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Objective: The purpose was to investigate the effects of respiratory-swallow coordination training with bimodal signal biofeedback on swallowing function in patients with post-stroke dysphagia.

Methods: Post-stroke dysphagia Patients were randomly assigned to either the control group or the experimental group. The control group received conventional rehabilitation, while the experimental group underwent additional respiratory-swallow coordination training based on biofeedback. The training protocol consisted of three phases, conducted at an intensity of 30 min/day, 6 days/week, for two consecutive weeks. Outcome measures included the Functional Oral Intake Scale (FOIS) score, the Rosenbek Penetration-Aspiration Scale (PAS) score, respiratory-swallow coordination, and videofluoroscopic swallowing study temporal and kinematic parameter. Assessments were conducted at baseline, post-treatment, and at a one-month follow-up.

Results: Thirty patients were enrolled. Both groups showed significant improvement in FOIS scores from baseline to both two-week post-treatment and one-month follow-up (p < 0.001). Compared to the controls, the experimental group demonstrated significantly greater FOIS scoreimprovement at both post-treatment and follow-up (p < 0.001). The proportion of patients with a ≥ 2-point increase in FOIS scores was significantly higher in the experimental group than in the control group at both post-treatment (p < 0.01) and one-month follow-up (p < 0.01). After two weeks of treatment, the percentage of PAS scores ≥6 was significantly lower in the experimental group than in the control group (p < 0.001). Additionally, the percentage of optimal respiratory-swallow pattern was significantly higher in the experimental group than in the control group (p < 0.001).

Conclusion: Bimodal signal biofeedback-based respiratory-swallow coordination training can effectively improve respiratory-swallow coordination and swallowing function in patients with post-stroke dysphagia.

Background: To validate the clinical efficacy of non-invasive prenatal diagnosis (NIPD) for spinal muscular atrophy (SMA) in the first trimester and extend its applicability to families without probands.

Method: From December 2020 to October 2024, 288 high-risk pregnancies were recruited prospectively, with 81 qualifying for NIPD after genetic counseling. Among the eligible cases, parent-based haplotypes were successfully constructed in 75 families (92.6%), while grandparent-based haplotype reconstruction was performed for the remaining 6 cases (7.4%) where proband samples were unavailable. Through targeted sequencing of the SMN1/SMN2 gene and flanking informative SNPs in maternal plasma, fetal haplotypes were inferred by analyzing dosage changes in cell-free DNA (cfDNA) using Bayes factor. All NIPD results were subsequently validated through invasive diagnostic procedures (chorionic villus sampling or amniocentesis).

Results: The haplotypes were successfully constructed in 81 families through parents or grandparents of the identified variant carriers. 76 families (93.8%) successfully obtained NIPD results, among which the earliest gestational week for successful NIPD was 7⁺³weeks, with a minimum fetal fraction of 1.9%. 5 cases were classified 'no call' results due to pathogenic variant-adjacent recombination events (2/5), insufficient or unevenly distributed informative SNPs (2/5), and subthreshold fetal fraction (1/5). The average gestational age of NIPD blood drawing is 9 weeks. Validation test showed the NIPD results accuracy was 100%.

Conclusion: This study demonstrates the clinical feasibility of grandparent-assisted haplotype construction for SMA families without probands and enables accurate early prenatal diagnosis of SMA in first-trimester pregnancies.

Background: Disease stability is an achievable goal in chronic obstructive pulmonary disease (COPD) management. However, the clinical implications of disease stability in patients with COPD remain unclear.

Methods: We conducted a single-center retrospective cohort study using the electronic medical records of treated patients with symptomatic COPD. Patients who had newly initiated inhaler therapy with long-acting β2-agonist/long-acting muscarinic antagonist (LABA/LAMA) or inhaled corticosteroid/LABA/LAMA combinations were included. Disease stability was defined over a one-year assessment period as meeting all of the following criteria: (1) symptom stability; (2) no moderate or severe exacerbations; and (3) no rapid decline in lung function. The outcomes included acute exacerbations and all-cause mortality.

Results: Of the 725 screened patients, 405 were eligible for inclusion in the study. Among them, 158 (39.0%) achieved disease stability. The proportions of patients who met each criterion were 70.4% for symptom stability, 63.7% for no exacerbations, and 71.4% for a non-rapid lung function decline. Only 5.9% met none of these criteria. During the follow up duration of median 62 (interquartile ranges, 30-90) months, disease stability was significantly associated with a reduced risk of moderate-to-severe (adjusted hazard ratio [aHR] 0.521, 95% confidence interval [CI] 0.392-0.692) and severe (aHR 0.393, 95% CI 0.279-0.553) exacerbations after adjusting for confounders. It was also associated with a decreased mortality risk (aHR 0.345, 95% CI 0.135-0.883).

Conclusion: Disease stability was associated with a lower risk of exacerbation and mortality, suggesting its potential role as a treatment target and outcome measure for COPD.

Background: Pathogenic autoantibody subclass switch has been found in lots of autoimmune disease. However, the information on anti-phospholipase A2 receptor antibody subclass switch in membranous nephropathy (MN) is limited and controversial. Here, we aim to uncover the subclass change during the PLA2R-associated MN progression.

Methods: Biopsy-proven PLA2R-associated MN cases with sufficient tissue for light microscopy, immunofluorescence, and electron microscopy (October 2022 - March 2023) were included. Serum levels of PLA2R-IgG4 and PLA2R-IgG were measured by TRFIA. The correlation of the ratio with EM stage and other clinical parameters was analyzed.

Results: Among 116 enrolled patients, glomerular IgG1 (r = 0.15, p = .01; r = 0.18, p = .002) and IgG3 (r = 0.17, p = .005; r = 0.27, p < .001) intensities were positively correlated with C3 and C1q intensities, respectively. The PLA2R-IgG4/PLA2R-IgG ratio was significantly positively correlated with serum albumin (r = 0.26, p = .005) but inversely correlated with both the intensity of glomerular IgG1 (r = -0.20, p = .03) and IgG3 deposits (r = -0.24, p = .009), as well as with C1q staining intensity (r = -0.27, p = .004). The median PLA2R-IgG4/PLA2R-IgG ratio significantly increased with pathological stage (Stage I: 18.92%; Stage II: 39.74%; Stage III: 59.38%; Stage IV: 68.99%) and was strongly positively correlated with EM stage (r = 0.52, p < .001). Advanced EM stages were observed more frequently with higher PLA2R-IgG4/PLA2R-IgG ratio.

Conclusions: During the disease progression, EM stages were correlated with altered autoantibody IgG subclass profiles: early stages featured IgG1 or IgG3 autoantibodies, while late EM stages shifted to IgG4 predominance.

Background: Transbronchial cryobiopsy (TBCB) is a minimally invasive technique that yields larger specimens than conventional transbronchial forceps biopsies (TBFB) and demonstrates superior diagnostic rates for interstitial lung diseases. However, the efficacy of TBCB compared to TBFB in evaluating peripheral pulmonary lesions (PPLs) is not well established. This study aims to examine the diagnostic performance of TBCB relative to TBFB in PPLs.

Material and methods: Between May 2021 and December 2023, patients with PPLs were enrolled and underwent TBFB followed by TBCB. These procedures were performed either in a hybrid operating room (HOR) or a standard bronchoscopy room without fluoroscopy. The study compared histopathology diagnostic yield between the two methods.

Results: The study included 84 patients. The median lesion size was 37 mm (interquartile range: 26, 54), with 16 lesions (19.0%) measuring less than 2.0 cm. Among the participants, 44 (52.4%) were diagnosed with lung cancer, and 28 (33.3%) had infectious diseases. TBCB yielded significantly larger tissue samples [60 mm³ (range: 30, 144) vs. 4 mm³ (range: 2, 6), p < 0.001] and higher diagnostic yields (94.0% vs. 77.1%, p < 0.001) than TBFB. The higher diagnostic yield for TBCB were consistent in both the bronchoscopic room (97.2% vs. 77.8%, p = 0.008) and HOR (91.5% vs. 76.6%, p = 0.033). The incidence of ≥ grade 3 bleeding was 7.1%.

Conclusion: TBCB significantly improves the diagnostic yield for PPLs, irrespective of fluoroscopic guidance, and is effective for both malignant and benign lesions. Furthermore, it is associated with minimal complications, affirming its safety and efficacy as a diagnostic procedure.HighlightsTBCB consistently provided a higher pathological yield compared to TBFB, independent of lesion size, use of fluoroscopy, or the nature of the pathology (benign or malignant)TBCB yielded larger tissue sample and had high successful rates for NGS testing.Combination of an ultrathin bronchoscope, augmented fluoroscopy, ROSE, and TBCB can lead to high diagnostic yields.

Background: Pediatric sepsis represents a significant factor in the mortality rates among children, with survivors remaining highly fragile during the period following discharge. While in-hospital and short-term mortality have been widely studied, the long-term mortality of pediatric sepsis is not adequately synthesized or appreciated. This study aims to estimate the long-term mortality associated with pediatric sepsis, providing a basis for optimizing post-discharge surveillance and care protocols.

Methods: This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO (CRD420251137504). Exhaustive searches were conducted in PubMed, Embase, the Cochrane Library, and Web of Science for studies published from the inception of each database to June 30, 2025. Studies reporting long-term mortality in pediatric sepsis patients diagnosed using international consensus criteria were included. After literature screening, long-term mortality was pooled using a random effects meta-analysis in R statistical software.

Results: A total of 72,065 records were identified through database searching. After removing duplicates and screening, six studies comprising 11,318 pediatric sepsis patients were included. The pooled long-term mortality in pediatric sepsis was 11% (95% CI: 7-16%), though significant heterogeneity was observed (I² = 98.2%, p < 0.001). Sensitivity analyses yielded similar results, and evidence of publication bias was limited.

Conclusion: Long-term mortality after pediatric sepsis was 11%, highlighting the persistent risk of mortality after hospital discharge. Further high-quality longitudinal studies are required to identify modifiable risk factors and guide evidence-based follow-up and personalized care.

Hutchinson Gilford Progeria Syndrome (HGPS) is an ultra-rare pediatric premature aging disorder. It is caused by a point mutation in the LMNA gene leading to the production of the dominant-negative progerin isoform of the nuclear envelope protein lamin A. Most of the mechanistic insights into the disease have come from studies using cellular or mouse models of HGPS. To probe the clinical relevance of previously implicated cellular pathways and to address the extent of gene expression heterogeneity between patients, we performed transcriptomic analysis of a comprehensive set of HGPS patients. We find misexpression of several cellular pathways, including multiple signaling pathways, the Unfolded Protein Response (UPR) and mesodermal cell fate specification. Variability amongst individual patients was limited, with misregulation of the major pathways observed in most patients. Comparing the transcriptome of patients with an inducible HGPS cell model, we also identified the primary target pathways of the disease-causing progerin protein.

The immune system functions within tissue microenvironments of mechanical and geometrical constraints. Within these constraints, immune cells must rapidly move and execute effector functions to regulate innate and adaptive immunity. Here, we review the impact of nuclear mechanobiology on immune cell functionality. We define how non-genetic physical properties of the nucleus such as shape, stiffness and deformability are regulated and directly impact immune cell functions ranging from trafficking routes to pathogen killing. We highlight that studying immune cells allowed breakthroughs in understanding how the nucleus acts as a sensor for spatial constraints, as a break or enabler for cell migration, and as an extracellular trap to kill pathogens. Further, we discuss the unknowns of nuclear mechanobiology and consider the impact of chromatin, condensates, and nuclear membrane components. Together, this review provides an overarching framework of the cellular, physical, and immunological principles of nuclear mechanobiology in immune cells.