Beyond disclaimers: the need for a curation-based model of PubMed.

According to its own description, the biomedical meta-database PubMed exists "with the aim of improving health-both globally and personally." Unfortunately, PubMed contains an increasing amount of low-quality research that may detract from this goal. Currently, PubMed warns its users and protects itself from such problems with a disclaimer stating that the presence of any article, book, or document in PubMed does not imply an endorsement of, or concurrence with, its contents by the NLM, the National Institutes of Health (NIH), or the U.S. Federal Government. However, we are critical of a "disclaimer-only" stance and encourage PubMed to take further action against low-quality research being found and indexed in its database, and thus available for use. To address this problem, we offer two lines of reasoning to argue that PubMed should not function merely as a passive index of health-related research. Instead, we first argue that only trustworthy published research is able to further PubMed's goal of health improvement. Secondly, on the basis of surveys, we argue that researchers place a high level of trust in articles that are referenced in this meta-database. We cannot expect any one set of actors to ensure trustworthy content on PubMed, which requires collective responsibility among authors, peer reviewers, editors, and indexers alike. Instead, we propose a curation-based model that incorporates three mechanisms of collaborative content curation: open expert feedback on indexed content, journal auditing, and constant transparent reassessment of indexed entities.

Recalibrating the Risk-Benefit Profiles of Lecanemab and Donanemab: Scales, Immunoreactivity, and Changes in Amyloid-ß42.

Three recent anti-amyloid-ß antibody trials for Alzheimer's disease reported similar effect sizes, used non-reactive saline as placebo, and showed large numbers of adverse events including imaging anomalies (ARIA) that correlate with cognitive changes. Conversely, all previous antibody trials were less reactive and pronounced ineffective. We argue that these observations point to unblinding bias, inflating apparent efficacy and thus altering the risk-benefit balance. Further, we highlight data demonstrating that beyond reducing amyloid, monoclonal antibodies increase monomeric amyloid-ß42 in cerebrospinal fluid, which may explain potential benefits. We should recalibrate the efficacy of these antibodies and devote more resources into strategies beyond removing amyloid.

Against "silent" retractions in neuroscience.

When an academic paper is published in a journal that assigns a digital object identifier (DOI) to papers, this is a de facto fait accompli. Corrections or retractions are supposed to follow a specific protocol, especially in journals that claim to follow the Committee on Publication Ethics (COPE) guidelines. In this paper, we highlight a case of a new, fully open access neuroscience journal that claims to be COPE-compliant, yet has silently retracted two papers since all records, bibliometrics, and PDF files related to their existence have been deleted from the journal's website. Although this phenomenon does not seem to be common in the neurosciences, we consider that any opaque corrective measures in journals whose papers could be cited may negatively impact the wider neuroscience literature and community. Instead, we encourage transparency in retraction to promote truthfulness and trustworthiness.

Active Surveillance of Powassan Virus in Massachusetts Ixodes scapularis Ticks, Comparing Detection Using a New Triplex Real-Time PCR Assay with a Luminex Vector-Borne Panel.

Powassan virus is an emerging tick-borne pathogen capable of causing severe neuroinvasive disease. As the incidence of human Powassan virus grows both in magnitude and geographical range, the development of sensitive detection methods for diagnostics and surveillance is critical. In this study, a Taqman-based triplex real-time PCR assay was developed for the simultaneous and quantitative detection of Powassan virus and Powassan virus lineage II (deer tick virus) in Ixodes scapularis ticks. An exon-exon junction internal control was built-in to allow for accurate detection of RNA quality and the failure of RNA extraction. The newly developed assay was also applied to survey deer tick virus in tick populations at 13 sites on Cape Cod and Martha's Vineyard Island in Massachusetts. The assay's performance was compared with the Luminex xMAP MultiFLEX Vector-borne Panel 2. The results suggested that the real-time PCR method was more sensitive. Powassan virus infection rates among ticks collected from these highly endemic tick areas ranged from 0.0 to 10.4%, highlighting the fine-scale geographic variations in deer tick virus presence in this region. Looking forward, our PCR assay could be adopted in other Powassan virus surveillance systems.

Against Over-reliance on PRISMA Guidelines for Meta-analytical Studies.

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were elaborated to allow authors of such papers to identify quality articles for inclusion in their scholarly work. However, we have identified several issues that point to an over-reliance on the PRISMA guidelines. Firstly, we question the rigor of implementation by authors and the rigor of verification by peer reviewers and editors, and whether they have screened papers to ensure adherence to the PRISMA guidelines. Secondly, we have identified cases where the PRISMA criteria led to as much as 99.97% of the published literature being ignored, suggesting that valid publications meeting these criteria might be at risk of being ignored. Thirdly, we have noted that exclusion is not only a quantitative problem-it is also a qualitative one, since the screening procedure groups all non-conforming literature into one basket. Fourthly, we have noted that seven copies of the PRISMA guidelines exist. This being the case, which one should be cited? To replace over-reliance on PRISMA screening, we encourage authors, peer reviewers, and editors to publish systematic reviews and meta-analyses that respect the dual criteria of scientific plausibility and diversity of included papers.

Dementia Prevention Guidelines Should Explicitly Mention Deprivation.

The brain requires sustained interaction with a rich physical and social environment to stay healthy. Individuals without access to such enabling environments and who instead live and grow in disabling environments tend to have greater risk of developing dementia. But research and policymaking as regards dementia risk reduction have so far focused almost exclusively on the role of how individuals' health behaviors change their risk profile. This exclusive focus on "lifestyle" is both ethically problematic and therapeutically inadequate. I highlight a growing literature on three different kinds of deprivation, an independent and overlooked risk factor for dementia that invites upstream action against inequalities. Future prevention guidelines should include explicit mention of deprivation as a risk factor and be developed around the need to make society fairer. Meanwhile, interventions and discourse based on lifestyle modification should respect the principle of "no ought without support."

Editors and Authors of Medical Journals Should Be Mindful of the New ICMJE Disclosure Form and Updated Policies.

The International Committee of Medical Journal Editors (ICMJE) recommendations are used by medical journals worldwide to guide editors and authors regarding "best practices" related to the intersection between research and publishing. In this opinion paper, we bring two discussion points to the attention of readers and users of the ICMJE recommendations. The first pertains to journals' use of the old conflicts of interest form, replaced in 2021 with a new disclosure form. The second relates to inconsistent or outdated policies in journals' instructions for authors mismatching the current ICMJE recommendations. The ICMJE does not monitor how journals use or apply the ICMJE recommendations. Thus, the editors must be mindful of updates and changes relevant to the authors. Furthermore, authors should carefully examine journals before submission to ensure that journals use updated forms and policies and should be mindful of submitting to non-ICMJE-recommendations-conforming journals despite claiming to follow them.

Improving Clinical Trials of Antioxidants in Alzheimer's Disease.

Maintaining diversity in drug development in research into Alzheimer's disease (AD) is necessary to avoid over-reliance on targeting AD neuropathology. Treatments that reduce or prevent the generation of oxidative stress, frequently cited for its causal role in the aging process and AD, could be useful in at-risk populations or diagnosed AD patients. However, in this review, it is argued that clinical research into antioxidants in AD could provide more useful feedback as to the therapeutic value of the oxidative stress theory of AD. Improving comparability between randomized controlled trials (RCTs) is vital from a waste-reduction and priority-setting point of view for AD clinical research. For as well as attempting to improve meaningful outcomes for patients, RCTs of antioxidants in AD should strive to maximize the extraction of clinically useful information and actionable feedback from trial outcomes. Solutions to maximize information flow from RCTs of antioxidants in AD are offered here in the form of checklist questions to improve ongoing and future trials centered around the following dimensions: adhesion to reporting guidelines like CONSORT, biomarker enrichment, simple tests of treatment, and innovative trial design.

If deprivation worsens dementia outcomes, stimulation should improve them.

It is still not known what causes Alzheimer's Disease (AD). In this period of uncertainty, an emerging literature on risk factors suggests that the concept of "stimulation" is a useful pragmatic tool both before and after diagnosis to improve cognitive health. Before diagnosis of AD, stimulation of the brain through education, exercise, and social stimulation provides fortification against later cognitive decline. After diagnosis, specific electrical stimulation of brain circuits may protect cognitive function, and non-specific stimulation through different kinds of environmental enrichment may help to compensate for cognitive decline. Pragmatic guidelines are offered here to maximise enabling stimulation (physical, cognitive, and social activity) and minimise disabling stimulation across the lifetime (e.g. stress, pollution, and poor diet). However, much deeper structural changes in society are needed to struggle against socioeconomic and environmental deprivation and the inaccessibility of education for women across the globe.

JAD: A Forum for Philosophy in Science.

The Journal of Alzheimer's Disease (JAD) is already an established forum for cutting-edge science as well as ethical reflection. But I argue that beyond science and ethics, JAD is also a forum for philosophy in science, and that interdisciplinary researchers asking innovative questions about AD should publish their reflections and findings in JAD.

Ticagrelor: A Rare, Delayed Case of Angioedema.

Dual antiplatelet therapy (DAPT) with P2Y12 receptor inhibitors in conjunction with aspirin is the gold standard treatment for acute coronary syndrome (ACS) and to prevent stent thrombosis after percutaneous coronary intervention (PCI). While there have been reported allergic effects-particularly angioedema-linked to clopidogrel there is limited data on hypersensitivity reactions to ticagrelor. Here, we discuss a case of delayed-onset ticagrelor-induced angioedema in a patient, three weeks following initiation of DAPT with aspirin and ticagrelor status post-PCI with DES placement. The patient presented with acute onset tongue swelling and was successfully treated with epinephrine, steroids, and antihistamine. The C1 esterase inhibitor and tryptase levels were within normal limits. Ticagrelor was discontinued and the patient was transitioned to prasugrel for DAPT, without recurrence of symptoms. Given the few cases reported involving ticagrelor-induced angioedema, and the even rare, delayed onset cases such as those described above, it is imperative that clinicians be made aware of this adverse effect and its management.