Goodbye to Berlin –Where is OA Heading?

The Facts: Perhaps 10 to 20% of all peer-reviewed articles are published in OA. Almost 10,000 journals listed in the DOAJ.Reed Elsevier and Wiley’s share prices are doing well. Subscription publishing seems in great health. What is Going On? Full Gold OA is a major threat to the economics of subscription publishers...with significant possible repercussions on the company’s overall performance. But OA Implementation is Failing: Definition remains vague, probably because objectives are vague. Europeans are from Mars, Americans are from Venus”. Hybrid model is effectively impossible to monitor. Expectations that OA will address the serial costs crisis are fading away The Problem If You Are a Librarian... The Problem If You Are a Tax Payer... ...and If You Are a Publisher? Right now, it looks like most publishers are OK... ...but adding costs to a dysfunctional model may be a recipe for future problems. If funding for science will contract, there will be pressure again on budgets for dissemination (whether this is funding for libraries or for APCs) Disclosure Appendix – Valuation Methodology & Risk

A Roadmap for Action: Academic Community Control of Data Infrastructure

The need for academic institutions to act to retain control of infrastructure, data and data analytics is here to stay. It is critical for academic leaders to acknowledge that data and its uses play a central role in the operations and the future of their institutions, and take control of how it is managed as a strategic asset. The time to act is now. Many of the actions outlined in the Risk Mitigation section of this roadmap can be taken relatively quickly, and many institutions already have a head start on these processes in response to GDPR or other requirements. Progress can be accelerated by developing and sharing resources that can help meet common needs. There is an important role for higher education professional associations, consortia, compacts, and other community organizations that can provide platforms and channels for disseminating best practices, templates and guides. Similarly, discussions on key issues outlined in the “Strategic Choices” section are already underway on many campuses, and identifying forums to amplify and share these conversations would be both valuable and productive. Finally, opportunities for galvanizing Community Action abound. SPARC is committed to participating in this process to the extent appropriate, and we encourage community leaders to fully engage as well. Only by working together can we successfully create research and education data infrastructure environment that is open and transparent, that allows and encourages competition, and that operates in a way that is fully aligned with our community values. 32 pp

A functional assay for the clinical annotation of genetic variants of uncertain significance in Diamond\u2013Blackfan anemia

Diamond-Blackfan anemia (DBA) is a rare genetic hypoplasia of erythroid progenitors characterized by mild to severe anemia and associated with congenital malformations. Clinical manifestations in DBA patients are quite variable and genetic testing has become a critical factor in establishing a diagnosis of DBA. The majority of DBA cases are due to heterozygous loss-of-function mutations in ribosomal protein (RP) genes. Causative mutations are fairly straightforward to identify in the case of large deletions and frameshift and nonsense mutations found early in a protein coding sequence, but diagnosis becomes more challenging in the case of missense mutations and small in-frame indels. Our group recently characterized the phenotype of lymphoblastoid cell lines established from DBA patients with pathogenic lesions in RPS19 and observed that defective pre-rRNA processing, a hallmark of the disease, was rescued by lentiviral vectors expressing wild-type RPS19. Here, we use this complementation assay to determine whether RPS19 variants of unknown significance are capable of rescuing pre-rRNA processing defects in these lymphoblastoid cells as a means of assessing the effects of these sequence changes on the function of the RPS19 protein. This approach will be useful in differentiating pathogenic mutations from benign polymorphisms in identifying causative genes in DBA patients

Lymphoblastoid cell lines from Diamond Blackfan anaemia patients exhibit a full ribosomal stress phenotype that is rescued by gene therapy

Diamond Blackfan anaemia (DBA) is a congenital bone marrow failure syndrome characterised by selective red cell hypoplasia. DBA is most often due to heterozygous mutations in ribosomal protein (RP) genes that lead to defects in ribosome biogenesis and function and result in ribosomal stress and p53 activation. The molecular mechanisms underlying this pathology are still poorly understood and studies on patient erythroid cells are hampered by their paucity. Here we report that RP-mutated lymphoblastoid cell lines (LCLs) established from DBA patients show defective rRNA processing and ribosomal stress features such as reduced proliferation, decreased protein synthesis, and activation of p53 and its target p21. These phenotypic alterations were corrected by gene complementation. Our data indicate that DBA LCLs could be a useful model for molecular and pharmacological investigations

Dissecting the transcriptional phenotype of ribosomal protein deficiency: implications for Diamond-Blackfan Anemia

Defects in genes encoding ribosomal proteins cause Diamond Blackfan Anemia (DBA), a red cell aplasia often associated with physical abnormalities. Other bone marrow failure syndromes have been attributed to defects in ribosomal components but the link between erythropoiesis and the ribosome remains to be fully defined. Several lines of evidence suggest that defects in ribosome synthesis lead to "ribosomal stress" with p53 activation and either cell cycle arrest or induction of apoptosis. Pathways independent of p53 have also been proposed to play a role in DBA pathogenesis. We took an unbiased approach to identify p53-independent pathways activated by defects in ribosome synthesis by analyzing global gene expression in various cellular models of DBA. Ranking-Principal Component Analysis (Ranking-PCA) was applied to the identified datasets to determine whether there are common sets of genes whose expression is altered in these different cellular models. We observed consistent changes in the expression of genes involved in cellular amino acid metabolic process, negative regulation of cell proliferation and cell redox homeostasis. These data indicate that cells respond to defects in ribosome synthesis by changing the level of expression of a limited subset of genes involved in critical cellular processes. Moreover, our data support a role for p53-independent pathways in the pathophysiology of DBA

Off-label long acting injectable antipsychotics in real-world clinical practice: a cross-sectional analysis of prescriptive patterns from the STAR Network DEPOT study

Introduction Information on the off-label use of Long-Acting Injectable (LAI) antipsychotics in the real world is lacking. In this study, we aimed to identify the sociodemographic and clinical features of patients treated with on- vs off-label LAIs and predictors of off-label First- or Second-Generation Antipsychotic (FGA vs. SGA) LAI choice in everyday clinical practice. Method In a naturalistic national cohort of 449 patients who initiated LAI treatment in the STAR Network Depot Study, two groups were identified based on off- or on-label prescriptions. A multivariate logistic regression analysis was used to test several clinically relevant variables and identify those associated with the choice of FGA vs SGA prescription in the off-label group. Results SGA LAIs were more commonly prescribed in everyday practice, without significant differences in their on- and off-label use. Approximately 1 in 4 patients received an off-label prescription. In the off-label group, the most frequent diagnoses were bipolar disorder (67.5%) or any personality disorder (23.7%). FGA vs SGA LAI choice was significantly associated with BPRS thought disorder (OR = 1.22, CI95% 1.04 to 1.43, p = 0.015) and hostility/suspiciousness (OR = 0.83, CI95% 0.71 to 0.97, p = 0.017) dimensions. The likelihood of receiving an SGA LAI grew steadily with the increase of the BPRS thought disturbance score. Conversely, a preference towards prescribing an FGA was observed with higher scores at the BPRS hostility/suspiciousness subscale. Conclusion Our study is the first to identify predictors of FGA vs SGA choice in patients treated with off-label LAI antipsychotics. Demographic characteristics, i.e. age, sex, and substance/alcohol use co-morbidities did not appear to influence the choice towards FGAs or SGAs. Despite a lack of evidence, clinicians tend to favour FGA over SGA LAIs in bipolar or personality disorder patients with relevant hostility. Further research is needed to evaluate treatment adherence and clinical effectiveness of these prescriptive patterns

The Role of Attitudes Toward Medication and Treatment Adherence in the Clinical Response to LAIs: Findings From the STAR Network Depot Study

Background: Long-acting injectable (LAI) antipsychotics are efficacious in managing psychotic symptoms in people affected by severe mental disorders, such as schizophrenia and bipolar disorder. The present study aimed to investigate whether attitude toward treatment and treatment adherence represent predictors of symptoms changes over time. Methods: The STAR Network \u201cDepot Study\u201d was a naturalistic, multicenter, observational, prospective study that enrolled people initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centers were assessed at three time points: baseline, 6-month, and 12-month follow-up. Psychopathological symptoms, attitude toward medication and treatment adherence were measured using the Brief Psychiatric Rating Scale (BPRS), the Drug Attitude Inventory (DAI-10) and the Kemp's 7-point scale, respectively. Linear mixed-effects models were used to evaluate whether attitude toward medication and treatment adherence independently predicted symptoms changes over time. Analyses were conducted on the overall sample and then stratified according to the baseline severity (BPRS < 41 or BPRS 65 41). Results: We included 461 participants of which 276 were males. The majority of participants had received a primary diagnosis of a schizophrenia spectrum disorder (71.80%) and initiated a treatment with a second-generation LAI (69.63%). BPRS, DAI-10, and Kemp's scale scores improved over time. Six linear regressions\u2014conducted considering the outcome and predictors at baseline, 6-month, and 12-month follow-up independently\u2014showed that both DAI-10 and Kemp's scale negatively associated with BPRS scores at the three considered time points. Linear mixed-effects models conducted on the overall sample did not show any significant association between attitude toward medication or treatment adherence and changes in psychiatric symptoms over time. However, after stratification according to baseline severity, we found that both DAI-10 and Kemp's scale negatively predicted changes in BPRS scores at 12-month follow-up regardless of baseline severity. The association at 6-month follow-up was confirmed only in the group with moderate or severe symptoms at baseline. Conclusion: Our findings corroborate the importance of improving the quality of relationship between clinicians and patients. Shared decision making and thorough discussions about benefits and side effects may improve the outcome in patients with severe mental disorders

Goodbye to Berlin –Where is OA Heading?

The Facts: Perhaps 10 to 20% of all peer-reviewed articles are published in OA. Almost 10,000 journals listed in the DOAJ.Reed Elsevier and Wiley’s share prices are doing well. Subscription publishing seems in great health. What is Going On? Full Gold OA is a major threat to the economics of subscription publishers...with significant possible repercussions on the company’s overall performance. But OA Implementation is Failing: Definition remains vague, probably because objectives are vague. Europeans are from Mars, Americans are from Venus”. Hybrid model is effectively impossible to monitor. Expectations that OA will address the serial costs crisis are fading away The Problem If You Are a Librarian... The Problem If You Are a Tax Payer... ...and If You Are a Publisher? Right now, it looks like most publishers are OK... ...but adding costs to a dysfunctional model may be a recipe for future problems. If funding for science will contract, there will be pressure again on budgets for dissemination (whether this is funding for libraries or for APCs) Disclosure Appendix – Valuation Methodology & Risk

Scholarly Publishing Is Broken. How Do We Fix It?

Scholarly publishing has been criticized for decades because of its commercialization and its exclusionary design. The problem is even deeper: scholarly publishing as it is designed today is unable to address major scientific emergencies, as the COVID pandemic demonstrated, as publishers were pressured to suspend licenses to access backfiles and many researchers and practitioners used preprints to communicate their ongoing findings. These ad hoc actions do not address other global emergencies (such as climate change and the loss of biodiversity) and it is morally indefensible to adopt them for some diseases and not others. In addition, scholarly publishing has developed into a system of research evaluation and career advancement, introducing distortions that do not benefit the equitable advancement of knowledge, while its high cost (and prices) trigger inequities that affect the most disadvantaged communities and individuals. There is vast experimentation, however, and there will be new models that we cannot even conceive of. It is impossible to be prescriptive about what each of these new or emerging models can do to address the current failings, but some principles can be identified. We are proposing a four-part test that can help decide which models to support, with the goal of starting a debate on what are the appropriate principles that should be adopted

In pursuit of open science, open access is not enough

After decades of debate on the feasibility of open access (OA) to scientific publications, we may be nearing a tipping point. A number of recent developments, such as Plan S, suggest that OA upon publication could become the default in the sciences within the next several years. Despite uncertainty about the long-term sustainability of OA models, many publishers who had been reluctant to abandon the subscription business model are showing openness to OA (1). Although more OA can mean more immediate, global access to scholarship, there remains a need for practical, sustainable models, for careful analysis of the consequences of business model choices, and for “caution in responding to passionate calls for a ‘default to open’” (2). Of particular concern for the academic community, as subscription revenues decline in the transition to OA and some publishers prioritize other sources of revenue, is the growing ownership of data analytics, hosting, and portal services by large scholarly publishers. This may enhance publishers' ability to lock in institutional customers through combined offerings that condition open access to journals upon purchase of other services. Even if such “bundled” arrangements have a near-term benefit of increasing openly licensed scholarship, they may run counter to long-term interests of the academic community by reducing competition and the diversity of service offerings. The healthy functioning of the academic community, including fair terms and conditions from commercial partners, requires that the global marketplace for data analytics and knowledge infrastructure be kept open to real competition