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Hematological Correlates of Hemoglobinopathies in Women of Reproductive Age With Anemia: A High-Performance Liquid Chromatography (HPLC)-Based Cross-Sectional Study

Cureus. 2026 Jun 29;18(6):e111733. doi: 10.7759/cureus.111733. eCollection 2026 Jun.

ABSTRACT

BACKGROUND: Anemia continues to pose a significant public health challenge, particularly among women of reproductive age. Despite ongoing nutritional intervention programs and iron supplementation strategies, the burden of anemia remains persistently high. In addition to iron deficiency anemia (IDA), inherited hemoglobin disorders such as β-thalassemia and sickle cell disease are important contributors to anemia. High-performance liquid chromatography (HPLC) has emerged as a reliable and widely used method for the identification of hemoglobin variants and the quantification of hemoglobin A₂ (HbA₂) and hemoglobin F (HbF). The objective of our study was to investigate the range of hemoglobinopathies identified by HPLC and to compare them with routine hematological parameters.

METHODS: Our study was conducted in the Department of Pathology, Rajendra Institute of Medical Sciences, Ranchi, over 18 months from August 2024 to January 2026. A total of 277 anemic females aged 19-49 years with hemoglobin levels below 11 g/dL were enrolled. Hematological parameters were analyzed using an automated hematology analyzer, while hemoglobin fraction analysis was performed using cation-exchange HPLC. Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 27 (Released 2019; IBM Corp., Armonk, New York, United States).

RESULTS: The mean age of participants was 33.2 ± 9.07 years, and the mean hemoglobin level was 9.7 ± 0.95 g/dL. Microcytic hypochromic anemia was the predominant pattern with elevated red cell distribution width (RDW) values indicating anisocytosis. HPLC analysis revealed abnormal hemoglobin patterns in 44% of participants. Sickle cell trait was the most common abnormality (26%), followed by sickle cell disease (11%) and β-thalassemia trait (7%). RDW showed significantly superior discriminative ability for predicting hemoglobinopathies compared to mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH).

CONCLUSION: Hemoglobinopathies were common among anemic women of reproductive age, with sickle cell trait being the predominant abnormality detected on HPLC analysis. Routine hematological parameters showed considerable overlap, whereas RDW demonstrated better discriminatory ability but was insufficient alone. HPLC improved the detection and characterization of hemoglobin variants and may be useful in the targeted evaluation of high-risk populations.

PMID:42529704 | PMC:PMC13418751 | DOI:10.7759/cureus.111733

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Sense of coherence as a pathway linking war trauma and post-migration stress to mental health functioning among refugees and asylum seekers in the Netherlands

Front Psychiatry. 2026 Jul 15;17:1890660. doi: 10.3389/fpsyt.2026.1890660. eCollection 2026.

ABSTRACT

INTRODUCTION: Refugees carry a cumulative burden of past trauma and ongoing post-migration stress, yet the mechanisms linking these to mental health functioning remain incompletely understood. Sense of coherence – a salutogenic orientation comprising comprehensibility, manageability, and meaningfulness – may help account for these associations. We tested sense of coherence as a mediator of both associations and compared the relative weight of the two stressor domains.

METHODS: A cross-sectional sample of 151 refugees and asylum seekers in the Netherlands (84.1% with a residence permit) completed the LEC-5, PMLP, SOC-13, and OQ-45.2 in person with research-assistant support across Dutch, English, and Arabic. We conducted multiple regression and three PROCESS Model 4 mediation analyses, including a parallel mediation with sense of coherence and post-migration stress as simultaneous mediators.

RESULTS: Both stressors predicted poorer functioning, with post-migration stress substantially stronger than trauma exposure (b = .40 vs. .17). Sense of coherence was the strongest correlate of functioning (r = -.57) and statistically mediated both cross-sectional associations. In the parallel mediation, sense of coherence and post-migration stress mediated the trauma-functioning association, and the direct effect was no longer statistically significant once both were included. Family-oriented stressors dominated the burden profile: worries about family in the country of origin (78.8%), missing family (73.5%), and uncertainty about the future (70.9%).

DISCUSSION: As a personal-resilience construct shaped by – not insulated from – external conditions, sense of coherence warrants sustained attention in this population.

PMID:42529696 | PMC:PMC13418565 | DOI:10.3389/fpsyt.2026.1890660

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Cellular Logistics and Synaptic Vesicle Vulnerability in Major Depressive Disorder and Amyotrophic Lateral Sclerosis Comorbidity: Insights From Nicotinamide Mononucleotide Rescue and Transcriptome-Wide Association Study Integration

Cureus. 2026 Jul 28;18(7):e113549. doi: 10.7759/cureus.113549. eCollection 2026 Jul.

ABSTRACT

BACKGROUND: Major depressive disorder (MDD) and amyotrophic lateral sclerosis (ALS) are usually treated as unrelated, yet depressive symptoms occur in a substantial minority of people with ALS and may appear early. These symptoms are heterogeneous and may reflect syndromal MDD, psychological and functional burden, fatigue, apathy, pseudobulbar affect, frontotemporal involvement, sleep or respiratory disturbance, medication effects, or shared affective vulnerability. A proposed pruning-continuum model suggests both disorders may share vulnerability in microglia-mediated synaptic pruning, with ALS amplified by autophagy and protein-quality-control failure and MDD by RNA-processing, stress, and immune dysregulation. We performed an exploratory secondary transcriptome-wide association study (TWAS)/pathway-integration analysis to test whether predefined nicotinamide mononucleotide (NMN)-nominated pathways map onto this vulnerability.

METHODS: We integrated precomputed S-PrediXcan outputs for MDD and ALS across available brain-relevant tissues. Ten Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were predefined from a prior re-analysis of NMN-associated transcriptional programs in aged mouse metabolic tissues. Mouse-derived candidates were represented by human ortholog symbols before the human TWAS screen. The analysis tested nominated pathways rather than the 35-gene NMN-robust list as a standalone set. Cross-tissue screening used Stouffer Z aggregation, tissue-level Wilcoxon testing, competitive permutation testing, percentile bootstrap intervals, pairwise disease statistics, Levene variance tests, concordance measures, and leave-one-out sensitivity analysis. No analysis was treated as confirmatory or evidence of causal mediation.

RESULTS: MDD showed the strongest Stouffer-based exploratory signal in the synaptic vesicle cycle pathway, with a meta-across-tissue Stouffer Z of 3.41 and a wide bootstrap 95% confidence interval of -0.46 to 7.40. This signal did not survive competitive permutation testing (p = 0.1222) or Wilcoxon testing (p = 0.1926). The strongest tissue-level result occurred in the amygdala (Z = 4.057; nominal Wilcoxon p = 0.0093), although tissue-level permutation testing was not performed in the multi-gene-set run. ALS showed no significant meta-across-tissue enrichment among the 10 nominated pathways but displayed candidate gene-level signals in autophagy, endosomal, and vesicle-related genes, including TBK1 and C9orf72. Exploratory Levene tests indicated variance heterogeneity in the regulation of the actin cytoskeleton, endocytosis, and neuroactive ligand-receptor interaction; the actin cytoskeleton and endocytosis remained significant in pooled global false discovery rate (FDR) analysis. Fourteen genes were influential in at least two focus pathways, including EGF, KNG1, FGF8, RAC1, PAK1, PAK2, RAF1, MAPK1, and FGFR1.

CONCLUSIONS: These findings are hypothesis-generating. MDD and ALS may stress overlapping cellular logistics processes while engaging largely different genes. MDD showed the strongest exploratory pathway-level signal in synaptic vesicle biology, whereas ALS showed candidate gene-level coherence in autophagy and endosomal processes without significant meta-pathway enrichment. NMN/NAD+ repletion is not established as a treatment for MDD, ALS, or their comorbidity. These findings generate hypotheses about NAD+-linked cellular stress pathways for future preclinical and clinical studies.

PMID:42529685 | PMC:PMC13419321 | DOI:10.7759/cureus.113549

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Forsythoside A alleviates experimental autoimmune encephalomyelitis by targeting Tnfaip2

Chin Med. 2026 Jul 29;21(1):204. doi: 10.1186/s13020-026-01476-z.

ABSTRACT

BACKGROUND: Multiple sclerosis (MS) is a debilitating neuroinflammatory disease. Experimental autoimmune encephalomyelitis (EAE) is a commonly used rodent model for MS. Forsythoside A (FA), a natural compound derived from Forsythia suspensa, exhibits anti-inflammatory and neuroprotective properties; however, its efficacy in EAE and its underlying mechanism remain unclear.

PURPOSE: To explore the therapeutic effect of FA on EAE and its mechanism.

METHODS: EAE was induced in C57BL/6 mice treated with FA (20/60 mg/kg) from day 7. Clinical scores, histopathology (H&E, LFB, immunofluorescence), flow cytometry, and spinal cord RNA sequencing were analyzed. Network pharmacology, molecular docking, molecular dynamics (MD) simulations, and surface plasmon resonance (SPR) were employed to identify and validate the target of FA. In vitro studies using BV2 microglia with Tnfaip2 knockdown/overexpression confirmed the mechanism via qRT-PCR and Western blot.

RESULTS: FA treatment dose-dependently alleviated clinical severity. While the 20 mg/kg dose showed a trend toward improvement without statistical significance, the 60 mg/kg dose significantly reduced CNS inflammation and demyelination. FA decreased peripheral Th1 cells in EAE mice. It suppressed microglial activation and pro-inflammatory markers (IL-1β, TNF-α, iNOS) expression. Transcriptomics and network analysis pinpointed TNF-α-induced protein 2 (Tnfaip2) in the TNF pathway. FA directly bound Tnfaip2 (KD = 28 µM), validated by docking, MD simulations, and SPR. In vitro, FA inhibited LPS-induced pro-inflammatory polarization and the Tnfaip2/NF-κB pathway in BV2 cells. Tnfaip2 overexpression abolished the anti-inflammatory effects of FA.

CONCLUSION: FA ameliorates EAE by suppressing pro-inflammatory microglial polarization via directly targeting Tnfaip2 and inhibiting the NF-κB pathway. This identifies the Tnfaip2/NF-κB axis as a potential therapeutic target for MS.

PMID:42527947 | DOI:10.1186/s13020-026-01476-z

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Habitat-related variation in daily activity patterns of Boutourlini’s blue monkey (Cercopithecus mitis boutourlinii) in Saja Forest, Kafa Biosphere Reserve, Southwest Ethiopia

BMC Zool. 2026 Jul 28;11(1):24. doi: 10.1186/s40850-026-00280-4.

ABSTRACT

BACKGROUND: Activity budgets provide insights into how primates respond to habitat variation. Through behavioural flexibility, primates, including blue monkeys, can adjust their activity patterns and resource use under changing environmental conditions. This study compared the activity budgets of two Boutourlini’s blue monkey groups inhabiting different forest zones of Saja Forest: the core and transition zones. We collected Behavioral data from August 2024 to October 2025 using the instantaneous scan sampling method.

RESULTS: A total of 19,725 behavioral observations were recorded. Feeding was the dominant activity (29.6%), while times allocated for other activities were a smaller proportion (7.5%). The core-zone group spent significantly more time on feeding (33.0%), whereas those in the transition study group spent more time on movement (29.5%), and both showed statistically significant differences. Social activity was also higher in the transition zone group (13.5%), but it was not significant. Feeding was higher in the dry season (32.11%), whereas moving was higher in the wet season (28.67%). Diurnal patterns were observed, with feeding peaking in the morning and afternoon, while resting was highest at midday. Activity budgets varied among sex-age categories, with adult females showing the highest proportion of feeding activity (33.3%).

CONCLUSIONS: These findings provide baseline information on the activity budgets of two Boutourlini’s blue monkey groups occupying different forest zones. The observed variation in activity budgets between study groups and across seasons suggests behavioural flexibility under different environmental conditions. Future studies involving multiple independent groups per habitat type and direct measurements of habitat characteristics are needed to better understand the ecological factors influencing behavioural variation and to support conservation planning.

PMID:42527926 | DOI:10.1186/s40850-026-00280-4

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Enhancing patient safety: factors influencing critical care nurses’ intravenous sedation practices in mechanically ventilated patients

BMC Nurs. 2026 Jul 27;25(1):667. doi: 10.1186/s12912-026-05093-x.

ABSTRACT

BACKGROUND: Patient safety is a major priority in intensive care units (ICUs), particularly among mechanically ventilated patients receiving intravenous sedation. Although sedative agents are essential for maintaining comfort and ventilator synchrony, inappropriate sedation practices may contribute to adverse clinical outcomes. Understanding the factors influencing nurses’ sedation practices is therefore essential to promote safe and effective patient care. This study aimed to explore the factors influencing critical care nurses’ intravenous sedation practices and examine their relationship with patient safety outcomes.

METHODS: A cross-sectional descriptive exploratory study was conducted among 105 nurses working in critical care units. Participants were recruited using a consecutive sampling technique and were directly involved in caring for mechanically ventilated patients receiving intravenous sedation. Data were collected using the Nurses’ Profile Questionnaire and the Nurse Sedation Practices Scale (NSPS). Descriptive statistics and multiple regression analysis were performed to identify predictors of nurses’ sedation practices. Statistical significance was considered at p < 0.05.

RESULTS: Sedation orders and goals achieved the highest mean score (81.5%), followed by sedation practices (74.2%) and attitudes toward sedation (72.4%). Subjective norms showed moderate scores (67.6%), while perceived behavioral control demonstrated lower scores (60.1%). Intention to sedate recorded the lowest score (41.1%), suggesting a preference for individualized sedation approaches. Multiple regression analysis identified subjective norms, perceived behavioral control, and intention to sedate as significant predictors of nurses’ sedation practices. Subjective norms were the strongest predictor (B = 0.328, p < 0.001), followed by perceived behavioral control (B = 0.210, p = 0.002). Intention to sedate showed a significant negative association with sedation practices (B = -0.139, p = 0.010).

CONCLUSION: Improving sedation practices among critical care nurses requires strengthening perceived behavioral control and promoting patient-centered sedation approaches to enhance patient safety outcomes in mechanically ventilated patients.

PMID:42527923 | DOI:10.1186/s12912-026-05093-x

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Conflicting views in experimental carcinogenesis: a commentary on design and methodological deficiencies in the follow-up validation studies on radiofrequency radiation

Environ Health. 2026 Jul 29;25(1):66. doi: 10.1186/s12940-026-01324-5.

ABSTRACT

Conflicting views in experimental carcinogenesis often arise due to differences in study design among reported studies. For carcinogenicity assessments, regulatory agencies, such as the US Food and Drug Administration (FDA), and intergovernmental advisory organizations, such as the Organization for Economic Co-operation and Development (OECD), specify the use of at least three dose levels plus control group for trend analyses, with the highest dose inducing a measurable toxic response. In addition, there needs to be a sufficient number of animals per group to have adequate power to detect a true carcinogenic effect. Departure from such recommendations can weaken the interpretations of study results. We examine here two recent carcinogenicity studies from Japan and Korea that were conducted following the positive carcinogenicity study of radiofrequency radiation (RFR) in experimental animals by the National Toxicology Program (NTP). The Japan and Korea follow-up studies used fewer animals per group, a single RFR exposure group, and a lower exposure level than the NTP study. Not surprisingly, while the NTP study revealed the carcinogenicity of RFR, the Japanese and Korean studies, which had reduced statistical power compared to the NTP study, issued conclusions conflicting with those of the more substantial NTP study on the health effects of RFR. In general, carcinogenicity studies with weaker doses, fewer exposure groups, and reduced statistical power should not be used to test the validity of more robust studies.

PMID:42527916 | DOI:10.1186/s12940-026-01324-5

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Patient-reported outcomes in Chinese patients with AQP4-IgG-positive neuromyelitis optica spectrum disorder on inebilizumab therapy: a cross-sectional study

BMC Neurol. 2026 Jul 22;26(1):484. doi: 10.1186/s12883-026-05163-2.

ABSTRACT

BACKGROUND: The treatment of neuromyelitis optica spectrum disorder (NMOSD) has entered the era of targeted biological agents. While relapse control has improved substantially, patient-reported outcomes (PROs) remain understudied. This study aimed to explore real-world patient-reported perceptions of inebilizumab therapy in AQP4-IgG-positive NMOSD.

METHODS: We conducted a nationwide cross-sectional survey of AQP4-IgG-positive NMOSD patients receiving inebilizumab using an anonymous online questionnaire (April-September 2025). Data collected included demographics, medication history, and multidimensional quality-of-life changes following inebilizumab initiation. Descriptive statistics and correlation analyses were performed. Key outcomes were patient-reported without objective validation.

RESULTS: A total of 275 valid questionnaires were analyzed. Respondents were predominantly female (90.5%) with a mean age of 39.7 ± 11.8 years. Mean inebilizumab treatment duration was 14.5 ± 8.4 months. Of all patients, 33.1% received inebilizumab as initial maintenance therapy, 42.9% had previously used conventional immunosuppressants, and 24.0% had switched from other biologics. Among respondents, 92.4% reported meaningful symptom improvement across multiple domains including bodily pain and mental health. Overall, 96.4% expressed willingness to continue therapy, with symptom improvement cited as the predominant reason (91.7%). Correlation analysis revealed weak associations between treatment duration and satisfaction (r = 0.12, p < 0.05) and between medication cost burden and satisfaction (r = – 0.24, p < 0.01).

CONCLUSIONS: In this cross-sectional survey, Chinese patients with AQP4-IgG-positive NMOSD receiving inebilizumab reported high satisfaction, perceived multidimensional benefit, and strong treatment continuation willingness. These findings provide exploratory patient-reported evidence regarding the acceptability of inebilizumab in routine practice. However, the observed improvements are self-reported and associative rather than causal; interpretation should account for the cross-sectional, non-comparative design, potential selection and recall biases, and lack of objective outcome validation. Prospective controlled studies are required to confirm these preliminary findings.

PMID:42527908 | DOI:10.1186/s12883-026-05163-2

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Residual-stream geometry of single-cell foundation models carries incremental gene-regulatory signal across tissues

BMC Bioinformatics. 2026 Jul 24;27(1):162. doi: 10.1186/s12859-026-06538-5.

ABSTRACT

BACKGROUND: Single-cell foundation models such as scGPT and Geneformer learn rich representations of gene expression programs, but whether these representations encode gene regulatory relationships beyond expression-level confounds remains unclear. Attention patterns in these models have been shown to capture co-expression rather than direct regulation, leaving open the question of whether deeper representations-particularly the residual stream-contain genuine regulatory information.

RESULTS: We systematically investigated residual-stream geometry in scGPT and Geneformer across four tissue contexts from the Tabula Sapiens atlas, evaluating whether geometric proximity between gene vectors provides incremental predictive value for curated TRRUST transcription factor-target edges beyond expression confounds. Under repeated stratified cross-validation, geometric features provided significant incremental signal in kidney and immune settings, validated by label-permutation and geometry-shuffle null controls; centered-cosine similarity, PCA projection and multi-layer bundling recovered comparable signal in lung tissues, and the multi-layer bundle improved every domain (kidney ΔAUROC = + 0.122, immune + 0.042, lung + 0.028, external lung + 0.027; geometry-augmented AUROC 0.60-0.69). The effect was fully robust to leave-TF-out and leave-target-out cross-validation and to harder degree- and expression-matched negative edges, but under the stricter leave-both-out split-no transcription factor and no target shared between folds-it collapsed to near-zero (ΔAUROC at most + 0.003, and not statistically significant in kidney or immune), marking the ceiling of out-of-entity generalization. With a comparable per-layer residual-stream extraction applied to both models, the apparent Geneformer advantage mostly disappeared (small residual gaps remained in three of four domains), indicating it largely reflected representation-construction choices rather than a substantial architectural difference. Asymmetric geometric features predicted regulatory edge orientation (AUROC 0.80-0.90), and the geometric signal added incremental value on top of expression-based gene regulatory network (GRN) inference (GENIE3, co-expression).

CONCLUSION: Foundation model residual streams carry incremental, regulatory-relevant geometric signal that is distributed across layers and that complements expression-based GRN inference for retrospective edge prioritization. The signal is statistical enrichment rather than a stand-alone regulatory classifier: absolute performance is modest and out-of-entity generalization is limited, so its practical role is as an orthogonal evidence channel for edge re-ranking and hypothesis prioritization in multi-evidence frameworks.

PMID:42527907 | DOI:10.1186/s12859-026-06538-5

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Artificial intelligence for pediatric fracture detection: impact on diagnostic revisions and patient recall rates in a tertiary emergency setting

BMC Emerg Med. 2026 Jul 29;26(1):204. doi: 10.1186/s12873-026-01697-3.

ABSTRACT

PURPOSE: Artificial intelligence (AI) can support and enhance radiologists in musculoskeletal imaging, but evidence of clinical benefit is still lacking. This prospective study aimed to estimate the range of expected effect size on patient recall rates whether after implementation of an AI system for fracture detection affects in a paediatric emergency setting during out-of-hourse care.

METHODS: Children and adolescents (2-18 years) undergoing appendicular skeletal radiography between April and September 2025 during on-call hours at a tertiary referral hospital were eligible. On every second day, automated fracture detection by a commercial AI system (TechCare Kids, Milvue, Paris, France) was available for the treating physician. Endpoints were the rate of diagnostic revisions leading to patient recall the next day, therapeutic changes, length of stay at the emergency department, need for senior consultation, subjective diagnostic confidence, and AI accuracy.

RESULTS: Among 1515 screened patients, 667 were enrolled (median age 11.0 years, 61% male). Fractures were present in 296 cases (44.3%). AI accuracy was 95.1%. Diagnostic revisions occurred in 8.6% without AI, in 5.7% with AI support (risk ratio 0.66; 95% CI 0.37-1.19). Resulting therapeutic changes were rare in both groups (2.0% vs. 0.4%; p = 0.10). No significant differences were observed for secondary endpoints, including need for senior consultation (14.3% vs. 12.5%), subjective diagnostic confidence, or length of stay (2.3 h vs. 2.4 h).

CONCLUSION: Given the small effect size for patient recall rates in an academic medical setting, it is questionable whether the efforts conducting a confirmatory study with adequate statistical power would be justified by the expected incremental benefit for the investigated outcomes.

PMID:42527905 | DOI:10.1186/s12873-026-01697-3