TD Group Research Articles

Effect of Temporal Decentration of Orthokeratologic Lens on Corneal Aberrations in Swept-source Optical Coherence Tomography

Purpose: This study used anterior segment swept-source optical coherence tomography (AS SS-OCT) to explore the effect of temporal decentration within the orthokeratologic lens treatment zone on corneal aberrations.Methods: After lens placement, AS SS-OCT was used to evaluate anterior, posterior, and total corneal astigmatism and the magnitudes of the individual 1st- to 4th-order aberrations of the anterior and entire corneal fields. Also, the 4th-to 7th-order root mean square (RMS), and the low- and high-ordered RMSs of both the anterior and entire corneal areas were recorded. We compared subjects lacking (the no decentration [ND] group) to those exhibiting (the temporal decentration [TD] group) temporal decentration.Results: In all, 61 eyes of 32 patients (44 eyes in the ND group and 17 in the TD group) were included. In the TD group, the average temporal decentration was 0.74 ± 0.15 mm. The baseline axial length, spherical equivalent, anterior mean corneal power, and anterior corneal astigmatism did no difference between the two groups. However, the TD group exhibited more anterior and total corneal horizontal tilts, and horizontal coma, than the ND group. That group also had less with-the-rule (WTR)/against-therule (ATR) astigmatism, elevated anterior and total corneal 5th-order RMS values, and greater low- and high-ordered RMS levels. However, despite these differences, the extent of myopia correction did not significantly differ between the groups.Conclusions: Although myopia reduction was not significantly compromised by temporal decentration of an orthokeratologic lens, the anterior and total corneal low- and high-ordered RMS values increased. In terms of individual aberrations, the low-ordered horizontal tilt and the high-ordered horizontal coma increased.

Parental and Child Sleep: Children with Vision Impairment, Autistic Children, and Children with Comorbid Vision Impairment and Autism.

Parents report associations between children's sleep disturbances and behaviors. Children with neurodevelopmental conditions (e.g., Williams Syndrome and autism) are consistently reported to experience increased sleeping problems. Sleep in children with vision impairment and children with a dual diagnosis of vision impairment and autism remains understudied. Our exploratory study compared sleep profiles in 52 children (aged 4-12 years) and their parents (n = 37), across four groups: children with vision impairment (VI; n = 9), autism (n = 10), comorbid vision impairment + autism (n = 6), and typically developing children (n = 27). Childhood sleep was measured using the parental report Childhood Sleep Habits Questionnaire and sleep diaries. Children's cognitive functioning was measured using digit span, semantic, and phonemic verbal fluency measures. Parental sleep was measured via the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale. Clinically disordered sleep was reported in all child groups (p ≤ 0.001), particularly children with VI + autism. Age, not sleep quality/quantity, predicted cognitive task performance in TD and autistic groups, but not in VI and VI + autism groups. The child's diagnosis affected parental sleep, particularly in children with a dual diagnosis of VI + autism. All participants experienced problematic sleep to varying degrees. Those most affected were children and parents in the VI + autism group, suggesting that autism may be the main driver of sleep problems in our sample.

Mean length of utterance of Jordanian Arabic-speaking children with language impairment

This study serves as an explanatory investigation of the validity of mean length of utterance (MLU) to distinguish children with typical development from those with language impairment. Data were taken from 15 typically developing children and 11 children with language impairment, all aged 4–9 years old. A minimum of 100 utterances were taken from each participant which were then analyzed using Brown's rules of counting MLU-w with some adaptations. The results of this study showed statistically significant differences between the two groups, in favor of the unaffected group (children with typical development): the MLU-w was 2.59 (SD = 0.76)for the group with language impairments and 5.37 (SD =1.67)for the TD group. The results of this study can serve as a good index to reflect language development and point to any delayed production of language.

Safety and immunogenicity of a single dose of Tdap compared to Td in pregnant women in Mali and 3 its effect on infant immune responses: a single-centre, randomised, double-blind, active-controlled phase 2 study

While maternal pertussis vaccination is a strategy to reduce infant morbidity, safety and immunogenicity data are limited in sub-Saharan Africa. We aimed to evaluate the safety of a single dose of tetanus, diphtheria and acellular pertussis vaccine (Tdap) vaccine compared to tetanus and diphtheria vaccine (Td) vaccine in pregnant women in Bamako, Mali and to assess the pertussis toxin (PT) antibody response at birth. In this phase 2, single-centre, randomised, double-blind, active-controlled study, from 23 January 2019 to 10 July 2019, healthy 18-39 year old women in the second trimester of a singleton pregnancy were randomised 2:1 to receive Tdap or Td. Blood was tested for serum immunoglobulin G (IgG) against PT and other vaccine antigens using a qualified Meso Scale Discovery multiplex immunoassay. The co-primary objectives evaluated safety and birth anti-PT levels. Infant immune responses to whole-cell pertussis vaccine (DTwP) were assessed. Statistical analysis was descriptive. This trial is registered with clinicaltrials.gov, NCT03589768. 133 women received Tdap and 67 received Td, with 126 and 66 livebirths, respectively. In the Tdap group, 22 serious adverse events (SAEs) including one maternal death occurred in 20 participants (15·0%), with 10 SAEs in 10 participants (14·9%) in the Td group. Among infants, 18 events occurred among 13 participants (10.3%) and 8 SAEs in 6 participants (9.1%), including three and two infant deaths, occurred in Tdap and Td groups, respectively. None were related to study vaccines. Anti-PT geometric mean concentration (GMC) at birth in the Tdap group was higher than in the Td group (55.4 [46.2-66.6] IU/ml vs 7.9 [5.4-11.5] IU/ml). One month after the third dose of DTwP, the GMC in infants born to mothers in the Tdap group were lower compared to the Td group (20.2 [13.7-29.9] IU/ml vs 77.2 [32.2-184.8] IU/ml). By 6 months of age, the anti- PT GMCs were 17.3 [12.8-23.4] IU/ml and 67.1 [35.5-126.7] IU/ml in Tdap and Td groups, respectively. At birth, anti-tetanus toxin (TT) GMCs were higher in infants in the Td vs Tdap group (5.9 [5.0-7.0] IU/ml vs 4.1 [3.5-4.8] IU/ml). Anti-diphtheria toxin GMCs were similar in both groups. Tdap administered to pregnant women in Mali is safe and well-tolerated. Infants of mothers who received Tdap were born with high PT and protective anti-TT antibody levels. By six months of age, after primary vaccination, the PT levels were lower in the Tdap group compared to the Td group. The blunted immune responses to primary DTwP vaccination in the Tdap infant group warrant further study. This project was funded by National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), under contract numbers 75N93021C00012 (The Emmes Company), and HHSN27220130000221 (University of Maryland, Baltimore). Dr. Susana Portillo was supported by NIH award no. T32AI007524. NIAID, NIH provided Tdap vaccine (BOOSTRIX).

Untargeted metabolomic, and proteomic analysis identifies metabolic biomarkers and pathway alterations in individuals with 22q11.2 deletion syndrome

IntroductionThe chromosome 22q11.2 deletion syndrome (22q11.2DS) is characterized by a well-defined microdeletion and is associated with a wide range of brain-related phenotypes including schizophrenia spectrum disorders (SCZ), autism spectrum disorders (ASD), anxiety disorders and attention deficit disorders (ADHD). The typically deleted region in 22q11.2DS contains multiple genes which haploinsufficiency has the potential of altering the protein and the metabolic profiles.Objectives Alteration in metabolic processes and downstream protein pathways during the early brain development may help to explain the increased prevalence of the observed neurodevelopmental phenotypes in 22q11.2DS. However, relatively little is known about the correlation of dysregulated protein/metabolite expression and neurobehavioral impairments in individuals who developed them over time.Methods In this study, we performed untargeted metabolic and proteomic analysis in plasma samples derived from 30 subjects including 16 participants with 22q11.2DS and 14 healthy controls (TD) enrolled in a longitudinal study, aiming to identify a metabolic and protein signature informing about the underlying mechanisms involved in disease development and progression. The metabolic and proteomic profiles were also compared between the participants with 22q11.2DS with and without various comorbidities, such as medical involvement, psychiatric conditions, and autism spectrum disorder (ASD) to detect potential changes among multiple specimens, collected overtime, with the aim to understand the basic underlying mechanisms involved in disease development and progression.ResultsWe observed a large number of statistically significant differences in metabolites between the two groups. Among them, the levels of taurine and arachidonic acid were significantly lower in 22q11.2DS compared to the TD group. In addition, we identified 16 proteins that showed significant changes in expression levels (adjusted P < 0.05) in 22q11.2DS as compared to TD, including those involved in 70 pathways such as gene expression, the PI3K-Akt signaling pathway and the complement system. Within participants with 22q11.2DS, no significant changes in those with and without medical or psychiatric conditions were observed.ConclusionTo our knowledge, this is the first report on plasma metabolic and proteomic profiling and on the identification of unique biomarkers in 22q11.2DS. These findings may suggest the potential role of the identified metabolites and proteins as biomarkers for the onset of comorbid conditions in 22q11.2DS. Ultimately, the altered protein pathways in 22q11.2DS may provide insights of the biological mechanisms underlying the neurodevelopmental phenotype and may provide missing molecular outcome measures in future clinical trials to assess early-diagnosis treatment and the efficacy of response to targeted treatment.

Attentional processing of preserved face and scrambled face distractors in preschool children with autism spectrum condition

ABSTRACT The current study investigated attentional processing of preserved neutral face and scrambled neutral face distractors at both involuntary and voluntary orienting levels in children with and without autism spectrum condition (ASC). The findings suggest similar influences of face configuration on reflexive orienting in both groups but reveal group differences in voluntary disengagement from face-related distractors. The ASC group exhibited difficulties in disengaging from the central neutral faces, and the TD group showed longer latencies for scrambled faces. These group differences suggest inefficiency in adopting a global face processing strategy at the voluntary attentional level in ASC. We discuss how the observed effects might impact upon the development of social communication skills in ASC.

Association between Mastery Motivation, Executive Function, and Daily Participation of Young Children with and without Global Developmental Delays.

This study aimed to examine the group differences in participation level between children with and without global delays and to explore the associations between mastery motivation, executive function, and participation in young children with and without global developmental delays (GDD). Methods: we recruited 26 children with GDD aged 2 to 5 years and 26 children with sex- and mental age-matched developing typically (TD). The participants were assessed child development using the standardized developmental test, and their mothers were asked to fill in questionnaires, including the revised Dimension of Mastery Questionnaire (DMQ 18) with preschool version to assess mastery motivation, the Behavior Rating Inventory of Executive Function with preschool version (BRIEF-P) to assess executive function, and the Young Children's Participation and Environment Measure (YC-PEM) used to obtain participation levels. Results and conclusions: young children with GDD showed significantly lower participation levels at home, daycare, and community than TD group. We found that for young children, child mastery pleasure, health condition, and total persistence were significant predictors of child participation. Therefore, coaching parents to observe and facilitate their children's motivation and executive function, as well as child developmental abilities, is important in order to enhance children's participation in daily activities.

Characterization of a Novel TiF4 Inclusion Complex and in vitro Evaluation of Its Effect on Inhibiting Enamel Demineralization

Introduction: Titanium tetrafluoride (TiF4) is an anticariogenic agent with high remineralizing potential. However, the acidic pH of TiF4 solution can limit its clinical application. The present study aimed to prepare and characterize a new TiF4-dendrimer inclusion complex and evaluate its ability to inhibit enamel demineralization under pH cycling conditions. Methods: PEG-citrate dendrimer and TiF4-dendrimer inclusion complex were synthesized and their molecular structures were evaluated using Fourier-transform Infrared Spectroscopy (FTIR), Hydrogen Nuclear Magnetic Resonance (HNMR), and Liquid Chromatography-Mass Spectrometry (LC-MS) tests. Forty-eight enamel samples were prepared and randomly divided into four groups: distilled water (negative control), TiF4 solution (T), dendrimer solution (D), and TiF4-dendrimer solution (TD). The microhardness of the samples was measured initially. Next, the samples underwent pH cycling, were exposed to the solutions, the microhardness was measured again, and microhardness loss was calculated. EDX analysis was performed on the surface and cross-sectional segments of the samples. Results: The microhardness loss was significantly higher in control (−65.1 ± 6.0) compared to other groups. No significant difference was observed between T (−47.9 ± 5.6) and D (−41.7 ± 12.0) and also D and TD (−40.5 ± 9.4) in this regard. Microhardness loss was significantly higher in T compared to TD group. The TD samples showed similar fluoride and titanium content in both surface and subsurface regions, while the T group had higher concentrations in the surface region. Moreover, the TD solution had a higher pH of 3.4 compared to the T solution’s pH of 1.1. Conclusion: No significant difference was observed between the efficacy of TiF4-dendrimer and TiF4 solution in inhibiting demineralization while TiF4-dendrimer solution had the added advantage of having a higher pH.

Assessment of Sensory Processing Issues in Children with Neurodevelopmental Disorders and Experiences of Maltreatment.

This study aims to identify the sensory characteristics of children with both developmental disabilities such as ASD and ADHD and a history of child maltreatment (DM group), children with developmental disabilities (DD group), and typically developed children (TD group). The sensory characteristics of 24 children were assessed through virtual reality and self-administered questionnaires. The results elucidated that the duration of gazing at the "teacher" (60-75 s) was significantly different with the DM group's gaze being shorter than the DD group's gaze (p = 0.042). The duration of the "others" gaze (45-60 s) was also significantly different with the DM group's gaze being longer than the DD and TD groups' gaze (p = 0.018; p = 0.030). Additionally, the scores for tactile sensitivity, taste/smell sensitivity, under-responsive/seeks sensation, and the total short-term sensory profile were significantly different between the DM-DD and DD-TD groups. The scores of the heart rate perception test and Multidimensional Assessment of Interoceptive Awareness were significantly lower in the DM and DD groups. In conclusion, children who have experienced trauma and developmental disabilities may have different sensory characteristics than children with only developmental disabilities or none, implying the need for further research and tailored care.

Cardioprotective effects of aerobic training in diabetic rats: Reducing cardiac apoptotic indices and oxidative stress for a healthier heart.

The present study evaluated the effects of aerobic training with variable intensities on apoptotic indices of cardiac tissue in fatty diabetic rats. Twenty-four male Wistar rats were randomly divided into non-diabetic (ND, n=8), trained diabetic (TD, n=8), and control diabetic (CD, n=8) groups. Following a high-fat dietary regimen, type 2 diabetes was induced by streptozotocin, with blood glucose levels above 300 mg/dL considered indicative of diabetes. The TD group underwent aerobic exercise five times a week for six weeks. Subsequently, measurements were taken for left ventricular end-diastolic (LVEDV) and end-systolic volumes (LVESV), ejection fraction (EF%), catalase, caspase-9, P53, glucose, insulin, and HOMA-IR. Aerobic training led to a significant decrease in blood glucose levels (P < 0.01), caspase-9 (P < 0.05), HOMA-IR (P < 0.05), and P53 expression (P < 0.001) compared with the CD group. LVEDV and LVESV decreased significantly (P < 0.05 for both), while LVEF increased significantly (P < 0.05). Catalase activation showed an insignificant increase in the TD group pre- to post-training compared to CD. Incremental aerobic exercise training (6 weeks) may exert a cardioprotective effect in diabetic rats by reducing apoptosis and oxidative stress indices, while simultaneously increasing aerobic fitness and reducing body weight.

Comparison of Visual Functions and Ocular Health in Children with Autism Spectrum Disorder versus Typically Developing Peers

PURPOSE: To compare the visual functions and ocular health between children with Autism Spectrum Disorder and Typically Developing Peers. METHOD: A comparative cross-sectional study was conducted in different autistic centers to evaluate the visual functions and ocular health of 80 individuals in which 40 were diagnosed with ASD and 40 were typically developing. Different tests were carried out to assess visual functions in which visual acuity was tested by Snellen chart, contrast sensitivity on Pelli-Robson, color vision by primary colors detection and visual field by handheld peripheral field perimeter. Ocular health was checked by ocular examination of individuals. RESULTS: Out of 40 children with ASD, 15(37.5%) had VA≤ 0.5. 19(23.75%) had reduced contrast sensitivity. 3(3.75%) had some color vision defect. Out of 40 TD peers, 17(42.5%) had VA≤ 0.5. 17(21.25%) had reduced contrast sensitivity. All TD peers had normal color vision. Both groups had 2(2.50%) individuals with reduced field. While checking ocular health of ASD group, only 20 had some ocular health problems in which 7(8.75%) had strabismus, 3(3.75%) had eye movement disorders, 2(2.50%) had hypertelorism and ptosis respectively and 1(1.25%) had nystagmus. Similarly, in TD group, 16 had ocular problems in which 6(7.50%) had strabismus, 2(2.50%) had hypertelorism, 1(1.25%) had ptosis and eye movement disorders respectively. The statistical test was performed by using Mann Whitney test and Chi-square test (p value ≤ 0.05). CONCLUSION: There was no significant difference in visual functions and ocular health of children who had ASD and TD Peers.

Association of verbal and non-verbal theory of mind abilities with non-coding variants of OXTR in youth with autism spectrum disorder and typically developing individuals: a case-control study

BackgroundThe ability to attribute mental states to others is called theory of mind (ToM) and is a substantial component of social cognition. This ability is abnormally developed in individuals with autism spectrum disorder (ASD). Several studies over the past decade have identified the oxytocin receptor gene (OXTR) and its variants as promising components for explaining the molecular mechanisms underlying Theory of Mind (ToM). The main aim of this study is to examine the association between rs2268498 and rs53576, two functional single nucleotide polymorphisms (SNPs), and verbal and non-verbal ToM in children and adolescents with ASD and a group of typically developing youth.MethodsThe study involved 44 children and adolescents with high-functioning ASD aged 8 to 18 years old and 44 TD individuals who were matched on age and sex. In all participants, blood samples were collected and rs2268498 and rs53576 were genotyped. Happe’s Strange Stories test and the moving shapes paradigm were used to measure verbal and non-verbal ToM in all participants.ResultsThe results of permutation tests and logistic regression suggested that in TD group, rs2268498 AA carriers showed significant higher scores in variables representing verbal ToM (ToM stories and appropriateness score) whereas, in ASD group, rs53576 AA carriers exhibited significant better performance in parameters related to non-verbal ToM (ToM general rule and intentionality score). The results of hierarchical clustering in both groups support the findings by distinguishing between language-related and language-independent aspects of ToM.ConclusionsIn the present study, we examined the association between rs2268498 and rs53576 and social functioning in individuals with ASD and TD group. We found preliminary evidence that rs2268498 and rs53576 are associated with ToM related abilities in healthy individuals as well as in autistic individuals. Accordingly, rs2268498 and rs53576 may play an important role in predicting ToM capabilities. It will be necessary to conduct further research to address the association of genetic variants with a deficit in ToM in individuals with ASD.

Rs12411980 single-nucleotide polymorphism related to PRTFDC1 expression is significantly associated with phantom tooth pain.

Phantom tooth pain (PTP) is one type of non-odontogenic neuropathic toothache, which rarely occurs after appropriate pulpectomy or tooth extraction. The cause of PTP is unknown. We investigated pain-related genetic factors that are associated with PTP. Four pain-associated genes, including G protein-coupled receptor 158 (GPR158) and phosphoribosyl transferase domain containing 1 (PRTFDC1), are adjacent to each other on the human genome. Some of these four genes or their genomic region may be related to PTP. We statistically analyzed associations between single-nucleotide polymorphisms (SNPs) in the genomic region and PTP in patients with PTP (PTP group), other orofacial pain (OFP group), and healthy control subjects. We then performed a database search of expression quantitative trait loci (eQTLs). For the seven SNPs that were significantly associated with PTP even after Bonferroni correction, we focused on the rs12411980 tag SNP (p = 9.42 × 10-4). Statistical analyses of the PTP group and healthy subject groups (group labels: NOC and TD) revealed that the rate of the GG genotype of the rs12411980 SNP was significantly higher in the PTP group than in the healthy subject groups (PTP group vs. NOC group: p = 2.92 × 10-4, PTP group vs. TD group: p = 5.46 × 10-4; percentage of GG: 30% in PTP group, 12% in NOC group, 11% in TD group). These results suggest that the GG genotype of the rs12411980 SNP is more susceptible to PTP. The rs2765697 SNP that is in strong linkage disequilibrium with the rs12411980 SNP is an eQTL that is associated with higher PRTFDC1 expression in the minor allele homozygotes in the healthy subject groups of the rs2765697 SNP. Thus, PRTFDC1 expression similarly increases in the minor allele homozygotes (GG genotype) in the healthy subject groups of the rs12411980 SNP, which would lead to greater susceptibility to PTP.

Is language impaired in Spanish-speaking children with autism spectrum disorder level 1?

Our main aim was to explore whether children with ASD-Level 1 (ASD-L1) present difficulties in the acquisition of structural language, as little work has been done in this regard so far. As a secondary aim we evaluated the degree to which the potential language impairment in ASD is directly associated with their social communication deficits or it represents a distinct deficit. To further clarify the nature and characteristics of putative language difficulties in ASD-L1, we evaluated language skills in 89 children and preadolescents diagnosed with ASD-L1, and a group of typically developing participants (TD). All of them were between 8 and 13 years old and had similar socioeconomic backgrounds. Children with ASD-L1 obtained lower scores than those in TD group in repeating sentences, in finding the semantic relationships between words, and in applying word structure rules (morphology). Congruently, the core language standard score was lower in the ASD-L1 group, and the proportion of language delay was significantly higher in the ASD-L1 group than in the control group. Language scores were associated with autistic traits; thus, language performance in ASD-L1 is closely related to autistic symptoms. These results are discussed according to the literature on linguistic deficits in ASD-L1 and their relations with phonological working memory.

Open Microdiscectomy or Tubular Discectomy: What Is Better for Lumbar Disc Herniation

Introduction: Many different minimally invasive procedures can be used to treat lumbar disc herniation. In the management of lumbar disc herniation, Open microdiscectomy MD is the gold standard and is used as a benchmark for comparison with more recent techniques like tubular discectomy. The purpose of this study was to assess the complication rates of tubular discectomy and to compare the postoperative outcomes of individuals undergoing tubular discectomy with those undergoing MD. Material &amp; Methods: A retrospective analysis of 250 patients who underwent single-level lumbar discectomy either by tubular TD or MD between JULY 2018- JUNE 2023 was performed. The differences in the 2 groups' demographics, surgical length, intraoperative blood loss, overall hospital stay, pain score on the visual analogue scale (VAS), Oswestry Disability Index (ODI) score both before and after the procedure, and complications were assessed. Results: Out of the 250 patients, 130 patients were treated with MD and 120 by tubular discectomy TD. The mean age in MD and tubular TD group was 45.5 and 45.8 years. There was a improvement in VAS and ODI scores at 4 weeks in both the groups. There was a greater reduction of back pain in the TD group at 2 weeks compared to MD group but at 1 month both are comparable. Average surgical time was shorter in MD (71.6 min) as compared to TD group (80.2 min). the Average blood loss was higher (90.2 mL) in MD group as compared to TD group (35.8 mL) (Table 3 ). Length of incision as measured from the surgical scar was 1.7 cm in TD while it was 3.0 cm in MD group. Average hospital length of stay in TD (1.2 days) which was less than MD group (2.1 days). Likewise, MD group patients took 5.9 weeks to return to activity which was higher than the TD group (4.1 weeks). There were 9 cases (6.9%) of dural tear in MD and 10 cases (8.3%) in TD group. Conclusion: Sciatica caused by disc herniation can be effectively and safely treated with lumbar discectomy, whether it is TD or MD. In comparison to MD, the TD method for treating symptomatic lumbar radiculopathy is superior in that it causes less postoperative back pain, less blood loss, a shorter hospital stay, and a quicker return to work. Despite the learning curve, TD has been demonstrated to be a viable choice for treating lumbar disc herniation in patients who are carefully chosen.

The Relationship of Text Inference Abilities and Reading Comprehension in Children with High-Functioning Autism Spectrum Disorder

Objectives: Reading comprehension in school-age children is an essential ability facilitates acquisition of information from general education. Yet, even with average or above cognitive and word recognition abilities, children with High Functioning Autism Spectrum Disorder (HF-ASD) demonstrate difficulties with reading comprehension. The purpose of the this study was to investigate that identifying the reading comprehension competence with a focus on text inference abilities (coherence processing, metalinguistic, theory of mind) in children with HF-ASD in the lower grades of elementary school.Methods: 15 HF-ASD and 15 age matched typically developing peers (TD) participated in this study. The participants performed reading comprehension tasks and text inferencing tasks (coherence processing, metalinguistic, theory of mind).Results: First, the reading comprehension accuracy of the HF-ASD group was significantly lower than the TD group. Second, the text inference accuracy of the HF-ASD group was significantly lower compared with the TD group. Third, in the TD group, there was a significant correlation between all text inference abilities (coherence processing, metalinguistic, theory of mind) and reading comprehension competence. In contrast, in the HF-ASD group, there was a positive correlation between coherence processing, metalinguistic and reading comprehension competence; however no significant relationship was found between theory of mind and reading comprehension competence. Finally, the coherence processing task predicted reading comprehension competence of children with HF-ASD by 52.2% and TD children by 42.1%.Conclusion: This study suggests that supporting connecting information within a text, local inferencing, and focusing on the coherence processing intervention is necessary for reading comprehension of children with HF-ASD in the lower grades of elementary school.

Treatment- Sensitive, Dependent, and Refractory Chronic Gvhd: Incidence and Clinical Outcomes

Introduction Chronic graft-versus-host disease (cGVHD) remains a limitation to the long-term success of allogeneic hematopoietic cell transplantation (HCT). The clinical characteristics and outcomes associated with treatment-sensitive, -dependent, and -refractory cGVHD are unknown. We investigated risk factors associated with distinct cGVHD treatment response groups and analyzed the impact of treatment response on clinical outcomes of cGVHD following HCT. Methods The study population included 185 consecutive adult and pediatric patients who developed cGVHD after first allogeneic HCT for malignant and non-malignant disorders at the University of Minnesota between 2008 and 2016. All graft and donor sources, GVHD prophylaxis strategies, and conditioning regimens were included. Only cGVHD cases that started treatment within 30 days of diagnosis are included. We defined cGVHD diagnosis and overall severity using the 2014 NIH Consensus Criteria. We predefined treatment response categories as either treatment-sensitive (TS), -dependent (TD), or -refractory (TR) at 6, 12, and 24 months after cGVHD onset. TS requires clinical improvement after 12 months of initial therapy with discontinuation of therapy by 24 months. TR criteria include disease progression during therapy, addition of new systemic therapies, or death before 6 months of cGVHD treatment. TD patients meet TS criteria, however still require systemic therapy 24 months after initiation of cGVHD therapy. Outcomes by response group were analyzed in a landmark analysis at the time at which treatment response was determined, excluding any with the event of interest (relapse, death) before the landmark time. To compare treatment response categories with a no-cGVHD control group, the landmark time was set to the median day of cGVHD onset (day 220) plus treatment response category ascertainment time (e.g. 12 months). Disease-free survival (DFS) was defined as survival without relapse or death. Failure-free-survival (FFS) after cGVHD was defined as survival without relapse, death, or new systemic treatment initiated more than 30 days after cGVHD onset. Results Patient and transplant characteristics are shown in Table 1. Among 1142 allografts, 222 (19%) developed cGVHD and of those 185 (83%) received systemic cGVHD therapy within 30 days of onset and were included in this analysis. Median time to onset of cGVHD was 216 days (range 71-945) with 7.4 years median time follow up time after cGVHD. The 3-year cumulative incidence of mild, moderate, and severe cGVHD was 3.4%, 11.5%, and 4.4%, respectively. The distribution of treatment response categories as TS, TD, or TR cGVHD are shown at 6, 12, and 24 months in the Sankey plot (Figure 1). Patients were most often TD at 6 months after diagnosis and transitioned to TS or TR by 24 months. Patients with moderate and severe cGVHD were equally likely to be either TD or TR at 6 months. By 12 months, most severe cGVHD cases were TR, while the TD group consisted mostly of moderate cGVHD cases. Patients with prior aGVHD, especially maximum grade III-IV aGVHD, were more likely to have TR cGVHD at 12 months. Patients over 18 were more likely to have TD or TR cGVHD. We noted no other significant risk factors associated with treatment response groups. The most common second-line cGVHD therapy used in addition to systemic corticosteroids was largely sirolimus, followed by cyclosporine and tacrolimus. We analyzed clinical outcomes by treatment response at 12 months from cGVHD diagnosis. 10-year FFS was lowest in TR followed by TD and TS groups (38%, 66%, 79%, respectively; P=0.01). Similarly, both 10-year overall survival and DFS were lowest in TR group followed by TD and TS groups. 10-year NRM was highest in TR and TD groups compared to the TS group (33%, 23%, 5%, respectively; P=0.13). In multivariate analysis, TR cGVHD was associated with worse overall survival at 12 months after cGVHD (HR 2.5 vs. no cGVHD; 95% CI, 1.7-3.7; P &amp;lt; .01) Conclusions We identified TR cGVHD as a significant risk factor for lower OS and FFS at 12 months post-diagnosis. TS and TD cGVHD groups showed similar prognoses, both better than the TR group. Our findings suggest that cGVHD treatment response states are important predictors of clinical outcomes. Additionally, we have shown that long term follow-up after cGVHD treatment is necessary to determine treatment sensitivity and therefore predict long term outcomes.

Red Blood Cell Transfusion Dependence Is Associated with Greater Healthcare Resource Utilization, Higher Medical Cost, and Poorer Prognosis in Patients with Lower-Risk Myelodysplastic Syndromes: A 28-Year Retrospective Observation Study Result

Myelodysplastic syndromes (MDS) encompass a heterogeneous group of myeloid neoplasms characterized by cytopenia due to inefficient hematopoiesis, with a considerable risk of progression to acute myeloid leukemia (AML) or early mortality. In lower-risk MDS (LR-MDS) patients, anemia and its associated complications have been the focus of clinical attention. A significant portion of these patients eventually develop red blood cell transfusion dependence (RBC TD), which has been linked to a poorer prognosis. Given the limited efficacy of available treatments in reducing RBC TD, most patients face increased risks of chronic anemia and various complications. Moreover, RBC TD is known to be associated with reduced overall survival (OS) and leukemia-free survival (LFS). This study aimed to assess the impact of RBC TD on the socioeconomic burden and clinical prognosis of LR-MDS patients, utilizing an electronic medical records (EMR) database spanning nearly 30 years of MDS patient data. This retrospective observational study examined adult MDS patients (≥ 18 years of age) treated at Samsung Medical Center in the Republic of Korea. Eligible patients were diagnosed with MDS between Sep 1, 1994, to Apr 1, 2022 (index period), with the observation period spanning from Sep 1, 1994, to Sep 1, 2022. Baseline assessments included estimation of revised international prognostic scoring system (IPSS-R) scores, categorizing patients with very low, low or intermediate risks as lower-risk MDS (LR-MDS). TD was defined as the occurrence of any 16-week period with RBC transfusion of ≥ 2 units per 8 weeks, without consecutive 56-day period without transfusion. Healthcare resource utilization (HCRU), medical costs, and prognosis indicators including overall survival (OS) and AML-free survival (AFS) were analyzed and compared between patients who experiencing TD and those not (non-TD). Out of 831 MDS patients, 349 (42.0%) were classified as lower-risk at baseline. Among LR-MDS patients, 29.5% (103/349) experienced TD while 23.3% (194/831) experienced TD in the entire study population. The median age at diagnosis of MDS was 63 (ranging from 18 to 89), and 65.3% (543/831) were male. In LR-MDS patients, there were no significant differences in either baseline age (61 vs 63, P=0.16) or gender (71.8% vs 61.0% males, P=0.053) between TD and non-TD groups. However, TD group exhibited significantly higher median erythropoietin (EPO) level than non-TD group (290.5U/L vs. 112U/L, P&amp;lt;0.001) among LR-MDS patients with available baseline serum EPO levels (76 TD and 178 non-TD). Among the 76 TD LR-MDS patients with baseline serum EPO levels, 51 (67.1%) exhibited &amp;gt; 200U/L, which is considered a clinical threshold for erythropoiesis-stimulating agent (ESA) treatment. As shown in Table 1, RBC TD was consistently associated with greater HCRU and higher medical costs, especially in LR-MDS patients. TD LR-MDS patients had higher rates of outpatient department and emergency room visits (15676 vs. 8303 visits and 587 vs. 328 visits per 1000 person-years [PY], respectively), and increased hospitalizations (709 vs. 456 per 1000 PY), with longer hospital stays (13343 vs. 8272 days per 1000 PY). Furthermore, TD LR-MDS patients required over four-times of packed RBC units than non-TD patients (31107 vs. 7073 units per 1000 PY). Consequently, TD LR-MDS patients incurred higher total medical cost than their non-TD counterpart (13.5 million vs. 6.1 million USD per 1000 PY). Median OS (58.4 months vs. 103.1 months) and AFS (52.7 months vs. 102.7 months) were both significantly shorter in the TD group compared to the non-TD group among LR-MDS patients, while the differences in OS and AFS did not reach the level of significance in the entire study population (Table 1 and Figure 1). Notably, median OS after the first documented RBC TD event was 33.8 months (95% confidence interval: 24.7-58.5 months) in LR-MDS patients. The findings of this study indicate that RBC TD can be a strong predictor of increased HCRU and medical costs, as well as decreased OS and AFS over a 20-year period following the initial diagnosis of LR-MDS. Given that a majority of LR-MDS patients experiencing TD may not be eligible for ESA treatment due to elevated EPO levels exceeding 200U/L, and the use of cytotoxic agents is not usually recommended for these patients, these results highlight a substantial unmet need for alternative treatment options to address RBC TD in LR-MDS patients.

Declarative Learning Mechanisms Support Declarative but Not Probabilistic Feedback-Based Learning in Children with Developmental Language Disorder (DLD).

Declarative and probabilistic feedback-based learning was evaluated in 8-12-year-old school-age children with developmental language disorder (DLD; n = 14) and age-matched children with typical development (TD; n = 15). Children performed a visual two-choice word-learning task and a visual probabilistic classification task while their electroencephalogram (EEG) was recorded non-invasively from the scalp. Behavioral measures of accuracy and response to feedback, and electrophysiological responses to feedback were collected and compared between the two groups. While behavioral data indicated poorer performance by children with DLD in both learning paradigms, and similar response patterns to positive and negative feedback, electrophysiological data highlighted processing patterns in the DLD group that differed by task. More specifically, in this group, feedback processing in the context of declarative learning, which is known to be dominated by the medial temporal lobe (MTL), was associated with enhanced N170, an event-related brain potential (ERP) associated with MTL activation. The N170 amplitude was found to be correlated with declarative task performance in the DLD group. During probabilistic learning, known to be governed by the striatal-based learning system, the feedback-related negativity (FRN) ERP, which is the product of the cortico-striatal circuit dominated feedback processing. Within the context of probabilistic learning, enhanced N170 was associated with poor learning in the TD group, suggesting that MTL activation during probabilistic learning disrupts learning. These results are interpreted within the context of a proposed feedback parity hypothesis suggesting that in children with DLD, the system that dominates learning (i.e., MTL during declarative learning and the striatum during probabilistic learning) dominates and supports feedback processing.

Utilizing artificial intelligence-based eye tracking technology for screening ADHD symptoms in children.

To explore the potential of using artificial intelligence (AI)-based eye tracking technology on a tablet for screening Attention-deficit/hyperactivity disorder (ADHD) symptoms in children. We recruited 112 children diagnosed with ADHD (ADHD group; mean age: 9.40 ± 1.70 years old) and 325 typically developing children (TD group; mean age: 9.45 ± 1.59 years old). We designed a data-driven end-to-end convolutional neural network appearance-based model to predict eye gaze to permit eye-tracking under low resolution and sampling rates. The participants then completed the eye tracking task on a tablet, which consisted of a simple fixation task as well as 14 prosaccade (looking toward target) and 14 antisaccade (looking away from target) trials, measuring attention and inhibition, respectively. Two-way MANOVA analyses demonstrated that diagnosis and age had significant effects on performance on the fixation task [diagnosis: F(2, 432) = 8.231, ***p < 0.001; Wilks' Λ = 0.963; age: F(2, 432) = 3.999, *p < 0.019; Wilks' Λ = 0.982], prosaccade task [age: F(16, 418) = 3.847, ***p < 0.001; Wilks' Λ = 0.872], and antisaccade task [diagnosis: F(16, 418) = 1.738, *p = 0.038; Wilks' Λ = 0.938; age: F(16, 418) = 4.508, ***p < 0.001; Wilks' Λ = 0.853]. Correlational analyses revealed that participants with higher SNAP-IV score were more likely to have shorter fixation duration and more fixation intervals (r = -0.160, 95% CI [0.250, 0.067], ***p < 0.001), poorer scores on adjusted prosaccade accuracy, and poorer scores on antisaccade accuracy (Accuracy: r = -0.105, 95% CI [-0.197, -0.011], *p = 0.029; Adjusted accuracy: r = -0.108, 95% CI [-0.200, -0.015], *p = 0.024). Our AI-based eye tracking technology implemented on a tablet could reliably discriminate eye movements of the TD group and the ADHD group, providing a potential solution for ADHD screening outside of clinical settings.