Grapheme-phoneme learning in an unknown orthography: a study in typical reading and dyslexic children

In this study, we examined the learning of new grapheme-phoneme correspondences in individuals with and without dyslexia. Additionally, we investigated the relation between grapheme-phoneme learning and measures of phonological awareness, orthographic knowledge and rapid automatized naming, with a focus on the unique joint variance of grapheme-phoneme learning to word and non-word reading achievement. Training of grapheme-phoneme associations consisted of a 20-min training program in which eight novel letters (Hebrew) needed to be paired with speech sounds taken from the participant's native language (Dutch). Eighty-four third grade students, of whom 20 were diagnosed with dyslexia, participated in the training and testing. Our results indicate a reduced ability of dyslexic readers in applying newly learned grapheme-phoneme correspondences while reading words which consist of these novel letters. However, we did not observe a significant independent contribution of grapheme-phoneme learning to reading outcomes. Alternatively, results from the regression analysis indicate that failure to read may be due to differences in phonological and/or orthographic knowledge but not to differences in the grapheme-phoneme-conversion process itself

Grapheme-Phoneme Learning in an Unknown Orthography: A Study in Typical Reading and Dyslexic Children

In this study, we examined the learning of new grapheme-phoneme correspondences in individuals with and without dyslexia. Additionally, we investigated the relation between grapheme-phoneme learning and measures of phonological awareness, orthographic knowledge and rapid automatized naming, with a focus on the unique joint variance of grapheme-phoneme learning to word and non-word reading achievement. Training of grapheme-phoneme associations consisted of a 20-min training program in which eight novel letters (Hebrew) needed to be paired with speech sounds taken from the participant's native language (Dutch). Eighty-four third grade students, of whom 20 were diagnosed with dyslexia, participated in the training and testing. Our results indicate a reduced ability of dyslexic readers in applying newly learned grapheme-phoneme correspondences while reading words which consist of these novel letters. However, we did not observe a significant independent contribution of grapheme-phoneme learning to reading outcomes. Alternatively, results from the regression analysis indicate that failure to read may be due to differences in phonological and/or orthographic knowledge but not to differences in the grapheme-phoneme-conversion process itself

Effects of Digested Onion Extracts on Intestinal Gene Expression: An Interspecies Comparison Using Different Intestine Models.

Human intestinal tissue samples are barely accessible to study potential health benefits of nutritional compounds. Numbers of animals used in animal trials, however, need to be minimalized. Therefore, we explored the applicability of in vitro (human Caco-2 cells) and ex vivo intestine models (rat precision cut intestine slices and the pig in-situ small intestinal segment perfusion (SISP) technique) to study the effect of food compounds. In vitro digested yellow (YOd) and white onion extracts (WOd) were used as model food compounds and transcriptomics was applied to obtain more insight into which extent mode of actions depend on the model. The three intestine models shared 9,140 genes which were used to compare the responses to digested onions between the models. Unsupervised clustering analysis showed that genes up- or down-regulated by WOd in human Caco-2 cells and rat intestine slices were similarly regulated by YOd, indicating comparable modes of action for the two onion species. Highly variable responses to onion were found in the pig SISP model. By focussing only on genes with significant differential expression, in combination with a fold change > 1.5, 15 genes showed similar onion-induced expression in human Caco-2 cells and rat intestine slices and 2 overlapping genes were found between the human Caco-2 and pig SISP model. Pathway analyses revealed that mainly processes related to oxidative stress, and especially the Keap1-Nrf2 pathway, were affected by onions in all three models. Our data fit with previous in vivo studies showing that the beneficial effects of onions are mostly linked to their antioxidant properties. Taken together, our data indicate that each of the in vitro and ex vivo intestine models used in this study, taking into account their limitations, can be used to determine modes of action of nutritional compounds and can thereby reduce the number of animals used in conventional nutritional intervention studies

Structure, controlled release mechanisms and health benefits of pectins as an encapsulation material for bioactive food components

Encapsulation of food and feed ingredients is commonly applied to avoid the loss of functionality of bioactive food ingredients. Components that are encapsulated are usually sensitive to light, pH, oxygen or highly volatile. Also, encapsulation is also applied for ingredients that might influence taste. Many polymers from natural sources have been tested for encapsulation of foods. In the past few years, pectins have been proposed as emerging broadly applicable encapsulation materials. The reasons are that pectins are versatile and inexpensive, can be tailored to meet specific demands and provide health benefits. Emerging new insight into the chemical structure and related health benefits of pectins opens new avenues to use pectins in food and feed. To provide insight into their application potential, we review the current knowledge on the structural features of different pectins, their production and tailoring process for use in microencapsulation and gelation, and the impact of the pectin structure on health benefits and release properties in the gut, as well as processing technologies for pectin-based encapsulation systems with tailor-made functionalities. This is reviewed in view of application of pectins for microencapsulation of different sensitive food components. Although some critical factors such as tuning of controlled release of cargo in the intestine and the impact of the pectin production process on the molecular structure of pectin still need more study, current insight is that pectins provide many advantages for encapsulation of bioactive food and feed ingredients and are cost-effective

Dutch multidisciplinary guideline on Achilles tendinopathy

Objective To provide a comprehensive, evidence-based overview of the risk factors, prevention, diagnosis, imaging, treatment and prognosis for Achilles tendinopathy. To make clinical recommendations for healthcare practitioners and patients. Design Comprehensive multidisciplinary guideline process funded by the Quality Foundation of the Dutch Federation of Medical Specialists. This process included a development, commentary and authorisation phase. Patients participated in every phase. Data sources Multiple databases and existing guidelines were searched up to May 2019. Information from patients, healthcare providers and other stakeholders were obtained using a digital questionnaire, focus group interview and invitational conference. Study eligibility criteria Studies on both insertional and/or midportion Achilles tendinopathy were eligible. Specific eligibility criteria were described per module. Data extraction and synthesis To appraise the certainty of evidence, reviewers extracted data, assessed risk of bias and used the Grading of Recommendations Assessment, Development and Evaluation method, where applicable. Important considerations were: patient values and preferences, costs, acceptability of other stakeholders and feasibility of implementation. Recommendations were made based on the results of the evidence from the literature and the considerations. Primary outcome measure The primary and secondary outcome measures were defined per module and defined based on the input of patients obtained in collaboration with the Netherlands Patient Federation and healthcare providers from different professions. Results Six specific modules were completed: risk factors and primary prevention, diagnosis, imaging, treatment prognosis and secondary prevention for Achilles tendinopathy. Summary/conclusion Our Dutch multidisciplinary guideline on Achilles tendinopathy provides six modules developed according to the standards of the Dutch Federation of Medical Specialists. Evidence-based recommendations for clinical practice are given for risk factors, prevention, diagnosis, imaging, treatment and prognosis. This guideline can assist healthcare providers and patients in clinical practice

RNA interference in Lepidoptera: an overview of successful and unsuccessful studies and implications for experimental design

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Neoadjuvant immunotherapy with nivolumab and ipilimumab induces major pathological responses in patients with head and neck squamous cell carcinoma

Surgery for locoregionally advanced head and neck squamous cell carcinoma (HNSCC) results in 30‒50% five-year overall survival. In IMCISION (NCT03003637), a non-randomized phase Ib/IIa trial, 32 HNSCC patients are treated with 2 doses (in weeks 1 and 3) of immune checkpoint blockade (ICB) using nivolumab (NIVO MONO, n = 6, phase Ib arm A) or nivolumab plus a single dose of ipilimumab (COMBO, n = 26, 6 in phase Ib arm B, and 20 in phase IIa) prior to surgery. Primary endpoints are feasibility to resect no later than week 6 (phase Ib) and primary tumor pathological response (phase IIa). Surgery is not delayed or suspended for any patient in phase Ib, meeting the primary endpoint. Grade 3‒4 immune-related adverse events are seen in 2 of 6 (33%) NIVO MONO and 10 of 26 (38%) total COMBO patients. Pathological response, defined as the %-change in primary tumor viable tumor cell percentage from baseline biopsy to on-treatment resection, is evaluable in 17/20 phase IIa patients and 29/32 total trial patients (6/6 NIVO MONO, 23/26 COMBO). We observe a major pathological response (MPR, 90‒100% response) in 35% of patients after COMBO ICB, both in phase IIa (6/17) and in the whole trial (8/23), meeting the phase IIa primary endpoint threshold of 10%. NIVO MONO’s MPR rate is 17% (1/6). None of the MPR patients develop recurrent HSNCC during 24.0 months median postsurgical follow-up. FDG-PET-based total lesion glycolysis identifies MPR patients prior to surgery. A baseline AID/APOBEC-associated mutational profile and an on-treatment decrease in hypoxia RNA signature are observed in MPR patients. Our data indicate that neoadjuvant COMBO ICB is feasible and encouragingly efficacious in HNSCC

Different skeletal effects of the peroxisome proliferator activated receptor (PPAR)α agonist fenofibrate and the PPARγ agonist pioglitazone

<p>Abstract</p> <p>Background</p> <p>All the peroxisome proliferator activated receptors (PPARs) are found to be expressed in bone cells. The PPARγ agonist rosiglitazone has been shown to decrease bone mass in mice and thiazolidinediones (TZDs) have recently been found to increase bone loss and fracture risk in humans treated for type 2 diabetes mellitus. The aim of the study was to examine the effect of the PPARα agonist fenofibrate (FENO) and the PPARγ agonist pioglitazone (PIO) on bone in intact female rats.</p> <p>Methods</p> <p>Rats were given methylcellulose (vehicle), fenofibrate or pioglitazone (35 mg/kg body weight/day) by gavage for 4 months. BMC, BMD, and body composition were measured by DXA. Histomorphometry and biomechanical testing of excised femurs were performed. Effects of the compounds on bone cells were studied.</p> <p>Results</p> <p>The FENO group had higher femoral BMD and smaller medullary area at the distal femur; while trabecular bone volume was similar to controls. Whole body BMD, BMC, and trabecular bone volume were lower, while medullary area was increased in PIO rats compared to controls. Ultimate bending moment and energy absorption of the femoral shafts were reduced in the PIO group, while similar to controls in the FENO group. Plasma osteocalcin was higher in the FENO group than in the other groups. FENO stimulated proliferation and differentiation of, and OPG release from, the preosteoblast cell line MC3T3-E1.</p> <p>Conclusion</p> <p>We show opposite skeletal effects of PPARα and γ agonists in intact female rats. FENO resulted in significantly higher femoral BMD and lower medullary area, while PIO induced bone loss and impairment of the mechanical strength. This represents a novel effect of PPARα activation.</p

Reproducible radiomics through automated machine learning validated on twelve clinical applications

Radiomics uses quantitative medical imaging features to predict clinical outcomes. Currently, in a new clinical application, findingthe optimal radiomics method out of the wide range of available options has to be done manually through a heuristic trial-anderror process. In this study we propose a framework for automatically optimizing the construction of radiomics workflows perapplication. To this end, we formulate radiomics as a modular workflow and include a large collection of common algorithms foreach component. To optimize the workflow per application, we employ automated machine learning using a random search andensembling. We evaluate our method in twelve different clinical applications, resulting in the following area under the curves: 1)liposarcoma (0.83); 2) desmoid-type fibromatosis (0.82); 3) primary liver tumors (0.80); 4) gastrointestinal stromal tumors (0.77);5) colorectal liver metastases (0.61); 6) melanoma metastases (0.45); 7) hepatocellular carcinoma (0.75); 8) mesenteric fibrosis(0.80); 9) prostate cancer (0.72); 10) glioma (0.71); 11) Alzheimer’s disease (0.87); and 12) head and neck cancer (0.84). Weshow that our framework has a competitive performance compared human experts, outperforms a radiomics baseline, and performssimilar or superior to Bayesian optimization and more advanced ensemble approaches. Concluding, our method fully automaticallyoptimizes the construction of radiomics workflows, thereby streamlining the search for radiomics biomarkers in new applications.To facilitate reproducibility and future research, we publicly release six datasets, the software implementation of our framework,and the code to reproduce this study

Allogeneic Hematopoietic Stem Cell Transplantation After Prior Lung Transplantation for Hereditary Pulmonary Alveolar Proteinosis: A Case Report

Pulmonary alveolar proteinosis (PAP) is a rare, diffuse lung disorder characterized by surfactant accumulation in the small airways due to defective clearance by alveolar macrophages, resulting in impaired gas exchange. Whole lung lavage is the current standard of care treatment for PAP. Lung transplantation is an accepted treatment option when whole lung lavage or other experimental treatment options are ineffective, or in case of extensive pulmonary fibrosis secondary to PAP. A disadvantage of lung transplantation is recurrence of PAP in the transplanted lungs, especially in hereditary PAP. The hereditary form of PAP is an ultra-rare condition caused by genetic mutations in genes encoding for the granulocyte macrophage-colony stimulating factor (GM-CSF) receptor, and intrinsically affects bone marrow derived-monocytes, which differentiate into macrophages in the lung. Consequently, these macrophages typically display disrupted GM-CSF receptor-signaling, causing defective surfactant clearance. Bone marrow/hematopoietic stem cell transplantation may potentially reverse the lung disease in hereditary PAP. In patients with hereditary PAP undergoing lung transplantation, post-lung transplant recurrence of PAP may theoretically be averted by subsequent hematopoietic stem cell transplantation, which results in a graft-versus-disease (PAP) effect, and thus could improve long-term outcome. We describe the successful long-term post-transplant outcome of a unique case of end-stage respiratory failure due to hereditary PAP-induced pulmonary fibrosis, successfully treated by bilateral lung transplantation and subsequent allogeneic hematopoietic stem cell transplantation. Our report supports treatment with serial lung and hematopoietic stem cell transplantation to improve quality of life and prolong survival, without PAP recurrence, in selected patients with end-stage hereditary PAP