Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Postoperative opioids administered to inpatients with major or orthopaedic surgery: A retrospective cohort study using data from hospital electronic prescribing systems

Background Opioids administered in hospital during the immediate postoperative period are likely to influence post-surgical outcomes, but inpatient prescribing during the admission is challenging to access. Modified-release(MR) preparations have been especially associated with harm, whilst certain populations such as the elderly or those with renal impairment may be vulnerable to complications. This study aimed to assess postoperative opioid utilisation patterns during hospital stay for people admitted for major/orthopaedic surgery.Methods Patients admitted to a teaching hospital in the North-West of England between 2010-2021 for major/orthopaedic surgery with an admission for ≥1 day were included. We examined opioid administrations in the first seven days post-surgery in hospital, and “first 48 hours” were defined as the initial period. Proportions of MR opioids, initial immediate-release(IR) oxycodone and initial morphine milligram equivalents (MME)/day were calculated and summarised by calendar year. We also assessed the proportion of patients prescribed an opioid at discharge. Results Among patients admitted for major/orthopaedic surgery, 71.1% of patients administered opioids during their hospitalisation. In total 50,496 patients with 60,167 hospital admissions were evaluated. Between 2010-2017 MR opioids increased from 8.7% to 16.1% and dropped to 11.6% in 2021. Initial use of oxycodone IR among younger patients (≤70 years) rose from 8.3% to 25.5% (2010-2017) and dropped to 17.2% in 2021. The proportion of patients on ≥50MME/day ranged from 13% (2021) to 22.9% (2010). Of the patients administered an opioid in hospital, 26,920 (53.3%) patients were discharged on an opioid. Conclusions In patients hospitalised with major/orthopaedic surgery, 4 in 6 patients were administered an opioid. We observed a high frequency of administered MR opioids in adult patients and initial oxycodone IR in the ≤70 age group. Patients prescribed with ≥50MME/day ranged between 13-22.9%. This is the first published study evaluating UK inpatient opioid use, which highlights opportunities for improving safer prescribing in line with latest recommendations. <br/

Machine learning identifies risk factors associated with long-term opioid use in fibromyalgia patients newly initiated on an opioid

ObjectivesFibromyalgia is frequently treated with opioids due to limited therapeutic options. Long-term opioid use is associated with several adverse outcomes. Identifying factors associated with long-term opioid use is the first step in developing targeted interventions. The aim of this study was to evaluate risk factors in fibromyalgia patients newly initiated on opioids using machine learning. Methods A retrospective cohort study was conducted using a nationally representative primary care dataset from the UK from the Clinical Research Practice Datalink. Fibromyalgia patients without prior cancer who were new opioid users were included. Logistic regression, a random forest model and Boruta feature selection were used to identify risk factors related to long-term opioid use. Adjusted odds ratios and feature importance scores were calculated to gauge the strength of these associations. Results In this study, 28,552 fibromyalgia patients initiating opioids were identified of which 7,369 patients (26%) had long-term opioid use. High initial opioid dose (adjusted odds ratio [aOR]: 31.96, mean decrease accuracy [MDA] 135), history of self-harm (aOR: 2.00, MDA 44), obesity (aOR: 2.43, MDA 36), high deprivation (aOR: 2.01, MDA 31) and substance use disorder (aOR: 2.08, MDA 25) were the factors most strongly associated with long-term use. Conclusions High dose of initial opioid prescription, a history of self-harm, obesity, high deprivation, substance use disorder and age were associated with long-term opioid use. This study underscores the importance of recognising these individual risk factors in fibromyalgia patients to better navigate the complexities of opioid use and facilitate patient-centred care. <br/

Coconut Shell-Derived Activated Carbon for High-Performance Solid-State Supercapacitors

Coconut shells, low-cost and renewable agro-wastes, were used as a starting material in the synthesis of hierarchical activated carbons via hydrothermal, KOH-activation, and carbonization techniques. The ratio of KOH to hydrochar was varied in a systemic manner to study how it influences the texture and electrochemical behavior of the capacitor. Coconut shell-based carbon coated on nickel foams presented a surface area of 1567 m2 g−1, with micropores as well as mesopores widely distributed. The sample showed superior electrochemical performance, attaining 449 F g−1 at 1 A g−1 in 6 M LiNO3 aqueous solution. The solid-state symmetric supercapacitor device delivered a specific capacitance of 88 F g−1 at 1 A g−1 and a high energy density of 48.9 Whkg−1 at a power density of 1 kW kg−1. At a wide voltage window of 2.0 V, the sample was highly stable during the cycle test, showing a 92% capacitance retention at 2 A g−1 after cycling for 5000 times. The superior performance is due to the sample possessing great BET surface area, a good distribution of pores, and the usage of a suitable electrolyte. This facilitates an electrical double layer that can be deployed for applications to store energy

Screening therapeutic EMT blocking agents in a three-dimensional microenvironment

10.1039/c2ib20209cIntegrative Biology (United Kingdom)52381-38