowing offline use, encryption, and integration of multilingual audio and images. Privacy safeguards were embedded, including screen codes replacing text to prevent disclosure in shared settings and restricted staff access to individual responses.Pilot testing revealed critical operational considerations. Many women lacked prior experience with digital tools and required extra support during the introductory phase. Adjustments included re-recording unclear questions, reordering items to reduce priming effects, and randomising response lists to enhance validity. Additional measures, such as repeating select questions at different points, improved internal consistency checks. Despite these challenges, participants demonstrated increasing confidence with the tool, and CAB feedback confirmed that ACASI was more acceptable for sensitive questions than face-to-face interviewing.Our experience demonstrates that ACASI is a feasible and culturally appropriate method to collect sexual behaviour data in The Gambia, even within low-literacy, conservative populations. The use of familiar images, validated translations, and community engagement enhanced usability, while technical refinements addressed privacy and confidentiality concerns. Key challenges related to computer literacy and dialect variation were addressed through training, piloting, and iterative refinement. This process illustrates that by prioritizing community involvement, technical adaptation, and cultural sensitivity, ACASI offers a promising framework to enhance the acceptability and potentially the accuracy of sexual behaviour reporting in large-scale epidemiological surveys. These lessons can be applied to similar sub-Saharan African contexts seeking to generate high-quality data to inform HPV (human papillomavirus), STI (sexually transmitted infection), and sexual health research.
Vascular injury during total knee arthroplasty (TKA) is rare, but potentially catastrophic, leading to ischemia, the need for vascular repair, or limb loss. Robotic-assisted TKA (RA-TKA) incorporates computed tomography (CT)-based three-dimensional planning, intraoperative balancing, and haptic boundaries that may reduce intraoperative saw excursion and mitigate neurovascular risk. This study compared the incidence of vascular injuries between RA-TKA and conventional manual TKA (M-TKA). A retrospective query of a nationwide insurance claims database (2010 to 2022) identified 2,522,651 primary TKAs (21,921 RA-TKA; 2,500,730 M-TKA). The RA-TKA was defined by robotic-assisted procedure codes and CT scan within 60 days of surgery. Vascular injuries within 30 days of surgery were identified using International Classification of Diseases, Ninth/Tenth Revision (ICD-9/10) diagnosis and procedure codes. A 1:5 nearest-neighbor matching algorithm controlled for age, sex, and comorbidities. Before matching, RA-TKA patients differed in age, sex, and comorbidity profiles compared with M-TKA. After matching, the cohorts were well-balanced. Multivariable logistic regressions calculated odds ratios (OR) with 95% confidence intervals (CI) for vascular complications, with significance set at P < 0.05. Popliteal artery injuries occurred in 49 M-TKA (0.002%) and zero RA-TKA (0%) cases. After adjustment, RA-TKA was associated with significantly lower odds of vascular injury compared with M-TKA (adjusted OR 0.21, 95% CI 0.05 to 0.86, P = 0.030). The absolute risk difference was 0.002%, corresponding to a number needed to treat of 50,000. In this large national cohort, RA-TKA was associated with a substantially reduced risk of popliteal artery injury compared with M-TKA. While rare overall, the catastrophic consequences of vascular injury underscore the clinical importance of this association. As TKA utilization rises, robotic platforms may offer a meaningful clinical benefit by helping surgeons reduce the incidence of these devastating neurovascular complications.
Approximately 2% of the human genome encodes proteins, while the remaining non-coding regions 19 may play critical roles in human diseases. Among these, long non-coding RNAs (lncRNAs) are 20 emerging as key regulators of gene expression through epigenetic, transcriptional, and post-21 transcriptional mechanisms, and may serve as potential biomarkers. In this pilot study, we investigated 22 lncRNAs in Parkinson's disease (PD) patients undergoing a six-week intensive multidisciplinary 23 rehabilitation program. Plasma samples from 26 PD patients were collected before (T0) and after (T1) 24 the intervention. Array profiling of 84 inflammation- and immunity-related lncRNAs revealed that 25 86% were differentially expressed post-intervention, with 55 upregulated (fold change >2) and 17 26 downregulated. Quantitative PCR confirmed significant upregulation of MALAT1, TUG1, and XIST 27 at T1 (p < 0.05). Plasma IL-1β levels were also significantly reduced after rehabilitation (p = 0.01). A 28 2 significant reduction in UPDRS-III scores was observed at T1 (p = 0.031), reflecting improved motor 29 function; however, no significant correlation was found between clinical changes and molecular 30 findings. These preliminary, hypothesis-generating results suggest that rehabilitation may modulate 31 immune-related lncRNAs and inflammatory markers in PD, providing insights into their regulatory 32 roles in neuroinflammation and potential as biomarkers of response to rehabilitative interventions.
Trypanosoma carassii, a typical freshwater fish trypanosome, has recently been identified as the etiological agent of a trypanosomiasis outbreak in cage-cultured large yellow croaker (Larimichthys crocea) in China and has been designated as T. c. larimichthys. To date, publicly available genomic data for trypanosomes have been limited to terrestrial species, particularly those of medical importance. Here, we present a chromosome-level genome assembly of T. carassii, the first genome of an aquatic trypanosome, generated using PacBio HiFi long-read sequencing and Hi-C scaffolding technologies. A preliminary genome survey based on Illumina sequencing data estimated the genome size at 56.38 Mb with a heterozygosity of 1.17%. The final assembled genome spans 48.55 Mb, with contig N50 and scaffold N50 values of 139.15 Kb, and achieves 100.00% BUSCO completeness. Hi-C data resolved the assembly into 34 chromosomes and 9 unanchored scaffolds. Repetitive elements account for 53.29% of the genome (approximately 25.87 Mb). A total of 11,584 protein-coding genes were predicted, 95.36% of which were functionally annotated. Synonymous substitution rates analysis of paralogous genes indicates a recent burst of gene duplication, which likely corresponds to a whole-genome duplications. This high-quality genome assembly provides invaluable resources for understanding the evolution and host adaptation of aquatic trypanosomes.
Long non-coding RNAs (lncRNAs) play key roles in gene regulation. One potential regulation mechanism involves the formation of RNA•DNA:DNA triplexes. In these triplexes, the lncRNA binds in the major groove of a target DNA via Hoogsteen base pair formation. Here, we investigated the impact of the underlying RNA binding on the on the stability of the DNA duplex target to gain insights into the triplex stability at base pair resolution. Quantification of the temperature-dependent exchange of imino hydrogen atoms with solvent of the target DNA duplex allows determination of the changes of the stability of individual DNA duplex base pairs upon triplex formation. The data shown here investigates an antiparallel triplex, formed between the lncRNA hypoxia-inducible factor 1-alpha Antisense RNA 1 (HIF1α-AS1) and the DNA target Adrenomedullin (ADM), important in cardiovascular diseases. Triplex formation alters DNA structure and stability by affecting both hydrogen bonding strength and nucleobase-stacking interactions. These thermodynamic insights support bioinformatic methods to predict triplex stability and enhance our understanding of RNA•DNA:DNA triplex formation.
Elevated low-density lipoprotein cholesterol (LDL-C) leads to atherosclerotic plaque buildup and drives cardiovascular disease. Despite the availability of effective therapies for LDL-C reduction, elevated LDL-C is common in the United States. To measure the success of a pharmacist-led telephonic outreach program designed to proactively address individuals with hyperlipidemia who were not being treated in accordance with cholesterol guidelines and collaborate with their primary care clinicians (PCCs) to increase guideline-based care. The 3-month outreach occurred from September through November 2023. Health plan members with 1 inpatient or 2 outpatient claims for hyperlipidemia within the previous year were determined using International Classification of Diseases, Tenth Revision, Clinical Modification codes. Members not managed in accordance with the 2018 American Heart Association/American College of Cardiology (ACC)/Multisociety Guideline and 2022 ACC Expert Consensus Decision Pathway, based on available claims data, received a personalized action recommendation. The outreach team contacted the member and scheduled a phone call with a pharmacist. If the member agreed to the pharmacist's clinical recommendation, the outreach team contacted the member's PCC directly (by fax or e-mail). PCCs were responsible for the final clinical decision and action. Of 14,979 members who met the inclusion criteria, 883 were selected at random for contact by the outreach team. Of these, 667 members (76%) accepted a call with a pharmacist and were considered the intervention group. An additional 5,266 members who were not contacted and did not share a PCC with someone in the intervention group were included as the control group. In the intervention group, 92.4% of members accepted the guideline-based hyperlipidemia recommendation, allowing the pharmacist to contact their PCC. The overall percentage of members moving toward guideline-recommended care in the intervention group (25.5%) was approximately twice that in the control group (11.1%). Members could undergo an LDL-C test if they had no LDL-C result available, initiated lipid-lowering therapy (LLT) if they were not already being treated for hypercholesterolemia, or intensified their existing statin regimen or added a nonstatin LLT. The difference in proportion of members remaining on no statin throughout the program was significantly lower in the intervention group (-7.9% [95% CI = -11.3% to -4.5%]) vs the control group. At the end of the pilot, 8.7% (58 of 667) of intervention group members received LLT in accordance with current guidelines vs 6.0% (316 of 5,266) in the control group. This study demonstrated that a health plan-driven, pharmacist-led, educational outreach program increased movement toward guideline-based LDL-C management in a 3-month pilot. Similar programs could increase the proportion of members receiving guideline-based care in a variety of chronic disease settings.
Stroke is a leading cause of long-term disability, and many patients experience persistent neurological and functional impairments after the acute phase. The Korean government launched a national pilot reimbursement program for herbal decoctions to improve access to Korean Medicine (KM) rehabilitation and generate real-world evidence on its safety and effectiveness. This study aimed to analyze the utilization patterns, clinical outcomes, and safety of herbal medicine (HM) among patients with post-stroke sequelae participating in the pilot program. A retrospective analysis was conducted using nationwide health insurance claims data from the Health Insurance Review and Assessment Service (HIRA). Patients diagnosed with sequelae of cerebrovascular disease (KCD codes I69 or U234) who received reimbursed HM prescriptions between November 2020 and April 2024 were included. Demographic characteristics, prescription patterns, and symptom severity were analyzed. Symptom changes between the first and last visits were assessed using the Wilcoxon signed-rank test, and adverse events (AEs) were identified from newly added diagnostic codes after HM treatment. A total of 942 eligible patients were analyzed, with a mean age of 73.2 ± 6.0 years. The majority (57%) initiated KM treatment more than 1 year after stroke onset. The most frequently prescribed formulas were Gamidaebo-tang (23.1%), Mangeum-tang (5.8%), and Gagampalmi-hwan (5.1%). Among 609 patients with paired symptom records, 19.4% showed improvement, 71.9% remained stable, and 8.7% worsened (p < 0.001). AEs occurred in 1.03% (10/962) of patients, predominantly gastrointestinal symptoms such as diarrhea (55.6%). All reported AEs were mild and self-limiting. This study provides the first nationwide real-world evidence on the use, effectiveness, and safety of HM for post-stroke sequelae under Korea's pilot reimbursement program. Individualized herbal decoctions were widely prescribed and generally well tolerated, showing meaningful symptom stabilization in chronic stroke care. These findings support the feasibility and clinical safety of reimbursed HM and highlight the need for prospective studies to evaluate long-term outcomes, safety, and cost-effectiveness under the expanded second-phase program.
Black women diagnosed with ductal carcinoma in situ (DCIS) experience disproportionately higher risk of second breast cancer events (SBEs), including both ipsilateral and contralateral recurrences, yet remain underrepresented in molecular biomarker studies compared to non-Hispanic White women. We performed RNA sequencing on 200 archival DCIS samples from the Resource of Archival Breast Tissue cohort, including 33% self-reported Black women. We correlated transcriptomic and clinical data to identify predictors of SBEs. Cases (n = 100) who developed SBEs between 1999 and 2019 were matched 1:1 to controls (n = 100) on age, race, and margin status, who remained event-free during a comparable follow-up period in this observational study. RNA-seq was conducted using the Illumina NovaSeq 6000 platform, which yielded high-quality transcriptomic profiles (13,460 protein-coding genes) from 141 out of 200 samples. Differential gene expression and pathway analyses were used to identify molecular predictors of SBE risk. Principal component analysis demonstrated that transcriptomic variance was associated with race and follow-up duration. Four genes, CHGB, RBM20, SYP, and SYNJ2BP, were significantly associated with ipsilateral SBEs (FDR P value < 0.05). Interferon-alpha signaling was the most significantly enriched pathway in DCIS cases compared with controls. Gene signatures varied by recurrence site (e.g., contralateral SBEs) and covariates, including self-reported race. Our findings demonstrate the feasibility and value of RNA-seq from diverse archival DCIS specimens. We identified novel transcriptomic alterations associated with second breast cancer events in DCIS. Our results support the inclusion of racially diverse biospecimens in biomarker discovery. These findings warrant validation in independent cohorts. These molecular insights have the potential to refine risk prediction tools and inform equitable strategies for DCIS management.
Resistance to first-line multikinase inhibitors (MKIs) sorafenib and lenvatinib critically limits hepatocellular carcinoma (HCC) treatment efficacy. It remains largely unknown how long non-coding RNAs (lncRNAs) affect resistance to MKIs. Through integrated analysis of resistant HCC models, we identified lncRNA LMCD1-AS1 as a critical driver of MKI resistance. LMCD1-AS1 overexpression correlates with advanced tumor stage, shortened survival, and resistance to MKI therapy in HCC patients. LMCD1-AS1 confers dual resistance to sorafenib and lenvatinib by suppressing apoptosis, while its knockdown restored drug sensitivity. Mechanistically, LMCD1-AS1 directly bind histone demethylase PHF8, promoting H4K20me1 to epigenetically activate oncogenes (e.g., c-Myc, β-catenin) and upregulate lactate dehydrogenase A (LDHA). This triggers lactate overproduction and alters the NAD+/NADH ratio, establishing a protumorigenic metabolic state. Crucially, PHF8 ablation reverses LMCD1-AS1-driven resistance, and in vivo xenografts confirm attenuated sorafenib efficacy with LMCD1-AS1 overexpression. Our work unveils the LMCD1-AS1/PHF8/H4K20me1 axis as a unified epigenetic-metabolic mechanism underlying MKI resistance, representing a promising therapeutic target and prognostic biomarker for HCC.
Children with painful disorders of gut brain interaction (DGBIs) report stigmatization from medical providers, school personnel, family members, and peers. The consequences of pain-related stigma include concealment of symptoms, lower mood, and poorer functioning. Stigma from other identities (e.g., race, gender) can intersect with pain-related stigma. Unfortunately, intersectional stigma remains understudied in the pediatric pain literature. Furthermore, chronic pain research tends to focus on deficits, rather than strengths. Thus, the current study aimed to understand the experiences of stigma and means of resilience in a sample of Black youth with painful DGBIs. Twenty Black youth between 8 and 18 years old completed semi-structured qualitative interviews. Thematic analysis was conducted via a combined deductive (a priori codes based on theory) and inductive (codes emerging from the data) approach. Codes were grouped into 4 major themes including 1) Experiences of Stigma, 2) Responses from Social Spheres of Influence, 3) Coping Strategies, and 4) Patient-centered Approaches to Treatment, and 8 subthemes. Overall, participants reported stigma from providers, teachers and nurses, family, and peers, while also relying on these groups for support. They were most sensitive to support from caregivers. Others' lack of knowledge about DGBIs appeared to be the largest risk factor for stigma, indicating a potential role for providers in mitigating stigma. Some youth also described the ways that intersecting identities (i.e., race, age, and gender) influenced how others viewed and interacted with their pain. Considerations for reducing stigma and facilitating coping are discussed. PERSPECTIVE: This article presents qualitative data on the experiences of Black youth with painful disorders of gut brain interaction. This study contributes to efforts to diversify pain research. Findings may aid in developing patient-centered interventions for chronic pain.
Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. It is characterized by inflammation, areas of demyelination and axonal loss called plaques, recruitment of lymphocytes and monocytes, and bursts of focal blood-brain barrier leakage. Treatment strategies for MS focus on delaying disease progression and increasing patients' quality of life. However, most therapies have inconsistent efficacies and are associated with various side effects. Recently, long non-coding RNAs have been found to play a major role in the pathogenesis and development of several diseases. Several long non-coding RNAs have been correlated with MS. We focus on the role of AFAP1-AS1 in regulating the function of M2 macrophages, one of the immune cells believed to attenuate MS. Assessing this long non-coding RNA will improve our understanding of the molecular mechanics of immune cells in MS. We observe the impact of AFAP1-AS1 silencing in M2 macrophages on essential effector and regulatory proteins like MMP9, CCL5 and CXCL10 in MS patients receiving different treatments (Fingolimod, Interferon beta-1a, Interferon beta-1b, Teriflunomide or Dimethyl fumarate). Our results reported an upstream regulatory effect of AFAP1-AS1 on MMP9, CCL5, and CXCL10 in differently treated patients. By measuring the levels of proteins upon silencing of AFAP1-AS1, it was confirmed that this lncRNA has varying effects on the expression of these proteins depending on the treatment the patient is undergoing. These data shed light on the potential role of manipulating the anti-inflammatory activity of M2 cells making it a possible therapeutic target for certain MS patients.
Attention is a cornerstone of cognition and neural computation, enabling the brain to select relevant information, bind features into coherent objects, and guide behavior. However, we currently lack a unifying computational model that connects the diverse phenomena of attention, from spatial and feature-based selection to object-based binding, within a single, neurally plausible computational framework. Here, we propose a bidirectional recurrent gating mechanism integrated into a principled architecture of the ventral visual stream. In this architecture, feedforward pathways extract visual features, while top-down and lateral connections transmit context- and task-dependent modulatory signals that control information flow. We demonstrate that our model, trained on recognition and segmentation problems, successfully performs the canonical attention tasks of orienting, filtering, and visual search on complex scenes. It replicates key psychophysical phenomena, such as perceptual load and inattentional blindness, while its internal units develop neural properties consistent with primate physiology, including multiplicative gain modulation and border-ownership coding. Our work provides evidence that this diverse set of attentional and binding phenomena can emerge from error-backpropagation combined with architectural constraints upon information flow, offering a powerful tool for neuroscience and a compelling, bio-inspired alternative to standard AI architectures.
The transition of embryonic stem cells (ESCs) from a pluripotent state to lineage commitment is governed by complex regulatory mechanisms, including chromatin remodeling, as well as transcriptional and post-transcriptional processes. Recent studies have emphasized the interplay between these mechanisms, revealing intricate, multilayered regulatory networks that require further elucidation. In this study, we reveal a new connection between the RNA-binding protein LIN28A and the epigenetic regulation of ESC differentiation. LIN28A is upregulated during the early stages of neural commitment and undergoes a shift in subcellular localization from the nucleus to the cytoplasm upon differentiation. Generation and analysis of Lin28a knockout (KO) ESCs revealed that, although these cells can self-renew, they exhibit a pronounced defect in differentiating into neural precursors. However, mesodermal and endodermal differentiation proceeds normally in Lin28a KO cells, suggesting a neuronal-specific function for LIN28A. Proteomic analyses revealed a dynamic, context-dependent LIN28A interactome, with distinct sets of putative interacting partners in ESCs compared to those in differentiating cells. Among the ESC-specific putative interactors, we validated an RNA-dependent association of LIN28A with components of Polycomb Repressive Complex 2 (PRC2), a key chromatin-modifying complex that deposits the repressive histone modification H3K27me3. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) demonstrated that loss of LIN28A results in persistent PRC2 occupancy at the promoters of developmental genes, accompanied by partial uncoupling between PRC2 binding and H3K27me3 deposition. Lin28a KO causes differentiation defects that are not rescued by pharmacological inhibition of PRC2 enzymatic activity, suggesting that LIN28A regulates PRC2 chromatin dynamics independently of H3K27me3 deposition. Furthermore, we identified an interaction between LIN28A and the long non-coding RNA Neat1, which may serve as a scaffold facilitating PRC2 eviction from chromatin. Taken together, our findings reveal a previously unrecognized role for LIN28A in regulating PRC2-mediated chromatin dynamics and underscore its importance in epigenetic control of neuronal differentiation.
To observe the effects of long non-coding RNA H19(lncRNA H19) transfection on the expression of multiple osteogenic and angiogenic factors and the osteogenic capacity in human umbilical cord mesenchymal stem cells (hUC-MSCs), so as to provide a preliminary research basis for the future development of bone defect fillers with favorable blood supply. Bioinformatics analysis was performed to confirm that H19 could regulate bone formation-related microRNAs (miRNAs) and their downstream osteogenic and angiogenic factors. The target molecules were finally identified as miR-137-3p, miR-383-5p, and their regulated factors including integrin-binding sialoprotein (IBSP), Runt-related transcription factor 2 (RUNX2), and fibroblast growth factor 5 (FGF5). Human umbilical cord mesenchymal stem cells were cultured in vitro. lncRNA H19 was then transfected into hUC-MSCs. Reverse transcription-polymerase chain reaction(RT-PCR) was used to detect the expression abundance of miR-137-3p and miR-383-5p in transfected cells. Western blot was applied to measure the expression levels of IBSP, Runx2 and FGF5. Alkaline phosphatase (ALP) staining and alizarin red S staining were conducted to evaluate the osteogenic capacity of cells after H19 transfection. We verified whether lncRNA H19 transfection could downregulate the expression of miR-137-3p and miR-383-5p, thereby upregulating the expression of osteogenic and angiogenic factors IBSP, Runx2 and FGF5, and confirmed that lncRNA H19 transfection promoted osteogenic differentiation of hUC-MSCs. The expression levels of miR-137-3p and miR-383-5p were downregulated in hUC-MSCs transfected with lncRNA H19, whereas the expression levels of Runx2, IBSP and FGF5 were significantly increased from (0.533±0.058), (0.633±0.058), (0.500±0.100) before transfection to (1.300±1.100), (1.233±0.058), (0.967±0.115) after transfection, respectively, with statistically significant differences (P=0.000, P=0.000, P=0.006). Moreover, hUC-MSCs exhibited enhanced osteogenic capacity after H19 transfection. Transfection with lncRNA H19 promotes the expression of several osteogenic and angiogenic factors and enhances the osteogenic capacity of hUC-MSCs. This provides a potential basis for the future development of tissue-engineered bone incorporating lncRNA H19 to improve its osteogenic and angiogenic performance.
Ischemic stroke in Saudi Arabia arises in a highly consanguineous population with a distinctive genetic architecture, likely enriching rare coding variants that influence stroke risk. Yet the contribution of these variants to stroke susceptibility, age at onset, and subtype patterns in this setting remains incompletely defined. We analyzed whole-exome sequencing data from 514 stroke patients in a case only study design. Gene-based rare variant burden analyses was performed using SAIGE-GENE+ burden and SKAT-O tests across predefined phenotype contrasts within the cohort, stroke severity (modified Rankin Scale, mild < 3 vs. severe ≥ 3 ,), age at onset (early-onset < 25 years vs. late-onset > 45 years; mid-life onset < 45 vs. > 45), etiological subtypes (TOAST classification), and vascular imaging patterns (intracranial vs. extracranial).Post-association functional annotations included GTEx expression, gnomAD constraint metrics, and draggability insights. Gene-level associations at a suggestive threshold (p < 0.005) identified several candidates including HSP90AB1, PRR23A, and LRRC42 (severity and age-at-onset); POGZ and SMIM34 (age-at-onset); and COL9A3, DCP1B, and ADGRV1 (imaging and etiology subtypes). The highlighted genes showed varying expression across brain and vascular tissues and intolerance to loss-of-function variation. Notably, HSP90AB1, a molecular chaperone highly expressed in the brain and vasculature, has small-molecule inhibitors, supporting its potential relevance to stroke biology. Our findings identify exploratory candidate gene-level signals across clinically defined ischemic stroke phenotypes based on case-only within-cohort comparisons, in underrepresented population. These results should be considered hypothesis-generating and require replication and functional validation before biological or clinical inferences can be made.
To quantitatively assess parental engagement, perceptions, and decision-making attitudes toward fluorescence-guided surgery (FGS) in pediatric solid tumors. A structured questionnaire was administered to caregivers of children with Beckwith-Wiedemann syndrome in collaboration with the "Associazione Italiana Sindrome di Beckwith-Wiedemann", facilitating outreach to families within the national support network. Emotional responses (optimism, hope, confidence, anxiety, worry, and uncertainty) and perceived support were assessed using 5-point Likert scales (1 = not at all, 5 = extremely). The survey also explored prior awareness of FGS, perceived impact on surgical outcomes and recurrence risk, openness to clinical trial enrollment, concerns, and information needs. Data were analyzed descriptively; open-ended responses were thematically coded. Twenty-eight caregivers completed the survey. 86% of children had undergone tumor resection, predominantly for nephroblastoma (85%). Preoperative counseling was considered clear by 79% of caregivers, and perceived support from the medical team was high, with 68% reporting the maximum Likert score (5/5). Prior awareness of FGS was limited (11%); however, after explanation, acceptance was strong. Trust in surgical innovation was high (75% reporting maximum confidence), and 86% believed FGS could improve surgical safety and effectiveness. All respondents reported increased reassurance from the availability of technological support, and 71% perceived a potential reduction in recurrence risk. Emotional responses were predominantly positive, with high levels of confidence, hope, and optimism (75% maximum score), while anxiety, worry, and uncertainty were generally low. Qualitative analysis identified 3 main themes: strong trust and reassurance toward innovation, safety-related concerns focused on toxicity and long-term effects, and a clear need for transparent, detailed risk-benefit information prior to decision-making and potential clinical trial enrollment. Parents demonstrate high engagement and strong support for FGS, emphasizing the importance of transparent communication, shared decision-making, and active parent-patient involvement to facilitate clinical translation.