Athina Samara

• D'Antonio, Francesco; Flacco, Maria Elena; Manzoli, Lamberto; Samara, Athina & Khalil, Asma (2026). GLP-1 receptor agonist exposure in the periconceptional period and adverse obstetric outcomes: A systematic review and meta-analysis. Med. ISSN 2666-6359. p. 101267–101267. doi: 10.1016/j.medj.2026.101267. Full text in Research Archive Show summary

  Background This systematic review and meta-analysis assesses whether exposure to glucagon-like peptide-1 receptor agonists (GLP-1 RAs) during pregnancy or the periconceptional period is associated with adverse maternal and perinatal outcomes. Methods Medline, Embase, and the Cochrane Library were searched for observational studies comparing pregnancies exposed and unexposed to GLP-1 RAs within 6 months before a positive pregnancy test. Outcomes included miscarriage, intrauterine death, congenital anomalies, preterm birth (PTB), hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), fetal growth restriction (FGR), small for gestational age (SGA), large for gestational age (LGA), and excess gestational weight gain. Random-effects meta-analyses and subgroup analyses by indication were performed. Findings Ten studies included 2,118,215 women, of whom 8,325 were exposed and 2,109,890 were unexposed. Pooled estimates did not show a clearly detectable increase in miscarriage or intrauterine death, congenital anomalies, preterm birth, HDP, gestational diabetes, abnormal fetal growth, or excess gestational weight gain. A lower pooled estimate for preeclampsia was observed (odds ratio [OR]: 0.87, 95% confidence interval [CI]: 0.78–0.98; p = 0.02), but this was based on two datasets and should be interpreted cautiously. Subgroup analyses showed no clearly detectable differences by indication. The exposure-window sensitivity analysis, covering 90 days before conception through the end of the first trimester, used the same four studies as the primary congenital-malformation analysis and therefore was not independent. Conclusion Available observational evidence did not identify a clearly detectable increase in adverse maternal or perinatal outcomes following periconceptional exposure to GLP-1 RAs. However, these findings do not establish safety because of heterogeneity, residual confounding, and limited datasets.

• Esposito, Alessio; Fortunato, Gabriele Maria; Stasi, Mauro Di; Fradinho, Ana C.; Pacetta, Guglielmo & Soriano, Maria Grazia [Show all 16 contributors for this article] (2026). A Biomimetic Eye In Vitro Model to Investigate the Blood-Retinal Barrier Pathophysiology. ACS Biomaterials Science and Engineering. doi: 10.1021/acsbiomaterials.6c00764. Full text in Research Archive Show summary

  Abstract Existing in vivo models for retinal pathologies are costly, time-consuming, and subject to regulatory challenges, promoting interest in advanced in vitro models that replicate the blood-retinal barrier. Challenges related to vascularization and structural multiscale interactions hinder the development of in vitro models, which are useful to study nutrient and drug exchange between the retina and systemic circulation. To address these issues, we developed a blood-retinal barrier in vitro model for studying retinal pathophysiology. It features an electrospun scaffold (Bruch’s membrane) placed between a culture chamber (vitreous humor) and a bioinspired microfluidic network (choroidal vasculature). The network, modelled from indocyanine green angiography of the human retina, is laser-engraved into a 15 mm PDMS disc with channels 70–800 μm wide. PLGA and gelatin electrospun scaffold were investigated to mimic Bruch’s membrane. The scaffold is fixed to the microfluidic network, assembled into a culture chamber, and integrated within a bioreactor. A peristaltic pump ensures a consistent flow in the channels. Biological validation included ARPE-19 cells cultured on Transwell, PLGA, or gelatin membranes, HUVECs within membrane-coupled microchannels, and dual-layer constructs. Cells were examined separately and together, allowing evaluation of epithelial, endothelial, and construct responses. All configurations showed progressive increases in metabolic activity and limited LDH release over 28 days. Cell-seeded constructs reduced FITC–dextran transport relative to acellular controls, with stable values between days 21 and 28. Blank-corrected TEER likewise increased during ARPE-19 culture and plateaued by day 21. PLGA constructs showed the greatest electrical and solute-transport resistance, although acellular controls confirmed a substantial material contribution. Confocal microscopy demonstrated HUVEC attachment and F-actin organization along the microchannels, while ARPE-19 monolayers exhibited continuous junction-associated ZO-1 staining that remained stable between days 21 and 28. Overall, the platform supported long-term epithelial–endothelial culture and provided a stable, perfusable system for studying oBRB transport and cellular interactions.

• Hlinková, Jana; Huo, Yiru; Sukul, Mousumi; Lewis, David J.; Reseland, Janne Elin & Haugen, Håvard Jostein [Show all 8 contributors for this article] (2026). Dual-crosslinked chitosan nanofibres - Balancing mechanical enhancement with cytotoxic risk. Biomaterials Advances. ISSN 2772-9516. p. 215050–215050. doi: 10.1016/j.bioadv.2026.215050. Full text in Research Archive Show summary

  This study evaluated the effects of dual-crosslinking strategies on the mechanical performance and biocompati- bility of chitosan-norbornene (Chi-NB) nanofibres for tissue reconstruction. Chi-NB, bearing 28.6 ± 1.4 mol% alkene groups, was processed into nanofibres via solution blow spinning. Dual crosslinking was conducted by photo-initiated thiol-ene crosslinking with dithiothreitol (DTT), achieving >95% norbornene conversion with minimal thiol oxidation, followed by exposure to tannic acid (TA). Structural and chemical validation was per- formed using SEM, NMR, XPS, FT-IR, and tensile testing. In vitro, unmodified fibres supported robust cell viabil- ity, however, TA/DTT-modified fibres caused up to 15-fold higher LDH release at low seeding-densities, mirrored in indirect conditioned medium exposure, implicating cytotoxic leachates. Confocal imaging confirmed cell ad- hesion and cytoskeletal organisation whereas transcript analysis revealed altered expression of genes related to stress response, metabolism, growth, and differentiation. Overall, TA/DTT crosslinking improved nanofibre me- chanical properties but introduced bioactive residues, highlighting the need for post-processing and seeding den- sity optimisation. These findings support the translational potential of Chi-NB scaffolds in skin and neural tissue engineering, but future refinements are required for these applications.

• Samara, Athina & Khalil, Asma (2026). Moving beyond associations: The role of mechanistic evidence in prenatal paracetamol safety. Med. ISSN 2666-6359. 7(6), p. 101142–101142. doi: 10.1016/j.medj.2026.101142. Full text in Research Archive Show summary

  Prenatal paracetamol safety has been debated due to inconsistent observational findings and inherent confounding. Here we argue that epidemiology alone cannot resolve biological plausibility. Human-relevant mechanistic models, including organoid and microphysiological systems, can complement population studies by testing causal pathways, refining interpretation, and enabling integrated evidence triangulation to better inform clinical guidance. Med home. Opens in new tab

• Agger, Anne Eriksson; Hlinkova, Jana; Reseland, Janne Elin & Samara, Athina (2026). 3D models for oral inflammation using gingival fibroblasts, lipopolysaccharides and hypoxia | Scientific Reports. Scientific Reports. doi: 10.1038/s41598-026-47648-7. Full text in Research Archive Show summary

  Three-dimensional (3D) in vitro models that more faithfully recapitulate human tissue architecture are essential to advance mechanistic insight into inflammatory diseases. We developed and characterized a 3D human gingival fibroblast spheroid-system to dissect the combined effects of hypoxia and inflammation, two central features of host–pathogen interactions in periodontal disease and other chronic inflammatory conditions. Using controlled oxygen environments and stimulation with E. coli lipopolysaccharide (LPS) and IL-1β, we show that hypoxia alone markedly alters spheroid morphology, producing smaller aggregates with thinner rims, while the combination of hypoxia and inflammation yields the most prominent structural disruption. Cross-section analyses reveal condition-dependent remodeling of extracellular matrix and cytoskeletal organization, with coordinated reductions in fibronectin, collagen I/III, integrin β1, and filamentous actin. Gene expression profiling confirms suppression of extracellular matrix (ECM)-related and adhesion genes under hypoxia and combined stress, whereas secretome analysis demonstrates robust upregulation of pro-inflammatory cytokines and chemokines (IL-6, IL-8, MCP-1, TNFα) and angiogenic VEGFα. Despite these marked structural and immunological shifts, cell viability remained largely preserved. This 3D system captures key features of fibroblast responses to inflammatory and hypoxic cues, providing a human-relevant platform for studies of tissue remodeling, cytokine signaling, and microenvironmental stress relevant to host–pathogen–driven disease.

• Samara, Athina & Khalil, Asma (2026). Cardiovascular Changes in Pregnancy: Reference Ranges and Role of Maternal Characteristics. In Maulik, Dev (Eds.), Doppler ultrasound in obstetrics and gynecology. Springer Publishing Company. ISSN 9783540230885. p. 21–41. doi: 10.1007/978-3-032-10702-2_3. Full text in Research Archive Show summary

  Pregnancy induces profound cardiovascular adaptations that ensure adequate maternal perfusion and fetal development. These changes involve systemic, structural, and functional modifications, driven by hormonal, metabolic, and haemodynamic factors. Maternal blood volume expands with disproportionate plasma volume rise, causing physiologic anaemia, while increased cardiac output, stroke volume, and heart rate accommodate growing circulatory demands. Hormones such as progesterone, estrogen, and relaxin mediate vasodilation, reduce systemic vascular resistance, and remodel the vasculature. Additionally, the uteroplacental circulation undergoes extensive vascular remodelling, including spiral artery transformation, enabling low-resistance, high-capacitance blood flow essential for fetal growth. Longitudinally, adaptations evolve across trimesters, with early vasodilation and cardiac output rising in the first, peak blood volume and compliance in the second, and maximal cardiac output with potential vena cava compression in the third. The peri-partum period features dramatic shifts, including auto-transfusion during labour and rapid post-partum normalisation. Non-invasive assessments, such as echocardiography, Doppler ultrasound, impedance cardiography, and emerging wearable technologies, can enable monitoring of maternal haemodynamics and placental function. Clinical implications are also significant. Inadequate cardiovascular or uteroplacental adaptation may lead to complications such as pre-eclampsia, intrauterine growth restriction, or placental insufficiency. Standardised protocols for assessing arterial stiffness, cardiac output, venous haemodynamics, and volume homeostasis have been proposed by International Working Groups. Moreover, reference ranges and functional haemodynamic testing further aid risk stratification, whereas future integration of biomarkers, artificial intelligence, and digital health tools promises personalised patient monitoring for improved maternal-fetal outcomes.

• D'Antonio, Francesco; Flacco, Maria Elena; Valle, Lorenza Della; Prasad, Smriti; Manzoli, Lamberto & Samara, Athina [Show all 7 contributors for this article] (2026). Prenatal paracetamol exposure and child neurodevelopment: a systematic review and meta-analysis. The Lancet Obstetrics, Gynaecology, & Women's Health. doi: 10.1016/s3050-5038(25)00211-0. Full text in Research Archive Show summary

  Background Concerns have emerged about the impact of paracetamol use in pregnancy on child neurodevelopment, particularly in relation to autism spectrum disorder. We aimed to synthesise available evidence to investigate associations between prenatal paracetamol exposure and autism spectrum disorder, attention-deficit hyperactivity disorder (ADHD), and intellectual disability. Methods For this systematic review and meta-analysis, we searched MEDLINE, Embase, ClinicalTrials.gov, and the Cochrane Library from inception to Sept 30, 2025, for cohort studies reporting adjusted estimates of the risk of autism spectrum disorder, ADHD, and intellectual disability. Eligible studies used validated questionnaires or medical records to define outcomes, reported maternal comorbidities and treatments, and compared pregnancies with and without paracetamol exposure, whereas unadjusted studies were excluded. Quality assessment of the included studies was conducted using the Quality In Prognosis Studies (QUIPS) tool. The primary outcomes were the associations between prenatal paracetamol exposure and the likelihood of autism spectrum disorder, ADHD, and intellectual disability. Analyses were restricted to sibling-comparison studies with adjusted estimates, and odds ratios (OR) were calculated. Random-effects meta-analyses used the generic inverse variance method. Subgroup analyses were performed when possible (trimester, duration of use, offspring sex, and follow-up length). This study was registered with PROSPERO, CRD420251156690. Findings 43 studies were included in the systematic review, and 17 studies in the meta-analysis. When considering sibling comparison studies, paracetamol exposure during pregnancy was not associated with the risk of autism spectrum disorder (OR 0·98, 95% CI 0·93–1·03; p=0·45), ADHD (0·95, 0·86–1·05; p=0·31), or intellectual disability (0·93, 0·69–1·24; p=0·63). There was also no association between paracetamol intake during pregnancy and autism spectrum disorder (OR 1·03, 95% CI 0·86–1·23; p=0·78), ADHD (0·97, 0·89–1·05; p=0·49), or intellectual disability (1·11, 0·92–1·34; p=0·28) when considering only studies at low risk of bias according to QUIPS. This absence of association persisted when considering all studies with adjusted estimates and those with more than 5 years of follow-up. Interpretation Current evidence does not indicate a clinically important increase in the likelihood of autism spectrum disorder, ADHD, or intellectual disability in children of pregnant individuals who use paracetamol as directed, supporting existing recommendations on its safety.

• Samara, Athina & Khalil, Asma (2026). Pregnancy as a stress test: Reframing the fourth trimester as a window of intervention and postpartum precision medicine. Med. ISSN 2666-6359. 7(1), p. 100969–100969. doi: 10.1016/j.medj.2025.100969. Full text in Research Archive Show summary

  Pregnancy triggers profound physiological changes, yet postpartum recovery remains under-recognized despite its predictive significance for lifelong health. The fourth trimester offers a critical window to detect cardiometabolic, immunological, and mental-health vulnerabilities. We propose a precision postpartum medicine framework integrating human-relevant models, longitudinal multi-omics, and AI-enabled risk stratification to transform postpartum care.

• Samara, Athina; Hanton, Thomas; Thakar, Ranee; Jauniaux, Eric & Khalil, Asma (2025). Impact of climate change and environmental adversities on maternal and fetal health: the role of clinical practices and providers in mitigating effects and prioritising women's health in the UK. Frontiers in Global Women's Health. 6. doi: 10.3389/fgwh.2025.1483938. Full text in Research Archive Show summary

  The climate crisis poses profound risks to women particularly during pregnancy. With rising global temperatures and increasing frequency of extreme weather events, there is an urgent need for health initiatives and guidelines tailored to the unique vulnerabilities of pregnant individuals. We conducted a review of English-language literature from 2000–2024 using PubMed, Scopus, and Web of Science, focusing on “climate change,” “pregnancy,” and “maternal health,” and included original studies, reviews. Relevant policy documents, including some published in 2025 were also included. We examine the multifaceted challenges posed by climate change, such as extreme weather events, water scarcity, malnutrition, and exposure to environmental pollutants like contaminated air and water, which directly and indirectly affect maternal and fetal health. The review explores the associations between these environmental stressors and adverse pregnancy outcomes, including preterm births, low birth weight, and developmental complications. These challenges are compounded in low-resource settings where healthcare infrastructure is limited, exacerbating inequities in maternal care. Furthermore, we focus on key areas for further investigation, including the long-term health effects of in-utero exposure to pollutants. The review addresses evidence-based strategies to reduce the environmental impact of healthcare through early interventions, innovation, and strengthened initiatives. It emphasises empowering healthcare professionals to educate others, raise awareness among policymakers, advocate for climate-conscious policies, and promote sustainable practices reducing the carbon footprint of the healthcare system, with a focus on the UK. In response to these pressing concerns, leading professional organizations, such as the Royal College of Obstetricians and Gynaecologists (RCOG) in the UK, and the American College of Obstetricians and Gynaecologists (ACOG) in the US, are prioritizing the intersection of climate change and women's health. Their initiatives, which aim to mitigate the climate-change impacts on pregnancies and fetal health by promoting research, raising awareness, and developing actionable strategies, are also highlighted. By amplifying awareness and global collaboration, the suggested strategies aim to protect maternal and fetal health in the face of an escalating climate crisis.

• Hlinkova, Jana; Dziemidowicz, Karolina; Ullrich, Mathilde M.; Agger, Anne Eriksson; Lian, Aina-Mari & Reseland, Janne Elin [Show all 7 contributors for this article] (2025). Neural growth patterns: how random and aligned fibers guide 3D cell organization and pseudospheroid formation. Frontiers in Bioengineering and Biotechnology. 13. doi: 10.3389/fbioe.2025.1659965. Full text in Research Archive Show summary

  Background and purpose Electrospun biomaterials replicate the structural complexity of the extracellular matrix (ECM), providing mechanical support and promoting neural cell survival and organization. Fiber orientation is a key determinant of neural cell behavior, influencing adhesion, migration, and differentiation. This study investigates how high seeding density combined with fiber directionality shapes SH-SY5Y culture morphology, gene expression, and early network formation; all critical factors for the design of next-generation scaffolds for neural tissue engineering. Methods Polycaprolactone (PCL) scaffolds with either random or aligned fiber orientation were fabricated via monoaxial electrospinning. Human SH-SY5Y neuroblastoma cells were seeded at high density and cultured for 7 days, and cell viability was assessed by lactate dehydrogenase (LDH) activity. Neural, ECM, and differentiation markers were analyzed using quantitative PCR, Luminex cytokine profiling, and confocal immunofluorescence. Results Hydrophobic PCL fibers supported cell adhesion, migration, and proliferation when cells were seeded in small clusters. After 7 days, cell coverage of the fiber-mat was significantly higher on random fibers compared to aligned ones (27.7% vs. 15.8%). Fiber orientation influenced both culture morphology and gene expression. Pseudospheroids formed on both substrates, that differed in perimeter (348.5 µm on random vs. 450.5 µm on aligned fibers, p < 0.05), with no significant difference in thickness (38.4 ± 7.7 µm vs. 43.2 ± 5.5 µm). mRNA expression of connexin 43 and β3-tubulin increased significantly from day 1 to day 7 on random fibers. On aligned fibers, mRNA patterns resembled cells cultured on glass (control), with elevated connexin 31 and doublecortin over time. Immunofluorescence showed early enrichment of nestin on aligned fibers (day 1), and greater expression of β3-tubulin, acetylated tubulin, and connexin 31 on aligned substrates, whereas fibronectin 1 was more prominent on random fibers. Conclusion Fiber orientation significantly affected SH-SY5Y cell behaviour, including adhesion, formation of pseudospheroids, and differentiation marker expression under high-density conditions. Random and aligned fibers elicited distinct structural patterns and molecular responses, highlighting the importance of scaffold architecture in the rational design of neuroregenerative platforms. To our knowledge, this is the first study to describe scaffold-anchored neural pseudospheroids as a distinct model from conventional suspension spheroids.

• Samara, Athina; Coutinho, Conrado Milani; Heath, Paul T. & Khalil, Asma (2025). Is maternal SARS-CoV-2 infection in the first trimester associated with congenital heart defects? Frontiers in Pediatrics. doi: 10.3389/fped.2025.1643423. Full text in Research Archive Show summary

  Emerging evidence suggests a potential link between maternal SARS-CoV-2 infection during early pregnancy and the development of congenital heart defects (CHD) in offspring. Although vertical transmission of SARS-CoV-2 is rare, the virus has been associated with placental complications and increased maternal morbidity. Recent studies from China report increased rates of CHD and anomalies such as situs inversus when infection occurs during gestational weeks 4–6, a critical window for cardiac development. Additional reports from different parts of the world also highlight post-pandemic increases in specific cardiac anomalies, including ventricular septal defects (VSDs). Multiple mechanisms may underlie these associations. SARS-CoV-2 can induce placental inflammation, compromise the cytotrophoblast barrier, and impair nutrient and gas exchange, potentially leading to fetal hypoxia and disrupted morphogenic signalling. Furthermore, maternal inflammation and elevated cytokines, along with viral effects on ACE2-expressing fetal cardiac progenitors, could further affect proliferation, differentiation, and apoptosis during cardiac development. Co-infections, hormone disruption, and maternal stress could also contribute. There is an urgent need for longitudinal studies with comprehensive maternal-fetal data, including infection timing, vaccine status, and biological sampling. These will be essential to delineate the multifactorial impacts of maternal infection on fetal cardiac development and long-term outcomes. Special focus should be placed on infections during early pregnancy (weeks 4–7), the period of cardiac septation and left-right asymmetry establishment, to determine causality and inform prevention strategies.

• Saghir, Saloua; Hlinkova, Jana; Samara, Athina & Schiavone, Giuseppe (2025). Protocol for fabricating a reusable plate-well insert with a 3D-printed mounter and hydrogel scaffolds for 3D cell culture and functional assays. STAR Protocols. 6(3). doi: 10.1016/j.xpro.2025.104014. Full text in Research Archive Show summary

  We present a protocol for the fabrication of reusable inserts for standard 24-well plates, comprising a 3D-printed mounter and a hydrogel scaffold for 3D cell culture studies. We cover the design and production of the mounter, hydrogel scaffold synthesis, lyophilization for storage, sterilization, and hydrophilization before cell culture. Downstream applications include cytotoxicity assessment, imaging, and qPCR. Streamlining hydrogel preparation and mounting minimizes batch-to-batch variation, reduces costs, and supports synthetic biology studies.

• Munir, Arooj; Agger, Anne Eriksson; Samara, Athina; Reseland, Janne Elin & Solberg, Lene Bergendal (2025). Enhancing human osteoblast to osteocyte-like cell differentiation using 25-hydroxyvitamin D3 and all-trans retinoic acid combination. European Cells and Materials. p. 145–157. doi: 10.22203/eCM.v051a09. Full text in Research Archive Show summary

  Background: The individual effects of the 25-hydroxyvitamin D3 (25(OH)D3) and all-trans retinoic acid (ATRA) on osteogenesis have been studied in two-dimensional (2D) in vitro models, but the combined effect of these vitamins remains largely unexplored. Therefore, to address this knowledge gap we evaluated the effect of different concentrations of 25(OH)D3 and ATRA, individually and in combination, on differentiation of primary human osteoblasts (hOBs) over a 21-day period. Methods: The growth of hOBs, alkaline phosphatase (ALP) activity (cell bound and secreted), and the expression of bone-related markers were comprehensively evaluated at both gene expression level using real-time polymerase chain reaction (RT-PCR) and the proteins secretion through multiplex immunoassays. Results: Both 25(OH)D3 and ATRA enhanced hOBs differentiation. However, the combination of 10−6 M 25(OH)D3 and 10−5 M ATRA demonstrated the most pronounced effect, characterized by reduction in cell growth and enhancement in differentiation. This was further validated by elevated relative expression of osteoblast and osteocyte markers at both mRNA level (collagen type I alpha 1 (COL1A1), podoplanin (E11), and dentin matrix acidic phosphoprotein 1 (DMP1), and at protein level (osteopontin (OPN), osteocalcin (OCN), sclerostin (SOST), and fibroblast growth factor 23 (FGF23)). Additionally, 25(OH)D3 and ATRA were found to regulate the expression of key receptors involved in osteoblasts differentiation, including retinoic acid receptor alpha (RARα), retinoid X receptor beta (RXRβ), and vitamin D receptor (VDR). Conclusions: This study demonstrates that a combination of 10−6 M 25(OH)D3 and 10−5 M ATRA effectively enhanced the differentiation of hOBs to osteocyte-like cells in vitro.

• Samara, Athina; Souter, Vivienne; Coutinho, Conrado Milani & Khalil, Asma (2024). In need of robust evidence of non-association of pregestational and early pregnancy SARS-CoV-2 infections with congenital anomalies. EClinicalMedicine. 74. doi: 10.1016/j.eclinm.2024.102729. Full text in Research Archive Show summary

  SARS-CoV-2 infection during pregestational and early pregnancy periods has an unclear impact on fetal development. Although vertical transmission is rare, potential effects on the developing fetal brain are plausible. However, robust evidence linking maternal SARS-CoV-2 infection to congenital anomalies is limited due to inadequate tracking of infection history and methodological flaws in published studies. This is further complicated by limitations, such as restricted testing access and undiagnosed infections, particularly in low- and middle-income countries. Most data focus on hospitalized women near term, lacking information on first- and second-trimester infections. Thus, an accurate assessment of the impact of COVID-19 on congenital anomalies is essential. It should however be emphasised that we have robust evidence that vaccination against COVID-19 before or during early pregnancy is not associated with malformations, ruling out any role of COVID-19 vaccines in these increased rates of congenital abnormalities. This viewpoint discusses findings from surveillance registries, highlights study limitations, and offers research recommendations to inform clinical guidelines and public health strategies, aiming to mitigate the effects of viral infections on early neurodevelopment.

• Phillips, Wiktor S.; Ramadan, Naify; Samara, Athina & Herlenius, Eric (2024). Protocol to dissect and dissociate the mouse brainstem for single-cell RNA-seq applications. STAR Protocols. 5(1). doi: 10.1016/j.xpro.2024.102908. Full text in Research Archive Show summary

  Processing dissociated cells for transcriptomics is challenging when targeting small brain structures, like brainstem nuclei, where cell yield may be low. Here, we present a protocol for dissecting, dissociating, and cryopreserving mouse brainstem that allows asynchronous sample collection and downstream processing of cells obtained from brainstem tissue in neonatal mice. Although we demonstrate this protocol with the isolated preBötzinger complex and downstream SmartSeq3 cDNA library preparation, it could be readily adapted for other brainstem areas and library preparation approaches.

• Reising, Jan Philipp; Gonzalez-Sanchez, Ana Cristina; Samara, Athina & Herlenius, Eric (2024). Astrocytic Calcium Signaling Toolkit (astroCaST): efficient analysis of dynamic astrocytic calcium events. Frontiers in Cellular Neuroscience. 18. doi: 10.3389/fncel.2024.1408607. Full text in Research Archive Show summary

  The Astrocytic Calcium Signaling Toolkit (astroCaST) is a novel solution to a longstanding challenge in neuroscience research: the specialized analysis of astrocytic calcium events within fluorescence time-series imaging. Distinct from existing neuron-centric tools, astroCaST is adept at detecting and clustering astrocytic calcium events based on their unique spatiotemporal characteristics, thus filling a gap in astrocytic research methodologies. This toolkit not only facilitates the detection of such events but also extends its utility to provide comprehensive end-to-end analysis. This feature is absent in most tools targeting astrocytic activity. AstroCaST's development was motivated by the critical need for dedicated software that supports researchers in transitioning from raw video data to insightful experimental conclusions, efficiently managing large-scale datasets without compromising computational speed. It offers a user-friendly interface that caters to both novice and expert users, incorporating both a graphical user interface (GUI) for detailed explorations and a command-line interface (CLI) for extensive analyses. Expected outcomes from utilizing astroCaST include the ability to process and analyze a significantly larger volume of data. This enables a more profound and comprehensive analysis than previously possible, addressing the demands of large-scale astrocytic studies. In summary, astroCaST aims to advance astrocytic calcium imaging analysis, offering a tailored, efficient, and comprehensive toolset that enhances our understanding of astrocytic functions and their implications in neuroscience.

• Khalil, A.; Samara, Athina; Coutinho, C.M. & Ladhani, S.N. (2024). Global efforts needed to address burden of preventable stillbirth. Ultrasound in Obstetrics and Gynecology. ISSN 0960-7692. 63(4), p. 441–445. doi: 10.1002/uog.27543. Full text in Research Archive
• Khalil, Asma; Samara, Athina; Campbell, Helen; Ladhani, Shamez N. & Amirthalingam, Gayatri (2024). Recent increase in infant pertussis cases and the critical importance of antenatal immunisations: we must do better…quickly. International Journal of Infectious Diseases. ISSN 1201-9712. doi: 10.1016/j.ijid.2024.107148. Full text in Research Archive Show summary

  Authors Khalil A, Samara A, Campbell H, Ladhani SN, Amirthalingam G

• Khalil, Asma; Samara, Athina; Campbell, Colin & Ladhani, Shamez N. (2024). Pregnant women and measles: we need to be vigilant during outbreaks. EClinicalMedicine. 72. doi: 10.1016/j.eclinm.2024.102594. Full text in Research Archive Show summary

  A number of countries including the UK are currently experiencing large outbreaks of measles affecting mainly young children but also adolescents and young adults. Women of childbearing age are a particular group of concern because the 1988 Wakefield Lancet paper, which falsely asserted a connection between the MMR vaccine and autism, was associated with a large and sharp decline in childhood MMR uptake over several years. This has left large cohorts of non-immune adolescents and young adults (born between 1998 and 2004), including young women who are now of childbearing age and remain susceptible to measles as well as rubella. Pregnant mothers are at higher risk of serious complications, such as pneumonia, with adverse pregnancy complications including fetal loss, premature birth, and neonatal death. Measles infection may also result in subacute sclerosing panencephalitis (SSPE), a very rare but very severe and invariably fatal neurodegenerative complication that typically manifests many years after acute measles infection but can have a short-onset latency with a fulminant course in pregnant women. Here, we summarise the epidemiology of measles infection, factors associated with the current measles outbreaks, as well as the risks and outcomes of measles, including SSPE, in pregnancy. We propose an algorithm for clinical management of measles infection in pregnancy. We also highlight the importance of early liaison with local health protection teams for risk assessment, diagnosis and management of suspected measles in pregnancy and close contacts as well as susceptible pregnant women exposed to a person with measles in the community.

• Spildrejorde, Mari Roberts; Leithaug, Magnus; Samara, Athina; Aass, Hans Christian; Sharma, Ankush & Acharya, Ganesh [Show all 9 contributors for this article] (2024). Citalopram exposure of hESCs during neuronal differentiation identifies dysregulated genes involved in neurodevelopment and depression. Frontiers in Cell and Developmental Biology. 12. doi: 10.3389/fcell.2024.1428538. Full text in Research Archive Show summary

  Selective serotonin reuptake inhibitors (SSRIs), including citalopram, are widely used antidepressants during pregnancy. However, the effects of prenatal exposure to citalopram on neurodevelopment remain poorly understood. We aimed to investigate the impact of citalopram exposure on early neuronal differentiation of human embryonic stem cells using a multi-omics approach. Citalopram induced time- and dose-dependent effects on gene expression and DNA methylation of genes involved in neurodevelopmental processes or linked to depression, such as BDNF, GDF11, CCL2, STC1, DDIT4 and GAD2. Single-cell RNA-sequencing analysis revealed distinct clusters of stem cells, neuronal progenitors and neuroblasts, where exposure to citalopram subtly influenced progenitor subtypes. Pseudotemporal analysis showed enhanced neuronal differentiation. Our findings suggest that citalopram exposure during early neuronal differentiation influences gene expression patterns associated with neurodevelopment and depression, providing insights into its potential neurodevelopmental impact and highlighting the importance of further research to understand the long-term consequences of prenatal SSRI exposure.

• Agger, Anne Eriksson; Samara, Athina; Geng, Tianxiang; Olstad, Ole Kristoffer & Reseland, Janne Elin (2024). Mimicking and in vitro validating chronic inflammation in human gingival fibroblasts. Archives of Oral Biology. ISSN 0003-9969. 169, p. 1–11. doi: 10.1016/j.archoralbio.2024.106113. Full text in Research Archive Show summary

  Objective The aim of this study was to identify and validate in vitro conditions that may mimic the translational, cytokine and chemokine profiles observed in human inflamed gingiva in vivo. Design Primary human gingiva fibroblast cells (HFIB-G) were cultured under serum starvation conditions (0 – 10 %), supplemented with increasing lipopolysaccharide (LPS) concentrations (0.1, 1, or 10 µg/ml) from two bacterial strains E. coli and P. gingivalis and 0.1, 1, or 10 ng/ml recombinant interleukin 1β (IL-1β), alone or in combinations. The levels of cytokines/chemokines were measured in the cell culture medium by Luminex, and gene expression was quantified by Affymetrix microarrays at 24, 48 and 72 h. Results Inflammation markers were not elevated after stimulation with P. gingivalis LPS, while E. coli LPS and IL-1β individually increased the secretion of interleukin 6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) to the cell culture medium. IL-1β administration also increased the secretion of several factors, including tumor necrosis factor (TNFα). However, the combination of 1 µg/ml E. coli LPS, 1 ng/ml IL-1β and serum starvation led to increased secretion of IL-6, TNFα, in addition to other factors found in inflamed tissue. Gene expression analyses revealed that this combination not only enhanced the expression interleukins/chemokines genes but also T helper cell signaling and matrix metalloproteinases. Conclusion Serum reduction in cell culture medium together with the administration of E. coli LPS and IL-1β resulted in gene expression and secreted cytokine/chemokine profiles similar to that found in vivo during chronic inflammation.

• Samara, Athina; Hanton, T. & Khalil, A. (2024). Evidence-based interventions to address persistent maternal mortality rates. Ultrasound in Obstetrics and Gynecology. ISSN 0960-7692. doi: 10.1002/uog.27712. Full text in Research Archive
• Samara, Athina (2024). A forward-thinking biocompatibility assessment: drafting future considerations now. Trends in Biotechnology. ISSN 0167-7799. doi: 10.1016/j.tibtech.2024.11.013. Full text in Research Archive
• Samara, Athina; Coutinho, Conrado Milani; Veal, Philip; Osborne, Jane; Duarte, Geraldo & Ladhani, Shamez [Show all 7 contributors for this article] (2024). Potential vertical transmission of Oropouche virus during the current outbreak. The Lancet Infectious Diseases. ISSN 1473-3099. doi: 10.1016/S1473-3099(24)00571-1. Full text in Research Archive
• Khalil, A & Samara, Athina (2023). Treatment and prevention of mpox in pregnant people and young children. The Lancet Infectious Diseases. ISSN 1473-3099. doi: 10.1016/S1473-3099(23)00054-3. Full text in Research Archive Show summary

  Authors Khalil A, Samara A, O’ Brien P, Ladhani S

• Khalil, A & Samara, Athina (2023). A call to action: the global failure to effectively tackle maternal mortality rates. The Lancet Global Health. ISSN 2572-116X. doi: 10.1016/S2214-109X(23)00247-4. Full text in Research Archive Show summary

  Khalil A, Samara A, O’ Brien P, CM Coutinho, SM Quintana, Ladhani S

• Khalil, A & Samara, Athina (2023). Do not forget pregnant and postpartum women during group A streptococcal (GAS) disease outbreaks. Lancet Microbe. doi: 10.1016/S2666-5247(23)00064-2. Full text in Research Archive Show summary

  Authors Khalil A, Samara A, O’ Brien P, Ladhani S

• Samara, Athina; Khalil, A & O'Brien, P (2023). SARS-CoV-2 infection and COVID-19 vaccination in pregnancy. The global library of women's medicine. doi: 10.3843/GLOWM.419433. Full text in Research Archive
• Mateu-Sanz, Miguel; Fuenteslópez, Carla V.; Uribe-Gomez, Juan; Haugen, Håvard Jostein; Pandit, Abhay & Ginebra, Maria-Pau [Show all 9 contributors for this article] (2023). Redefining biomaterial biocompatibility: challenges for artificial intelligence and text mining. Trends in Biotechnology. ISSN 0167-7799. doi: 10.1016/j.tibtech.2023.09.015. Full text in Research Archive Show summary

  The surge in ‘Big data’ has significantly influenced biomaterials research and development, with vast data volumes emerging from clinical trials, scientific literature, electronic health records, and other sources. Biocompatibility is essential in developing safe medical devices and biomaterials to perform as intended without provoking adverse reactions. Therefore, establishing an artificial intelligence (AI)-driven biocompatibility definition has become decisive for automating data extraction and profiling safety effectiveness. This definition should both reflect the attributes related to biocompatibility and be compatible with computational data-mining methods. Here, we discuss the need for a comprehensive and contemporary definition of biocompatibility and the challenges in developing one. We also identify the key elements that comprise biocompatibility, and propose an integrated biocompatibility definition that enables data-mining approaches.

• Geng, Tianxiang; Zheng, Mengxue; Wang, Yongfeng; Reseland, Janne Elin & Samara, Athina (2023). An artificial intelligence prediction model based on extracellular matrix proteins for the prognostic prediction and immunotherapeutic evaluation of ovarian serous adenocarcinoma. Frontiers in Molecular Biosciences. 10. doi: 10.3389/fmolb.2023.1200354. Full text in Research Archive Show summary

  Background: Ovarian Serous Adenocarcinoma is a malignant tumor originating from epithelial cells and one of the most common causes of death from gynecological cancers. The objective of this study was to develop a prediction model based on extracellular matrix proteins, using artificial intelligence techniques. The model aimed to aid healthcare professionals to predict the overall survival of patients with ovarian cancer (OC) and determine the efficacy of immunotherapy. Methods: The Cancer Genome Atlas Ovarian Cancer (TCGA-OV) data collection was used as the study dataset, whereas the TCGA-Pancancer dataset was used for validation. The prognostic importance of 1068 known extracellular matrix proteins for OC were determined by the Random Forest algorithm and the Lasso algorithm establishing the ECM risk score. Based on the gene expression data, the differences in mRNA abundance, tumour mutation burden (TMB) and tumour microenvironment (TME) between the high- and low-risk groups were assessed. Results: Combining multiple artificial intelligence algorithms we were able to identify 15 key extracellular matrix genes, namely, AMBN, CXCL11, PI3, CSPG5, TGFBI, TLL1, HMCN2, ESM1, IL12A, MMP17, CLEC5A, FREM2, ANGPTL4, PRSS1, FGF23 , and confirm the validity of this ECM risk score for overall survival prediction. Several other parameters were identified as independent prognostic factors for OC by multivariate COX analysis. The analysis showed that thyroglobulin (TG) targeted immunotherapy was more effective in the high ECM risk score group, while the low ECM risk score group was more sensitive to the RYR2 gene-related immunotherapy. Additionally, the patients with low ECM risk scores had higher immune checkpoint gene expression and immunophenoscore levels and responded better to immunotherapy. Conclusion: The ECM risk score is an accurate tool to assess the patient’s sensitivity to immunotherapy and forecast OC prognosis.

• Spildrejorde, Mari; Samara, Athina; Sharma, Ankush; Leithaug, Magnus; Falck, Martin Bengt Alfred & Modafferi, Stefania [Show all 12 contributors for this article] (2023). Multi-omics approach reveals dysregulated genes during hESCs neuronal differentiation exposure to paracetamol. iScience. 26:107755(10), p. 1–29. doi: 10.1016/j.isci.2023.107755. Full text in Research Archive Show summary

  Prenatal paracetamol exposure has been associated with neurodevelopmental outcomes in childhood. Pharmacoepigenetic studies show differences in cord blood DNA methylation between unexposed and paracetamol-exposed neonates, however, causality and impact of long-term prenatal paracetamol exposure on brain development remain unclear. Using a multi-omics approach, we investigated the effects of paracetamol on an in vitro model of early human neurodevelopment. We exposed human embryonic stem cells undergoing neuronal differentiation with paracetamol concentrations corresponding to maternal therapeutic doses. Single-cell RNA-seq and ATAC-seq integration identified paracetamol-induced chromatin opening changes linked to gene expression. Differentially methylated and/or expressed genes were involved in neurotransmission and cell fate determination trajectories. Some genes involved in neuronal injury and development-specific pathways, such as KCNE3, overlapped with differentially methylated genes previously identified in cord blood associated with prenatal paracetamol exposure. Our data suggest that paracetamol may play a causal role in impaired neurodevelopment.

• Yang, Yang; Geng, Tianxiang; Samara, Athina; Olstad, Ole Kristoffer; He, Jianying & Agger, Anne Eriksson [Show all 11 contributors for this article] (2023). Recombinant irisin enhances the extracellular matrix formation, remodeling potential, and differentiation of human periodontal ligament cells cultured in 3D. Journal of Periodontal Research. ISSN 0022-3484. 58(2), p. 336–349. doi: 10.1111/jre.13094. Full text in Research Archive Show summary

  Abstract Background Irisin is expressed in human periodontal ligament (hPDL), and its administration enhances growth, migration and matrix deposition in hPDL cells cultured in monolayers in vitro. Objectives To identify whether irisin affects the gene expression patterns directing the morphology, mechanical properties, extracellular matrix (ECM) formation, osteogenic activity and angiogenic potential in hPDL cell spheroids cultured in 3D. Materials and Methods Spheroids of primary human hPDL cells were generated in a rotational 3D culture system and treated with or without irisin. The gene expression patterns were evaluated by Affymetrix microarrays. The morphology of the spheroids was characterized using histological staining. Mechanical properties were quantified by nanoindentation. The osteogenic and angiogenic potential of spheroids were assessed through immunofluorescence staining for collagen type I, periostin fibronectin and von Willebrand factor (vWF), and mRNA expression of osteogenic markers. The secretion of multiple myokines was evaluated using Luminex immunoassays. Results Approximately 1000 genes were differentially expressed between control and irisin-treated groups by Affymetrix. Several genes related to ECM organization were differentially expressed, and multiple deubiquitinating enzymes were upregulated in the irisin-exposed samples analyzed. These represent cellular and molecular mechanisms indicative of a role for irisin in tissue remodeling. Irisin induced a rim-like structure on the outer region of the hPDL spheroids, ECM-related protein expression and the stiffness of the spheroids were enhanced by irisin. The expression of osteogenic and angiogenetic markers was increased by irisin. Conclusions Irisin altered the morphology in primary hPDL cell-derived spheroids, enhanced its ECM deposition, mechanical properties, differentiation and remodeling potential.

• Reseland, Janne Elin; Heyward, Catherine Anne & Samara, Athina (2023). Revisiting ameloblastin; addressing the EMT-ECM axis above and beyond oral biology. Frontiers in Cell and Developmental Biology. 11. doi: 10.3389/fcell.2023.1251540. Full text in Research Archive Show summary

  Ameloblastin (AMBN) is best characterized for its role in dental enamel formation, regulating cell differentiation and mineralization, and cell matrix adhesion. However, AMBN has also been detected in mesenchymal stem cells in addition to bone, blood, and adipose tissue. Using immunofluorescence in a pilot scheme, we identified that AMBN is expressed in different parts of the gastrointestinal (GI) tract. AMBN mRNA and protein detection in several tissues along the length of the GI tract suggests a role for AMBN in the structure and tissue integrity of the extracellular matrix (ECM). Intracellular AMBN expression in subsets of cells indicates a potential alternative role in signaling processes. Of note, our previous functional AMBN promoter analyses had shown that it contains epithelial–mesenchymal transition (EMT) regulatory elements. ΑΜΒΝ is herein presented as a paradigm shift of the possible associations and the spatiotemporal regulation of the ECM regulating the EMT and vice versa, using the example of AMBN expression beyond oral biology.

• Khalil, A & Samara, Athina (2022). Monkeypox in pregnancy: Update on current outbreak. The Lancet Infectious Diseases. ISSN 1473-3099. doi: 10.1016/S1473-3099(22)00612-0. Full text in Research Archive Show summary

  Authors Khalil A, Samara A, O’Brien P, Milani Coutinho C, Duarte G, Quintana SM, Ladhani, SN.

• Khalil, A & Samara, Athina (2022). Monkeypox and pregnancy: what do obstetricians need to know? Ultrasound in Obstetrics and Gynecology. ISSN 0960-7692. doi: 10.1002/uog.24968. Full text in Research Archive Show summary

  Authors Khalil A, Samara A, O’ Brien P, Morris E, Draycott T, Lees C, Ladhani S

• Samara, Athina; Spildrejorde, Mari; Sharma, Ankush; Falck, Martin; Leithaug, Magnus & Modafferi, Stefania [Show all 11 contributors for this article] (2022). A multi-omics approach to visualize early neuronal differentiation from hESCs in 4D. iScience. 25(11). doi: 10.1016/j.isci.2022.105279. Full text in Research Archive Show summary

  Neuronal differentiation of pluripotent stem cells is an established method to study physiology, disease, and medication safety. However, the sequence of events in human neuronal differentiation and the ability of in vitro models to recapitulate early brain development are poorly understood. We developed a protocol optimized for the study of early human brain development and neuropharmacological applications. We comprehensively characterized gene expression and epigenetic profiles at four timepoints, because the cells differentiate from embryonic stem cells towards a heterogeneous population of progenitors, immature and mature neurons bearing telencephalic signatures. A multi-omics roadmap of neuronal differentiation, combined with searchable interactive gene analysis tools, allows for extensive exploration of early neuronal development and the effect of medications.

• Samara, Athina; Khalil, A & Herlenius, Eric (2022). The effect of the Delta SARS-CoV-2 variant in maternal infection and pregnancy. iScience. doi: 10.1016/j.isci.2022.104295. Full text in Research Archive
• Samara, Athina; Herlenius, Eric; O’Brien, Pat & Khalil, Asma (2022). Potential role of neurofilament in COVID-19 and preeclampsia. Cell Reports Medicine. doi: 10.1016/j.xcrm.2021.100490. Full text in Research Archive
• Khalil, Asma; Samara, Athina; O'Brien, Pat & Ladhani, Shamez (2022). The need for better diagnostics to support diagnosis and surveillance in monkeypox endemic countries. Lancet Microbe. doi: 10.1016/S2666-5247(22)00304-4. Full text in Research Archive
• Samara, Athina (2022). Robust neuronal differentiation of human embryonic stem cells for neurotoxicology. BioRxiv. ISSN 0362-4331. doi: 10.1101/2022.01.26.477818. Full text in Research Archive Show summary

  A shorter version not including the VPA treatments is published at STAR Protoc. 2022 Sep 16;3(3):101533. doi: 10.1016/j.xpro.2022.101533

• Samara, Athina & Belle, Branson (2021). Nanomaterials Upscaling Cell Production and Advancing Exosome-Based Stem Cell Therapies. Frontiers in Nanotechnology. 3, p. 1–5. doi: 10.3389/fnano.2021.714824. Full text in Research Archive Show summary

  The COVID-19 pandemic underlined that by investing in both basic and clinical life science research and if there are enough volunteers, it is feasible to have -validated by Phase III clinical trials- vaccines in less than a year. Regarding the treatment options for the people who were infected by COVID-19, we know that it was the large clinical trials - like SOLIDARITY (WHO) and RECOVERY (UK)- that gave the most valid results, and that although hundreds of drugs were repurposed, sadly, most proved to be unsuccessful. Repurposing drugs and compassionate use, were the only options for the first half of 2020. The same applied to the convalescent plasma (CP) approach; however, apart from CP, other cell derived therapeutics were deployed, such as synthetic monoclonal antibodies, which were also tested and given provisional licences by health authorities. Unfortunately, synthetic antibody production comes with problems related to low and slow yield that were not overcome, while SARS-CoV-2 viral mutations may possibly render them less effective. One approach that works and is currently assessed in several clinical trials, is mesenchymal stromal cell (MSCs) and extracellular vesicle (EV) administration for therapy. Interdisciplinarity may prove key here. Easy to produce nanomaterials and biomaterials should be further investigated to increase bioproduction of MSCs, both at the level of therapeutics, as the base substrate for EV production and to upscale synthetic antibody production for therapy.

• Kondratskaya, Elena; Oleksandr, Ievglevskyi; Züchner, Mark; Samara, Athina; Glover, Joel & Boulland, Jean-Luc (2019). Locomotor central pattern generator excitability states and serotonin sensitivity after spontaneous recovery from a neonatal lumbar spinal cord injury. Brain Research. ISSN 0006-8993. 1708, p. 10–19. doi: 10.1016/j.brainres.2018.12.001. Full text in Research Archive
• E, Hristoforou & Samara, Athina (2017). Over-hyperthermia using magnetic Fe nanoparticles. Biointerface Research in Applied Chemistry. ISSN 2069-5837. Full text in Research Archive
• Bjørnstad, Sigrid; Samara, Athina; Erichsen, Aage; Paulsen, Ragnhild Elisabeth; Glover, Joel & Roald, Borghild (2016). Hampered lung maturation in methimazole-induced hypothyroidism in fetal chicken: morphological and molecular correlates to human fetal development. Neonatology. ISSN 1661-7800. 110(2), p. 83–92. doi: 10.1159/000444656. Full text in Research Archive
• Paronis, E & Samara, Athina (2015). Maternal weight as an alternative determinant of the gestational day of Wistar rats housed in individually-ventilated cages. Laboratory Animals. ISSN 0023-6772. doi: 10.1177/0023677214562846. Full text in Research Archive Show summary

  Authors E Paronis, A Samara, A Polyzos, C Spyropoulos, N G Kostomitsopoulos

• Lymperi, Stefania; Taraslia, Vasiliki; Tsatsoulis, Ioannis N.; Samara, Athina; Velentzas, Athanasios D. & Agrafioti, Anastasia [Show all 8 contributors for this article] (2015). Dental stem cell migration on pulp ceiling cavities filled with MTA, dentin chips, or Bio-Oss. BioMed Research International. ISSN 2314-6133. 2015:189872. doi: 10.1155/2015/189872. Full text in Research Archive
• Paronis, Euthimios; Samara, Athina; Polyzos, A.; Spyropoulos, Constantine & Kostomitsopoulos, NG (2015). Maternal weight as an alternative determinant of the gestational day of Wistar rats housed in individually-ventilated cages. Laboratory Animals. ISSN 0023-6772. 49(3), p. 188–195. doi: 10.1177/0023677214562846. Full text in Research Archive
• Stasinopoulou, Marianna; Mantziaras, George; Paronis, Euthimios; Balafas, Evangelos; Lelovas, Pavlos & Samara, Athina [Show all 7 contributors for this article] (2014). Use of real-time ultrasonography as an alternative method for early detection, confirmation and evaluation of rat pregnancy. Ultrasound in Medicine and Biology. ISSN 0301-5629. 40(6), p. 1372–1378. doi: 10.1016/j.ultrasmedbio.2013.11.016. Full text in Research Archive
• Samara, Athina; Galbiati, Mariarita; Luciani, Paola; Deledda, Cristiana; Messi, Elio & Peri, Alessandro [Show all 7 contributors for this article] (2014). Altered expression of 3-betahydroxysterol delta-24-reductase/selective Alzheimer's disease indicator-1 gene in Huntington's disease models. Journal of Endocrinological Investigation. ISSN 0391-4097. 37(8), p. 729–737. doi: 10.1007/s40618-014-0098-1. Full text in Research Archive
• Samara, Athina (2013). Aberrant expression of collapsin response mediator proteins-1, -2 and -5 in the brain of intrauterine growth restricted rats. International Journal of Developmental Neuroscience. ISSN 0736-5748. doi: 10.1016/j.ijdevneu.2012.10.004. Full text in Research Archive Show summary

  Authors Aravidou E, Tsangaris G, Samara A, Dontas I, Botsis D, Aravidis C, Chrousos GP, Malamitsi-Puchner A.

• Samara, Athina (2013). Single neurons needed for brain asymmetry studies. Frontiers in Genetics. 4. doi: 10.3389/fgene.2013.00311. Full text in Research Archive
• Samara, Athina (2012). Brain proteome response following whole body exposure of mice to mobile phone or wireless DECT base radiation. Electromagnetic Biology and Medicine. ISSN 1536-8378. doi: 10.3109/15368378.2011.631068. Full text in Research Archive Show summary

  Authors Fragopoulou AF, Samara A, Antonelou MH, Xanthopoulou A, Papadopoulou A, Vougas K, Koutsogiannopoulou E, Anastasiadou E, Stravopodis DJ, Tsangaris GT, Margaritis LH.

• Samara, Athina & Tsangaris, GTh (2011). Brain asymmetry: both sides of the story. Expert Review of Proteomics. ISSN 1478-9450. doi: 10.1586/epr.11.62. Full text in Research Archive
• Samara, Athina (2011). Proteomics reveal rat hippocampal lateral asymmetry. Hippocampus. ISSN 1050-9631. doi: 10.1002/hipo.20727. Full text in Research Archive Show summary

  Authors A Samara, K Vougas, A Papadopoulou, E Anastasiadou, N Baloyanni, E Paronis, GP Chrousos, G Th Tsangaris

• Samara, Athina; Sarri, Y; Stravopodis, D; Kontakiotis, E; Tzanetakis, GN & Anastasiadou, E (2011). A comparative study of the effects of three root-end filling materials on proliferation and adherence of human periodontal ligament fibroblasts. Journal of Endodontics. ISSN 0099-2399. doi: 10.1016/j.joen.2011.03.011. Full text in Research Archive
• Samara, Athina (2010). Silicon scaffolds promoting three-dimensional neuronal web of cytoplasmic processes. Tissue Engineering Part C: Methods. ISSN 1937-3384. doi: 10.1089/ten.TEC.2009.0216. Full text in Research Archive
• Vougas, K; Samara, Athina & Tsangaris, G.Th (2009). Position dominant sequence elements in experimentally verified human promoters and their putative relation to cancer. Cancer Genomics & Proteomics. ISSN 1109-6535. Full text in Research Archive
• Piva, F; Samara, Athina & Maggi, R (2006). Role of glucocorticoid receptors in mouse neurons secreting gonadotropin releasing hormone. Frontiers in Neuroendocrinology (FIN). ISSN 0091-3022. doi: 10.1016/j.yfrne.2006.03.156. Full text in Research Archive
• Maggi, Roberto & Samara, Athina (2005). Factors involved in the migration of neuroendocrine hypothalamic neurons. Archives Italiennes de Biologie. ISSN 0003-9829. Full text in Research Archive Show summary

  Maggi R, Cariboni A, Zaninetti R, Samara A, Stossi F, Pimpinelli F, Giacobini P, Consalez GG, Rugarli E, Piva F. Factors involved in the migration of neuroendocrine hypothalamic neurons. Arch Ital Biol. 2005 Sep;143(3-4):171-8. PMID: 16097493.

• Dondi, Donatella; Samara, Athina; Maggi, Roberto; Cariboni, Anna; Gonzalez, CC & Messi, Elio (2005). Expression and differential effects of activation of glucocorticoid receptors in mouse GnRH neurons. Neuroendocrinology. ISSN 0028-3835. doi: 10.1159/000091693. Full text in Research Archive
• Samara, Athina & Maggi, Roberto (2005). Rattus norvegicus 24-dehydrocholesterol reductase (Dhcr24) mRNA, Complete cds. GenBank: AY921220.2. NCBI. Full text in Research Archive Show summary

  www.ncbi.nlm.nih.gov/nuccore/AY921220 LOCUS AY921220 1613 bp mRNA linear ROD 13-SEP-2005

• Samara, Athina & Maggi, Roberto (2005). Rattus norvegicus 24-dehydrocholesterol reductase (Dhcr24) mRNA, partial cds. GenBank: AY921220.1. NCBI. Full text in Research Archive Show summary

  LOCUS AY921220 695 bp mRNA linear ROD 13-MAR-2005 On Sep 13, 2005 this sequence was replaced by AY921220.2.

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• Saghir, Saloua; Samara, Athina; Hlinkova, Jana & Schiavone, Giuseppe (2026). REUSABLE PLATE-WELL INSERTS WITH HYDROGEL SCAFFOLDS FOR 3D CELL CULTURE. Full text in Research Archive
• Samara, Athina & Khalil, Asma (2026). Paracetamol in Pregnancy: Reassurance Amidst Uncertainty. BJOG: An International Journal of Obstetrics and Gynaecology. ISSN 1470-0328. 133(5), p. 877–883. doi: 10.1111/1471-0528.70129. Full text in Research Archive
• Samara, Athina & Khalil, Asma (2023). Unravelling human placental (patho-) physiology at the epigenetic and transcriptome level. 11. doi: 10.3389/fcell.2023.1228803. Full text in Research Archive
• Khalil, Asma & Samara, Athina (2023). Listeria outbreaks cause maternal and perinatal mortality and morbidity: we must do better. doi: 10.1016/S2666-5247(22)00388-3. Full text in Research Archive Show summary

  Authors Khalil A, Samara A, O’ Brien P, Ladhani S.

• Samara, Athina & Khalil, A (2022). Monkeypox vaccines in pregnancy: lessons must be learned from COVID-19. doi: 10.1016/S2214-109X(22)00284-4. Full text in Research Archive Show summary

  Authors Khalil A, Samara A, O'Brien P, Morris E, Draycott T, Lees C, Ladhani S

• Khalil, A & Samara, Athina (2022). The current global state of monkeypox in children. doi: 10.1016/j.lanepe.2022.100521. Full text in Research Archive Show summary

  Authors Khalil A, Samara A, O’ Brien P, Ladhani S

• Khalil, A; Samara, Athina; O'Brien, P & Ladhani, S (2022). The current monkeypox epidemic: a unique opportunity to set-up global systems for monkeypox data collection and vaccination in pregnancy. The Lancet. ISSN 0140-6736. doi: 10.1016/S0140-6736(22)01793-7. Full text in Research Archive
• Samara, Athina; Falck, Martin; Spildrejorde, Mari; Leithaug, Magnus; Acharya, Ganesh & Lyle, Robert [Show all 7 contributors for this article] (2022). Robust neuronal differentiation of human embryonic stem cells for neurotoxicology. STAR Protocols. 3(3). doi: 10.1016/j.xpro.2022.101533. Full text in Research Archive Show summary

  Here, we describe a protocol for rapid neuronal differentiation from human embryonic stem cells (hESCs) toward a heterogenous population of telencephalic progenitors, immature and mature neurons, for drug-screening and early-brain differentiation studies. hESC neuronal differentiation depends on adhesion and minimal cell-passaging to avert monolayer cross-connectivity rupture. In this protocol, we detail optimized cell-seeding densities and coating conditions with high cell viability suitable for neurotoxicology and high-resolution single-cell omics studies. Daily media changes reduce compound instability and degradation for optimal screening. For complete details on the use and execution of this protocol, please refer to Samara et al. (2022).

• Khalil, Asma & Samara, Athina (2022). Call for a unified approach to Monkeypox infection in pregnancy: Lessons from the COVID-19 pandemic. Nature Communications. doi: 10.1038/s41467-022-32638-w. Full text in Research Archive Show summary

  Khalil A, Samara A, O'Brien P, Ladhani S.

• Samara, Athina (2021). Does COVID-19 cause pre-eclampsia? doi: 10.1002/uog.24809. Full text in Research Archive
• Samara, Athina & Herlenius, Eric (2021). Is there an effect of fetal mesenchymal cells in the mother fetus dyad in COVID-19 pregnancies and vertical transmission? Frontiers in Physiology. doi: 10.3389/fphys.2020.624625. Full text in Research Archive
• Samara, Athina (2015). Expression of 5-HT receptors in human blastocysts and ESCs. Full text in Research Archive
• Samara, Athina (2012). Molecular and Cellular Characterisation of Dental Stem Cells. Full text in Research Archive Show summary

  It has been recently demonstrated that stem cells exist in all tissues of the human organism, including the dental pulp. Four different types of dental stem cells have been isolated from dental tissue. According to their origin, they are divided in: (i) Dental pulp stem cells (DPSCs), (ii) Stem cells from human exfoliated teeth (SHED), (iii) Stem cells from apical papillae (SCAP) and (iv) periodontal ligament stem cells (PDLSCs). The various dental stem cell populations have a differential multilineage differentiation potential with variable efficiency, whereas diversity is also observed in the protein expression and in the gene profile. Even though a detailed characterization of these different subpopulations has been attempted the last decades, the results of the studies are not always clear and consistent. Therefore, further characterization is required and more importantly, their response in the presence of various dental materials remain unraveled. We aim to address the above topics by focusing on SHEDs. Various samples were isolated from the pulp of exfoliated teeth and characterized using as markers the surface molecules CD73, CD90, CD105, CD34, and CD31. All the samples demonstrated extremely high measurements of MSC markers, while CD34 and CD31 were almost not detected, as expected. Although, previous studies have showed the multiple cell lineages ability of dental MSCs, in our setting, no adipogenic lineage was successfully achieved. Surprisingly, the proliferation property of SHEDs was tremendous, reach- ing more than 20 passages. Moreover, these cells behaved differently in the presence of well-established dental materials commonly used in endodontics, such as Pro- Root-MTA, MTA-Angelus, super-EBA. Our data demonstrated that super-EBA is the most toxic substrate and proliferation was significantly inhibited. On the con- trary, the two forms of MTA, proved to be biocompatible, with the ProRoot-MTA presenting the best scaffold properties, probably due to the roughness of its surface. https://www.researchgate.net/publication/260751854_MOLECULAR_AND_CELLULAR_CHARACTERIZATION_OF_DENTAL_STEM_CELLS

• Samara, Athina (2010). The essential role of DHCR24 in brain development. Full text in Research Archive Show summary

  https://www.vizbi.org/Posters/2010/F13

• C, Organisti; Samara, Athina; Galbiati, Rita & Maggi, Roberto (2009). Seladin1/DHCR24 gene overexpression decreased migration of immature immortalised neurons. Full text in Research Archive
• Samara, Athina & Chrousos, George (2008). Studying Cholesterol production in zebrafish; the essential role of DHCR24 in brain development. Full text in Research Archive
• Samara, Athina (2008). Proteomic Analysis of Superathletes Plasma in a model of severe, sustained physical stress, reveal yet unknown mediator changes. The FEBS Journal. ISSN 1742-464X. Full text in Research Archive Show summary

  Balfoussia, E., Samara, A., Vougas, K., Parthimos, N., & Panayotou, G. (2008). Proteomic Analysis of Superathletes Plasma in a model of severe, sustained physical stress, reveal yet unknown mediator changes. FEBS Journal, 275(S1), 116.

• Samara, Athina; Galbiati, M; Cariboni, A & Maggi, R (2007). Low expression of Seladin-1/DHCR24 gene confers resistance to toxic insults in immature GnRH neurons. Journal of Endocrinological Investigation. ISSN 0391-4097. Full text in Research Archive Show summary

  ISSN 1121-1369. - 30:4(2007), pp. 67-67.

• Samara, Athina (2006). Stress and cholesterol: Seladin-1/DHCR24 as a sensor of well-being or stress in neurons and astrocytes. Full text in Research Archive Show summary

  Authors A Samara, M Galbiati, N Andrade, J Nimpf, R Maggi

• Samara, Athina; Casulari, L.A.; Pratesi, G; Piva, F & Maggi, R (2004). Action of Glucocorticoid/Progesterone Antagonist RU486 on Human Neuroblastoma Cells. Full text in Research Archive
• Cariboni, A; Zaninetti, R; Samara, Athina; Conzalez, GG; Vastagh, C & Maggi, R [Show all 8 contributors for this article] (2004). Role of THE Ebf2 transcription factor in the development of LHRH neurons. Full text in Research Archive
• Samara, Athina (2004). Characterization of DOPA-ergic properties of immortalized neuroendocrine neurons. Full text in Research Archive

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