This Perspective outlines a framework for clinicians navigating physiologic data from wearable devices, referred to as “results of unknown significance,” including the need for universal evidentiary standards and shared language.
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Blood marker tracks hidden progression in multiple sclerosis
Modern therapies have transformed care for people with multiple sclerosis (MS). Yet the disease continues to progress in a substantial proportion of patients, even in the absence of relapses. Detecting and treating this gradual worsening of disability remains one of the greatest challenges in MS care. Researchers from the University of Basel, Switzerland, now report on a blood marker that could help track disease progression and monitor treatment response.
Relapses are only part of the disease process in MS. In some patients, physical and cognitive abilities continue to gradually decline even in the absence of relapses. Experts refer to this as progression independent of relapse activity (PIRA). This process develops slowly and is difficult to detect and quantify. A currently available blood test measures neurofilament light chain (NfL), a biomarker that mainly reflects neuroaxonal damage caused by acute inflammatory disease activity. A blood marker that captures the progressive component of the disease has so far been lacking.
“One of the key questions for us was whether progression leaves a different biological fingerprint than inflammation,” says Professor Jens Kuhle from the University of Basel and the Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB) at University Hospital Basel. “If these processes are biologically distinct, we also need biomarkers that reflect different aspects of the disease rather than expecting a single marker to capture everything.”
MIT engineers find a way to deliver drugs directly to the esophagus
There are few treatment options available for people with disorders of the esophagus. Delivering drugs directly to this part of the body is difficult, so patients are usually treated with systemic drugs, which can have unwanted side effects.
To overcome that challenge, MIT engineers developed a gel-like oral drug formulation that can coat the mucosal lining of the esophagus after being swallowed, allowing drugs to pass through the tissue.
The formulation, which includes a hydrogel and other key ingredients that promote rapid drug absorption, could be used to deliver antibodies including infliximab, used to treat a number of autoimmune diseases, or other types of antibodies or small-molecule drugs.
Restricting select amino acids may mimic protein restriction’s healthy aging benefits
A review finds that restricting protein, particularly methionine, isoleucine, and valine, may improve metabolism and influence key aging pathways, largely in experimental models. Short human studies suggest metabolic benefits, but effects on lifespan remain unknown and restriction may harm people with unmet or increased protein needs.
The Cterminal region of TENT5 proteins drives ERassociated mRNA polyadenylation via FNDC3 interaction
Viviani et al. identify the molecular determinants that recruit TENT5 poly(A) polymerases to the endoplasmic reticulum. A divergent C-terminal region mediates interaction with FNDC3 proteins, enabling ER localization and broad stabilization of transcripts encoding secretory pathway components. This spatial mechanism explains functional divergence among TENT5 paralogs.
Linkerology in PROTACs: learnings for proximityinducing therapeutics
Targeted protein degradation has rapidly evolved from a chemical biology concept into a therapeutic modality, with the first proteolysis-targeting chimera (PROTAC) degrader now approved as a medicine. Linkers play a central role in governing ternary complex formation and conferring drug-like properties on bifunctional compounds. However, linker optimisation remains one of the least rationalised steps in degrader design. In this review, we introduce a linkerology framework that integrates a data-driven analysis of PROTAC linker chemotypes with historical context, representative case studies, emerging proximity-based modalities, and clinical-stage trends. We reveal persistent biases in the explored linker space and identify linker features that are preferentially retained in clinical-stage degraders.
Bilateral Idiopathic Posterior Scleritis A Case Report
Background: A case of bilateral idiopathic posterior scleritis in a patient who developed headache, hypermetropic refractive shift, and bilateral choroidal folds, supported by multimodal ophthalmic imaging. A 52-year-old woman presented with a two-week history of headache and difficulty reading, and was found to have bilateral choroidal folds. She had initially been treated for sinusitis by her general practitioner with oral antibiotics, but did not improve and was referred to our ophthalmology outpatient department. Bilateral posterior scleritis was diagnosed based on B-scan ultrasonography, optical coherence tomography (OCT), and fluorescein angiography findings. An idiopathic aetiology was confirmed after a negative systemic workup. Oral prednisolone resulted in complete resolution of the choroidal folds and full reversal of the hypermetropic shift, with best-corrected visual acuity (BCVA) maintained at 20/20. Conclusion: Bilateral posterior scleritis is uncommon and easily misdiagnosed. A combination of B-scan ultrasonography, OCT, and fluorescein angiography confirmed the diagnosis in this case, and oral prednisolone produced a complete response.
Posterior Scleritis, Choroidal Folds, Multimodal Imaging, Corticosteroids, Hypermetropic Shift
How autophagy helps to reduce inflammation
During context-dependent decision-making, anterior lateral motor cortex is required to configure stimulus-response mappings. Two-photon imaging reveals neurons that jointly encode context and choice, suggesting that flexible behavior arises from dynamic reconfiguration of local circuits rather than abstract context representations.
