Search Results (409)

Chronic hepatitis B virus (HBV) infection remains one of the main causes of hepatocellular carcinoma (HCC), even though vaccination and long-term viral suppression have reduced new infections and circulating viral replication. This residual cancer risk suggests that serum HBV DNA alone does not capture the full biology of HBV-related carcinogenesis. Hepatitis B virus X protein (HBx) is a relevant entry point because it maintains the transcriptional competence of covalently closed circular DNA (cccDNA), engages host chromatin regulators, and may persist in tumors as cccDNA-derived, integration-derived, full-length, truncated, or fusion forms. This review focuses on a specific question: does the available literature support HBx-associated reactivation of the IGF2 locus in chronic HBV infection and HBV-related hepatocarcinogenesis, and, if so, at which regulatory layer is the claim defensible? The most direct evidence remains promoter-proximal. Classic mechanistic work shows acute HBx-dependent activation of IGF2 promoter P4 through Sp1- and PKC/ERK-dependent signaling. Human tissue and cell-based studies also support a broader fetal-promoter compartment, including P3/P4 transcript enrichment, local promoter hypomethylation, MBD2-HBx-CBP/p300 recruitment, and increased histone H3/H4 acetylation. These observations do not, however, establish HBV exclusivity, uniform loss of imprinting, or direct HBx-mediated rewiring of the human IGF2/H19 topological domain. Recent integration-aware and long-read studies further argue against treating tumor-stage HBx as a single biological variable. In the present evidence framework, HBx-associated IGF2 locus reactivation is therefore more appropriately viewed as a stage-aware, promoter-resolved, biomarker-oriented hypothesis than as a universal mechanism or a treatment algorithm for HBV-related HCC. Full article

Background/Objectives: Therapeutic plasma exchange (TPE) is an extracorporeal treatment used in thrombotic microangiopathies (TMAs) and various autoimmune and neurological disorders. However, data regarding its use during early pregnancy remain limited. This study aimed to evaluate maternal laboratory response and perinatal outcomes in pregnant women who underwent TPE before 26 weeks of gestation. Methods: This retrospective case series included 10 pregnant women diagnosed before 26 weeks of gestation who underwent TPE between 2010 and 2023. Clinical and laboratory parameters before and after TPE were compared. Results: Indications for TPE included HELLP syndrome (n = 4), thrombotic thrombocytopenic purpura (n = 3), presumed atypical haemolytic uremic syndrome (n = 1), neuromyelitis optica (n = 1), and Guillain–Barré syndrome (n = 1). The mean gestational age at diagnosis was 22.1 ± 3.1 weeks, and the mean gestational age at delivery was 27.1 ± 6.9 weeks. Five fetuses (50%) died and five (50%) survived to discharge. In patients with TMAs, TPE was associated with significant decreases in LDH, INR, APTT, ALT, AST, and total bilirubin levels, along with a significant increase in platelet count and ADAMTS13 activity (p < 0.01). No maternal complications occurred in neurological cases, all of which resulted in term deliveries with healthy neonates. Conclusions: In this uncontrolled case series, TPE was associated with rapid maternal clinical and laboratory improvement in selected pregnant women with TMAs, although a causal effect cannot be established from these data. However, perinatal outcomes were primarily determined by gestational age at delivery: all fetal losses occurred before 26 weeks, whereas all infants survived when delivery occurred after 26 weeks. Larger studies are needed to confirm these findings. Full article

In small ruminants, up to 40% of fertilized ova are lost during early gestation due to inadequate progesterone. This study evaluated post-transfer progestogen supplementation in goats. A total of 207 thawed embryos were transferred into 111 recipients assigned to progestogen-supplemented (n = 37) or non-progestogen-supplemented (n = 74) groups. Pregnancy and embryo survival did not differ between treatments (p > 0.05). However, fetal and neonatal survival were significantly lower in supplemented goats (29%) compared with non-supplemented goats (100%; p < 0.05). Infectious causes were excluded. Possible mechanisms postulated in fetal losses comprise a sharp decline in progesterone after sponge removal or increased oxytocin and prostaglandin due to vaginal mechanical stimulation, inducing luteolysis. In conclusion, intravaginal progestogen supplementation is not recommended for recipient goats in embryo transfer programs. Full article

Neospora caninum is a major cause of reproductive failure in cattle, responsible for epidemic abortion outbreaks that inflict annual billion-dollar losses on the global livestock industry. In water buffaloes (Bubalus bubalis), however, a phylogenetically close relative often raised in the same environments, the same parasite typically establishes a subclinical persistent infection with markedly lower rates of clinical abortion. This review inverts the traditional narrative by arguing that the key to next-generation control strategies lies in understanding the tolerant host (buffalo) rather than solely the susceptible host (cattle). By dissecting this “Neospora paradox”, we explore the molecular and immunological crosstalk that dictates pregnancy outcomes. We examine the parasite’s invasion proteins, revealed by CRISPR-Cas9 screens, and the maternal–fetal interface, where the balance between immune tolerance and parasite control determines the fate of pregnancy. We also compare N. caninum with the related zoonotic parasite Toxoplasma gondii to highlight how differential host immune recognition shapes infection outcomes. Finally, we propose that deciphering the buffalo’s successful equilibrium with N. caninum can illuminate novel pathways for vaccines and immunotherapeutic strategies, transforming the management of neosporosis worldwide. Full article

Non-invasive fetal electrocardiogram (FECG) extraction from maternal abdominal ECG (AECG) is crucial for prenatal monitoring but remains challenging due to strong interference from maternal ECG (MECG), baseline drift, and noise. We propose an FECG extraction method based on minimal channel attention (MCA) and flow matching (FM), learning a deterministic mapping from AECG to FECG via a probabilistic path. To balance the preservation of physiological signals and separation of interference, we employ bridge variance scheduling for the diffusion process. Target matching loss is introduced to regress the FECG directly, enhancing training stability and waveform fidelity. For feature selection, a minimal channel attention module with global average pooling and a single linear layer is embedded after feature extraction, capturing cross-channel dependencies with minimal parameters. Enhanced residual connections are incorporated to retain underlying features and optimize gradient flow in deep networks. Experiments on two public datasets (ADDB and BDDB) with a leave-one-out cross-validation strategy show that our method achieves average Pearson correlation coefficients (PCCs) of 0.94 ± 0.050 on ADDB and 0.91 ± 0.122 on BDDB, demonstrating robust performance across diverse real-world recording conditions. The method balances high accuracy with efficient feature extraction, offering a reliable solution for non-invasive fetal heart health monitoring. Full article

Background: Obstetric anal sphincter injuries (OASIS) are a major cause of long-term maternal morbidity. Identification of risk factors is central to prevention strategies. Methods: A retrospective cohort study was conducted including all singleton, term, cephalic vaginal births over a four-year period (September 2018 to September 2022) at a UK tertiary maternity unit. OASIS was defined as third- or fourth-degree perineal tears according to RCOG criteria. Multivariable logistic regression analysis was used to identify independent predictors. A pre-specified sensitivity analysis restricted to nulliparous women was performed. Secondary outcomes included postpartum haemorrhage (PPH), defined as blood loss >1 L. Reporting follows the STROBE statement for cohort studies. Results: Among 9586 vaginal births, 270 OASIS cases were identified, corresponding to an incidence of 2.82%. Independent predictors included nulliparity (aOR 7.12, 95% CI 5.07–10.01), Asian ethnicity (aOR 3.50, 95% CI 2.55–4.81), shoulder dystocia (aOR 3.45, 95% CI 1.89–6.32), and birthweight ≥4000 g (aOR 1.85, 95% CI 1.16–2.95). Maternal age ≥35 years showed a borderline association (aOR 1.34, 95% CI 0.99–1.80, p = 0.056). Using forceps as the reference, ventouse (aOR 0.28, 95% CI 0.17–0.47) and spontaneous vaginal delivery (aOR 0.23, 95% CI 0.13–0.39) were associated with lower OASIS odds. Episiotomy (recorded as a binary variable) was associated with lower adjusted odds of OASIS (aOR 0.27, 95% CI 0.17–0.44). PPH occurred in 21.5% of women with OASIS versus 6.5% without (p < 0.001). Conclusions: OASIS risk is driven by a combination of maternal, fetal, and intrapartum factors. Selective mediolateral episiotomy was associated with lower adjusted odds of OASIS in this cohort, but this is an observational finding and does not constitute proof of a causal protective effect. It should be interpreted cautiously given the retrospective design, the recording of episiotomy as a binary variable without procedural detail, and the substantial potential for residual confounding by indication. The findings support targeted perineal protection strategies and selective rather than routine episiotomy use. Full article

Cell replacement therapy is a promising investigational approach for Parkinson’s disease (PD), a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra. Although current PD therapies provide symptomatic relief, none halt or reverse disease progression. Early transplantation studies using fetal dopaminergic neurons provided proof of concept for PD cell replacement, with recent efforts focusing on pluripotent stem cell-derived dopaminergic progenitors that are now entering clinical testing. These strategies face challenges, however, including immune compatibility, tumorigenic risk, and the need for controlled differentiation and functional integration. Multi-lineage differentiating stress-enduring (Muse) cells are endogenous, non-tumorigenic pluripotent-like stem cells that home to sites of tissue injury and differentiate in response to the host microenvironment. A targeted literature search of PubMed and Scopus, however, did not identify prior reviews specifically addressing Muse cells in the context of PD, highlighting a gap in the literature. Here, we examine current limitations of established cell-replacement approaches and consider whether Muse cells may represent a mechanistically distinct cell source. Early clinical studies of Muse cell therapy in stroke and amyotrophic lateral sclerosis suggest an encouraging safety profile and preliminary signals of potential therapeutic benefit, although these findings are based on small, early-stage trials and require confirmation. The evidence supporting Muse cell therapy in PD is currently limited to a single preclinical animal study, supported by mechanistic in vitro findings and indirect evidence from other neurologic disease models; therefore, its relevance to PD remains to be established, and current evidence is insufficient to support conclusions regarding clinical efficacy. Together, these observations provide a rationale for further targeted preclinical investigation and support the systematic evaluation of Muse cells as a mechanistically distinct candidate for regenerative therapy in PD. Full article

Pregnancy represents a critical eco-biological window during which maternal physiology integrates environmental exposures, lifestyle factors, and interconnected microbial ecosystems to shape fetal development and long-term health. From a One Health perspective, defined here as the interconnection between maternal health, environmental determinants, and microbial ecosystems across generations, the maternal microbiome functions as a dynamic interface linking the external environment to the intrauterine milieu, translating ecological signals into immunological, metabolic, and neuroendocrine pathways that influence placental function and developmental programming. Across gut, vaginal, oral, and mammary niches, maternal microbial communities operate as an integrated network regulating systemic inflammation, metabolic homeostasis, and the production of bioactive metabolites, including short-chain fatty acids, bile acids, and tryptophan derivatives. This review proposes an integrated systems framework in which pregnancy is viewed as a transient ecological system shaped by ten interconnected maternal determinants, encompassing microbial niches, nutrition, lifestyle factors, medical interventions, mode of delivery, and postnatal microbial transmission, that converge on shared microbiome-mediated signaling pathways affecting fetal and neonatal immune, metabolic, and neurodevelopmental trajectories. Broader macro-environmental drivers, including biodiversity loss, urbanization, pollution, and industrialized lifestyles, are considered as upstream modulators of maternal microbial ecology within a One Health context. A systems model is presented to illustrate how environmental inputs are biologically transduced through maternal microbial networks to influence placental function, fetal development, and early-life health trajectories. Framing pregnancy as an integrated eco-biological continuum highlights the maternal microbiome as a central hub of intergenerational health and may support microbiome-informed preventive strategies and public health approaches aimed at reducing the burden of non-communicable diseases (NCDs) of early-life origin. Full article

Hepatitis E is a liver inflammation caused by the hepatitis E virus (HEV). In pregnant women, the infection significantly increases the risk of acute liver failure, fetal loss, and maternal death. According to the World Health Organization, infection by HEV during the third trimester of pregnancy may increase the risk of maternal mortality in 20–25% of cases. In Tunisia, little is known about HEV infection and its outcome, especially in pregnant women. This study aims to evaluate the prevalence of HEV infection in a large cohort of pregnant women in Tunisia. A total of 891 women who attended the Centre of Maternity and Neonatology of Tunis during 2021–2023 were included. Serum samples were screened to detect HEV-antibodies and RNA using commercial ELISA tests and molecular assays, respectively. Statistical analyses were conducted using SPSS 21.0 software and the EPISTAT package version 7.2.6. Seroprevalence of HEV infection was 3.82%, based on the detection of anti-HEV IgG. The distribution of the seroprevalence according to age was statistically significant (p < 0.05), showing a higher seroprevalence among women over 30 years. Among the 51 women with composite outcomes, viral RNA was detected in one case by real-time RT-PCR. Our findings indicate a low HEV prevalence among pregnant women in Tunisia. Expanding the study to other cohorts and to environmental surveillance would improve understanding of HEV burden in Tunisia and support hepatitis elimination efforts. Full article

Pathologic pregnancies including recurrent pregnancy loss, stillbirth, early-onset pre-eclampsia and early-onset fetal growth restriction form a continuous spectrum throughout gestation and have attracted wide attention. Autoimmune disorders and associated acquired thrombophilia are key etiological factors. However, because of the complicated associations between various clinical manifestations, laboratory examinations and treatments, the management of pathologic pregnancies with autoimmune disorders and associated acquired thrombophilia are difficult. This viewpoint article presents a comprehensive full gestation management strategy emphasizing early identification and multidisciplinary management to improve pregnancy outcomes in these patients. Future research should focus on novel biomarkers, therapeutic methods and crosstalk mechanisms between autoimmune disorders and thrombophilia to optimize clinical strategies. Full article

Annually, there are more than two million deaths from liver disease. This is driven by organ inflammation and scarring, leading to a decline in function and regeneration. Frequently, this can develop into decompensated liver disease, resulting in the loss of physiological balance and toxin build-up within the body, with an increased risk of patient mortality. Currently, there are no approved medicines for the long-term treatment of liver cirrhosis. The only successful treatment option for end-stage liver disease patients is donor organ transplantation. However, patient requirement outstrips the number of donated organs. To address this bottleneck, researchers around the world have developed cell-based prototype systems to restore failing liver function, with some in clinical trials. Although significant progress has been made, no mainstream commercial liver assist products are available for routine clinical use. In this study we developed a stem cell-derived vascularized liver tissue implant prototype from pluripotent cells. The liver tissue was produced from a stem cell line that is banked at clinical grade, and displayed stable and mature liver function over a 6-week period in vitro. This included decreasing levels of the fetal marker, alpha-fetoprotein, when the serum albumin increased. This was further supported by stable alpha-1-antitrypsin secretion and cytochrome P450 function. Following the establishment of stable liver tissue, it was delivered as a cell product or attached to an electrospun polycaprolactone scaffold, to form a tissue implant. Next, cellular material was quality-controlled, and subsequently shipped to a contract research organization for external in vivo validation. The transplanted liver tissue functioned when implanted into the kidney capsule and subcutaneously, remaining functional for up to two weeks in vivo. Full article

Background: Non-invasive prenatal testing (NIPT) examines cell-free DNA (cfDNA) in maternal serum, which includes both maternal DNA and apoptotic placental DNA. The presence of multiple aneuploidies or widespread abnormal patterns of gains and losses across chromosomes in a structurally normal fetus has been linked to maternal cancer. Case Presentation: The patient was a 22-year-old G1P0 with a history of classical Hodgkin’s lymphoma in remission. Her NIPT collected at 14 weeks and 3 days was reported as a “no call”. A second NIPT at a different laboratory showed multiple chromosomal aneuploidies (trisomy 18, 21, and monosomy X) with normal fetal anatomy on ultrasound. The patient was asymptomatic and was referred to hematology–oncology specifically to address the concern that these NIPT results could be related to cancer recurrence. Imaging was deferred as she was already on an established surveillance protocol for her Hodgkin’s lymphoma. At 26 weeks of gestation, the patient presented with a cough and dyspnea. Chest x-ray raised concern for disease recurrence, and biopsy confirmed recurrent Hodgkin’s lymphoma. She received two cycles of ICE chemotherapy. Cesarean delivery at 34 weeks and 2 days was performed for non-reassuring fetal heart tones. She continued chemotherapy, followed by BEAM conditioning and autologous stem cell transplantation. Genetic testing of the neonate revealed a normal karyotype; the placenta karyotype yielded no interpretable results. Discussion and Conclusions: Certain patterns of abnormal NIPT results may be associated with maternal malignancy and warrant further investigation. The absence of standardized protocols for reporting such NIPT results can complicate timely interdisciplinary evaluation and treatment. However, diagnostic testing should be offered with a positive NIPT result, a no-call or test failure, and abnormal ultrasound results, even with a “low-risk” NIPT result. Full article

Background and Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy has raised concerns regarding possible fetal consequences, including potential effects on auditory system development. Although the current literature suggests that overt congenital hearing loss is uncommon among newborns exposed in utero, subtle cochlear functional alterations may not be detectable through conventional threshold-based screening alone. The objective of this study is to investigate whether in utero exposure to maternal COVID-19 is associated with early cochlear functional changes in newborns, as assessed by frequency-specific transient evoked otoacoustic emission (TEOAE) amplitude ratios, and to determine whether such alterations are accompanied by differences in click-evoked auditory brainstem response (ABR) thresholds. Materials and Methods: This prospective cohort study was conducted between October 2021 and September 2022 and included 61 pregnant women: 30 with laboratory-confirmed SARS-CoV-2 infection during pregnancy (study group) and 31 without documented infection (control group). All newborns underwent standardized audiological evaluation shortly after birth, including otoscopy, TEOAE, click-evoked ABR, and tympanometry. Frequency-specific TEOAE amplitude ratios at 500, 1000, 1500, 2000, and 4000 Hz were compared between groups. A logistic regression analysis was performed to identify audiological predictors of newborn exposure to SARS-CoV-2 in utero. Results: No significant differences were observed in ABR thresholds or in TEOAE “pass/refer” outcomes between the control and study groups, indicating the absence of clinically overt HL. However, newborns exposed to SARS-CoV-2 in utero showed significantly reduced TEOAE amplitude ratios at 2000 Hz (p = 0.0077) and 4000 Hz (p = 0.020). Logistic regression identified the 4000 Hz amplitude ratio as an independent negative predictor of in utero exposure (OR = 0.75; p = 0.0352). No significant differences were detected at lower frequencies. Conclusions: Maternal COVID-19 during pregnancy was not associated with immediate neonatal HL but was linked to subtle high-frequency cochlear functional modulation. Longitudinal audiological follow-up is needed to clarify the clinical significance of these findings. Full article

Background: Adverse pregnancy outcomes such as preeclampsia (PE), preterm birth, low birth weight (LBW), small for gestational age (SGA), and stillbirth are major contributors to maternal and neonatal morbidity and mortality. Elevated maternal homocysteine (Hcy) levels, influenced by genetic, dietary, and lifestyle factors, have been increasingly associated with placental dysfunction and adverse pregnancy outcomes. This review aims to evaluate the link between hyperhomocysteinemia and pregnancy complications to inform clinical practice. Methods: A comprehensive search of PubMed, Scopus, Web of Science, and Cochrane Central Library was conducted up to December 2024. Observational studies assessing maternal Hcy levels in relation to pregnancy complications were included. Heterogeneity was measured using the I² statistic, and a random-effects model using the DerSimonian–Laird method was applied to account for study variability. Effect sizes were reported as odds ratios (ORs) with 95% confidence intervals (CIs). Results: Thirteen studies were included in this meta-analysis. Elevated maternal Hcy was significantly associated with: PE (OR: 2.49; 95% CI: 1.41–4.40; I² = 96.03%; n = 9), preterm birth (OR: 4.01; 95% CI: 1.84–8.72; I² = 91.08%; n = 6), fetal loss (OR: 1.76; 95% CI: 1.22–2.52; I² = 41.47%; n = 6), SGA (OR: 1.69; 95% CI: 1.35–2.11; I² = 0.00%; n = 3), and LBW (OR: 2.46; 95% CI: 1.37–4.43; I² = 77.71%; n = 3). Conclusions: This review highlights a significant association between elevated maternal Hcy levels and various pregnancy complications. However, given the substantial heterogeneity and reliance on observational evidence, these findings should be interpreted with caution. Future well-designed prospective cohort studies with standardized definitions of hyperhomocysteinemia, consistent timing of exposure assessment across pregnancy trimesters, and adjustment for key confounders are needed to better clarify these associations and underlying mechanisms. Full article

Objective: The study aimed to assess the accuracy of two distinct methods for estimating blood loss (EBL) and to identify potential factors contributing to early-onset postpartum hemorrhage (PPH) following a vaginal delivery (VD). Methods: Women in singleton pregnancies undergoing spontaneous/induced VD were recruited for this prospective observational cohort study. Methods of EBL included: (1) visual assessment by an attending obstetrician (sEBL) and (2) implementation of a mathematical formula (fEBL). Early PPH was defined as a cumulative blood loss exceeding 500 mL within the first 24 h after delivery as reflected by clinical assessment. Results: During the study period, 485 women delivered vaginally, and early PPH was diagnosed in 29 cases (5.97%). Among patients with PPH, a significant increase in the duration of the 2nd (61 min. vs. 33.5 min., p < 0.05) and 3rd (13 min. vs. 7 min., p < 0.001) stages of labor, as well as in the application of a dinoprostone insert (31% vs. 10.5%, p < 0.01) was noted. Additionally, in the same cohort, uterine atony (41.4% vs. 1.5%, p < 0.001), 3rd/4th degree perineal rupture (6.9% vs. 0%, p < 0.01), fetal macrosomia (17.2% vs. 4.8%, p < 0.05) and stillbirth (6.9% vs. 0.2%, p < 0.05) occurred significantly more frequently. In both groups visual estimation of blood loss was significantly lower compared to fEBL: (PPH sEBL: 800 mL vs. fEBL 1439.6 mL, p < 0.001; control sEBL: 250 mL vs. fEBL 621.8 mL, p < 0.001). In the multivariate analysis, factors such as third stage of delivery time ≥ 30 min. (OR 11.6; 95% CI: 4.18–32.33), FBW ≥ 4000 g (OR 6.37; 95% CI: 1.54–26.3), and dinoprostone insert application (OR 4.33; 95%CI: 1.63–11.48) were selected as independent predictors of the PPH. Conclusions: Compared to mathematical formula, visual estimation of blood loss by an attending obstetrician is significantly decreased. Prolonged third stage of delivery, fetal macrosomia, and application of a dinoprostone insert are the strongest contributors to early PPH following a VD. Full article