Pregnant individuals perspectives towards receiving COVID-19 vaccination during their pregnancy: an in-depth qualitative study.

Introduction: Pregnant individuals have an increased risk of severe illness from coronavirus disease 2019 (COVID-19) infection. Vaccination is an effective strategy to prevent severe illness and complications for pregnant individuals. Pregnant individuals are often excluded from research and remain hesitant to receive vaccination against COVID-19. It is pivotal to study factors related to vaccine uptake and hesitancy among pregnant individuals. We studied barriers and facilitators for pregnant individuals choice and motivation regarding vaccination against COVID-19 during pregnancy to aid future pregnant individuals in their decision to vaccinate against various infectious agents. Methods: In this qualitative study, pregnant individuals were interviewed between October 2021 and January 2022 using a semi-structured approach. A topic list was used to explore their feelings, perceptions and ideas regarding vaccination against COVID-19 during pregnancy. Interviews were transcribed verbatim and thematic analyses was performed using MAX QDA. Results: After nine interviews, saturation was reached. Three main themes were identified that influenced pregnant individuals choice and motivation regarding vaccination: health consequences, ambiguity of information and societal motivation. Health consequences mainly concerned the effect for their offspring, and the unknown long-term effects of COVID-19 vaccination. The advice from the Dutch institute for Public Health and Environment changed from not vaccinating pregnant individuals after release of the developed vaccine, to routinely vaccinating all pregnant individuals after research data were available from the United States of America (USA). This change of policy fuelled doubt and confusion for vaccination. Arguments in favor of vaccination from the social perspective were specific behaviour rules and restrictions due to the pandemic. E.g. without vaccination people were unable to travel abroad and having to take a COVID-19 test every time entering a public place. Conclusion: Pregnant individuals need clear, unambiguous information concerning health consequences, short- and long-term, particularly for their offspring, in the decision-making process regarding COVID-19 vaccination. Additionally, the societal perspective needs to be addressed. Besides the aforementioned themes, general counselling should focus on misperceptions of vaccine safety and the role of misinformation which are also important in the non-pregnant population. This study underlines the importance of including pregnant individuals in research programs to obtain specific information targeted to their needs.

European Association of Perinatal Medicine (EAPM), European Board and College of Obstetricians and Gynaecologists (EBCOG), European Midwives Association (EMA). Joint position statement: Substandard and disrespectful care in labour - because words matter.

Substandard or disrespectful care during labour should be of serious concern for healthcare professionals, as it can affect one of the most important events in a woman's life. Substandard care refers to the use of interventions that are not considered best-practice, to the inadequate execution of interventions, to situations where best-practice interventions are withheld from patients, or there is lack of adequate informed consent. Disrespectful care refers to forms of verbal and non-verbal communication that affect patients' dignity, individuality, privacy, intimacy, or personal beliefs. There are many possible underlying causes for substandard and disrespectful care in labour, including difficulties in modifying behaviours, judgmental or paternalistic attitudes, personal interests and individualism, and a human tendency to make less arduous, less difficult, or less stressful clinical decisions. The term "obstetric violence" is used in some parts of the world to describe various forms of substandard and disrespectful care in labour, but suggests that it is mainly carried out by obstetricians and is a serious form of aggression, carried out with the intent to cause harm. We believe that this term should not be used, as it does not help to identify the underlying problem, its causes, or its correction. In addition, it is generally seen by obstetricians and other healthcare professionals as an unjust and offensive term, generating a defensive and less collaborative mindset. We reach out to all individuals and institutions sharing the common goal of improving women's experience during labour, to work together to address the underlying causes of substandard and disrespectful care, and to develop common strategies to deal with this problem, based on mutual comprehension, trust and respect.

Is the fetus fit for labor? Introducing fast-and-frugal trees (FFTrees) to simplify triage of women for STAN monitoring: An interobserver agreement comparison with traditional classification.

INTRODUCTION: It is a shortcoming of traditional cardiotocography (CTG) classification table formats that CTG traces are frequently classified differently by different users, resulting in poor interobserver agreements. A fast-and-frugal tree (FFTree) flow chart may help provide better concordance because it is straightforward and has clearly structured binary questions with understandable "yes" or "no" responses. The initial triage to determine whether a fetus is suitable for labor when utilizing fetal ECG ST analysis (STAN) is very important, since a fetus with restricted capacity to respond to hypoxic stress may not generate STAN events and therefore may become falsely negative. This study aimed to compare physiology-focused FFTree CTG interpretation with FIGO classification for assessing the suitability for STAN monitoring. MATERIAL AND METHODS: A retrospective study of 36 CTG traces with a high proportion of adverse outcomes (17/36) selected from a European multicenter study database. Eight experienced European obstetricians evaluated the initial 40 minutes of the CTG recordings and judged whether STAN was a suitable fetal surveillance method and whether intervention was indicated. The experts rated the CTGs using the FFTree and FIGO classifications at least 6 weeks apart. Interobserver agreements were calculated using proportions of agreement and Fleiss' kappa (κ). RESULTS: The proportions of agreement for "not suitable for STAN" were for FIGO 47% (95% confidence interval [CI] 42%-52%) and for FFTree 60% (95% CI 56-64), ie a significant difference; the corresponding figures for "yes, suitable" were 74% (95% CI 71-77) and 70% (95% CI 67-74). For "intervention needed" the figures were 52% (95% CI 47-56) vs 58% (95% CI 54-62) and for "expectant management" 74% (95% CI 71-77) vs 72% (95% CI 69-75). Fleiss' κ agreement on "suitability for STAN" was 0.50 (95% CI 0.44-0.56) for the FIGO classification and 0.57 (95% CI 0.51-0.63) for the FFTree classification; the corresponding figures for "intervention or expectancy" were 0.53 (95% CI 0.47-0.59) and 0.57 (95% CI 0.51-0.63). CONCLUSIONS: The proportion of agreement among expert obstetricians using the FFTree physiological approach was significantly higher compared with the traditional FIGO classification system in rejecting cases not suitable for STAN monitoring. That might be of importance to avoid false negative STAN recordings. Other agreement figures were similar. It remains to be shown whether the FFTree simplicity will benefit less experienced users and how it will work in real-world clinical scenarios.

IFNγ protects motor neurons from oxidative stress via enhanced global protein synthesis in FUS-associated amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis type 6 (ALS6) is a familial subtype of ALS linked to Fused in Sarcoma (FUS) gene mutation. FUS mutations lead to decreased global protein synthesis, but the mechanism that drives this has not been established. Here, we used ALS6 patient-derived induced pluripotent stem cells (hIPSCs) to study the effect of the ALS6 FUSR521H mutation on the translation machinery in motor neurons (MNs). We find, in agreement with findings of others, that protein synthesis is decreased in FUSR521H MNs. Furthermore, FUSR521H MNs are more sensitive to oxidative stress and display reduced expression of TGF-ß and mTORC gene pathways when stressed. Finally, we show that IFNγ treatment reduces apoptosis of FUSR521H MNs exposed to oxidative stress and partially restores the translation rates in FUSR521H MNs. Overall, these findings suggest that a functional IFNγ response is important for FUS-mediated protein synthesis, possibly by FUS nuclear translocation in ALS6.

Neurodegeneration-associated protein VAPB regulates proliferation in medulloblastoma.

VAMP (Vesicle-associated membrane protein)-associated protein B and C (VAPB) has been widely studied in neurodegenerative diseases such as ALS, but little is known about its role in cancer. Medulloblastoma is a common brain malignancy in children and arises from undifferentiated cells during neuronal development. Therefore, medulloblastoma is an interesting model to investigate the possible relationship between VAPB and tumorigenesis. Here we demonstrate that high VAPB expression in medulloblastoma correlates with decreased overall patient survival. Consistent with this clinical correlation, we find that VAPB is required for normal proliferation rates of medulloblastoma cells in vitro and in vivo. Knockout of VAPB (VAPBKO) delayed cell cycle progression. Furthermore, transcript levels of WNT-related proteins were decreased in the VAPBKO. We conclude that VAPB is required for proliferation of medulloblastoma cells, thus revealing VAPB as a potential therapeutic target for medulloblastoma treatment.

What is the future of artificial intelligence in obstetrics? A qualitative study among healthcare professionals.

OBJECTIVE: This work explores the perceptions of obstetrical clinicians about artificial intelligence (AI) in order to bridge the gap in uptake of AI between research and medical practice. Identifying potential areas where AI can contribute to clinical practice, enables AI research to align with the needs of clinicians and ultimately patients. DESIGN: Qualitative interview study. SETTING: A national study conducted in the Netherlands between November 2022 and February 2023. PARTICIPANTS: Dutch clinicians working in obstetrics with varying relevant work experience, gender and age. ANALYSIS: Thematic analysis of qualitative interview transcripts. RESULTS: Thirteen gynaecologists were interviewed about hypothetical scenarios of an implemented AI model. Thematic analysis identified two major themes: perceived usefulness and trust. Usefulness involved AI extending human brain capacity in complex pattern recognition and information processing, reducing contextual influence and saving time. Trust required validation, explainability and successful personal experience. This result shows two paradoxes: first, AI is expected to provide added value by surpassing human capabilities, yet also a need to understand the parameters and their influence on predictions for trust and adoption was expressed. Second, participants recognised the value of incorporating numerous parameters into a model, but they also believed that certain contextual factors should only be considered by humans, as it would be undesirable for AI models to use that information. CONCLUSIONS: Obstetricians' opinions on the potential value of AI highlight the need for clinician-AI researcher collaboration. Trust can be built through conventional means like randomised controlled trials and guidelines. Holistic impact metrics, such as changes in workflow, not just clinical outcomes, should guide AI model development. Further research is needed for evaluating evolving AI systems beyond traditional validation methods.

Loss of Shp1 impairs myeloid cell function and causes lethal inflammation in zebrafish larvae.

PTPN6 encodes SHP1, a protein tyrosine phosphatase with an essential role in immune cell function. SHP1 mutations are associated with neutrophilic dermatoses and emphysema in humans, which resembles the phenotype seen in motheaten mice that lack functional SHP1. To investigate the function of Shp1 in developing zebrafish embryos, we generated a ptpn6 knockout zebrafish line lacking functional Shp1. Shp1 knockout caused severe inflammation and lethality around 17 days post fertilization (dpf). During early development, the myeloid lineage was affected, resulting in a decrease in the number of neutrophils and a concomitant increase in the number of macrophages. The number of emerging hematopoietic stem and progenitor cells (HSPCs) was decreased, but due to hyperproliferation, the number of HSPCs was higher in ptpn6 mutants than in siblings at 5 dpf. Finally, the directional migration of neutrophils and macrophages was decreased in response to wounding, and fewer macrophages were recruited to the wound site. Yet, regeneration of the caudal fin fold was normal. We conclude that loss of Shp1 impaired neutrophil and macrophage function, and caused severe inflammation and lethality at the larval stage.

Autonomy-supportive decision-making in maternity care during prenatal consultations: a qualitative interaction analysis.

OBJECTIVES: The aim of this study was to identify mechanisms of autonomy-supportive consultation (ASC) that maternity care professionals use during decision-making in prenatal consultations. DESIGN: This study was a descriptive, qualitative analysis of professional-patient interactions in maternity care, using concepts and analytic procedures of conversation analysis. SETTING: The prenatal consultations took place in hospitals and midwifery practices in the Netherlands. This study was part of a larger project. For the current study, we selected prenatal consultations concerning three topics in which patients make their own choices. PARTICIPANTS: The first author invited the patient who was waiting in the waiting room. Participants were not selected a priori. MAIN OUTCOME MEASURES: The main outcome measures were mechanisms of ASC. RESULTS: We selected 20 consultations which were conducted by 20 different professionals. We found eight mechanisms in the professional-patient interaction which were categorised into three overarching themes. The first theme, 'Lightheartedness', comprises the interactional mechanisms 'minimising language' and 'humour'. The theme 'Orientation to agreement' describes how professionals and patients seem to be oriented towards demonstrating agreement and mutual understanding. The last theme, 'Offering information and options', describes the professional formally giving factual information almost completely without verbal interaction between the professional and the patient. CONCLUSION: The results of this study show that the model of ASC can be enriched by adding minimising language and humour to the mechanisms that can be used to fulfil the psychological need 'relatedness'. Second, our results show that professionals use only few mechanisms to meet the patients' psychological needs 'competence' and 'autonomy'. They mainly use information giving to meet patients' need competence. To meet patients' need for autonomy, the professionals keep all options open. This suggests that professionals could pay more attention to other mechanisms to meet patients' needs for 'competence' and 'autonomy'.

Chromosomal Instability Characterizes Pediatric Medulloblastoma but Is Not Tolerated in the Developing Cerebellum.

Medulloblastoma is a pediatric brain malignancy that consists of four transcriptional subgroups. Structural and numerical aneuploidy are common in all subgroups, although they are particularly profound in Group 3 and Group 4 medulloblastoma and in a subtype of SHH medulloblastoma termed SHHα. This suggests that chromosomal instability (CIN), the process leading to aneuploidy, is an important player in medulloblastoma pathophysiology. However, it is not known if there is ongoing CIN in medulloblastoma or if CIN affects the developing cerebellum and promotes tumor formation. To investigate this, we performed karyotyping of single medulloblastoma cells and demonstrated the presence of distinct tumor cell clones harboring unique copy number alterations, which is suggestive of ongoing CIN. We also found enrichment for processes related to DNA replication, repair, and mitosis in both SHH medulloblastoma and in the highly proliferative compartment of the presumed tumor cell lineage-of-origin, the latter also being sensitive to genotoxic stress. However, when challenging these tumor cells-of-origin with genetic lesions inducing CIN using transgenic mouse modeling, we found no evidence for large chromosomal aberrations in the cerebellum or for medulloblastoma formation. We therefore conclude that without a background of specific genetic mutations, CIN is not tolerated in the developing cerebellum in vivo and, thus, by itself is not sufficient to initiate medulloblastoma.

cGAS-STING drives the IL-6-dependent survival of chromosomally instable cancers.

Chromosomal instability (CIN) drives cancer cell evolution, metastasis and therapy resistance, and is associated with poor prognosis1. CIN leads to micronuclei that release DNA into the cytoplasm after rupture, which triggers activation of inflammatory signalling mediated by cGAS and STING2,3. These two proteins are considered to be tumour suppressors as they promote apoptosis and immunosurveillance. However, cGAS and STING are rarely inactivated in cancer4, and, although they have been implicated in metastasis5, it is not known why loss-of-function mutations do not arise in primary tumours4. Here we show that inactivation of cGAS-STING signalling selectively impairs the survival of triple-negative breast cancer cells that display CIN. CIN triggers IL-6-STAT3-mediated signalling, which depends on the cGAS-STING pathway and the non-canonical NF-κB pathway. Blockade of IL-6 signalling by tocilizumab, a clinically used drug that targets the IL-6 receptor (IL-6R), selectively impairs the growth of cultured triple-negative breast cancer cells that exhibit CIN. Moreover, outgrowth of chromosomally instable tumours is significantly delayed compared with tumours that do not display CIN. Notably, this targetable vulnerability is conserved across cancer types that express high levels of IL-6 and/or IL-6R in vitro and in vivo. Together, our work demonstrates pro-tumorigenic traits of cGAS-STING signalling and explains why the cGAS-STING pathway is rarely inactivated in primary tumours. Repurposing tocilizumab could be a strategy to treat cancers with CIN that overexpress IL-6R.

The quality of intrapartum cardiotocography in preterm labour.

OBJECTIVES: The aim of this study is to determine the quality of the foetal heart rate (FHR) recording, defined as signal loss, during preterm labour below 28 weeks gestational age (GA) and contribute to the discussion if cardiotocography (CTG) is of value for the extreme preterm foetus. METHODS: From January 2010 to December 2019 a retrospective study was conducted with data of 95 FHR recordings of singletons born between 24 and 28 weeks GA at the Amsterdam University Medical Centre, location VUmc. FHR tracings had a duration of at least 30 min and were obtained via external ultrasound mode. Data of all recordings were divided in two groups according to gestation (24-26 weeks and 26-28 weeks). Signal loss was analysed. Statistical significance was calculated by non-parametric tests and chi-square tests. The median signal loss and the proportion of cases exceeding the International Federation of Gynaecology and Obstetrics Guidelines (FIGO) threshold of 20% signal loss were calculated. RESULTS: One-third of the recordings exceeded the 20% FIGO-criterion for adequate signal quality during the first stage of labour. In the second stage, this was nearly 75%. Similarly, the median signal loss was 13% during the first and 30% during the second stage of labour (p<0.01). CONCLUSIONS: The quality of FHR monitoring in the extreme preterm foetus is inadequate in a large proportion of the foetuses, especially during the second stage. FHR monitoring is therefore controversial and should be used with caution.

Care Pathway for Foetal Joint Contractures, Foetal Akinesia Deformation Sequence, and Arthrogryposis Multiplex Congenita.

INTRODUCTION: The majority of arthrogryposis multiplex congenita (AMC) and lethal forms of AMC such as foetal akinesia deformation sequence (FADS) cases are missed prenatally. We have demonstrated the additional value of foetal motor assessment and evaluation in a multidisciplinary team for the period 2007-2016. An applied care pathway was developed for foetuses presenting with joint contracture(s) in one anatomic region (e.g., talipes equinovarus [TEV]), more than one body part with non-progressive contractures and motility (AMC) and with deterioration over time (FADS). METHODS: The multidisciplinary team of Amsterdam University Medical Centre Expertise Centre FADS and AMC developed the care pathway. Additional tools are provided including a motor assessment by ultrasound examination and a post-mortem assessment form. RESULTS: An eight-step care pathway is presented with a proposed timing for prenatal sonographic examination, genetic examinations, multidisciplinary meetings, prenatal and postnatal counselling of the parents by a specialist also treating after birth, and the follow-up of prenatal and postnatal findings with counselling for future pregnancies. DISCUSSION/CONCLUSION: The scheduled serial structural and motor sonograpahic assessment together with follow-up examinations and genetic analysis should be tailored per prenatal centre per available resources. The multidisciplinary care pathway may pave the way to increase the detection rate and diagnosis of isolated contracture(s), TEV with underlying genetic causes, and the rare phenotypes AMC/FADS and prompt treatment after birth within expertise teams.

The H3.3K27M oncohistone affects replication stress outcome and provokes genomic instability in pediatric glioma.

While comprehensive molecular profiling of histone H3.3 mutant pediatric high-grade glioma has revealed extensive dysregulation of the chromatin landscape, the exact mechanisms driving tumor formation remain poorly understood. Since H3.3 mutant gliomas also exhibit high levels of copy number alterations, we set out to address if the H3.3K27M oncohistone leads to destabilization of the genome. Hereto, we established a cell culture model allowing inducible H3.3K27M expression and observed an increase in mitotic abnormalities. We also found enhanced interaction of DNA replication factors with H3.3K27M during mitosis, indicating replication defects. Further functional analyses revealed increased genomic instability upon replication stress, as represented by mitotic bulky and ultrafine DNA bridges. This co-occurred with suboptimal 53BP1 nuclear body formation after mitosis in vitro, and in human glioma. Finally, we observed a decrease in ultrafine DNA bridges following deletion of the K27M mutant H3F3A allele in primary high-grade glioma cells. Together, our data uncover a role for H3.3 in DNA replication under stress conditions that is altered by the K27M mutation, promoting genomic instability and potentially glioma development.

A synthetic lethal screen identifies HDAC4 as a potential target in MELK overexpressing cancers.

Maternal embryonic leucine zipper kinase (MELK) is frequently overexpressed in cancer, but the role of MELK in cancer is still poorly understood. MELK was shown to have roles in many cancer-associated processes including tumor growth, chemotherapy resistance, and tumor recurrence. To determine whether the frequent overexpression of MELK can be exploited in therapy, we performed a high-throughput screen using a library of Saccharomyces cerevisiae mutants to identify genes whose functions become essential when MELK is overexpressed. We identified two such genes: LAG2 and HDA3. LAG2 encodes an inhibitor of the Skp, Cullin, F-box containing (SCF) ubiquitin-ligase complex, while HDA3 encodes a subunit of the HDA1 histone deacetylase complex. We find that one of these synthetic lethal interactions is conserved in mammalian cells, as inhibition of a human homolog of HDA3 (Histone Deacetylase 4, HDAC4) is synthetically toxic in MELK overexpression cells. Altogether, our work identified a novel potential drug target for tumors that overexpress MELK.

Thermal Proteome Profiling in Zebrafish Reveals Effects of Napabucasin on Retinoic Acid Metabolism.

Thermal proteome profiling (TPP) allows for the unbiased detection of drug-target protein engagements in vivo. Traditionally, 1 cell type is used for TPP studies, with the risk of missing important differentially expressed target proteins. The use of whole organisms would circumvent this problem. Zebrafish embryos are amenable to such an approach. Here, we used TPP on whole zebrafish embryo lysate to identify protein targets of napabucasin, a compound that may affect signal transducer and activator of transcription 3 (Stat3) signaling through an ill-understood mechanism. In zebrafish embryos, napabucasin induced developmental defects consistent with inhibition of Stat3 signaling. TPP profiling showed no distinct shift in Stat3 upon napabucasin treatment, but effects were detected on the oxidoreductase, Pora, which might explain effects on Stat3 signaling. Interestingly, thermal stability of several aldehyde dehydrogenases was affected. Moreover, napabucasin activated aldehyde dehydrogenase enzymatic activity in vitro. Aldehyde dehydrogenases have crucial roles in retinoic acid metabolism, and functionally, we validated napabucasin-mediated activation of the retinoic acid pathway in zebrafish in vivo. We conclude that TPP profiling in whole zebrafish embryo lysate is feasible and facilitates direct correlation of in vivo effects of small molecule drugs with their protein targets.

Acute systemic loss of Mad2 leads to intestinal atrophy in adult mice.

Chromosomal instability (CIN) is a hallmark of cancer, leading to aneuploid cells. To study the role that CIN plays in tumor evolution, several mouse models have been engineered over the last 2 decades. These models have unequivocally shown that systemic high-grade CIN is embryonic lethal. We and others have previously shown that embryonic lethality can be circumvented by provoking CIN in a tissue-specific fashion. In this study, we provoke systemic high-grade CIN in adult mice as an alternative to circumvent embryonic lethality. For this, we disrupt the spindle assembly checkpoint (SAC) by alleviating Mad2 or truncating Mps1, both essential genes for SAC functioning, with or without p53 inactivation. We find that disruption of the SAC leads to rapid villous atrophy, atypia and apoptosis of the epithelia of the jejunum and ileum, substantial weight loss, and death within 2-3 weeks after the start of the CIN insult. Despite this severe intestinal phenotype, most other tissues are unaffected, except for minor abnormalities in spleen, presumably due to the lower proliferation rate in these tissues. We conclude that high-grade CIN in vivo in adult mice is most toxic to the high cell turnover intestinal epithelia.

Intrapartum non-invasive electrophysiological monitoring: A prospective observational study.

INTRODUCTION: Doppler ultrasound cardiotocography is a non-invasive alternative that, despite its poor specificity, is often first choice for intrapartum monitoring. Doppler ultrasound suffers from signal loss due to fetal movements and is negatively correlated with maternal body mass index (BMI). Reported accuracy of fetal heart rate monitoring by Doppler ultrasound varies between 10.6 and 14.3 bpm and reliability between 62.4% and 73%. The fetal scalp electrode (FSE) is considered the reference standard for fetal monitoring but can only be applied after membranes have ruptured with sufficient cervical dilatation and is sometimes contra-indicated. A non-invasive alternative that overcomes the shortcomings of Doppler ultrasound, providing reliable information on fetal heart rate, could be the answer. Non-invasive fetal electrocardiography (NI-fECG) uses a wireless electrode patch on the maternal abdomen to obtain both fetal and maternal heart rate signals as well as an electrohysterogram. We aimed to validate a wireless NI-fECG device for intrapartum monitoring in term singleton pregnancies, by comparison with the FSE. MATERIAL AND METHODS: We performed a multicenter cross-sectional observational study at labor wards of 6 hospitals located in the Netherlands, Belgium, and Spain. Laboring women with a healthy singleton fetus in cephalic presentation and gestational age between 36 and 42 weeks were included. Participants received an abdominal electrode patch and FSE after written informed consent. Accuracy, reliability, and success rate of fetal heart rate readings were determined, using FSE as reference standard. Analysis was performed for the total population and measurement period as well as separated by labor stage and BMI class (≤30 and >30 kg/m2 ). RESULTS: We included a total of 125 women. Simultaneous registrations with NI-fECG and FSE were available in 103 women. Overall accuracy is -1.46 bpm and overall reliability 86.84%. Overall success rate of the NI-fECG is around 90% for the total population as well as for both BMI subgroups. Success rate dropped to 63% during second stage of labor, similar results are found when looking at the separate BMI groups. CONCLUSIONS: Performance measures of the NI-fECG device are good in the overall group and the separate BMI groups. Compared with Doppler ultrasound performance measures from the literature, NI-fECG is a more accurate alternative. Especially, when women have a higher BMI, NI-fECG performs well, resembling FSE performance measures.

Altering microtubule dynamics is synergistically toxic with spindle assembly checkpoint inhibition.

Chromosomal instability (CIN) and aneuploidy are hallmarks of cancer. As most cancers are aneuploid, targeting aneuploidy or CIN may be an effective way to target a broad spectrum of cancers. Here, we perform two small molecule compound screens to identify drugs that selectively target cells that are aneuploid or exhibit a CIN phenotype. We find that aneuploid cells are much more sensitive to the energy metabolism regulating drug ZLN005 than their euploid counterparts. Furthermore, cells with an ongoing CIN phenotype, induced by spindle assembly checkpoint (SAC) alleviation, are significantly more sensitive to the Src kinase inhibitor SKI606. We show that inhibiting Src kinase increases microtubule polymerization rates and, more generally, that deregulating microtubule polymerization rates is particularly toxic to cells with a defective SAC. Our findings, therefore, suggest that tumors with a dysfunctional SAC are particularly sensitive to microtubule poisons and, vice versa, that compounds alleviating the SAC provide a powerful means to treat tumors with deregulated microtubule dynamics.

Digital vs face-to-face information provision in patient counselling for prenatal screening: A noninferiority randomized controlled trial.

OBJECTIVE: To evaluate face-to-face information provision in patient counselling for prenatal screening compared with two forms of digital information provision, namely, noninteractive instructional video or interactive video. METHOD: We performed a prospective, noninferiority, cluster-randomized controlled trial comparing face-to-face (usual care) with two forms of digital information provision (intervention) in counselling for prenatal screening. This study was performed in the Amsterdam UMC, the Netherlands, in 2017, and included women in the first trimester of pregnancy. Main outcomes were knowledge gained by the patient and counselling duration. We performed a noninferiority analysis. RESULTS: One hundred forty-one women were included, randomized, and analysed. The baseline characteristics were comparable. The intervention group was noninferior compared with the control group regarding the level of satisfaction. The knowledge grade difference was higher after using intervention, and the duration was significantly longer in the face-to-face group at 23 minutes versus 16 minutes. The addition of interaction with the video made no difference in any of the outcomes. CONCLUSION: Adding an instructional video to patient counselling is of added value to improve patient's knowledge and shorten time consumption of the counsellor, therefore possibly saving costs. But this form of counselling maintains the same level of satisfaction.