Category: Statistics

Ophthalmic Physiol Opt. 2026 Jun 22. doi: 10.1007/s44402-026-00124-1. Online ahead of print.

ABSTRACT

Laboratory and patient-oriented research on photoreceptors and vision in ageing and early and intermediate age-related macular degeneration (AMD) were conducted in parallel starting in the 1990s by Christine Curcio and Cynthia Owsley, respectively. They joined forces in two longitudinal observation studies, the Alabama Study on Age-related Macular Degeneration (ALSTAR) in 2009 and in ALSTAR2 in 2019, together involving >1100 participants. These studies established rod-mediated dark adaptation (RMDA) measured close to the fovea as the first functional biomarker for incident early AMD and the progression of AMD. These studies used standardised grading of colour fundus photography and prioritised large samples for statistical power. RMDA is a global measure of dysregulated transport between the circulation and photoreceptors, involving at least seven different steps in a retinoid re-supply route especially needed by rods, and a surrogate for the delivery of other essentials across this route. The choice of functional and imaging outcome measures was informed by a model of AMD pathophysiology based on drusen biology, as discovered in the laboratory using high-quality human donor eyes. Specifically, high-risk drusen in the central retina were thought to result from large lipoproteins constitutively made by the retinal pigment epithelium and impaired in transit to circulation by ageing changes in Bruch’s membrane and choriocapillaris. Imaging studies in ALSTAR/2 thus included optical coherence tomography (OCT) angiography assessments of choriocapillaris flow signal and OCT assessments of outer bands involved in intercellular transfer (interdigitation zone). Of seven vision tests utilised in ALSTAR2, only RMDA achieved a Minimum Clinically Important Difference at 3 years follow-up. This research highlights the importance of developing functionally valid structural endpoints for use in early and intermediate AMD intervention trials. Research to date supports the idea that functional changes emerge earlier than structural changes in early and intermediate AMD. Clinicaltrials.gov # NCT04112667 (registration date October 7, 2019).

PMID:42332292 | DOI:10.1007/s44402-026-00124-1

Support Care Cancer. 2026 Jun 22;34(7):679. doi: 10.1007/s00520-026-10914-5.

ABSTRACT

PURPOSE: Fear of cancer recurrence (FCR) is one of the most prevalent and distressing psychological concerns among cancer survivors. This study examined the association between somatosensory amplification (SSA) and FCR and tested whether emotion regulation (ER) difficulties moderate this relationship.

METHODS: A sample of 116 adult cancer survivors (Mage = 47.24) completed validated self-report measures assessing SSA, ER difficulties, and FCR. Hierarchical regression analyses were conducted, controlling for anxiety symptom severity, age, gender, and time since treatment completion.

RESULTS: Neither SSA nor ER difficulties were associated with FCR. Yet, the interaction between SSA and ER difficulties was statistically significant. Specifically, the positive association between SSA and FCR was evident at low and mean levels of ER difficulties, but not at high levels.

CONCLUSIONS: Findings suggest that the relationship between heightened bodily sensitivity and FCR may differ according to levels of ER difficulties. Future research should explore longitudinal pathways and relevant intervention-based outcomes.

IMPLICATIONS FOR CANCER SURVIVORS: Screening for SSA and ER difficulties in survivorship care may help identify individuals for whom heightened bodily sensitivity is associated with increased FCR.

PMID:42332285 | DOI:10.1007/s00520-026-10914-5

Neurocrit Care. 2026 Jun 23. doi: 10.1007/s12028-026-02563-7. Online ahead of print.

ABSTRACT

BACKGROUND: Subsequent to an intracerebral hemorrhage (ICH), a cascade of neuroinflammatory response drives the process of secondary brain injury. At present, no anti-inflammatory nor neuroprotective pharmacological interventions have been demonstrated to improve functional outcome after ICH. This Phase 2b study was designed to establish the safety and feasibility of CN-105, a neuroprotective and anti-inflammatory pentapeptide designed from the receptor binding region of apolipoprotein E, in patients with acute primary supratentorial ICH.

METHODS: The Singapore CN-105 in Participants with Acute Supratentorial ICH Trial (S-CATCH, NCT03711903) was a randomized, double-blind, placebo-controlled trial involving 60 patients (30 CN-105, 30 placebo) treated within 12 h of symptom onset. Safety was assessed through adverse events (AEs) and serious AEs (SAEs), while efficacy was evaluated using functional outcome measures, including the modified Rankin Scale (mRS) at 90 days.

RESULTS: CN-105 was safe and well tolerated in patients with acute ICH, with no significant differences in incidence of SAEs between groups (30% SAEs in placebo vs. 26.7% in CN-105). Notably, fewer patients treated with CN-105 group experienced in-hospital neurological deterioration (0 vs. 10% in placebo). While treatment was not associated with a statistically significant improvement in 90-day mRS, higher proportion of patients treated with CN-105 achieved favorable mRS scores (≤ 3) compared with those in the placebo group (77.8 vs. 66.7%; p = 0.35).

CONCLUSIONS: This Phase 2b trial confirmed the safety and feasibility of CN-105 administration in the acute setting of ICH. Although no statistically significant improvements in neurological outcomes were found, the observed trends warrant further investigation. Future Phase 3 trials should focus on refining patient selection and assessing the therapeutic efficacy of CN-105 in more targeted subgroups such as those with medium-sized subcortical ICH. Trial registration NCT03711903, https://clinicaltrials.gov/ https://clinicaltrials.gov/study/NCT03711903?term=NCT03711903&rank=1 . Registered 16 October 2018.

PMID:42332280 | DOI:10.1007/s12028-026-02563-7

Int Orthop. 2026 Jun 22. doi: 10.1007/s00264-026-06921-0. Online ahead of print.

ABSTRACT

PURPOSE: Accurate acetabular cup placement is essential in total hip arthroplasty (THA). We hypothesized that the newly introduced Computed Tomography (CT)-based portable navigation system would demonstrate accuracy comparable to that of the imageless portable navigation system. The aim of this study was to compare cup placement accuracy between the CT-based and imageless portable navigation systems of the same platform in THA performed in the lateral decubitus position.

METHODS: This retrospective cross-sectional study included 36 patients who underwent primary THA via a direct lateral approach in the lateral decubitus position. In all cases, both imageless and CT-based portable navigation systems were used concurrently. Postoperative cup alignment was evaluated using three-dimensional CT (3D-CT). The primary outcome was the absolute error in cup inclination and anteversion, defined as the difference between intraoperative navigation values and postoperative 3D-CT measurements in the functional. Secondary outcomes included outlier rates and registration success rates.

RESULTS: No statistically significant differences were observed between the imageless and CT-based portable navigation systems in the mean absolute error for inclination (2.2 ± 1.8° vs. 2.3 ± 1.8°, p = 0.93) or anteversion (2.3 ± 2.3° vs. 2.6 ± 2.5°, p = 0.41). There were no significant differences in outlier proportions. The registration success rate was 92% (36/39) due to three technical failures.

CONCLUSION: In this preliminary study, the CT-based portable navigation system demonstrated cup placement accuracy comparable to that of the imageless portable navigation system. Although the CT-based system may provide additional spatial information intraoperatively, its impact on clinical outcomes remains unclear and requires further longitudinal investigation.

PMID:42332259 | DOI:10.1007/s00264-026-06921-0

Pediatr Res. 2026 Jun 22. doi: 10.1038/s41390-026-05217-8. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) results from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, causing multisystem disease and impaired quality of life. CFTR modulators have improved pulmonary and nutritional outcomes, yet potential metabolic effects such as dyslipidemia remain a concern, particularly in adults. Pediatric data are limited. This study evaluated the effects of CFTR modulators on lipid and lipoprotein profiles in children with CF.

METHODS: This retrospective study was conducted at a tertiary pediatric pulmonology center. Body mass index (BMI) Z-scores, lung function tests, and serum lipid profiles were compared between baseline and six months after initiation of CFTR modulator therapy.

RESULTS: Twenty-six patients were included finally. The median age was 11 (5.9-15.6) years; 53.8% were female, and 80.8% received elexacaftor/tezacaftor/ivacaftor. After six-month therapy, significant improvements were observed in BMI (p = 0.047), FEV₁ (p = 0.005), and FVC Z-scores (p = 0.001). Although HDL, LDL, VLDL, triglycerides, and total cholesterol increased numerically, none reached statistical significance. No difference was found between BMI changes and lipid alterations.

CONCLUSION: Over six months of continuous CFTR modulator therapy, we observed improvements in pulmonary and nutritional outcomes without evidence of clinically meaningful lipid deterioration.

IMPACT: This study adds real-world pediatric data regarding lipid profile changes during CFTR modulator therapy. While these therapies significantly improve pulmonary and nutritional outcomes, we observed no evidence of lipid deterioration over six months of treatment. These findings contribute to the evolving understanding of the systemic effects of CFTR modulators in childhood and underscore the importance of ongoing cardiometabolic evaluation as survival improves.

PMID:42332244 | DOI:10.1038/s41390-026-05217-8

Pediatr Res. 2026 Jun 22. doi: 10.1038/s41390-026-05199-7. Online ahead of print.

ABSTRACT

BACKGROUND: We sought to evaluate oxidative changes in premature infants receiving 100% oxygen compared with 30% during deferred cord clamping (DCC).

METHODS: Premature infants born at 22^0/7 to 28^6/7 weeks received DCC in conjunction with either 30% (LO Group) or 100% (HI Group) oxygen. Blood was extracted from a preserved umbilical segment and a postnatal sample was collected from umbilical vascular lines within two hours of birth. Reduced-to-oxidized glutathione (GSH/GSSG) ratios were analyzed using liquid chromatography coupled to tandem mass spectrometry.

RESULTS: Sixty-eight infants had data available for analysis. The median (IQR) gestational age of infants was 26^4/7 (24^6/7, 28^2/7) weeks in both groups. Among infants receiving 100% versus 30% oxygen, median (IQR) GSH/GSSG ratio were not statistically different in arterial cord blood [7.5 (0.6, 290) vs 37 (1.1, 265), p = 0.52] or venous cord blood [8.4 (2,50) vs 76 (5, 210), p = 0.12] or postnatal samples [14 (2, 290) vs 8 (2, 280), p = 0.98)].

CONCLUSION: Briefly providing 30% vs. 100% oxygen for 90 seconds during DCC showed no significant difference in GSH/GSSG ratios, but redox effects remain unclear given variability, sample size and limited power. Further studies are needed to ascertain potential oxidative damage during neonatal resuscitation and deferred cord clamping. THIS TRIAL IS REGISTERED ON CLINICALTRIALS.

GOV ID: NCT04413097 IMPACT: The effect of oxygen administration during deferred cord clamping on redox status is unclear due to large variability in GSH and GSSG values and small sample size. These data provide some insights about umbilical arterial and venous oxygen levels and the effect of placenta on GSH/GSSG in preterm infants. Further basic and clinical studies are needed to better ascertain the potential for oxidative damage during neonatal resuscitation and deferred cord clamping.

PMID:42332243 | DOI:10.1038/s41390-026-05199-7

J Imaging Inform Med. 2026 Jun 22. doi: 10.1007/s10278-026-02061-4. Online ahead of print.

ABSTRACT

Accurate kidney ultrasound segmentation is fundamental for clinical measurement and computer-aided diagnosis. However, domain shifts across devices and centers-manifested as differences in grayscale intensity, contrast, and speckle texture statistics-can substantially degrade model generalization, while acquiring new pixel-level annotations is costly. To address this, we propose a statistical spectral-similarity-guided ultrasound-to-ultrasound translation method to improve kidney segmentation performance without target-domain annotations. Motivated by frequency-domain analysis of renal ultrasound data, we observe that mid-to-low frequency components, which encode global organ structure, exhibit high consistency across domains, whereas mid-to-high frequency components, dominated by device-dependent speckle and texture statistics, vary substantially. Based on dataset-level frequency statistics, our method automatically identifies spectrally similar frequency bands shared by the source and target domains and derives structural guidance from them. This guidance is injected as a soft condition throughout a diffusion-based image generation process, enabling translation to target-device appearance while preserving anatomical structure. The translated images, paired with source-domain labels, are then used to train a segmentation network without requiring any target-domain annotations. Experiments on two public renal ultrasound datasets (OKUS and UNK) and an in-house multi-center dataset demonstrate superior structural preservation in image translation and consistently improved downstream segmentation performance, with particularly large reductions in boundary error. In the challenging OKUS to UNK adaptation scenario, our method boosts the mean Dice score by up to 20.52% (from 56.05% to 76.57%) and drastically reduces the 95% Hausdorff Distance (HD95) boundary error by 71.96 mm compared to the direct transfer baseline. Furthermore, consistent performance gains are achieved across the in-house multi-center dataset. These results indicate that the proposed spectral-similarity-based guidance effectively handles ultrasound domain shifts, substantially improving robustness and generalization for kidney segmentation under zero-shot and cross-center settings.

PMID:42332239 | DOI:10.1007/s10278-026-02061-4

J Imaging Inform Med. 2026 Jun 22. doi: 10.1007/s10278-026-02029-4. Online ahead of print.

ABSTRACT

Breast density is a breast cancer risk factor. The accurate quantification of breast density requires reliable segmentation of dense tissue in mammograms, but it is a challenging task due to large variations in tissue appearance across hospitals and imaging devices. We propose MammoDenseSegNet, a new deep encoder-decoder convolutional neural network designed to enhance segmentation performance through two complementary modules: a) Adaptive dual attention module, which captures long-range spatial and channel interdependencies to provide focused attention on relevant dense tissue areas regardless of their location; and b) Multi kernel receptive field module, which enlarges the network’s receptive field at the bottleneck layer to aggregate multi-scale contextual features. Additionally, a multi-scale dice loss with deep supervision guides learning across decoder levels to improve robustness. We evaluated MammoDenseSegNet on two public digital mammogram datasets (VinDR-Mammo and EMBED) and one private dataset, spanning a variety of breast densities and imaging artifacts in a total of 1499 images from 606 women. Statistical analysis was done using generalized linear models accounting for correlation among images from the same women and adjusting for potential confounders (proc genmod, proc mixed, SAS v.9.4, SAS Institute, Cary, NC). MammoDenseSegNet demonstrated consistently high performance across various conditions (with Recall ranging from 0.64 to 0.90 and Dice from 0.63 to 0.91) and significantly (p < 0.001) outperformed the publicly available state-of-the-art algorithm based on the VGG16 (with Recall from 0.04 to 0.91 and Dice from 0.06 to 0.82 across the same conditions). The improvement was largest for low-density tissue, where the baseline algorithm practically fails (with the mean Recall of 0.14 and Dice of 0.16) while MammoDenseSegNet remained clinically useful (with the mean Recall of 0.66 and Dice of 0.63).

PMID:42332236 | DOI:10.1007/s10278-026-02029-4

Ann Dyslexia. 2026 Jun 22. doi: 10.1007/s11881-026-00372-3. Online ahead of print.

ABSTRACT

Many children with oral language difficulties also experience challenges with word reading, as evidenced in the high comorbidity rate between developmental language disorders and dyslexia. The current study investigated a sample of students (n = 357) with language and literacy difficulties classified into latent classes based on pre-intervention performance on word reading and listening comprehension measures. Specifically, this study sought to determine the extent to which latent classes responded to an evidence-based, narrative language program at immediate post-test and a five-month follow-up time point, and whether performance varied as a function of class membership. Findings revealed that students in all latent profiles showed statistically significant improvements in narrative language at post-test, a primary target of the intervention. However, intervention effects varied at a five-month follow-up time point, with students with the greatest listening comprehension and word reading difficulties showing the most notable gains. Instructional response also varied according to performance on a narrative writing measure. These findings suggest that assessing initial performance on key variables may be able to help educators predict student response and adapt intervention plans to more effectively meet individual needs.

PMID:42332233 | DOI:10.1007/s11881-026-00372-3

Bone Marrow Transplant. 2026 Jun 23. doi: 10.1038/s41409-026-02934-w. Online ahead of print.

ABSTRACT

Gastrointestinal graft-versus-host disease (GI-GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), often requiring invasive endoscopy for diagnosis. Fecal calprotectin (FC) offers a non-invasive marker of intestinal inflammation, but its utility in GI-GVHD needs clarification. In this prospective observational study of 165 adult allo-HSCT recipients, FC was measured on days +7, +14, and +21 post-transplant, at GI-GVHD onset, and 7 days post-treatment, alongside clinical, endoscopic, and histological data. GI-GVHD developed in 52.7% of patients, with histological confirmation in 90.3% of cases. FC lacked predictive value on day +7 (AUC = 0.50) but showed moderate-to-high accuracy on days +14 (AUC = 0.69) and +21 (AUC = 0.77), with an optimal day +21 cutoff of 52.5 µg/g (sensitivity 75%, specificity 87%). At diagnosis, median FC was 120 µg/g, correlating with endoscopic severity (r = 0.31; p = 0.02) but not clinical or histological grades. FC declined significantly post-treatment (120 to 51.5 µg/g; p = 0.04), though concurrent infections elevated levels without compromising discriminative ability. FC serves as a dynamic biomarker for predicting, diagnosing, and monitoring GI-GVHD, but requires integrated clinical interpretation due to limited specificity amid other inflammations.

PMID:42332220 | DOI:10.1038/s41409-026-02934-w