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1.
Mol Autism ; 15(1): 24, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38845057

RESUMO

BACKGROUND: Brief questionnaires that comprehensively capture key restricted and repetitive behaviours (RRBs) across different informants have potential to support autism diagnostic services. We tested the psychometric properties of the 20-item Repetitive Behaviours Questionnaire-3 (RBQ-3), a questionnaire that includes self-report and informant-report versions enabling use across the lifespan. METHOD: In Study 1, adults referred to a specialised adult autism diagnostic service (N = 110) completed the RBQ-3 self-report version, and a relative or long-term friend completed the RBQ-3 informant-report version. Clinicians completed the abbreviated version of the Diagnostic Interview for Social and Communication Disorders (DISCO-Abbreviated) with the same adults as part of the diagnostic process. For half of the assessments, clinicians were blind to the RBQ-3 ratings. We tested internal consistency, cross-informant reliability and convergent validity of the RBQ-3. In Study 2, a follow-up online study with autistic (N = 151) and non-autistic (N = 151) adults, we further tested internal consistency of the RBQ-3 self-report version. We also tested group differences and response patterns in this sample. RESULTS: Study 1 showed good to excellent internal consistency for both self- and informant-report versions of the RBQ-3 (total score, α = 0.90, ω = 0.90, subscales, α = 0.76-0.89, ω = 0.77-0.88). Study 1 also showed cross-informant reliability as the RBQ-3 self-report scores significantly correlated with RBQ-3 informant-report scores for the total score (rs = 0.71) and subscales (rs= 0.69-0.72). Convergent validity was found for both self and informant versions of the RBQ-3, which significantly correlated with DISCO-Abbreviated RRB domain scores (rs = 0.45-0.54). Moreover, the RBQ-3 scores showed significantly weaker association with DISCO -Abbreviated scores for the Social Communication domain, demonstrating divergent validity. Importantly, these patterns of validity were found even when clinicians were blind to RBQ-3 items. In Study 2, for both autistic and non-autistic groups, internal consistency was found for the total score (α = 0.82-0.89, ω = 0.81-0.81) and for subscales (α = 0.68-0.85, ω = 0.69-0.85). A group difference was found between groups. LIMITATIONS: Due to the characteristics and scope of the specialist autism diagnostic service, further testing is needed to include representative samples of age (including children) and intellectual ability, and those with a non-autistic diagnostic outcome. CONCLUSIONS: The RBQ-3 is a questionnaire of RRBs that can be used across the lifespan. The current study tested its psychometric properties with autistic adults without intellectual disability and supported its utility for both clinical diagnostic and research settings.


Assuntos
Psicometria , Autorrelato , Humanos , Adulto , Masculino , Feminino , Inquéritos e Questionários , Pessoa de Meia-Idade , Adulto Jovem , Reprodutibilidade dos Testes , Transtorno Autístico/diagnóstico , Transtorno Autístico/psicologia , Adolescente , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/psicologia
2.
Respirology ; 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802282

RESUMO

BACKGROUND AND OBJECTIVE: Chest x-ray (CXR) remains a core component of health monitoring guidelines for workers at risk of exposure to crystalline silica. There has however been a lack of evidence regarding the sensitivity of CXR to detect silicosis in artificial stone benchtop industry workers. METHODS: Paired CXR and high-resolution computed tomography (HRCT) images were acquired from 110 artificial stone benchtop industry workers. Blinded to the clinical diagnosis, each CXR and HRCT was independently read by two thoracic radiologists from a panel of seven, in accordance with International Labour Office (ILO) methodology for CXR and International Classification of HRCT for Occupational and Environmental Respiratory Diseases. Accuracy of screening positive (ILO major category 1, 2 or 3) and negative (ILO major category 0) CXRs were compared with identification of radiological features of silicosis on HRCT. RESULTS: CXR was positive for silicosis in 27/110 (24.5%) workers and HRCT in 40/110 (36.4%). Of the 83 with a negative CXR (ILO category 0), 15 (18.1%) had silicosis on HRCT. All 11 workers with ILO category 2 or 3 CXRs had silicosis on HRCT. In 99 workers ILO category 0 or 1 CXRs, the sensitivity of screening positive CXR compared to silicosis identified by HRCT was 48% (95%CI 29-68) and specificity 97% (90-100). CONCLUSION: Compared to HRCT, sensitivity of CXR was low but specificity was high. Reliance on CXR for health monitoring would provide false reassurance for many workers, delay management and underestimate the prevalence of silicosis in the artificial stone benchtop industry.

3.
Breast Cancer Res Treat ; 205(3): 567-577, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38520597

RESUMO

PURPOSE: Recruit and sequence breast cancer subjects in Guatemalan and US Hispanic populations. Identify optimum strategies to recruit Latin American and Hispanic women into genetic studies of breast cancer. METHODS: We used targeted gene sequencing to identify pathogenic variants in 19 familial breast cancer susceptibility genes in DNA from unselected Hispanic breast cancer cases in the US and Guatemala. Recruitment across the US was achieved through community-based strategies. In addition, we obtained patients receiving cancer treatment at major hospitals in Texas and Guatemala. RESULTS: We recruited 287 Hispanic US women, 38 (13%) from community-based and 249 (87%) from hospital-based strategies. In addition, we ascertained 801 Guatemalan women using hospital-based recruitment. In our experience, a hospital-based approach was more efficient than community-based recruitment. In this study, we sequenced 103 US and 137 Guatemalan women and found 11 and 10 pathogenic variants, respectively. The most frequently mutated genes were BRCA1, BRCA2, CHEK2, and ATM. In addition, an analysis of 287 US Hispanic patients with pathology reports showed a significantly higher percentage of triple-negative disease in patients with pathogenic variants (41% vs. 15%). Finally, an analysis of mammography usage in 801 Guatemalan patients found reduced screening in women with a lower socioeconomic status (p < 0.001). CONCLUSION: Guatemalan and US Hispanic women have rates of hereditary breast cancer pathogenic variants similar to other populations and are more likely to have early age at diagnosis, a family history, and a more aggressive disease. Patient recruitment was higher using hospital-based versus community enrollment. This data supports genetic testing in breast cancer patients to reduce breast cancer mortality in Hispanic women.


Assuntos
Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Hispânico ou Latino , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/etnologia , Neoplasias de Mama Triplo Negativas/epidemiologia , Hispânico ou Latino/genética , Hispânico ou Latino/estatística & dados numéricos , Guatemala/epidemiologia , Pessoa de Meia-Idade , Adulto , Idoso , Estados Unidos/epidemiologia , Seleção de Pacientes
4.
Eur J Surg Oncol ; 50(4): 108245, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38484493

RESUMO

INTRODUCTION: Targeted axillary dissection (TAD) is performed after neoadjuvant systemic therapy (NST) to decrease the rate of non-therapeutic axillary dissection (ALND) for patients with node-positive breast cancer. In order to ensure the oncologic safety of TAD, eligibility criteria resulting in a low false negative rate (FNR) have been proposed. The purpose of this study was to evaluate the utility of the traditional criteria. METHODS: Data was collected from a prospective multicenter registry. In order to ascertain FNRs, pathologic findings in the sentinel lymph nodes (LN)s, malignant clipped LN, and axillary contents were determined. The FNRs within TAD eligibility criterion groups were compared. RESULTS: A total of 110 patients underwent TAD and ALND, and were therefore eligible for analysis. TAD retained a low FNR in advanced clinical T-N stage compared with earlier disease (T stage: 95% CI 0.00-11.93, p = 0.42; N stage: 95% CI 0.00-8.76, p = 0.31). Presentation with ≥4 abnormal LNs on axillary ultrasound did not predict a high TAD FNR (95% CI 0.00-5.37, p = 0.16). No significant differences were noted in TAD FNR when single was compared with dual tracer (blue dye vs dual tracer 95% CI 0.72-52.49, p = 0.13; radiotracer vs dual tracer 0.04-20.11, p = 0.51). Excision of the clipped LN and only one SLN was as accurate as excision of the clipped LN and ≥2 SLNs (95% CI 0.00-10.61, p = 0.38). CONCLUSIONS: TAD retained a low FNR among patients traditionally considered ineligible for this technique. However, excision of the clipped LN and at least one SLN remained essential to a low FNR.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Terapia Neoadjuvante/métodos , Biópsia de Linfonodo Sentinela/métodos , Estudos Prospectivos , Metástase Linfática/patologia , Excisão de Linfonodo/métodos , Axila/patologia , Sistema de Registros , Linfonodos/patologia , Estadiamento de Neoplasias
5.
Res Dev Disabil ; 148: 104714, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38484422

RESUMO

BACKGROUND: Children with Developmental Coordination Disorder (DCD) can experience sensory differences. There has been limited exploration of these differences and their impact on children with DCD. AIMS: i) To explore the presence and impact of sensory differences in children with DCD compared to children without DCD; ii) To examine whether sensory differences are related to motor ability, attention deficit hyperactivity disorder (ADHD), or autistic traits. METHOD: Parents of children (8-12 years) with (n = 23) and without (n = 33) DCD used standardised questionnaires to report on their children's sensory differences, autistic traits, and ADHD traits. Motor abilities were assessed through the Movement Assessment Battery for Children-2. Data were explored both categorically (between-groups) and dimensionally. RESULTS: Children with DCD had significantly higher levels of sensory differences than children without DCD. Sensory differences also had a significantly greater impact on daily activities for children with DCD. Higher levels of ADHD and autistic traits, but not motor ability, were significant independent predictors of higher levels of sensory difference. CONCLUSION: Children with DCD experience high levels of sensory differences, which impact on their daily lives. These sensory differences may be a marker for additional neurodivergence in children with DCD. Practitioners should consider the sensory needs of children with DCD. WHAT THIS PAPER ADDS: This paper provides insight into the sensory features of children with DCD and the impact that sensory differences can have on daily living. Using parent-report, we found that children with DCD had increased sensory differences relative to children without DCD. These included increased hyperresponsiveness, increased hyporesponsiveness, and increased sensory interests, repetitions, and seeking behaviours (SIRS). We also found that sensory differences had a greater impact on daily living for children with DCD compared to children without DCD. Across the whole sample, autistic traits predicted hyperresponsivity and hyporesponsivity patterns; whereas traits of hyperactivity and impulsivity predicted SIRS. Motor abilities did not uniquely predict sensory differences, suggesting that other traits of neurodivergence may contribute to the sensory differences in DCD. Taken together, these findings highlight the necessity of considering sensory needs when supporting children with DCD. They also suggest that if sensory differences are identified in children with DCD, it may be due to the presence of co-occurring neurodivergent traits or conditions.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtornos das Habilidades Motoras , Criança , Humanos , Movimento , Inquéritos e Questionários , Síndrome de Resposta Inflamatória Sistêmica
6.
Dev Psychobiol ; 66(3): e22477, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38433461

RESUMO

Response inhibition difficulties are reported in individuals with eating disorders (EDs), anxiety, and depression. Although ED symptoms and internalizing symptoms co-occur in preadolescence, there is limited research examining associations between these symptoms and response inhibition in this age group. This study is the first to investigate the associations between behavioral and neural markers of response inhibition, disordered eating (DE), and internalizing symptoms in a community sample of preadolescents. Forty-eight children (M age = 10.95 years, 56.3% male) completed a Go/NoGo task, whereas electroencephalography was recorded. Self-report measures of DE and internalizing symptoms were collected. Higher levels of anxiety and depression were associated with neural markers of suboptimal response inhibition (attenuated P3NoGo amplitudes) in preadolescence. In contrast, higher levels of depression were associated with greater response inhibition at a behavioral level. These findings suggest internalizing symptoms in preadolescence are associated with P3-indexed difficulties in evaluation and monitoring, but these are not sufficient to disrupt behavioral performance on a response inhibition task. This pattern may reflect engagement of compensatory processes to support task performance. DE was not significantly associated with response inhibition, suggesting that difficulties in response inhibition may only be reliably observed in more chronic and severe DE and ED presentations.


Assuntos
Ansiedade , Transtornos da Alimentação e da Ingestão de Alimentos , Criança , Masculino , Humanos , Feminino , Transtornos de Ansiedade , Eletroencefalografia
7.
IUCrJ ; 11(Pt 2): 260-274, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38446458

RESUMO

The discovery of lytic polysaccharide monooxygenases (LPMOs), a family of copper-dependent enzymes that play a major role in polysaccharide degradation, has revealed the importance of oxidoreductases in the biological utilization of biomass. In fungi, a range of redox proteins have been implicated as working in harness with LPMOs to bring about polysaccharide oxidation. In bacteria, less is known about the interplay between redox proteins and LPMOs, or how the interaction between the two contributes to polysaccharide degradation. We therefore set out to characterize two previously unstudied proteins from the shipworm symbiont Teredinibacter turnerae that were initially identified by the presence of carbohydrate binding domains appended to uncharacterized domains with probable redox functions. Here, X-ray crystal structures of several domains from these proteins are presented together with initial efforts to characterize their functions. The analysis suggests that the target proteins are unlikely to function as LPMO electron donors, raising new questions as to the potential redox functions that these large extracellular multi-haem-containing c-type cytochromes may perform in these bacteria.


Assuntos
Gammaproteobacteria , Oxirredução , Oxigenases de Função Mista , Polissacarídeos
9.
JMIR Form Res ; 8: e48668, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319695

RESUMO

BACKGROUND: There are disparities in the prevalence of physical activity (PA) with women engaging in less PA than men, a gap which widens during midlife. Walking is a generally accepted form of PA among women and should be encouraged. Motivations, barriers, and attitudes to engaging in walking change with age, but the influencing factors are not well understood nor are the features of mobile apps that facilitate daily walking. OBJECTIVE: This study explores the relationship between age and women's self-reported motivations, barriers, attitudes, and beliefs toward daily walking. It further assesses attitudes toward features of a mobile app designed to sync with a wearable step tracker to increase and maintain levels of daily walking among women. METHODS: A web-based anonymous survey was completed by 400 women, aged 21-75 years. The 31-item survey captured women's perceived barriers and motivators toward daily walking and attitudes toward mobile apps to support and maintain daily walking. For analysis, responses to the survey were grouped into 2 categories of women: ages 21-49 years and ages 50-75 years. Bivariate analyses were conducted through SPSS (IBM Corp) for each of the survey questions using chi-square for dichotomous variables and 1-tailed t tests for scales and continuous variables to identify significant differences between the groups. One-tailed t tests were run for scaled variables to identify significant differences between the 10-year age increments. RESULTS: Significant barriers to daily walking were observed in the 21-49-year group for personal and work responsibilities, motivational and psychosocial factors, and physical and environmental factors. Motivators to walk daily in the 21- 49-year group were significantly higher to reduce stress and anxiety, and motivators to walk daily in the 50-75-year group were significantly higher to help manage or lose weight and to reduce the risk of chronic illness. Women's walking preferences, beliefs around their walking behaviors, and their perceived importance of the features of a future mobile app for walking designed specifically for women showed significant variation according to age. When asked about the importance of features for a mobile app, women aged 21-49 years indicated a significantly higher number of positive responses for the following features: digital community support, rewards or point system, and seeing a daily or weekly or monthly progress chart. CONCLUSIONS: Our findings indicate that barriers, motivators, and beliefs around daily walking and the importance of preferred features of a mobile app vary according to women's ages. Messaging and app features should be tailored to different age groups of women. These study results can be viewed as a foundation for future research and development of mobile health interventions to effectively increase daily walking among women of all ages.

10.
Autism ; 28(6): 1328-1343, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38197398

RESUMO

LAY ABSTRACT: Some autistic people describe trying to hide autistic behaviour and seem more neurotypical. Researchers called this 'social camouflaging' and have linked it with mental health difficulties. We used a step-by-step approach to identify research where autistic people talk about social camouflaging to explore the relationship between camouflaging and poor mental health. Thirteen studies were combined. The results describe how society negatively impacts autistic people's mental health, and camouflaging is a way to try and cope with this. Many autistic people find their camouflaging strategies have accidental negative consequences which also affect their mental health. Strategies which seemed 'successful' involved a lot of self-monitoring, were very mentally demanding or were very habitual and seemed to have more of an effect on mental health. This might be important for clinicians who support autistic people with mental health difficulties.


Assuntos
Antropologia Cultural , Transtorno Autístico , Saúde Mental , Humanos , Transtorno Autístico/psicologia , Adaptação Psicológica
11.
Br J Radiol ; 97(1153): 180-185, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263827

RESUMO

OBJECTIVES: To investigate the impact of adding 68Ga-DOTATATE PET/MRI to standard MRI for target volume delineation in Gamma Knife® stereotactic radiosurgery (GKSRS) for meningioma. METHODS: Seventeen patients with 18 lesions undergoing GKSRS for WHO grade 1 meningioma were enrolled in a prospective study. All patients underwent pre-treatment 68Ga-DOTATATE PET/MRI examination in addition to standard procedures. Five clinicians independently contoured the gross tumour volume (GTV) based on standard MRI (GTVMRI) and PET/MRI (GTVPET/MRI) on separate occasions. Interobserver agreement was evaluated using Cohen's Kappa statistic (CKS), Dice similarity coefficient (DC), and Hausdorff distance (HD). Statistical analysis was performed with paired t-test and Wilcoxon signed rank test. RESULTS: The addition of PET/MRI significantly increased GTV contour volume (mean GTVPET/MRI 3.59 cm3 versus mean GTVMRI 3.18 cm3, P = .008). Using the treating clinician's pre-treatment GTVMRI as the reference, median CKS (87.2 vs 77.5, P = .006) and DC (87.2 vs 77.4, P = .006) were significantly lower, and median HD (25.2 vs 31.0, P = .001) was significantly higher with the addition of PET/MRI. No significant difference was observed in interobserver contouring reproducibility between GTVMRI and GTVPET/MRI. CONCLUSION: The addition of 68Ga-DOTATATE PET/MRI for target volume delineation in GKSRS for meningioma is associated with an increase in GTV volume and greater interobserver variation. PET/MRI did not affect interobserver contouring reproducibility. ADVANCES IN KNOWLEDGE: This study provides novel insights into the impact of 68Ga-DOTATATE PET/MRI on GTV delineation and interobserver agreement in meningioma GKSRS, highlighting its potential for improving GKSRS treatment accuracy.


Assuntos
Neoplasias Meníngeas , Meningioma , Compostos Organometálicos , Radiocirurgia , Humanos , Estudos Prospectivos , Reprodutibilidade dos Testes , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons
12.
Rehabil Psychol ; 69(2): 129-134, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38166293

RESUMO

PURPOSE/OBJECTIVE: Walking dysfunction, depression, and anxiety are prevalent, burdensome, and interrelated outcomes in persons with multiple sclerosis (MS). The 12-item Multiple Sclerosis Walking Scale (MSWS-12) is a common patient-reported outcome (PRO) of walking dysfunction in research and practice involving MS, but the construct validity of its scores might be influenced by symptoms of depression and anxiety. This study examined if symptoms of depression and anxiety influenced the construct validity of MSWS-12 scores. RESEARCH METHOD/DESIGN: The sample included 189 participants with MS who completed the MSWS-12, Hospital Anxiety and Depression Scale (HADS-Depression subscale [HADS-D] and HADS-Anxiety subscale [HADS-A]), 6-minute walk (6MW), and timed 25-foot walk (T25FW). We conducted bivariate correlation analysis to examine the associations between MSWS-12 scores and both the 6MW and T25FW, while controlling for HADS-D and HADS-A scores. RESULTS: MSWS-12 scores were significantly correlated with the 6MW (r = -.752), T25FW (r = .694), HADS-D (r = .405), and HADS-A (r = .235). The correlations between MSWS-12 and 6MW (pr = -.725) and T25FW (pr = .685) did not change when controlling for HADS-D and HADS-A scores. The correlations between MSWS-12 and 6MW (r = -.708 and r = -.726) and T25FW (r = .687 and r = .748) were strong in subsamples with elevated HADS-D and HADS-A scores. CONCLUSIONS/IMPLICATIONS: Our results strengthen the validity evidence for MSWS-12 scores as a PRO of walking dysfunction in MS, including among those with symptoms of depression and anxiety. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Assuntos
Esclerose Múltipla , Caminhada , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Esclerose Múltipla/psicologia , Reprodutibilidade dos Testes , Adulto , Psicometria , Transtornos de Ansiedade/psicologia , Transtornos de Ansiedade/diagnóstico , Idoso , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/psicologia , Transtorno Depressivo/complicações
13.
Autism ; 28(3): 644-655, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37421130

RESUMO

LAY ABSTRACT: Multi-sensory environments, often called sensory rooms, are widely used with autistic children. However, we know very little about how autistic children choose to spend their time in multi-sensory environments. We also do not know how their equipment preferences relate to their individual characteristics such as their sensory differences, level of ability or general autistic behaviours. We measured the frequency and duration of visits to multi-sensory environment equipment of 41 autistic children during 5 min of free play. The bubble tube and touch, sound and light board were both highly popular, with the fibre optics and tactile board receiving less attention. The children displayed significantly more sensory seeking behaviours in the multi-sensory environment than sensory-defensive behaviours. These sensory seeking behaviours, as well as the sensory behaviours that their parents reported they showed in daily life, were associated with specific patterns of multi-sensory environment equipment use. Non-verbal ability was also associated with multi-sensory environment equipment use, but broader autistic behaviours were not. Our findings show that the multi-sensory environment equipment preferences of autistic children are related to individual differences in sensory behaviours and non-verbal ability. This information could be useful for teachers and other practitioners who want to know how best to use multi-sensory environments with autistic children.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Pessoal de Educação , Criança , Humanos , Transtorno Autístico/complicações , Transtorno do Espectro Autista/complicações , Comportamento Estereotipado , Pais
14.
Eur Radiol ; 34(2): 810-822, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37606663

RESUMO

OBJECTIVES: Non-contrast computed tomography of the brain (NCCTB) is commonly used to detect intracranial pathology but is subject to interpretation errors. Machine learning can augment clinical decision-making and improve NCCTB scan interpretation. This retrospective detection accuracy study assessed the performance of radiologists assisted by a deep learning model and compared the standalone performance of the model with that of unassisted radiologists. METHODS: A deep learning model was trained on 212,484 NCCTB scans drawn from a private radiology group in Australia. Scans from inpatient, outpatient, and emergency settings were included. Scan inclusion criteria were age ≥ 18 years and series slice thickness ≤ 1.5 mm. Thirty-two radiologists reviewed 2848 scans with and without the assistance of the deep learning system and rated their confidence in the presence of each finding using a 7-point scale. Differences in AUC and Matthews correlation coefficient (MCC) were calculated using a ground-truth gold standard. RESULTS: The model demonstrated an average area under the receiver operating characteristic curve (AUC) of 0.93 across 144 NCCTB findings and significantly improved radiologist interpretation performance. Assisted and unassisted radiologists demonstrated an average AUC of 0.79 and 0.73 across 22 grouped parent findings and 0.72 and 0.68 across 189 child findings, respectively. When assisted by the model, radiologist AUC was significantly improved for 91 findings (158 findings were non-inferior), and reading time was significantly reduced. CONCLUSIONS: The assistance of a comprehensive deep learning model significantly improved radiologist detection accuracy across a wide range of clinical findings and demonstrated the potential to improve NCCTB interpretation. CLINICAL RELEVANCE STATEMENT: This study evaluated a comprehensive CT brain deep learning model, which performed strongly, improved the performance of radiologists, and reduced interpretation time. The model may reduce errors, improve efficiency, facilitate triage, and better enable the delivery of timely patient care. KEY POINTS: • This study demonstrated that the use of a comprehensive deep learning system assisted radiologists in the detection of a wide range of abnormalities on non-contrast brain computed tomography scans. • The deep learning model demonstrated an average area under the receiver operating characteristic curve of 0.93 across 144 findings and significantly improved radiologist interpretation performance. • The assistance of the comprehensive deep learning model significantly reduced the time required for radiologists to interpret computed tomography scans of the brain.


Assuntos
Aprendizado Profundo , Adolescente , Humanos , Radiografia , Radiologistas , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Adulto
15.
Reprod Biomed Online ; 48(1): 103418, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37944257

RESUMO

RESEARCH QUESTION: What are the support needs of donor conceived individuals who are searching for or open to matching with genetic connections? DESIGN: A total of 88 donor conceived adults in the UK participated in an online survey open between January and August 2022. Participants were asked about their level of awareness of current resource provision, recommendations for resources to support the process of searching for genetic connections, and recommendations for resources to support with feelings about searching for or being found by genetic connections. RESULTS: Participants were found to have varying levels of awareness of the resources available to them, with 39% describing themselves as aware, 41% as partly aware and 20% as unaware. Their recommendations for practical and emotional resources also varied. The most recommended resources for practical support were DNA testing and changes to UK law. The most recommended resources for emotional support were counselling and peer and other support groups. CONCLUSIONS: The impact of legal and technological changes such as direct-to-consumer DNA testing and the legal transition to identifiable donation may be felt by donor conceived individuals irrespective of their year of birth. The wishes of donor conceived individuals for different support resources should be borne in mind by practitioners, regulatory bodies, and policy makers going forward.


Assuntos
Doação de Oócitos , Doadores de Tecidos , Adulto , Humanos , Doação de Oócitos/psicologia , Doadores de Tecidos/psicologia , Aconselhamento , DNA , Reino Unido
16.
J Clin Invest ; 134(1)2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-37883178

RESUMO

Physiologic activation of estrogen receptor α (ERα) is mediated by estradiol (E2) binding in the ligand-binding pocket of the receptor, repositioning helix 12 (H12) to facilitate binding of coactivator proteins in the unoccupied coactivator binding groove. In breast cancer, activation of ERα is often observed through point mutations that lead to the same H12 repositioning in the absence of E2. Through expanded genetic sequencing of breast cancer patients, we identified a collection of mutations located far from H12 but nonetheless capable of promoting E2-independent transcription and breast cancer cell growth. Using machine learning and computational structure analyses, this set of mutants was inferred to act distinctly from the H12-repositioning mutants and instead was associated with conformational changes across the ERα dimer interface. Through both in vitro and in-cell assays of full-length ERα protein and isolated ligand-binding domain, we found that these mutants promoted ERα dimerization, stability, and nuclear localization. Point mutations that selectively disrupted dimerization abrogated E2-independent transcriptional activity of these dimer-promoting mutants. The results reveal a distinct mechanism for activation of ERα function through enforced receptor dimerization and suggest dimer disruption as a potential therapeutic strategy to treat ER-dependent cancers.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Proliferação de Células , Dimerização , Estradiol/farmacologia , Estradiol/metabolismo , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Ligantes , Mutação
17.
Eur J Neurosci ; 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37731194

RESUMO

Doll play may provide opportunities for children to rehearse social interactions, even when playing alone. Previous research has found that the posterior superior temporal sulcus (pSTS) was more engaged when children played with dolls alone, compared to playing with tablet games alone. Children's use of internal state language (ISL) about others was also associated with pSTS activity. As differences in social cognition are frequently observed in autistic people, we were interested in the brain and language correlates of doll play in children with varying levels of autistic traits. We investigated children's (N = 57, mean age = 6.72, SD = 1.53) use of ISL and their pSTS brain activity using functional near-infrared spectroscopy (fNIRS) as they played with dolls and tablet games, both alone and with a social partner. We also investigated whether there were any effects of autistic traits using the parent-report Autism Spectrum Quotient-Children's Version (AQ-Child). We found that the left pSTS was engaged more as children played with dolls or a tablet with a partner, and when playing with dolls alone, compared to when playing with a tablet alone. Relations between language and neural correlates of social processing were distinct based on the degree of autistic traits. For children with fewer autistic traits, greater pSTS activity was associated with using ISL about others. For children with more autistic traits, greater pSTS activity was associated with experimenter talk during solo play. These divergent pathways highlight the importance of embracing neurodiversity in children's play patterns to best support their development through play.

18.
Cortex ; 168: 1-13, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37634268

RESUMO

AIM: There is emerging evidence that the Mirror Neuron System (MNS) might contribute to the motor learning difficulties characteristic of Developmental Coordination Disorder (DCD). This study aimed to identify whether MNS activity differed between children with and without DCD during action observation, action execution and during a non-action baseline. METHODS: Electroencephalography (EEG) was used to measure mu rhythm (a proxy for MNS activation) in 8-12-year-old children either with (n = 20) or without (n = 19) a diagnosis of DCD. The mu rhythm was recorded at rest and during five experimental conditions: (1) observation of gross motor and (2) fine motor actions; (3) execution of gross motor and (4) fine motor actions; and (5) non-biological movement. To address whether potential co-occurring traits of other neurodevelopmental conditions were associated with differences in mu rhythm, parents reported their child's attention and social communication skills. Mixed and repeated measure ANOVAs were conducted to examine differences in mu desynchronization and mu power respectively. RESULTS: The non-DCD group showed greater mu rhythm desynchronization than children with DCD (i.e., more MNS activity), with both groups demonstrating increasing desynchronization from observation of fine actions to execution of gross actions. However, we also found that the children with DCD had less mu power during the non-biological movement condition than the non-DCD children, although mu power did not differ between groups during the resting condition. Correlations between mu desynchronization and children's attention and motor skills showed that poorer attention and motor abilities were associated with reduced MNS activity. CONCLUSION: Compared to children without DCD, the MNS in children with DCD did not distinguish between biological and non-biological movement. It is possible that the reduced specificity of the MNS in children with DCD is an underlying factor in the motor impairments observed in the disorder. The differential MNS activity could reflect broader atypical activity in perceptual networks that feed into the MNS in DCD.

19.
G3 (Bethesda) ; 13(9)2023 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-37395764

RESUMO

Sequenced shark nuclear genomes are underrepresented, with reference genomes available for only four out of nine orders so far. Here, we present the nuclear genome, with annotations, of the spiny dogfish (Squalus acanthias), a shark of interest to biomedical and conservation efforts, and the first representative of the second largest order of sharks (Squaliformes) with nuclear genome annotations available. Using Pacific Biosciences Continuous Long Read data in combination with Illumina paired-end and Hi-C sequencing, we assembled the genome de novo, followed by RNA-Seq-supported annotation. The final chromosome-level assembly is 3.7 Gb in size, has a BUSCO completeness score of 91.6%, and an error rate of less than 0.02%. Annotation predicted 33,283 gene models in the spiny dogfish's genome, of which 31,979 are functionally annotated.


Assuntos
Tubarões , Squalus acanthias , Animais , Squalus acanthias/genética , Tubarões/genética , Sequência de Bases
20.
Diagnostics (Basel) ; 13(14)2023 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-37510062

RESUMO

This retrospective case-control study evaluated the diagnostic performance of a commercially available chest radiography deep convolutional neural network (DCNN) in identifying the presence and position of central venous catheters, enteric tubes, and endotracheal tubes, in addition to a subgroup analysis of different types of lines/tubes. A held-out test dataset of 2568 studies was sourced from community radiology clinics and hospitals in Australia and the USA, and was then ground-truth labelled for the presence, position, and type of line or tube from the consensus of a thoracic specialist radiologist and an intensive care clinician. DCNN model performance for identifying and assessing the positioning of central venous catheters, enteric tubes, and endotracheal tubes over the entire dataset, as well as within each subgroup, was evaluated. The area under the receiver operating characteristic curve (AUC) was assessed. The DCNN algorithm displayed high performance in detecting the presence of lines and tubes in the test dataset with AUCs > 0.99, and good position classification performance over a subpopulation of ground truth positive cases with AUCs of 0.86-0.91. The subgroup analysis showed that model performance was robust across the various subtypes of lines or tubes, although position classification performance of peripherally inserted central catheters was relatively lower. Our findings indicated that the DCNN algorithm performed well in the detection and position classification of lines and tubes, supporting its use as an assistant for clinicians. Further work is required to evaluate performance in rarer scenarios, as well as in less common subgroups.

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