30 research outputs found

    GestaltMatcher Database - A global reference for facial phenotypic variability in rare human diseases

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    The most important factor that complicates the work of dysmorphologists is the significant phenotypic variability of the human face. Next-Generation Phenotyping (NGP) tools that assist clinicians with recognizing characteristic syndromic patterns are particularly challenged when confronted with patients from populations different from their training data. To that end, we systematically analyzed the impact of genetic ancestry on facial dysmorphism. For that purpose, we established the GestaltMatcher Database (GMDB) as a reference dataset for medical images of patients with rare genetic disorders from around the world. We collected 10,980 frontal facial images - more than a quarter previously unpublished - from 8,346 patients, representing 581 rare disorders. Although the predominant ancestry is still European (67%), data from underrepresented populations have been increased considerably via global collaborations (19% Asian and 7% African). This includes previously unpublished reports for more than 40% of the African patients. The NGP analysis on this diverse dataset revealed characteristic performance differences depending on the composition of training and test sets corresponding to genetic relatedness. For clinical use of NGP, incorporating non-European patients resulted in a profound enhancement of GestaltMatcher performance. The top-5 accuracy rate increased by +11.29%. Importantly, this improvement in delineating the correct disorder from a facial portrait was achieved without decreasing the performance on European patients. By design, GMDB complies with the FAIR principles by rendering the curated medical data findable, accessible, interoperable, and reusable. This means GMDB can also serve as data for training and benchmarking. In summary, our study on facial dysmorphism on a global sample revealed a considerable cross ancestral phenotypic variability confounding NGP that should be counteracted by international efforts for increasing data diversity. GMDB will serve as a vital reference database for clinicians and a transparent training set for advancing NGP technology.</p

    Distinct neural signatures of cognitive subtypes of dyslexia with and without phonological deficits

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    AbstractDevelopmental dyslexia can be distinguished as different cognitive subtypes with and without phonological deficits. However, despite some general agreement on the neurobiological basis of dyslexia, the neurofunctional mechanisms underlying these cognitive subtypes remain to be identified. The present BOLD fMRI study thus aimed at investigating by which distinct and/or shared neural activation patterns dyslexia subtypes are characterized. German dyslexic fourth graders with and without deficits in phonological awareness and age-matched normal readers performed a phonological decision task: does the auditory word contain the phoneme/a/? Both dyslexic subtypes showed increased activation in the right cerebellum (Lobule IV) compared to controls. Subtype-specific increased activation was systematically found for the phonological dyslexics as compared to those without this deficit and controls in the left inferior frontal gyrus (area 44: phonological segmentation), the left SMA (area 6), the left precentral gyrus (area 6) and the right insula. Non-phonological dyslexics revealed subtype-specific increased activation in the left supramarginal gyrus (area PFcm; phonological storage) and angular gyrus (area PGp). The study thus provides the first direct evidence for the neurobiological grounding of dyslexia subtypes. Moreover, the data contribute to a better understanding of the frequently encountered heterogeneous neuroimaging results in the field of dyslexia

    The role of phonological awareness in treatments of dyslexic primary school children

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    The present study investigated whether phonological awareness training is an effective intervention to significantly improve reading in German dyslexic third and fourth graders with a phonological awareness deficit, and whether these children can equally benefit from a phonology-based reading training or a visually-based reading training. German speaking dyslexic elementary school children (n=30; M=9.8 years) were matched by forming triplets based on IQ, reading quotient and phonological awareness and then randomly assigned to one out of three interventions (n=10): a phonological awareness training, a phonology-based reading training (phonics instruction), and a visually-based reading training (repeated reading of sight words). A total of 20 training sessions (30 minutes each) were distributed over four weeks. Typical readers (n=10; M=9.5 years) were assigned to the control group. Phonological awareness training directly improves reading comprehension in German dyslexic children with a phonological awareness deficit. However, these children can equally benefit from a visually-based reading training. In contrast, the phonology-based reading training has a direct selective effect on decoding but not on reading comprehension. Despite divergent short-term patterns, long-term improvement of reading comprehension and decoding is similar across all training groups, irrespective of the training method. Phonological awareness may but does not need to be part of reading remediation in dyslexic children with a phonological deficit when learning to read a consistent orthography. Rather, a visually-based reading strategy might compensate for the phonological deficit in dyslexic children after the initial stage of reading acquisition

    Devil in the details? Developmental dyslexia and visual long-term memory for details

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    Cognitive theories on causes of developmental dyslexia can be divided into language-specific and general accounts. While the former assume that words are special in that associated processing problems are rooted in language-related cognition (e.g., phonology) deficits, the latter propose that dyslexia is rather rooted in a general impairment of cognitive (e.g., visual and/or auditory) processing streams. In the present study, we examined to what extent dyslexia (typically characterized by poor orthographic representations) may be associated with a general deficit in visual long-term memory for details. We compared object- and detail-related visual long-term memory performance (and phonological skills) between dyslexic primary school children and IQ-, age- and gender-matched controls. The results revealed that while the overall amount of long-term memory errors was comparable between groups, dyslexic children exhibited a greater portion of detail-related errors. The results suggest that not only phonological, but also general visual resolution deficits in long-term memory may play an important role in developmental dyslexia

    Subtypen-spezifisches Training bei Dyslexie

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    Kognitive Subtypen von Entwicklungsdyslexie können Defizite vor allem in der Phonologie oder der visuell-räumlichen Aufmerksamkeit haben, die mit hirnfunktionellen Unterschieden zu Normallesern einhergehen. Die subtypenspezifische Aktivierungsänderung durch ein visuelles Aufmerksamkeitstraining wurde bisher noch nicht untersucht.Die vorliegende fMRT-Studie untersucht den Einfluss von defizitspezifischen Trainings vs. Lesetrainings auf die neuronalen Korrelate dyslektischer Subtypen verglichen wiederum mit Normallesern. Dritt- und Viertklässler wurden psychometrischen Tests unterzogen, u. a. zu phonologischen und Aufmerksamkeitsfähigkeiten. Alle Dyslektiker erhielten ein vierwöchiges Training: Dyslektiker mit primär phonologischem Defizit ein rein phonologisches Training, Kinder mit primärem Aufmerksamkeitsdefizit ein Aufmerksamkeitstraining. Ein reines Lesetraining erhielt eine dritte Dyslexiegruppe: Dyslektiker unabhängig von ihrem kognitiven Defizit. Mittels fMRT wurde vor und nach dem Training das Posner Paradigma zur visuell-räumlichen Aufmerksamkeitsausrichtung mit den drei Trainingsgruppen und einer vierten Gruppe, den Normallesern, durchgeführt, um zu untersuchen, wie sich das Training auf die neurofunktionelle Verarbeitung der drei Dyslexiegruppen auswirkt. Die fMRT-Daten ergaben für alle Trainingsgruppen eine signifikante Veränderung im linken inferioren Frontalcortex. Das Maximum dieser Aktivierungsveränderung lag jedoch jeweils an verschiedenen Stellen innerhalb dieser Region: für die Trainingsgruppe Phonologie auf dem GFI in der Broca-Region, für die Trainingsgruppen Aufmerksamkeit und Lesen jeweils im Sulcus frontalis inferior. Die drei Gruppen verarbeiten möglicherweise verschiedene Funktionen in dieser sehr heterogenen Region. Das linkshemisphärische Aktivierungsmuster könnte somit auf unterschiedliche Kompensation nach den verschiedenen Dyslexie-Trainings hinweisen, die nicht in klassischen rechts-hemisphärischen Aufmerksamkeitsarealen, sondern im linkshemispärischen Sprachnetzwerk lokalisiert sind

    Shared vs. specific brain activation changes in dyslexia after training of phonology, attention, or reading

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    Whereas the neurobiological basis of developmental dyslexia has received substantial attention, only little is known about the processes in the brain during remediation. This holds in particular in light of recent findings on cognitive subtypes of dyslexia which suggest interactions between individual profiles, training methods, and also the task in the scanner. Therefore, we trained three groups of German dyslexic primary school children in the domains of phonology, attention, or visual word recognition. We compared neurofunctional changes after 4 weeks of training in these groups to those in untrained normal readers in a reading task and in a task of visual attention. The overall reading improvement in the dyslexic children was comparable over groups. It was accompanied by substantial increase of the activation level in the visual word form area (VWFA) during a reading task inside the scanner. Moreover, there were activation increases that were unique for each training group in the reading task. In contrast, when children performed the visual attention task, shared training effects were found in the left inferior frontal sulcus and gyrus, which varied in amplitude between the groups. Overall, the data reveal that different remediation programmes matched to individual profiles of dyslexia may improve reading ability and commonly affect the VWFA in dyslexia as a shared part of otherwise distinct networks

    Controlling the Self-Metalation Rate of Tetraphenylporphyrins on Cu(111) via Cyano Functionalization.

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    The reaction rate of the self-metalation of free-base tetraphenylporphyrins (TPPs) on Cu(111) increases with the number of cyano groups (n=0, 1, 2, 4) attached at the para positions of the phenyl rings. The findings are based on isothermal scanning tunneling microscopy (STM) measurements. At room temperature, all investigated free-base TPP derivatives adsorb as individual molecules and are aligned with respect to densely packed Cu substrate rows. Annealing at 400 K leads to the formation of linear dimers and/or multimers via CN-Cu-CN bonds, accompanied by self-metalation of the free-base porphyrins following a first-order rate equation. When comparing the non-cyano-functionalized and the tetracyano-functionalized molecules, we find a decrease of the reaction rate by a factor of more than 20, corresponding to an increase of the activation energy from 1.48 to 1.59 eV. Density functional theory (DFT) calculations give insights into the influence of the peripheral electron-withdrawing cyano groups and explain the experimentally observed effects
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