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Objective A systematic review and pooled analysis was carried out to estimate whether the increase in the quantity of cell-free fetal DNA (cffDNA) before the onset of pre-eclampsia (PE) can predict the disease using real-time polymerase chain reaction (PCR). Method A comprehensive literature search of the PubMed, Scopus, and Web of Knowledge databases was conducted to identify relevant studies that included evaluated cffDNA levels in pregnant women before the clinical onset of PE. A simulation model was generated to calculate the detection rate (DR) of cffDNA for PE, and a random variable was generated using the same number of cases and same statistical measurements of central tendency and dispersion as those reported in the papers considered for the analysis. Simulation of the receiver operating characteristic (ROC) curves was also carried out. Results Four studies (82 cases and 1315 controls) evaluated cffDNA in early-onset PE, with DRs of 18 and 68.8% at 11–13 and 17–28 weeks, respectively, at a false positive rate of 10%. Nine studies (including two considered for early-onset PE) encompassing 376 cases and 1270 controls were available for the evaluation of ‘any PE’. At 11–14 weeks no significant DR was found, while at 15–28 weeks the DR was 37%. Conclusion CffDNA quantification is a marker for predicting the development of both early-onset PE and ‘any PE’; however, it can probably only be used from the beginning of the second trimester, otherwise its predictive value is burdened with a DR that is too low or not significant. Due to the heterogeneity and difficulty in interpreting the published data, no conclusion regarding the statistical and clinical relevance, especially for screening ‘any PE’, can be made at present.

Preeclampsia (PE) is a major cause of maternal and perinatal morbidity or mortality, and early onset disease requiring iatrogenic preterm delivery is associated with even higher risks of maternal and neonatal complications. Identification of pregnancies at high risk of subsequent PE development is beneficial so that the focus on therapy and prevention (including prophylactic use of low-dose aspirin, closer surveillance and earlier delivery) can be more appropriate. Therefore, in recent years, many efforts have been made to screen for the disease before onset to minimize its impact on pregnancy outcome [1]. In their paper, Goto et al. performed an external validation of the Fetal Medicine Foundation (FMF) algorithm for PE risk calculation in a Japanese population.

Immune checkpoint inhibitors (ICI), i.e., anti-PD1/PDL1 and anti-CTLA-4, have reshaped the prognosis of many cancers. Increased use of ICI has led to the onset of new adverse events. Neurological immune-related adverse events are rare, heterogenous, and potentially life-threatening. Chronic intestinal pseudo-obstruction (CIPO) is an immune-related autonomic plexus neuropathy that may be caused by infiltration of the myenteric plexus by CD8 + T cells. It is a rare and potentially fatal side effect that can be difficult to diagnose early because of initial nonspecific clinical presentation including vomiting, nausea, diarrhea, and constipation. Some rare cases have been described in the literature reporting a frequent resistance to corticosteroids making it necessary to use other immunosuppressive therapy. Vedolizumab is an antibody (Ab) blocking integrin α4-β7 used to treat inflammatory bowel disease. We report the first three cases of ICI-induced CIPO-treated with vedolizumab after corticosteroid failure, with very limited benefits (only one patient with transitory improvement). Based on our results in three cases, vedolizumab does not currently appear to be a therapeutic option. Earlier administration with a standardized dose and frequency schedule may provide better outcomes.

The increasing integration of digital technologies in the construction sector is transforming the processes of buildings design, management, and evaluation throughout their life cycle. Life Cycle Costing (LCC), Building Information Modeling (BIM), and openBIM standards play a key role in promoting economic and environmental sustainability. More recently, Artificial Intelligence (AI) has unlocked novel possibilities for data-driven decision-making and cost optimization. However, the integration of LCC, BIM, and AI is insufficiently explored in the current literature. This study presents a systematic literature review (SLR) aimed at analyzing two distinct lines of research, LCC–BIM and LCC–AI, and identifying underexplored opportunities for their future convergence. A dual-stream approach was adopted to analyze scientific contributions based on LCC–BIM and LCC–AI separately, using bibliometric analysis and the systematic screening of peer-reviewed articles from 2015 to 2025. The findings reveal that while LCC–BIM integration shows growing methodological maturity, AI-based applications are still in an early stage, with limited implementation in construction-specific contexts. The review identifies key challenges, including data fragmentation, a lack of interoperability, and limited standardization, as significant impediments to integrated digital workflows. By highlighting these gaps and proposing actionable future directions, the paper outlines future research directions focused on open data models, AI-enhanced cost estimation, and the development of interoperable frameworks to support sustainable and intelligent cost management in the Architecture, Engineering, and Construction (AEC) sector.

The aim of this study was to evaluate if moderate-severe endometriosis impairs uterine arteries pulsatility index (UtA-PI) during pregnancy when compared to unaffected controls. In this prospective cohort study, pregnant women with stage III–IV endometriosis according to the revised American Fertility Society (r-AFS) classification were matched for body mass index and parity in a 1:2 ratio with unaffected controls. UtA-PIs were assessed at 11–14, 19–22 and 26–34 weeks of gestation following major reference guidelines. A General Linear Model (GLM) was implemented to evaluate the association between endometriosis and UtA-PI Z-scores. Significantly higher third trimester UtA-PI Z-scores were observed in patients with r-AFS stage III–IV endometriosis when compared to controls (p = 0.024). In the GLM, endometriosis (p = 0.026) and maternal age (p = 0.007) were associated with increased third trimester UtA-PI Z-scores, whereas conception by in-vitro fertilization with frozen-thawed embryo transfer significantly decreased UtA-PI measures (p = 0.011). According to these results, r-AFS stage III–IV endometriosis is associated with a clinically measurable impaired late placental perfusion. Closer follow-up may be recommended in pregnant patients affected by moderate-severe endometriosis in order to attempt prediction and prevention of adverse pregnancy and perinatal outcomes due to a defective late placental perfusion.

Background—There are conflicting data in the international literature on the risks of abnormal fetal growth in fetuses presenting an isolated single umbilical artery (SUA), and the pathophysiology of this complication is poorly understood. Objective—To evaluate if changes in diameter of the remaining umbilical artery in fetuses presenting an isolated SUA are associated with different fetal growth patterns. Study design—This was a two-center prospective longitudinal observational study including 164 fetuses diagnosed with a SUA at the 20–22-week detailed ultrasound examination and 200 control fetuses with a three-vessel cord. In all cases, the diameters of the cord vessels were measured in a transverse view of the central portion of the umbilical cord, and the number of cord vessels was confirmed at delivery. Logistic regression and nonparametric receiver operating characteristic (ROC) analysis were carried out to evaluate the association of the umbilical artery diameter in a single artery with small for-gestational age (SGA) and with fetal growth restriction (FGR). The impact of artery dimension was adjusted for maternal BMI, parity, ethnicity, side of the remaining umbilical artery and umbilical resistance index (RI) in the regression model. Results—A significantly (p < 0.001) larger mean diameter was found for the remaining artery in fetuses with SUA compared with controls (3.0 ± 0.9 vs. 2.5 ± 0.6 mm). After controlling for BMI and parity, we found no difference in umbilical resistance and side of the remaining umbilical artery between the SUA and control groups. A remaining umbilical artery diameter of >3.1 mm was found to be associated with a lower risk of FGR, but this association failed to be statistical significant (OR = 0.60, 95% CI = 0.33–1.09, p value = 0.089). We also found that the mean vein-to-artery area ratio was significantly (p < 0.001) increased in the SUA group as compared with the controls (2.4 ± 1.8 vs. 1.8 ± 0.9; mean difference = 0.6; Cohen’s d = 0.46). Conclusion—In most fetuses with isolate SUA, the remaining artery diameter at 20-22 weeks is significantly larger than in controls. When there are no changes in the diameter and, in particular, if it remains <3.1 mm, the risk of abnormal fetal growth is higher, and measurements of the diameter of the remaining artery could be used to identify fetuses at risk of FGR later in pregnancy.

Background: Anti-Yo antibodies, which target the onconeural antigen cerebellar degeneration-related 2-like (CDR2L), have been only sporadically reported in patients with post-immune checkpoint inhibitor (post-ICI) neurological syndromes. Objectives: To analyze the clinical and tumor features of patients with post-ICI anti-Yo neurological syndromes identified in a national reference center. Design: Retrospective observational study. Methods: All patients with post-ICI neurological syndromes and anti-Yo antibody positivity confirmed in a national reference center (2019–2024) were included. Comparative genomic hybridization array, immunohistochemistry against CDR2L, and analysis of Yo immunoreactivity using biotinylated anti-Yo sera were performed on the available tumor samples. Results: In the five patients (4/5 female, median age 61 years) included, the neurological syndrome occurred after a median of 2 cycles of PD1 inhibitor. Four patients developed a rapidly progressive cerebellar syndrome (RPCS), while one presented with myelitis. All cases were severe (modified Rankin scale score 4–5) and did not improve with treatment. Cancer types were lung adenocarcinoma (2/5), endometrial serous carcinoma (2/5), and ovarian clear cell carcinoma (1/5). Anti-Yo antibodies were retrospectively detected before ICI initiation in one patient with RPCS and an ovarian tumor. This tumor showed a gain in the CDR2L locus, CDR2L overexpression, and Yo immunoreactivity with biotinylated anti-Yo sera, similar to ovarian tumors from patients with spontaneous anti-Yo paraneoplastic neurological syndrome. By contrast, CDR2L was not overexpressed in the lung tumor from one patient with myelitis, which nevertheless had a strong immunoreactivity with anti-Yo sera, absent in the control lung tumor. Conclusion: Post-ICI anti-Yo neurological syndromes may occur with atypical cancer associations, but mostly manifest with a RCPS indistinguishable from spontaneous anti-Yo paraneoplastic neurological syndromes, suggesting a similar immune-mediated attack on the cerebellum. The CDR2L antigen overexpression and the pre-ICI anti-Yo antibody positivity in the patient with ovarian cancer suggest that the ICI boosted a pre-formed, tumor-driven anti-Yo autoimmunity. Further studies are needed to clarify whether this mechanism applies to all patients and if other types of tumor alterations and/or immune dysfunctions could be involved.

Right aortic arch presents a reported incidence of 0.1% of the general population; the aim of our study was to evaluate the risk of associated intracardiac (ICA), extracardiac (ECA), or chromosomal abnormalities in fetuses with right aortic arch (RAA) and concomitant right ductal arch (RDA). A systematic review of the literature selected 18 studies including 60 cases of RAA/RDA. A meta-analysis with a random effect model calculated for each outcome the pooled crude proportion of associated abnormal outcomes in cases of RAA/RDA and the pooled proportions and odds ratios in RAA with LDA or RDA. Quality assessment of the included studies was achieved using the NIH quality assessment tool for case series studies. RAA/RDA presents risk of associated conotruncal CHDs of about 30% and risk of 22q11 microdeletion in the region of 1%. Two-thirds of 22q11 microdeletions had concomitant thymic hypoplasia and no other chromosomal defects were described. Risks for ICA, ECA, 22q11 microdeletion, and aberrant left subclavian artery are not substantially different in RAA with right or left arterial duct. RAA increases the risk of associated cardiac defects regardless of laterality of the ductal arch. In isolated RDA/RAA cases, absolute risks of extracardiac associated problems or surgery are rather low, we would therefore recommend reassurance, particularly when the thymus and karyotype are normal.

The present pilot study investigates whether an abnormal miRNA profile in NIPT plasma samples can explain the finding of a low cell-free DNA (cfDNA) fetal fraction (cfDNAff) in euploid fetuses and non-obese women. Twelve women who underwent neoBona® NIPT with a normal fetal karyotype were studied. Six with a cfDNAff < 4% were matched with a control group with normal levels of cfDNAff > 4%. Samples were processed using the nanostring nCounter® platform with a panel of 800 miRNAs. Four of the maternal miRNAs, miR-579, miR-612, miR-3144 and miR-6721, had a significant abnormal expression in patients. A data filtering analysis showed that miR-579, miR-612, miR-3144 and miR-6721 targeted 169, 1, 48 and 136 placenta-specific genes, respectively. miR-579, miR-3144 and miR-6721 shared placenta-specific targeted genes involved in trophoblast invasion and migration pathways (IGF2R, PTCD2, SATB2, PLAC8). Moreover, the miRNA target genes encoded proteins localized in the placenta and involved in the pathogenesis of pre-eclampsia, including chorion-specific transcription factor GCMa, PRG2, Lin-28 Homolog B and IGFBP1. In conclusion, aberrant maternal miRNA expression in circulating plasma could be a source of dysregulating trophoblast invasion and migration and could represent a novel cause of a low cfDNAff in the sera of pregnant women at the time of NIPT analysis.

Introduction: The objective of this randomized controlled study was to demonstrate whether acoustic stimulation in utero is associated with fetal reactivity which is documentable by cardiotocography. Materials and methods: A monocentric randomized controlled trial was performed at a single university tertiary hospital between September 2016 and July 2017. This study was registered as a randomized clinical trial on clinicaltrail.gov (registration number NCT04622059). Unselected pregnancies at term of gestation were consecutively recruited for the purpose of this study. After 10 min of normal cardiotocography without accelerations (non-stress-test with a basal frequency between 110 and 150 beats/min, normal variability between 6 and 15 b/min, no accelerations, and no fetal movements), fetuses were randomized at a 1:1 ratio to either of the two groups. Fetuses in group A (n = 105) received acoustic stimulation after 10 min from the beginning of the CTG, whereas fetuses in group B received no stimulation (n = 105). The outcome variables investigated were the lapse of time between the beginning of the CTG and the occurrence of the first acceleration, and the lapse of time between the beginning of the CTG and the first fetal movement noticed. Results: The lapse of time between the beginning of the CTG and the occurrence of the first acceleration was significantly shorter in the group with acoustic stimulation compared to the other group (14.87 ± 5.01 vs. 21.90 ± 6.94 min, p-value < 0.001 log-rank test). Similarly, the lapse of time between the beginning of the CTG and the occurrence of the first fetal movement was significantly shorter in group A compared to group B (17.77 ± 7.62 vs. 23.28 ± 7.61 min, p-value < 0.001, log-rank test). Fetal cardiac acceleration and the occurrence of a fetal movement during the first 20 min of the CTG were more frequently recorded in group A compared to group B (respectively, 15% vs. 5% and 20% vs. 8%). Conclusion: This RCT showed an early fetal reaction following auditive stimulus, documentable by cardiotocography. Further research is needed to investigate a possible role of acoustic stimulation in utero for the prenatal diagnosis of congenital hypoacusis.