Methods to Adjust for Confounding in Test-Negative Design COVID-19 Effectiveness Studies: Simulation Study.

Background: Real-world COVID-19 vaccine effectiveness (VE) studies are investigating exposures of increasing complexity accounting for time since vaccination. These studies require methods that adjust for the confounding that arises when morbidities and demographics are associated with vaccination and the risk of outcome events. Methods based on propensity scores (PS) are well-suited to this when the exposure is dichotomous, but present challenges when the exposure is multinomial.

Establishment and Maintenance of a Digital Therapeutic Alliance in People Living With Negative Symptoms of Schizophrenia: Two Exploratory Single-Arm Studies.

Background: Evidence-based digital therapeutics represent a new treatment modality in mental health, potentially providing cost-efficient, accessible means of augmenting existing treatments for chronic mental illnesses. CT-155/BI 3972080 is a prescription digital therapeutic under development as an adjunct to standard of care treatments for patients 18 years of age and older with experiential negative symptoms (ENS) of schizophrenia. Individual components of CT-155/BI 3972080 are designed based on the underlying principles of face-to-face treatment.

Endovascular Thrombectomy for Extracranial Internal Carotid Artery Occlusions With Large Ischemic Strokes: Insights From the SELECT2 Trial.

Background And Objectives: Although previous trials have established the efficacy and safety of endovascular thrombectomy (EVT) in large ischemic core strokes, most of them excluded patients with extracranial internal carotid artery (e-ICA) occlusion. We aimed to compare outcomes in patients with e-ICA occlusion and large ischemic core infarcts treated with EVT vs medical management (MM).

Methods: This was a secondary analysis of the SELECT2 trial, a randomized controlled trial conducted at 31 international sites.

Clinical Activity of Mitogen-Activated Protein Kinase Inhibitors in Patients With MAP2K1 (MEK1)-Mutated Metastatic Cancers.

Purpose: MAP2K1/MEK1 mutations are potentially actionable drivers in cancer. MAP2K1 mutations have been functionally classified into three groups according to their dependency on upstream RAS/RAF signaling. However, the clinical efficacy of mitogen-activated protein kinase (MAPK) pathway inhibitors (MAPKi) for MAP2K1-mutant tumors is not well defined.

Elective Discontinuation of Larotrectinib in Pediatric Patients With TRK Fusion Sarcomas and Related Mesenchymal Tumors.

Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor with efficacy in children with TRK fusion tumors. We evaluated patient outcomes after elective discontinuation of larotrectinib in the absence of disease progression in a protocol-defined wait-and-see subset analysis of eligible patients where treatment resumption with larotrectinib was allowed if disease progressed. We also assessed the safety and efficacy of larotrectinib in all pediatric patients with sarcoma.

Botensilimab (Fc-enhanced anti-cytotoxic lymphocyte-association protein-4 antibody) Plus Balstilimab (anti-PD-1 antibody) in Patients With Relapsed/Refractory Metastatic Sarcomas.

Purpose: Outcomes for patients with advanced sarcomas are poor and there is a high unmet need to develop novel therapies. The purpose of this phase I study was to define the safety and efficacy of botensilimab (BOT), an Fc-enhanced anti-cytotoxic lymphocyte-association protein-4 antibody, plus balstilimab (BAL), an anti-PD-1 antibody, in advanced sarcomas.

Methods: BOT was administered intravenously (IV) at 1 mg/kg or 2 mg/kg once every 6 weeks in combination with BAL IV at 3 mg/kg once every 2 weeks for up to 2 years.

How can we make sound replication decisions?

Replication and the reported crises impacting many fields of research have become a focal point for the sciences. This has led to reforms in publishing, methodological design and reporting, and increased numbers of experimental replications coordinated across many laboratories. While replication is rightly considered an indispensable tool of science, financial resources and researchers' time are quite limited.

The present and future of peer review: Ideas, interventions, and evidence.

What is wrong with the peer review system? Is peer review sustainable? Useful? What other models exist? These are central yet contentious questions in today's academic discourse. This perspective critically discusses alternative models and revisions to the peer review system. The authors highlight possible changes to the peer review system, with the goal of fostering further dialog among the main stakeholders, including producers and consumers of scientific research.

Discourse on measurement.

Measurement literacy is required for strong scientific reasoning, effective experimental design, conceptual and empirical validation of measurement quantities, and the intelligible interpretation of error in theory construction. This discourse examines how issues in measurement are posed and resolved and addresses potential misunderstandings. Examples drawn from across the sciences are used to show that measurement literacy promotes the goals of scientific discourse and provides the necessary foundation for carving out perspectives and carrying out interventions in science.

Comprehensive guide for epigenetics and transcriptomics data quality control.

Host response to environmental exposures such as pathogens and chemicals can include modifications to the epigenome and transcriptome. Improved signature discovery, including the identification of the agent and timing of exposure, has been enabled by advancements in assaying techniques to detect RNA expression, DNA base modifications, histone modifications, and chromatin accessibility. The interrogation of the epigenome and transcriptome cascade requires analyzing disparate datasets from multiple assay types, often at single-cell resolution, derived from the same biospecimen.

Protocol for recording physiological signals from the human cerebellum using electroencephalography.

As Purkinje cells of the cerebellum have a very fast firing rate, techniques with high temporal resolution are required to capture cerebellar physiology. Here, we present a protocol to record physiological signals in humans using cerebellar electroencephalography (cEEG). We describe steps for electrode placement and recording.

Translating PK-PD principles into improved methodology for clinical trials which compare intermittent with prolonged infusion of beta-lactam antibiotics.

Based on the fact that beta-lactam antibiotics demonstrate time-dependent killing, different dosing strategies have been implemented to increase the time that free (f) (unbound) antibiotic concentrations remain above the Minimal Inhibitory Concentration (MIC), including prolonged and continuous infusion. Multiple studies have been performed that compared continuous with traditional intermittent infusion to improve outcomes in patients with severe sepsis and/or septic shock. These studies have yielded inconsistent results for patients as measured by clinical response to treatment and mortality due to heterogeneity of included patients, pathogens, dosing strategies and the absence of Therapeutic Drug Monitoring (TDM).

Approach to Therapy for Chronic Pouchitis.

Chronic pouchitis (CP) occurs in approximately 20% of patients with ulcerative colitis after total proctocolectomy with ileal pouch anal anastomosis and is categorized as antibiotic dependent, antibiotic refractory, or Crohn's disease-like. The management of CP is challenging because of limited evidence and few randomized controlled trials. In this review, we discuss the medical management of CP and its supporting data delineated by type of therapy.

Botulinum toxin injections for the treatment of hip instability in the pediatric population with cerebral palsy: a systematic review.

The purpose of this review was to examine the effects of hip muscle botulinum toxin injections for the treatment of hip instability reported in studies of children with cerebral palsy. Searches in PubMed, CINAHL, and Web of Science were performed using the term hips combined with botulinum toxin and its various abbreviations and brand names. Reference lists and citations of the reviewed studies were also searched.

Is the FAB test associated with fall occurrence in older adults? A retrospective analysis of outpatient fall risk assessment.

Methods: We conducted a single-center, retrospective cohort study of French older adults. Participants with Mini-Mental State Examination (MMSE) ≥ 24 were recruited from a fall clinic in a geriatrics department. We recorded history of falls in the preceding 6 months, as well as Timed Up and Go test and mobility assessment at baseline and at 6- and 12-month follow-up.

Entomopathogenic Nematode Species Vary in Their Behavior and Virulence in Response to Cardiac Glycosides Within and Around Insect Hosts.

Plants produce defensive toxins to deter herbivores. In response, some specialized herbivores evolved resistance and even the capacity to sequester toxins, affecting interactions at higher trophic levels. Here, we test the hypothesis that potential natural enemies of specialized herbivores are differentially affected by plant toxins depending on their level of adaptation to the plant-herbivore system.

Role of Glial Cells and Receptors in Schizophrenia Pathogenesis.

The specific pathogeneses of schizophrenia (SCZ) remain an enigma despite extensive research that has implicated both genetic and environmental factors. Recent revelations that dysregulated immune system caused by glial cell overactivation result in neuroinflammation, a key player in neurodegenerative as well as neuropsychiatric disorders including SCZ are providing novel clues on potential therapeutic interventions. Here, we review the roles of glial cells (Dr.

Glioprotective Effects of Resveratrol Against Glutamate-Induced Cellular Dysfunction: The Role of Heme Oxygenase 1 Pathway.

Resveratrol, a natural polyphenol, has shown promising neuroprotective effects in several in vivo and in vitro experimental models. However, the mechanisms by which resveratrol mediates these effects are not fully understood. Glutamate is the major excitatory neurotransmitter in the brain; however, excessive extracellular glutamate levels can affect neural activity in several neurological diseases.

The Johns Hopkins Hope at Hopkins Clinic: supporting the comprehensive needs of individuals with metastatic breast cancer.

Purpose: Individuals with metastatic breast cancer (MBC) may live with their disease for many years. We initiated the Johns Hopkins Hope at Hopkins Clinic to assess the needs and optimize the care of these patients.

Patients And Methods: Patients with MBC who agreed to participate in the Clinic in addition to usual care completed patient-reported outcome (PRO) surveys.

The underlying mechanisms of the association of bone health with depression - an experimental study.

Background: Depression constitutes a risk factor for osteoporosis, but underlying molecular and cellular mechanisms are not fully understood. MiRNAs influence gene expression and are carried by extracellular vesicles (EV), affecting cell-cell communication.

Aims: (1) Identify the difference in miRNA expression between depressed patients and healthy controls; (2) Analyze associations of these miRNAs with bone turnover markers; (3) Analyze target genes of differentially regulated miRNAs and predict associated pathways regarding depression and bone metabolism.

Improved Protective Efficacy in Rainbow Trout (Oncorhynchus mykiss) Against Vibrio anguillarum Through Immunization with a Combination of Formalin-Killed and Auxotrophic-Live V. anguillarum.

Vibriosis caused by Vibrio anguillarum has been an important bacterial disease in cultured rainbow trout (Oncorhynchus mykiss). In the present study, we evaluated the protective efficacy of a vaccine that consists of formalin-killed (FK) V. anguillarum and the alr genes knockout auxotrophic-live (AL) V.