Roadmap to discovery and early development of an mRNA loaded LNP formulation for liver therapeutic genome editing.

Introduction: mRNA therapeutics were a niche area in drug development before COVIDvaccines. Now they are used in vaccine development, for non-viral therapeuticgenome editing, chimericantigen receptor T  (CAR T) celltherapies and protein replacement.  mRNAis large, charged, and easily degraded by nucleases.

Omission of postoperative radiotherapy after breast-conserving surgery in low-risk breast cancer.

Background: This prospective cohort study aimed to assess whether postoperative radiotherapy could safely be omitted in women ≥ 65 years with low-risk, estrogen receptor (ER)-positive T1N0 breast cancer treated with breast-conserving surgery and adjuvant endocrine therapy.

Methods: Eligible patients were women ≥ 65 years with unifocal, non-lobular, grade 1 or 2, ER-positive, pT1N0 breast cancer treated with breast-conserving surgery and endocrine therapy for five years. Patients were followed up with mammography at least annually for 10 years.

Toll-like receptor activation induces airway obstruction and hyperresponsiveness in guinea pigs.

Background: Microbial infections, particularly those caused by rhinovirus (RV) and respiratory syncytial virus (RSV), are major triggers for asthma exacerbations. These viruses activate toll-like receptors (TLRs), initiating an innate immune response. To better understand microbial-induced asthma exacerbations, animal models that closely mimic human lung characteristics are essential.

Using an integrated motor imagery and physical training intervention after knee injury: an interim analysis of the MOTIFS randomised controlled trial.

Objectives: Physical function is often a main focus of knee injury rehabilitation, but recent recommendations include increasing attention to psychological factors. We have developed the MOTor Imagery to Facilitate Sensorimotor re-learning (MOTIFS) training model which integrates dynamic motor imagery into physical rehabilitation. The objective is to report interim analysis results of an adaptive randomised controlled trial regarding the pre-defined continuation criteria.

Buffer-free high pH mobile phase LC-MS/MS for determination of the alcohol biomarker phosphatidylethanol 16:0/18:1 and 20 drugs and metabolites in whole blood.

Background: Acidic mobile phases are commonly used in reversed phase liquid chromatography tandem mass spectrometry (LC-MS/MS) bioanalysis. However, increased sensitivity, improved peak symmetry, and increased retention, especially for basic hydrophilic drugs have been observed using basic mobile phases. In our previous acidic mobile phase LC-MS/MS method we needed two injections (0.

Are Primary Health Care Visits Associated With Reduced Risk of Hospital Readmissions After Discharge From Geriatric Inpatient Departments? Evidence From Stockholm County.

Introduction/objectives: Primary health care visits post-discharge could potentially play an important role in efforts of reducing hospital readmission. Focusing on a single or a particular type of visit obscures nuances in types of primary care contacts over time and fails to quantify the intensity of primary health care visits during the follow-up period. The aim of this study was to explore associations between the number and type of primary health care visits post-discharge and the risk of hospital readmission within 30 days.

High levels of neurofilament light and YKL-40 in cerebrospinal fluid are related to poor outcome in ALS.

Amyotrophic lateral sclerosis (ALS) is a neurological disease without effective treatment. No pathognomonic test can diagnose ALS in sporadic cases. Routine investigation in suspected cases includes neurological examination, imaging of the brain and spine and electromyography supported by blood and cerebrospinal fluid (CSF) analyses.

Plasma Protein Profiling to Discern Indolent from Advanced Systemic Mastocytosis.

Mastocytosis is a heterogeneous disorder characterized by abnormal mast cell accumulation, in which the clinical severity may be explained by distinct molecular mechanisms. This study aimed to explore plasma protein biomarkers associated with systemic mastocytosis subtypes, as well as the cellular origin of the identified proteins. Plasma samples from patients with mastocytosis, including cutaneous mastocytosis (CM), indolent systemic mastocytosis (ISM), and advanced systemic mastocytosis (AdvSM), and a reference group of patients with polycythemia vera, were analyzed by Proximity Extension Assay technology targeting 275 proteins.

Predictors of early mortality following surgical or nonsurgical treatment of subaxial cervical spine fractures: a retrospective nationwide registry study.

Background: Traumatic subaxial cervical spine fractures are a significant public health concern due to their association with spinal cord injuries (SCI). Despite being mostly caused by low-energy trauma, these fractures significantly contribute to morbidity and mortality. Currently, research regarding early mortality based on the choice of treatment following these fractures is limited.

An optimized method for IgE-mediated degranulation of human lung mast cells.

Background: Mast cells are critically involved in IgE-mediated diseases, e.g., allergies and asthma.

Phosphoproteomic changes in response to anoxia are tissue-specific in the anoxia-tolerant crucian carp ().

Crucian carp (), a freshwater fish, can survive chronic anoxia for several months at low temperatures. Consequently, anoxia-related physiological and biochemical adaptations in this species have been studied for more than half a century. Still, despite for the well-known role of protein phosphorylation in regulating cellular processes, no studies have comprehensively characterized the phosphoproteome in crucian carp.

Long-term outcomes after surgery for subaxial cervical spine injuries in octogenarians, a matched population-based cohort study.

Purpose: We aimed to investigate surgical outcomes in octogenarians with subaxial cervical spine injuries and determine the predictors of complications and mortality.

Methods: Eligible for inclusion were all patients surgically treated between 2006 and 2018, with either anterior or posterior fixation for subaxial spine injuries. A cohort of octogenarians was identified and matched 1:1 to a corresponding cohort of younger adults.

Predictors of failure after primary anterior cervical discectomy and fusion for subaxial traumatic spine injuries.

Introduction: Traumatic subaxial fractures account for more than half of all cervical spine injuries. The optimal surgical approach is a matter of debate and may include anterior, posterior or a combined anteroposterior (360º) approach. Analyzing a cohort of patients initially treated with anterior cervical discectomy and fusion (ACDF) for traumatic subaxial injuries, the study aimed to identify predictors for treatment failure and the subsequent need for supplementary posterior fusion (PF).

Patients' expectations of primary health care from both patients' and physicians' perspectives: a questionnaire study with a qualitative approach.

Background: Patients' ideas, concerns, and expectations are three important concepts in consultation techniques. Limited studies on these concepts include responses from both health care providers and care recipients of the same consultation. Highlighting both perspectives provides an increased understanding of the consultation.

Stability indicating ion-pair reversed-phase liquid chromatography method for modified mRNA.

Modified messenger RNA (mRNA) represents a rapidly emerging class of therapeutic drug product. Development of robust stability indicating methods for control of product quality are therefore critical to support successful pharmaceutical development. This paper presents an ion-pair reversed-phase liquid chromatography (IP-RPLC) method to characterise modified mRNA exposed to a wide set of stress-inducing conditions, relevant for pharmaceutical development of an mRNA drug product.

Dysphagia, health-related quality of life, and return to work after occipitocervical fixation.

Purpose: The purpose of this study was to evaluate patient-reported outcome measures (PROMS) on dysphagia, health-related quality of life (HRQoL) and return to work after occipitocervical fixation (OCF). Postoperative radiographic measurements were evaluated to identify possible predictors of dysphagia.

Methods: All individuals (≥ 18 years) who underwent an OCF at the study center or were registered in the Swedish spine registry (Swespine) between 2005 and 2019, and were still alive when the study was conducted, were eligible for inclusion.

Expression of prolyl hydroxylase domains, the upstream regulators of HIF, in the brain of the anoxia-tolerant crucian carp during anoxia-reoxygenation.

The hypoxia-inducible factor (HIF) is considered key in the transcriptional response to low oxygen. Yet, the role of HIF in the absence of oxygen (anoxia) and in preparation for reoxygenation remains unclear. Recent studies suggest that mounting a HIF response may be counterproductive for anoxia survival.