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Vaccine Jan 2024To systematically review immunogenicity and safety data of maternal group B streptococcal (GBS) vaccines in published clinical trials until July 2023. (Review)
Review
PURPOSE
To systematically review immunogenicity and safety data of maternal group B streptococcal (GBS) vaccines in published clinical trials until July 2023.
METHODS
EMBASE, MEDLINE, Cochrane Library and clinicaltrial.gov. databases were searched for clinical studies that reported immunogenicity and/or safety of GBS vaccine in non-pregnant adults, pregnant women and infants between 1st of January 1996 to 31st of July 2023. Pairs of reviewers independently selected, data extracted, and assessed the risk of bias of the studies. Discrepancies were resolved by consensus. (PROSPERO CRD42020185213).
RESULTS
We retrieved 1472 records from the literature search; 20 studies and 6 sub-studies were included, involving 4440 non-pregnant participants and 1325 pregnant women with their newborns. There was a significantly higher IgG Geometric Mean Concentration (GMC) and IgG placental transfer ratios in vaccinated compared to placebo groups, with peak response 4-8 weeks after vaccination. Placental transfer ratio varied from 0.4 to 1.4 across five studies. The different clinical trials used different assays that limited direct comparison. There were no significant differences in the risk of serious adverse events (adjusted OR 0.73; 95 % CI 0.49-1.07), serious adverse events leading to withdrawal (adjusted OR 0.44; 95 % CI 0.13-1.51), and systemic illness or fever (adjusted OR 1.05; 95 % CI 0.26-4.19) between the vaccine and placebo groups.
CONCLUSIONS
The published clinical trials show significant IgG GMC response in subjects receiving the conjugated capsular polysaccharide and surface subunit protein vaccines compared to placebo. In current clinical trials of experimental GBS maternal vaccines, there have been no observed serious adverse events of special interest directly linked to vaccination.
Topics: Infant; Adult; Humans; Infant, Newborn; Female; Pregnancy; Placenta; Vaccines; Vaccination; Streptococcus agalactiae; Immunoglobulin G; Immunogenicity, Vaccine
PubMed: 38072754
DOI: 10.1016/j.vaccine.2023.11.056 -
Cureus May 2024Microplastic (MP) pollution is a growing global concern because of its potential to impair human health, particularly with regard to fetal development. However, the... (Review)
Review
Microplastic (MP) pollution is a growing global concern because of its potential to impair human health, particularly with regard to fetal development. However, the origins of prenatal MP exposure and its effects on fetal development have not been well studied. This study aimed to provide a systematic review of the literature regarding the impact of microplastics on pregnancy and fetal development. PubMed, Embase, ScienceDirect, Web of Science, Scopus, and Google Scholar were searched from 2010 until March 2024. Original publications exploring the impact of microplastics on pregnancy and fetal development were included in the study. After selecting papers, two independent reviewers extracted data regarding study characteristics, microplastics identified, and reproductive impacts. The quality of studies was assessed using the Critical Appraisal Checklists for Studies created by the Joanna Briggs Institute (JBI). Twelve studies, including 234 subjects, were selected from a total of 2,809 citations for the final qualitative analysis. Articles were published between 2021 and 2024, and most were conducted in China. The results of the included studies confirmed the existence of microplastics with varying sizes (2.1 to 100 micrometers) in the placenta and the fetal body. Studies revealed correlations between lifestyle choices and the presence of microplastics in the placenta. They also reported correlations between the level of microplastics and diminished microbiome diversity, reduced birthweights, affected gestational age, and fetal growth and development. Microplastics may be detrimental to a developing fetus during pregnancy. Nonetheless, more thorough research is required to comprehend the impact of microplastic exposure on pregnancy and fetal development.
PubMed: 38903343
DOI: 10.7759/cureus.60712 -
Ultrasound in Obstetrics & Gynecology :... Jan 2024Type-III vasa previa (VP) is a rare form of VP, not necessarily associated with other placental or vascular anomalies, in which aberrant vessels run from the placenta to... (Review)
Review
OBJECTIVE
Type-III vasa previa (VP) is a rare form of VP, not necessarily associated with other placental or vascular anomalies, in which aberrant vessels run from the placenta to the amniotic membranes, near the internal cervical os, before returning to the placenta. Early diagnosis of Type-III VP is important but technically challenging. The objective of this study was to gather the current available evidence on the perinatal diagnosis and outcome of Type-III VP.
METHODS
A systematic review of the literature on the perinatal diagnosis of atypical Type-III VP was carried out in PubMed, MEDLINE and EMBASE accordingto PRISMA guidelines from inception to March 2023. Data extraction and tabulation were performed by two operators and checked by a third senior author. The quality of the included studies was evaluated using the National Institutes of Health tool for the quality assessment of case-series studies. Our local ultrasound database was searched for previously unreported recent cases. Characteristics of prenatally and postnatally diagnosed Type-III VP, including clinical features and perinatal outcomes, were summarized using descriptive statistics.
RESULTS
Eighteen cases of Type-III VP were included, of which 16 were diagnosed prenatally (14 cases were retrieved from 10 publications and two were unpublished cases from our center) and two were diagnosed postnatally (retrieved from two publications). All prenatal cases were diagnosed on transvaginal ultrasound at a mean gestational age of 29 weeks (median, 31 weeks; range, 19-38 weeks). Conception was achieved with in-vitro fertilization in 4/16 (25.0%) cases. There were no prenatal symptoms in 15/18 (83.3%) cases, while in two (11.1%) cases there was vaginal bleeding and in one (5.6%) preterm labor occurred. In 15/18 (83.3%) cases, at least one placental abnormality was observed, including low-lying insertion (9/17), succenturiate or accessory lobe (1/17), velamentous cord insertion (3/18) and marginal insertion (9/18). All prenatally diagnosed cases were liveborn and were delivered by Cesarean section before rupture of membranes at a median gestational age of 35 weeks (range, 32-38 weeks) without neonatal complications. Emergency Cesarean section was performed in 2/16 (12.5%) cases with a prenatal diagnosis and 1/2 (50.0%) cases with a postnatal diagnosis (P = 0.179). Among those with data available, an Apgar score of ≤ 7 was observed in the prenatally vs postnatally diagnosed group in 5/13 vs 1/1 cases, respectively, at the 1-min evaluation and 3/13 vs 1/1 cases, respectively, at the 5-min evaluation.
CONCLUSIONS
The prenatal diagnosis of Type-III VP is challenging, with few cases reported in the literature; however, it is crucial for minimizing the risk of adverse outcome by enabling early-term elective Cesarean delivery prior to rupture of membranes. Given that clinical manifestations and risk factors are non-specific, and that Type-III VP cannot be excluded when there is a normal cord insertion or a singular placental mass, systematic screening by transvaginal ultrasound in the general pregnant population is recommended, particularly in those with a low-lying or morphologically abnormal placenta and those who conceived using assisted reproductive technology. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Cesarean Section; Placenta; Placenta Diseases; Prenatal Diagnosis; Ultrasonography, Prenatal; Vasa Previa
PubMed: 37470694
DOI: 10.1002/uog.26315 -
The Cochrane Database of Systematic... Jul 2023Fetal growth restriction (FGR) is a condition of poor growth of the fetus in utero. One of the causes of FGR is placental insufficiency. Severe early-onset FGR at < 32... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fetal growth restriction (FGR) is a condition of poor growth of the fetus in utero. One of the causes of FGR is placental insufficiency. Severe early-onset FGR at < 32 weeks of gestation occurs in an estimated 0.4% of pregnancies. This extreme phenotype is associated with a high risk of fetal death, neonatal mortality, and neonatal morbidity. Currently, there is no causal treatment, and management is focused on indicated preterm birth to prevent fetal death. Interest has risen in interventions that aim to improve placental function by administration of pharmacological agents affecting the nitric oxide pathway causing vasodilatation.
OBJECTIVES
The objective of this systematic review and aggregate data meta-analysis is to assess the beneficial and harmful effects of interventions affecting the nitric oxide pathway compared with placebo, no therapy, or different drugs affecting this pathway against each other, in pregnant women with severe early-onset FGR.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (16 July 2022), and reference lists of retrieved studies.
SELECTION CRITERIA
We considered all randomised controlled comparisons of interventions affecting the nitric oxide pathway compared with placebo, no therapy, or another drug affecting this pathway in pregnant women with severe early-onset FGR of placental origin, for inclusion in this review.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane Pregnancy and Childbirth methods for data collection and analysis.
MAIN RESULTS
We included a total of eight studies (679 women) in this review, all of which contributed to the data and analysis. The identified studies report on five different comparisons: sildenafil compared with placebo or no therapy, tadalafil compared with placebo or no therapy, L-arginine compared with placebo or no therapy, nitroglycerin compared with placebo or no therapy and sildenafil compared with nitroglycerin. The risk of bias of included studies was judged as low or unclear. In two studies the intervention was not blinded. The certainty of evidence for our primary outcomes was judged as moderate for the intervention sildenafil and low for tadalafil and nitroglycerine (due to low number of participants and low number of events). For the intervention L-arginine, our primary outcomes were not reported. Sildenafil citrate compared to placebo or no therapy (5 studies, 516 women) Five studies (Canada, Australia and New Zealand, the Netherlands, the UK and Brazil) involving 516 pregnant women with FGR were included. We assessed the certainty of the evidence as moderate. Compared with placebo or no therapy, sildenafil probably has little or no effect on all-cause mortality (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.80 to 1.27, 5 studies, 516 women); may reduce fetal mortality (RR 0.82, 95% CI 0.60 to 1.12, 5 studies, 516 women), and increase neonatal mortality (RR 1.45, 95% CI 0.90 to 2.33, 5 studies, 397 women), although the results are uncertain for fetal and neonatal mortality as 95% confidence intervals are wide crossing the line of no effect. Tadalafil compared with placebo or no therapy (1 study, 87 women) One study (Japan) involving 87 pregnant women with FGR was included. We assessed the certainty of the evidence as low. Compared with placebo or no therapy, tadalafil may have little or no effect on all-cause mortality (risk ratio 0.20, 95% CI 0.02 to 1.60, one study, 87 women); fetal mortality (RR 0.11, 95% CI 0.01 to 1.96, one study, 87 women); and neonatal mortality (RR 0.89, 95% CI 0.06 to 13.70, one study, 83 women). L-Arginine compared with placebo or no therapy (1 study, 43 women) One study (France) involving 43 pregnant women with FGR was included. This study did not assess our primary outcomes. Nitroglycerin compared to placebo or no therapy (1 studies, 23 women) One study (Brazil) involving 23 pregnant women with FGR was included. We assessed the certainty of the evidence as low. The effect on the primary outcomes is not estimable due to no events in women participating in both groups. Sildenafil citrate compared to nitroglycerin (1 study, 23 women) One study (Brazil) involving 23 pregnant women with FGR was included. We assessed the certainty of the evidence as low. The effect on the primary outcomes is not estimable due to no events in women participating in both groups.
AUTHORS' CONCLUSIONS
Interventions affecting the nitric oxide pathway probably do not seem to influence all-cause (fetal and neonatal) mortality in pregnant women carrying a baby with FGR, although more evidence is needed. The certainty of this evidence is moderate for sildenafil and low for tadalafil and nitroglycerin. For sildenafil a fair amount of data are available from randomised clinical trials, but with low numbers of participants. Therefore, the certainty of evidence is moderate. For the other interventions investigated in this review there are insufficient data, meaning we do not know whether these interventions improve perinatal and maternal outcomes in pregnant women with FGR.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Fetal Growth Retardation; Sildenafil Citrate; Nitric Oxide; Premature Birth; Nitroglycerin; Tadalafil; Placenta; Fetal Death
PubMed: 37428872
DOI: 10.1002/14651858.CD014498 -
Psychoneuroendocrinology Aug 2024The placenta acts as a buffer to regulate the degree of fetal exposure to maternal cortisol through the 11-Beta Hydroxysteroid Dehydrogenase isoenzyme type 2 (11-β... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The placenta acts as a buffer to regulate the degree of fetal exposure to maternal cortisol through the 11-Beta Hydroxysteroid Dehydrogenase isoenzyme type 2 (11-β HSD2) enzyme. We conducted a systematic review and meta-analysis to assess the effect of prenatal psychological distress (PPD) on placental 11-β HSD2 gene expression and explore the related mechanistic pathways involved in fetal neurodevelopment.
METHODS
We searched PubMed, Embase, Scopus, APA PsycInfo®, and ProQuest Dissertations for observational studies assessing the association between PPD and 11-β HSD2 expression in human placentas. Adjusted regression coefficients (β) and corresponding 95% confidence intervals (CIs) were pooled based on three contextual PPD exposure groups: prenatal depression, anxiety symptoms, and perceived stress.
RESULTS
Of 3159 retrieved records, sixteen longitudinal studies involving 1869 participants across seven countries were included. Overall, exposure to PPD disorders showed weak negative associations with the placental 11-β HSD2 gene expression as follows: prenatal depression (β -0.01, 95% CI 0.05-0.02, I2=0%), anxiety symptoms (β -0.02, 95% CI 0.06-0.01, I2=0%), and perceived stress (β -0.01 95% CI 0.06-0.04, I2=62.8%). Third-trimester PPD exposure was more frequently associated with lower placental 11-β HSD2 levels. PPD and placental 11-β HSD2 were associated with changes in cortisol reactivity and the development of adverse health outcomes in mothers and children. Female-offspring were more vulnerable to PPD exposures.
CONCLUSION
The study presents evidence of a modest role of prenatal psychological distress in regulating placental 11-β HSD2 gene expression. Future prospective cohorts utilizing larger sample sizes or advanced statistical methods to enhance the detection of small effect sizes should be planned. Additionally, controlling for key predictors such as the mother's ethnicity, trimester of PPD exposure, mode of delivery, and infant sex is crucial for valid exploration of PPD effects on fetal programming.
Topics: Humans; Pregnancy; 11-beta-Hydroxysteroid Dehydrogenase Type 2; Female; Placenta; Stress, Psychological; Pregnancy Complications; Psychological Distress; Depression; Gene Expression; Anxiety; Hydrocortisone; Prenatal Exposure Delayed Effects
PubMed: 38677195
DOI: 10.1016/j.psyneuen.2024.107060 -
Ultrasound in Obstetrics & Gynecology :... Nov 2023To identify all prediction models for fetal and neonatal outcomes in pregnancies with preterm manifestations of placental insufficiency (gestational hypertension,... (Review)
Review
OBJECTIVES
To identify all prediction models for fetal and neonatal outcomes in pregnancies with preterm manifestations of placental insufficiency (gestational hypertension, pre-eclampsia, HELLP syndrome or fetal growth restriction with its onset before 37 weeks' gestation) and to assess the quality of the models and their performance on external validation.
METHODS
A systematic literature search was performed in PubMed, Web of Science and EMBASE. Studies describing prediction models for fetal/neonatal mortality or significant neonatal morbidity in patients with preterm placental insufficiency disorders were included. Data extraction was performed using the CHARMS checklist. Risk of bias was assessed using PROBAST. Literature selection and data extraction were performed by two researchers independently.
RESULTS
Our literature search yielded 22 491 unique publications. Fourteen were included after full-text screening of 218 articles that remained after initial exclusions. The studies derived a total of 41 prediction models, including four models in the setting of pre-eclampsia or HELLP, two models in the setting of fetal growth restriction and/or pre-eclampsia and 35 models in the setting of fetal growth restriction. None of the models was validated externally, and internal validation was performed in only two studies. The final models contained mainly ultrasound (Doppler) markers as predictors of fetal/neonatal mortality and neonatal morbidity. Discriminative properties were reported for 27/41 models (c-statistic between 0.6 and 0.9). Only two studies presented a calibration plot. The risk of bias was assessed as unclear in one model and high for all other models, mainly owing to the use of inappropriate statistical methods.
CONCLUSIONS
We identified 41 prediction models for fetal and neonatal outcomes in pregnancies with preterm manifestations of placental insufficiency. All models were considered to be of low methodological quality, apart from one that had unclear methodological quality. Higher-quality models and external validation studies are needed to inform clinical decision-making based on prediction models. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Infant, Newborn; Pregnancy; Humans; Female; Fetal Growth Retardation; Pre-Eclampsia; Placental Insufficiency; Placenta; Prenatal Care
PubMed: 37161550
DOI: 10.1002/uog.26245 -
International Journal of Reproductive... Nov 2023Pregnancy with assisted reproductive technology (ART) is accompanied by fetal and maternal outcomes. This systematic review aimed to assess the relationship between... (Review)
Review
Pregnancy with assisted reproductive technology (ART) is accompanied by fetal and maternal outcomes. This systematic review aimed to assess the relationship between ART and maternal outcomes. In this systematic review, the electronic databases, including PubMed, MEDLINE, Web of Science, Scopus, Science Direct, Cochrane Library, Google Scholar, Magiran, Irandoc, and Scientific Information Database were searched for maternal outcomes reported from 2010-2021. The Newcastle-Ottawa Scale for cohort studies was used to assess the methodological quality of studies. A total of 3362 studies were identified by searching the databases. After screening abstracts and full-text reviews, 19 studies assessing the singleton pregnancy-related complications of in vitro fertilization/intracytoplasmic sperm injection were included in the study. The results demonstrated that singleton pregnancies conceived through ART had higher risks of pregnancy-related complications and adverse maternal outcomes, such as vaginal bleeding, cesarean section, hypertension induced by pregnancy, pre-eclampsia, placenta previa, and premature membrane rupture than those conceived naturally. In conclusion, an increased risk of adverse obstetric outcomes was observed in singleton pregnancies conceived by ART. Therefore, obstetricians should consider these pregnancies as high-risk cases and should pay special attention to their pregnancy process.
PubMed: 38292514
DOI: 10.18502/ijrm.v21i11.14651 -
Children (Basel, Switzerland) Aug 2023Transient hypogammaglobulinemia of infancy (THI) is a primary immunodeficiency caused by a temporary decline in serum immunoglobulin G (IgG) levels greater than two... (Review)
Review
Transient hypogammaglobulinemia of infancy (THI) is a primary immunodeficiency caused by a temporary decline in serum immunoglobulin G (IgG) levels greater than two standard deviations below the mean age-specific reference values in infants between 5 and 24 months of age. Preterm infants are particularly susceptible to THI, as IgG is only transferred across the placenta from mother to infant during the third trimester of pregnancy. This study aimed to conduct a systematic review of the diagnostic criteria for transient hypogammaglobulinemia of infancy. Systematic review: Three electronic databases (PubMed, MEDLINE, and Google Scholar) were manually searched from September 2021 to April 2022. Abstracts were screened to assess their fit to the inclusion criteria. Data were extracted from the selected studies using an adapted extraction tool (Cochrane). The studies were then assessed for bias using an assessment tool adapted from Cochrane. Of the 215 identified articles, 16 were eligible for examining the diagnostic criteria of THI. These studies were also assessed for bias in the six domains. A total of five studies (31%) had a low risk of bias, while four studies (25%) had a high risk of bias, and bias in the case of seven studies (44%) was unclear. We conclude that THI is only definitively diagnosed after abnormal IgG levels normalise. Hence, THI is not a benign condition, and monitoring for subsequent recurrent infections must be conducted. The diagnostic criteria should also include vaccine and isohaemagglutinin responses to differentiate THI from other immunological disorders in infants.
PubMed: 37628357
DOI: 10.3390/children10081358 -
American Journal of Obstetrics &... May 2024This study aimed to examine the association between cervical length and the risk of adverse outcomes in placenta previa pregnancies. In addition, the diagnostic accuracy... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to examine the association between cervical length and the risk of adverse outcomes in placenta previa pregnancies. In addition, the diagnostic accuracy of cervical length in predicting emergency cesarean delivery due to hemorrhage was evaluated.
DATA SOURCES
PubMed, Web of Science, and Embase were systematically searched up to January 21, 2023.
STUDY ELIGIBILITY CRITERIA
Observational studies investigating the relationship between cervical length and maternal adverse outcomes in patients with placenta previa were considered eligible. The primary outcome was the diagnostic accuracy of cervical length measured at 28 to 34 weeks of gestation for the prediction of emergency cesarean delivery due to hemorrhage. The secondary outcomes were the probability of antenatal bleeding, preterm birth (both iatrogenic and spontaneous), and postpartum hemorrhage >2000 mL. Insufficient data were available on the transfusion procedure in cases where the cervical length was <30 mm.
METHODS
For prognostic analysis, the random-effects model was used to pool the odds ratios and the corresponding 95% confidence intervals. For the diagnostic part, we used a summary receiver-operating characteristic curve, pooled sensitivities and specificities, area under the curve, and summary likelihood ratios.
RESULTS
A total of 13 studies presenting data on 1462 pregnancies with placenta previa were included. Cervical length ≤30 mm at 28 to 34 weeks of gestation had a sensitivity of 61% (95% confidence interval, 43-77), specificity of 83% (95% confidence interval, 76-88), and area under the curve of 0.83 (95% confidence interval, 0.80-0.86) for the prediction of emergency cesarean delivery. Furthermore, cervical length ≤30 mm was associated with antenatal bleeding (odds ratio, 3.62; 95% confidence interval, 2.09-6.26; P<.001; I=54.8%), preterm birth (odds ratio, 8.46; 95% confidence interval, 3.05-23.44; P<.001; I=83.6%), and postpartum hemorrhage (odds ratio, 6.89; 95% confidence interval, 4.51-10.53; P<.001; I=0.00%).
CONCLUSION
Short cervical length (≤30 mm) measured at 28 to 34 weeks of gestation can assist in predicting the risk of emergency cesarean delivery due to hemorrhage in pregnancies with placenta previa. Furthermore, short cervical length is significantly associated with the risk of antenatal bleeding, preterm birth, and postpartum hemorrhage in pregnancies with placenta previa.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Placenta Previa; Premature Birth; Postpartum Hemorrhage; Cesarean Section; ROC Curve
PubMed: 37778698
DOI: 10.1016/j.ajogmf.2023.101172 -
Sexual Medicine Reviews Dec 2023Erectile dysfunction (ED) is a common condition that negatively affects men's quality of life. It can have various causes, including psychological, vascular, and...
INTRODUCTION
Erectile dysfunction (ED) is a common condition that negatively affects men's quality of life. It can have various causes, including psychological, vascular, and neurologic factors. Existing treatments for ED mainly focus on symptom relief rather than addressing the underlying cause. Stem cells (SCs) have shown potential as a therapeutic approach for ED due to their anti-inflammatory properties.
OBJECTIVES
This systematic review aims to assess the current status of trials and determine the potential impact of SCs on male sexual health.
METHODS
A comprehensive search strategy was employed to gather relevant articles from 6 electronic databases. The search included articles published until March 2023. The reference lists of articles were manually reviewed to identify additional studies of relevance. The eligibility criteria for inclusion in the analysis focused on clinical trials involving humans that evaluated the safety and efficacy of SC therapy for ED. Exclusion criteria encompassed case reports, case series, abstracts, reviews, and editorials, as well as studies involving animals or SC derivatives. Data extraction was performed via a standardized form with a focus on erectile outcomes.
RESULTS
A total of 2847 articles were initially identified; 18 were included in the final analysis. These studies involved 373 patients with ED and various underlying medical conditions. Multiple types of SC were utilized in the treatment of ED: mesenchymal SCs, placental matrix-derived mesenchymal SCs, mesenchymal SC-derived exosomes, adipose-derived SCs, bone marrow-derived mononuclear SCs, and umbilical cord blood SCs.
CONCLUSION
SC therapy shows promise as an innovative and safe treatment for organic ED. However, the lack of standardized techniques and controlled groups in many studies hampers the ability to evaluate and compare trials.
Topics: Female; Pregnancy; Animals; Male; Humans; Erectile Dysfunction; Quality of Life; Placenta; Stem Cell Transplantation; Penile Erection
PubMed: 37758225
DOI: 10.1093/sxmrev/qead040