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The genetic etiology of spontaneous abortion: insights from chromosomal microarray analysis and whole-exome sequencing

Sci Rep. 2026 Jun 8. doi: 10.1038/s41598-026-53777-w. Online ahead of print.

ABSTRACT

Spontaneous abortion is one of the most common adverse pregnancy outcomes, with an incidence of approximately 15-25% in clinically recognized pregnancies. Chromosomal abnormalities are recognized as a primary genetic etiology, yet the specific underlying molecular mechanisms and pathways remain incompletely understood. Embryonic tissue samples from 1585 patients with spontaneous abortion were collected from January 2019 to June 2025. Chromosomal microarray analysis (CMA) was used for whole-genome detection of chromosomal abnormalities, including aneuploidy and copy number variations (CNVs). Functional enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were conducted on CNV-related genes. 34 cases with negative CMA results and a history of recurrent pregnancy loss (≥ 2 episodes) were randomly selected to undergo whole-exome sequencing (WES) for the screening of monogenic variants. Statistical analysis included chi-square tests for inter-group comparisons, restricted cubic splines (RCS), and multivariate logistic regression for assessing risk factors. The detection rate of chromosomal abnormalities was 54.44%, mainly numerical abnormalities, with trisomy 16 and X monosomy being the most common subtypes. Structural variants include CNVs, loss of heterozygosity (LOH) and Runs of homozygosity(ROH). The results of the GO enrichment analysis indicated that genes associated with CNVs are primarily involved in hemostasis regulation and monocyte migration; KEGG enrichment analysis indicated that the Toll-like receptor signaling pathway and the neuroactive ligand-receptor interaction pathway may play a significant role in the pathogenesis of miscarriage. Multivariate Logistic regression analysis revealed that a mother’s age of ≥ 35 years was an independent risk factor (OR = 1.72, 95%CI: 1.31-2.26), while a gestational age of ≥ 12 weeks had a protective effect (OR = 0.27, 95%CI: 0.21-0.34). The RCS model revealed a U-shaped relationship between maternal age and the risk of chromosomal abnormalities. The risk was lowest at ages 28-29 (OR = 0.99) and increased gradually after age 30; the risk of chromosomal abnormalities peaked between 8 and 10 weeks of gestation. The diagnostic yield of WES in recurrent miscarriage cases with normal CMA results reached 26.47%. This approach identified a variant in the MOS gene associated with oocyte maturation defects, along with clinically significant variants in possible miscarriage-implicated genes such as TTC7A. Chromosomal abnormalities, particularly trisomy 16 and monosomy X, along with dysregulation of hemostatic and immune pathways, are central to spontaneous abortion etiology. Advanced maternal age, defined as 30 years or older, and early gestational loss are key risk factors, challenging the conventional threshold of 35 years. The use of a combined CMA and WES strategy has effectively improved the genetic diagnosis rate, demonstrating the complementary value and advantages of combining chromosomal and single-gene testing technologies in diagnosing the causes of miscarriage.

PMID:42260280 | DOI:10.1038/s41598-026-53777-w

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tMIP-CTA Application in Infra-knee Artery Angiography for Diabetic Lower Extremity Disease

J Imaging Inform Med. 2026 Jun 8. doi: 10.1007/s10278-025-01751-9. Online ahead of print.

ABSTRACT

To investigate the feasibility of time-resolved maximum intensity projection computed tomography angiography (tMIP-CTA) in assessing below-the-knee arterial lesions in diabetic patients. A prospective study enrolled 79 patients (53 males, 26 females; mean age 71.6 ± 10.2 years) with diabetic foot and lower extremity vascular disease between June 2023 and May 2024. Standard lower extremity arterial CTA was performed, followed by a low-dose dynamic CTA scan after a 5-min delay. tMIP images were generated by fusing data points from the time when the maximum CT value was reached during the enhancement process. Patients were divided into three groups: Group A (D-CTA, optimal phase of dynamic CTA), Group B (tMIP-CTA, full-phase maximum intensity projection CTA), and Group C (S-CTA, standard CTA). Regions of interest (ROIs) were selected in the popliteal, anterior tibial, peroneal, posterior tibial, and tibiofibular trunk arteries. Arterial vessel CT values and image noise (IN) were measured, and signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. A 5-point scale was used for subjective scoring of each segment of the below-the-knee arteries. Statistical analyses were performed to compare objective indicators and subjective scores. Differences in below-the-knee arterial stenosis severity, collateral vessels, distal foot artery visualization, and lower extremity venous contamination were also compared. Group B exhibited significantly lower IN, higher muscle CT values, SNR, and CNR compared to groups A and C, with statistically significant differences (p < 0.05). The diagnosability rate of below-the-knee arteries was significantly higher in group B than in group C (p < 0.01). There were no significant differences in subjective scores for stenosis severity among the three groups for bilateral below-the-knee arteries. Strong inter-observer agreement was observed in subjective scoring of below-the-knee arterial image quality (weighted kappa values of 0.919, 0.957, and 0.960, respectively). Compared to group C, group B showed significantly reduced lower extremity venous contamination (p < 0.05) and a significantly higher number of visualized foot arteries (p < 0.05). The number of visualized collateral vessels was higher in group B than in group C, although the difference was not statistically significant. The tMIP-CTA technique significantly improves image quality in below-the-knee arterial imaging for patients with diabetic foot and lower extremity vascular disease. It offers higher reliability in assessing arterial stenosis and enhances the visualization of foot arteries and small collateral vessels.

PMID:42260260 | DOI:10.1007/s10278-025-01751-9

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Changes in Serum Uric Acid After Laparoscopic Sleeve Gastrectomy: Are They Associated with Baseline Renal Hyperfiltration?

Obes Surg. 2026 Jun 8. doi: 10.1007/s11695-026-08790-3. Online ahead of print.

ABSTRACT

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) provides durable, stable weight loss and ameliorates renal dysfunction, hyperuricemia (HUA), and other obesity-related metabolic disorders. Renal function is tightly linked to serum uric acid (SUA) metabolism, but conventional estimated glomerular filtration rate (eGFR) equations have well-documented substantial bias in individuals with obesity.

METHODS: We retrospectively collected clinical data from 202 patients who underwent LSG, with assessments performed at baseline and 1, 3, and 6 months postoperatively. Patients were stratified into the renal hyperfiltration (HF, 1n = 147) and normal filtration (NF, n = 55) groups using a baseline eGFR cutoff of 125 mL/min/1.73 m². 1:1 propensity score matching (PSM) was conducted using 7 covariates to balance baseline between-group heterogeneity.

RESULTS: The main effect of time on SUA levels was marginally significant pre-PSM (P = 0.054), but reached statistical significance post-PSM (P = 0.034). A significant main effect of group was observed at both stages (pre-PSM P = 0.008; post-PSM P = 0.037), with consistently higher SUA levels in the NF group. No significant time-by-group interaction effect was detected in either pre- or post-PSM analyses (both P > 0.05). Bonferroni-adjusted post hoc pairwise comparisons revealed significant SUA reductions at 3 and 6 months postoperatively relative to baseline in the pre-PSM HF group, with no significant temporal changes in the pre-PSM NF group; no significant pairwise differences across time points were seen in the matched cohort.

CONCLUSION: Temporal changes in SUA levels after LSG are not significantly associated with baseline renal filtration status.

KEY POINTS: • The time-by-group interaction effect was not significant in either pre- or post-PSM analyses, meaning the temporal trends of SUA levels after LSG did not differ significantly by baseline renal filtration status (HF vs. NF). • Both before and after PSM, SUA levels were consistently lower in the HF group than in the NF group; therefore, a longer duration of SUA monitoring may be necessary for the NF group.

PMID:42260255 | DOI:10.1007/s11695-026-08790-3

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Additional vertebrae are imaged in 44% of pediatric patients when limited CTs are ordered: a pilot study

Spine Deform. 2026 Jun 8. doi: 10.1007/s43390-026-01464-1. Online ahead of print.

ABSTRACT

PURPOSE: To determine how often physician-ordered limited CTs in pediatric spine patients are not followed, and if this leads to excess radiation.

METHODS: Single-center retrospective review of a tertiary pediatric spine practice.

INCLUSION: CT scans ordered for specific vertebrae (e.g., L4-5) Exclusion: generalized regions (cervical, thoracic, lumbar). Demographics, CT orders and scans, and radiation data were obtained from electronic records. A vertebra was considered imaged only if the entire vertebral body was imaged. Analyses used descriptive statistics, chi-square tests, and one-way ANOVA with Tukey-adjusted post-hoc pairwise comparison.

RESULTS: 93 patients (mean age 16.1 ± 3.4) with 121 CT scans met criteria. In 53 (44%) CTs, more vertebrae were imaged than ordered, yielding a mean of 2.1 times more radiation. Scans occurred at 30 sites. A tertiary medical center with a new limited CT protocol performed 61 (50.4%) scans, with 49.2% scanning additional vertebrae. A private network of 3 outpatient imaging centers with established imaging protocols performed 26 scans, with 3.8% scanning additional vertebrae. The remaining 34 scans were performed at 23 external sites, with 64.7% scanning additional. The imaging center was significantly associated with additional vertebrae imaging frequency (X2 = 23.6, P = 0.0002).

CONCLUSION: 44% of patients with limited CT scans of the spine had additional vertebrae scanned compared to what was ordered. This corresponded to an estimated mean of twice the intended radiation dose. Limited CTs at centers with established imaging protocols do not image additional vertebrae in > 96% of patients. Pediatric spine centers should look to develop specific limited CT protocols to help decrease radiation exposure.

PMID:42260251 | DOI:10.1007/s43390-026-01464-1

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Predictive value of inferior mesenteric artery size in type 2 endoleak after endovascular abdominal aortic aneurysm repair-a systematic review and meta-analysis

CVIR Endovasc. 2026 Jun 9;9(1):66. doi: 10.1186/s42155-026-00715-6.

ABSTRACT

BACKGROUND: Type II endoleak after endovascular aneurysm repair is the most common endoleak type. Identifying pre-operative anatomical features that could signal higher risk will improve surveillance post-procedure. This systematic review and meta-analysis evaluated the association between inferior mesenteric artery (IMA) diameter and type II endoleak.

METHODS: MEDLINE and EMBASE were searched via OVID (1946/1974 respectively to January 2025), in line with the PRISMA statement, for adult patients undergoing endovascular aneurysm repair for infrarenal abdominal aortic aneurysm with reported pre-operative inferior mesenteric artery diameter and post-operative type II endoleak outcomes. Both retrospective and prospective observational studies were eligible. Meta-analysis via a random-effects model evaluated the pooled mean IMA diameter among patients with type II endoleak and the mean difference in IMA diameter between patients with and without endoleak. The risk of bias was assessed using the Newcastle-Ottawa scale.

RESULTS: Twenty studies met inclusion criteria; ten provided extractable quantitative data for pooling (2176 patients; 532 type II endoleaks). Assessment with the Newcastle-Ottawa scale demonstrated that the studies had scores between 6 and 8 out of 9. The pooled mean inferior mesenteric artery diameter among cases with endoleak was 2.95 mm (95% CI 2.64-3.26 mm; p < 0.01; I2 = 95%). The pooled mean difference in diameter between patients with and without endoleak was 0.50 mm (95% CI 0.36-0.64 mm; p < 0.01; I2 = 62%), indicating larger arteries in those who developed type II endoleak. Substantial heterogeneity reflected differences in endoleak definitions, imaging protocols, and measurement methods. Subsequent sac expansion and the need for reintervention were not reported uniformly across all studies, and when reported, insufficient data were available regarding these outcomes and their relation to IMA diameter.

CONCLUSION: Larger pre-operative inferior mesenteric artery diameter was associated with an increased likelihood of type II endoleak after endovascular aneurysm repair. However, the clinical relevance of a 0.5 mm difference remains uncertain, particularly in view of potential inter-observer measurement variability. Multicentre randomised controlled trials are needed to define actionable thresholds for treatment, considering confounding factors and clinical significance of the endoleak.

PMID:42260250 | DOI:10.1186/s42155-026-00715-6

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177Lutetium-PSMA-I&T therapy for metastatic castration-resistant prostate cancer (mCRPC): the first multicenter real-world study of 177Lu-PSMA-I&T in Brazil

EJNMMI Rep. 2026 Jun 9;10(1):22. doi: 10.1186/s41824-026-00305-8.

ABSTRACT

PURPOSE: Despite the approval of 177Lu-PSMA-617 as standard treatment for patients with mCRPC, at least 50% of patients do not respond to the therapy, especially those with visceral disease. This study analyzes real-world outcomes of 177Lu-PSMA-I&T used in heavily pretreated patients in Brazil.

METHODS: Retrospective analysis of patients with mCRPC previously treated with at least one androgen receptor pathway inhibitor (ARPI) who underwent 177Lu-PSMA-I&T between 2020 and 2025 in two large oncology centers. Our primary endpoint was prostate-specific antigen (PSA) response rate of 50% or more (PSA50). Secondary endpoints included overall survival (OS) and time to next sequential therapies (TNST). Statistical analyses were performed in JAMOVI and RStudio.

RESULTS: Forty-three patients were included, with median age 74 years and median baseline PSA 41 ng/mL. Prior to 177Lu-PSMA-I&T, 86% received more than one ARPI line and 23.3% underwent more than one taxane-based chemotherapy. Visceral disease was present in 41.9%. The overall PSA50 response for all patients was 44.2% and for patients with visceral disease was 33.3%. Median OS was 13.9 months [95% confidence interval (CI) 10.9-19.2] and 12-month survival was 55.5% [95% CI 42.1%-73.3%]. Out of the 24 patients who received subsequent therapies, median TNST was 2.9 months [95% CI 1.6-5.4].

CONCLUSIONS: Our results showed that 177Lu-PSMA-I&T achieved a PSA response comparable to those treated with 177Lu-PSMA-617 in randomized trials, despite our heavily treated patients’ characteristics. A significant number of patients had visceral disease with expected lower PSA response, highlighting the need for more active combinations in this subgroup.

PMID:42260246 | DOI:10.1186/s41824-026-00305-8

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Analysis and development of the learning curve in robotic colorectal surgery at a specialized center

J Robot Surg. 2026 Jun 9;20(1):582. doi: 10.1007/s11701-026-03486-3.

ABSTRACT

Robotic colorectal surgery has emerged as an alternative to laparoscopy, offering technical advantages particularly in complex procedures such as rectal surgery. However, its adoption is influenced by the learning curve, which remains incompletely characterized according to tumor location. Cumulative sum (CUSUM) analysis provides an objective method to assess surgical learning curves. A retrospective analysis of 60 consecutive patients undergoing robotic colorectal surgery was performed. The learning curve was evaluated using CUSUM analysis of total operative time. Patients were stratified according to tumor location into right colon (n = 23), sigmoid colon (n = 16), and rectum (n = 21). Perioperative outcomes, including operative time, console time, and postoperative complications, were compared among groups. Non-parametric tests and proportion analyses were used, with statistical significance set at p < 0.05. Operative time was significantly longer in rectal surgery compared to right colon and sigmoid procedures (median: 205.0 vs 145.0 vs 175.0 min; p = 0.000306). Similarly, console time was higher in the rectal group (180.0 vs 127.5 vs 154.0 min; p = 0.000215). No significant differences were observed in postoperative complication rates among groups (p = 0.191). CUSUM analysis identified inflection points at case 6 for right colon, case 5 for sigmoid colon, and case 8 for rectal surgery, indicating a more prolonged learning curve for rectal procedures. The learning curve in robotic colorectal surgery depends on tumor location. Right colectomies show a faster acquisition of technical skills, whereas rectal surgery requires a greater number of cases to achieve stabilization of operative performance. Likewise, procedural safety is maintained during the learning phase, reaching a stable point on the curve after approximately 20 cases, in agreement with the global literature.

PMID:42260235 | DOI:10.1007/s11701-026-03486-3

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Red fescue (Festuca rubra L.) variety recognition using subset division and neural networks

Theory Biosci. 2026 Jun 9;145(3):28. doi: 10.1007/s12064-026-00480-z.

ABSTRACT

The classification of plant varieties is a key task in plant breeding and variety registration. Red fescue (Festuca rubra L.), a widely cultivated grass species, includes numerous closely related varieties, making automated classification a challenging multi-class problem. This study aimed to develop and evaluate a multilayer perceptron (MLP) neural network combined with a subset-based decision framework for accurate classification of red fescue varieties and recognition of previously unseen varieties. The study analyzed 76 varieties described by seven morphological features. To address the complexity of the multi-class problem, the dataset was divided into multiple subsets and the effectiveness of different partitioning strategies was evaluated. A confidence-based and majority-based decision rule (majority ratio ≥ 0.9 and mean Softmax confidence ≥ 0.8) was introduced to improve the reliability of final predictions and enable open set recognition. The model was evaluated using accuracy, precision, F1 score, and recall. The most optimal solution was to divide the dataset into 15 subsets, with the first subset containing six varieties and the remaining subsets containing five varieties each. This approach provided the best balance between predictive performance and decision consistency, enabling correct classification of known varieties and stable detection of unknown samples. Combining MLP neural networks with strategic subset division and confidence-driven decision rules offers a robust solution to high-dimensional, multi-class classification challenges in plant variety recognition. The model’s ability to recognize new varieties is crucial for its practical application, ensuring the algorithm’s flexibility. This is particularly useful in agriculture and horticulture, where new varieties are bred over the years.

PMID:42260232 | DOI:10.1007/s12064-026-00480-z

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Associations between multiple metabolic indices and circadian syndrome: a cross-sectional study with mediation analysis of the C-reactive protein triglyceride glucose index

Hormones (Athens). 2026 Jun 8. doi: 10.1007/s42000-026-00794-z. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study is to comprehensively investigate the independent associations between a wide array of novel metabolic indices and the prevalence of circadian syndrome (CircS), as well as to explore, within a cross‑sectional framework, whether the C‑reactive protein triglyceride glucose index (CTI) shows statistical associations consistent with mediation.

METHODS: A cross‑sectional analysis was conducted using data from the China Health and Retirement Longitudinal Study (CHARLS) 2015 wave, involving 6,507 participants aged ≥ 45 years. Multivariable logistic regression, restricted cubic splines, and mediation analyses were employed to assess associations, non‑linearity, and indirect effects (cross‑sectionally consistent with mediation).

RESULTS: In fully adjusted models, multiple metabolic indices – including dynapenic abdominal obesity, frailty, TyG‑related indices, and the cardiometabolic index (CMI) – showed significant positive associations with CircS prevalence (all P < 0.001), while CCR was inversely associated. Restricted cubic spline analyses revealed significant non‑linear relationships for all indices (log‑likelihood ratio test P < 0.001). Mediation analysis indicated that CTI had a statistically significant indirect effect (cross‑sectionally consistent with mediation), with the proportion of the total effect statistically attributable to CTI ranging from 20.8% to 86.5%.

CONCLUSION: This large‑scale cross‑sectional study identified significant, often non‑linear, associations between multiple novel metabolic indices and CircS. CTI, a composite marker of inflammation and metabolism, showed a substantial indirect effect cross‑sectionally consistent with mediation in these associations. These hypothesis‑generating findings highlight the potential importance of the “metabolic‑inflammatory” axis in relation to CircS and offer epidemiological clues for early identification and risk stratification. Prospective studies are needed to assess temporality and causality.

PMID:42260226 | DOI:10.1007/s42000-026-00794-z

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Prognostic factors for cardiovascular complications induced by catecholamines in pheochromocytomas and paragangliomas: a systematic review and meta-analysis

Hormones (Athens). 2026 Jun 8. doi: 10.1007/s42000-026-00798-9. Online ahead of print.

ABSTRACT

PURPOSE: Pheochromocytomas and paragangliomas (PPGLs) can trigger major cardiovascular events (MACEs) due to unpredictable release of catecholamines. The aim of this systematic review and meta-analysis was to determine prognostic factors associated with MACEs in PPGLs patients.

METHODS: A literature search was conducted in PubMed and the Cochrane Library from January 1980 to March 2026. Assessment of clinical, laboratory, imaging, histological, and genetic parameters was performed on the pooled data.

RESULTS: Nine retrospective cohort studies involving 1566 patients with PPGL were included. MACEs were observed in 302 patients [pooled estimate of 21% (95% CI 14-29%)], 95 of those having Takotsubo syndrome [pooled estimate 39% (95% CI 23-54%)]. Tumor necrosis/hemorrhage and diabetes were associated with increased risk of MACEs [71% (95% CI 25-115%, p < 0.001) and 56% (95% CI 2-109%, p = 0.02), respectively]; additional predictors of MACES were dyspnea and chest pain [5-fold (95% CI 3.3-7.4, p < 0.001) and 2.7-fold (95% CI 1.5-4, p < 0.001) increased risk of MACEs]. Patients with MACEs had an average maximum diastolic blood pressure increase of 19.3 mmHg (95% CI 2.5-36mmHg, p = 0.02) and 9.4 mm larger tumor size (95% CI 1.2-17.56, p = 0.02) than those without. No significant associations between age, adrenergic-noradrenergic phenotype, metastatic disease, familial PPGLs, and MACEs were found.

CONCLUSION: This is, to the best of our knowledge, the first meta-analysis of cohort studies of catecholamine-induced MACEs in patients with PPGL. 21% of PPGL cases developed MACEs. Necrosis/hemorrhage, dyspnea, chest pain, and diabetes were associated with an increased likelihood of development of MACEs. However, these results should be interpreted with caution due to statistical and methodological heterogeneity.

PMID:42260224 | DOI:10.1007/s42000-026-00798-9