The data described was acquired as part of a clinical study with the aim to investigate the potential of tumor-reactive T-cell response as response to vaccination of pancreatic can-cer patients... Show moreThe data described was acquired as part of a clinical study with the aim to investigate the potential of tumor-reactive T-cell response as response to vaccination of pancreatic can-cer patients with an allogenic tumor cell lysate vaccine (Lau et al., 2022). Proteomics analysis was carried out to iden-tify tumor antigens that are shared between the allogeneic tumor cell lysate used for the vaccine and pancreatic duc-tal adenocarcinoma (PDAC) tissue samples. To this objective, cell lysates of the vaccine and of nine tissue samples were enzymatically digested and isotopically labeled with tandem mass tags (TMT) in a so-called six-plex manner (Thermo Fisher Scientific). Three pools were prepared by mixing the samples according to their TMT-labels. Subsequently, the three sample pools were fractionated into 24 fractions with high-pH reversed phase chromatography. These frac-tions were first analyzed on a nano-liquid chromatog-raphy (LC) system online coupled to a high-resolution Eclipse Orbitrap mass spectrometer (MS) equipped with a high-field asymmetric-waveform ion-mobility spectrome-try (FAIMS) source using a data-dependent MS2 shotgun method. Overall, 126,618 unique peptide sequences, on ba-sis of 768,638 peptide spectra matches and corresponding to 7,597 protein groups, were identified in the total sam-ple set including 61 tumor antigens (Supplement Table S2 in Lau et al. 2022) that were prioritized by Cheever and co-workers as vaccine target antigens on basis of a series of objective criteria (Cheever et al., 2009). In the second phase of the experiment, this set of tumor antigens was tar-geted using a serial precursor selection (SPS) MS3 method. From this data, ion trap MS2 and Orbitrap MS3 fragment spectra were extracted for peptide identification (protein se-quence database-dependent search) and relative quantifica-tion using the TMT labels, respectively. The dataset ulti-mately allowed the identification and quantification of 51 proteins and 163 related peptide precursors with the TMT labels (see Fig. 2B and Supplemental Fig. 8, Lau et al. 2022).(c) 2022 Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ ) Show less
De afgelopen jaren zijn zowel in het beleid om armoede tegen te gaan als in de maatschappelijke denkbeelden over armoede een aantal zaken ten goede veranderd. Dat betekent niet dat we nu op onze... Show moreDe afgelopen jaren zijn zowel in het beleid om armoede tegen te gaan als in de maatschappelijke denkbeelden over armoede een aantal zaken ten goede veranderd. Dat betekent niet dat we nu op onze han den kunnen gaan zitten. Het aantal huishoudens dat met armoede en schulden kampt, stijgt immers nog steeds. Roeland van Geuns en Mirre Stallen zetten uiteen wat er volgens hen nog meer nodig is om daad werkelijk een eind te maken aan armoede en schuldenproblematiek Show less
Eikmans, M.; Morales-Prieto, D.M.M.; Hoorn, M.L. van der; Markert, U.R.R. 2022
Huntington's disease is the most frequent autosomal dominant neurodegenerative disorder; however, no disease-modifying interventions are available for patients with this disease. The molecular... Show moreHuntington's disease is the most frequent autosomal dominant neurodegenerative disorder; however, no disease-modifying interventions are available for patients with this disease. The molecular pathogenesis of Huntington's disease is complex, with toxicity that arises from full-length expanded huntingtin and N-terminal fragments of huntingtin, which are both prone to misfolding due to proteolysis; aberrant intron-1 splicing of the HTT gene; and somatic expansion of the CAG repeat in the HTT gene. Potential interventions for Huntington's disease include therapies targeting huntingtin DNA and RNA, clearance of huntingtin protein, DNA repair pathways, and other treatment strategies targeting inflammation and cell replacement. The early termination of trials of the antisense oligonucleotide tominersen suggest that it is time to reflect on lessons learned, where the field stands now, and the challenges and opportunities for the future. Show less
Recentelijk verscheen Discours sur le colonialisme van de Martinikaanse denker Aimé Césaire in een mooie Nederlandse vertaling van Grâce Ndjako. Waarom is dit boek zo belangrijk geweest voor de... Show moreRecentelijk verscheen Discours sur le colonialisme van de Martinikaanse denker Aimé Césaire in een mooie Nederlandse vertaling van Grâce Ndjako. Waarom is dit boek zo belangrijk geweest voor de antikoloniale strijd in de 20e eeuw? En wat kan het betekenen voor het Nederlandse debat over het koloniale verleden? Show less
Neuromuscular disorders (NMDs) are a heterogenous group of rare inherited diseases that compromise the function of peripheral nerves and/or muscles. With limited treatment options available, there... Show moreNeuromuscular disorders (NMDs) are a heterogenous group of rare inherited diseases that compromise the function of peripheral nerves and/or muscles. With limited treatment options available, there is a growing need to design effective preclinical studies that can lead to greater success in clinical trials for novel therapeutics. Here, I discuss recent advances in modelling NMDs to improve preclinical studies as well as two articles from this issue that work in parallel to enable a deeper understanding of a particularly rare NMD, known as X-linked myotubular myopathy. Show less
Long-term care homes play an essential role within health and social care. Successful measures to support older people at home for longer have led to increased prevalence of disability, frailty and... Show moreLong-term care homes play an essential role within health and social care. Successful measures to support older people at home for longer have led to increased prevalence of disability, frailty and cognitive impairment in those who live in care homes over the last two decades. The need for care home places is projected to increase for the next two decades. Modern care homes provide care for people who are predominantly over 80, have multiple long-term conditions, take multiple medicines, are physically dependent and live with cognitive impairment. Residents do better when services recognise the contributions of staff and care home providers rather than treating residents as individual patients living in a communal setting. There is a strong case given residents' frailty, multimorbidity and disability, that care should be structured around Comprehensive Geriatric Assessment (CGA). Care should be designed to allow opportunities for multiprofessional teams to come together for CGA, particularly if healthcare professionals are based outside care homes. Good data about care homes and residents are central to efforts to deliver high quality care-in some countries, these data are collected but not collated. Collating such data is a priority. Care home staff are under-recognised and underpaid-parity of pay and opportunity with NHS staff is the bare minimum to ensure that the best are recruited and retained in the sector. During the COVID-19 pandemic, residents and relatives have frequently been left out of decisions about policies that affect them, and better consultation is needed to deliver high quality care. Show less
The ISSCR has developed the Informed Consent Standards for Human Fetal Tissue Donation and Research to promote uniformity and transparency in tissue donation and collection. This standard is... Show moreThe ISSCR has developed the Informed Consent Standards for Human Fetal Tissue Donation and Research to promote uniformity and transparency in tissue donation and collection. This standard is designed to assist those working with and overseeing the regulation of such tissue and reassure the wider community and public. Show less
In celebration of the ISSCR's 20th anniversary we asked past ISSCR presidents the question, "During your presidential year, what key achievements or issue(s) in the field stood out to you?'' The... Show moreIn celebration of the ISSCR's 20th anniversary we asked past ISSCR presidents the question, "During your presidential year, what key achievements or issue(s) in the field stood out to you?'' The collection of responses provides a glimpse of the evolution of the field and the ISSCR over the past 20 years. Show less
