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PubMed2026

Enhancing Hemoglobin Bart's hydrops fetalis syndrome prevention: a single-tube multiplex real-time PCR assay for the comprehensive detection of four significant α0-thalassemia deletions (--SEA, --THAI, --CR, and --SA) found in Thailand.

BACKGROUND: Hemoglobin (Hb) Bart's hydrops fetalis is a major public health concern in Southeast Asia, particularly in Thailand. Current screening strategies target the two most common α0 -thalassemia deletions (--SEA and --THAI). METHOD: In this study, we developed a single-tube multiplex real-time PCR assay for the simultaneous detection of four clinically relevant α0-thalassemia deletions (--SEA, --THAI, --CR, and --SA). The assay was validated using 538 clinical samples with diverse thalassemia genotypes and compared against conventional gap-PCR as the reference method. Analytical performance, including sensitivity, specificity, and limit of detection (LOD), was evaluated. In addition, clinical utility was assessed in 22 prenatal diagnosis cases at risk of Hb Bart's hydrops fetalis. RESULTS: The study cohort demonstrated substantial genetic heterogeneity, comprising 43 distinct genotypes. The developed assay achieved 100% sensitivity and specificity for all targeted deletions, with complete concordance with gap-PCR results. No cross-reactivity was observed with α+-thalassemia. The assay demonstrated a high analytical sensitivity with a LOD of 9.76 × 10-3 ng per reaction. Whereas in prenatal diagnosis, all 22 fetal genotypes were accurately identified, including five cases of homozygous --SEA and one rare compound heterozygous --SEA/--CR fetus. CONCLUSIONS: This study presents a rapid, accurate, and cost-effective multiplex real-time PCR assay capable of detecting both common and rare α0-thalassemia deletions in a single reaction. The assay demonstrates strong potential for implementation in routine clinical laboratories and large-scale population screening, contributing to improved prevention and control of severe thalassemia syndromes in high-prevalence regions.

Humans↗

PubMed2026

Prevalence and risk factors of red blood cell alloimmunization among sickle cell disease patients in resource-limited countries: A systematic review and meta-analysis.

BACKGROUND: Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by hemoglobin S production, in which homozygous individuals (HbSS) develop a broad range of acute and chronic complications. While disease-modifying and curative therapies are increasingly available in high-income settings, red blood cell (RBC) transfusion remains the mainstay of treatment in resource-limited countries and is associated with high rates of alloimmunization. This systematic review and meta-analysis aimed to estimate the prevalence of alloimmunization and identify associated risk factors among patients with SCD living in resource-limited settings. METHODS: Africa Journals Online (AJOL), Embase, PubMed, Scopus, and Web of Science were searched for original studies published from inception to December 15, 2025. Only studies conducted in low- and lower-middle-income countries (LMICs) were included. Eligible studies evaluated the prevalence of alloimmunization in patients with SCD receiving RBC transfusions. A random-effects meta-analysis of proportions was performed to pool quantitative data, while qualitative findings were systematically summarized in tabular form. Statistical heterogeneity was assessed using the I² statistic and further explored using Baujat plots, leave-one-out analyses, and meta-regression. RESULTS: Our analysis included 27 studies conducted in Africa (n = 23) and Asia (n = 4), predominantly from lower-middle-income countries (n = 19) and mainly employing a cross-sectional design (n = 20), comprising 3128 previously transfused patients with SCD. The pooled prevalence of RBC alloimmunization was 8.76% (95% CI: 6.71-11.37%; I² = 75%). Higher alloimmunization rates were observed in West and North Africa, particularly in Côte d'Ivoire, Egypt, and Nigeria, whereas lower rates were reported in Asia and East Africa. The most frequently identified antibodies belonged to the Rh blood group system (n = 153), followed by the Kell system (n = 65). CONCLUSION: In resource-limited settings, RBC alloimmunization is a frequent and clinically significant complication in patients with SCD, contributing to increased morbidity and potential mortality. Targeted and economically viable antigen matching may reduce alloimmunization rates and improve transfusion safety in LMICs.

Humans↗

PubMed2026

The effect of dietetic counseling combined with digital tools intervention on hemodynamic markers in Greek adults: The GATEKEEPER Study.

BACKGROUND AND AIM: Hypertension is a leading cardiovascular risk factor with substantial global impact on morbidity, mortality, and healthcare costs. While lifestyle interventions remain central to management, mHealth technologies offer promising adjunctive support, though their clinical effectiveness remains uncertain. This study evaluated whether combining dietetic counseling with digital tools improves hemodynamic markers in adults aged ≥55 years with increased cardiometabolic risk. METHODS AND RESULTS: This 3-month RCT (NCT05031299) included 954 adults with at least one metabolic syndrome risk factor, allocated 1:1:1 to Standard Care (dietetic counseling), Platform (counseling plus web-based platform), or Platform + Devices (counseling plus platform plus wearables). Outcomes included anthropometrics, lifestyle characteristics, blood pressure, pulse pressure, and estimated pulse wave velocity, analyzed using linear mixed-effects models adjusted for age and sex. All groups improved over 3 months. Waist circumference decreased by -6.29, -4.92, and -4.69 cm across Standard Care, Platform, and Platform + Devices groups respectively, and systolic blood pressure declined by -4.84 to -7.15 mmHg across groups. The Platform + Devices group showed greater increases in physical activity (94.62 MET-min/week; 95% CI 66.49 to 122.76) and greater reductions in pulse pressure (-3.90 mmHg; -6.58 to -1.22) versus Standard Care. Weight loss was associated with lower odds of hypertension (OR 0.4; 95% CI 0.2-0.7), greater likelihood of hypertension reversal (OR 3.6; 1.2-10.3), and higher probability of achieving normal pulse pressure (OR 1.8; 1.1-3.1). CONCLUSIONS: Dietary lifestyle intervention improved cardiometabolic outcomes, with limited added benefit from digital tools. Weight loss was the primary driver of hemodynamic improvement.

Aged↗

PubMed2026

Alternative End Joining Dependency Imposed by miR-21-5p Defines Radiation Resistance and a Targetable Vulnerability in Oral Squamous Cell Carcinoma.

PURPOSE: Clinical control of oral squamous cell carcinoma (OSCC) is constrained by heterogeneous radiosensitivity driven by divergent DNA damage response programs. The architecture and functional contribution of alternative end joining (Alt-EJ), an error-prone DNA double-strand break (DSB) repair pathway frequently upregulated in cancer, to radiation resistance remains poorly defined. METHODS AND MATERIALS: We profiled microRNAs in radioresistant OSCC clones and performed multiomic integration across an institutional OSCC cohort, an external OSCC cohort from the Gene Expression Omnibus, The Cancer Genome Atlas pan-cancer tumors, and cell lines characterized by Sanger Genomics of Drug Sensitivity in Cancer to infer DNA damage response characteristics, genomic scar features, drug sensitivity, and radiation therapy outcomes. DSB repair capacity and pathway usage were validated using functional assays, including Alt-EJ reporters and droplet digital PCR quantification of microhomology-mediated repair events. Core Alt-EJ effectors such as PARP1 and POLQ were perturbed genetically and pharmacologically. Therapeutic efficacy of PARP or POLQ inhibition with or without irradiation was tested in a syngeneic OSCC model, followed by bulk tumor transcriptomics to assess pathway engagement. RESULTS: Upregulation of miR-21-5p was not only selectively detected in radioresistant OSCC, but also modulated radiosensitivity in vitro and in vivo, and was associated with inferior postradiation therapy survival. A calibrated miR-21-5p target-gene signature tracked Alt-EJ activity across patient and mouse tumors and cancer cell lines, correlated with microhomology-mediated indels and broader genomic scarring, and predicted sensitivity to clinically available PARP inhibitors. Functionally, enforced miR-21-5p expression increased Alt-EJ usage and accelerated DSB repair, whereas inhibition or depletion of key Alt-EJ effectors reduced repair efficiency and restored radiosensitivity. In vivo, Alt-EJ targeting with PARP or POLQ inhibitor abrogated miR-21-5p-driven radiation resistance; transcriptomic profiling supported suppression of Alt-EJ programs as the operative mechanism. CONCLUSIONS: These findings establish a mechanistic link between miR-21-5p activity and Alt-EJ dependence, provide a clinically deployable signature to identify Alt-EJ-dependent OSCC, and support rational combinations of Alt-EJ targeting agents with radiation therapy to overcome treatment failure and advance precision radiation oncology.

MicroRNAs↗

PubMed2026

Artificial intelligence-assisted detection and optical differentiation of colorectal lesions in Lynch syndrome surveillance (CADLY2): a multicentre, open-label, randomised controlled superiority trial.

BACKGROUND: Artificial intelligence (AI)-based computer-aided detection (CADe) systems improve adenoma detection in average-risk colorectal cancer screening. Meanwhile, evidence in Lynch syndrome surveillance is sparse and inconsistent. We assessed the effect of CADe on adenoma detection during Lynch syndrome surveillance. Computer-aided optical diagnosis (CADx) performance for optical differentiation of colorectal lesions was evaluated as a secondary aim. METHODS: CADLY2 was an international, multicentre, open-label, randomised controlled superiority trial at nine specialised hereditary cancer surveillance centres in Belgium, Germany, the Netherlands, and Spain. Adults aged 18 years or older with genetically confirmed Lynch syndrome scheduled for surveillance colonoscopy were randomly assigned (1:1) to high-definition white-light (HD-WL) colonoscopy alone or to HD-WL colonoscopy with computer-aided assistance from CAD EYE (Fujifilm, Tokyo, Japan). CAD EYE was used for CADe during withdrawal and for CADx after lesion detection. Randomisation was done centrally through a secure web-based system using Pocock's minimisation algorithm with a stochastic component and was stratified by centre, sex, previous colorectal cancer, underlying pathogenic variant, and interval since previous colonoscopy. Allocation concealment was ensured through the centralised web-based system. Patients were masked to group allocation until the start of withdrawal in procedures with mild sedation, or until completion of the procedure in procedures with propofol-based sedation. Endoscopists were not masked. The primary outcome was adenoma detection rate, defined as the proportion of patients with at least one histopathologically confirmed adenoma, analysed in the full analysis set (defined as all randomly allocated patients with available data for the primary outcome). The diagnostic performance of the CADx system was evaluated as a secondary outcome. The safety analysis set comprised all randomly allocated patients who underwent a study colonoscopy. This study is registered with the German Clinical Trials Register, DRKS00030695, and is completed. FINDINGS: Between May 9, 2023, and Oct 30, 2025, 757 patients were randomly allocated to HD-WL colonoscopy (377 patients) or to AI-assisted colonoscopy (380 patients); 733 patients were included in the full analysis set (369 HD-WL and 364 AI-assisted). The median age was 49 years (IQR 38-59) in the HD-WL group and 50 years (38-59) in the AI-assisted group; 213 (58%) were female and 156 (42%) male in the HD-WL group, and 207 (57%) were female and 157 (43%) male in the AI-assisted group. The adenoma detection rate was 30·9% (114 of 369 patients) with HD-WL versus 33·8% (123 of 364 patients) with CADe assistance (odds ratio 1·14 [95% CI 0·83-1·57], p=0·41). For CADx differentiation of neoplastic versus non-neoplastic lesions in the paired lesion-level analysis, with histopathology as the reference standard and sessile serrated lesions and traditional serrated adenomas classified as non-neoplastic, CADx sensitivity was 85·9% (95% CI 82·0-89·1) and specificity was 91·4% (89·4-93·0). Three adverse events occurred in the AI-assisted group: two mild post-polypectomy bleedings and one serious pulmonary embolism or deep venous thrombosis unrelated to the procedure. No adverse events occurred in the HD-WL group. INTERPRETATION: CADe-assisted colonoscopy did not show the absolute improvement in adenoma detection rate that was assumed in the prespecified sample-size calculation. CADx did not clearly improve lesion differentiation beyond expert optical diagnosis in expert Lynch syndrome surveillance settings. FUNDING: Third-party research funding of the National Center for Hereditary Tumor Syndromes, University Hospital Bonn.

Humans↗

PubMed2026

Cochlear Implantation in Sickle Cell Disease: A Systematic Review of Feasibility and Outcomes.

INTRODUCTION: Sickle cell disease (SCD) is associated with systemic complications, including sensorineural hearing loss (SNHL) from microvascular occlusion and chronic inflammation. Although reports link SCD to higher rates of SNHL, current evidence is limited by small sample size, varied audiologic methods, and lack of standardized screening. This systematic review summarizes available literature on SNHL and cochlear implantation (CI) in SCD. METHODS: A literature search of PubMed MEDLINE, Embase, Scopus, Web of Science, and CINAHL identified 79 citations. After removal of duplicates, 35 records were screened in Rayyan. Studies published between January 1, 2000, and June 30, 2025, were eligible if they reported patients with SCD who developed hearing loss and underwent CI. Nine full texts were reviewed, and 4 met the inclusion criteria. Screening and review were performed independently by 2 authors per PRISMA guidelines. RESULTS: Across 4 case reports, a total of 5 patients with SCD underwent CI, ranging in age from 2 to 42 years. Four presented with bilateral severe-to-profound SNHL and one with unilateral loss. Implantation was technically feasible in all cases, including patients with cochlear fibrosis or ossification requiring modified insertion techniques. Postoperative outcomes were favorable: all patients demonstrated reliable device function and low impedances. Only 60% showed meaningful auditory benefit, characterized by improved functional speech perception in 2 patients (40%) and access to the speech frequency range with hearing testing going from moderate/profound hearing loss to mild hearing loss in 3 patients (60%). Complications occurred in 2 patients (40%): one developed unilateral middle ear infection leading to meningitis, and another experienced a postoperative pulmonary embolism requiring anticoagulation. The remaining 3 patients (60%) had uncomplicated recoveries with reported improved hearing from moderate/profound hearing loss to mild hearing loss post implantation. CONCLUSION: While CI appears feasible in SCD, our findings suggest that additional data are needed to assess its effectiveness in this patient population. However, evidence is limited to case reports, and complications such as thromboembolism and rapid cochlear fibrosis highlight the need for close perioperative management. More comprehensive studies with larger sample size are required to define surgical risk, optimize management, and establish best practices for timely implantation in this population.

Humans↗

PubMed2026

Advanced/Novel Stenting for Pediatric Dynamic Airway Collapse.

Pediatric dynamic airway collapse is a complex condition that can impact all levels of the pediatric airway. These conditions can pose life threatening risk to pediatric patients and carry lasting impacts. While traditionally, tracheostomy has been used to address all levels of dynamic collapse, recent advances have allowed for more individualized, anatomy-specific stenting and splinting strategies for treatment. This article covers pathophysiology and the latest evidence on strategies to address nasopharyngeal, oropharyngeal, proximal trachea, and tracheobronchial dynamic collapse.

Humans↗

PubMed2026

A novel peptide encoded by circTLL1 drives osimertinib resistance in lung cancer by modulating the NT5C2/Ras/PI3K axis.

BACKGROUND: Acquired resistance to osimertinib, a third-generation EGFR tyrosine kinase inhibitor, remains a major clinical challenge in the treatment of non-small cell lung cancer (NSCLC). Although circular RNAs (circRNAs) have been increasingly implicated in drug resistance, most studies have focused on their canonical role as microRNA sponges, while their capacity to encode functional micropeptides remains largely unexplored. This study aimed to identify novel circRNAs involved in osimertinib resistance and to characterize their regulatory functions at the protein level. METHODS: Osimertinib-resistant (OR) NSCLC cell lines were established and validated. High-throughput RNA sequencing was performed to compare the circRNA expression profiles between parental and OR cells. The function of the candidate circRNA was assessed through a series of in vitro and in vivo experiments, including cell viability assays, apoptosis analysis, and xenograft mouse models. Mechanistic investigations involved mass spectrometry, co-immunoprecipitation and western blotting to explore its protein-coding potential and downstream signaling pathways. RESULTS: We identified a novel circRNA, termed circTLL1, that was stably and significantly upregulated in OR-NSCLC cells. Functionally, overexpression of circTLL1 promoted osimertinib resistance, whereas its knockdown restored drug sensitivity both in vitro and in vivo. Mechanistically, we discovered that circTLL1 harbors an open reading frame (ORF) that is translated into a novel 90-amino-acid protein, which we designated circTLL1-90aa. Further investigation revealed that circTLL1-90aa directly interacts with and promotes the degradation of 5'-nucleotidase, cytosolic II (NT5C2), thereby uncoupling nucleotide metabolism from its normal regulatory constraints. The consequent downregulation of NT5C2 leads to elevated GTP levels and leading to the sustained activation of the downstream Ras/PI3K/AKT signaling pathway. CONCLUSION: Our findings unveil a previously unrecognized circRNA/micropeptide/metabolism cascade underlying osimertinib resistance. The identification of the circTLL1-90aa/NT5C2/Ras/PI3K axis not only expands the functional repertoire of the non-coding genome but also provides new insights into the complexity of drug resistance. Given its selective upregulation in resistant cells, circTLL1-90aa holds promise both as a predictive biomarker for treatment stratification and as an actionable therapeutic target, offering a novel strategy to overcome osimertinib resistance in NSCLC patients.

Pyrimidines↗

PubMed2026

Matched targeted therapy use after broad genomic profiling in advanced Non-Small cell lung cancer.

INTRODUCTION: While broad genomic profiling is increasingly used in advanced NSCLC (aNSCLC), the impact of test results on subsequent guideline-concordant targeted therapy selection remains incompletely understood. METHODS: Using a merged dataset of two large, nationwide, patient-level databases, we identified patients who were diagnosed with aNSCLC 2017-2023, had potentially actionable genomic profiling findings, and initiated systemic therapy. Patients were categorized into actionability subgroups based on contemporaneous regulatory approvals and NCCN guideline recommendations. Within each subgroup, we assessed receipt of guideline-concordant targeted therapy within 24 months, including potential underuse (non-receipt of recommended treatment) and overuse (receipt of non-recommended treatment). RESULTS: Among 6620 patients (67.4% ≥65 years, 54.6% female, 68.9% White), guideline-concordant targeted therapy use varied substantially by actionability category: 2313 (89.6%) of 2582 patients with available 1st-line on-label options received them (10.4% underuse), while 212 (67.3%) of 315 patients with available later-line on-label options received them after 1st-line (32.7% underuse). Among 441 patients with available guideline-concordant off-label options, only 122 (27.7%) received them (72.3% underuse). Conversely, 238 (8.6%) of 3282 patients received matched but guideline-discordant off-label options, representing overuse of ineffective or unestablished therapies. Smoking history, squamous histology, and high PD-L1 expression were associated with lower targeted therapy receipt. CONCLUSIONS: In this cohort study of aNSCLC care, the guideline concordance of targeted therapy use varied by clinical actionability of molecular testing results. Underuse was more common in patients with later-line and off-label targeted therapy options. Patients with classical smoking-related risk profiles were substantially less likely to receive targeted therapy even when actionable alterations were identified.

Journal Article↗

PubMed2026

The Homozygous p.(Arg215Ter) Variant in XRCC2 Is Associated With Atypical Fanconi Anemia Without Major Hematological Abnormalities in Childhood.

Fanconi Anemia (FA) is the most frequent inherited bone marrow failure syndrome. A role for the XRCC2 gene in FA was suspected in 2012 and confirmed in 2016, but only two affected individuals have been described thus far, and no long-term follow-up is available. Here we present two young related adults born to consanguineous parents, in whom we identified the homozygous p.(Arg215Ter) variant in XRCC2. Both patients presented with mild intellectual disability, microcephaly, distinctive facial features, short stature, thumb abnormalities, and abnormal skin pigmentation. Unlike in FA, DEB test resulted negative in peripheral blood during childhood and no cytopenia, clonal evolution, or other hematological complications were detected until the age of 19 and 20 years, respectively. Our report suggests that the homozygous p.(Arg215Ter) variant in XRRC2 causes a distinctive FA-like disorder, characterized by the typical physical characteristics seen in FA, but a lack of major hematological manifestations in childhood, and the presence of a more pronounced neurodevelopmental phenotype than that seen in FA.

Humans↗

PubMed2026

DNM1L depletion leads to accelerated heteroplasmy shifting of m.10191C allele through ATG7-dependent pathways.

Nucleotide composition bias in mitochondrial DNA (mtDNA) makes the heavy strand prone to form a DNA secondary structure called a guanine quadruplex (G4). This secondary structure has been shown to inhibit polymerase processivity in vitro. We previously identified pathogenic mtDNA variants that lead to increased G4-forming propensity, including a T to C mutation at m.10191 (m.10191 T > C) that causes Leigh syndrome. Cells treated with G4 binding agent (G4BA) berberine show a reduction in m.10191C pathogenic heteroplasmy levels. To help better understand the underlying mechanism behind berberine-induced heteroplasmy shift, we examined the relationship between mitochondrial fission and berberine-mediated shift. Here we show that knockdown of the fission factor DNM1L leads to an accelerated heteroplasmy shift towards the healthy mtDNA allele, lowering m.10191C by 10% in 3 weeks, compared to the 5 weeks required for berberine alone. The specific mechanism involves ATG7, as knockdown of ATG7 is able to partially delay this accelerated heteroplasmy shift. Taken together, we show that DNM1L knockdown is able to accelerate berberine-induced m.10191C heteroplasmy shifting through an autophagy-related mechanism.

Humans↗

PubMed2026

Frequent readmissions after hospitalization for alcohol withdrawal: a systematic review and meta-analysis.

BACKGROUND: Alcohol use disorder and alcohol withdrawal syndrome impose substantial clinical and economic burdens, with repeated hospitalizations being common. We aimed to systematically review readmission rates following inpatient detoxification, assess variation across study designs and hospital settings, and identify key risk and protective factors. METHODS: We performed a literature search in Embase and Pubmed on 10/04/2026 focusing on studies assessing in hospital alcohol detoxification. Exclusion criteria included studies on substance use other than alcohol and outpatient or residential treatment. Main outcome was rehospitalization, and meta-analysis was performed to estimate pooled readmission proportions. Secondary outcomes were risk factors and protective factors influencing the rate of rehospitalization. RESULTS: Twenty-five studies were included. The pooled proportion of readmissions following alcohol detoxification was estimated at 17% (95% CI: 14%-21%; 13 studies, n = 287,896) within 1 month, increasing to 44% (95% CI: 36%-52%; 8 studies, n = 2,877) at 1 year. Substantial between-study heterogeneity was observed. Subgroup analyses found no significant differences by hospital setting or time period. Findings for study aim and study design were mixed and based on limited data A small number of studies suggested associations with housing stability, employment, and treatment engagement. CONCLUSIONS: This meta-analysis suggests that approximately one in six patients are readmitted within 1 month and nearly half within 1 year after inpatient alcohol detoxification. However, readmission rates varied considerably across settings and populations. Future research should evaluate targeted interventions to reduce readmissions among high-risk patient groups.

Humans↗

PubMed2026

Prevalence and cardiometabolic impact of mild autonomous cortisol secretion in primary aldosteronism: a systematic review and meta-analysis.

Many primary aldosteronism (PA) patients harbor concomitant mild autonomous cortisol secretion (MACS), termed "Connshing syndrome." The prevalence and cardiometabolic impact of this co-secretion have not been quantitatively synthesized. To determine the pooled prevalence of MACS in PA and evaluate its association with cardiovascular (CV) events, type 2 diabetes mellitus (T2DM), and obesity. PubMed, Embase, Cochrane, Web of Science, and Scopus through January 2026. Following PRISMA 2020 and MOOSE guidelines (PROSPERO: CRD420261334965), studies reporting MACS prevalence [post-1 mg dexamethasone suppression test (DST) cortisol ≥1.8 μg/dl] in PA were included. Prevalence was pooled using random-effects models. Odds ratios (ORs) were calculated for cardiometabolic outcomes. Certainty was evaluated using GRADE. Fourteen studies (2356 patients) were included. Pooled MACS prevalence was 26.2% [95% confidence interval (CI): 24.1-28.4; I2 = 24.2%; prediction interval: 21.6-31.4%], consistent across European (27.0%) and East Asian (25.2%) cohorts ( P = 0.62). MACS + PA patients had higher odds of CV events (OR 1.60; 95% CI: 1.07-2.38; P = 0.021) and T2DM (OR 1.37; 95% CI: 1.00-1.86; P = 0.048), but not obesity (OR 1.10; P = 0.411). Sensitivity analyses confirmed robustness. GRADE certainty was moderate for prevalence and low for CV events. Approximately one in four PA patients has MACS, associated with a 60% higher CV event risk. These findings support routine DST screening in PA and have implications for perioperative management and cardiometabolic risk stratification.

Humans↗

PubMed2026

Exploring the Diagnostic Utility of Ferumoxytol for Brachial Plexus MR Neurography.

Background Ferumoxytol has been described as an alternative contrast agent for vascular suppression in MR neurography (MRN), but its diagnostic utility in patients has yet to be evaluated. Purpose To evaluate the impact of ferumoxytol on vascular suppression, nerve conspicuity, and evaluation of nerve abnormalities at three-dimensional (3D) brachial plexus MRN, compared with noncontrast and gadolinium-enhanced MRN, in participants with suspected Parsonage-Turner syndrome (PTS) or thoracic outlet syndrome (TOS). Materials and Methods This prospective study included participants who underwent 3D MRN with and/or without gadolinium chelate for clinical suspicion of PTS or TOS and subsequently underwent 3D MRN with ferumoxytol (within 3 months of the clinical examination). Two musculoskeletal radiologists qualitatively evaluated 3D short-tau inversion-recovery fast spin-echo scans for the degree of vascular suppression, nerve conspicuity, and presence of nerve abnormalities. Wilcoxon signed-rank or McNemar tests were used for comparing noncontrast and gadolinium-enhanced scans with ferumoxytol-enhanced scans. Results This study included 18 participants (mean age, 42 years ± 15.2 [SD]; 10 men). Ferumoxytol-enhanced scans demonstrated improved vascular suppression compared with both noncontrast scans (both raters, P < .001) and gadolinium-enhanced scans (both P = .04). For rater 2, ferumoxytol-enhanced acquisitions demonstrated improved conspicuity of several nerve segments relative to the noncontrast scan, including segments of the suprascapular (P = .01), axillary (P = .02), and long thoracic nerves (P = .004). The distribution of scores for these nerve segments for rater 1 also favored ferumoxytol-enhanced versus noncontrast scans, but the differences were not statistically significant (all P ≥ .06). There was no evidence of a difference in nerve conspicuity between ferumoxytol-enhanced and gadolinium-enhanced scans (P ≥ .17 for all nerve segments) and also no evidence of discrepancies in abnormal nerve findings between the acquisitions (all P ≥ .48). Conclusion Ferumoxytol improved vascular suppression compared with noncontrast and gadolinium-enhanced 3D short-tau inversion-recovery fast spin-echo sequences in brachial plexus MRN, enhancing the conspicuity of several nerve branches versus noncontrast scans, with similar detection of abnormal nerve findings. © RSNA, 2026 Supplemental material is available for this article.

Humans↗

PubMed2026

Suppression of AAV-Delivered Transgene Expression Using Artificial MicroRNAs Delivered by an Alternative AAV Serotype.

Adeno-associated virus (AAV) gene transfer vectors mediate long-term expression in nondividing cells, an advantage for treating chronic disorders. However, current platforms lack a way to selectively shut down transgene expression if adverse effects arise. To create an "off switch," we hypothesized that incorporating unique artificial microRNA (amiRNA) target sequences into an AAV expression cassette would allow subsequent suppression of transgene expression using a second AAV vector encoding the cognate amiRNA. We introduced 22-nt sequences absent from human and mouse transcriptomes into the 3' untranslated region (UTR) of a therapeutic AAV cassette. To identify optimal amiRNAs, two tandem copies of each amiRNA were cloned into the 3'UTR of an mCherry reporter gene. In vitro assessment of six amiRNA/target pairs using a dual luciferase assay identified four amiRNAs that efficiently suppressed reporter expression. Cells cotransfected with target site 3 (TS3) and amiRNA-T3B showed the greatest reduction in luciferase activity (80%, p < 0.0001) and were selected for further study. The "off-switch" system was then evaluated using an AAV5 therapeutic vector expressing a recombinant humanized anti-IgE monoclonal antibody (AAV5-TBG-anti-IgE-TS3), designed for long-term suppression of allergen-induced reactions. Co-transfection of HEK293T cells with anti-IgE-TS3 and amiRNA-T3B significantly reduced anti-IgE mRNA and protein levels relative to a control amiRNA (p < 0.0001). In vivo testing in Balb/c mice (n = 5) involved intravenous administration of AAV5-anti-IgE-TS3 (3.2 × 1010 gc), followed 4 weeks later by an AAVrh.10 amiRNA vector (AAVrh.10-TBG-amiRNA-T3B; 1 × 1011 gc). Control mice receiving only the therapeutic vector expressed 18.4 ± 13.8 µg/mL serum anti-IgE at 10 weeks. In contrast, mice receiving the amiRNA "off" vector showed marked suppression of anti-IgE (0.3 ± 0.15 µg/mL, p < 0.0001). These findings provide proof-of-concept that AAV-delivered amiRNAs can selectively switch off transgene expression, offering a strategy to improve the safety of AAV-mediated gene therapies.

Dependovirus↗

PubMed2026

Effect of Smoking in Oropharyngeal Cancer Treated With TORS: Systematic Review and Meta-Analysis.

OBJECTIVE: While smoking has been implicated as a risk factor for recurrence in HPV-associated oropharyngeal squamous cell cancer (OPSCC) treated with definitive chemoradiation, its prognostic impact on surgically treated OPSCC is less clear. DATA SOURCES: MEDLINE, Embase, CENTRAL, and Scopus. REVIEW METHODS: Articles describing patients with HPV-associated OPSCC treated with transoral robotic surgery (TORS), which reported oncologic outcomes by smoking history, were included. RESULTS: 2079 patients were included across 12 studies. Median age was 58.5 years, and 1808 (87.0%) were male. HPV-associated disease was reported in 1681 (80.9%) patients. T stage was most commonly T2 in 831 (40.0%) and T1 in 764 (36.7%). N stage was N2 in 854 (41.1%), N1 in 544 (26.2%), and N0 in 307 (14.8%). 931 (44.8%) were considered individuals with a smoking history, while 1045 (50.3%) were considered without a smoking history. Median follow up was 33.7 months. Meta-analysis using a fixed effects model demonstrated an overall hazard ratio of 1.4 (95% confidence interval 1.0-2.0) for disease recurrence, 2.7 (95% confidence interval 1.5-4.8) for overall survival, and 1.4 (95% confidence interval 0.4-4.6) for disease specific survival. CONCLUSIONS: In this population of predominantly HPV-associated OPSCC treated with TORS, meta-analysis demonstrated no significant difference in recurrence-free survival or disease-specific survival between individuals with and without a smoking history. Individuals with a smoking history appeared to have worse overall survival, although only five studies reported on this outcome. Further research is required to clarify the prognostic influence of smoking on OPSCC treated with TORS.

Humans↗

PubMed2026

The association of 25-hydroxyvitamin D deficiency with neuroinflammation and prognosis in HIV-negative cryptococcal meningitis.

BACKGROUND: Cryptococcal meningitis (CM) in HIV-negative individuals is increasing, yet the role of vitamin D remains unclear. This study investigates serum 25-hydroxyvitamin D [25(OH)D] levels and their clinical implications in HIV-negative CM patients. METHODS: We conducted a retrospective case-control study of 93 HIV-negative CM patients and 191 healthy controls (HCs). Serum 25(OH)D levels, cerebrospinal fluid (CSF) fungal burden, cytokine profiles, the incidence of postinfectious inflammatory response syndrome (PIIRS), and one-year mortality were assessed. Bivariate logistic regression models identified predictors of mortality. RESULTS: CM patients had significantly lower serum 25(OH)D levels than HCs (18.33 vs. 23.69 ng/mL, p < 0.001), with a higher rate of deficiency (<20 ng/mL) in the CM group (59.14% vs. 34.03%, p < 0.001). Lower 25(OH)D levels were associated with elevated CSF levels of IL-6 and IL-8 (p < 0.05). Deficiency was linked to increased PIIRS incidence (43.64% vs. 21.05%, p = 0.028). Bivariate logistic regression showed a protective trend for 25(OH)D levels (OR 0.939, 95% CI 0.877-1.006, p = 0.075), although deficiency was not associated with higher mortality. CONCLUSIONS: Serum 25(OH)D deficiency is prevalent in HIV-negative CM patients and linked to neuroinflammation and increased risk of PIIRS. Serum 25(OH)D levels may serve as a useful prognostic marker, although further research is needed.

Humans↗

PubMed2026

Integrated bioinformatics analysis reveals cross-talking hub genes and therapeutic agents between sepsis and acute myocardial infarction.

BACKGROUND: Sepsis and acute myocardial infarction (AMI) are two significant diseases that may share overlapping etiological mechanisms. This study aims to systematically identify core genes common to both conditions and to explore their potential as therapeutic targets and drug candidates through an integrative analysis of clinical data and bioinformatics. METHODS: The AMI dataset was obtained from the GEO database, and RNA sequencing data were collected from blood samples of patients with sepsis at our hospital. Common genes were identified using differential expression gene analysis (DEG) and weighted gene co-expression network analysis (WGCNA). Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were performed. A protein-protein interaction (PPI) network was constructed, and hub genes were identified using the MCC/Degree algorithm. Diagnostic value was assessed via receiver operating characteristic curve analysis. Immune infiltration patterns, single-cell sequencing data, and molecular docking simulations were employed to evaluate immune relevance and identify potential therapeutic compounds. RESULTS: A total of 417 genes were identified between sepsis and AMI, with enrichment analysis revealing significant involvement in inflammatory responses. Three hub genes-JAK2, MYD88, and TIMP1-were selected for further investigation. ROC curves confirmed their strong diagnostic performance for both diseases. Immune infiltration analysis showed that these core genes were significantly correlated with the infiltration levels of various immune cell types. Molecular docking indicated that quercetin exhibited stable binding affinity with the proteins encoded by these genes. qPCR validation further confirmed the upregulation of these three genes, supporting the anti-inflammatory effects of quercetin as a potential targeted therapy. CONCLUSION: JAK2, MYD88, and TIMP1 were identified as shared core genes in sepsis and AMI. These genes not only serve as potential diagnostic biomarkers but also offer novel targets for developing common therapeutic strategies for both conditions. Furthermore, quercetin emerges as a promising candidate for targeted treatment.

Humans↗