A new species of Hemiphyllodactylus (Squamata, Gekkonidae) from southwest Yunnan, China.

A new species of gekkonid, Hemiphyllodactylusgengmaensissp. nov., is described based on six specimens from Gengma Dai and Wa Autonomous County, Yunnan, China. The new species can be distinguished from its congeners by a significant genetic divergence of greater than 9.7% in the mitochondrial ND2 gene and a combination of the following characters: a maximum SVL of 43.24mm; 8 or 9 chin scales; six circumnasal scales; 2 or 3 internasal scales; 9-11 supralabial scales; 8 or 9 infralabial scales; 11-18 dorsal scales; 8-10 ventral scales; a manual lamellar formula of 5-5-5-4 or 5-6-5-4 and a pedal lamellar formula of 5-5-6-5; 20-25 precloacal and femoral pore-bearing scales contiguous in males; dark postorbital stripes or striping on body; dark dorsal transverse blotches present; and a brown postsacral mark bearing anteriorly projecting arms. The discovery of this new species brings the number of Hemiphyllodactylus species in China to 15.

The Zymoseptoria tritici avirulence factor AvrStb6 accumulates in hyphae close to stomata and triggers a wheat defense response hindering fungal penetration.

Zymoseptoria tritici, the causal agent of septoria tritici blotch, is one of Europe's most damaging wheat pathogens, causing significant economic losses. Genetic resistance is a common strategy to control the disease, Stb6 being a resistance gene used for over 100 years in Europe. This study investigates the molecular mechanisms underlying Stb6-mediated resistance. Utilizing confocal microscopy imaging, we identified that Z. tritici epiphytic hyphae mainly accumulates the corresponding avirulence factor AvrStb6 in close proximity to stomata. Consequently, the progression of AvrStb6-expressing avirulent strains is hampered during penetration. The fungal growth inhibition co-occurs with a transcriptional reprogramming in wheat characterized by an induction of immune responses, genes involved in stomata regulation, and cell wall-related genes. Overall, we shed light on the gene-for-gene resistance mechanisms in the wheat - Z. tritici pathosystem at the cytological and transcriptomic level, and our results highlight that stomata penetration is a critical process for pathogenicity and resistance.

Genome Re-Annotation and Transcriptome Analyses of Sanghuangporus sanghuang.

Sanghuangporus sanghuang, the generic type of Sanghuangporus belonging to Hymenochaetaceae, is a precious medicinal wood-inhabiting macrofungus with high commercial potential. To facilitate the medicinal utilization of this fungal resource, transcriptome sequences are newly generated from S. sanghuang strain MS2. In association with the previously generated genome sequences from the same strain by our lab and all available fungal homologous protein sequences in the UniProtKB/Swiss-Prot Protein Sequence Database, a new methodology was employed for genome assembly and annotation. A total of 13,531 protein-coding genes were identified from the new version of the genome of S. sanghuang strain MS2 with a complete BUSCOs of 92.8%, which indicates a remarkable improvement in the accuracy and completeness of the genome assembly. In general, more genes involved in medicinal functions were annotated compared with the original version of the genome annotation, and most of these genes were also found in the transcriptome data of the currently sampled growth period. Given the above, the current genomic and transcriptomic data provides valuable insights into the evolution and metabolites analysis of S. sanghuang.

Effect of salinity stress on nitrogen and sulfur removal performance of short-cut sulfur autotrophic denitrification and anammox coupling system.

The effects of salinity on anaerobic nitrogen and sulfide removal were investigated in a coupled anammox and short-cut sulfur autotrophic denitrification (SSADN) system. The results revealed that salinity had significant nonlinear effects on the nitrogen and sulfur transformations in the coupled system. When the salinity was <2 %, the anammox and SSADN activities increased with increasing salinity, and the total nitrogen removal rate, S0 production rate, and nitrite production rate were 0.41 kg/(m3·d), 0.37 kg/(m3·d), and 0.28 kg/(m3·d), respectively. With continuous increase of salinity, the performances of the anammox and SSADN gradually decreased, and the three indicators decreased to 0.14 kg/(m3·d), 0.22 kg/(m3·d), and 0.14 kg/(m3·d) at 5 % salinity, respectively. When the salinity reached 5 %, the nitrogen removal contribution of anammox decreased to 68.4 %, while the contribution of the sulfur autotrophic denitrification increased to 31.6 %. The coupled system recovered in a short time after alleviation of the salinity stress, and the SSADN activity recovery was faster than anammox. The microbial community structure and functional microbial abundance in the coupled system changed significantly with increasing salinity, and the functional microbial abundance after recovery was considerably different from the initial state.

Retrieval of Leaf Chlorophyll Contents (LCCs) in Litchi Based on Fractional Order Derivatives and VCPA-GA-ML Algorithms.

The accurate estimation of leaf chlorophyll content (LCC) is a significant foundation in assessing litchi photosynthetic activity and possible nutrient status. Hyperspectral remote sensing data have been widely used in agricultural quantitative monitoring research for the non-destructive assessment of LCC. Variable selection approaches are crucial for analyzing high-dimensional datasets due to the high danger of overfitting, time-intensiveness, or substantial computational requirements. In this study, the performance of five machine learning regression algorithms (MLRAs) was investigated based on the hyperspectral fractional order derivative (FOD) reflection of 298 leaves together with the variable combination population analysis (VCPA)-genetic algorithm (GA) hybrid strategy in estimating the LCC of Litchi. The results showed that the correlation coefficient (r) between the 0.8-order derivative spectrum and LCC had the highest correlation coefficients (r = 0.9179, p < 0.01). The VCPA-GA hybrid strategy fully utilizes VCPA and GA while compensating for their limitations based on a large number of variables. Moreover, the model was developed using the selected 14 sensitive bands from 0.8-order hyperspectral reflectance data with the lowest root mean square error in prediction (RMSEP = 5.04 µg·cm-2). Compared with the five MLRAs, validation results confirmed that the ridge regression (RR) algorithm derived from the 0.2 order was the most effective for estimating the LCC with the coefficient of determination (R2 = 0.88), mean absolute error (MAE = 3.40 µg·cm-2), root mean square error (RMSE = 4.23 µg·cm-2), and ratio of performance to inter-quartile distance (RPIQ = 3.59). This study indicates that a hybrid variable selection strategy (VCPA-GA) and MLRAs are very effective in retrieving the LCC through hyperspectral reflectance at the leaf scale. The proposed methods could further provide some scientific basis for the hyperspectral remote sensing band setting of different platforms, such as an unmanned aerial vehicle (UAV) and satellite.

Highly Stretchable and Biocompatible Wrinkled Nanoclay-Composite Hydrogel With Enhanced Sensing Capability for Precise Detection of Myocardial Infarction.

It is challenging to balance high biocompability with good mechanical-electrical sensing performance, especially when triggering inflammatory stress response after in vivo implantation. Herein, a bioinspired wrinkle-reinforced adaptive nanoclay-interlocked soft strain-sensor based on a highly stretchable and elastic ionic-conductive hydrogel is reported. This novel nanoclay-composite hydrogel exhibits excellent tensile properties and high sensing capacity with steady and reliable sensing performance due to the structural-mechanical-electrical integrity of the nanoclay crosslinked and nano-reinforced interpenetrating network. The incorporation of amphiphilic ions provides the hydrogel with significant protein resistance, reducing its non-specific adsorption to proteins upon implantation, improving its biosafety as an implanted device, and maintaining the authenticity of the sensing results. Based on the revealed sensing enhanced mechanism based on hierarchical ordered structures as a proof-of-concept application, this hydrogel sensor is demonstrated to be able to accurately localize the region where myocardial infarction occurs and may become a novel strategy for real-time monitoring of pathological changes in heart disease.

Effects of salinity on nitrite and elemental sulfur accumulation in a double short-cut sulfur autotrophic denitrification process.

Double short-cut sulfur autotrophic denitrification (DSSADN) coupled with Anammox is of great significance in the low-carbon treatment of nitrogen-containing wastewater. In order to achieve high salinity autotrophic nitrogen removal, the effects of different salinities on the accumulation characteristics of NO2--N and S0 and microorganisms in DSSADN process were studied. The results showed that the effect of salinity on the DSSADN process could be categorized into the stimulation, stable, and inhibition. When the salinity gradually increased to 2.5 %, the highest NO2--N production rate (NiPR) and S0 production rate (S0PR) of DSSADN were 0.54 kg/(m3·d) and 1.1 kg/(m3·d) respectively. NiPR and S0PR gradually decreased as the salinity increased to more than 3 %. However, salinity had a relatively low impact on nitrite accumulation efficiency and S0 accumulation efficiency, which were 80 % and 81.5 %, respectively, when the salinity reached 5 %. Salinity has a great influence on the structure and abundance of microbial communities in the system.

Alloexidiopsis gen. nov., A Revision of Generic Delimitation in Auriculariales (Basidiomycota).

Auriculariales is a fungal order with highly diverse morphological traits of basidiomes, which partially leads to a poor understanding of its taxonomic system at the generic level. To identify our recently collected specimens of Auriculariales to a species level, we perform a comprehensive phylogenetic analysis of the generic relationships in Auriculariales. In association with morphological characteristics, a new genus Alloexidiopsis belonging to Auriculariaceae is erected with two new species, namely, A. australiensis and A. schistacea. Moreover, Exidiopsis calcea separated from the generic type E. effusa and Heteroradulum niveum and H. yunnanense recently inaccurately described as members of Heteroradulum are recovered in the clade of Alloexidiopsis. These three species are thus transferred to this new genus. One collection of Exidiopsis grisea also falls in the clade of Alloexidiopsis, whereas another collection of this species is separated far from Alloexidiopsis and E. effusa. Since we have no collection to confirm the species identity of E. grisea, its generic position is uncertain. The main taxonomic morphological differences among Alloexidiopsis and related corticioid genera in Auriculariales are summarized. A key to all the five accepted species of Alloexidiopsis is provided. As two unnamed lineages exist in Alloexidiopsis besides the abovementioned five species, it is assumed that more new species will be revealed from this genus under its current circumscription.

A review for recent advances on soil washing remediation technologies.

Contaminated soils have caused serious harm to human health and the ecological environment due to the high toxicity of organic and inorganic pollutants, which has attracted extensive attention in recent years. Because of its low cost, simple operation and high efficiency, soil washing technology is widely used to permanently remove various pollutants in contaminated soils and is considered to be the most promising remediation technology. This review summarized the recent developments in the field of soil washing technology and discusses the application of conventional washing agents, advanced emerging washing agents, the recycling of washing effluents and the combination of soil washing and other remediation technologies. Overall, the findings provide a comprehensive understanding of soil washing technology and suggest some potential improvements from a scientific and practical point of view.

MTCLF: A multitask curriculum learning framework for unbiased glaucoma screenings.

BACKGROUND AND OBJECTIVE: Glaucoma is a disease that causes irreversible damage to the optic nerve. Research on accurate automatic screening algorithms is essential for the prevention and treatment of glaucoma. However, due to the imbalance of existing datasets and the existence of some hard samples that accompany other diverse and complex fundus diseases, the performance of current glaucoma screening algorithms is limited. In addition, the lack of interpretability also makes it difficult for the current algorithms to meet the requirements of clinical applications. METHOD: In this paper, we propose a new multitask curriculum learning framework (MTCLF) for unbiased glaucoma screenings and visualizations of model decision-making areas. MTCLF is a teacher-student framework. The teacher network is used to generate the label evidence map. The student network can diagnose glaucoma and predict the evidence map at the same time with the well-designed dual-branch CNN structure and collaborative learning module. We design two curriculum coefficients θ and σ to guide the training process of the student network in the sample space so that the student network can adaptively balance the sample contribution, reduce the prediction bias and mine hard samples. RESULTS: The experimental results show that the accuracy, sensitivity, specificity, AUC and F2-score of MTCLF based on the LAG dataset for glaucoma diagnoses are 0.967, 0.961, 0.970, 0.996, and 0.958, respectively. These results are superior to those of the state-of-the-art methods. CONCLUSION: MTCLF not only achieves the best performance for unbiased glaucoma diagnoses but also generates a reliable evidence map to help clinicians explore fine lesion areas.

DilUnet: A U-net based architecture for blood vessels segmentation.

BACKGROUND AND OBJECTIVE: Retinal image segmentation can help clinicians detect pathological disorders by studying changes in retinal blood vessels. This early detection can help prevent blindness and many other vision impairments. So far, several supervised and unsupervised methods have been proposed for the task of automatic blood vessel segmentation. However, the sensitivity and the robustness of these methods can be improved by correctly classifying more vessel pixels. METHOD: We proposed an automatic, retinal blood vessel segmentation method based on the U-net architecture. This end-to-end framework utilizes preprocessing and a data augmentation pipeline for training. The architecture utilizes multiscale input and multioutput modules with improved skip connections and the correct use of dilated convolutions for effective feature extraction. In multiscale input, the input image is scaled down and concatenated with the output of convolutional blocks at different points in the encoder path to ensure the feature transfer of the original image. The multioutput module obtains upsampled outputs from each decoder block that are combined to obtain the final output. Skip paths connect each encoder block with the corresponding decoder block, and the whole architecture utilizes different dilation rates to improve the overall feature extraction. RESULTS: The proposed method achieved an accuracy: of 0.9680, 0.9694, and 0.9701; sensitivity of 0.8837, 0.8263, and 0.8713; and Intersection Over Union (IOU) of 0.8698, 0.7951, and 0.8184 with three publicly available datasets: DRIVE, STARE, and CHASE, respectively. An ablation study is performed to show the contribution of each proposed module and technique. CONCLUSION: The evaluation metrics revealed that the performance of the proposed method is higher than that of the original U-net and other U-net-based architectures, as well as many other state-of-the-art segmentation techniques, and that the proposed method is robust to noise.

Genetic and epigenetic characteristics in ovarian tissues from polycystic ovary syndrome patients with irregular menstruation resemble those of ovarian cancer.

BACKGROUND: Irregular menstruation is clinically associated with an increased risk for ovarian cancer and disease-related mortality. This relationship remains poorly understood, and a mechanism explaining it has yet to be described. METHODS: Ovarian tissues from women with polycystic ovary syndrome (PCOS) and regular menstruation (n = 10) or irregular menstruation (n = 10) were subjected to DNA methylation sequencing, real-time PCR array, whole-exome sequencing, and bioinformatics analysis. RESULTS: We demonstrated that ovarian tissue from PCOS patients with irregular menstruation displayed global DNA hypomethylation, as well as hypomethylation at several functionally and oncologically significant regions. Furthermore, we showed that several cancer-related genes were aberrantly expressed in ovarian tissue from patients with irregular menstruation, and that their mRNA and microRNA profiles shared appreciable levels of coincidence with those from ovarian cancer tissue. We identified multiple point mutations in both the BRCA1 and MLH1 genes in patients with irregular menstruation, and predicted the potential pathogenicity of these mutations using bioinformatics analyses. CONCLUSIONS: Due to the nature of ovarian cancer, it is important to broaden our understanding of the pathogenesis and risk factors of the disease. Herein, we provide the first description of a genetic and epigenetic basis for the clinical relationship between irregular menstruation and an increased risk for ovarian cancer.

Characterization of the Sperm Proteome and Reproductive Outcomes with in Vitro, Fertilization after a Reduction in Male Ejaculatory Abstinence Period.

Semen samples from men after a short ejaculatory abstinence show improved sperm quality and result in increased pregnancy rates, but the underlying mechanisms remain unclear. Herein, we report that ejaculates from short (1-3 h) compared with long (3-7 days) periods of abstinence showed increases in motile sperm count, sperm vitality, normal sperm morphology, acrosome reaction capacity, total antioxidant capacity, sperm mitochondrial membrane potential, high DNA stainability, and a decrease in the sperm DNA fragmentation index (p, < 0.05). Sperm proteomic analysis showed 322 differentially expressed proteins (minimal fold change of ±1.5 or greater and p, < 0.05), with 224 upregulated and 98 downregulated. These differentially expressed proteins are profoundly involved in specific cellular processes, such as motility and capacitation, oxidative stress, and metabolism. Interestingly, protein trimethyllysine modification was increased, and butyryllysine, propionyllysine, and malonyllysine modifications were decreased in ejaculates from a short versus, long abstinence (p, < 0.05). Finally, the rates of implantation, clinical pregnancy, and live births from in vitro, fertilization treatments were significantly increased in semen samples after a short abstinence. Our study provides preliminary mechanistic insights into improved sperm quality and pregnancy outcomes associated with spermatozoa retrieved after a short ejaculatory abstinence.

Assessment of the development of assisted reproductive technology in Liaoning province of China, from 2012 to 2016.

BACKGROUND: The development of assisted reproduction techniques (ART) has resulted in rapid advances in the treatment of infertility. However, a systematic assessment of ART and its processes and outcomes in China has never been carried out. The goal of this study was to assess the features of ART status from 2012 to 2016 in clinics and in vitro fertilization (IVF) laboratories in Liaoning, the largest IVF province in the northeast of China. METHODS: Data from Jan 1, 2012 to Dec 31, 2016 was retrieved from the assisted reproductive certificate registry of Liaoning province. We extracted data from: i) fresh and thawed cycles; ii) donor sperm and donor egg cycles; iii) intrauterine insemination with husband semen and donor semen (AIH and AID). RESULTS: We showed that: (i) there has been a significant increase in the number of IVF fresh and thawed cycles, and the proportion of cases of primary infertility and secondary infertility has decreased and increased, respectively; (ii) standard long GnRH agonist was the major ovarian stimulation protocol. During the observation period, increasing trends in the use of GnRH antagonists, mild stimulation, and natural cycles were observed; (iii) significant differences in the number of cycles, number of retrieved oocytes, fertilization rates, implantation rates, and sex ratio were noticed between conventional IVF and intracytoplasmic sperm injection; (iv) significant differences in age at treatment for infertility, number of cycles, and ectopic pregnancy rates were noticed between donor sperm cycles and donor egg cycles; (v) significant differences in number of thawed cycles, number of thawed embryos, embryo recovery rates, implantation rates, and clinical pregnancy rates were noticed between day 3 and day 5 embryos; (vi) significant differences in age at treatment for infertility, number of cycles, clinical pregnancy rates, ectopic pregnancy rates, and live birth ratio were noticed between AIH and AID. CONCLUSIONS: ART in Liaoning province has undergone substantial development from 2012 to 2016 in clinics and IVF laboratories. This presentation of detailed ART data will provide researchers, policy makers, and potential ART users a rich source of information about IVF characteristics in the northeast of China.

Selective serotonin reuptake inhibitor use during early pregnancy and congenital malformations: a systematic review and meta-analysis of cohort studies of more than 9 million births.

BACKGROUND: In 2005, the FDA cautioned that exposure to paroxetine, a selective serotonin reuptake inhibitor (SSRI), during the first trimester of pregnancy may increase the risk of cardiac malformations. Since then, the association between maternal use of SSRIs during pregnancy and congenital malformations in infants has been the subject of much discussion and controversy. The aim of this study is to systematically review the associations between SSRIs use during early pregnancy and the risk of congenital malformations, with particular attention to the potential confounding by indication. METHODS: The study protocol was registered with PROSPERO (CRD42018088358). Cohort studies on congenital malformations in infants born to mothers with first-trimester exposure to SSRIs were identified via PubMed, Embase, Web of Science, and the Cochrane Library databases through 17 January 2018. Random-effects models were used to calculate summary relative risks (RRs). RESULTS: Twenty-nine cohort studies including 9,085,954 births were identified. Overall, use of SSRIs was associated with an increased risk of overall major congenital anomalies (MCAs, RR 1.11, 95% CI 1.03 to 1.19) and congenital heart defects (CHD, RR 1.24, 95% CI 1.11 to 1.37). No significantly increased risk was observed when restricted to women with a psychiatric diagnosis (MCAs, RR 1.04, 95% CI 0.95 to 1.13; CHD, RR 1.06, 95% CI 0.90 to 1.26). Similar significant associations were observed using maternal citalopram exposure (MCAs, RR 1.20, 95% CI 1.09 to 1.31; CHD, RR 1.24, 95% CI 1.02 to 1.51), fluoxetine (MCAs, RR 1.17, 95% CI 1.07 to 1.28; CHD, 1.30, 95% CI 1.12 to 1.53), and paroxetine (MCAs, RR 1.18, 95% CI 1.05 to 1.32; CHD, RR 1.17, 95% CI 0.97 to 1.41) and analyses restricted to using women with a psychiatric diagnosis were not statistically significant. Sertraline was associated with septal defects (RR 2.69, 95% CI 1.76 to 4.10), atrial septal defects (RR 2.07, 95% CI 1.26 to 3.39), and respiratory system defects (RR 2.65, 95% CI 1.32 to 5.32). CONCLUSIONS: The evidence suggests a generally small risk of congenital malformations and argues against a substantial teratogenic effect of SSRIs. Caution is advisable in making decisions about whether to continue or stop treatment with SSRIs during pregnancy.

Multiparameter Analysis of Gas Transport Phenomena in Shale Gas Reservoirs: Apparent Permeability Characterization.

The large amount of nanoscale pores in shale results in the inability to apply Darcy's law. Moreover, the gas adsorption of shale increases the complexity of pore size characterization and thus decreases the accuracy of flow regime estimation. In this study, an apparent permeability model, which describes the adsorptive gas flow behavior in shale by considering the effects of gas adsorption, stress dependence, and non-Darcy flow, is proposed. The pore size distribution, methane adsorption capacity, pore compressibility, and matrix permeability of the Barnett and Eagle Ford shales are measured in the laboratory to determine the critical parameters of gas transport phenomena. The slip coefficients, tortuosity, and surface diffusivity are predicted via the regression analysis of the permeability data. The results indicate that the apparent permeability model, which considers second-order gas slippage, Knudsen diffusion, and surface diffusion, could describe the gas flow behavior in the transition flow regime for nanoporous shale. Second-order gas slippage and surface diffusion play key roles in the gas flow in nanopores for Knudsen numbers ranging from 0.18 to 0.5. Therefore, the gas adsorption and non-Darcy flow effects, which involve gas slippage, Knudsen diffusion, and surface diffusion, are indispensable parameters of the permeability model for shale.

Autophagy is activated in the ovarian tissue of polycystic ovary syndrome.

The importance of autophagy in polycystic ovary syndrome (PCOS)-related metabolic disorders is increasingly being recognized, but few studies have investigated the role of autophagy in PCOS. Here, transmission electron microscopy demonstrated that autophagy was enhanced in the ovarian tissue from both humans and rats with PCOS. Consistent with this, ovarian granulosa cells from PCOS rats showed increases in the autophagy marker protein light chain 3B (LC3B), whereas levels of the autophagy substrate SQSTM1/p62 were decreased. In addition, the ratio of LC3-II/LC3-I was markedly elevated in human PCOS ovarian tissue compared with normal ovarian tissue. Real-time PCR arrays indicated that 7 and 34 autophagy-related genes were down- and up-regulated in human PCOS , Signal-Net, and regression analysis suggested that there are a wide range of interactions among these 41 genes, and a potential network based on EGFR, ERBB2, FOXO1, MAPK1, NFKB1, IGF1,TP53 and MAPK9 may be responsible for autophagy activation in PCOS. Systematic functional analysis of 41 differential autophagy-related genes indicated that these genes are highly involved in specific cellular processes such as response to stress and stimulus, and are linked to four significant pathways, including the insulin, ERBB, mTOR signaling pathways and protein processing in the endoplasmic reticulum. This study provides evidence for a potential role of autophagy disorders in PCOS in which autophagy may be an important molecular event in the pathogenesis of PCOS.

Fluoxetine and congenital malformations: a systematic review and meta-analysis of cohort studies.

AIMS: To investigate the safety of fluoxetine use during pregnancy, and to better understand the relationship between maternal fluoxetine use during the first trimester and congenital malformations in infants. METHODS: PubMed and Web of Science databases were systematically searched from inception to 21 March 2016. Additional studies were identified in a manual search of the reference lists. Two reviewers independently extracted data. A third reviewer checked the data. Estimates were pooled using a random-effects model to calculate the summarized relative ratios (RR) and 95% confidence intervals (CI). RESULTS: Among 1918 initially identified articles, 16 cohort studies were included. The offspring of pregnant women exposed to fluoxetine during the first trimester had a statistically increased risk of major malformations (RR = 1.18, 95% CI = 1.08-1.29), cardiovascular malformations (RR = 1.36, 95% CI = 1.17-1.59), septal defects (RR = 1.38, 95% CI = 1.19-1.61), and non-septal defects (RR = 1.39, 95% CI = 1.12-1.73) with low heterogeneity in infants. There were no significant observations of other system-specific malformations in the nervous system, eye, urogenital system, digestive system, respiratory system, or musculoskeletal system, respectively. There was no indication of publication bias. CONCLUSIONS: The results of this meta-analysis indicate maternal fluoxetine use is associated with a slightly increased risk of cardiovascular malformations in infants. Health care providers and pregnant women must weigh the risk-benefit potential of these drugs when making decisions about whether to treat with fluoxetine during pregnancy.

Use of selective serotonin-reuptake inhibitors in the first trimester and risk of cardiovascular-related malformations: a meta-analysis of cohort studies.

The relationship between selective serotonin-reuptake inhibitors (SSRIs) use during first trimester and cardiovascular-related malformations of infants is still uncertain. Therefore, we conducted this systematic review and meta-analysis to assess the aforementioned association. A systematic literature review identified studies for cohort studies about SSRIs use and cardiovascular-related malformations in PubMed and Web of Science. We summarized relative risk (RRs) and 95% confidence intervals (CIs) of cardiovascular-related malformations using random-effects model, and heterogeneity and publication-bias analyses were conducted. Eighteen studies met the inclusion criteria. Pregnant women who were exposed to SSRIs at any point during the first trimester had a statistically significant increased risk of infant cardiovascular-related malformations (RR = 1.26, 95%CI = 1.13-1.39), with moderate heterogeneity (I2 = 53.6). The corresponding RR of atrial septal defects (ASD), ventricular septal defects (VSD), ASD and/or VSD was 2.06 (95%CI = 1.40-3.03, I2 = 57.8), 1.15 (95%CI = 0.97-1.36; I2 = 30.3), and 1.27 (95%CI = 1.14-1.42; I2 = 40.0), respectively. No evidence of publication bias and significant heterogeneity between subgroups was detected by meta-regression analyses. In conclusion, SSRIs use of pregnant women during first trimester is associated with an increased risk of cardiovascular-related malformations of infants including septal defects. The safety of SSRIs use during first trimester should be discussed to pregnant women with depression.

Sertraline use in the first trimester and risk of congenital anomalies: a systemic review and meta-analysis of cohort studies.

AIM: To perform a meta-analysis of available cohort studies on the association between sertraline use by pregnant women in the first trimester and the findings of congenital anomalies in infants. METHODS: A comprehensive search of articles published from the index date up to 31st December 2015 investigating the aforementioned associations was conducted on PubMed and Web of Science. Mesh headings used included the terms "serotonin reuptake inhibitor," "sertraline," "congenital anomalies" and "obstetrical outcome." RESULTS: Twelve cohort studies that involved 6 468 241 pregnant women were identified. We summarized odds ratios (ORs) and 95% confidence intervals (CIs) of congenital anomalies using the random-effects model. Pregnant women who used sertraline in the first trimester had a statistically significant increased risk of infant cardiovascular-related malformations (OR = 1.36; 95% CI = 1.06-1.74; I2  = 64.4%; n = 12) as well as atrial and/or ventricular septal defects (OR = 1.36, 95% CI = 1.06-1.76; I2  = 62.2%; n = 8). Additionally, positive but nonsignificant associations between sertraline use and congenital anomalies of the nervous system (OR = 1.39; 95% CI = 0.83-2.32; I2  = 0%; n = 5), digestive system (OR = 1.23; 95% CI = 0.76-1.98; I2  = 0%; n = 5), eye, ear, face and neck (OR = 1.08; 95% CI = 0.33-3.55; I2  = 32.1%; n = 3), urogenital system (OR = 1.03; 95% CI = 0.73-1.46; I2  = 0%; n = 5), and musculoskeletal system (OR = 0.97; 95% CI = 0.69-1.36; I2  = 0%; n = 5) were observed. CONCLUSION: This meta-analysis suggested that the use of sertraline use by pregnant women in the first trimester had an increased risk of cardiovascular-related malformations as well as atrial and/or ventricular septal defects in infants. Meanwhile, nonsignificant associations between sertraline use and other congenital anomalies were found. More cohort studies are warranted to provide detailed results of other congenital anomalies.