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Development of Social Capabilities inside Preschool: A Latent Course Progress Modeling Approach.
The genetic alteration underlying the great majority of primary angioedema with normal C1 inhibitor (nl-C1-INH-HAE) cases remains unknown. To search for variants associated with nl-C1-INH-HAE, we genotyped 133 unrelated nl-C1-INH-HAE patients using a custom next-generation sequencing platform targeting 55 genes possibly involved in angioedema pathogenesis. Patients already diagnosed with F12 alterations as well as those with histaminergic acquired angioedema were excluded. A variant pathogenicity curation strategy was followed, including a comparison of the results with those of genotyping 169 patients with hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE), and only filtered-in variants were studied further. Among the examined nl-C1-INH-HAE patients, carriers of neither the ANGPT1 p.Ala119Ser nor the KNG1 p.Met379Lys variant were found, whereas the PLG p.Lys330Glu was detected in four (3%) unrelated probands (one homozygote). In total, 182 different variants were curated, 21 of which represented novel mutations. Although the frequency of variants per gene was comparable between nl-C1-INH-HAE and C1-INH-HAE, variants of the KNG1 and XPNPEP1 genes were detected only in nl-C1-INH-HAE patients (six and three, respectively). Twenty-seven filtered variants in 23 different genes were detected in nl-C1-INH-HAE more than once, whereas 69/133 nl-C1-INH-HAE patients had compound heterozygotes of filtered variants located in the same or different genes. Pedigree analysis was performed where feasible. Our results indicate the role that alterations in some genes, like KNG1, may play in disease pathogenesis, the complex trait that is possibly underlying in some cases, and the existence of hitherto unrecognized disease endotypes.Grasping is one of the first dominant motor behaviors that enable interaction of a newborn infant with its surroundings. Although atypical grasping patterns are considered predictive of neuromotor disorders and injuries, their clinical assessment suffers from examiner subjectivity, and the neuropathophysiology is poorly understood. Therefore, the combination of technology with functional magnetic resonance imaging (fMRI) may help to precisely map the brain activity associated with grasping and thus provide important insights into how functional outcomes can be improved following cerebral injury. This work introduces an MR-compatible device (i.e., smart graspable device (SGD)) for detecting grasping actions in newborn infants. Electromagnetic interference immunity (EMI) is achieved using a fiber Bragg grating sensor. Its biocompatibility and absence of electrical signals propagating through the fiber make the safety profile of the SGD particularly favorable for use with fragile infants. Firstly, the SGD design, fabrication, and metrological characterization are described, followed by preliminary assessments on a preterm newborn infant and an adult during an fMRI experiment. The results demonstrate that the combination of the SGD and fMRI can safely and precisely identify the brain activity associated with grasping behavior, which may enable early diagnosis of motor impairment and help guide tailored rehabilitation programs.Relapse after allogeneic hematopoietic stem cell transplantation (AHSCT) in myelofibrosis (MF) patients remains as a significant issue despite advances in transplantation procedures and significant prolongation in survival. Second AHSCT is a potential treatment option but associated with high treatment-related mortality and novel less toxic conditioning regimens are needed. In 33 MF patients with relapse after AHSCT and failure to donor lymphocyte infusion (DLI) we investigated treosulfan (36-42 g/m2) in combination with fludarabine and anti-thymocyte globulin (ATG) as conditioning regimen for a second AHSCT with matched related (n = 2), unrelated (n = 23), or mismatched unrelated (n = 8) donors. All patients achieved leukocyte engraftment after a median of 11 days, and 56 ± 13% experienced acute GVHD grade II-IV at day 100. The therapy-related mortality at day 100 and at 3 years was 16% and 31%, respectively. The cumulative incidence of relapse at 5 years was 16%, resulting in a 5-year disease-free and overall survival of 45% and 47%, respectively. Treosulfan-based conditioning for second allograft in relapsed MF patients resulted in about 50% of the patients in long-term freedom from disease.Rift Valley fever phlebovirus (RVFV) is an arthropod-borne zoonotic pathogen, which is endemic in Africa, causing large epidemics, characterized by severe diseases in ruminants but also in humans. As in vitro and field investigations proposed amphibians and reptiles to potentially play a role in the enzootic amplification of the virus, we experimentally infected African common toads and common agamas with two RVFV strains. Lymph or sera, as well as oral, cutaneous and anal swabs were collected from the challenged animals to investigate seroconversion, viremia and virus shedding. Furthermore, groups of animals were euthanized 3, 10 and 21 days post-infection (dpi) to examine viral loads in different tissues during the infection. Our data show for the first time that toads are refractory to RVFV infection, showing neither seroconversion, viremia, shedding nor tissue manifestation. In contrast, all agamas challenged with the RVFV strain ZH501 carried virus genomes in the spleens at 3 dpi, but the animals displayed neither viremia nor virus shedding. In conclusion, the results of this study indicate that amphibians are not susceptible and reptiles are only susceptible to a low extent to RVFV, indicating that both species play, if at all, rather a subordinate role in the RVF virus ecology.Gold nanoparticles offer the possibility to combine both imaging and therapy of otherwise difficult to treat tumors. To validate and further improve their potential, we describe the use of gold nanostars that were functionalized with a polyethyleneglycol-maleimide coating for in vitro and in vivo photoacoustic imaging (PAI), computed tomography (CT), as well as photothermal therapy (PTT) of cancer cells and tumor masses, respectively. Nanostar shaped particles show a high absorption coefficient in the near infrared region and have a hydrodynamic size in biological medium around 100 nm, which allows optimal intra-tumoral retention. Using these nanostars for in vitro labeling of tumor cells, high intracellular nanostar concentrations could be achieved, resulting in high PAI and CT contrast and effective PTT. Erastin activator By injecting the nanostars intratumorally, high contrast could be generated in vivo using PAI and CT, which allowed successful multi-modal tumor imaging. PTT was successfully induced, resulting in tumor cell death and subsequent inhibition of tumor growth.
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