搜索结果：Birth defects research

Children with birth defects often require complex medical care, contributing to increased healthcare costs. Understanding the economic burden of birth defects is important for resource planning, but recent Texas-specific data are lacking. A retrospective data analysis was conducted using the Texas Hospital Inpatient Discharge Public Use Data File (PUDF) for all pediatric discharges (ages 0-17&#x2009;years) documented between 2021 and 2023. We identified hospitalizations with birth defects based on the presence of an ICD-10 code (Q00-Q99) in any of the 26 diagnosis code fields. Median inflation-adjusted hospitalization charges were calculated for hospitalizations with and without birth defects and were then stratified by characteristics of interest. Median charges were compared using the Wilcoxon-rank sum test. Among hospitalizations of children with a birth defect in the principal diagnosis code field, charges were examined by birth defect phenotype. A sub-analysis assessed charges for hospitalizations that occurred primarily in the Intensive Care Unit (ICU). In Texas, 12.5% of all pediatric hospitalizations were for children with a birth defect. Aggregate total charges for these hospitalizations exceeded $26&#x2009;billion and comprised 34.9% of all pediatric hospitalization charges. Hospitalizations for children with a birth defect had significantly higher median charges ($12,876 vs. $7,813) compared to hospitalizations for children without birth defects (p&#x2009;<&#x2009;0.001). Higher charges were observed for hospitalizations among several subgroups (e.g., ICU hospitalizations). Inpatient hospitalization charges for children with birth defects had a disproportionately high impact on hospitalization charges in Texas.

Globally, births to women in their early thirties have become more prevalent. The current study aimed to examine the association of maternal age (30-34 years) with adverse perinatal outcomes, especially congenital birth defects and stillbirth. A literature search was conducted using PubMed, Web of Science, and Google Scholar for relevant studies published between July 1989 and August 2025. The primary outcomes were congenital birth defects (i.e., composite of Down syndrome and structural birth defects) and stillbirth. The secondary outcomes were preterm birth, low birthweight (LBW), neonatal mortality, small-for-gestational age (SGA), and intrauterine growth restriction (IUGR). Adverse perinatal outcomes were examined in women aged 30-34 compared with younger cohorts aged 18-29 years. The quality of the included studies and potential publication bias were evaluated. For the meta-analysis, forest plots were created for each outcome, and heterogeneity was assessed using the I2 statistic. Data were synthesized employing both random- and mixed-effects models. Sixty studies were included in this meta-analysis. Maternal age (30-34 years) was associated with a significantly higher risk of overall congenital birth defects (OR, 1.10; 95% CI, 1.03, 1.17; P = 0.007; I 2 = 92) compared with a reference age group of 18-29 years. The pooled subgroup analysis revealed that maternal age (30-34 years) showed a significant association with Down syndrome (OR, 1.97; 95% CI, 1.79, 2.16; P < 0.00001; I 2 = 0) but a non-significant association with structural birth defects (OR, 0.99; 95% CI, 0.94, 1.05; P = 0.8; I 2 = 84). Moreover, maternal age (30-34 years) showed a non-significant association with stillbirth (OR, 1.07; 95% CI, 0.94, 1.23; P = 0.3; I 2 = 100), preterm birth, LBW, neonatal mortality, SGA, and IUGR. Maternal age 30-34 years was associated with a significantly higher risk of congenital birth defects, especially Down syndrome, but was not associated with other adverse perinatal outcomes, when compared to the 18-29 age group. https://www.crd.york.ac.uk/prospero/, identifier CRD420251105683.

To evaluate perspectives of counseling and decision making among birthing parents who chose termination or hospice birth due to a fetal congenital heart defect (CHD). Qualitative analysis of semi-structured interviews with birthing parents who chose either termination or hospice birth due to severe fetal CHD. Participants were recruited from a purposive sample of those who received multidisciplinary counseling at a tertiary congenital heart surgical center between 2019-2023. Thematic analysis was conducted in five stages, using an integrated deductive-inductive approach. In total, 20 individuals were eligible; 10 completed interviews. Identified themes were categorized in two domains: Experiences During Counseling and Individual Factors Affecting Decision Making. Themes in the first domain included: areas for improvement during counseling, perceived strengths of counseling, patient attributes affecting counseling, and views on provider recommendations. Themes in the second domain included: emotions affecting decision making, value for reproductive autonomy, family factors, internal factors, outside input, and desire for resources. In this study, birthing parents who chose termination or hospice for fetal CHD appreciated information extending beyond clinical outcomes to include family and financial impacts. Their value for reproductive autonomy reflects the need for clinicians to gain skills in empathetic and neutral counseling of all management options.

ObjectiveTo evaluate the associations between maternal cigarette smoking and preterm birth (PTB) among infants with orofacial clefts (OFCs).DesignPopulation-based retrospective cohort study.SettingUsing data from the National Birth Defects Prevention Study (NBDPS, 1997-2011 deliveries) and the Birth Defects Study To Evaluate Pregnancy exposureS (2014-2021 deliveries), we evaluated the association between maternal smoking and PTB (<37 weeks) among liveborn infants with cleft lip with/without cleft palate (CL&#xb1;P), cleft palate only (CP), or any OFC.ParticipantsIn total, 5618 liveborn infants with OFCs (3699 CL&#xb1;P and 1919 CP).Main Outcome Measure(s)Adjusted relative risks (aRRs) and 95% confidence intervals (CIs) were calculated using Poisson regression, adjusted for covariates. For each OFC group, smoking (any vs none) was evaluated during 5 pregnancy timepoints (eg, first trimester). Analyses were repeated for smoking intensity (none, 1-14, &#x2265;15 cigarettes/day) (NBDPS only). Any smoking and smoking intensity were also evaluated for extremely-to-very (<32 weeks) and moderate-to-late preterm (32 to <37 weeks).ResultsAmong infants with OFCs, 14.5% were born preterm. Heavy smoking (&#x2265;15 cigarettes/day vs none) in the second trimester was associated with PTB among infants with CP (aRR: 1.89, 95% CI: 1.03-3.45) and extremely-to-very PTB among infants with any OFC (aRR: 3.37, 95% CI: 1.47-7.73). Associations were generally stronger for CP than for CL&#xb1;P, though imprecise.ConclusionsHeavy smoking during the second trimester may increase the risk of extremely-to-very PTB in infants with OFCs and PTB among infants with CP, further supporting the importance of promoting maternal smoking cessation or reduction.

Congenital heart defects (CHD) constitute a prevalent group of structural birth anomalies, characterised by substantial genetic heterogeneity and diverse clinical phenotypes. To investigate the underlying genetic architecture, we performed whole-genome sequencing (WGS) in a cohort of 50 patients with echocardiographically confirmed CHD, followed by systematic variant identification and functional annotation. Our analysis reveals the limited discriminatory capacity of current genomic annotation databases and underscores the necessity of stratifying genetic risk assessments by specific CHD subtypes. By integrating clinical classifications, genomic data, and tissue-specific expression profiles, we identified novel coding and non-coding variants alongside putative regulatory signals that may contribute to CHD pathogenesis. Within cardiac-specific genes, we identified CHD subtype-specific genetic associations, including JARID2 with PDA, GOSR2/TBX18 with VSD, PCDHA9 with ASD, and a multi-gene signature (CREBBP, ZFPM2, SLC27A6, ADAM17, ETS1) with atrioventricular septal defects. Among coding variants in non-CHD-associated genes, we identified COL11A2 and PCOLCE2 as plausible collagen-related candidates for CHD pathogenesis. These findings reinforce the polygenic architecture of CHD and highlight the value of context-aware, phenotype-driven interpretation of genetic variants. Collectively, this study expands the understanding of the genetic landscape underlying congenital heart anomalies and emphasises the need for larger, deeply phenotyped cohorts to translate these preliminary insights into clinically applicable predictors.

Neonatal mortality remains disproportionately high in sub-Saharan Africa, where an estimated 27 neonatal deaths per 1,000 live births occur annually. Infections, including sepsis and meningitis, account for a substantial proportion of these deaths, while neural tube defects (NTDs) contribute significantly to both neonatal mortality and long-term disability. Existing surveillance systems in the region are predominantly facility-based, missing the substantial proportion of births and deaths that occur in the community. Population-based surveillance platforms that capture community-level data are urgently needed to generate accurate incidence estimates, identify modifiable risk factors, and guide evidence-based interventions. The Consortium to Reduce Infant Mortality (CONRIM) is a multi-institutional partnership among Ugandan physicians and scientists, Yale University, Penn State University, Boston Children's Hospital/Harvard Medical School, and Uganda's National Planning Authority. CONRIM conducts prospective, community-based neonatal surveillance within the Busoga Kingdom in eastern Uganda. A network of 813 trained Village Health Team members conducts household-level visits using a structured Open Data Kit (ODK)-based mobile questionnaire to capture every birth, assess for danger signs of possible serious bacterial infection (pSBI), screen for NTDs, and record maternal nutrition and folic acid use, water, sanitation and hygiene (WASH) conditions, and health care utilization. Since surveillance began in June 2025, the platform has registered approximately 22,200 household submissions and over 5,700 newborn encounters across the Jinja District (population 660,000). Early data have identified higher than expected rates of infants with NTDs including encephalocele and spina bifida; documented folic acid non-use in before and during most pregnancies; characterized WASH conditions in birthplaces; and mapped geospatial hotspots of neonatal infection risk in northeastern rural subcounties. Prospective 28-day follow-up of all live births has demonstrated a neonatal mortality rate of 21.5 per 1000 live births. A real-time data quality monitoring system with 21 automated quality control flags maintains a 99% clean-record rate. Ongoing and planned activities include laboratory-based confirmation of neonatal sepsis via blood culture and cerebrospinal fluid analysis with polymerase chain reaction capacity, portable neuroimaging for NTDs, environmental sampling, genomic studies of folate metabolism pathway genes, linkage with facility-based records at Jinja Regional Referral Hospital and Mulago National Referral Hospital, and community-level interventions informed by surveillance findings.

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD). Early diagnosis is therefore critical for improving patient outcomes.However, traditional clinical biomarkers are constrained by diagnostic latency and limited sensitivity, particularly in cases of non-albuminuric DKD. To address these limitations, this review systematically explores the technical framework of the pathology-anchored strategy and proposes a two-phase translational approach, consisting of Pathology Anchoring Discovery and Prospective Early Validation. This strategy employs renal biopsy as the pathological gold standard in conjunction with multi-omics technologies to correlate circulating or urinary molecules with specific renal histological lesions, ultimately identifying non-invasive biomarkers with definitive pathological relevance. While numerous biomarkers demonstrate early warning potential in high-risk populations with normal conventional indicators, the pathology-anchored framework serves as a critical bridge linking these clinical biomarkers and distinct pathological changes. This review presents potential insights for early identification, risk stratification, and prognostic assessment of DKD.

The escalating problem of bacterial drug resistance poses a severe threat to global public health, with Acinetobacter baumannii (A. baumannii) exhibiting particularly high resistance rates that are closely linked to its Quorum Sensing (QS) system. This narrative review synthesizes current knowledge on the A. baumannii QS system, focusing on its essential role in mediating antimicrobial resistance, as well as the latest progress in developing QS inhibitors. Key findings indicate that the A. baumannii QS system enhances bacterial survival by promoting biofilm formation, and regulating the expression of efflux pump and resistance genes. However, significant translational challenges remain, including the risk of inducing resistance, the poor bioavailability and suboptimal pharmacokinetic properties, and their reduced efficacy in complex biological systems. In conclusion, while QS inhibitors represent a promising therapeutic target, overcoming current developmental bottlenecks requires combining them with traditional antibiotics, exploring novel drug delivery strategies, and integrating cutting-edge tools to accelerate drug discovery and clinical application.

Maternal autoimmune diseases (ADs) are associated with adverse pregnancy outcomes, yet their specific impact on offspring structural congenital heart disease (CHD) remains inconclusive. This study aimed to evaluate the risk of structural CHD in children born to mothers with various ADs using a nationwide population-based database. We conducted a nationwide retrospective cohort study using the Maternal and Child Health Database in Taiwan (2004-2019), a comprehensive data set linking the National Health Insurance Research Database with birth registries. We identified 4708 live births from mothers with ADs and matched them 1:2 with 9416 control births. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for structural CHD, adjusting for maternal age, comorbidities, and pregnancy-related factors. Offspring of mothers with ADs had a significantly higher risk of CHD compared with the control group (aHR, 1.51 [95% CI, 1.24-1.85]). Specific maternal ADs significantly associated with offspring CHD included systemic lupus erythematosus (aHR, 2.01 [95% CI, 1.55-2.60]) and Sj&#xf6;gren syndrome (aHR, 1.47 [95% CI, 1.10-1.96]). Maternal ADs are independent risk factors for offspring structural CHD. These findings underscore the importance of multidisciplinary counseling and specialized fetal echocardiographic screening for pregnant women with ADs to ensure early detection and management of potential cardiac defects in their offspring. URL: https://www.clinicaltrials.gov; Unique identifier: CS19009.

Recurrent reproductive failure impairs women's health, and the efficacy of immunosuppressants for this condition remains uncertain. This study aimed to explore the clinical application of common immunosuppressive agents including cyclosporine A, tacrolimus, etanercept and adalimumab for recurrent reproductive failure, which covers recurrent spontaneous abortion and recurrent implantation failure after IVF/ICSI, and to assess their efficacy and safety so as to provide evidence-based references for clinical practice. We retrieved eligible randomized controlled trials and cohort studies published from January 1, 2005 to February 28, 2025 from PubMed, Web of Science, CNKI and Wanfang databases, and conducted a systematic review and meta-analysis. This study was registered on PROSPERO (ID: CRD420251057130). A total of 13 randomized controlled trials and 7 cohort studies involving 2266 patients were finally included. Meta-analysis revealed that compared with the control group, immunosuppressive therapy significantly elevated live birth rate (RR=1.33, 95%CI:1.20-1.47, P&#x202f;<&#x202f;0.00001) and clinical pregnancy rate (RR=1.24, 95%CI:1.11-1.39, P&#x202f;=&#x202f;0.0001), while lowering miscarriage rate (RR=0.45, 95%CI:0.37-0.54, P&#x202f;<&#x202f;0.00001). No significant differences were found in the incidence of adverse events (RR=0.96, 95%CI:0.69-1.34, P&#x202f;=&#x202f;0.83) and birth defect rate (RR=0.63, 95%CI:0.19-2.07, P&#x202f;=&#x202f;0.45) between the two groups. In conclusion, the above immunosuppressive drugs can improve pregnancy outcomes in patients with recurrent reproductive failure and do not obviously increase adverse reactions and birth defects. Considering the limited quality of existing evidence and potential publication bias, the results should be interpreted cautiously, and the use of these drugs is recommended to be limited to clinical trials until verified by more large-scale and high-quality randomized studies.

Research engaged with AI has dramatically increased due to a huge improvement of technologies in terms of cost and time-effectiveness as well as decreasing use of animals. High throughput screening (HTS) is a frequently used method in drug discovery. Here, we combined two powerful tools for AI-driven identification of Zika virus (ZIKV) inhibitors. The main complication from ZIKV is microcephaly and other related birth defects when pregnant women become infected with this virus. To date, there are no specific vaccines and antiviral drugs for the treatment of ZIKV infection. We have successfully developed an HTS (1536 well-plate format) cell viability-based zika virus cytopathic effect (CPE) assay. To evaluate an AI-driven method, we implemented the CPE assay into a miniaturized format and screened 1,280 unique compounds. In addition, we incorporated an ultra-high throughput imager for 1536 well-plate HTS to rapidly obtain high-quality, brightfield images which were then analyzed by two different platforms. One platform, AVIA, uses deep convolutional neural networks (CNNs) to automate viral infectivity scoring based on CPEs long before signs of infection are visible to the human eye. The second, AutoHCS, utilizes a segmentation-free feature classification approach to develop probabilistic phenotypic profiles of antiviral compounds. Ultimately, AVIA was able to distinguish between infected and uninfected cells with high accuracy as early as 40 hours post infection, demonstrating a meaningful reduction in assay duration compared to the CPE readout. Furthermore, phenotypic profiling of 1,280 compounds using AutoHCS phenotypic profiling overlaid with AVIA infectivity scores identified many compounds that showed possible anti-viral effect. Interestingly, 12 out of 20 compounds that were identified as hit compounds in the original cell viability-based CPE assay were found by AVIA and AutoHCS, demonstrating reasonable concordance and reliability of this method. Further, by comparing AVIA infectivity scores against AutoHCS morphological profiles, we were able to also eliminate compounds as false-positives without additional counterscreens or orthogonal assays. Overall, we demonstrate a robust, sensitive assay that produces high quality imaging data which results in promising cost- and time-effective HTS when combined with modern AI/ML tooling.

Seasonal influenza remains an important public health concern worldwide, and pregnant women represent a particularly vulnerable population due to physiological and immunological changes associated with gestation. Influenza infection during pregnancy has been associated with adverse maternal, fetal and neonatal outcomes. This narrative review summarizes current evidence regarding maternal influenza infection and influenza vaccination during pregnancy. A structured literature search was conducted using PubMed, Embase and Cochrane Library databases. Studies published between 2020 and 2025 addressing maternal influenza infection, pregnancy outcomes and influenza vaccination were reviewed. Current evidence suggests that maternal influenza infection is associated with increased risks of spontaneous abortion, preterm birth, hospitalization and congenital malformations, especially neural tube defects and congenital heart defects when infection occurs during the first trimester. In contrast, evidence regarding long-term neurodevelopmental outcomes remains inconsistent. Influenza vaccination during pregnancy demonstrates moderate-to-high effectiveness in preventing maternal and neonatal influenza infection and shows a favorable safety profile. Available evidence also suggests that neuraminidase inhibitors, particularly oseltamivir, can be used safely during pregnancy without increasing the risk of congenital malformations or adverse neonatal outcomes. Influenza vaccination during pregnancy should continue to be promoted as a safe and effective public health strategy to protect both mothers and infants.

The TreeScan method is an emerging tool for active safety signal surveillance and has been increasingly applied in post-marketing monitoring of pharmaceuticals and vaccines. To evaluate methodological developments and application patterns of the TreeScan method. A scoping review was conducted by searching Embase, Medline, Cochrane Library, China National Knowledge Infrastructure, Wanfang, VIP, and SinoMed from inception to 16 May 2025. Two researchers independently screened studies and extracted data. Descriptive analyses were performed on study characteristics, methodologies, and application domains. Included studies were categorized as methodological or applied research. Forty-four articles were included, comprising 13 methodological studies (29.5%) and 31 applied studies (70.5%). Applied studies included drug safety surveillance (n = 10), vaccine safety surveillance (n = 16), and other areas such as drug repurposing and epidemiology (n = 5). Most studies originated from the United States (n = 28) and South Korea (n = 8). The Bernoulli model (43.2%), Poisson model (18.2%), and tree-temporal scan statistic (29.5%) were the most frequently used approaches. Positive controls we1re used in 63.6% of studies, while 36.4% employed within-group controls. Vaccine safety surveillance represented the most common application area, whereas methodological innovations focused on improving statistical performance, controlling confounding, and extending TreeScan to new data structures. TreeScan research is increasingly application-oriented, particularly in vaccine safety surveillance Recent methodological advances have improved its performance in handling confounding, hierarchical outcomes, and complex data structures. Future research should should prioritize validating newer TreeScan variants across diverse real-world databases and expanding applications beyond safety surveillance.

Cleft lip is a craniofacial anomaly, a developmental defect originating in the embryonic period. Cleft lip repair is most often performed between 3 and 6 months after birth. The scar that develops after repair is aesthetically and functionally improved through revision using various grafting techniques. The V-shaped mini-flap method is frequently used for the closure of mini-microform cleft lips. The aim of this study was to present the cosmetic and functional results. This was a retrospective observational study conducted from June 1, 2018 to June 30, 2024 including all patients who underwent secondary cleft lip revision. All patients had previously undergone primary cleft lip reconstruction, and all underwent revision for secondary cleft lip repair. A V-shaped mini flap was used to correct vermilion deviation, and a dermofat graft was used to prevent collapse. Some patients underwent simultaneous alveolar bone grafting. Numerical data were calculated by frequency analysis. The sample consisted of 30 patients who underwent secondary cleft lip revision. After primary cleft lip repair, whistling deformity occurred in 23.3% of the patients, vermilion irregularity in 26.7%, depression in 23.3%, pigmentation in 73.3%, and abnormal lip movements in 56.7%. Cleft lip was bilateral in 20% of patients and 40% had a history of concomitant cleft palate. Intraoperatively, 60% of the patients underwent V-shaped mini flap and 40% underwent V-shaped mini flap&#x2005;+&#x2005;alveolar bone graft. After secondary revision, hematoma developed in 6.7%, graft loss in 20%, and donor site morbidity in 13.4%, wound dehiscence, seroma in 10%, cyst formation in 6.7%, 10% of the patients were reoperated on. Secondary revision with a V-shaped mini flap or V-shaped mini flap&#x2005;+&#x2005;alveolar bone graft appears to be somewhat advantageous in correcting cosmetic and functional defects that arise after primary cleft lip repair, as it is associated with few manageable complications and may require a third cleft lip repair.

The 3 Abrahamic religions, namely Judaism, Christianity, and Islam, regard the human being as the most noble and perfect being due to their monotheistic attitude and value him above all creatures. This dignity is such that even the human embryo is viewed as a complete and perfect human being. All 3 religions place a high value on unborn life generally and prohibit abortion but allow exceptions when the mother's life is in danger. In Judaism, abortion is permitted to save the mother's life based on the concept of rodef, and some scholars allow it for pregnancies resulting from adultery or potential birth defects. Catholicism uses the principle of "double effect" to justify abortion when necessary to save the mother. Islam prioritizes warding off harm over gaining benefits, permitting abortion only when a certain benefit to the mother outweighs the harm to the fetus. Although there is a controversy over the human embryo in the early days of its formation, all 3 religions agree on the illegitimacy of abortion in the final months of pregnancy. Perhaps the permission of abortion in the event of a risk for the mother's health to preserve her health and well-being is the most important common ground of these 3 heavenly religions. The abortion permission in other cases, such as disability, maiming, is a matter of dispute between the 3 religions.

HR-positive HER2-low-expressing breast cancer is a unique subtype that has been refined from the traditional HER2 binary classification system in recent years, accounting for nearly 60% of the overall incidence of breast cancer. It has significant value for precise diagnosis and treatment research. This review systematically elaborates on the epidemiological characteristics, biological basis, diagnostic technology progress, and treatment strategy evolution of this subtype. HR-positive HER2-low-expressing breast cancer is characterized by the dominance of the estrogen receptor pathway and the core molecular feature of the intersection of HER2 low-expression signals. Its diagnosis requires a balance between the fundamental role of endocrine therapy and the precise screening of anti-HER2 targeted therapy. In terms of diagnosis, the initial screening by immunohistochemistry combined with fluorescence in situ hybridization has formed a standardized process. The integration of digital pathology, next-generation sequencing, and circulating tumor DNA in liquid biopsy technologies has effectively improved diagnostic accuracy and dynamic monitoring capabilities. In terms of treatment, endocrine therapy is the cornerstone, and the CDK4/6 inhibitor combination regimen is the standard for advanced first-line treatment. Antibody-drug conjugates, especially deruxtecan, have significantly improved patient prognosis and reshaped the treatment landscape. In summary, HR-positive HER2-low-expressing breast cancer has entered the era of individualized precise treatment guided by molecular typing. In the future, further exploration of new biomarkers, optimization of combination therapy strategies, and high-quality clinical research are needed to continuously improve patient survival outcomes.

Fragile X syndrome (FXS), the most common inherited form of intellectual disability and the leading monogenic cause of autism, results from the loss of the fragile X mental retardation protein (FMRP). Dysregulated translation of FMRP target mRNAs is believed to underlie the aberrant synaptic plasticity observed in FXS. Identification of these targets is critical for elucidating disease mechanisms and developing therapeutic strategies. We confirmed the interaction between FMRP and FYN mRNA by RNA immunoprecipitation in HEK293 and SH-SY5Y cells and assessed FYN translational regulation via polyribosome profiling in FXS and control lymphoblastoid cells. The role of FYN in ERK hyperactivation was examined in FXS lymphoblastoid cells, FMR1-knockdown SH-SY5Y cells, and dfmr1 mutant flies. Additionally, we tested whether reducing or inhibiting Src64B, a Drosophila Src family kinase with homology to human FYN, could rescue neural and behavioral defects in dfmr1 mutants. FMRP bound to FYN mRNA and suppressed its translation without affecting mRNA stability. Phosphorylated ERK1/2 levels were markedly elevated in FXS lymphoblastoid cells, and this hyperactivation was largely reversed by either the Src family kinase inhibitor PP2 or siRNA-mediated FYN knockdown, supporting an important role for FYN in ERK1/2 dysregulation. Similar changes were observed in FMR1-knockdown SH-SY5Y cells, with increased FYN expression and ERK1/2 phosphorylation, and PP2 treatment attenuated the abnormal ERK1/2 phosphorylation. Furthermore, genetic or pharmacological suppression of Src64B restored ERK signaling and rescued mushroom body defects and memory deficits in dfmr1 mutants. This study identifies FYN as a novel translational target of FMRP and suggests that its upregulation may contribute to hyperactivation of ERK1/2 signaling in FXS.

Infertile patients initially undergoing in vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI) with fresh embryo transfer often lack baseline indications for Preimplantation Genetic Testing for Aneuploidy (PGT-A); however, after multiple failed transfers, they may become eligible for PGT-A, which can be performed on residual vitrified-thawed embryos (a strategy termed "Midway PGT-A"), whose clinical value remains unconfirmed. This study aimed to assess the clinical utility of Midway PGT-A and whether fertilization methods (IVF vs. ICSI) affect its chromosomal testing results and clinical outcomes. A 2020-2023 retrospective cohort study analyzed 463 PGT-A cycles, comprising 202 Midway PGT-A cycles (132 IVF and 70 ICSI subcycles) and 261 traditional PGT-A cycles, with comparisons made regarding blastocyst aneuploidy profiles and clinical pregnancy outcomes. The results showed that compared with traditional PGT-A, Midway PGT-A was associated with fewer biopsied blastocysts (P<0.05), a higher rate of numerical chromosomal abnormalities (P<0.05), and a lower rate of structural chromosomal abnormalities (P<0.05). Within the Midway PGT-A group, IVF and ICSI subcycles had similar euploidy and aneuploidy rates, but the IVF subcycle exhibited significantly higher clinical pregnancy rate (P<0.05) and implantation rate (P<0.05).Multivariable logistic regression confirmed that ICSI was independently associated with lower clinical pregnancy rate vs IVF. In summary, Midway PGT-A delivers equivalent outcomes to traditional PGT-A. IVF does not alter the chromosomal detection results of Midway PGT-A and may further optimize clinical reproductive performance, validating the clinical value of Midway PGT-A for patients with post-transfer PGT-A eligibility. Many people having fertility treatments do not need embryo genetic testing initially. But after repeated failed pregnancies, miscarriages, or having a baby with birth defects, they may need this test later. We tested the genetic health of their leftover frozen embryos-a strategy we call "Midway testing".Our study of 463 cycles found that Midway testing worked as well as standard testing done earlier. The number of embryos tested was lower for Midway testing, but it found more whole-chromosome issues and fewer chromosome-structure issues. Fertilization methods did not change test results, but one method led to higher pregnancy and implantation rates.This testing offers a valuable option for people who need genetic embryo checks after failed fertility cycles, helping them use existing frozen embryos effectively.

Medication non-adherence is widely occurring in children and adolescents with ADHD, which may lead to adverse consequences. However, the pooled adherence rate and influencing factors are inconsistent in different studies. We searched PubMed, Embase (Ovid), Cochrane Library, and four Chinese Databases from inception to 20 February 2024. All types of studies were included. Two researchers independently extracted data and assessed the risk of bias based on ROBINS-I, NOS, and AHRQ. A random-effects meta-analysis was conducted to pool the prevalence estimates and factors that can be combined. After screening 2,360 publications, 63 studies were finally included, involving 450,759 participants. The general quality of the included studies was moderate to high quality. Adherence rates were reported in 50 studies, and a pooled adherence rate was 43.6% (95% Confidence Interval [CI] 39.0%-48.3%). The sensitivity analysis shows robust study results. However, both the primary analysis and the sensitivity analysis indicated high heterogeneity. The results of Meta-analysis identified five factors influencing adherence, of which female (Odds Ratio [OR] = 1.07, 95%CI:1.03-1.11), fewer medication doses (OR = 0.45, 95%CI:0.27-0.75), parental agreement with the medication plan (OR = 1.87, 95%CI:1.16-3.02), single-child families (OR = 1.80, 95%CI:1.29-2.52), and medication education for parents (OR = 6.34, 95%CI:3.97-10.12) can improve medication adherence. Besides, we also identified seven factors influencing adherence by qualitative analysis. Medication adherence is challenging for children and adolescents with ADHD, moreover, the meta-analysis of adherence rates showed high heterogeneity. We identified five modifiable factors by meta-analysis that are related to medication adherence, while other factors require further research. identifier CRD42024514310.