Category: Statistics

Interdiscip Sci. 2025 Jun 26. doi: 10.1007/s12539-025-00728-0. Online ahead of print.

ABSTRACT

Recent advancements in spatial transcriptomics (ST) technologies have greatly revolutionized our understanding of tissue heterogeneity and cellular functions. However, popular ST, such as 10x Visium, still fall short in achieving true single-cell resolution, underscoring an urgent need for in-silico methods that can accurately resolve cell type composition within ST data. While several methods have been proposed, most rely solely on gene expression profiles, often neglecting spatial context, which results in suboptimal performance. Additionally, many deconvolution methods dependent on scRNA-seq data fail to align the distribution of ST and scRNA-seq reference data, consequently affecting the accuracy of cell type mapping. In this study, we propose stGNN, a novel spatially-informed graph learning framework powered by statistical modeling for resolving fine-grained cell type compositions in ST. To capture comprehensive features, we develop a dual encoding module, utilizing both a graph convolutional network (GCN) and an auto-encoder to learn spatial and non-spatial representations respectively. Following that, we further design an adaptive attention mechanism to integrate these representations layer-by-layer, capturing multi-scale spatial structures from low to high order and thus improving representation learning. Additionally, for model training, we adopt a negative log-likelihood loss function that aligns the distribution of ST data with scRNA-seq (or snRNA-seq) reference data, enhancing the accuracy of cell type proportion prediction in ST. To assess the performance of stGNN, we applied our proposed model to six ST datasets from various platforms, including 10x Visium, Slide-seqV2, and Visium HD, for cell type proportion estimation. Our results demonstrate that stGNN consistently outperforms seven state-of-the-art methods. Notably, when applied to mouse brain tissues, stGNN successfully resolves clear cortical layers at a high resolution. Additionally, we show that stGNN is able to effectively resolve ST at different resolutions. In summary, stGNN provides a powerful framework for analyzing the spatial distribution of diverse cell populations in complex tissue structures. stGNN’s code is openly shared on https://github.com/LiangSDNULab/stGNN .

PMID:40571903 | DOI:10.1007/s12539-025-00728-0

Paediatr Drugs. 2025 Jun 26. doi: 10.1007/s40272-025-00702-9. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Ustekinumab (USTE) and vedolizumab (VEDO) are increasingly used in paediatric patients with inflammatory bowel diseases (pIBD). However, data on the usefulness of therapeutic drug monitoring (TDM) in children are scarce. The primary objective of this study was to evaluate the association between disease activity, measured by faecal calprotectin (F-CPT), and serum trough levels (TLs) of USTE and VEDO. Secondary outcomes were to explore factors potentially associated with the outcome and exposure, to determine the optimal USTE or VEDO dose that predicts remission (defined as F-CPT < 250 µg/g), to validate our hypothesis using a proof-of-concept cohort (POCC) and to assess the occurrence of serum antibodies to USTE and VEDO.

METHODS: This was a prospective single-centre observational study performed at the University Hospital Motol, Prague, Czech Republic. Of the 87 patients (51 Crohn’s disease (CD), 30 ulcerative colitis (UC), and 6 IBD unclassified (IBD-U)), drug serum TLs and antibodies were measured in 282 observations (49 treatment courses) of USTE and 359 observations (38 courses) of VEDO. Serum and stool samples were collected before each study drug application during both the induction and maintenance phases of the treatment throughout the entire study period (January 2020 to June 2024). Clinical and laboratory data were obtained from the nationwide prospective registry CREdIT. Patients with perianal disease and those with previous major bowel surgery were not excluded from the study. As a POCC, we analysed a group of pIBD treated at our centre with anti-TNF agents-adalimumab or infliximab.

RESULTS: In a linear multiple regression mixed model, an association was observed between logF-CPT levels and USTE treatment duration (β -0.0010, 95% confidence interval (CI) -0.0015 to -0.0006, p < 0.001) but not with USTE TLs (p = 0.12). VEDO TLs and logF-CPT levels were negatively associated both in the linear (β -0.0173, 95% CI -0.0292 to -0.0053, p = 0.005) and categorical models (p = 0.026), even after adjusting for time. A VEDO TL of 15.1 µg/mL showed the best, though still poor, combination of sensitivity (0.82) and specificity (0.32) to predict F-CPT < 250 µg/g (area under the curve (AUC) 0.56, 95% CI 0.49-0.63). Intensification, induction phase, undetectable TLs, and type of IBD (CD, UC, IBD-U) were not associated with logF-CPT. Slightly elevated anti-drug antibodies were detected in 5 USTE and 16 VEDO observations, with no clinical implications.

CONCLUSIONS: TDM of USTE does not appear to be useful in pIBD. TDM of VEDO may assist in therapeutic strategy decisions, although establishing clinically useful cut-offs remains challenging.

PMID:40571898 | DOI:10.1007/s40272-025-00702-9

Drugs. 2025 Jun 26. doi: 10.1007/s40265-025-02205-w. Online ahead of print.

ABSTRACT

BACKGROUND: Plecanatide is a novel guanylate cyclase-C agonist for the treatment of functional constipation (FC). Its efficacy may vary across different racial populations.

OBJECTIVE: This study aimed to comprehensively evaluate the efficacy, safety, and pharmacokinetics of plecanatide in Chinese patients with FC.

METHODS: This phase III, randomized, double-blind, placebo-controlled trial was conducted across 40 hospitals in China. A total of 648 patients with FC were randomly assigned in a ratio of 1:1 to receive either plecanatide 3 mg or placebo for 12 weeks, followed by a 2-week follow-up. The primary efficacy endpoint was the durable overall complete spontaneous bowel movement (CSBM) response rate. Data on adverse events were collected. A post hoc logistic regression analysis was performed to identify predictors of durable overall CSBM response.

RESULTS: After 12 weeks of continuous treatment, the durable overall CSBM response rates were 23.5% in the plecanatide group and 10.2% in the placebo group (p < 0.001). Plecanatide significantly increased the mean weekly frequency of CSBM (1.89 vs 0.9) and SBM (2.33 vs 1.03) compared with placebo throughout the treatment period. In addition, all other secondary efficacy endpoints showed statistically significant improvements with plecanatide compared with placebo. The most common treatment-related emergent adverse event was diarrhea, which occurred in 4.3% of plecanatide-treated patients and 0.6% of placebo-treated patients (p = 0.002). Plasma concentrations of plecanatide and its metabolite SP-338 remained below the lower limit of quantification (0.500 ng/ml) at all assessed time points. Weekly CSBM response at week 2 (odds ratio 43.476; 95% confidence interval 18.274-103.432) and baseline stool consistency (odds ratio 0.550; 95% confidence interval 0.366-0.827) were identified as effective predictors of durable overall CSBM response. Even among plecanatide non-responders, a significant improvement in SBM frequency compared with placebo was observed over the 12-week treatment period.

CONCLUSIONS: Plecanatide 3 mg was effective and well tolerated in the treatment of Chinese patients with FC. A weekly CSBM response at week 2 may serve as a predictor of 12-week durable overall efficacy. Patients who did not achieve the primary endpoint may still benefit from plecanatide treatment.

CLINICALTRIALS: GOV: NCT0515132.

PMID:40571893 | DOI:10.1007/s40265-025-02205-w

J Appl Res Intellect Disabil. 2025 Jul;38(4):e70089. doi: 10.1111/jar.70089.

ABSTRACT

BACKGROUND: To date, no studies have examined the prevalence of hoarding behaviour and domestic squalor among individuals with mild intellectual disability. To address this gap, we conducted a prevalence study within a population supported by a medium-sized care organisation in the Netherlands.

METHOD: Data were collected on 437 individuals with mild intellectual disability receiving care in residential facilities or through outpatient services. Assessments were conducted using the Hoarding Rating Scale-Interview, the Environmental Cleanliness and Clutter Scale, and the Clutter Image Rating Scale.

RESULTS: Hoarding behaviour and/or domestic squalor were observed in 16.8% of the residents. Support staff identified 8.3% of dwellings as posing significant safety risks or health hazards. Additionally, 6.7% of residents had been threatened with eviction due to hoarding or squalor.

CONCLUSIONS: Hoarding behaviour and domestic squalor appear to be more prevalent among individuals with mild intellectual disability in care settings than among the overall population.

PMID:40571875 | DOI:10.1111/jar.70089

J Gastrointest Cancer. 2025 Jun 27;56(1):141. doi: 10.1007/s12029-025-01260-6.

ABSTRACT

BACKGROUND: The combination of FOLFOX/FOLFIRI with an EGFR-antibody (cetuximab/panitumumab) is a first-line standard for RAS wild-type metastatic colorectal cancer (mCRC). The OPTIMOX stop-and-go regimen, which reduces oxaliplatin-induced neuropathy, and fluorouracil/folinic acid (FU/FA) were standard maintenance-therapies in the pre-antibody era. Whether an EGFR-antibody adds value to the OPTIMOX strategy in the RAS wild-type setting remains unknown.

METHODS: In the open-label, randomized, multicenter phase II ERBIMOX trial, patients with KRAS wild-type mCRC received either first-line induction-therapy with 8 cycles of mFOLFOX7 followed by maintenance-therapy with FU/FA (OPTIMOX arm) or mFOLFOX7 + cetuximab followed by FU/FA + cetuximab (ERBIMOX arm). Primary objective was to demonstrate superiority of additional cetuximab to mFOLFOX7 during induction/maintenance-therapy. Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. The trial is registered at EudraCT (No.2006-002744-28).

RESULTS: From 2006-2011, 138 patients with KRAS wild-type mCRC from 23 German sites were randomly assigned to either OPTIMOX (N = 63) or ERBIMOX (N = 75). ORR numerically favored the ERBIMOX arm (64.0% vs. 54.0%, P = 0.3071). Median PFS (ERBIMOX vs. OPTIMOX) was 9.6 vs. 8.8 months (P = 0.7612), median OS 25.6 vs. 30.9 months (P = 0.5821). Most common grade 3/4 adverse events (AEs) were skin reactions (21.9% vs. 2.1%) and gastrointestinal disorders (13.5% vs. 9.5%). No cetuximab-related deaths occurred.

CONCLUSION: In treatment-naïve KRAS wild-type mCRC, adding cetuximab to mFOLFOX7 resulted in numerically higher ORR than mFOLFOX alone, but no statistically significant differences in ORR, PFS or OS; probably because of the premature stop due to poor recruitment. The safety profile was as expected, with few discontinuations.

PMID:40571867 | DOI:10.1007/s12029-025-01260-6

AAPS J. 2025 Jun 27;27(5):113. doi: 10.1208/s12248-025-01096-9.

ABSTRACT

Herein, we report a new modified nanoprecipitation method for the fabrication of water-dispersible Poly(lactic-co-glycolic acid) (PLGA) nanoparticles encapsulating three poorly water-soluble anticancer agents as model drugs: paclitaxel (PTX), docetaxel (DTX) or curcumin (Cur). These nanoparticles were water dispersible with favourable size for anticancer applications (below 200 nm) and relatively high drug loading (6.3-8.9%). These nanoparticles were stable for four weeks in solid state and up to 48 h when dispersed in water. PTX and Cur nanoparticles showed a very minimal release of the payload during a 72-h in vitro release study. The new method also yielded reproducible results across three different batches of each type of nanoparticles and following three times upscaling of PTX nanoparticles. PTX and Cur nanoparticles were more effective than the free drugs against MDA-MB-231 cells (p < 0.05). In addition, PTX nanoparticles showed a significant enhanced induction of early apoptosis in MDA-MB-231 cells (42.3%) in comparison to free PTX (23.7%, p < 0.05). Both flow cytometry and confocal microscopy confirmed the uptake of the nanoparticles by MDA-MB-231 cells. In conclusion, our modified nanoprecipitation method produces PLGA nanoparticles loaded with different anticancer agents and suitable for cancer therapy.

PMID:40571866 | DOI:10.1208/s12248-025-01096-9

Eur J Orthop Surg Traumatol. 2025 Jun 26;35(1):281. doi: 10.1007/s00590-025-04404-3.

ABSTRACT

PURPOSE: The aim of this study was to analyze the functional and radiological outcomes of delay arthroscopic repair of traumatic massive rotator cuff tears (mRCTs).

METHODS: This is a prospective study of patients with traumatic mRCTs treated by arthroscopic repair within the first 12 months after trauma. Degenerative tears, single tendon tears, associated fractures, severe arthropathy, irreparable tears, patients older than 75, and those with less than 1 year of follow-up were excluded. Range of motion, pain, and the ASES score were analyzed. MRI was performed preoperatively to assess the rotator cuff tear and 6 months after surgery to evaluate tendon healing. The average follow-up was 22 (± 6.3) months. A p value of < 0.05 was considered statistically significant.

RESULTS: A total of 20 patients were included, with a mean age of 61.7 (± 8) years, 60% male, 65% dominant side affected, and 65% manual workers. The mean time to diagnosis was 4.5 (± 2.7) months, and the mean time to surgery was 7.6 (± 3) months. The mean ASES score was 80.6 ± 15 95% of patients achieved satisfactory results. Elevation improved by a mean difference of – 38 degrees (p < 0.001), external rotation – 29 degrees (p < 0.001), pain decreased by 6 points (p < 0.001), and the ASES score improved by 41 points (p < 0.001). The rate of retear was 60% and patients in whom surgery was performed more than 6 months after the trauma had a 4.7-fold increased risk of retear (p = 0.018). Patients without a retear demonstrated better postoperative external rotation (p = 0.013) and ASES scores (p = 0.033).

CONCLUSIONS: Delayed arthroscopic repair of massive traumatic rotator cuff tears led to good functional outcomes in 95% of patients, despite a rate of retear of 60%. Patients operated on more than 6 months after trauma had a relative risk of 4.7 for presenting a retear.

PMID:40571862 | DOI:10.1007/s00590-025-04404-3

Eur J Orthop Surg Traumatol. 2025 Jun 26;35(1):280. doi: 10.1007/s00590-025-04380-8.

ABSTRACT

PURPOSE: The purpose of this study was to evaluate the short-term postoperative outcomes of patients undergoing patella open reduction internal fixation procedures based on the type of anesthesia administered.

METHODS: A retrospective review was conducted of patients who were surgically treated for displaced patella fractures from 2012 to 2024 at a single multi-site academic institution. Patients were included if they were > 18 years of age, sustained an isolated patella fracture, and had a minimum of 6-month follow-up. Patients were divided into groups based on the anesthetic modality used during their surgery: regional anesthesia only (RA), general/neuraxial anesthesia (NR), and a combination of these methods (CA). Comparisons of statistics were performed using Pearson chi-squared tests, one-way ANOVA tests, and linear regression tests as appropriate.

RESULTS: There were no complications associated with the administration of anesthesia within each cohort. There was no significant difference in fracture healing rates (p = .210) nor complication rates between the anesthesia groups (p = .088). The RA and CA groups had significantly shorter operating room (wheels in to wheels out) times than the NR group (p < .001), significantly greater 3-month (p = .001) and 6-month knee ROM (p = .016) than the NR group when controlling for age, fracture pattern, and repair method.

CONCLUSION: This study demonstrates the efficacy of the use of regional anesthesia only for repair of a patella fracture. This technique is associated with greater early range of knee motion in patients after surgery and a shorter surgical time with no increase in intra or postoperative complications.

PMID:40571850 | DOI:10.1007/s00590-025-04380-8

J Perinatol. 2025 Jun 26. doi: 10.1038/s41372-025-02343-9. Online ahead of print.

ABSTRACT

Small for gestational age (SGA) infants face increased morbidity, mortality, and long-term health risks, yet causes of SGA remain unclear. While placental insufficiency and environmental factors contribute, genetic disorders play a significant role. Syndromes like Silver-Russell and Noonan are linked to SGA, but the overall genetic contribution remains uncertain. We reviewed literature on genomic sequencing in SGA and fetal growth restriction (which often precedes SGA) and identified 161 single-gene disorders. The top ten genes explained one-third of cases, but half were attributable to unique genes. Genetic disorders were frequently accompanied by congenital anomalies (often skeletal dysplasia) and developmental delays. Current guidelines for genetic evaluation of SGA are limited. Our findings support consideration of exome or genome sequencing, particularly in the setting of congenital anomalies or developmental delays. Early identification of genetic disorders can enable tailored therapy. Given the complexity of the SGA genetic landscape, prospective genomic studies are urgently needed.

PMID:40571843 | DOI:10.1038/s41372-025-02343-9

Support Care Cancer. 2025 Jun 26;33(7):631. doi: 10.1007/s00520-025-09690-5.

ABSTRACT

OBJECTIVE: This study aims to explore the effects and safety of Baduanjin on lung cancer patients post-surgery.

METHODS: We conducted a comprehensive search of ten databases for relevant studies up to November 1, 2024. Studies included RCTs where Baduanjin was compared with respiratory training, routine care or no treatment. Statistical analyses and forest plots were generated using Review Manager 5.4.1. Results were expressed as mean difference with 95% confidence interval. The GRADE tool was used to assess the level of evidence for all outcomes.

RESULTS: Nine RCTs involving 795 lung cancer patients who underwent lung resection surgery were included in meta-analysis. Baduanjin showed significant improvements compared to comparison group in 6-min walk distance (MD = 22.93, 95% CI [10.60, 35.26], P = 0.0003), FEV₁ (MD = 0.27, 95% CI [0.11, 0.44], P = 0.001), FVC (MD = 0.34, 95% CI [0.14, 0.54], P = 0.0008), and FACT-L (MD = 20.46, 95% CI [9.48, 31.44], P = 0.0003). Additionally, Baduanjin significantly reduced the self-rating anxiety scale (MD = – 6.68, 95% CI [- 10.05, – 3.32], P = 0.0001) and self-rating depression scale scores (MD = – 6.15, 95% CI [- 7.83, – 4.46], P < 0.0001). No adverse events were reported in the included studies.

CONCLUSION: Baduanjin is a safe and effective home-based feasible rehabilitation measure for enhancing postoperative activity tolerance, lung function, and quality of life while reducing negative emotions in patients after lung cancer surgery. However, due to the limitations, including low-quality evidence, high heterogeneity, and insufficient safety data in this review, the results should be interpreted cautiously. More rigorously designed, high-quality RCTs should be conducted in the future while emphasizing patient compliance and the safety of the interventions.

PMID:40571840 | DOI:10.1007/s00520-025-09690-5