Category: Nevin Manimala

Clin Rheumatol. 2026 Jul 4. doi: 10.1007/s10067-026-08281-x. Online ahead of print.

ABSTRACT

OBJECTIVE: Behçet’s disease is a chronic, inflammatory vasculitis affecting multiple systems. In addition to existing laboratory parameters used for the diagnosis and monitoring of Behçet’s disease, new biomarkers are needed to improve diagnostic accuracy. The levels and activity of DNASE1L3, an enzyme that degrades chromatin released into circulation during apoptotic processes and can initiate autoimmune mechanisms, have been associated with autoimmune diseases. This study was designed to determine the levels of DNASE1L3 in patients with Behçet’s disease, assess its relationship with clinical and inflammatory parameters, and evaluate its potential as a diagnostic biomarker.

METHODS: This study included 45 patients diagnosed with Behçet’s disease and 45 age and sex-matched healthy controls. Serum DNASE1L3 levels were measured in both groups using the enzyme-linked immunosorbent assay (ELISA).

RESULTS: Serum DNASE1L3 levels were significantly lower in patients with Behçet’s disease (7.14 ± 1.81 ng/mL) compared to the healthy control group (15.79 ± 3.14 ng/mL) (p < 0.001). A statistically significant negative correlation was observed between serum DNASE1L3 levels and both CRP (r = – 0.684, p < 0.001) and ESR (r = – 0.524, p < 0.001). According to ROC curve analysis, a serum DNASE1L3 cutoff value of 9.53 ng/mL distinguished patients with Behçet’s disease from healthy individuals with 96% sensitivity and 93% specificity. For this threshold, the positive predictive value was 95% and the negative predictive value was 93% (AUC = 0.983; p < 0.001; positive likelihood ratio, 21.13; negative likelihood ratio, 0.07).

CONCLUSION: The findings of this preliminary study suggest that serum DNASE1L3 may represent a promising candidate biomarker for Behçet’s disease. However, further validation in larger, independent cohorts is required before its potential clinical utility can be established. Key Points • Serum DNASE1L3 levels are significantly lower in patients with Behçet’s disease compared to healthy individuals. • DNASE1L3 levels show a strong negative correlation with acute phase reactants, including CRP and ESR. • Low DNASE1L3 levels may reflect impaired extracellular DNA clearance and contribute to the inflammatory process in Behçet’s disease. • Serum DNASE1L3 levels show potential as an exploratory biomarker for the clinical evaluation of Behçet’s disease, providing a basis for further validation in larger clinical cohorts.

PMID:42400811 | DOI:10.1007/s10067-026-08281-x

Mol Cell Biochem. 2026 Jul 4. doi: 10.1007/s11010-026-05631-w. Online ahead of print.

ABSTRACT

While the epidemiological association between inflammatory bowel disease (IBD) and stroke is well-established, the shared genetic architecture underlying these diseases remains unclear. This study utilized genome-wide association studies (GWAS) summary statistics to explore genetic overlaps between IBD and stroke subtypes. Mendelian randomization (MR) was applied to assess potential causal relationships. Cross-trait meta-analysis identified shared loci, followed by colocalization testing to pinpoint causal variants. Furthermore, functional prediction analysis of variants and verification through in vitro experiments. Finally, use mediation MR to explore potential mechanisms in multiple dimensions. We identified eight pairs with potential genetic correlations, with common genetic variants contributing more on ulcerative colitis (UC) and multiple stroke subtypes than Crohn’s disease (CD). Among them, there is a potential causal relationship between IBD/UC and large arterial atherosclerotic stroke (LAS), which is consistent with previous epidemiological statistics. In addition, one locus (rs7522794) was initially identified through cross-trait analysis, and colocalization pointed out that the variant rs7522794 on the FCGR2A promoter was the culprit of the comorbid phenotype. The rs7522794-T allele predicted to be more prone to bind SPI1, thereby increasing FCGR2A expression and susceptibility to stroke in IBD patients. Finally, evidence suggests that gut microbes, blood metabolites, and immune cells may play a crucial regulatory role in the shared pathophysiology of IBD/UC and LAS. The study highlights the shared genetics architecture that exists between IBD and stroke, and demonstrates two different (FCGR2A-mediated immune pathways and other indirect regulation) but complementary verification mechanisms, providing new insights into IBD-stroke comorbidities.

PMID:42400809 | DOI:10.1007/s11010-026-05631-w

Ir J Med Sci. 2026 Jul 4. doi: 10.1007/s11845-026-04532-7. Online ahead of print.

ABSTRACT

BACKGROUND: Knee osteoarthritis (KOA) is a major cause of pain and functional limitation, and conventional physiotherapy is widely used in its management. Although kinesiotaping (KT) is commonly applied as an adjunct intervention, its additional effectiveness remains unclear.

AIMS: This study investigated the additional effects of kinesiotaping combined with conventional physiotherapy on pain, functional status, and kinesiophobia in individuals with unilateral KOA.

METHODS: Forty-four participants with unilateral KOA were randomly assigned to either a conventional physiotherapy (CP) group or a kinesiotaping (KT) group. Both groups received a 4-week rehabilitation program including ultrasound, transcutaneous electrical nerve stimulation, patellofemoral mobilization, and exercise therapy. Kinesiotaping was additionally applied every 3 days in the KT group. Outcome measures included pain intensity (VAS), kinesiophobia (TSK), fear-avoidance beliefs (FABQ), functional performance (30-s sit-to-stand and stair climb tests), dynamic balance (Functional Reach Test), and WOMAC scores. Statistical analyses included non-parametric tests and ANCOVA adjusted for baseline values.

RESULTS: Both groups demonstrated significant improvements in all outcome measures after treatment (p < 0.05). Change-score analyses indicated greater improvements in kinesiophobia, fear-avoidance beliefs, and stair-climbing performance in the KT group. However, baseline-adjusted ANCOVA showed no significant between-group differences in pain, WOMAC scores, sit-to-stand performance, or dynamic balance (p > 0.05). Significant differences in kinesiophobia, fear-avoidance beliefs, and stair-climbing performance favored the CP group (p < 0.05).

CONCLUSIONS: Both interventions improved clinical outcomes in individuals with KOA. However, baseline-adjusted analyses indicated that kinesiotaping did not provide additional benefit beyond conventional physiotherapy.

PMID:42400805 | DOI:10.1007/s11845-026-04532-7

Methods Mol Biol. 2026;3024:101-107. doi: 10.1007/978-1-0716-5202-2_10.

ABSTRACT

Chimeric RNA molecules-formed from nucleotide sequences of multiple genes-can arise through chromosomal rearrangements, transcriptional read-through events, or trans-splicing between distinct transcripts. These chimeric RNAs have been shown to play functional roles in both disease states and normal physiological processes, underscoring their biological relevance. Despite this, there are currently a limited number of tools available that aim to quantify chimeric RNA expression. Here, we introduce a metric called the Relative Index of Chimeric Expression (RICE), which assesses the expression of chimeric transcripts relative to their corresponding wild-type parental transcript, and we describe an easy-to-use bioinformatic tool called FusionBlaster for calculating RICE values from RNA sequencing data. After following this guide, users can apply the FusionBlaster pipeline to perform differential RICE analysis on their own RNA sequencing data by applying the appropriate statistical methods.

PMID:42400792 | DOI:10.1007/978-1-0716-5202-2_10

Clin Transl Oncol. 2026 Jul 4. doi: 10.1007/s12094-026-04494-3. Online ahead of print.

ABSTRACT

INTRODUCTION: The fusion mutation occurring in the anaplastic lymphoma kinase (ALK) gene is one of the most important driver mutations detected in the adenocarcinoma subtype of non-small cell lung cancer (NSCLC). In first-line treatment, second- and third-generation ALK inhibitors are recommended at the category 1 evidence. Data on the choice of sequential ALK inhibitor use are limited. This study aimed to evaluate real-life data of second-line treatments after potent ALK inhibitors.

METHODS: Patients who received a second- or third-generation ALK inhibitor in the first-line treatment of metastatic ALK-positive NSCLC and received any subsequent treatment in the second line were included in the study. Demographic, clinical, and laboratory data were collected retrospectively. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Survival outcomes were estimated using the Kaplan-Meier method. Response rates and safety data were analyzed using descriptive statistics.

RESULTS: 98 patients were included in the study. In the first-line treatment, 88.8% (n = 87) of the patients received alectinib, 5.1% (n = 5) brigatinib, 4.1% (n = 4) ceritinib, and 2% (n = 2) lorlatinib. 38.8% (n = 38) of the patients received chemotherapy before ALK inhibitor. The most common second-line treatment was lorlatinib with 74.5% (n = 73). 17.3% (n = 17) patients received chemotherapy, 5.1% (n = 5) patients received brigatinib, one patient each (1%) received alectinib, ceritinib and pembrolizumab. At a median follow-up of 12.2 months, the estimated median OS was 7.3 months (95% CI, 1.9-12.7) and the median PFS was 4.6 months (95% CI, 2.6-6.6). Median OS was 11.6 months (95% CI, 6.5-16.8) in patients receiving ALK inhibitors in second-line treatment and 4 months (95% CI, 2.7-5.3) in patients receiving chemotherapy (p = 0.001). The median PFS in these groups was 5.9 months (95% CI, 4.4-7.5) and 2.5 months (95% CI, 1.2-3.8), respectively (p = 0.001).

CONCLUSIONS: The efficacy of second-line ALK inhibitors is limited in patients receiving potent treatments such as second- and third-generation ALK inhibitors. These findings highlight the limited efficacy of currently available second-line treatment options after failure of potent ALK inhibitors and underscore the need for improved treatment strategies in this setting. Lorlatinib is the most important treatment option in second line, and our results are consistent with real-life data.

PMID:42400766 | DOI:10.1007/s12094-026-04494-3

Environ Sci Pollut Res Int. 2026 Jul 4. doi: 10.1007/s11356-026-37991-7. Online ahead of print.

ABSTRACT

Microplastic contamination in bottled drinking water is an emerging environmental and public health concern, particularly when bottles are exposed to varying storage and thermal conditions. This study introduces FMIND (fuzzy microplastic inference for detection risk), an IoT-enabled fuzzy inference framework for rapid and low-cost microplastic contamination risk assessment. Bottled water stored in PET and stainless-steel containers under sunlight, shade, and freezer conditions was evaluated using IoT sensors measuring temperature, turbidity, and total dissolved solids (TDS) before and after 30 days of storage. Statistical analysis revealed strong correlations between sensor variations and contamination-related physicochemical indicators, including turbidity (r = 0.861), TDS (r = 0.793), and temperature (r = 0.565) (p < 0.001). The FMIND fuzzy model applied 12 Sugeno rules to generate a contamination risk score (0-100), while the HFIRM-GT enhanced configuration improved classification consistency within the experimental dataset, achieving an F1 score of 0.91. Laboratory validation using FTIR spectroscopy, SEM imaging, and EDAX elemental analysis on selected high-risk samples supported the presence of polymer-associated microplastic fragments in sunlight-exposed PET bottles. The proposed framework does not directly quantify microplastics through IoT sensors; instead, it estimates contamination risk using indirect physicochemical indicators supported by laboratory validation. FMIND integrates IoT sensing, fuzzy reasoning, and chemical validation into a unified and interpretable framework for periodic bottled water contamination risk assessment. The reported predictive performance reflects evaluation within a limited experimental dataset and should be interpreted as preliminary proof-of-concept validation rather than generalized field-scale performance. The system provides a scalable and cost-effective approach that supports Sustainable Development Goal 3 (Good Health and Well-Being), Sustainable Development Goal 6 (Clean Water and Sanitation), and Sustainable Development Goal 12 (Responsible Consumption and Production).

PMID:42400762 | DOI:10.1007/s11356-026-37991-7

Vet Res Commun. 2026 Jul 4;50(5):438. doi: 10.1007/s11259-026-11365-3.

ABSTRACT

Opisthorchis viverrini infection remains a major public health concern in Southeast Asia, particularly in the Greater Mekong Subregion. Although animal reservoirs contribute to sustaining parasite transmission, comprehensive evidence on infections in these hosts remains limited. This study conducted a systematic review and meta-analysis to assess O. viverrini infection in animal reservoirs (cats and dogs). Pooled prevalence and infection intensity were estimated using random-effects models and meta-regression, and associated factors were synthesized. Subgroup analyses were performed to examine variability, and heterogeneity was evaluated using the Q statistic and the I² index. The pooled prevalence of O. viverrini infection in animal reservoirs was 4.76% (95% confidence interval (CI): 2.83-7.90%, prediction interval (PI): 0.15-61.76%). After trim-and-fill adjustment, the estimate increased to 16.31% (95% CI: 10.00-25.49%, PI: 0.28-93.09%), with wide prediction intervals indicating substantial heterogeneity. Cats showed significantly higher prevalence (11.97%) than dogs (1.89%; p < 0.01). Infection intensity followed a similar pattern, with mean eggs per gram (EPG) higher in cats (151.07) than in dogs (45.77; p < 0.01). No significant difference in overall prevalence was observed between Thailand (4.36%) and Lao PDR (13.44%; p = 0.19), although significant subgroup differences were detected for cats (p = 0.01) and dogs (p < 0.01). Overall reservoir-host prevalence was higher in endemic areas (5.64%) than in non-endemic regions (2.28%; p < 0.001); this difference was significant in cats but not in dogs. Meta-regression showed no significant temporal trend. Linear regression revealed positive associations between human and animal infections, with stronger correlation for cats (R² = 0.86, p < 0.01) than dogs (R² = 0.62, p = 0.02). These findings support an important role of animal reservoirs, particularly cats, in transmission and emphasize the need for improved surveillance and integrated control strategies.

PMID:42400729 | DOI:10.1007/s11259-026-11365-3

J Interv Card Electrophysiol. 2026 Jul 4. doi: 10.1007/s10840-026-02392-w. Online ahead of print.

ABSTRACT

BACKGROUND: Pulmonary vein isolation (PVI) is an established treatment for symptomatic atrial fibrillation (AF). To date, cryoballoon (CB) ablation has been the most widely adopted single-shot approach, while pulsed field ablation (PFA) has emerged as a non-thermal alternative designed to preferentially ablate myocardial tissue and reduce collateral injury. PulseSelect™ is a CE-marked and FDA approved PFA system specifically developed for PVI. We compared acute and one-year outcomes of PulseSelect PFA versus fourth-generation cryoballoon (CB4) ablation in routine clinical practice.

METHODS: This multicenter analysis included 254 consecutive patients undergoing first-time PVI in 10 Italian medium-volume centers between January 2024 and February 2025: 121 treated with PulseSelect and 133 with CB4. Baseline clinical and echocardiographic characteristics were prospectively collected. Procedural workflow, anesthesia strategy, procedure duration, fluoroscopy time, and periprocedural complications were assessed. Follow-up consisted of scheduled visits with rhythm monitoring, and arrhythmia recurrence was evaluated using Kaplan-Meier analysis.

RESULTS: A total of 254 consecutive patients (mean age 62 ± 9 years, 28.3% women with paroxysmal AF in 76.4%) undergoing first-time PVI were included in the analysis: 133 treated with CB4 and 121 with PS PFA, with largely comparable baseline characteristics. General anesthesia was more frequently used with PulseSelect than with CB4 (74.4% vs. 16.5%). Mean skin-to-skin procedure duration was shorter with PulseSelect (62.4 ± 18 min) compared with CB4 (71.4 ± 30 min; p = 0.005), while fluoroscopy time was longer with PulseSelect. No acute complications occurred in the PulseSelect group; three transient phrenic nerve palsies were observed with CB4. At 12 months, no statistically significant difference in arrhythmia recurrence was observed between PulseSelect and CB4 (17.4% vs. 15.0%; p = 0.46).

CONCLUSIONS: In this real-world multicenter cohort, PulseSelect PFA and CB4 ablation showed excellent acute safety and no statistically significant differences in one-year arrhythmia recurrence were observed between the two treatment strategies.

PMID:42400724 | DOI:10.1007/s10840-026-02392-w

J Artif Organs. 2026 Jul 4;29(3):42. doi: 10.1007/s10047-026-01570-x.

ABSTRACT

Impella is increasingly used as a bridge to durable left ventricular assist device (dLVAD) implantation in patients with advanced heart failure. However, Impella support may worsen aortic insufficiency (AI), raising concerns regarding both AI progression during support and subsequent late AI progression after dLVAD implantation. This study evaluated the impact of Impella bridging on AI progression and clinical outcomes after dLVAD implantation. This retrospective single-center study included 64 patients who underwent primary dLVAD implantation and consisted of three analyses. First, baseline characteristics, perioperative variables, and early postoperative outcomes were compared between the aortic valve (AV) Intervention (n = 12) and No AV Intervention (n = 52) groups at dLVAD implantation. Second, changes in AI severity during Impella support were evaluated in patients with preoperative Impella support (n = 19). Third, long-term outcomes were compared between the Impella Bridging (n = 14) and No Impella Bridging (n = 38) groups after excluding patients who underwent concomitant AV intervention. Preoperative clinical severity was generally comparable between the AV Intervention and No AV Intervention groups, although hospital mortality was higher in the AV Intervention group. AI severity worsened significantly during Impella support (p < 0.001), whereas AV intervention rates did not differ significantly according to preoperative Impella support status (p = 0.32). During long-term follow-up, no statistically significant association was observed between Impella bridging and subsequent AI progression or clinical outcomes. Impella support as a bridge to dLVAD implantation was associated with significant worsening of AI during support. Under the current treatment strategy, including careful assessment of AV function and selective concomitant AV intervention at dLVAD implantation, no statistically significant association was observed between prior Impella bridging and subsequent late AI progression or adverse clinical outcomes. However, given the significantly higher in-hospital mortality in the AV Intervention group, careful patient selection for concomitant AV intervention remains essential.

PMID:42400721 | DOI:10.1007/s10047-026-01570-x

Discov Oncol. 2026 Jul 4. doi: 10.1007/s12672-026-05522-y. Online ahead of print.

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is a prevalent malignant tumor with increasing incidence and mortality rates worldwide. Exosomes are secretory vesicles generated by the endosomal system within cells. Previous studies have reported that exosome-related genes (ERGs) are associated with the progression of malignancies. This study investigates the role of ERGs in CRC, evaluates their impact on CRC prognosis, and explores inter-individual differences among CRC patients in different risk groups.

METHODS: Weighted Gene Co-expression Network Analysis (WGCNA) algorithm was employed to identify ERGs associated with CRC. Subsequently, various bioinformatics approaches, including enrichment analysis, consensus clustering, and survival analysis, were utilized to investigate the role of ERGs in individual CRC patients. Furthermore, exosome-related signature genes were refined using the Random Forest (RF) and Least Absolute Shrinkage and Selection Operator (LASSO) algorithms based on colon cancer samples from The Cancer Genome Atlas (TCGA) database. An ERG-related gene signature was then constructed to calculate the ERG-associated risk score for each patient, which was validated using data from the Gene Expression Omnibus (GEO) database. Based on the risk scores, we assessed the responsiveness of different CRC individuals to immunotherapy and chemotherapy. Finally, single-cell analysis provided deeper insights into the relationship between ERGs and CRC, and a nomogram was established to enhance their clinical utility.

RESULTS: This study identified two ERG-related subtypes that exhibited significant differences in prognosis, enriched pathways, clinicopathological features, and immune characteristics. Moreover, CRC individuals with high ERG-related risk scores were associated with poor responsiveness to immunotherapy and increased sensitivity to various chemotherapeutic agents. Single-cell analysis revealed that ERGs were highly expressed in monocytes. The model developed in this study demonstrated strong predictive accuracy for assessing ERG-related risk in CRC patients.

CONCLUSIONS: This study identified two hub genes, CUL4A and UCHL1, highlighting the diagnostic and prognostic significance of ERGs in CRC and offering new insights into CRC treatment. Additionally, the ERG signature plays a crucial role in predicting individualized prognosis and facilitating the development of novel therapeutic strategies for CRC patients. Nevertheless, further studies are necessary to bring statistically derived risk models into clinically applicable assays.

PMID:42400715 | DOI:10.1007/s12672-026-05522-y