Preterm birth is a public health concern globally. In low- and middle-income countries, like Ethiopia, preterm birth is under reported and underestimated. Therefore, this systematic review and meta-analysis assessed the pooled prevalence and associated risk factors for preterm birth in Ethiopia.In this review the databases used were PubMed, Google scholar, EMBASE, HINARI and African journal online. Publication bias was checked using a funnel plot and Eggers test.A total of 30 studies were included in this systematic review and meta-analysis. The overall pooled prevalence of preterm birth in Ethiopia was 11.4% . On pooled analysis, preterm birth was associated with pregnancy-induced hypertension being HIV-positive, premature rupture of membrane, rural residence, the mother having a history of abortion, multiple pregnancies, and anemia during pregnancy.The national prevalence of preterm birth in Ethiopia was low. Early identifying those pregnant women who are at risk of the above determinants and proving quality healthcare and counsel them how to prevent preterm births, which decrease the rate of preterm birth and its consequences. So, both governmental and non-governmental health sectors work on the minimization of these risk factors. According to WHO definition, preterm birth is a birth that occurs before 37 completed weeks of conception or fewer than 259 days from the first date of a woman's last menstrual period for singleton pregnancy. Based on gestational age, it is classified as extremely preterm (<28 weeks), very preterm (28 to < 32 wks.), and moderate to (32 to < 34 weeks) and late preterm (34 to 37 weeks). In other ways on the basis of birth weight, preterm can be classified as low birth weight (1500gm to <2500gm), very low birth weight (<1500 to 1000gm) and extremely very low birth (<1000gm). In addition, on the basis of initiation of labor preterm birth can be categorized into two spontaneous or induced. Spontaneous preterm birth occurs when a pregnant mother goes into labor without the use of drugs or techniques to induce labor before 37 weeks of gestation. Induced preterm birth is a delivery involving labor induction, where drugs or manual techniques are used to initiate the process of labor before 37 weeks of gestation for maternal and fetal indicationsGlobally, different studies reported that more than 15 million (11%) babies are estimated to be PTB each year and about 12 million (more than 81%) of these PTB occur in Sub-Sahara Africa and South Asia. Besides, the burden of Pre-term birth ranges between 5% and 18% in the world. In the lower and middle -income countries, on average, 12% of babies are born premature compared with 9% in higher-income countriesStudies conducted across the world identified risk factors associated with preterm birth, such as having a history preterm birth, short cervical length, smoking, chronic cough, Short inter-pregnancies interval, anemia, urinary tract infection, certain pregnancy-related complications , lack of antenatal care follow-ups, lifestyle factors ) guidelineWe have searched the following finding Items for this review (PRISMA) which was strictly followed by systematic review and meta-analysis guidelines. The databases used were PubMed, Google scholar, EMBASE, HINARI AJOL . There were no restriction articles based on publication period. Searching engines were based on adapted PICO principles to search through the above-listed databases to access all the essential articles. To conduct a search of the literature databases, we have used Boolean logic, connectors “OR,” “AND” in combinationsCross-sectional, cohort, and case-control studies were included. Articles included in this review were reported the prevalence, or magnitude and associated factors, or determining factors among mothers who were giving birth. Articles were included that were published only in English language literature, published from 2009–2020. Articles without full text and inaccessibility of abstract, commentaries, letters, duplicated studies, anonymous reports, and editorials were excluded.Findings from all databases were exported to Microsoft Excel spreadsheet. Two reviewers  independently extracted the data and reviewed the screened articles. Differences were recon reviewers . Finally, the consensus was reached through a discussion between reviewers. Newcastle-Ottawa Quality Assessment Scale (NOS) for cross-sectional, cohort, and case-control studies were used to assess the methodological quality of a study and to determine the extent to which a study addressed the possibility of bias in its design, conduct, and analysis. All reviewers independently assessed the articles which were included in the review. The average mean score for the cross-sectional studies was 8.91 out of 11, for case-control studies 10.66 out of 22 and Cohort study 14 out of 22. No study that scored below the cutoff point was excluded from the review. All of the included articles scored (NOS) 7 and more can be considered a “good” study and have a low risk of bias for cross-sectional studies and 9 or more scores for case-control and cohort chosen to indicate a high standard for comparative observational studies, stated . The last search date was Aprl 15,2020.Two independent reviewers  extracted data by using structured data extraction form. The name of the first author, year of study, year of publication, study of region, study area, study design, sample size, the prevalence rate, determinants of preterm birth, and AOR (95% CI) were extracted.The measurement outcome of this study had two main outcome variables. The prevalence of preterm birth was the primary outcome of the study, whereas associated factors/determinant for preterm birth were the second outcome variable. The odds ratio was calculated for the common factors of the reported studies. The most common associated factors included in this systematic review and meta-analysis were pregnancy-induced hypertension, being HIV-positive, premature rupture of membrane, rural residence, mother having a history of abortion, anemia during pregnancy and multiple pregnancy.Heterogeneity was checked using I2 and its corresponding p-value. A value of 25%, 50%, and 75% was used to state the heterogeneity test as low, moderate and marked heterogeneity, respectivelyStata 11 software with forest plots were used to report the estimated pooled prevalence and determinants of each study with the 95% confidence interval (CI). We have conducted subgroup analysis by sample size of participants and year of publication of study due to marked heterogeneity I2 =96.3%. We have also conducted Trim fill and sensitivity analysis to see the effects of a single study on the prevalence of preterm birth. Finally, the odds ratio with 95% CI of pregnancy induced hypertension, being HIV-positive, premature rupture of membrane, rural residence, mother having a history of abortion, anemia during pregnancy and multiple pregnancy were computed.A total of 540 articles were retrieved related to preterm birth through electronic searches. Of those retrieved, 303 papers were from PubMed/MIDLINE, 30 from Google scholars, and 207 from other sources. From the total papers, 88 duplicate and 400 non-eligible papers were identified and excluded during the screening of the titles and abstracts. The remaining 42 articles were given full test review, resulting in 30 papers being considered appropriate and eligible for analysis. Twelve articles were excluded based on the exclusion criteria stated below .As a result, 30 studies were met the inclusion criteria to undergo the final systematic review and Meta-analysis. This systematic review and Meta-analysis consist of 23 cross-sectional, 6 case-control and 1 cohort studies with total 17,403 study participants in different regions in Ethiopia .The overall pooled prevalence of preterm birth in Ethiopia is presented with a forest plot . TherefoSubgroup analysis was done with the evidence of heterogeneity. Hence, the Cochrane I2 statistic =96.3%, P≤0.001) with evidence of marked heterogeneity. Therefore, subgroup analysis was conducted using the sample size of participants and year of publication of the articles. Based on the subgroup analysis, the prevalence of preterm birth in Ethiopia was 10.73%  I2=97.3%, P≤0.001) in which sample size was≥400 .A funnel plot was assessed for the asymmetry distribution of preterm birth among mothers who gave birth at health institutions in Ethiopia by visual inspection. Egger's regression test showed with a p-value of 0.003 indicated for the existence of publication bias. Hence, trim and fill analysis was conducted to overcome the publication bias. Eleven studies filled with 25 studies and overall, 36 studies were enrolled and computed through the trim and fill analysis with a pooled prevalence of 6.52%  using a random effect model  & b.This review showed that the point estimate of its omitted analysis lies under the confidence interval of the combined analysis .Risk factors associated with preterm birth among mothers who gave birth at health institutions in EthiopiaThe most common associated factors included in this systematic review and meta-analysis were pregnancy-induced hypertension, being HIV-positive, premature rupture of membrane, rural residence, mother having a history of abortion, multiple pregnancy, and anemia during pregnancy.Women who have pregnancy-induced hypertension ) was positively associated with preterm birth. No heterogeneity  was detected among the included studies; due this reason, the fixed effect model was calculated. Moreover, the possibility of publication bias was not detected using Egger's tests with a p-value of 0.568.Women who is HIV-positive were the predictors of preterm birth . No heterogeneity  was detected among the included studies; for this reason, the fixed effect meta-analysis model was computed. Moreover, no possibility of publication bias was detected using Egger's tests with a p-value of 0.595.We found that women who had premature rupture of membrane four times ) greater at increased risk the likelihood of having a preterm birth compared to their counterparts. Moderate heterogeneity  was detected among the studies. Therefore, random effect model meta-analysis was employed. Furthermore, no possibility of publication bias was detected using Egger's tests with a p-value of 0.762.Being a rural residency was one the significant risk factor for preterm birth . No heterogeneity  was detected among the included studies; for this reason, the Fixed effect meta-analysis model was computed. Moreover, no existence of publication bias was declared d using the Egger's tests with a p-value of 0.314.Pregnant women who were anemic ) were positively associated with preterm birth. Low heterogeneity  was detected among the included studies; for this reason, the random effect meta-analysis model was computed. Furthermore, publication bias was not detected using Egger's tests with a p-value of 0.657.Pregnant women who have two or more fetus in intrauterine  were positively associated with preterm birth. No heterogeneity  was detected among the included studies; for this reason, the fixed effect meta-analysis model was computed. Furthermore, publication bias was not detected using Egger's tests with a p-value of 0.835.Women having a history of abortion  were the determining factor of preterm birth. No heterogeneity  was detected. Hence, the fixed effect meta-analysis model was computed. Furthermore, the existence of publication bias was not detected using Egger's tests with a p-value of 0.835 .In this meta-analysis, the overall pooled prevalence of preterm birth among mothers who gave birth at health institutions in Ethiopia was 11.4% . This finding agrees with studies conducted in Tanzania 13% The finding of this review and meta-analysis was lower than the study done in India 15% The finding of this review was higher than the studies conducted in Kenya 8.3%, two different studies in Iran 6.3% The study determined that women who had developed pregnancy-induced hypertension were 5.11-time ) greater risk with preterm birth than the counterpart. The finding is consistent with the study done in East Africa This review showed that HIV-positive pregnant mothers were 4.7 times  more at increased risk of having a preterm birth than negative mothers. This is in agreement with a study conducted in South Africa We found that women who had premature rupture of membrane four times ) greater at increased risk the likelihood of having preterm birth as compared to their counterparts. This is in agreement with a study done in two different studies in Iran Pregnant women who are living in rural areas 2.4 times  more at increased risk for preterm birth than in urban areas, which is consistent with a study conducted in KenyaPregnant women who were anemic ) were positively associated with preterm birth. This is in agreement a study done in India This review showed that multiple gestation has been associated with the increased likelihood of preterm birth . This finding agrees with those studies done in Kenya Another risk factor associated with preterm birth had a history of abortion ), which is consistent those studies done in Brazil This review seems to be done first in Ethiopia. In addition, the included studies in this review were cross-sectional, case-control, and cohort show temporal cause effect relationships due to its nature of the design.This review has been limited to articles published only in English languages that cause reporting bias. Data were not found in all regions of the country this can cause representative problems.The national prevalence of preterm birth in Ethiopia was low. The most common associated factors included in this systematic review and meta-analysis were pregnancy-induced hypertension, being HIV-positive, premature rupture of membrane, rural residence, the mother having a history of abortion, multiple pregnancy, and anemia during pregnancy. This review can be used to base line for health policy makers, clinicians, and program officers to design action plan work for prevention and intervention measures on preterm birth. Early identifying those pregnant women who are at risk of the above determinants and proving quality healthcare and counsel them how to prevent preterm birth which may decrease the rate of preterm birth and its consequences.


Speech and language acquisition is one of the key development indicators of optimal literacy development in infancy and early childhood. Over the last decade there has been increasing interest in the development of theoretical frameworks which underpin the underlying complexity of a child’s language developmental landscapes. This longitudinal study aims to measure the impact of genetic and environmental risk and protective factors on speech, language, and communication development (SLCN) among 5000 infants in Australia. Using robust panel fixed-effects models, the results demonstrate that there are clear and consistent effects of protective factors and SLCN associated with the infant’s family , the in utero environment  and early infant health . The impact of family and in utero health is dominant at aged 2 to 3 years (relative to 0 to 1 years) across the domains of language and communication and more dominant from birth to 1 years for speech acquisition. In contrast, the evidence for the impact of genetics on SLCN acquisition in infancy, is less clear. The evidence from this study can be used to inform intervention policies. The first 1000 days of life are recognized as a critical and sensitive period in the acquisition of speech and language, where the foundations of optimal literacy development are established. There are several theoretical frameworks which seek to explain the underlying complexity of a child’s developmental landscapes ,4,5,6,7 This longitudinal study was part of the Longitudinal Study of Australian Children (LSAC), whereby infants and parents were interviewed initially in the first year of the child’s life  and then subsequently every 2 years, to measure the child’s ongoing health and development. Interviewers were trained by psychologists to directly assess young children’s development profile, according to screening guidelines. The present study used data from a nationally representative sample of infants in the birth cohort of LSAC. The LSAC used a two-stage sampling design, stratified by state and geographic area and clustered by postcode and then child. Some remote postcodes were excluded, due to the costs associated with data collection and the population estimates were adjusted accordingly. The sample was weighted for attrition. Full details of the LSAC study design have been previously published . The stuThe LSAC birth cohort was the primary source of data in this study as it tracks a sample of approximately 5000 infants at birth through their first 1000 days or life (2 waves). The advantage of using these longitudinal data is that it allows the exploration of the speech and language acquisition and social communication, while controlling for a rich set of individual and family characteristics.For the purposes of our analysis, we used the CATALISE criteria to define a continuous variable of language ability . This vaThe SLCN index includes 11 components, across five measures: communication and symbolic behavior scales (CSBS) , parent The panel nature of these data considers both the timing (age of the child) and frequency (number of times the measures are reported) of the components, which allows us to capture the infant’s language acquisition trajectory. Results are reported as an overall SLCN index and the individual domains  separately. It was not possible to define the individual domains as mutually exclusive as several of the components overlap domains. Consequently, components are categorized by their primary focus. E.g., parent reported concern of speech and understanding is categorized in the “speech” domain. Speech pathology is considered in each index to account for identification of difficulties in each of the three domains. These measures are summarized in To account for the impact that these risk and protective factors have on an individual’s SLCN development, we included several measures reported in LSAC  as covariates in the analysis , Table 1To account for the different aspects of language that are sensitive to social and language background we considered information on socio-demographic characteristics including: ethnicity, educational level, employment status, household size, financial stress, and hardship and monthly household income, which was obtained through parent self-report. In addition, positive parenting was captured in three variables: self-efficacy, warmth, and hostility. A “family risk index” was then calculated as the equal weighted average of the z-score of 11 variables: socio-economic position, equivalized household income, non-English-speaking background (yes/no), indigenous (yes/no), parents health status, receiver of single parent allowance (yes/no), hardship (higher score is less hardship), stressful life (number of events), mother’s depression (K6 depression score), mother education (Year 12 and above), parental self-efficacy, warmth, and hostility (reverse coded).Information on perinatal risk factors was considered to capture the effects of the in utero environment on the infant’s growth and development . These iInformation on birth outcomes, namely gestational age at birth, birth weight and length, extra medical care at birth, whether it was a single of multiple birth and time spent in hospital were extracted from parent self-reported records, when the infant was 0 to 1 years of age. Low birth weight (LBW) was defined as weight at birth of less than 2.5 kg . GestatiVariables relating to the infant’s surrounding community were considered to capture any wider neighborhood effects on language development, often categorized as socio-economic index for areas (SEIFA), which is based on the five-yearly Census . A “commThere is evidence in the literature that genetic influences play a significant role in early communication development ,3,5,9, wThe analysis considered that speech and language development can be influenced by other co-morbidities such as neurodevelopmental disorders and can commonly co-exist with conditions such as cognitive and motor dysfunction ,37. ThesFrom the original sample of 5107 infants, 9 were excluded as outliers in the distribution of SLCN. A sample of 5098 infants, across 2 waves were used in the analysis, from birth to 3 years of age. To control for missing observations, we use ad hoc imputation methods outlined by Hox (2002) .p < 0.10 + p < 0.05 *, p < 0.01 **. Interactions with time were also considered. Data were analyzed using STATA Statistics version 14.1 software StataCorp LP, College Station, TX, USA.Panel random effects analysis was used to explore the relationship between the independent variables of interest and SLCN. Results for the main indexes  were presented as standard deviation (SD) and standard errors (SE) and the level of significance was set at Characteristics of the infants and families are shown in communication development,  when compared to speech  and language . In terms of specific risk indices, the coefficient for family protective factors on communication development (col 4) is the largest (0.241 **), followed by birth (0.10 **) and perinatal protective factors (0.095 **). In terms of the other SLCN domains, it appears that both family and birth factors play an important role in the development of speech and language, but the magnitude of the effects are not as high. The coefficient for family and birth protective factors on speech development is 0.081 ** and 0.092 **, respectively. The coefficient for family and birth protective factors on language development is 0.143 ** and 0.052 **, respectively. In terms of individual infant characteristics, male infants (−0.073 **) , infants with special health care needs (−0.048 **), with older siblings (−0.050 **) and those with average and below health (−0.104 **)  have poorer language development. The gender differences in SLCN appears to be mediated by strong communication skills in girls.The remaining columns of In terms of perinatal risk (row 3), the most important markers appear to be mother’s age (one-year increase in age is associated with −0.069 ** lower communication and −0.049 ** lower speech), and healthy pregnancy behaviors. Notably, excluding high-risk foods during pregnancy (0.012 +) and reduced smoking appears to have a consistently positive effect on SLCN .In terms of birth risk factors (row 4), LBW and gestational age appear to be the most important birth risk factors for SLCN development. Infants with LBW recorded 0.071(NS) lower SLCN, which was largely driven by lower language development (−0.089 * +), when compared to normal weight infants. Similarly, infants who were born somewhat early (33 to 37 weeks) or very early (32 weeks and below), reported −0.018 * and −0.179 ** lower SLCN respectively, when compared to infants born on time (37 to 42 weeks). In contrast to the consistent environmental effects observed, there is mixed evidence of the effects of genetics on early SLCN. The effects of multi-generational  risk have a small and inconsistent effect on language acquisition. There are significant differences by age and across the components of multi-generational risk.The final stage of the analysis is to consider the complexity of how key environmental influences interact over time, and with an individual’s genetic makeup. To test the importance of these interactions, we re-estimate the analysis, including interactions of the key risk indices with time or age of the child. The coefficient can be interpreted as the effect of one standard deviation increase of family index for the sample when they are aged at either 1 to 2 years or 2 to 3 years. The basis for this interaction is that if the age of the child does not matter, then the size of the re-specified coefficients should be consistent with the average from  and remaUsing the interaction model from Overall, the results from this study show that environmental protective factors play a vital role in the development of speech, language, and communication for infants up to 3 years of age. The interaction specifications highlighted that risk models should consider not only the number of risk factors, but the interaction effects over time.The aim of this study was to explore the impact of risk and protective environmental and genetic factors on speech language and communication acquisition for infants aged from 0 to 3 years of age. Using robust panel fixed-effects models, the results demonstrate that there are clear and consistent effects of protective factors associated with the infant’s family, the in utero environment, and early infant health. It is well documented in the literature that the family environment is an important predictor of children’s language and literacy , particuIn addition, our results support Barker’s Hypothesis, which suggests that fetal and infant origins can influence the development of disease later in life . For insIn contrast to the consistent effects observed for environmental risk factors, our study found limited evidence of the impact of genetics on SLCN acquisition in infancy. These findings are consistent with the literature which investigated longitudinal patterns of speech and language acquisition using studies of twins ,13. The speech acquisition between birth and 1 years. It is possible that the genetic information available in the LSAC did not adequately capture the genetic components relevant to speech acquisition. The variable in LSAC were limited to multi-generational long-term medical conditions (including speech) but did not capture any childhood conditions of the parents or grandparents. This poor association is demonstrated in The authors of the twins study also suggest that there is a useful distinction to be made, in terms of etiology, in the acquisition of language and speech skills. Differences in young children’s language skills, appear to be largely due to environmental influences, while differences in speech skills, appear to be mostly due to genetic effects. This contrasts with the results of our study, which found clear and consistent effects of family and birth risk factors on The differences in etiology and longitudinal development patterns have implications for the value of intervention in early infancy. The dominance of environmental factors over genetics suggests that interventions targeting the specific domains of language and communication at this age should be broad in scope, focusing on the in utero and home environment. In contrast speech development interventions at this age, which may more dominantly influenced by genetics should have a targeted component, which specifically focuses on speech remediation .Our study highlighted higher rates of speech and communication acquisition for infants from non-English-speaking backgrounds, when compared to English speakers. Chan and Silva (2015) investigated first- and second-language attrition in a second-language environment and found that home influences, transferable lexical growth, and cognitive maturity may lead to Language 2 learners accumulating vocabulary and understanding more rapidly. .Finally, we found inconsistent effects of the influence on the community environment on emerging language, which is consistent with the literature which found that neighborhood was positively associated with the early child development domains of physical health and wellbeing and social competence, rather than language. As children get older, neighborhood and peer effects were positively associated with literacy development through children’s social-emotional development, and engagement in school ,48.Several limitations need to be considered in the present study. The first is that it is recognized in the literature that there is wide interindividual variation in language development in children under 5 years of age. Studies by Centre of Research Excellence in Child Language have shown that language development can accelerate, plateau or even go backwards within the space of a year . These fIn this paper, we present new evidence that improving environmental protective factors can lead to significant expansion in the acquisition of speech, language, and communication skills in infants. The study identified specific aspects of the environment to be leveraged to produce optimal language development. Interventions focused on supporting families to optimize home learning environments and enabling improvements in environmental protective factors, are key and even children with a poor start to life can catch up, but the compounding effects of perinatal care and birth should not be overlooked.


Streptanthus tortuosus, were scored both manually by human observers and by a mask R-CNN object detection model to (1) evaluate the concordance between ML and manually-derived phenological data and (2) determine whether ML-derived data can be used to reliably assess phenological patterns. The ML model generally underestimated the number of reproductive structures present on each specimen; however, when these counts were used to provide a quantitative estimate of the phenological stage of plants on a given sheet , the ML and manually-derived PI’s were highly concordant. Moreover, herbarium specimen age had no effect on the estimated PI of a given sheet. Finally, including ML-derived PIs as predictor variables in phenological models produced estimates of the phenological sensitivity of this species to climate, temporal shifts in flowering time, and the rate of phenological progression that are indistinguishable from those produced by models based on data provided by human observers. This study demonstrates that phenological data extracted using machine learning can be used reliably to estimate the phenological stage of herbarium specimens and to detect phenological patterns.Machine learning (ML) can accelerate the extraction of phenological data from herbarium specimens; however, no studies have assessed whether ML-derived phenological data can be used reliably to evaluate ecological patterns. In this study, 709 herbarium specimens representing a widespread annual herb,  Within and among plant species, the study of phenological traits such as the timing of bud break or flowering can provide key insights into how species respond to climate . Measurihttps://www.gbif.org/ (accessed on 1 October 2020))and iDigBio (https://www.idigbio.org/ (accessed on 1 October 2020)), to advance phenological research.Natural history collections, such as herbarium specimens, provide a long temporal record of phenology for hundreds of thousands of taxa globally and offer a data-rich resource with which to fill this gap . MoreoveThe majority of herbarium specimens include the name of the sampled species , the precise date of collection, and a text description of the location at which the specimen was collected, which may include a note indicating whether or not the specimen was collected in flower. A smaller fraction of herbarium specimens have also been georeferenced to provide the latitude and longitude of the site of collection . These attributes of specimens, when available, are routinely included in electronic databases provided by the herbaria that archive the physical specimens. By contrast, electronic records of herbarium specimens rarely include reports of the numbers of flower buds, open flowers, developing ovaries, and full-sized or mature fruits. Previous work by Love et al. , Love anRecently, machine learning techniques—specifically, convolutional neural networks (CNN)—have been used to harvest accurate phenological data from imaged herbarium specimens ,18,19, aMachine learning has also been used successfully to detect and count individual reproductive structures on herbarium sheets  using instance segmentation . GoëStreptanthus tortuosus Kellogg (Brassicaceae) that were scored both manually (by human observers) and by using mask R-CNN to assess the concordance between human- and machine-learning-derived phenological data and to evaluate the use of automated phenological scoring in phenological research. Specifically, we addressed the following questions:Can machine learning be used to obtain counts of reproductive organs on herbarium specimens that match those recorded by human observers?Do distinct organ types  differ with respect to the degree to which machine-learned counts match those recorded by human observers?quantitative metric of the phenological status of an herbarium specimen that reflects the proportions of different types of reproductive organs —does the machine-generated PI match the PI calculated from counts reported by human observers?When counts obtained via machine learning are used to estimate the phenological index (PI)—a Does the year of specimen collection affect counting error or estimation of the phenological status? For example, does the fading of floral pigments over time make it more difficult for machine learning algorithms to distinguish between buds and open flowers as herbarium specimens age?When the phenological status (PI) of specimens generated by machine learning is used to construct models that provide estimates of the rate of temporal shifts in flowering date, the sensitivity to climate, and the rate of phenological progression, do these estimates match those based on data derived from human observers?In this study, we use a set of 709 herbarium specimens of Despite the potential for errors in human-derived counts of reproductive structures, in the current study we assume that human-counted values are more correct than machine-learning counted values. We treat human-observed values as the true values against which we compare values derived from machine learning to assess its accuracy in extracting phenological data from herbarium specimens.max) and cumulative winter precipitation experienced at each collection site during the year of specimen collection ranged from 1.4–24.6 °C (SD = 4.8 °C) and 88–2167 mm (SD = 357.8 mm), respectively.Our final testing dataset consisted of 709 georeferenced herbarium specimens that were scored both manually and via the machine-learning model. These specimens’ collection dates spanned a 112-year period (1902–2013) and the sites of collection were distributed throughout S. tortuosus’ geographic range . The meaThe 21 herbarium specimens used to train the mask R-CNN model were collected between 1899 and 1983. The number of reproductive organs per sheet depended on the type of organ, as follows: buds , flowers , immature fruits , and mature fruits . The manually-derived PI of the training set ranged from 1.12 to 3.96 .p < 0.0001; mature fruits = 0.28 ± 0.009 predicted per manually-counted mature fruit, p < 0.0001; 2 for all models ranged from 0.32 (flowers) to 0.56  across all categories  or the machine-learning-derived estimation of the PI  or machine-learning-derived counts  of reproductive structures.The two models constructed to estimate shifts in flowering date while controlling for either the manually-derived or the machine-learning-derived PI produced similar estimates of the phenological shift through time . The modS. tortuosus to climate while controlling for either the manually-derived or machine-learning-derived PI produced similar estimates of sensitivity to both spring Tmax and winter PPT  it takes individual plants 43.7–58.1 days to progress from the first stage of reproduction (the production of flower buds) through the last stage of reproduction (the completion of fruit ripening).Both sets of models produced similar estimates of the rate of phenological progression (days/PI unit), regardless of whether the PI was estimated using manually- or machine-learning-derived counts . Among aS. tortuosus generally underestimated the number of reproductive structures present on each specimen; however, when these predicted counts were used to estimate the phenological stage of plants on a given sheet , the machine-learning-derived and manually-derived PI’s were highly concordant. We also found that scoring older herbarium specimens resulted in slightly more counting errors than more recently collected specimens for some classes of reproductive structures, but specimen age had no effect on estimating the PI of a given sheet.The mask R-CNN models trained by  and applFinally, we found that machine-learning-derived estimates of the PI could be used in models to accurately evaluate phenological patterns and sensitivity to local climatic conditions. When the machine-learning-derived vs. manually-derived PI’s were used to construct phenological models, both models produced similar estimates of the phenological shift over time, phenological sensitivity to climate, and rates of phenological progression. These results are discussed in detail below.Use of machine learning in phenological scoring of herbarium specimens has recently advanced from lower-order scoring  to highS. tortuosus , and the number of counting errors was greater and more variable when more organs were present on a given sheet , they were highly concordant with the manually-derived PIs . BecauseThe current study demonstrates that machine-learning-derived counts of reproductive organs using an object detection approach can be used to accurately estimate a quantitative measure of a herbarium specimen’s phenological status; however, this attribute can be estimated using other machine-learning approaches as well. In contrast to this study, Lorieul et al.  used a gHerbarium specimens have recently emerged as reliable sources with which to detect and track phenological change through time ,7,11. AsThis is the first study to demonstrate that machine learning can be used to accurately estimate the phenological status of older herbarium specimens. Importantly, our training dataset included specimens collected as early as 1899 . IncludiHerbarium records are important sources of phenological data and can be used to reliably assess ecological patterns; however, no previous studies have been designed to test whether machine-learning-derived phenological scores of herbarium records can be used to accurately estimate such patterns. In the current study, we found that including machine-learning-derived PIs as predictor variables in phenological models produce similar estimates of the phenological sensitivity to climate, temporal shifts in flowering time, and the rate of phenological progression  control statistically for variation among specimens in their phenological status and (2) estimate the rate of phenological progression . HoweverStreptanthus species have morphologically similar reproductive structures, and the transferability of the model developed in the current study to other members of the genus will likely generate accurate estimates of specimen PIs.Creating masks to train object detection in machine learning models is a time intensive process; however, the ability to transfer models trained on one species to a closely related and morphological species would enhance our capacity to extract phenological data from imaged herbarium specimens. Davis et al.  showed tCommunity science or crowd-based approaches for scoring specimens could also be leveraged to extend the use of machine learning in phenological research . Crowd-bWe assembled and manually scored the phenological status of 1138 herbarium records from seven herbaria . We extracted the day of year of specimen collection (DOY) from the collection information on the label of each herbarium specimen. The DOY, which can range from 1 (1 January) to 365 (31 December), is a widely used estimate of flowering date derived from herbarium specimens and is used commonly as a response variable when estimating sensitivity of flowering date to climate and shifts in flowering time in phenological studies [Specimens were then scored using the ImageJ scoring protocol and phenophase definitions described in Love et al. . We usedxP is the proportion of reproductive units in each class, and i represents the index value assigned to each class of reproductive structure. A specimen with a PI of 1 would be bearing only buds, indicating that the specimen was at an early stage of phenological progression when collected. In contrast, a specimen with PI value of 4 would be bearing only mature fruits and would indicate that the specimen was collected at a late reproductive stage. Specimens with values of the PI between 1 and 4 would typically be bearing a combination of at least two of the four classes of reproductive structures used in the current study. Including the PI as a predictor variable in linear models designed to detect the effects of local climate or year on the day of year of specimen collection is useful because the value of PI is highly positively correlated with DOY  and therefore contributes significantly to the model R2. All else being equal, specimens with low values of the PI were collected earlier in the growing season than those with high values of the PI. In addition, the regression coefficient associated with the PI provides an estimate of how many days it takes for plants to increase their PI by a value of one .The manual counts were then used to calculate a quantitative estimate of the phenological stage of each herbarium record: the phenological index, or PI . The PI www.cch2.org (accessed on 3 March 2018)) or using the written description of the collection location to derive coordinates using GEOLocate (www.geo-locate.org (accessed on 3 March 2018)), a platform for georeferencing natural history specimens or electronic records. Each set of coordinates was also associated with an error radius (in meters) that represented the uncertainty of each location. After georeferencing, we excluded records with an error radius greater than 4000 m and duplicate records. This resulted in a set of 709 specimens that were then scored using the trained algorithm.Next, we georeferenced each specimen by either downloading the latitude and longitude for that record from the California Consortium of Herbaria  and the cumulative winter precipitation (winter PPT) during the year of specimen collection [For each of the georeferenced specimen records, we extracted from ClimateNA  two climllection ,14. Climhttps://github.com/jsbroks/coco-annotator (accessed on 2 February 2019), a web-based tool for object segmentation), in order to manually draw the full outline of each reproductive structure. This allowed us to capture the full shape of each reproductive organ identified on each specimen. When structures overlapped on the specimen, only the structure in the foreground was annotated, resulting in the exclusion of background structures from the segmentation in that part of the image. A total of 1036 reproductive structures from 21 herbarium specimens were annotated (flower buds (279), flowers (349), immature fruits (196), and mature fruits (212)). This dataset is freely available on the Zenodo platform [We uploaded images of herbarium specimens into COCO Annotator  on each herbarium sheet (i), which is defined as the difference between the number of organs counted manually by human observers  per class of reproductive structure, which measures the mean absolute error per class of reproductive structure across all sheets (N). We used the following equation:Second, we calculated the mean absolute error  of count errors for each of five ranges of reproductive organs present .10 transformed after adding 1 to each value, and the PI was square root transformed.To determine whether the year of collection affected the model’s ability to accurately count the number of reproductive structures on each sheet, we constructed one linear model for each of the four organ classes that assessed the effect of year of collection on the absolute value of the counting error. We used the absolute value of counting error in this analysis because we were interested in estimating the effect of year on the overall error rate and not whether the algorithm specifically over- or underestimates the organ count through time. We also used linear regression to assess whether the year of collection affected the estimation of the PI. To improve normality, the absolute value of counting error was logStreptanthus tortuosus where the date of specimen collection is used as a proxy for flowering date . For both sets of models, we calculated the 95% confidence interval of each coefficient estimate as well as the partial R2 for each main effect.We constructed two sets of multivariate linear regression models (with two models each) to determine whether the PI derived from machine learning counts (or predicted counts) could be used to construct models that accurately estimate (relative to the human observations) the rate of temporal shifts in flowering date (set 1) and the sensitivity of flowering date to climate (set 2). Models in each set controlled for variation in phenological status among specimens by including the PI derived from either manual or predicted counts, but otherwise included the same predictors. The first set of models (set 1) assessed the effect of year on the DOY to determine the rate of phenological change (days/year), and included year, PI, elevation, latitude, and longitude as main effects. The second set of models (set 2) assessed the sensitivity of flowering date (DOY) to climate during the year of specimen collection and included PI, cumulative winter precipitation, and spring maximum temperature. Temperature and precipitation have been demonstrated to affect flowering date in Because both sets of models included the PI as a main effect, this allowed us to compare the rate of phenological progression (days/PI unit) as estimated by the regression coefficient of the PI  among all four models. We used the 95% confidence interval to evaluate whether the estimated rate of phenological progression differed between counting methods  or among models. All statistical analyses were conducted using R version 4.0.3 .


Human health effects of airborne lower-chlorinated polychlorinated biphenyls (LC-PCBs) are largely unexplored. Since PCBs may cross the placenta, maternal exposure could potentially have negative consequences for fetal development. We aimed to determine if exposure to airborne PCB during pregnancy was associated with adverse birth outcomes. In this cohort study, exposed women had lived in PCB contaminated apartments at least one year during the 3.6 years before conception or the entire first trimester of pregnancy. The women and their children were followed for birth outcomes in Danish health registers. Logistic regression was performed to estimate odds ratios (OR) for changes in secondary sex ratio, preterm birth, major congenital malformations, cryptorchidism, and being born small for gestational age. We performed linear regression to estimate difference in birth weight among children of exposed and unexposed mothers. All models were adjusted for maternal age, educational level, ethnicity, and calendar time. We identified 885 exposed pregnancies and 3327 unexposed pregnancies. Relative to unexposed women, exposed women had OR 0.97  for secondary sex ratio, OR 1.13  for preterm birth, OR 1.28  for having a child with major malformations, OR 1.73  for cryptorchidism and OR 1.23  for giving birth to a child born small for gestational age. The difference in birth weight for children of exposed compared to unexposed women was − 32 g . We observed an increased risk of cryptorchidism among boys after maternal airborne LC-PCB exposure, but due to the proxy measure of exposure, inability to perform dose–response analyses, and the lack of comparable literature, larger cohort studies with direct measures of exposure are needed to investigate the safety of airborne LC-PCB exposure during pregnancy PCBs are some of the most widespread persistent organic pollutants in the environment due to their extensive use in electrical equipment and building materials from late 1920s to the 1970s and their continuous release from waste and building materials from that period . After dYet, human health effects of LC-PCBs remain largely unexplored , 14. HC-To date, no previous study has investigated if living in PCB contaminated buildings is safe for the pregnant woman and her child. If LC-PCBs can disrupt hormonal balance, plausible consequences could be changes in secondary sex ratio, increased risk of preterm birth, major malformations, and changes in fetal growth . We therThe current study was nested in the HESPAIR cohort, specifically designed to study health effects after exposure to PCB in indoor air. The cohort was established in 2019 by the Department of Occupational and Environmental Medicine . HESPAIR consists of 52 212 former or current residents of the building estates Farum Midtpunkt and Brøndby Strand Parkerne during the period 1970–2018. The estates were erected during 1969–1974 and include both PCB contaminated apartments and uncontaminated apartments. This is because PCB containing caulks and sealants were used during the first stages of construction, while other building materials were used in later stages . Measureafter their first relocation to the estates. The MBR holds data on health of pregnant women and their offspring, and all live and still births in Denmark. The register was established in 1973 and has been updated continuously. It underwent a major revision in 1997, where the register became electronic, and a list of new variables was added [In the present study, we included all women from the HESPAIR cohort who had lived in the estates up to or during their pregnancy by linking unique civil registration numbers from the HESPAIR cohort to the Danish Medical Birth Registry (MBR) . We idenas added .The Danish Central Person register (CPR) was used to extract information on dates and addresses of relocations. This enabled calculation of timing and duration of living in the estates, which served as a proxy for PCB exposure. Women were defined as exposed if they had lived in a contaminated apartment for at least one year during the 3.6-year period leading up to conception or during the entire first trimester Fig. . ConceptThe one year exposure criterium was based on a reanalysis of the data on plasma concentration of PCB-28 among 134 exposed and 139 non-exposed residents, obtained by Meyer et al.  that shoBirth outcomes were retrieved from birth records in the MBR available since 1973 and hospital contacts in the Danish National Patient Register (DNPR) available since 1977. The DNPR holds information on diagnoses and treatments for all patients admitted to any public or private hospital and was used to retrieve data on congenital malformations .The child’s sex was retrieved from birth records of live births, to examine secondary sex ratio. Secondary sex ratio was expressed as the chance of having a live born son. This is of interest since hormonal disruption could decrease the prevalence of boys . InformaPotential confounders were identified a priori using directed acyclic graphs , see FigIn analyses regarding secondary sex ratio, SGA, preterm birth, major congenital malformations, and cryptorchidism we performed logistic regression with adjustment for maternal age, educational level, ethnicity, and calendar time. We restricted the analyses of preterm birth and birth weight to children born from 1982, since before 1982 we found many missing values on gestational age and birth weight was coded in large weight intervals , as reported previously . In addiafter their first relocation to the estates. Of these, only 3307 women and their 4212 pregnancies fulfilled the criteria of being exposed or unexposed during the defined observation window, of which 885 (21%) pregnancies were exposed  (Table We found no difference in risk of preterm birth (before 37 completed weeks of gestation)  Table . SmokingIn adjusted analyses we observed an indicated 28% higher risk of major malformations    Table . No inteAdjusted analyses of birth weight on a continuous scale showed that the difference in birth weight was − 32 g  among children of exposed compared to children of unexposed women , and non-dioxin like PCBs (NDL-PCBs) which includes most HC-PCBs and LC-PCBs. Like dioxins, the 12 existing DL-PCBs  act through the Aryl Hydrocarbon Receptor (AhR). NDL-PCBs probably act on multiple other receptors and pathways, for instance the constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) . The effWe observed an increased risk of cryptorchidism for exposed pregnancies, but with a wide 95% confidence interval, which implies uncertainty of the risk estimate and could be due to chance but could also be due few cases in a population with a moderate size. However, a plausible mechanism could be the hypothesized estrogenic and anti-androgenic activity of LC-PCBs during the ‘male programming window’ in the first trimester . PreviouWe observed an indication of impaired organogenesis after airborne LC-PCB exposure, but again with a wide 95% confidence interval. However, as we only included major malformations diagnosed within the child’s first year, we could have missed some cases as the registration of diagnose codes in the DNPR started in 1977, and the estates—with contaminated apartments being built first—were available for living from the beginning of the 1970’ies. Nevertheless, when we studied children born 1991–2018, where registration of malformations and maternal smoking information were available for the whole period, we found an attenuated risk estimate. Teratogenic effects have been observed in ‘Yucheng’ children after their mothers accidently ingested polychlorinated dibenzofurans (PCDFs)—and PCB contaminated rice oil in 1978–1979 . ‘YuchenWe found no increased risk of preterm birth, and the main analysis was supported by the analysis among first born children where we expected the mothers to represent a more homogenous group independent of previous experiences with pregnancy and birth,. This is in contrast to a previous cross-sectional study reporting an inverse association between LC-PCBs in umbilical cord blood and gestational age at birth .We also found indications of affected gestational growth, but once again with wide 95% confidence intervals. If gestational growth is affected by LC-PCBs, it may be explained by a wide range of effects of PCBs on metabolism, e.g. alteration of insulin regulation , and thyIndoor LC-PCB contamination in private homes and public buildings is a global issue including countries like Germany and The United States –67. PresOur study has several strengths. The relationship was studied in a residence-based cohort, where people have unknowingly relocated themselves to contaminated and uncontaminated apartments, except for the first years of the cohort period where contaminated apartments were available first. Since contaminated apartments were built first, the chance of moving into a contaminated apartment were naturally higher during this period. Nevertheless, we expect residents from the estates to be similar in background exposure to PCBs, socioeconomic status, and health behavior, which previous studies on subsamples of the total HESPAIR cohort have demonstrated , 11. We The registers made it possible to avoid self-report of outcomes, but also presented some issues. First, the DNPR, the only source of information on congenital malformations prior to 1997, did not cover the entire cohort period, as the register was established in 1977, and the estates were available since the beginning of the 1970’s. Further, registration methods, quality, and especially the registration completeness in the MBR changed over time . For insLastly, a common source of bias is the ‘live birth bias’ arising when studying prenatal exposure . Only 60In conclusion, we observed increased risk of cryptorchidism among boys after maternal airborne LC-PCB exposure. Our results indicate LC-PCB might induce developmental toxicity, but due to the proxy nature of our measure of exposure, inability to perform dose–response analyses, and the lack of comparable literature, larger cohort studies are needed to investigate the safety of staying in PCB contaminated residences and workplaces up to and during pregnancy.


Bacteroidetes levels increased for all donors, donor-dependent increases in Bifidobacteria, Lactobacilli, and Firmicutes were observed, stressing the potential interindividual differences in microbial composition modulation upon Baobab fruit pulp powder treatment. Overall, Baobab fruit pulp powder fermentation displayed features of selective utilization by host microorganisms and, thus, has promising prebiotic potential . Further research will be required to better characterize this prebiotic potential, accounting for the interindividual differences, while aiming to unravel the potential resulting health benefits.Increasing insight into the impact of the gut microbiota on human health has sustained the development of novel prebiotic ingredients. This exploratory study evaluated the prebiotic potential of baobab fruit pulp powder, which consists of pectic polysaccharides with unique composition as compared to other dietary sources, given that it is rich in low methoxylated homogalacturonan (HG). After applying dialysis procedures to remove simple sugars from the product , 48 h fecal batch incubations were performed. Baobab fruit pulp powder boosted colonic acidification across three simulated human adult donors due to the significant stimulation of health-related metabolites acetate (+18.4 mM at 48 h), propionate (+5.5 mM at 48 h), and to a lesser extent butyrate (0.9 mM at 48 h). Further, there was a trend of increased lactate levels (+2.7 mM at 6h) and reduced branched chain fatty acid (bCFA) levels (−0.4 mM at 48 h). While  The v content . Colonic content ,5. The e content ,7,8. Cur content ,10. WhilIncreased understanding of the gut microbiota has triggered research toward improving human health through stimulation of beneficial gut bacteria. In this aspect, prebiotic substrates have gained a lot of attention ,13. WhilAdansonia digitate L.) indigenous to Africa, particularly Sudan, Ghana, Malawi, Burkina Faso, and Uganda, and it is a potential source of pectins. Baobab fruit is subdivided into pericarp, resistant outer shell, endocarp, and the inner ripe fruit. The ripe pulp is floury, dry, and powdery, including red fibrous structures and seeds. Although the nutritional values of baobab pulp vary among different regions, its fiber content is around 70–80% of its dry mass [The baobab fruit is derived from the baobab tree . To our knowledge, this is the first study demonstrating the potential of baobab fruit pulp powder to modulate the human gut microbiota.This study aimed to investigate the prebiotic potential of a novel ingredient rich in pectin-based polysaccharides (baobab fruit pulp powder). This ingredient is unique compared to other pectic polysaccharides given its high content of low methoxylated HG. A 48 h in vitro incubation strategy with the human fecal microbiota of three different human donors  was applied to investigate the potential modulation of microbial fermentation products ) and levels of five specific taxonomic groups (Baobab fruit pulp powder (BP) tested in the current study was provided by Döhler GmbH  . BP cont2O and introduced into a cylindrical dialysis membrane with a molecular weight cutoff of 0.5 kDa . After sealing, the membrane was submerged in 600 mL of dialysis fluid  for 24 h at 4 °C to prevent the growth of bacteria. During the dialysis procedure, sugars moved from the intestinal content to the dialysis suspension. On the other hand, due to osmotic pressure, water also moved from the dialysis solution toward the compartment simulating the intestinal content. This additional dilution of the test product was calculated by measuring both the initial (~100 g) and the final weight of the intestinal content. This dilution was then accounted for when adding the dialyzed product to the colonic incubations so that a fixed amount of test product was dosed, which was equivalent to 4 g of non-dialyzed test product/L colonic medium. In other words, when high quantities of water entered the intestinal content compartment, lower amounts of water were dosed at the start of the colonic incubation.As glucose, fructose, and sucrose (present in BP) are absorbed in the small intestine in vivo, upper gastrointestinal absorption was simulated via a dialysis procedure. This allowed testing the relevant fraction of the test product that would reach the GI tract . Dialysi2HPO4, 79.0 g/L KH2PO4, 9.7 g/L NaHCO3 , 9.7 g/L yeast extract, 9.7 g/L peptone , 4.8 g/L mucin, 2.4 g/L cysteine, 9.7 g/L Tween® 80 ) was administered to 120 mL penicillin bottles already containing 50 mL of dialyzed test product ). This medium was previously demonstrated to facilitate growth of a broad spectrum of microbes belonging to various phyla  [Short-term colonic batch incubations were performed to simulate the proximal colon of three healthy adults as previously described by Van den Abbeele et al.  with minacteria) . Additio® sachet (Oxoid). Fecal samples were stored at 4 °C in the anaerobic container until further processing. Fecal inocula were prepared by making a 7.5% (w/v) suspension of each of the freshly collected fecal samples with anaerobic phosphate buffer . After homogenization  and removal of large particles via centrifugation , 7 mL of inoculum was added to each penicillin bottle, yielding a total volume of 70 mL inside each reactor. Once the inoculum was added, the incubation started and lasted for a period of 48 h. Bottles were maintained at 37 °C and were continuously mixed in a temperature-controlled shaker (90 rpm). Given the high technical reproducibility of the assay as demonstrated before [Fresh fecal samples were collected from three healthy adults and immediately stored in an airtight container with an AnaeroGend before , it was The extent of acidification during the short-term incubations is a measure for the degree of bacterial fermentation activity. The pH was measured immediately using a SenseLine F410 . As the incubations were performed in a closed incubation system, one could determine the accumulation of gases in the headspace by penetrating the rubber septum with a needle connected to a pressure meter . Furthermore, short-chain fatty acids (SCFAs) and branched-chain fatty acids (bCFAs) were quantified by gas chromatography (GC) coupled to flame ionization detection (FID) as previously described by De Weirdt et al. . Lastly,Lactobacillus spp. [Bifidobacterium spp. [Akkermansia muciniphila [Bacteroidetes [Firmicutes [Luminal samples were subjected to quantitative polymerase chain reaction (qPCR) to quantify specific populations of the simulated human gut microbiota. DNA isolation and qPCR analyses were performed as described by Van den Abbeele et al. . Brieflylus spp. , Bifidobium spp. , Akkermainiphila , Bacteroroidetes , and Firrmicutes . All prohttps://biit.cs.ut.ee/clustvis/, accessed on 7 May 2021) [t-tests were performed. Differences were considered significant when p < 0.05, although different levels of significance were distinguished: * p < 0.05, ** p < 0.01. Statistical analysis was performed with Microsoft Excel . For exploratory data analysis, principal component analysis (PCA) was performed for both metabolic  and qPCR data via the online tool Clustvis (ay 2021) . To statTo gain insight into the overall changes in microbial activity upon BP treatment, a principal component analysis (PCA) was performed . The PCAp = 0.14), lactate was increased approximately sixfold upon treatment after 6 h of incubation. Lastly, BP tended to reduce the production of bCFAs at 48 h (p = 0.14). The average changes in microbial metabolic activity across donors allowed identifying potential consistent effects of BP . Gas proUpon plotting the kinetics of metabolite production for each individual donor , interinIn terms of overall kinetics, a peculiar finding was that lactate was exclusively detected at the initial 6 h timepoint in all incubations. The transient nature of lactate is likely explained through cross-feeding mechanisms in which lactate is consumed for the production of, e.g., acetate, propionate, and/or butyrate. Bifidobacteria, Lactobacilli, Bacteroidetes, Firmicutes, and Akkermansia muciniphila) again explained a high degree of variation . This composition is unique versus other pectic polysaccharides. Thus, 48 h in vitro incubations with fecal microbiota of three human adult donors were performed to investigate the potential selective utilization of baobab fruit pulp fiber by host microorganisms, a first essential feature to qualify as a prebiotic . A seconFirst, baobab fruit pulp powder consistently stimulated specific health-related metabolites, i.e., mostly acetate and propionate. Other consistent changes included the increase in lactate levels at the start of the incubation (6 h), followed by increased butyrate levels (24 h). Furthermore, there was a tendency to lower levels of bCFA. The stimulation of acetate and propionate is in line with other studies that investigated pectin-rich fruit fibers ,36. ThisBacteroidetes members that increased for each of the three donors tested. This is in line with the finding that Bacteroides spp. possess a versatile enzymatic potential, allowing them to depolymerize the backbone of HG [Bacteroides spp. are among the most abundant producers of propionate [Bacteroides spp. likely facilitated fermentation of degradation fragments of HG by other microbial groups. According to the current study, such contributing microbes seem to differ among donors. Donor A was, for example, the only donor for which Bifidobacteria increased. In contrast, for donor C, a marked increase in Lactobacilli was noted, which coincided with profound increases in lactate, i.e., the sole and main end product of carbohydrate metabolism by Lactobacilli [Lactobacilli by pectin has indeed been reported before [Firmicutes members, a phylum that indeed increased for donors A and C. Overall, these findings, even if only based on qPCR analysis (that has low taxonomic resolution as opposed to next-generation sequencing), suggest the involvement of specific host microorganisms in the fermentation of baobab fruit pulp powder, highlighting its prebiotic potential. Future research should, however, account for the marked interindividual differences among human subjects, which were apparent even after testing as few as three donors in the current study. The existence of marked interindividual differences is in line with observations during human in vivo studies [Investigation of changes in five specific taxonomic groups further confirmed the selective utilization of baobab fruit pulp powder by specific host microorganisms. Key contributors to baobab fruit pulp powder fermentation likely included ne of HG , a key copionate ,41, theiobacilli . Stimulad before . Moreoved before . While bd before  and/or bd before  Firmicut studies ,10.Now that the prebiotic potential of BP was confirmed in this first study, a next research question is how this potential relates to known prebiotic substrates. To put the findings of this study in perspective, the results were compared to those of a recent study where three different types of inulin, the ‘gold standard’ prebiotic , were teLactobacilli. While valid for donor C, this was not the case for donors A/B. Overall, this study supports further research toward the prebiotic potential of baobab fruit pulp powder and other pectin-based products, as well as their potential health-promoting effects.In conclusion, this exploratory in vitro study allowed attributing an interesting prebiotic potential to baobab fruit pulp powder with changes in both fermentation products and specific taxonomic groups, suggesting selective fermentation by host microorganisms. Although subject to interindividual variation at the microbial composition level, baobab fruit pulp powder constituently stimulated the production of health-related acetate, propionate, and to lesser extent butyrate. These effects were seemingly distinctly different from those exerted by the ‘gold standard’ prebiotic inulin that rather increases butyrate production. To our knowledge, this is the first evidence demonstrating the potential of baobab fruit pulp powder to modulate the human gut microbiota. Overall, our findings strongly support further research toward the potential of baobab fruit pulp powder as a prebiotic substrate. Such studies should account for the investigation of effects across multiple donors given the observed interindividual variation during the current study. Performing in vitro studies with a fecal inoculum of a single human donor could result in conclusions that are not representative of a broader number of donors. For example, if only donor C was tested, the conclusion would have been that baobab fruit pulp powder strongly stimulates


COVID-19 vaccines are recommended during pregnancy to prevent severe maternal morbidity and adverse birth outcomes; however, vaccination coverage among pregnant women has been low  diagnosis codes, Current Procedural Terminology codes, birth records, and electronic health record data  to identify the date and gestational age for live births . Females aged 16–49 years with estimated pregnancy start during May 17–October 24, 2020, and expected delivery dates, based on a 40-week gestation, during February 21–July 31, 2021, were included. This cohort was likely to be pregnant when COVID-19 vaccines were first authorized in the United States. Pregnancies ending in live birth were identified from standardized VSD files using a validated pregnancy algorithm. The algorithm uses Primary outcomes were preterm birth, defined as birth <37 weeks’ gestation, and SGA at birth, defined as birthweight <10th percentile for gestational age compared with a U.S. reference population , 926 with multiple  gestations, 2,489 with no documented care in the health system, 295 with implausible gestational age, and 5,815 with pregnancy start date outside the prespecified periods, 46,079 (82.8%) single-gestation pregnancies ending in live birth with data on gestational age remained. Among these, 10,064 pregnant women (21.8%) received ≥1 COVID-19 vaccine doses during pregnancy and during December 15, 2020–July 22, 2021. COVID-19 vaccination during pregnancy varied by maternal age, race/ethnicity, and selected maternal comorbidities . First .The overall prevalence of preterm birth and SGA at birth were 6.6 and 8.2 per 100 live births, respectively . COVID-1In this large, multisite, retrospective cohort study, receipt of COVID-19 vaccine during pregnancy was not associated with increased risk for preterm birth or SGA at birth. The absolute risk for severe morbidity associated with COVID-19 in pregnancy is low; however, women with symptomatic COVID-19 during pregnancy have a more than twofold increased risk for intensive care unit admission, invasive ventilation, and extracorporeal membrane oxygenation, and a 70% increased risk for death, compared with nonpregnant women with symptomatic infections  that might have affected propensity to be vaccinated were not fully identified through previous COVID-19 diagnoses. In addition, reduced risks for preterm birth after third-trimester vaccination or receipt of a single mRNA vaccine dose during pregnancy were likely due to residual immortal time bias. Third, because of the timing of COVID-19 vaccine availability and the timing of the births in this cohort, few first-trimester vaccinations were observed. Nevertheless, the second and third trimester are critical periods for fetal growth and development. Risks associated with vaccination during the first trimester should be evaluated in future studies that include vaccines administered throughout pregnancy. Finally, this retrospective cohort does not include more recent pregnancies in women who might have been eligible for additional or booster vaccine doses during pregnancy.Despite these limitations, the findings from this retrospective, multisite cohort of a large and diverse population with comprehensive data on vaccination, comorbidities, and birth outcomes add to the evidence supporting the safety of COVID-19 vaccination during pregnancy. CDC recommends COVID-19 vaccination for women who are pregnant, recently pregnant (including those who are lactating), who are trying to become pregnant now, or who might become pregnant in the future  to reducPregnant women with COVID-19 are at increased risk for severe illness and adverse birth outcomes, yet many remain reluctant to be vaccinated.In a retrospective cohort of >40,000 pregnant women, COVID-19 vaccination during pregnancy was not associated with preterm birth or small-for-gestational-age at birth overall, stratified by trimester of vaccination, or number of vaccine doses received during pregnancy, compared with unvaccinated pregnant women.These data support the safety of COVID-19 vaccination during pregnancy. CDC recommends COVID-19 vaccination for women who are pregnant, recently pregnant, who are trying to become pregnant now, or who might become pregnant in the future.


BackgroundDespite ongoing advances in the field of neonatology, the survival outcomes among critically ill preterm surgical neonates remain unfavorable. Intrahospital transport is one of the major risk factors associated with early mortality (within 30 days) in these newborns. To overcome this, the approach of performing bedside surgeries is being followed. We aim to assess the safety and feasibility of performing bedside neonatal surgeries by analyzing our archives.MethodsThe study focused on retrospective evaluation of all the newborns who have undergone surgical procedures in the neonatal intensive care unit (NICU) at our center from August 2015 through February 2021. Newborns were operated within the NICU if they had very low birth weight or other risk factors making their transport to the operation room risky. The outcomes of surgeries were assessed in terms of postoperative complications, one-month survival, and overall survival.ResultsThirteen children (M:F=9:4) underwent twenty-two surgical procedures. The median (range) gestational age and birth weight of our cohort were 30 (26-36) weeks and 1200 (500-2860) grams, respectively. One-month and overall survival rates in our cohort were 84% (11/13) and 77% (10/13), respectively. No major postoperative complications were observed. The requirement of multiple inotropes and/or high-frequency oscillatory ventilation (HFOV) was the only factor having a significant association with unfavorable survival outcomes.ConclusionsBedside surgery is a safe and feasible alternative to surgeries within the operation room for at-risk newborns. In the present study, the requirement of multiple inotropes and/or HFOV was the only factor significantly associated with early mortality. The care of a surgical newborn is extremely challenging and requires the continuous involvement of skilled neonatologists for favorable outcomes. Despite a better understanding of postnatal and transitional neonatal care, the mortality rates among surgical newborns can be as high as >60% in developing countries . NumerouPatient populationThe study included all neonates who have undergone procedures for pediatric surgical conditions in the NICU at our center from August 2015 through February 2021. The majority of these procedures were performed by a senior Pediatric Surgeon. An ethical waiver was given by the Institute’s ethical committee in view of the retrospective nature of the study and all procedures being performed as a part of the routine management of these newborns. Data including antenatal diagnosis of the anomaly, gestational age, place of birth (outborn or inborn), birth weight, gender, age at the time of first surgery, number of surgeries per newborn, details of each surgical procedure, outcomes of surgery, and follow-up details were retrieved from the archives. The outcomes of surgeries were assessed in terms of postoperative complications, one-month survival, and overall survival.Criteria of surgery within the NICU As per our institutional criteria, newborns are operated within the NICU when they have very low birth weight (VLBW), i.e. <1500 grams; or any birth weight with risk factors making their transport to the OR risky such as the requirement of multiple inotropes, need for high-frequency ventilation, etc. Preparation and planning of the surgical procedure There are a total of 15 beds including four isolation rooms in the NICU at our center. These isolation rooms have a room area of 120 square feet and laminar airflow with 12 air changes per hour. The newborn, who is planned for the surgical procedure, is either nursed in the isolation room only or is shifted from the adjacent NICU bed after negative swab cultures of the isolation room. The energy sources, instrument set, anesthetic drugs, and consumables are transferred to the NICU. The operating team consists of two surgeons, an anesthetist, a neonatologist, a scrubbed nurse, and an OR technician. The ventilator settings are adjusted as per the baby’s requirements and intravenous anesthesia is given throughout the procedure. Continuous monitoring of the vital parameters is ensured during the surgical procedure. After the surgery, the baby is kept in the isolation room until declared physiologically stable by the neonatologist.Statistical analysisData were expressed as numbers, proportion, median, and range. The qualitative variables were analyzed using Fischer’s exact test. Factors significantly associated with early mortality (within one month of surgery) were assessed. A p-value of <0.05 was considered to be statistically significant. Data entry was done using Microsoft Excel  and analysis was performed using Stata/SE 12.0 .A total of thirteen newborns  were included in the present study. Only five (38%) of them had an antenatal diagnosis of their surgical anomaly. The median (range) gestational age at the time of delivery was 30 (26-36) weeks with an outborn:inborn ratio of 9:4. The median (range) birth weight of our cohort was 1200 (500-2860) grams. Associated congenital anomalies were present in 54% (7/13) of the newborns. Ten babies (77%) required mechanical ventilation in the preoperative period. Table The surgeries were performed for perforation peritonitis , intestinal obstruction 2/13; 15%), feeding intolerance , and urinary tract abnormalities causing complicated urinary tract infections . Overall, 22 surgeries were done in the cohort at a median (range) age of 3 (2-60) days. Of these, 18 procedures (82%) were performed by the pediatric surgery team. The remaining four procedures (18%) including clipping of the patent ductus arteriosus (PDA) (n=3) and laser excision of the aryepiglottic fold (n=1) required the involvement of Cardiac and Otolaryngology surgery teams respectively. Table /13; 15%,No major postoperative complications were observed in these newborns. Minor complications included wound dehiscence 3/13; 23%), persistent ileus , and peristomal excoriation . The one-month survival in our cohort was 84% (11/13). There were two early postoperative deaths due to refractory septic shock. Both of them had perforation peritonitis at the time of presentation. The only factor that was significantly associated (p=0.01) with early postoperative mortality was sick newborns on multiple inotropes and/or HFOV (Table /13; 23%,Management of neonatal surgical conditions is challenging. For achieving the best outcomes, optimization of perioperative stress factors is required apart from a high degree of surgical precision. Factors significantly associated with poor survival outcomes after newborn surgery include preoperative - low birth weight, lesser gestational age, positive blood cultures, and associated congenital anomalies; intraoperative - prolonged duration of surgery, blood loss of >10% blood volume, and intraoperative hypothermia; and postoperative - a requirement of mechanical ventilation for a prolonged duration, need for high-dose of vasopressors, postoperative sepsis, major complications in the postoperative period, and prolonged fasting ,6.In the study by Beckmann et al., a total of 191 incidents were reported due to intra-hospital transport of critically ill patients. Of these, more than one-third were contributed by transport to or from the OR . This beCritically ill preterm newborns are considered to be the prime candidates for bedside surgery as their transport to OR is very risky. However, the selection criteria in terms of birth weight differ among different NICUs. While some centers follow a cutoff of 1000 grams, others believe newborns with birth weight <1200 grams benefit the most from surgery within the NICU -5. We inAround 60% of the bedside procedures performed at our center were for perforation peritonitis or intestinal obstruction. Similar results have been demonstrated by previously published studies -5. AdditOn analyzing various factors associated with early postoperative mortality, it was found that the only variable having a significant association with unfavorable survival outcomes was the requirement of multiple inotropes and/or HFOV in the perioperative period. To our surprise, neither gestational age nor birth weight had any significant association with early mortality; despite these factors been linked to increased susceptibility of newborns to nosocomial infection. The above can be explained by the low incidence of sepsis in our cohort due to separate nursing of these newborns in the controlled environment of isolation rooms. In contrast, the NICUs where surgeries are performed on the same bed have a higher infection rate and mortality rate ,10. There are few limitations of this study. Firstly, this is a retrospective study with a small sample size. Secondly, the present study doesn’t compare the characteristics and outcomes of the included newborns with those operated for similar conditions within the OR ,3. As deDespite the above limitations, we report favorable one-month and overall survival of the newborns operated within the NICU. Although we have not compared the perioperative physiological characteristics of our cohort with the already published literature, we believe this favorable outcome is mainly a result of the ideal NICU arrangement, i.e. the newborn is operated in a separate, sterile, isolation room that is fully equipped . It not Performing surgeries within the NICU is a safe and feasible alternative to OR in at-risk newborns. One-month survival of as high as 84% can be achieved if these surgeries are performed in an ideal setting, i.e. sterile isolation rooms. The only factor significantly associated with early mortality in our limited cohort of newborns was the requirement of multiple inotropes and/or HFOV.


Sargus bipunctatus , feeding on a human corpse. The morphology of collected imagines and larvae of S. bipunctatus was documented, and a standard COI barcode sequence was obtained. Morphology- and DNA-based methods were used to distinguish the larvae of S. bipunctatus and its relative, Hermetia illucens . The potential of S. bipunctatus for practical applications in forensic entomology is currently difficult to assess.In the current study, we present the first record of twin-spot centurion fly larvae, Hermetia illucens . Analysis of fauna found on a human corpse, discovered in central Poland, revealed the presence of feeding larvae of another species from this family: the twin-spot centurion fly Sargus bipunctatus . The investigated corpse was in a stage of advanced decomposition. The larvae were mainly observed in the adipocere formed on the back and lower limbs of the corpse, and in the mixture of litter and lumps of adipocere located under the corpse. Adult specimens and larvae were identified based on morphological characters, and final identification was confirmed using DNA barcoding. Implementing a combination of morphological and molecular methods provided a reliable way for distinguishing the larvae of S. bipunctatus and H. illucens. The potential of S. bipunctatus for practical applications in forensic entomology is currently difficult to assess. Wide and reliable use of S. bipunctatus in the practice of forensic entomology requires further studies of the bionomy of this fly.The only European Stratiomyidae species known for feeding on human corpses was the black soldier fly  The family Stratiomyidae (soldier flies), representing the suborder of Brachycera Orthorrhapha, includes more than 2600 described species . Large sHermetia illucens . This species, probably native to Central America, can currently be found in warmer regions around the world. In the northern part of North America, it reaches the province of Ontario , is widespread in Europe and the northwest of North America [Dociostaurus moroccanus , and Oldroyd [Cerioporus squamosus (Huds.) Quélet (1886). The variety of substrates from which larvae of S. bipunctatus has been collected indicates a broad feeding spectrum. Despite this, only Chick [S. bipunctatus and decaying animal remains. Numerous females of the species were observed on the carcass of a domestic pig on the 24th day of decomposition. Nineteen days later, larvae were found feeding in a mixture of soil, mulch, and the putrefactive liquid exuding from the carcass. Sukontason et al. [Sargus sp. larvae feeding on human bodies found in the forests of Thailand from 2000–2006.The twin-spot centurion fly, Scopoli, 763 [=Chr America ,17. Sing America ,20. Acco America , it is a America ,22,23,24 America , larvae  Oldroyd  recordedly Chick  has repon et al.  recordedS. bipunctatus are very distinctive and easy to distinguish from the specimens of other necrophagous flies by their dorsoventral flattening. The only species possible to misidentify it with is Hermetia illucens, which belongs to the same family Stratiomyidae. The geographic distributions of both species overlap [H. illucens will expand through both natural processes and the unintentional release of mature flies from black soldier fly breeding farms. Larvae of S. bipunctatus and H. illucens can be easily distinguished based on morphological features alone. Sargus bipunctatus has a distinct colouration pattern, with six longitudinal stripes on its abdominal segments, and very short dorsal, dorsolateral, lateral and ventral bristles , included in the red lists of threatened animals in Central European countries [N. littoralis development, conducted under laboratory conditions [S. bipunctatus. Further studies of this species should have a precise forensic profile and cover field studies of environmental preferences, preferred food sources and habitats, role in necrophagous insect community, and activity period during successional changes of carrion, as well as laboratory experiments concerning thermal requirements during the development of immature life stages.Imagines of  October . In the albiceps . More detomology . Based oountries ,39. Analountries ,40. Suchnditions ,42. Finanditions ,44. We h


This study examined the associations between maternal elements levels and birth outcomes, and sociodemographic factors contributing to elements levels. Maternal age, parity, body mass index, smoking, and education were linked to concentrations of some but not all elements. In adjusted models, one ln-unit increase in Pb levels was associated with increased gestational age  and decreased birth weight  and birth length  in the Salta sample. Toxic elements concentrations were not associated with birth outcomes in Ushuaia participants. Birth outcomes are multifactorial problems, and these findings provide a foundation for understanding how the body burden of toxic and essential elements, within the socioeconomic context, may influence birth outcomes.Pregnant women’s levels of toxic and essential minerals have been linked to birth outcomes yet have not been adequately investigated in South America. In Argentina,  Human exposure to metal contaminants is a problem of serious concern due to the ubiquitous presence, high environmental persistence, and the adverse health effects of cadmium (Cd), mercury (Hg), lead (Pb), arsenic (As), and other toxic elements . ConsequDespite the placental barrier, Pb, Hg, and As can transfer from mother to fetus via placenta or through breastfeeding and accumulate in fetal tissues ,6. DurinToxic elements exposure is a major and understudied public health concern for children in South America . A few sTo the best of our knowledge, the present study is the first to report maternal whole blood concentrations of toxic and essential elements related to pregnancy in Argentina. The aim was to examine newborn birth outcomes associated with maternal levels of toxic and essential elements, and sociodemographic factors contributing to maternal elements levels. Regional differences  and interactions with sex were also assessed.The EMASAR  study took place in Ushuaia in the south and Salta in the north of Argentina. Descriptions of the study areas have been provided in detail elsewhere . In brieUiT The Arctic University of Norway and Stavanger University Hospital in Norway were responsible for the project in partnership with the private Clínica San Jorge in Ushuaia and the Hospital Público Materno Infantil in Salta.n = 696 maternal whole blood samples collected from Ushuaia (n = 198) and Salta (n = 498) from singleton births at 36 ± 12 h after delivery.The study period was from April 2011 to March 2012. More than 90% of invited women consented to participate for a total of 717 women recruited at delivery; 698 women offered whole blood samples and were thus included in this study. Through personal interviews, participants completed questionnaires covering personal characteristics, socio-economic factors, previous children and breastfeeding history, environmental and health and lifestyle conditions, and dietary intake. Obstetrical information of current and previous delivery was acquired through medical records. Non-fasting maternal blood samples, height, and weight were obtained at 36 ± 12 h following delivery . For details about the study profile material and methods, refer to Økland et al. . Th. Th65]. In general, our observed whole blood levels of essential elements were in the middle to higher range compared with other studies . These eThis EMASAR study provides evidence of associations between exposure to toxic and essential elements and birth outcomes. We found positive associations between Pb concentrations and gestational age in Salta women. Significantly higher blood Pb levels were reported in women in their third trimester than those in the first trimester of pregnancy ,80. PrevMaternal blood Hg concentration showed a significant positive association with gestational age and negative relationships with birth weight, length, and head circumference in the entire sample. These findings were in agreement with previous studies ,88,89, wCu was an important exposure associated with birth outcomes in the present study. We found an association between higher levels of Cu in maternal blood and longer gestation length in the overall sample and lower birth weight, shorter birth length, and head circumference in Salta women. Due to the development of the placenta during pregnancy, blood Cu levels increasing in the late gestational stages . The safApart from Cu, Se is the main essential trace element associated with birth outcomes that showed negative relationships with neonatal anthropometric measurements. Our negative findings with increased Se were contrary to several studies that reported positive associations between cord and maternal blood and placenta Se levels and birth weight and birth height ,96,97; aA few studies have investigated the links between maternal Zn status and birth outcomes. We observed negative relationships between Zn levels and birth weight, birth length, and head circumference in the Salta sample. Similarly, McMichael et al. suggested that maternal mid-pregnancy zinc status was weakly negatively correlated with length of gestation and birth weight . HoweverNo significant associations between Mn exposure and birth outcomes were observed in this study. Similarly, several previous studies demonstrated that maternal Mn concentrations are not associated with birth outcomes ,105. ZotThe findings in the present study address the knowledge gap of maternal toxic and essential trace elements exposure in Argentinian pregnant women in two geographical areas. Demographic, socioeconomic, and lifestyle characteristics that differ between coastal inhabitants and high-altitude populations in Argentina were captured by this study and, together with biomonitoring and birth outcomes data, can offer novel insights in this area of maternal environmental health.Despite the strengths, the present study also has some limitations. The sample size is relatively small with some results showing large confidence intervals, and it is therefore important that our study results are replicated in larger studies among different sample groups. There were several residual confounding factors that were not considered, such as frequency of food intake, vitamin and folic acid supplements, and other interactions. Self-reported data including pre-pregnancy weight, smoking habits, and education might have contributed to bias. Maternal blood samples were only measured once after the delivery, which may not accurately reflect elements concentrations during the pregnancy and postpartum. Previous studies have reported a U-shaped curve in maternal blood lead concentrations during the pregnancy, for example, Nishioka et al. found that blood lead levels were decreased at 25 weeks and then increased at 36 weeks of gestation . A studyThe results of the present biomonitoring study provide novel insights relevant for public health in both northern and southern Argentina. The region of residence was one of the main determinants for both toxic and essential elements exposure. Maternal characteristics such as age, pre-pregnancy BMI, smoking, and education were also shown to predict maternal levels of certain elements postnatally. Delivering mothers in Salta had significantly lower education, showed higher levels of Cd, Hg, and Pb after adjustment for covariates, and nearly all toxic elements were detectable in Salta women, putting them and their children at risk. The differences between Ushuaia and Salta can be inferred to reflect differences in socioeconomic conditions, prior or current industry emissions, soil contamination, dietary intake, and other potential contributors of current and historical regional pollution. Birth outcomes are multifactorial problems, and these findings provide a foundation for understanding how the body burden of toxic and essential elements, within the socioeconomic context, may influence birth outcomes.