Deep Equilibrium Unfolding Learning for Noise Estimation and Removal in Optical Molecular Imaging.

In clinical optical molecular imaging, the need for real-time high frame rates and low excitation doses to ensure patient safety inherently increases susceptibility to detection noise. Faced with the challenge of image degradation caused by severe noise, image denoising is essential for mitigating the trade-off between acquisition cost and image quality. However, prevailing deep learning methods exhibit uncontrollable and suboptimal performance with limited interpretability, primarily due to neglecting underlying physical model and frequency information.

GABAergic Progenitor Cell Graft Rescues Cognitive Deficits in Fragile X Syndrome Mice.

Fragile X syndrome (FXS) is an inherited neurodevelopmental disorder characterized by a range of clinical manifestations with no effective treatment strategy to date. Here, transplantation of GABAergic precursor cells from the medial ganglionic eminence (MGE) is demonstrated to significantly improve cognitive performance in Fmr1 knockout (KO) mice. Within the hippocampus of Fmr1-KO mice, MGE-derived cells from wild-type donor mice survive, migrate, differentiate into functionally mature interneurons, and form inhibitory synaptic connections with host pyramidal neurons.

Deciphering transcription activity of mammalian early embryos unveils on/off of zygotic genome activation by protein translation/degradation.

Quantification of transcription activities in mammalian preimplantation embryos is challenging due to a huge amount of maternally stored transcripts and paucity of research materials. Here, we investigate genome-wide transcription activities of mouse and human preimplantation embryos by quantifying elongating RNA polymerase II. Two transcriptional waves are identified in early mouse embryos, with summits at the 2-cell and 8-cell stages.

Red Blood Cell Distribution Width May Predict Drug-Induced Anemia and Prognosis in Patients Affected by Primary/Secondary Myelofibrosis Treated with Ruxolitinib.

Introduction: Myelofibrosis (MF) is often characterized by a multifactorial anemia determined, in part, by bone marrow (BM) fibrosis, extramedullary erythropoiesis and splenomegaly. Ruxolitinib (RUX) is the first-in-class janus kinase 2 (JAK2) inhibitor approved for treatment of MF, proved to reduce spleen volume and decrease symptom burden. The red cell distribution width (RDW) is the measure of erythrocyte volume variability (anisocytosis).

Individualization of piperacillin dosage based on therapeutic drug monitoring with or without model-informed precision dosing: a scenario analysis.

Background: Model-informed precision dosing (MIPD) combines population pharmacokinetic knowledge with therapeutic drug monitoring (TDM) to optimize dosage adjustment. It could improve target concentration attainment over empirical TDM, still widely practised for broad-spectrum antibiotics.

Objectives: To evaluate the respective performance of TDM and MIPD in achieving target piperacillin exposure.

Recommendations for mitochondria transfer and transplantation nomenclature and characterization.

Intercellular mitochondria transfer is an evolutionarily conserved process in which one cell delivers some of their mitochondria to another cell in the absence of cell division. This process has diverse functions depending on the cell types involved and physiological or disease context. Although mitochondria transfer was first shown to provide metabolic support to acceptor cells, recent studies have revealed diverse functions of mitochondria transfer, including, but not limited to, the maintenance of mitochondria quality of the donor cell and the regulation of tissue homeostasis and remodelling.

Clinical implementation of next-generation sequencing testing and genomically-matched therapy: a real-world data in a tertiary hospital.

Next-generation sequencing (NGS) cancer profiling has gained traction in routine clinical practice in South Korea. Here, we evaluated the use of NGS testing and genomically-matched therapies for patients with advanced solid tumors in a real-world clinical practice. We analyzed results from NGS cancer panel tests (SNUBH pan-cancer version 2) ordered from June 2019 to June 2020.

Subcytotoxic transepidermal delivery using low intensity cold atmospheric plasma.

Cold atmospheric plasma (CAP) has been utilized in various medical devices using its oxidative nature. Recent studies have provided evidence that CAP can facilitate the delivery of large, hydrophilic molecules through the epidermis to the dermis. On the other hand, a new approach called low-intensity CAP (LICAP) has been developed, allowing the plasma level to be controlled within a subtoxic range, thereby demonstrating various biological benefits without tissue damage.

Epilepsy therapy beyond neurons: unveiling astrocytes as cellular targets.

Epilepsy is a leading cause of disability and mortality worldwide. However, despite the availability of more than 20 antiseizure medications, more than one-third of patients continue to experience seizures. Given the urgent need to explore new treatment strategies for epilepsy, recent research has highlighted the potential of targeting gliosis, metabolic disturbances, and neural circuit abnormalities as therapeutic strategies.

PET-Based Risk Stratification in Primary Mediastinal B-Cell Lymphoma: A Comparative Analysis of Different Segmentation Methods in the IELSG37 Trial Patient Cohort.

Standardizing tumor measurement on F-FDG PET is crucial for the routine clinical use of powerful PET-derived lymphoma prognostic factors such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG). The recent proposal of an SUV of 4 as a new reference segmentation threshold for most aggressive lymphomas may homogenize volume-based metrics and facilitate their clinical application. This study compared MTV and TLG in primary mediastinal B-cell lymphoma (PMBCL) patients estimated using an SUV of 4 and the current threshold at 25% of SUV Baseline PET metrics were evaluated in 501 PMBCL patients from the IELSG37 trial.

Dysgeusia in MASLD-related advanced chronic liver disease (ACLD): a silent driver towards the "Bermuda" triangle of malnutrition-sarcopenia-frailty severely affecting prognosis.

Background: Dysgeusia is a distortion of the sense of taste whose prevalence and relationship with nutritional status in Metabolic dysfunction-associated Steatotic Liver Disease (MASLD)-related advanced chronic liver disease (ACLD) have never been systematically explored.

Methods: 200 MASLD patients [60 ≤ F3 fibrosis, 70 compensated ACLD (cACLD), and 70 decompensated (dACLD)] were enrolled. At baseline, the Child-Pugh (CP) score was determined.

Crucial role of the cGAS N terminus in mediating flowable and functional cGAS-DNA condensate formation via DNA interactions.

The DNA-sensing protein cGAS plays a pivotal role in the innate immune response and pathogenesis of various diseases. DNA triggers liquid-liquid phase separation (LLPS) and enhances the enzymatic activity of cGAS. However, the regulatory mechanisms of the disordered N terminus remain unclear.

Pathological diagnosis of central nervous system tumours in adults: what's new?

In the course of the last decade, the pathological diagnosis of many tumours of the central nervous system (CNS) has transitioned from a purely histological to a combined histological and molecular approach, resulting in a more precise 'histomolecular diagnosis'. Unfortunately, translation of this refinement in CNS tumour diagnostics into more effective treatment strategies is lagging behind. There is hope though that incorporating the assessment of predictive markers in the pathological evaluation of CNS tumours will help to improve this situation.

Number of Previous Strokes and the Association With Clinical Outcomes of Patients With Atrial Fibrillation: Longitudinal Data From the GLORIA-AF Registry.

Background: Patients with atrial fibrillation (AF) who suffered a previous stroke are at increased risk of recurrent thromboembolic events and other major outcomes. The impact of the number of stroke episodes on the natural history of patients with AF is still unclear.

Methods And Results: Using data from the international, multicenter, and prospective GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation) Registry Phase III, we categorized patients with a recent diagnosis of non-valvular AF according to the number of previous strokes (either 0, 1, or ≥2 episodes).

Development and Clinical Validation of Model-Informed Precision Dosing for Everolimus in Liver Transplant Recipients.

Everolimus presents significant dosing challenges due to between- and within-patient pharmacokinetic variabilities. This study aimed to develop and validate a model-informed precision dosing strategy for everolimus in liver transplant recipients. The dosing strategy was initially developed using retrospective data, employing nonlinear mixed-effects modeling.

Multiple crosslinked, self-healing, and shape-adaptable hydrogel laden with pain-relieving chitosan@borneol nanoparticles for infected burn wound healing.

Next-generation wound dressings with multiple biological functions hold promise for addressing the complications and pain associated with burn wounds. A hydrogel wound dressing loaded with a pain-relieving drug was developed for treating infected burn wounds. Polyvinyl alcohol chemically grafted with gallic acid (PVA-GA), sodium alginate chemically grafted with 3-aminobenzeneboronic acid (SA-PBA), Zn, and chitosan-coated borneol nanoparticles with anti-inflammatory and pain-relieving activities were combined to afford a nanoparticle-loaded hydrogel with a PVA-GA/Zn/SA-PBA network crosslinked via multiple physicochemical interactions.

Precision Psychobiotics for Gut-Brain Axis Health: Advancing the Discovery Pipelines to Deliver Mechanistic Pathways and Proven Health Efficacy.

Advancing microbiome-gut-brain axis science requires systematic, rational and translational approaches to bridge the critical knowledge gaps currently preventing full exploitation of the gut microbiome as a tractable therapeutic target for gastrointestinal, mental and brain health. Current research is still marked by many open questions that undermine widespread application to humans. For example, the lack of mechanistic understanding of probiotic effects means it remains unclear why even apparently closely related strains exhibit different effects in vivo.

An exceptionally rare case of a diffuse midline glioma with concomitant H3.1 K27M and G34R mutations in the HIST1H3C (H3C3) gene.

Histone mutations (H3 K27M, H3 G34R/V) are molecular features defining subtypes of paediatric-type diffuse high-grade gliomas (HGG) (diffuse midline glioma (DMG), H3 K27-altered, diffuse hemispheric glioma (DHG), H3 G34-mutant). The WHO classification recognises in exceptional cases, these mutations co-occur. We report one such case of a 2-year-old female presenting with neurological symptoms; MRI imaging identified a brainstem lesion which was biopsied.

Resistance mechanisms to immune checkpoint inhibitors: updated insights.

The last decade has witnessed unprecedented succusses with the use of immune checkpoint inhibitors in treating cancer. Nevertheless, the proportion of patients who respond favorably to the treatment remained rather modest, partially due to treatment resistance. This has fueled a wave of research into potential mechanisms of resistance to immune checkpoint inhibitors which can be classified into primary resistance or acquired resistance after an initial response.

Digital twin assisted surgery, concept, opportunities, and challenges.

Computer-assisted surgery is becoming essential in modern medicine to accurately plan, guide, and perform surgeries. Similarly, Digital Twin technology is expected to be instrumental in the future of surgery, owing to its capacity to virtually replicate patient-specific interventions whilst providing real-time updates to clinicians. This perspective introduces the term Digital Twin-Assisted Surgery and discusses its potential to improve surgical precision and outcome, along with key challenges for successful clinical translation.

Massively parallel characterization of transcriptional regulatory elements.

The human genome contains millions of candidate cis-regulatory elements (cCREs) with cell-type-specific activities that shape both health and many disease states. However, we lack a functional understanding of the sequence features that control the activity and cell-type-specific features of these cCREs. Here we used lentivirus-based massively parallel reporter assays (lentiMPRAs) to test the regulatory activity of more than 680,000 sequences, representing an extensive set of annotated cCREs among three cell types (HepG2, K562 and WTC11), and found that 41.

Pulmonary Arterial Hypertension Incidence in Scleroderma Patients Treated with Bosentan for Digital Ulcers: Evidence from the Italian SPRING Registry.

Objective: Bosentan (BOS) is approved for treating pulmonary arterial hypertension (PAH) and preventing digital ulcers (DU) in systemic sclerosis (SSc). Our study aimed to evaluate whether BOS prescribed for DU could reduce the incidence of PAH in a large SSc cohort from the SPRING registry.

Methods: Patients with SSc from the SPRING registry, meeting ACR/EULAR 2013 classification criteria with data on PAH onset, DU status, BOS exposure, and at least a one-year follow-up between 2015 and 2020, and no known PAH at baseline were included.

Biallelic variants in SREBF2 cause autosomal recessive spastic paraplegia.

Hereditary spastic paraplegias (HSPs) refer to a genetically and clinically heterogeneous group of neurodegenerative disorders characterized by the degeneration of motor neurons. To date, a significant number of patients still have not received a definite genetic diagnosis. Therefore, identifying unreported causative genes continues to be of great importance.

Inhalable DNase I@Au hybrid nanoparticles for radiation sensitization and metastasis inhibition by elimination of neutrophil extracellular traps.

High-dose radiation therapy is a widely used clinical strategy to inhibit tumor growth. However, the rapid generation of excessive reactive oxygen species (ROS) triggers the formation of neutrophil extracellular traps (NETs), which capture free tumor cells in the bloodstream, promoting metastasis. In this study, we developed a hybrid nanoparticle composed of DNase I and gold (DNase I@Au) to enhance radiotherapy efficacy while mitigating metastasis by precisely eliminating NETs.