Degradation bottlenecks and resource competition in transiently and stably engineered mammalian cells.

Degradation tags, otherwise known as degrons, are portable sequences that can be used to alter protein stability. Here, we report that degron-tagged proteins compete for cellular degradation resources in engineered mammalian cells leading to coupling of the degradation rates of otherwise independently expressed proteins when constitutively targeted human degrons are adopted. We show the effect of this competition to be dependent on the context of the degrons.

One-Day Brentuximab-Bendamustine (120 mg/m2) Every 21 Days is a Feasible, Safe and Effective Treatment for Relapsed/Refractory Hodgkin Lymphoma.

Brentuximab vedotin (BV)-bendamustine (90 or 120 mg/m2 day 1 and 2) every 28 days is an effective treatment for relapsed/refractory Hodgkin lymphoma (R/R HL) but associated to high toxicity especially for elderly patients. We conducted in St Louis Hospital, Paris, between 2015 and 2021 a retrospective single-center analysis of 44 patients with R/R HL treated with one-day BV-bendamustine (120 mg/m2) every 21 days. Sixteen percent of patients were ≥ 60 years old (yo).

Assessment of the organ function as the primary intention of clinical reasoning applied to the critically ill patient.

This article examines how clinical reasoning about the critical patient is currently treated and draws attention to some critical issues already often highlighted in the literature. Traditional approaches to clinical reasoning, even when applied to critical patients, prioritize identifying structured diseases. In contrast, the critical care setting demands an alternative approach that aligns with the intensivist's goal of supporting or substituting vital organ functions.

Mild cognitive impairment and early Alzheimer's disease eligibility for disease modification therapies in a tertiary centre for cognitive disorders: A simultaneous real-word study on aducanumab and lecanemab.

Background And Purpose: The Food and Drug Administration approved two disease-modifying treatments (DMTs) for Alzheimer's disease (AD), aducanumab and lecanemab, with limited clinical impact but significant biomarker changes. Identifying suitable candidates for these DMTs outside randomized clinical trials (RCTs) remains uncertain.

Methods: This cross-sectional study, conducted in an Italian tertiary centre for cognitive disorders, aimed to evaluate how the RCT eligibility criteria for DMT treatments applies to participants with early AD.

Biofilm-mediated antibiotic tolerance in from spinal cord stimulation device-related infections.

is a predominant cause of infections in individuals with spinal cord stimulation (SCS) devices. Biofilm formation complicates these infections, commonly requiring both surgical and antibiotic treatments. This study explored the biofilm matrix composition and antimicrobial susceptibility of planktonic and biofilm-growing isolates from individuals with SCS-related infections.

An Atypical Case of Creutzfeldt-Jakob Syndrome Presenting with Cacosmia and Amyloid Positivity.

This report presents a challenging case of Creutzfeldt-Jakob Disease (CJD), a rare and rapidly progressing neurological disorder. The patient exhibited diverse and progressive neuro-psychiatric symptoms, including memory impairment, behavioral changes, and hallucinations associated with cacosmia. The diagnosis of CJD is complicated due to its variable clinical presentation, limited awareness, and the need for tissue pathology confirmation.

Coexisting Logopenic Variant of Primary Progressive Aphasia with Amyloid Pathology and Early Parkinsonism.

The presence of parkinsonism features in primary progressive aphasia (PPA) is a subject of ongoing research. These features are usually more pronounced in the advanced stages of the disease, particularly in the non-fluent/agrammatic subtype, and are exceptionally rare in the logopenic variant (lvPPA). Here we report a case of a 63-year-old man presenting as language impairment, predominantly naming and word-finding difficulties, emerged alongside a left-sided internal tremor.

CAR T-cell therapy induces a high rate of prolonged remission in relapsed primary CNS lymphoma: Real-life results of the LOC network.

The prognosis of relapsed primary central nervous system lymphoma (PCNSL) remains dismal. CAR T-cells are a major contributor to systemic lymphomas, but their use in PCNSL is limited. From the LOC network database, we retrospectively selected PCNSL who had leukapheresis for CAR-T cells from the third line of treatment, and, as controls, PCNSL treated with any treatment, at least in the third line and considered not eligible for ASCT.

Explainable machine learning radiomics model for Primary Progressive Aphasia classification.

Introduction: Primary Progressive Aphasia (PPA) is a neurodegenerative disease characterized by linguistic impairment. The two main clinical subtypes are semantic (svPPA) and non-fluent/agrammatic (nfvPPA) variants. Diagnosing and classifying PPA patients represents a complex challenge that requires the integration of multimodal information, including clinical, biological, and radiological features.

Deep Learning-based Approach for Brainstem and Ventricular MR Planimetry: Application in Patients with Progressive Supranuclear Palsy.

Purpose To develop a fast and fully automated deep learning (DL)-based method for the MRI planimetric segmentation and measurement of the brainstem and ventricular structures most affected in patients with progressive supranuclear palsy (PSP). Materials and Methods In this retrospective study, T1-weighted MR images in healthy controls ( = 84) were used to train DL models for segmenting the midbrain, pons, middle cerebellar peduncle (MCP), superior cerebellar peduncle (SCP), third ventricle, and frontal horns (FHs). Internal, external, and clinical test datasets ( = 305) were used to assess segmentation model reliability.

High-Throughput Spectroscopic Analysis of mRNA Capping Level.

Eukaryotic mRNAs are characterized by terminal 5' cap structures and 3' polyadenylation sites, which are essential for posttranscriptional processing, translation initiation, and stability. Here, we describe a novel biosensor method designed to detect the presence of both cap structures and polyadenylation sites on mRNA molecules. This novel biosensor is sensitive to mRNA degradation and can quantitatively determine capping levels of mRNA molecules within a mixture of capped and uncapped mRNA molecules.

Narcissistic Personality Disorder as Prodromal Feature of Early-Onset, GRN-Positive bvFTD: A Case Report.

Background: Behavioral variant frontotemporal dementia (bvFTD) typically involves subtle changes in personality that can delay a timely diagnosis.

Objective: Here, we report the case of a patient diagnosed of GRN-positive bvFTD at the age of 52 presenting with a 7-year history of narcissistic personality disorder, accordingly to DSM-5 criteria.

Methods: The patient was referred to neurological and neuropsychological examination.

Nucleus Basalis of Meynert Degeneration Predicts Cognitive Decline in Corticobasal Syndrome.

Background: Cognitive changes are common in corticobasal syndrome (CBS) and significantly impact quality of life and caregiver burden. However, relatively few studies have investigated the neural substrates of cognitive changes in CBS, and reliable predictors of cognitive impairment are currently lacking. The nucleus basalis of Meynert (NbM), which serves as the primary source of cortical cholinergic innervation, has been functionally associated with cognition.

Sleep and circadian rhythm disruptions in behavioral variant frontotemporal dementia.

Introduction: Sleep and rest-activity rhythm alterations are common in neurodegenerative diseases. However, their characterization in patients with behavioral variant frontotemporal dementia (bvFTD) has proven elusive. We investigated rest-activity rhythm alterations, sleep disturbances, and their neural correlates in bvFTD.

Mammalian cell growth characterisation by a non-invasive plate reader assay.

Automated and non-invasive mammalian cell analysis is currently lagging behind due to a lack of methods suitable for a variety of cell lines and applications. Here, we report the development of a high throughput non-invasive method for tracking mammalian cell growth and performance based on plate reader measurements. We show the method to be suitable for both suspension and adhesion cell lines, and we demonstrate it can be adopted when cells are grown under different environmental conditions.