The Importance of Diagnostics in the Treatment of Urinary Tract Infections in the United Kingdom.

Current diagnosis of urinary tract infections (UTIs) in the UK initially relies on self-reported patient symptoms with no point-of-care test robust enough to accurately identify the causative pathogen and inform on antibiotic susceptibility. In serious UTI cases, standard urine culture is regarded as the gold standard for diagnosis and involves direct isolation, culture and antibiotic susceptibility testing of pathogens. These methods are not suitable in initial UTI diagnosis and treatment because of the time taken to conduct these analyses (≥3 days).

Feto-maternal indicators of cardiac dysfunction as a justification for the cardiac origins for pre-eclampsia.

While the pathophysiology of pre-eclampsia has been postulated as being secondary to placental dysfunction, a cardiac origin has more recently been proposed. Although an association between fetal congenital cardiovascular disease and pre-eclampsia has been demonstrated, no precise pathophysiologic mechanism for this association has been described. This review highlights the current biophysical (including echocardiography and Doppler indices) and biochemical (including proteomic, metabolomic and genetic/transcriptomic) markers of cardiac dysfunction that have been investigated in maternal and fetal cardiac disease and their overlap with predictors of pre-eclampsia.

Microenvironment shapes small-cell lung cancer neuroendocrine states and presents therapeutic opportunities.

Small-cell lung cancer (SCLC) is the most fatal form of lung cancer. Intratumoral heterogeneity, marked by neuroendocrine (NE) and non-neuroendocrine (non-NE) cell states, defines SCLC, but the cell-extrinsic drivers of SCLC plasticity are poorly understood. To map the landscape of SCLC tumor microenvironment (TME), we apply spatially resolved transcriptomics and quantitative mass spectrometry-based proteomics to metastatic SCLC tumors obtained via rapid autopsy.

Stratifying risk of disease in haematuria patients using machine learning techniques to improve diagnostics.

Background: Detailed and invasive clinical investigations are required to identify the causes of haematuria. Highly unbalanced patient population (predominantly male) and a wide range of potential causes make the ability to correctly classify patients and identify patient-specific biomarkers a major challenge. Studies have shown that it is possible to improve the diagnosis using multi-marker analysis, even in unbalanced datasets, by applying advanced analytical methods.

Design and selection of anti-PD-L1 single-domain antibody and tumor necrosis factor superfamily ligands for an optimal vectorization in an oncolytic virus.

Arming oncolytic viruses with transgenes encoding immunomodulators improves their therapeutic efficacy by enhancing and/or sustaining the innate and adaptive anti-tumoral immune responses. We report here the isolation, selection, and vectorization of a blocking anti-human PDL1 single-domain antibody (sdAb) isolated from PDL1-immunized alpacas. Several formats of this sdAb were vectorized into the vaccinia virus (VV) and evaluated for their programmed cell death protein 1 (PD1)/PD1 ligand (PDL1) blocking activity in the culture medium of tumor cells infected .

The High-Risk Human Papillomavirus Type Influences the Tissue Microenvironment in Cervical Intraepithelial Neoplasia Grade 2.

High-risk, cancer-causing human papillomavirus (HPV) types are associated with cervical precancer and cancer. A high proportion of high-risk HPV precancer lesions undergo immune-mediated regression. The purpose of this study was to determine if the tissue microenvironment of HPV16 and 18 (HPV16/18) cervical intraepithelial neoplasia grade 2 lesions differed from other high-risk types (HPV 'other').

Large-Scale Plasma Proteome Epitome Profiling is an Efficient Tool for the Discovery of Cancer Biomarkers.

Current proteomic technologies focus on the quantification of protein levels, while little effort is dedicated to the development of system approaches to simultaneously monitor proteome variability and abundance. Protein variants may display different immunogenic epitopes detectable by monoclonal antibodies. Epitope variability results from alternative splicing, posttranslational modifications, processing, degradation, and complex formation and possesses dynamically changing availability of interacting surface structures that frequently serve as reachable epitopes and often carry different functions.

Impact of myocardial bridging on coronary artery plaque formation and long-term mortality after heart transplantation.

Objectives: This study aimed to explore the impact of myocardial bridging (MB) on early development of cardiac allograft vasculopathy and long-term graft survival after heart transplantation.

Background: MB has been reported to be associated with acceleration of proximal plaque development and endothelial dysfunction in native coronary atherosclerosis. However, its clinical significance in heart transplantation remains unclear.

Assessment of care timelines in intestinal malrotation with volvulus: A retrospective chart review.

Background: Patients with intestinal malrotation with volvulus (MWV) may suffer bowel ischemia, which can be correlated with the timing of surgical intervention. The purpose of this study was to identify and assess time-blocks in the care of patients from initial physician assessment (IPA) to surgical intervention to highlight potential opportunities for improvement.

Methods: Retrospective chart review of patients with MWV presenting to McMaster Children's Hospital between January 1st, 2000 and December 31st, 2020 (n = 31).

Analysis of reactive aldehydes in urine and plasma of type-2 diabetes mellitus patients through liquid chromatography-mass spectrometry: Reactive aldehydes as potential markers of diabetic nephropathy.

Introduction: Diabetes is a major public health issue that is approaching epidemic proportions globally. Diabetes mortality is increasing in all ethnic groups, irrespective of socio-economic class. Obesity is often seen as the main contributor to an increasing prevalence of diabetes.

Non-alcoholic fatty liver disease-A pilot study investigating early inflammatory and fibrotic biomarkers of NAFLD with alcoholic liver disease.

: Non-alcoholic fatty liver disease (NAFLD) is a condition where excess fat accumulates in the liver (hepatic steatosis) and there is no history of alcohol abuse or other secondary causes of chronic liver disease. NAFLD is a very common disorder, occurring in 25% of the global population. NAFLD is now the most common chronic liver disorder in Western countries.

Heterogeneous vascular response after implantation of bare nitinol self-expanding stents in the swine femoropopliteal artery.

Background: Mechanism of femoropopliteal in-stent restenosis has been underappreciated.

Aim: The aim of this animal study was to elucidate vascular response after femoropopliteal bare nitinol self-expanding stents (SESs) implantation.

Methods: Misago, Smart Flex, or Innova stent was randomly implanted in 36 swine femoropopliteal arteries.

The Program of All-Inclusive Care for the Elderly: An Update after 25 Years of Permanent Provider Status.

PACE is the gold standard for community-based integrated care. Over the 25 years as permanent provider status by Centers for Medicare and Medicaid Services, it has evolved in design and grown in numbers served. We review the evidence base, history, and future direction of PACE.

Biomarkers to assess the risk of bladder cancer in patients presenting with haematuria are gender-specific.

Introduction: Haematuria is a common red flag symptom of urinary tract cancer. Bladder cancer (BC) is the most common cancer to present with haematuria. Women presenting with haematuria are often underdiagnosed.

Biomarkers for Detecting Kidney Dysfunction in Type-2 Diabetics and Diabetic Nephropathy Subjects: A Case-Control Study to Identify Potential Biomarkers of DN to Stratify Risk of Progression in T2D Patients.

Introduction: Currently there are no biomarkers that are predictive of when patients with type-2 diabetes (T2D) will progress to more serious kidney disease i.e., diabetic nephropathy (DN).

A Novel Combination of Serum Markers in a Multivariate Model to Help Triage Patients Into "Low-" and "High-Risk" Categories for Prostate Cancer.

Background: Almost 50,000 men in the United Kingdom (UK) are diagnosed each year with prostate cancer (PCa). Secondary referrals for investigations rely on serum prostate-specific antigen (PSA) levels and digital rectal examination. However, both tests lack sensitivity and specificity, resulting in unnecessary referrals to secondary care for costly and invasive biopsies.

A novel algorithm for cardiovascular screening using conjunctival microcirculatory parameters and blood biomarkers.

Microvascular haemodynamic alterations are associated with coronary artery disease (CAD). The conjunctival microcirculation can easily be assessed non-invasively. However, the microcirculation of the conjunctiva has not been previously explored in clinical algorithms aimed at identifying patients with CAD.

Blimp-1 is a prognostic indicator for progression of cervical intraepithelial neoplasia grade 2.

Background: Progression of cervical intraepithelial neoplasia (CIN) to higher grade disease is associated with persistent human papillomavirus (HPV) infection and an absence of immune-mediated regression. However, the immune microenvironment that distinguishes progression from persistent or regressing lesions has not been well defined.

Methods: A total of 69 patients under the age of 25 with high-risk HPV-positive cytology and biopsy-confirmed p16-positive CIN2 were included in the study.

VEGF-A-related genetic variants protect against Alzheimer's disease.

The Apolipoprotein E () genotype has been shown to be the strongest genetic risk factor for Alzheimer's disease (AD). Moreover, both the lipolysis-stimulated lipoprotein receptor (LSR) and the vascular endothelial growth factor A (VEGF-A) are involved in the development of AD. The aim of the study was to develop a prediction model for AD including single nucleotide polymorphisms (SNP) of , and VEGF-A-related variants.

Postoperative management of pediatric patients undergoing minimally invasive repair of pectus excavatum: Where are we now?

Purpose: Minimally invasive repair of pectus excavatum (MIRPE) often leads to a painful and challenging recovery period. This study aims to describe the postoperative management of pediatric patients undergoing MIRPE and compare postoperative outcomes between patients using different routes of postoperative analgesia.

Methods: Retrospective chart review of pediatric patients who underwent MIRPE from July 2003 to September 2019 at a single pediatric tertiary care center.

Blood and urinary cytokine balance and renal outcomes at cardiac surgery.

Background: Increased perioperative pro-inflammatory biomarkers, renal hypoperfusion and ischemia reperfusion injury (IRI) heighten cardiac surgery acute kidney injury (CS-AKI) risk. Increased urinary anti-inflammatory cytokines attenuate risk. We evaluated whether blood and urinary anti-inflammatory biomarkers, when expressed as ratios with biomarkers of inflammation, hypoperfusion and IRI are increased in CS-AKI patients.

Multiplex Serum Biomarker Assays Improve Prediction of Renal and Mortality Outcomes in Chronic Kidney Disease.

Background: We investigated the predictive value of 11 serum biomarkers for renal and mortality end points in people with CKD.

Methods: Adults with CKD (=139) were enrolled from outpatient clinics between February 2014 and November 2016. Biomarker quantification was performed using two multiplex arrays on a clinical-grade analyzer.

Impact of Diastolic Vessel Restriction on Quality of Life in Symptomatic Myocardial Bridging Patients Treated With Surgical Unroofing: Preoperative Assessments With Intravascular Ultrasound and Coronary Computed Tomography Angiography.

[Figure: see text].

The ETS transcription factor ERF controls the exit from the naïve pluripotent state in a MAPK-dependent manner.

The naïve epiblast transitions to a pluripotent primed state during embryo implantation. Despite the relevance of the FGF pathway during this period, little is known about the downstream effectors regulating this signaling. Here, we examined the molecular mechanisms coordinating the naïve to primed transition by using inducible ESC to genetically eliminate all RAS proteins.