Paediatric Common Infections Pathways: improving antimicrobial stewardship and promoting ambulation for children presenting with common infections to hospitals in the UK and Ireland.

Paediatric common infection pathways have been developed in collaboration between the BSAC and national paediatric groups, addressing the management of cellulitis, lymphadenitis/lymph node abscess, pneumonia/pleural empyema, pyelonephritis, tonsillitis/peritonsillar abscess, otitis media/mastoiditis, pre-septal/post-septal (orbital) cellulitis, and meningitis. Guidance for the management of a child presenting with a petechial/purpuric rash and the infant under 3 months of age with fever is also provided. The aim of these pathways is to support the delivery of high-quality infection management in children presenting to a hospital.

DeepFrag: a deep convolutional neural network for fragment-based lead optimization.

Machine learning has been increasingly applied to the field of computer-aided drug discovery in recent years, leading to notable advances in binding-affinity prediction, virtual screening, and QSAR. Surprisingly, it is less often applied to lead optimization, the process of identifying chemical fragments that might be added to a known ligand to improve its binding affinity. We here describe a deep convolutional neural network that predicts appropriate fragments given the structure of a receptor/ligand complex.

Characteristics of post-mortem beta-hydroxybutyrate-positivet cases - A retrospective study on age, sex and BMI in 1407 forensic autopsies.

Background: Post-mortem biochemistry, including the analysis of beta-hydroxybutyrate (BHB), is increasingly employed in forensic medicine, especially in conditions such as diabetes and chronic alcoholism. However, not much is known about the associations between age, body mass index (BMI), and sex and BHB concentrations in ketoacidotic conditions.

Aim: To retrospectively study the association between age, BMI and sex in several conditions, such as diabetic ketoacidosis (DKA), alcoholic ketoacidosis (AKA), and elevated post-mortem BHB concentrations.

Social Media as a Platform for Recruitment to a National Survey During the COVID-19 Pandemic: Feasibility and Cost Analysis.

Background: With improved accessibility to social media globally, health researchers are capitalizing on social media platforms to recruit participants for research studies. This has particularly been the case during the COVID-19 pandemic, when researchers were not able to use traditional methods of recruitment. Nevertheless, there is limited evidence on the feasibility of social media for recruiting a national sample.

Clinical management of immune-related adverse events following immunotherapy treatment in patients with non-small cell lung cancer.

The advent of checkpoint blockade-based immunotherapy is rapidly changing the management of lung cancer. Whereas past anticancer drugs' primary toxicity was hematologic, the newer agents have primarily autoimmune toxicity. Thus, it is no longer enough for oncology practitioners to be skilled only in hematology.

A genome-wide association study identifies 5 loci associated with frozen shoulder and implicates diabetes as a causal risk factor.

Frozen shoulder is a painful condition that often requires surgery and affects up to 5% of individuals aged 40-60 years. Little is known about the causes of the condition, but diabetes is a strong risk factor. To begin to understand the biological mechanisms involved, we aimed to identify genetic variants associated with frozen shoulder and to use Mendelian randomization to test the causal role of diabetes.

DeepFrag: An Open-Source Browser App for Deep-Learning Lead Optimization.

Lead optimization, a critical step in early stage drug discovery, involves making chemical modifications to a small-molecule ligand to improve properties such as binding affinity. We recently developed DeepFrag, a deep-learning model capable of recommending such modifications. Though a powerful hypothesis-generating tool, DeepFrag is currently implemented in Python and so requires a certain degree of computational expertise.

Persistent neuropathy among early-stage breast cancer survivors in a population-based cohort.

Background: The prevalence of persistent peripheral neuropathy (PN) in early-stage breast cancer (ESBC) survivors is largely unknown. We explored the occurrence and risk factors of PN among long-term ESBC survivors treated with taxane chemotherapy.

Methods: A population-based cohort of 884 recurrence-free ESBC survivors diagnosed 2010-2015 in the South East Health Care region, Sweden and 1768 control women without prior cancer received a postal questionnaire that included the European Organisation for Research and Treatment of Cancer chemotherapy-induced peripheral neuropathy (CIPN20) items.

Circumstances, Postmortem Findings, Blood Concentrations and Metabolism in a Series of Methoxyacetylfentanyl-Related Deaths.

Methoxyacetylfentanyl is one of many fentanyl analogs available as new psychoactive substances. It have been encountered in both the European Union and the United States, and existing literature suggest that methoxyacetylfentanyl is around 3- to 5-fold less potent than fentanyl. The aim of the present work was to combine case information with blood concentrations and abundance of urinary metabolites to investigate the importance of these parameters for toxicological interpretation.

Pharmacological selection of cannabinoid receptor effectors: Signalling, allosteric modulation and bias.

The type-1 cannabinoid receptor (CB) is a promising drug target for a wide range of diseases. However, many existing and novel candidate ligands for CB have shown only limited therapeutic potential. Indeed, no ligands are currently approved for the clinic except formulations of the phytocannabinoids Δ-THC and CBD and a small number of analogues.

Enantioselective nickel-catalyzed -arylmetallative cyclizations onto acyclic electron-deficient alkenes.

Enantioselective nickel-catalyzed reactions of (hetero)arylboronic acids or alkenylboronic acids with substrates containing an alkyne tethered to various acyclic electron-deficient alkenes are described.

Technical in-depth comparison of two massive parallel DNA-sequencing methods for formalin-fixed paraffin-embedded tissue from victims of sudden cardiac death.

Sudden cardiac death (SCD) is a tragic and traumatic event. SCD is often associated with hereditary genetic disease and in such cases, sequencing of stored formalin fixed paraffin embedded (FFPE) tissue is often crucial in trying to find a causal genetic variant. This study was designed to compare two massive parallel sequencing assays for differences in sensitivity and precision regarding variants related to SCD in FFPE material.

Reaching underserved South Africans with integrated chronic disease screening and mobile HIV counselling and testing: A retrospective, longitudinal study conducted in Cape Town.

Background: Community-based, mobile HIV counselling and testing (HCT) and screening for non-communicable diseases (NCDs) may improve early diagnosis and referral for care in underserved populations. We evaluated HCT/NCD data and described population characteristics of those visiting a mobile clinic in high HIV disease burden settings in Cape Town, South Africa, between 2008 and 2016.

Methods: Trained counsellors registered patients ≥12 years old at a mobile clinic, which offered HCT and blood pressure, diabetes (glucose testing) and obesity (body mass index) screening.

Changes in characteristics and case-severity in patients hospitalised with influenza A (H1N1) pdm09 infection between two epidemic waves-England, 2009-2010.

Background: During 2009-2010, pandemic influenza A (H1N1) pdm09 virus (pH1N1) infections in England occurred in two epidemic waves. Reasons for a reported increase in case-severity during the second wave are unclear.

Methods: We analysed hospital-based surveillance for patients with pH1N1 infections in England during 2009-2010 and linked national data sets to estimate ethnicity, socio-economic status and death within 28 days of admission.

Post-Mortem Metabolomics: A Novel Approach in Clinical Biomarker Discovery and a Potential Tool in Death Investigations.

Metabolomics can be defined as the scientific field aiming at characterizing all low-weight molecules (so-called metabolites) in a biological system. At the time of death, the level and type of metabolites present will most likely reflect the events leading up to death.In this proof of concept study, we investigated the potential of post-mortem metabolomics by identifying post-mortem biomarkers, correlated these identified biomarkers with those reported in clinical metabolomics studies, and finally validated the models predictability of unknown autopsy cases.

Association of social network characteristics with HIV knowledge, stigma, and testing: findings from a study of racial and ethnic minority women in a small Western city.

Black and Latina women are disproportionately impacted by HIV/AIDS. Despite existing research linking social networks and HIV risk among men who have sex with men (MSM) and other high-risk populations, little research has examined how ethnic/racial minority women's social networks shape HIV prevention and intervention targets. Using interviews with a sample of 165 predominantly Black and Latina-identifying women from a small city in the Western U.

Co-quantification of crAssphage increases confidence in wastewater-based epidemiology for SARS-CoV-2 in low prevalence areas.

Wastewater surveillance of SARS-CoV-2 RNA is increasingly being incorporated into public health efforts to respond to the COVID-19 pandemic. In order to obtain the maximum benefit from these efforts, approaches to wastewater monitoring need to be rapid, sensitive, and relatable to relevant epidemiological parameters. In this study, we present an ultracentrifugation-based method for the concentration of SARS-CoV-2 wastewater RNA and use crAssphage, a bacteriophage specific to the human gut, to help account for RNA loss during transit in the wastewater system and sample processing.

Bridging the postpartum gap: best practices for training of obstetrical patient navigators.

The postpartum period represents a critical window of opportunity to improve maternal short- and long-term health, including optimizing postpartum recovery, providing effective contraception, caring for mood disorders, managing weight, supporting lactation, initiating preventive care, and promoting cardiometabolic health. However, inadequate postpartum care, especially for individuals facing social and structural barriers, is common in the United States and contributes to suboptimal health outcomes with lasting consequences. Patient navigation is a patient-centered intervention that uses trained personnel to identify financial, cultural, logistical, and educational obstacles to effective healthcare and to mitigate these barriers to facilitate comprehensive and timely access to needed health services.

Oxycodone findings and CYP2D6 function in postmortem cases.

Genetic disposition can cause variation in oxycodone pharmacokinetic characteristics and decrease or increase the expected clinical response. In forensic medicine, determination of cause of death or assessing time between drug intake and death can be facilitated by knowledge of parent and metabolite concentrations. In this study, the aim was to investigate if CYP2D6 genotyping can facilitate interpretation by investigating the frequency of the four CYP2D6 phenotypes, poor metabolizer, intermediate metabolizer, extensive metabolizer, and ultra-rapid metabolizer in postmortem cases, and to study if the CYP2D6 activity was associated with a certain cause of death, concentration, or metabolic ratio.

Examination of Mediators and Moderators to Understand How and in What Context Game Changers Increases HIV Prevention Advocacy Among Persons Living With HIV in Uganda.

Background: Our randomized controlled trial (RCT) of the group-based Game Changers intervention demonstrated effects on the primary goal of increased HIV-protective behaviors among social network members (alters), via the mechanism of increased participant engagement in HIV prevention advocacy with alters. We sought to understand how and in what context the intervention has its effects by examining specific mediators and moderators of the intervention's effect on increased prevention advocacy.

Methods: The RCT was conducted with 98 adult PLWH in Uganda.

Change in Kidney Function and 2-Year Mortality After Transcatheter Aortic Valve Replacement.

Importance: Chronic kidney disease (CKD) is prevalent in the population of patients undergoing transcatheter aortic valve replacement (TAVR). Data on the association of TAVR with kidney function are scarce, as are data on the relationship between changes in kidney function after TAVR and mortality.

Objective: To describe the changes in kidney function (both periprocedural and at steady state) after TAVR and to explore the association of TAVR with midterm mortality.

A sensitive LC-MS/MS method for the quantitation of oxycodone, noroxycodone, 6α-oxycodol, 6β-oxycodol, oxymorphone, and noroxymorphone in human blood.

The objective of this study was to develop and validate a highly sensitive method for the detection of oxycodone, noroxycodone, 6β-oxycodol, 6α-oxycodol, oxymorphone, and noroxymorphone in blood by liquid chromatography tandem mass spectrometry. The analytes were extracted from blood (0.5 mL) using Bond Elut Certify Solid Phase Extraction columns, evaporated to dryness and reconstituted before analysis was performed on an Acquity UPLC® I-class coupled to a Waters Xevo TQD.

Neurophysiological Responses to Interpersonal Emotional Images Prospectively Predict the Impact of COVID-19 Pandemic-Related Stress on Internalizing Symptoms.

Background: Exposure to stressful events related to the COVID-19 coronavirus pandemic has been associated with increases in the prevalence of depression and anxiety, raising questions about vulnerabilities that make some individuals more susceptible to internalizing symptoms following stress exposure.

Methods: This prospective study examined the effects of neurophysiological reactivity to positive and threatening interpersonal stimuli, indexed by the late positive potential (LPP) event-related potential, in conjunction with exposure to interpersonal pandemic-related stressors in the prediction of internalizing symptom changes from before to during the pandemic. Emerging adults (n= 75) initially completed measures of internalizing symptoms and an interpersonal emotional images task while an electroencephalogram was recorded pre-pandemic and were recontacted during the COVID-19 pandemic in May 2020 to complete measures of exposure to pandemic-related stressful events and current internalizing symptoms.