The influence of citrate buffer molarity on mRNA-LNPs: Exploring factors beyond general critical quality attributes.

Lipid nanoparticles (LNPs) are crucial in delivering mRNA vaccines and therapeutics. The properties of LNPs can be influenced by the choice of lipids and the manufacturing conditions, such as mixing parameters, lipid concentration, and the type and concentration of the aqueous buffer used. In this study, we investigated the impact of the citrate buffer molarity, the buffer commonly used to dissolve mRNA in the preparation of mRNA-LNPs.

A Translational Study of the ATR Inhibitor Berzosertib as Monotherapy in Four Molecularly Defined Cohorts of Advanced Solid Tumors.

Purpose: Preclinical studies have identified molecular correlates of sensitivity to ATR inhibition. This translational study was designed to test the ATR inhibitor berzosertib in patients with advanced solid tumors carrying alterations in ATRX, ataxia-telangiectasia-mutated (ATM), genes conferring replication stress (RS), or SDH.

Patients And Methods: Patients were recruited to four cohorts: T1: ATRX-mutant leiomyosarcoma; T2: ATM-mutant solid tumors; T3: solid tumors with mutations in RS-associated genes; and T4: SDH-deficient gastrointestinal stromal tumors (GIST).

Childhood maltreatment and outcomes following electroconvulsive therapy in adults with depression.

Objective: Childhood maltreatment is associated with less favourable treatment outcomes with pharmacotherapy and psychotherapy for depression. It is unknown whether this increased risk of treatment resistance in maltreated individuals extends to electroconvulsive therapy (ECT).

Methods: This retrospective cohort study included 501 consecutive adult referrals for an acute course of twice-weekly ECT for unipolar or bipolar depression at an academic inpatient centre in Ireland between 2016 and 2024.

Lessons Learned From Shared Decision-Making With Oral Anticoagulants: Viewpoint on Suggestions for the Development of Oral Chemotherapy Decision Aids.

Oral chemotherapy is commonly prescribed, and by using decision aids (DAs), clinicians can facilitate shared decision-making (SDM) to align treatment choices with patient goals and values. Although products exist commercially, little evidence informs the development of DAs targeting the unique challenges of oral chemotherapy. To address this gap in the literature, our objective was to review DAs developed for oral anticoagulation, DA use in oncology, and patient preference surveys to guide the development of DAs for oral chemotherapy.

Reliable Change Indices and Minimum Detectable Change for the Montreal Cognitive Assessment in Electroconvulsive Therapy for Depression.

Objective: The Montreal Cognitive Assessment (MoCA) is a commonly used brief cognitive screening tool for monitoring adverse cognitive effects of electroconvulsive therapy (ECT). The aim of this study was to examine three statistical methods for detecting reliable change in the MoCA following ECT.

Methods: In a prospective cohort study, 47 patients (mean age 55.

The glutathione S-transferase Gstt1 drives survival and dissemination in metastases.

Identifying the adaptive mechanisms of metastatic cancer cells remains an elusive question in the treatment of metastatic disease, particularly in pancreatic cancer (pancreatic adenocarcinoma, PDA). A loss-of-function shRNA targeted screen in metastatic-derived cells identified Gstt1, a member of the glutathione S-transferase superfamily, as uniquely required for dissemination and metastasis, but dispensable for primary tumour growth. Gstt1 is expressed in latent disseminated tumour cells (DTCs), is retained within a subpopulation of slow-cycling cells within existing metastases, and its inhibition leads to complete regression of macrometastatic tumours.

Core requirements of frailty screening in the emergency department: an international Delphi consensus study.

Introduction: Frailty is associated with adverse outcomes among patients attending emergency departments (EDs). While multiple frailty screens are available, little is known about which variables are important to incorporate and how best to facilitate accurate, yet prompt ED screening. To understand the core requirements of frailty screening in ED, we conducted an international, modified, electronic two-round Delphi consensus study.

Decreased Concussion Incidence Following the Implementation of the Targeting Rules: An Updated Epidemiology of National Football League Concussions From 2017 to 2022.

The incidence of concussions in football, and the ensuing media attention, has garnered scientific investigation, prompted technological advances in protective gear, and altered the rules of the game, including the National Football League's (NFL) "Targeting" rule, which began in 2018, but the impact of these changes is unclear. This study aims to describe the epidemiology of concussions that occurred in five NFL seasons from the 2017-2018 season through the 2021-2022 season and characterize positional differences in rate and games missed. There was a significant decrease (p = 0.

Study protocol for Ketamine as an adjunctive therapy for major depression (2): a randomised controlled trial (KARMA-Dep [2]).

Background: Depression is a common psychiatric disorder and a leading cause of disability worldwide. Conventional monoaminergic antidepressants have limited efficacy and take weeks to exert a therapeutic effect. Single infusions of subanaesthetic doses of ketamine exhibit rapid antidepressant action but effects are transient and relapse is common.

Wellness Among Interventional Radiologists: Results From a Multidimensional Survey.

Rationale And Objectives: To evaluate wellness among interventional radiologists using a multidimensional survey.

Materials And Methods: An anonymous 53-item survey, including 36 Perceived Wellness Survey (PWS) prompts, was created in Qualtrics (an online survey tool) to assess wellness among interventional radiology attendings and residents. The survey was open from June to September, 2022, 2 years into the COVID-19 Pandemic.

A Rare Presentation of Aggressive Renal Cell Carcinoma and the Utility of Early Molecular Testing in Rapidly Progressing Malignancies: A Case Report.

In rapidly progressing cancers, appropriate selection of first-line therapy is essential in prolonging survival. Alongside immunohistochemistry (IHC), comprehensive genomics, including whole exome and transcriptome sequencing (WES/WTS), can improve diagnostic accuracy and guide therapeutic management. Here, we report a young patient with rapidly progressing malignancy and unexpected post-mortem results, a scenario that may have been altered by early, comprehensive genomic sequencing.

Worsening of mental health outcomes in nursing home staff during the COVID-19 pandemic in Ireland.

Background: Mental health issues in nursing home staff during the COVID-19 pandemic have been significant; however, it is not known if these issues persist following widespread vaccination and easing of restrictions.

Objective: To quantify the mental health of nursing home staff at different timepoints during the COVID-19 pandemic in the Republic of Ireland.

Design/methods: Two identical, online, cross-sectional, nationwide, anonymous surveys of Republic of Ireland nursing home staff at two timepoints (survey 1 (S1, n = 390): November 2020 to January 2021; survey 2 (S2, N = 229: November 2021 to February 2022) during the COVID-19 pandemic.

Injury Patterns in Highly Specialized Youth Athletes: A Comparison of 2 Pathways to Specialization.

Context: Sport specialization, commonly defined as intensive year-round training in a single sport to the exclusion of other sports, has been associated with an increased risk for overuse injury. Two pathways to becoming highly specialized are recognized: (1) having only ever played 1 sport (exclusive highly specialized) and (2) quitting other sports to focus on a single sport (evolved highly specialized). Understanding the differences in injury patterns between these groups of highly specialized athletes will inform the development of injury-prevention strategies.

Association of Injury Rates Among Players in the National Football League With Playoff Qualification, Travel Distance, Game Timing, and the Addition of Another Game: Data From the 2017 to 2022 Seasons.

Background: Injury incidence is higher in the National Football League (NFL) than in other collision sports. Although previous research has identified that scheduling variations, including overseas games and bye week timing, does not affect concussion risk, data are currently lacking regarding the effects of scheduling variation on season-long musculoskeletal injury incidence.

Purpose: To determine whether higher cumulative travel distance, overseas play, an early season bye week, and an expansion of the regular season is associated with higher injury rates in the NFL.

Comparative efficacy, cognitive effects and acceptability of electroconvulsive therapies for the treatment of depression: protocol for a systematic review and network meta-analysis.

Introduction: There have been important advances in the use of electroconvulsive therapy (ECT) to treat major depressive episodes. These include variations to the type of stimulus the brain regions stimulated, and the stimulus parameters (eg, stimulus duration/pulse width). Our aim is to investigate ECT types using a network meta-analysis (NMA) approach and report on comparative treatment efficacy, cognitive side effects and acceptability.