Rethinking the residual approach: leveraging statistical learning to operationalize cognitive resilience in Alzheimer's disease.

Cognitive resilience (CR) describes the phenomenon of individuals evading cognitive decline despite prominent Alzheimer's disease neuropathology. Operationalization and measurement of this latent construct is non-trivial as it cannot be directly observed. The residual approach has been widely applied to estimate CR, where the degree of resilience is estimated through a linear model's residuals.

An Exploration of the Interplay Between Caffeine and Antidepressants Through the Lens of Pharmacokinetics and Pharmacodynamics.

Caffeine consumption is regarded as a widespread phenomenon, and its usage has continued to increase. In addition, the growing usage of antidepressants worldwide and increase in mental health disorders were shown in recent statistical analyses conducted by the World Health Organisation. The coadministration of caffeine and antidepressants remains a concern due to potential interactions that can alter a patient's response to therapy.

Sustaining the planet by sustaining ourselves.

The author transitions his career in oncology to one in planetary health. The career pivot begins after he recognizes similarities between the pandemic and the climate crisis. The author determines that stepping away from his role as chair of radiology for a one-year sabbatical is the most efficient way to learn about sustainability.

International myeloma working group immunotherapy committee recommendation on sequencing immunotherapy for treatment of multiple myeloma.

T-cell redirecting therapy (TCRT), specifically chimeric antigen receptor T-cell therapy (CAR T-cells) and bispecific T-cell engagers (TCEs) represent a remarkable advance in the treatment of multiple myeloma (MM). There are several products available around the world and several more in development targeting primarily B-cell maturation antigen (BCMA) and G protein-coupled receptor class C group 5 member D (GRPC5D). The relatively rapid availability of multiple immunotherapies brings the necessity to understand how a certain agent may affect the safety and efficacy of a subsequent immunotherapy so MM physicians and patients can aim at optimal sequential use of these therapies.

A compendium of Amplification-Related Gain Of Sensitivity genes in human cancer.

While the effect of amplification-induced oncogene expression in cancer is known, the impact of copy-number gains on "bystander" genes is less understood. We create a comprehensive map of dosage compensation in cancer by integrating expression and copy number profiles from over 8000 tumors in The Cancer Genome Atlas and cell lines from the Cancer Cell Line Encyclopedia. Additionally, we analyze 17 cancer open reading frame screens to identify genes toxic to cancer cells when overexpressed.

MCT1 lactate transporter blockade re-invigorates anti-tumor immunity through metabolic rewiring of dendritic cells in melanoma.

Dendritic cells (DC) are key players in antitumor immune responses. Tumors exploit their plasticity to escape immune control; their aberrant surface carbohydrate patterns (e.g.

msiFlow: automated workflows for reproducible and scalable multimodal mass spectrometry imaging and microscopy data analysis.

Multimodal imaging by matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI MSI) and microscopy holds potential for understanding pathological mechanisms by mapping molecular signatures from the tissue microenvironment to specific cell populations. However, existing software solutions for MALDI MSI data analysis are incomplete, require programming skills and contain laborious manual steps, hindering broadly applicable, reproducible, and high-throughput analysis to generate impactful biological discoveries. Here, we present msiFlow, an accessible open-source, platform-independent and vendor-neutral software for end-to-end, high-throughput, transparent and reproducible analysis of multimodal imaging data.

Characterizing olfactory brain responses in young infants.

Odor perception plays a critical role in early human development, but the underlying neural mechanisms are not fully understood. To investigate these, we presented appetitive and aversive odors to infants of both sexes at one month of age while recording functional magnetic resonance imaging (fMRI) and nasal airflow data. Infants slept during odor presentation to allow MRI scanning.

Prokaryotic and eukaryotic periphyton responses to warming, nutrient enrichment and small omnivorous fish: a shallow lake mesocosms experiment.

Global change stressors, including climate warming, eutrophication, and small-sized omnivorous fish, may exert interactive effects on the food webs and functioning of shallow lakes. Periphyton plays a central role in the primary production and nutrient cycling of shallow lakes but constitutes a complex community composed of eukaryotes and prokaryotes that may exhibit different responses to multiple environmental stressors with implications for the projections of the effects of global change on shallow lakes. We analyzed the effects of warming, nutrient enrichment, small omnivorous fish and their interactions on eukaryotic and prokaryotic periphyton structures in shallow lake mesocosms.

Long-Term Cognitive Outcomes in Adult Patients Receiving Chimeric Antigen Receptor T-Cell Therapies.

Background: CAR T-cell therapy (CAR-T) is leading to durable responses in patients with cancer but there is concern that cytokine release syndrome (CRS) and neurotoxicity may impact survivors' cognitive function. We assessed long-term cognitive function in CAR-T recipients and examine factors associated with change in cognition over time.

Methods: We assessed perceived cognition (Functional Assessment of Cancer Therapy - Cognition) and neurocognitive performance (standardized neuropsychological battery) in adult patients prior to receiving CAR-T and at 6 month follow-up.

Brain state forecasting for precise brain stimulation: Current approaches and future perspectives.

Transcranial magnetic stimulation (TMS) has the potential to yield insights into cortical functions and improve the treatment of neurological and psychiatric conditions. However, its reliability is hindered by a low reproducibility of results. Among other factors, such low reproducibility is due to structural and functional variability between individual brains.

Bioimpedance Measurements of Fibrotic and Acutely Injured Lung Tissues.

In injured and diseased tissues, changes in molecular and cellular compositions, as well as tissue architecture, lead to alterations in both physiological and physical characteristics. Notably, the electrical properties of tissues, which can be characterized as bioelectrical impedance (bioimpedance), are closely linked to the health and pathological conditions of the tissues. This highlights the significant role of quantitatively characterizing these electrical properties in improving the accuracy and speed of diagnosis and prognosis.

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.

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.

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.

Impact of Medicaid Policies on Pre-pregnancy Preventive Dental Care.

Background: Dental care before pregnancy is critical for preventing poor oral health, which is associated with adverse pregnancy outcomes. People with low incomes, however, may face insurance-related barriers to obtaining dental care. Medicaid expansion under the Affordable Care Act increased access to dental care utilization among adults with low incomes.

Masquelet's induced membrane technique in the upper limb: a systematic review of the current outcomes.

Background: The Masquelet induced membrane technique is a surgical procedure that allows the reconstruction of segmental bone defects using a relatively simple approach that requires minimal resources from both the healthcare facility and the patient. Historically applied to the lower limb, this technique is gaining increasing attention in the literature for its use in the upper limb.

Methods: A systematic review of the literature was conducted using the PubMed and Google Scholar databases to identify all studies reporting the outcomes of the Masquelet induced membrane technique in the long bones of the upper limb (humerus, radius, and ulna) with a sample size of at least 3 patients.

Evaluation of the importance of sediment organic matter composition for CH production by microcosm tests with and without addition of natural sources (cyanobacterial biomass and riparian pasture) in two subtropical, eutrophic reservoirs.

The biochemical composition of sediments, which depends on the origin of the organic matter (OM), is decisive in methane (CH) production. This study aimed to determine the CH produced under anaerobic conditions from different substrates: native reservoir sediments and sediments with the addition of complex OM from Microcystis spp. blooms and terrestrial plants (pasture), alongside the biochemical characterization of the substrates used.

Accuracy and variability in clinical predictions of speech recognition outcomes for cochlear implant users.

Objectives: An improvement in speech perception is a major well-documented benefit of cochlear implantation (CI), which is commonly discussed with CI candidates to set expectations. However, a large variability exists in speech perception outcomes. We evaluated the accuracy of clinical predictions of post-CI speech perception scores.

Ciliary Body Medulloepithelioma: Clinical and Pathologic Challenges with a Focus on Molecular Genetics.

Objective: Ciliary body medulloepithelioma (CBME), a pediatric intraocular tumor with potential for locally aggressive behavior and metastasis, may present with a diverse spectrum of clinical and histopathologic features leading to diagnostic and management challenges. Examination of unusual CBME cases highlights challenges and modern diagnostic techniques which facilitate accurate diagnosis and guide management.

Methods: A retrospective clinicopathologic analysis of 6 patients with unusual clinical or pathologic features of CBME was performed.

Emergence of a novel reassortant highly pathogenic avian influenza clade 2.3.4.4b A(H5N2) Virus, 2024.

Reassortant highly pathogenic avian influenza A(H5N2) clade 2.3.4.