Planning and adjusting the COVID-19 booster vaccination campaign to reduce disease burden.

As public health policies shifted in 2023 from emergency response to long-term COVID-19 disease management, immunization programs started to face the challenge of formulating routine booster campaigns in a still highly uncertain seasonal behavior of the COVID-19 epidemic. Mathematical models assessing past booster campaigns and integrating knowledge on waning of immunity can help better inform current and future vaccination programs. Focusing on the first booster campaign in the 2021/2022 winter in France, we used a multi-strain age-stratified transmission model to assess the effectiveness of the observed booster vaccination in controlling the succession of Delta, Omicron BA.1 and BA.2 waves. We explored counterfactual scenarios altering the eligibility criteria and inter-dose delay. Our study showed that the success of the immunization program in curtailing the Omicron BA.1 and BA.2 waves was largely dependent on the inclusion of adults among the eligible groups, and was highly sensitive to the inter-dose delay, which was changed over time. Shortening or prolonging this delay, even by only one month, would have required substantial social distancing interventions to curtail the hospitalization peak. Also, the time window for adjusting the delay was very short. Our findings highlight the importance of readiness and adaptation in the formulation of routine booster campaign in the current level of epidemiological uncertainty.

Predicting autism from young Infants' empathic responding: A prospective study.

Difficulties in empathy are frequent among children with autism spectrum disorder (ASD), and often considered a core feature of autism. Reduced empathy during the second year of life has been shown to predict subsequent ASD diagnosis. However, links between empathy in the first year and ASD have not yet been investigated. Moreover, prior work focused on empathy for others' distress but not for others' joy. To address these gaps, this prospective longitudinal study followed 60 infants (33% girls), 39 at high genetic risk of ASD (siblings of children with ASD) and a matching control group. Infants' empathic responses to others' distress and happiness were assessed at ages 6, 9, and 12 months, using simulations by the mother/experimenter and videos of crying and laughing infants. Diagnosis was determined between 18 and 36 months. Infants later diagnosed with ASD showed a reduced empathic response toward a person simulating distress, but not toward a video of a crying peer, and not in response to others' joy (either in simulation or video). Overall, reduced empathic concern during the first year of life appears to be an early prodromal marker of subsequent ASD. Implications for theory, research, and practice are discussed.

Single-voxel delay map from long-axial field-of-view PET scans.

Objective: We present an algorithm to estimate the delay between a tissue time-activity curve and a blood input curve at a single-voxel level tested on whole-body data from a long-axial field-of-view scanner with tracers of different noise characteristics. Methods: Whole-body scans of 15 patients divided equally among three tracers, namely [15O]H2O, [18F]FDG and [64Cu]Cu-DOTATATE, which were used in development and testing of the algorithm. Delay times were estimated by fitting the cumulatively summed input function and tissue time-activity curve with special considerations for noise. To evaluate the performance of the algorithm, it was compared against two other algorithms also commonly applied in delay estimation: name cross-correlation and a one-tissue compartment model with incorporated delay. All algorithms were tested on both synthetic time-activity curves produced with the one-tissue compartment model with increasing levels of noise and delays between the tissue activity curve and the blood input curve. Whole-body delay maps were also calculated for each of the three tracers with data acquired on a long-axial field-of-view scanner with high time resolution. Results: Our proposed model performs better for low signal-to-noise ratio time-activity curves compared to both cross-correlation and the one-tissue compartment models for non-[15O]H2O tracers. Testing on synthetically produced time-activity curves showed only a small and even residual delay, while the one-tissue compartment model with included delay showed varying residual delays. Conclusion: The algorithm is robust to noise and proves applicable on a range of tracers as tested on [15O]H2O, [18F]FDG and [64Cu]Cu-DOTATATE, and hence is a viable option offering the ability for delay correction across various organs and tracers in use with kinetic modeling.

Ubiquitin ligase signalling networks shape presynaptic development, function and disease.

Ubiquitin ligases are important regulators of nervous system development, function and disease. To date, numerous ubiquitin ligases have been discovered that regulate presynaptic biology. Here, we discuss recent findings on presynaptic ubiquitin ligases that include members from the three major ubiquitin ligase classes: RING, RBR and HECT. Several themes emerge based on findings across a range of model systems. A cadre of ubiquitin ligases is required presynaptically to orchestrate development and transmission at synapses. Multiple ubiquitin ligases deploy both enzymatic and non-enzymatic mechanisms, and act as hubs for signalling networks at the synapse. Both excitatory and inhibitory presynaptic terminals are influenced by ligase activity. Finally, there are several neurodevelopmental disorders and neurodegenerative diseases associated with presynaptic ubiquitin ligases. These findings highlight the growing prominence and biomedical relevance of the presynaptic ubiquitin ligase network.

Prevalence, impact and associated factors of abnormal preoperative investigation result in patients undergoing surgery in Dilla University referral hospital: cross-sectional study.

Background: As one domain of preoperative assessment, preoperative investigations are often ordered to evaluate patient's medical condition for risk stratification and assessing patient status to undergoing surgery. Despite the fact that laboratory testing can assist in ensuring the best possible preoperative condition, routine screening examinations have a number of drawbacks. Although there are evidence-based recommendations for which investigations should be done, the tradition of routine preoperative testing is still prevalent and clinical practice with abnormal results detected varies. Method: Institution-based cross-sectional study design was conducted from 1 November to January at Dilla University Referral Hospital. Data was collected from complete pre-anaesthesia check-up sheets, investigations already done. It was collected at the individual level by using, closed-ended self-guided questionnaire. The collected data was entered, cleaned, edited and checked using SPSS version 26 for data processing and analysis. Logistic regression was performed to examine the impacts of abnormal preoperative investigation results and summarised by using tables and figures. An Adjusted odds ratio with 95% CI was computed to determine the level of significance. Result: Data of 208 patients (65.9 female) with mean±standard deviation age 30.83±15.340 years and 22.59±2.99 BMI were analysed. Patients were mostly American Society of Anaesthesiologists I and II underwent National Institute of Clinical and Health Excellence Grade 2 surgeries and surgical shape class 3. Totally, 178 (44.5%) test results were abnormal. CBC is the most detected abnormal result. Only 15 (3.75%) abnormalities had an impact in terms of delay, further investigations, and surgical technique. Comorbidity (AOR 7.982, 95% CI, P=0.041), medication history (AOR 1.463, 95% CI, P=0.013), ASA physical status II (AOR 3.287, 95% CI, P=0.029) and history of smoking (AOR 1.577, 95% CI, P=0.049) were factors which was significantly associated with abnormal preoperative investigation result. Conclusion: Only 0.6% of all tests had a significant impact in terms of changing perioperative anaesthetic management. The significant impact of abnormal investigation result noticed was delayed surgery.

Pre-hospital delay intention and its associated factors in the high-risk population of stroke: A latent profile analysis.

AIM: To explore the possible latent classifications of pre-hospital delayed intention at high risk of stroke and to analyze the characteristics of different profiles. METHODS AND RESULTS: A cross-sectional study was conducted in one community in Shanghai, China. 470 individuals at high risk of stroke were recruited, and self-reported questionnaires (including socio-demographic, stroke knowledge, health belief, and pre-hospital delay behavior intention scale) were distributed between April and June 2023. A latent profile analysis was employed to identify the delay intention clusters, and multinomial logistic regression was utilized to ascertain the factors influencing the latent classes of delay intention. 457 high-risk populations with a response rate of 97.23% were finally enrolled in this study. Four distinct classes were identified: High warning signs-Low delay intention (26.3%), Low warning signs-Low delay intention (17.7%), moderate level of delay intention (37.3%), and high level of delay intention (18.7%). The influencing factors included stroke knowledge, health belief, age, education background, the nearest distance to the medical institution, and household income. CONCLUSION: The pre-hospital delay intention among high-risk populations of stroke was classified into four distinct classes. It is crucial for individuals at high risk to remain vigilant towards stroke symptoms and to take prompt action. Health promotion education may be explored as a strategy to bridge the gap between the recognition of stroke symptoms and the low pre-hospital delay intention.

The apple does not fall far: stable predictive relationships between parents' ratings of their own and their children's self-regulatory abilities.

Having control over your own behavior and impulses is a critical skill that influences children's academic, social, and emotional development. This study investigates the stability and predictive relationships between parents' ratings of their own and their children's executive function and delay aversion. Using data from approximately 1700 families collected during the COVID-19 pandemic, we employed hierarchical structural equation models and cross-lagged panel models to analyze the temporal stability and directional influences of executive function and delay aversion assessments.Our analysis revealed a substantial latent correlation (r = 0.48, p < 0.001) between parents' and children's executive function problems, indicating a shared variance of approximately 23%. Significant cross-lagged effects were found, with parental executive functions at T1 predicting child executive functions at T2 (ß = 0.16, p = 0.005). For delay aversion, we found a latent correlation of r = 0.53 (p < 0.001) and significant within-timepoint and temporal stability, but no cross-lagged effects.These findings suggest that higher levels of executive function problems reported by parents at T1 correspond to an increased perception of similar problems in their children at T2. This highlights the importance of parental self-perception in assessing children's abilities. Our results highlight the importance of incorporating family dynamics into interventions targeting executive function difficulties and delay aversion in children, and understanding this interplay enables the development of more effective, individualized approaches to support positive developmental outcomes.

Oxygen extraction fraction mapping based combining quantitative susceptibility mapping and quantitative blood oxygenation level-dependent imaging model using multi-delay PCASL.

BACKGROUND AND PURPOSE: The oxygen extraction fraction is an essential biomarker for the assessment of brain metabolism. A recently proposed method combined with quantitative susceptibility mapping and quantitative blood oxygen level-dependent magnitude enables noninvasive mapping of the oxygen extraction fraction. Our study investigated the oxygen extraction fraction mapping variations of single-delay and multi-delay arterial spin-labeling. MATERIALS AND METHODS: A total of twenty healthy participants were enrolled. The multi-echo spoiled gradient-echo, multi-delay arterial spin-labeling, and magnetization-prepared rapid gradient echo sequences were acquired at 3.0 T. The mean oxygen extraction fraction was generated under a single delay time of 1780 ms, multi-delay arterial spin-labeling of transit-corrected cerebral blood flow, and multi-delay arterial spin-labeling of arterial cerebral blood volume. The results were compared via paired t tests and the Wilcoxon test. Linear regression analyses were used to investigate the relationships among the oxygen extraction fraction, cerebral blood flow, and venous cerebral blood volume. RESULTS: The oxygen extraction fraction estimate with multi-delay arterial spin-labeling yielded a significantly lower value than that with single-delay arterial spin-labeling. The average values for the whole brain under single-delay arterial spin-labeling, multi-delay arterial spin-labeling of transit-corrected cerebral blood flow, and multi-delay arterial spin-labeling of arterial cerebral blood volume were 41.5 ±â€¯1.7 % (P < 0.05), 41.3 ±â€¯1.9 % (P < 0.001), and 40.9 ±â€¯1.9 % (N = 20), respectively. The oxygen extraction fraction also showed a significant inverse correlation with the venous cerebral blood volume under steady-state conditions when multi-delay arterial spin-labeling was used (r = 0.5834, p = 0.0069). CONCLUSION: These findings suggest that the oxygen extraction fraction is significantly impacted by the arterial spin-labeling methods used in the quantitative susceptibility mapping plus the quantitative blood oxygen level-dependent model, indicating that the differences should be accounted for when employing oxygen extraction fraction mapping based on this model in diseases.

COVID-19 pandemic impact on gynecologic cancer treatment pathways in a Finnish tertiary center.

INTRODUCTION: COVID-19 and new guidelines during the pandemic affected the gynecologic cancer treatment pathways, resulting in recorded delays and modifications in the treatment protocols. The aim of this study was to determine the impact of the COVID-19 pandemic in one of the major gynecologic cancer care centers in Finland, Tampere University Hospital. MATERIAL AND METHODS: Our retrospective register study included 909 patients that were new gynecologic cancer cases (uterine, cervical, vulvar, vaginal, or ovarian) referred to the Tampere University Hospital Gynecologic Oncology Outpatient Clinic between March 17th, 2018, and March 15th, 2022. The patients were divided into two separate groups depending on their time of referral: time before COVID (March 17th, 2018, to March 15th, 2020), and during COVID (March 16th, 2020, to March 15th, 2022). These groups were compared in terms of patient characteristics, different cancer types and stages, symptoms, and treatment methods. RESULTS: During the COVID-19 pandemic, patients generally suffered from cancer symptoms longer (p < 0.003) and were more likely to be overweight (p = 0.035). The improved multidisciplinary team meeting gave the patients a faster route to their first intervention during COVID (p < 0.05). An insignificant shift toward nonsurgical first interventions and non-curative intent was seen during COVID, but the multidisciplinary team treatment plans were mostly implemented accordingly on both eras. No decrease was seen in the number of new gynecologic cancer cases, and the one-year overall survival remained the same in both groups. CONCLUSIONS: Overall, the COVID-19 pandemic did not significantly alter treatment pathways in gynecologic cancer care at Tampere University Hospital. The number of new patients and given treatments remained relatively stable. During COVID, access from referral to cancer treatment was significantly accelerated, which is likely confounded by changes to the multidisciplinary team protocol made in early 2021.

Developmental 17-OHPC exposure disrupts behavior regulated by the mesocorticolimbic dopaminergic system in rats.

The synthetic progestin, 17α-hydroxyprogesterone caproate (17-OHPC), is administered to pregnant individuals with the intention of reducing preterm birth. Although there is evidence that 17-OHPC is likely transferred from mother to fetus, there is little information regarding the potential effects of 17-OHPC administration on behavioral and neural development in offspring. Neonatal 17-OHPC exposure disrupts the development of the mesocorticolimbic dopaminergic pathway and associated behaviors in rats. 17-OHPC exposure altered dopaminergic innervation of prelimbic medial prefrontal cortex (mPFC) in neonates and adolescents and altered performance in measures of decision-making, set-shifting, and reversal-learning tasks. The present study tested the effects of developmental 17-OHPC exposure on numerous cognitive behaviors mediated by the mesocorticolimbic dopaminergic system, such as decision-making in a delay discounting task, latent inhibition following conditioned taste aversion (CTA), and spatial memory in the Morris Water Maze (MWM). The present work also aimed to further investigate response omissions in rats exposed to 17-OHPC during development and the potential role of dopamine D2 receptor in altering omissions in a delay discounting task. 17-OHPC exposure rendered rats less sensitive to an Eticlopride-induced increase in omissions in a delay discounting task when compared to controls. Quinpirole flattened the discount curve in both groups but did not significantly affect omissions in 17-OHPC-exposed or control rats. Following CTA, sucrose-pre-exposed 17-OHPC-exposed rats demonstrated decreased latent inhibition when compared to controls. In Morris Water Maze testing, 17-OHPC-exposed rats did not differ from controls after the first day of testing or during probe testing. These results suggest that exposure to 17-OHPC altered aspects of decision-making and latent inhibition in adult male rats, without affecting performance in a measure of spatial learning and memory. Further, the insensitivity of 17-OHPC-exposed males to an Eticlopride-induced increase in omissions suggests a dysfunction in the D2 receptor following exposure to this clinically used synthetic progestin.

OBSESSIVE COMPULSIVE DISORDER AND CONSTITUTIONAL DELAY OF GROWTH AND PUBERTY IN WOLFRAM SYNDROME: NEW ASPECTS AND A NOVEL WFS1 MUTATION.

Introduction: Wolfram Syndrome (WS) is a rare autosomal recessively inherited disorder characterized by juvenile-onset diabetes mellitus (DM), diabetes insipidus, optic atrophy (OA), hearing loss and neurodegeneration. This report describes three cases with WS. Case report: The first case was diagnosed with DM and OA at the age of 6 and 11 years, respectively. Second patient was the sibling of the first patient, also had DM and was investigated for WS after his brothers' diagnosis. The third patient was diagnosed with DM at the age of 5 years and developed bilateral sensorineural hearing loss and OA at the ages of 7 and 12 years, respectively. Preliminary diagnoses of all patients were confirmed by Sanger sequencing of the WFS1 gene. Two previously reported and a novel mutation were detected. While our first patient was diagnosed with attention deficit hyperactivity disorder previously described in WS patients, obsessive compulsive disorder observed in case 2, was not previously reported in WS to the best of our knowledge. Puberty delay was detected in our first patient and was diagnosed as constitutional delay of puberty and growth. Conclusion: Early diagnosis of WS can lead to early detection of associated pathologies and to decrease complications, morbidity and mortality.

A framework for the acoustic simulation of passing vehicles using variable length delay lines.

The sound produced by vehicles driving on roadways constitutes one of the dominant noise sources in urban areas. The impact of traffic noise on human activities and the related investigation on modeling, assessment, and abatement strategies fueled the research on the simulation of the sound produced by individual passing vehicles. Simulators enable in fact to promote a perceptual assessment of the nature of traffic noise and of the impact of single road agents on the overall soundscape. In this work, we present TrafficSoundSim, an open-source framework for the acoustic simulation of vehicles transiting on a road. We first discuss the generation of the sound signal produced by a vehicle, represented as a combination of road/tire interaction noise and engine noise. We then introduce a propagation model based on the use of variable length delay lines, allowing to simulate acoustic propagation and Doppler effect. The proposed simulator incorporates the effect of air absorption and ground reflection, modeled via complex-valued reflection coefficients dependent on the road surface impedance, as well as a model of the directivity of sound sources representing the passing vehicles. The source signal generation and the propagation stages are decoupled, and all effects are implemented using finite impulse response filters. Moreover, no recorded data is required to run the simulation, making the framework flexible and independent on data availability. Finally, to validate the framework capability to accurately simulate passing vehicles, a comparison between synthetic and recorded pass-by events is presented. The validation shows that sounds generated with the proposed method achieve a good match with recorded events in terms of power spectral density and psychoacoustics metrics as well as a perceptually plausible result.

Time to Diagnose Endometriosis: Current Status, Challenges and Regional Characteristics-A Systematic Literature Review.

BACKGROUND: Endometriosis diagnosis reportedly faces delays of up to 10 years. Despite growing awareness and improved guidelines, information on the current status is limited. OBJECTIVES: To systematically assess the published evidence on the status of time to diagnosis in individuals with endometriosis, with respect to the definition of time to diagnosis, geographical location and patient characteristics. SEARCH STRATEGY: MEDLINE (via PubMed) and Embase were searched for publications reporting time to diagnosing endometriosis since 2018. No restrictions to population or comparators were applied. All publications were screened by two independent reviewers. SELECTION CRITERIA: Search results were limited to primary publications of randomised controlled trials, non-randomised trials and observational studies. Case reports, secondary publications and grey literature were excluded. No restrictions were made regarding language, provided that an English title and abstract were available. DATA COLLECTION AND ANALYSIS: Publications were assessed with respect to time to diagnosis, diagnostic methods, study type, study country and potential bias. MAIN RESULTS: The 17 publications eligible for inclusion in this literature review were all observational studies. The publications reported diagnosis times between 0.3 and 12 years, with variations depending on the definition of time to diagnosis (overall, primary, or clinical), geographical location and characteristics of the included study population. Evidence was of poor to good quality overall. CONCLUSIONS: Diagnostic delay is still present, primarily driven by physicians, and this review underscores the need for standardised definitions, increased awareness and targeted diagnostic interventions.

Fixed Rate vs Fixed Injection Duration In Single-Pass Contrast-Enhanced Abdominal Multi-Detector CT: Effects On Vascular Enhancement.

OBJECTIVES: To evaluate the effects on vascular enhancement of either a fixed rate (FR) or a fixed injection duration (FID) in single-pass (SP) contrast-enhanced abdominal multi-detector CT (CE-MDCT). MATERIALS & METHODS: Ninety-nine (54M; 45F; aged 18-86 yrs) patients with nontraumatic acute abdomen underwent a SP CE-MDCT after i.v. injection of 1.7 cc/Kg of a nonionic iodinated contrast-media (370 mgI/ml) performed with either a FR (2 cc/sec; Group A) or a FID (55 sec; Group B). In both groups, patients were further stratified according to total body weight (Kg) as follows: 40-60 (L); 61-80 (M); 81-100 (H). Signal- (SNR) and contrast-to-noise ratios (CNR) were calculated for the liver and for both abdominal aorta (AA) and main portal vein (MPV). Statistical analysis was performed by Student's T or Chi-square test for continuous and categorical data, respectively, whereas post-hoc analysis was performed by the Mann-Whitney test (p < 0.05). RESULTS: There were no significant differences in demographic and physical characteristics between Group A (n = 50; 53 ± 20 yrs; BMI = 23.4 ± 4.4) and B (n = 50; 51 ± 17 yrs; BMI 22.7 ± 4.2). Whereas overlapping findings were observed in the M sub-groups (n = 40), SNR and CNR were significantly higher (p < 0.01) in Group B for both AA and MPV in the high (H) weight sub-groups (n = 20) while not significant differences were observed in the low (L) weight sub-groups (n = 40) despite a significantly lower injection rate (1.6 ± 0.2 cc/sec, p < 0.01) in Group B. CONCLUSION: A FID results in an overall better vascular enhancement than a FR in SP CE-MDCT.

Predictors of success in left bundle branch area pacing with stylet-driven pacing leads: a multicenter investigation.

Purpose: Although left bundle branch area pacing (LBBAP) is an emerging conduction system pacing modality, it is unclear which parameters predict procedural success and how many implant attempts are acceptable. This study aimed to assess predictors of successful LBBAP, left bundle branch (LBB) capture, and factors associated with the number of LBBAP implant attempts. Methods: This retrospective observational multicenter study was conducted in Korea. LBBAP was attempted in 119 patients; 89.3% of patients had bradyarrhythmia (atrioventricular block 82.4%), and 10.7% of patients had heart failure (cardiac resynchronization therapy) indication. Procedural success and electrophysiological and echocardiographic parameters were evaluated. Results: The acute success rate of lead implantation in LBBAP was 95.8% (114 of 119 patients) and that of LBB capture was 82.4% (98 of 119 patients). Fewer implant attempts were associated with LBBAP success (three or fewer vs. over three times, p = 0.014) and LBB capture (three or fewer vs. over three times, p = 0.010). In the multivariate linear regression, the patients with intraventricular conduction delay (IVCD) required a greater number of attempts than those without IVCD [estimates = 2.33 (0.35-4.31), p = 0.02], and the larger the right atrial (RA) size, the more the attempts required for LBBAP lead implantation [estimates = 2.08 (1.20-2.97), p < 0.001]. Conclusion: An increase in the number of implant attempts was associated with LBBAP procedural failure and LBB capture failure. The electrocardiographic parameter IVCD and the echocardiographic parameter RA size may predict the procedural complexity and the number of lead implant attempts for LBBAP.

Early-onset preeclampsia/gestational hypertension may be associated with a low incidence of cerebral palsy at 3 years old in singleton very low-birth-weight infants born at 28-31 weeks of gestation (EOPE-DQ study): a multi-center retrospective cohort study in 2013-2016.

Our aim was to evaluate the effects of any types of hypertensive disorders of pregnancy (HDP) on the development of either cerebral palsy (CP) or developmental delay (DD) at 3 years old in singleton very low-birth-weight (VLBW) infants born at 24-31 weeks of gestation. This was a retrospective cohort study of VLBW infants born at 24-31 weeks in 2013-2016 in Japan, using a nationwide obstetrical database, and Neonatal Research Network Japan (NRNJ) Database, accompanied by a secondary survey of women complicated with HDP (EOPE-DQ study). In 529 candidates for long-term follow-up in 7 tertiary centers, the percentage undergoing follow-up for CP at 3 years old was 56.1%, and the percentage receiving follow-up for DD at 3 years old was 54.1%. The percentage of PE/SPE/GH was significantly lower in infants with CP than in controls (1/22 [4.5%] vs. 66/274 [24.1%], p = 0.034); especially, in infants born at 28-31 weeks, the percentage of PE/SPE/GH was significantly lower in infants with CP than in controls (0/13 [0%] vs. 44/151 [29.1%], p = 0.021). The percentage of PE/SPE/GH was not different between infants with DD and controls (9/49 [18.4%] vs. 54/237 [22.8%], p = 0.574). The percentage of composite risk factors (either bronchopulmonary dysplasia at a postmenstrual age of 36 weeks, intraventricular hemorrhage, hypoxic ischemic encephalopathy, sepsis, necrotizing enterocolitis, or periventricular leukomalacia) was significantly higher in infants with DD than in controls. In conclusion, PE/SPE/GH around 30 weeks may be associated with a low incidence of CP.

Novel loss-of-function variants in WDR26 cause Skraban-Deardorff syndrome in two Chinese patients.

Introduction: Mutations in the protein WD repeat structural domain 26 (WDR26, MIM 617424) have been identified as the cause of autosomal dominant Skraban-Deardorff syndrome, a rare genetic disorder characterized by intellectual disability (ID), developmental delay (DD), hypotonia, epilepsy, infant feeding difficulties, gait abnormalities and distinctive facial features. The objective of this study is to investigate the genetic factors that may contribute to the development of Skraban-Deardorff syndrome in affected individuals. Methods: In this study, we used whole-exome sequencing (WES) to analyze pathogenic and likely pathogenic variants in two unrelated Chinese patients with DD and ID. We confirmed the origin of the variants by conducting Sanger sequencing and classified them according to ACMG/AMP guidelines. Results: Here, two novel de novo variants (c.1797delC(p.His599fs*11) and c.1414C>T(p.Gln472*)) in the WDR26 gene have been identified in two Chinese patients with Skraban-Deardorff syndrome. These patients exhibit a range of symptoms, including varying degrees of ID, DD, speech delay, an abnormal wide-foot and/or stiff-legged gait, facial dysmorphism, behavioural abnormalities, with or without seizures. Conclusions: In this study, We report two unrelated Chinese patients with Skraban-Deardorff syndrome caused by novel de novo pathogenic variants of the WDR26 gene. These patients showed a clinical phenotype similar to that of patients with the WDR26 variant. Compared to reported cases with WDR26 pathogenic variants, patient 2 presented a novel complication of severe behavioural problems, including hyperactivity, social anxiety, self-mutilation, impulsivity and violent behaviour. This research broadens the range of genetic and clinical features of Skraban-Deardorff syndrome. In addition, the symptoms may become more pronounced as the patient ages. Furthermore, our report highlights the clinical diversity of Skraban-Deardorff syndrome. The findings may assist healthcare professionals in providing more accurate genetic testing and counselling to affected families and improving the overall management of the condition.

Case report: A novel FBXW7 gene variant causes global developmental delay.

Objective: To investigate a case of neurodevelopmental disorder caused by mutation of FBXW7. Methods: Clinical data were collected from the patient, trio-WES (whole-exome sequencing) was performed on the patient and his parents (trio), and the results were verified by Sanger sequencing. RESULTS: The patient was a 2-year and 1-month old male who presented with facial dysmorphism (prominent forehead, ocular hypertelorism, and low nasal bridge), global developmental delay, language impairment, hypertonia, labial hemangioma, hydrocele, and overgrowth. The trio-WES confirmed that the child had a pathogenic de novo FBXW7 gene variant, c.1612C>T (p.G1n538*), a heretofore unreported locus. Conclusion: This case of developmental delay, hypotonia, and impaired language (OMIM: #620012) related to a mutation in FBXW7, is a rare genetic disorder, newly identified in recent years, and seldom reported. The presence of hypertonia, labial hemangioma, and hydrocele in this child suggests significant phenotypic heterogeneity of the disease, and the discovery of new mutant loci enriches the spectrum of pathogenic variants of the disease.

Cultivating the imagination: Caregiver input during pretend play with toddlers at elevated likelihood for autism.

Toddlers with autism spectrum disorder (ASD) may exhibit less pretend play than their neurotypical counterparts. Previous research suggests that caregivers' input during play influences children's play behavior, and children's behavior may in turn prompt caregivers of differently developing children to talk about play in different ways. Caregiver input about pretend play during toy play at home was examined at 18- and 36-months in toddlers with an older sibling with ASD, who are at elevated likelihood (EL) for ASD (n = 40), and toddlers with typical likelihood (TL) for ASD (n = 12). EL toddlers were classified into three outcome groups: EL-ASD (n = 10), EL-no diagnosis (EL-ND; n = 14), or EL-language delays (EL-LD, n = 16). Caregiver utterances were categorized according to the types of pretend and non-pretend play suggested (e.g., pretending with inanimate objects vs. using objects for their intended function). Pretend utterances were further categorized as related or unrelated to the child's own actions. All caregivers produced proportionately more utterances about complex types of pretend play over time. At 36 months, caregivers of autistic toddlers produced proportionately fewer pretend play utterances, and proportionately fewer pretend play utterances were related to EL-ASD toddlers' actions compared to their neurotypical peers. These findings highlight bidirectional effects between caregivers and toddlers during play. While EL-ASD toddlers may provide less frequent opportunities for caregivers to talk about complex types of pretend play, the current study highlights caregivers' high levels of attunement to their toddlers' play skills.

Improved GPS tropospheric path delay estimation using variable random walk process noise.

Accurate positioning using the Global Positioning System relies on accurate modeling of tropospheric delay. Estimated tropospheric delay must vary sufficiently to capture true variations; otherwise, systematic errors propagate into estimated positions, particularly the vertical. However, if the allowed delay variation is too large, the propagation of data noise into all parameters is amplified, reducing precision. Here we investigate the optimal choice of tropospheric constraints applied in the GipsyX software, which are specified by values of random walk process noise. We use the variability of 5-min estimated positions as a proxy for tropospheric error. Given that weighted mean 5-min positions closely replicate 24-h solutions, our ultimate goal is to improve 24-h positions and other daily products, such as precise orbit parameters. The commonly adopted default constraint for the zenith wet delay (ZWD) is 3 mm/√(hr) for 5-min data intervals. Using this constraint, we observe spurious wave-like patterns of 5-min vertical displacement estimates with amplitudes ~ 100 mm coincident with Winter Storm Ezekiel of November 27, 2019, across the central/eastern USA. Loosening the constraint suppresses the spurious waves and reduces 5-min vertical displacement variability while improving water vapor estimates. Further improvement can be achieved when optimizing constraints regionally, or for each station. Globally, results are typically optimized in the range of 6-12 mm/√(hr). Generally, we at least recommend loosening the constraint from the current default of 3 mm/√(hr) to 6 mm/√(hr) for ZWD every 300 s. Constraint values must be scaled by √(x/300) for alternative data intervals of x seconds. Supplementary Information: The online version contains supplementary material available at 10.1007/s00190-024-01898-3.