Prevention of reading difficulties in children with and without familial risk:Short- and long-term effects of an early intervention

In a randomized-controlled trial we tested a computer-assisted intervention for the prevention of reading difficulties, delivered by nonprofessional tutors, running from kindergarten to halfway Grade 2. The full sample included 123 prereaders (M = 5; 6 years; 56 intervention; 67 controls) with low preliteracy skills. Parents were sent a questionnaire to assess family risk (FR) for reading difficulties. There was no intervention effect in the full sample, but, unexpectedly, the effect differed between subsamples that did and did not return the questionnaire. The intervention did not affect reading acquisition in the subsample (N = 49) without FR-data, mostly children from immigrant, non-Dutch speaking, low-socioeconomic status (SES) families, but had large effects in the subsample of Dutch-speaking, middle and high SES-parents with FR-data (N = 74). The latter subsample was followed until Grade 6, 4 years after the intervention, and included 36 intervention children and 38 controls. Long-lasting improvements were found in word-reading fluency, which transferred to reading fluency for pseudowords, English words: and texts, and to spelling. The intervention substantially reduced the need for remedial teaching and grade retention. On all measures, children with FR performed worse than children without FR. The intervention had similar effects on the progress of both groups, but the FR children needed more sessions. This study shows that a 2-year cost-effective early intervention can reduce the incidence of reading difficulties. However, it remains a challenge to make the intervention suited for children in which a lack of preliteracy skills merely seems to reflect a lack of learning opportunities

Industrial-scale production and purification of a heterologous protein in Lactococcus lactis using the nisin-controlled gene expression system NICE: The case of lysostaphin

BACKGROUND: The NIsin-Controlled gene Expression system NICE of Lactococcus lactis is one of the most widespread used expression systems of Gram-positive bacteria. It is used in more than 100 laboratories for laboratory-scale gene expression experiments. However, L. lactis is also a micro-organism with a large biotechnological potential. Therefore, the aim of this study was to test whether protein production in L. lactis using the NICE system can also effectively be performed at the industrial-scale of fermentation. RESULTS: Lysostaphin, an antibacterial protein (mainly against Staphylococcus aureus) from S. simulans biovar. Staphylolyticus, was used as a model system. Food-grade lysostaphin expression constructs in L. lactis were grown at 1L-, 300-L and 3000-L scale and induced with nisin for lysostaphin production. The induction process was equally effective at all scales and yields of about 100 mg/L were obtained. Up-scaling was easy and required no specific effort. Furthermore, we describe a simple and effective way of downstream processing to obtain a highly purified lysostaphin, which has been used for clinical phase I trials. CONCLUSION: This is the first example that shows that nisin-regulated gene expression in L. lactis can be used at industrial scale to produce large amounts of a target protein, such as lysostaphin. Downstream processing was simple and in a few steps produced a highly purified and active enzyme

Enhancing Open Access publishing @University of Groningen and @University Medical Center Groningen

The University of Groningen (UG) and the University Medical Centre Groningen (UMCG) have committed themselves to the Dutch National Open Science Plan. In addition, external research funders are increasingly demanding that research articles are published open access (e.g. through Plan S). In 2018, 50% of UG/UMCG-scientific articles were published open access. However, have we used all options for publishing open access in venues chosen by researchers, thereby maintaining the researchers’ quality standards, and reducing the costs as much as possible? The answer is "no." To maximize the open access uptake, while making the workflow as smooth as possible for researchers, the University Library and Central Medical Library have started an Open Access Services (OAS) project with the following objectives: Implementation of services for the provision of practical information and advice for researchers Establish communication channels to increase the overall visibility of open access services and to issue regular updates on changes and innovations in scholarly communication and open science; Provide information on available options, costs, copyright, licences, re-use rights and funders’ requirements, pre-funded open access deals and submission workflows; Establishment of expert networks for the provision of strategic information and advice: open access ambassadors (academic staff and/or research policy officers) within faculties to multiply  and disseminate between the OAS project team and individual researchers, research committees and faculty boards; support staff (research policy officers, funding officers, financial controllers), e.g. to include open access budgeting in grant applications; open access experts to identify obstacles to publish open access, and advise to eliminate them and advocate for policy changes with regard to research evaluation practices. Establishment of an open access training programme for young researchers Create and implement a programme of regular presentations and tutorials for young researchers about publication strategies and open access; Development of optimal workflows for monitoring and registering open access uptake and expenditures Registration of open access expenditures, including cost of pre-funded deals, support for diamond OA initiatives, unnecessary paid APCs and reimbursed by funders (grant budgets). Identification of missed opportunities to publish open access using pre-funded read and publish deals and repair them retroactively whenever possible. Improvement of standards for the registration of open access publications in the university’s CRIS system. Organization of UG’s participation in the Taverne Amendment pilot project i.e. the implementation of Article 25fa of the Dutch Copyright Act. Provision of extra support for open access publishing services offered by the UG Press Professionalize and improve the publishing services offered, to support diamond open access initiatives, with special emphasis on the humanities and social sciences. We will present on the main outcomes of this project

Pathways Into Literacy:The Role of Early Oral Language Abilities and Family Risk for Dyslexia

The present study investigated the role of early oral language and family risk for dyslexia in the two developmental pathways toward reading comprehension, through word reading and through oral language abilities. The sample contained 237 children (164 at family risk for dyslexia) from the Dutch Dyslexia Program. Longitudinal data were obtained on seven occasions when children were between 4 and 12 years old. The relationship between early oral language ability and reading comprehension at the age of 12 years was mediated by preliteracy skills and word-decoding ability for the first pathway and by later language abilities for the second pathway. Family risk influenced literacy development through its subsequent relations with preliteracy skills, word decoding, and reading comprehension. Although performance on language measures was often lower for the family-risk group than for the no-family-risk group, family risk did not have a specific relation with either early or later oral language abilities

Spontaneous changes in intermediate filament protein expression patterns in lung cancer cell lines

The usefulness of cell lines in the study and prediction of the clinical behaviour of lung cancer is still a matter of debate. However, lung tumour cell cultures have been of value in investigations concerning molecular and cell biological aspects of these neoplasms. Especially in the examination of characteristics specific for the main types of differentiation (squamous cell carcinoma, adenocarcinoma, small cell carcinoma), in vitro studies have been most important. Twenty eight lung cancer cell lines were cultured for up to four years, and were examined at regular intervals for their intermediate filament protein (IFP) expression patterns using a panel of cytokeratin (CK) and neurofilament (NF) antibodies. These studies showed that the classic type of small cell lung cancer (SCLC) cell lines contain CKs 8, 18, and occasionally CK 19, while the variant-type SCLC cell lines generally express no CKs but can contain NFs. Non-SCLC cell lines, such as squamous cell carcinoma and adenocarcinoma cell lines, contain CKs 7 (in most cases), 8, 18 and 19. In one variant SCLC cell line and in one adenocarcinoma cell line CKs 4, 10 and 13, characteristic of squamous cell differentiation, were found. Although most cell lines have remained stable with respect to growth characteristics and IFP expression patterns, five lung cancer cultures exhibited a transition from one cell type to another, paralleled by changes in IFP expression. Progressions from classic to variant SCLC cell lines have been observed, next to conversions from variant SCLC to cell lines re-expressing cytokeratins. In some cases this resulted in a coexpression of CKs and NFs within a cell line and even within individual tumour cells. These results strongly support the earlier finding that CK expression in SCLC cell lines is a reliable marker for the classic type of differentiation, while the absence of CKs and the presence of NFs marks the variant type of differentiation. Our results are discussed in view of previous histological findings

Trends and overall survival after combined liver resection and thermal ablation of colorectal liver metastases:a nationwide population-based propensity score-matched study

Background: In colorectal liver metastases (CRLM) patients, combination of liver resection and ablation permit a more parenchymal-sparing approach. This study assessed trends in use of combined resection and ablation, outcomes, and overall survival (OS). Methods: This population-based study included all CRLM patients who underwent liver resection between 2014 and 2022. To assess OS, data was linked to two databases containing date of death for patients treated between 2014 and 2018. Hospital variation in the use of combined minor liver resection and ablation versus major liver resection alone in patients with 2–3 CRLM and ≤3 cm was assessed. Propensity score matching (PSM) was applied to evaluate outcomes. Results: This study included 3593 patients, of whom 1336 (37.2%) underwent combined resection and ablation. Combined resection increased from 31.7% in 2014 to 47.9% in 2022. Significant hospital variation (range 5.9–53.8%) was observed in the use of combined minor liver resection and ablation. PSM resulted in 1005 patients in each group. Major morbidity was not different (11.6% vs. 5%, P = 1.00). Liver failure occurred less often after combined resection and ablation (1.9% vs. 0.6%, P = 0.017). Five-year OS rates were not different (39.3% vs. 33.9%, P = 0.145). Conclusion: Combined resection and ablation should be available and considered as an alternative to resection alone in any patient with multiple metastases.</p

Resectability and Ablatability Criteria for the Treatment of Liver Only Colorectal Metastases:Multidisciplinary Consensus Document from the COLLISION Trial Group

The guidelines for metastatic colorectal cancer crudely state that the best local treatment should be selected from a 'toolbox' of techniques according to patient- and treatment-related factors. We created an interdisciplinary, consensus-based algorithm with specific resectability and ablatability criteria for the treatment of colorectal liver metastases (CRLM). To pursue consensus, members of the multidisciplinary COLLISION and COLDFIRE trial expert panel employed the RAND appropriateness method (RAM). Statements regarding patient, disease, tumor and treatment characteristics were categorized as appropriate, equipoise or inappropriate. Patients with ECOG≤2, ASA≤3 and Charlson comorbidity index ≤8 should be considered fit for curative-intent local therapy. When easily resectable and/or ablatable (stage IVa), (neo)adjuvant systemic therapy is not indicated. When requiring major hepatectomy (stage IVb), neo-adjuvant systemic therapy is appropriate for early metachronous disease and to reduce procedural risk. To downstage patients (stage IVc), downsizing induction systemic therapy and/or future remnant augmentation is advised. Disease can only be deemed permanently unsuitable for local therapy if downstaging failed (stage IVd). Liver resection remains the gold standard. Thermal ablation is reserved for unresectable CRLM, deep-seated resectable CRLM and can be considered when patients are in poor health. Irreversible electroporation and stereotactic body radiotherapy can be considered for unresectable perihilar and perivascular CRLM 0-5cm. This consensus document provides per-patient and per-tumor resectability and ablatability criteria for the treatment of CRLM. These criteria are intended to aid tumor board discussions, improve consistency when designing prospective trials and advance intersociety communications. Areas where consensus is lacking warrant future comparative studies.</p

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways