Genome-wide association study of varenicline-aided smoking cessation.

Introduction: Varenicline is an α4β2 nicotinic acetylcholine receptor partial agonist with the highest therapeutic efficacy of any pharmacological smoking cessation aid and a 12-month cessation rate of 26%. Genetic variation may be associated with varenicline response, but to date no genome-wide association studies of varenicline response have been published.

Methods: In this study, we investigated the genetic contribution to varenicline effectiveness using two electronic health record-derived phenotypes.

Repurposing Licensed Drugs with Activity Against Epstein-Barr Virus for Treatment of Multiple Sclerosis: A Systematic Approach.

Background: Epstein-Barr virus (EBV) is implicated as a necessary factor in the development of multiple sclerosis (MS) and may also be a driver of disease activity. Although it is not clear whether ongoing viral replication is the driver for MS pathology, MS researchers have considered the prospect of using drugs with potential efficacy against EBV in the treatment of MS. We have undertaken scientific and lived experience expert panel reviews to shortlist existing licensed therapies that could be used in later-stage clinical trials in MS.

Ganaxolone: A Review in Epileptic Seizures Associated with Cyclin-Dependent Kinase-Like 5 Deficiency Disorder.

Oral ganaxolone (ZTALMY), a synthetic analogue of the endogenous neuroactive steroid allopregnanolone, acts as a positive allosteric modulator of synaptic and extra-synaptic γ-aminobutyric acid (GABA) type A receptor function in the CNS. In the EU and the UK, it is approved for the adjunctive treatment of epileptic seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) in patients aged 2-17 years. In a multinational phase III study (Marigold), 17 weeks' therapy with adjunctive ganaxolone, administered orally three times daily with food, significantly reduced 28-day major motor seizure frequency from baseline versus placebo in patients aged 2-19 years with CDD-associated refractory epilepsy.

Do you know your PSMA-tracer? Variability in the biodistribution of different PSMA ligands and its potential impact on defining PSMA-positivity prior to PSMA-targeted therapy.

Background: In clinical practice, several radiopharmaceuticals are used for PSMA-PET imaging, each with distinct biodistribution patterns. This may impact treatment decisions and outcomes, as eligibility for PSMA-directed radioligand therapy is usually assessed by comparing tumoral uptake to normal liver uptake as a reference. In this study, we aimed to compare tracer uptake intraindividually in various reference regions including liver, parotid gland and spleen as well as the respective tumor-to-background ratios (TBR) of different F-labeled PSMA ligands to today's standard radiopharmaceutical Ga-PSMA-11 in a series of patients with biochemical recurrence of prostate cancer who underwent a dual PSMA-PET examination as part of an individualized diagnostic approach.

Critical Structures of Bisphenol Analogues on Embryonic Toxicity Identified by a Computational Approach.

Safer chemical alternatives to bisphenol (BP) have been a major pursuit of modern green chemistry and toxicology. Using a chemical similarity-based approach, it is difficult to identify minor structural differences that contribute to the significant changes of toxicity. Here, we used omics and computational toxicology to identify chemical features associated with BP analogue-induced embryonic toxicity, offering valuable insights to inform the design of safer chemical alternatives.

A systematic review of salivary gland hypofunction and/or xerostomia induced by non-surgical cancer therapies: prevention strategies.

Purpose: This systematic review aimed to assess the updated literature for the prevention of salivary gland hypofunction and xerostomia induced by non-surgical cancer therapies.

Methods: Electronic databases of MEDLINE/PubMed, EMBASE, and Cochrane Library were searched for randomized controlled trials (RCT) that investigated interventions to prevent salivary gland hypofunction and/or xerostomia. Literature search began from the 2010 systematic review publications from the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) up to February 2024.

A Consistent Lack of Consistency: Definitions, Evidentiary Expectations and Potential Use of Meaningful Change Data in Clinical Outcome Assessments Across Stakeholders. Results from a DIA Working Group Literature Review and Survey.

Background: Clinical outcome assessments (COAs) measure how patients feel or function and can be used to understand which patients experience benefits of treatment and which do not. Interpretation of COA data is influenced by how meaningful change is defined. We aimed to compare how different stakeholders define, assess, and use meaningful change for decisions that impact patients.

Assessment of decision-making with locally run and web-based large language models versus human board recommendations in otorhinolaryngology, head and neck surgery.

Introduction: Tumor boards are a cornerstone of modern cancer treatment. Given their advanced capabilities, the role of Large Language Models (LLMs) in generating tumor board decisions for otorhinolaryngology (ORL) head and neck surgery is gaining increasing attention. However, concerns over data protection and the use of confidential patient information in web-based LLMs have restricted their widespread adoption and hindered the exploration of their full potential.

The Impact of Artificial Intelligence and Machine Learning in Organ Retrieval and Transplantation: A Comprehensive Review.

This narrative review examines the transformative role of Artificial Intelligence (AI) and Machine Learning (ML) in organ retrieval and transplantation. AI and ML technologies enhance donor-recipient matching by integrating and analyzing complex datasets encompassing clinical, genetic, and demographic information, leading to more precise organ allocation and improved transplant success rates. In surgical planning, AI-driven image analysis automates organ segmentation, identifies critical anatomical features, and predicts surgical outcomes, aiding pre-operative planning and reducing intraoperative risks.

Cardiovascular magnetic resonance-estimated pulmonary capillary wedge pressure, congestion markers, and effect of empagliflozin in patients with heart failure with reduced ejection fraction and dysglycaemia (SUGAR-DM-HF).

Aims: A cardiovascular magnetic resonance (CMR) approach to non-invasively estimate left ventricular (LV) filling pressure was recently developed and shown to correlate with invasively measured pulmonary capillary wedge pressure (PCWP). We examined the association between CMR-estimated PCWP (CMR-PCWP) and other imaging and biomarker measures of congestion, and the effect of empagliflozin on these, in the SUGAR-DM-HF trial (NCT03485092).

Methods And Results: SUGAR-DM-HF enrolled 105 patients with heart failure with reduced ejection fraction (HFrEF) and pre-diabetes or type 2 diabetes who were randomly assigned to empagliflozin 10 mg or placebo once daily for 36 weeks.

Novel digital leakage notification system can promote better stoma management routines: a multicentre clinical trial.

Background: Most people with a stoma are anxious about stoma-related leakage.

Aims: To investigate the impact of a novel digital leakage notification system on worry related to stoma leakage, and to evaluate the effect on overall stoma care management.

Method: A 12-week interventional, single-arm, multicentre study was conducted in the UK to evaluate the novel digital leakage notification system, including a telemedicine-based support service (=test product), as part of routine stoma care in patients with a recent stoma formation (ClinicalTrials.

Developing structured clinical review templates in an integrated respiratory team during COVID-19: a qualitative review.

Introduction: In response to the SARS-CoV-2 pandemic in March 2020 and required adherence to infection control measures and patient and staff safety, an integrated respiratory team (IRT) developed guideline-based templates to support the team in teleconsultation reviews of their patients. Patients had been diagnosed with sleep disordered breathing, chronic obstructive pulmonary disease, asthma, interstitial lung disease or had oxygen assessment needs.

Methods: Nine IRT members collaboratively developed content for the templates to assist in clinical reviews.

Effect of Chirality and Amphiphilicity on the Antimicrobial Activity of Tripodal Lysine-Based Peptides.

A series of tripodal (three-arm) lysine-based peptides were designed and synthesized and their self-assembly properties in aqueous solution and antimicrobial activity were investigated. We compare the behaviors of homochiral tripodal peptides (KKY)K and a homologue containing the bulky aromatic fluorenylmethoxycarbonyl (Fmoc) group Fmoc-(KKY)K, and heterochiral analogues containing k (d-Lys), (kkY)K and Fmoc-(kkY)K. The molecular conformation and self-assembly in aqueous solutions were probed using various spectroscopic techniques, along with small-angle X-ray scattering (SAXS) and cryogenic-transmission electron microscopy (cryo-TEM).

Organ-specific malperfusion in acute type A aortic dissection: epidemiological meta-analysis of incidence rates.

Background: Acute type A aortic dissection is a life-threatening clinical emergency that necessitates immediate surgical intervention with an estimated mortality rate of approximately 1-2% per hour. When complicated by malperfusion, the perioperative mortality rate is reported to be increased by up to 39%. Malperfusion can affect many vascular beds with varying incidence and severity, resulting in coronary, cerebral, visceral, peripheral, renal or spinal malperfusion.

A review of Kilovoltage (kV) Radiotherapy Treatment in the UK: Quality Control, Radiation Dosimetry, Treatment Equipment and Workload.

Objectives: To survey kilovoltage (kV) radiotherapy in the UK, updating a 2016 study, focussing on radiotherapy physics, including equipment quality control (QC) and radiation dosimetry, with information on installed equipment and clinical activity.

Methods: All UK radiotherapy physics departments (n = 68) were invited to complete a comprehensive survey. An analysis of the installed equipment base, patient numbers, clinical activity, QC testing and radiation dosimetry processes were undertaken.

Epidemiology of Shiga toxin-producing other than serotype O157:H7 in England, 2016-2023.

Shiga toxin-producing (STEC) infections are of public health concern as STEC can cause large national foodborne outbreaks of severe gastrointestinal disease, particularly in the young and elderly. In recent years, the implementation of PCR by diagnostic microbiology laboratories has improved the detection of STEC, and there has been an increase in notifications of cases of non-O157 STEC. However, the extent this increase in caseload can be attributed to the improved detection by PCR, or a true increase in non-O157 STEC infections, is unknown.

Comment on "Dolphin and porpoise detections by the F-POD are not independent: Implications for sympatric species monitoring" [JASA Express Lett. 4, 031202 (2024)].

Dolphin and porpoise detections by the F-POD are not independent: Implications for sympatric species monitoring, Cosentino, Marcolin, Griffiths, Sánchez-Camí, and Tougaard [(2024). JASA Express Lett. 4, 031202] address a significant issue, the reliability of the discrimination of dolphins and porpoises in recordings of their acoustic clicks by F-POD loggers, but unfortunately present a misleading interpretation of the process and results.

Brief Report: Cystatin C Provides Substantially Higher Glomerular Filtration Rate Estimates Than Creatinine in a Subset of Black People With HIV on Current Antiretroviral Regimens.

Background: In African populations, estimated glomerular filtration rate by cystatin C (eGFRcys) is better aligned with gold-standard GFR measurements than eGFR by creatinine (eGFRcr). Moreover, eGFRcys is unaffected by the effects of antiretroviral therapy (ART) on tubular secretion and may thus provide better estimates of GFR in people with HIV on ART.

Setting: Observational cohort study of people of African ancestry living with suppressed HIV RNA on ART in London, United Kingdom.

Sox10 is required for systemic initiation of bone mineralization.

Heterozygous variants in SOX10 cause congenital syndromes affecting pigmentation, digestion, hearing, and neural development, primarily attributable to failed differentiation or loss of non-skeletal neural crest derivatives. We report here an additional novel requirement for Sox10 in bone mineralization. Neither crest- nor mesoderm-derived bones initiate mineralization on time in zebrafish sox10 mutants, despite normal osteoblast differentiation and matrix production.

Preventative self-regulatory primary care leadership in urban China: impact on physician well-being and medical service quality.

Purpose: The study aims to address the gap between leaders' preventative self-regulatory focus and its impact on Chinese primary care physicians (PCPs) well-being, measured by work-family spillover stress and work exhaustion and on healthcare quality, measured by preventive service delivery and clinical guideline adherence.

Design/methodology/approach: This paper conducted a cross-sectional in-person survey with 38 leaders and 224 PCPs in 38 primary health centers (PHCs) in Jinan, Tianjin, Shenzhen and Shanghai. Guided by the regulatory focus theory, this paper built hierarchical linear regression models to examine the association between the leadership's regulatory focus and physician burnout, work-family conflict, clinic guideline adherence and preventive service delivery.

Moving Beyond Static, Individualistic Approaches to Agency: Theories of Agency for Medical Education Researchers: AMEE Guide No. 177.

Agency - the capacity to produce an effect - is a foundational aspect of medical education. Agency is usually conceptualized at the level of the , with each learner charged with taking responsibility to pull themselves up by their bootstraps. This conceptualization is problematic.

What Impact Does Net Zero Action on Road Transport and Building Heating Have on Exposure to UK Air Pollution?

This study explores the cobenefits of reduced nitrogen dioxide (NO), ozone (O), and particulate matter (PM), through net zero (NZ) climate policy in the UK. Two alternative NZ scenarios, the balanced net zero (BNZP) and widespread innovation (WI) pathways, from the UK Climate Change Committee's Sixth Carbon Budget, were examined using a chemical transport model (CTM). Under the UK existing policy, Business as Usual (BAU), reductions in NO and PM were predicted by 2030 due to new vehicle technologies but plateau by 2040.

Access in all areas? A roundup of developments in market access and health technology assessment: part 6.

In this update, we discuss an article covering the implementation challenges of the upcoming European Union Health Technology Assessment regulation, particularly focusing on the complexity of population, intervention, comparator and outcomes requirements across member states; a user guide to applying generalized cost-effectiveness analysis for broader value assessment and finally highlight an ongoing debate surrounding National Institute for Health and Care Excellence's severity modifier implementation.

Laser Synthesis of Platinum Single-Atom Catalysts for Hydrogen Evolution Reaction.

Platinum (Pt)-based heterogeneous catalysts show excellent performance for the electrocatalytic hydrogen evolution reaction (HER); however, the high cost and earth paucity of Pt means that efforts are being directed to reducing Pt usage, whilst maximizing catalytic efficiency. In this work, a two-step laser annealing process was employed to synthesize Pt single-atom catalysts (SACs) on a MOF-derived carbon substrate. The laser irradiation of a metal-organic framework (MOF) film (ZIF67@ZIF8 composite) by rapid scanning of a ns pulsed infrared (IR; 1064 nm) laser across the freeze-dried MOF resulted in a metal-loaded graphitized film.