Publications by authors named "McLauchlan J"

Background: Risk evaluation of lymph node metastasis for early-stage (T1 and T2) colorectal cancers is critical for determining therapeutic strategies. Traditional methods of lymph node metastasis prediction have limited accuracy. This systematic review aimed to review the potential of artificial intelligence in predicting lymph node metastasis in early-stage colorectal cancers.

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Background: Textbook outcome (TO) is an objective, composite measure of clinical outcomes in surgery. TO in liver surgery has been used in previous international studies to define and compare performance across centres. This study aimed to review TO rates following liver resection at a single institution.

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Introduction: Oral language skills are associated with children's later self-regulation and academic skills; in turn, self-regulation in early childhood predicts successful functioning later in life. The primary objective of this study is to evaluate the separate and combined effectiveness of an oral language intervention (Enhancing Rich Conversations, ENRICH) and a self-regulation intervention (Enhancing Neurocognitive Growth with the Aid of Games and Exercise, ENGAGE) with early childhood teachers and parents for children's oral language, self-regulation and academic functioning.

Methods And Analysis: The Kia Tīmata Pai (Best Start) study is a cluster randomised controlled trial with teachers and children in approximately 140 early childhood centres in New Zealand.

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Background: There is an increasing incidence of early-onset colorectal cancer; however, the psychosocial impacts of this disease on younger adults have been seldom explored.

Methods: A systematic review was conducted according to the PRISMA guidelines. The Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, PubMed, and Scopus were searched, and papers were included if published in English within the last 10 years and if they reported results separately by age (including early-onset colorectal cancer, defined as colorectal cancer diagnosed before the age of 50 years).

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Article Synopsis
  • Despite progress in fighting hepatitis C in the UK, concerns remain about future disease impacts due to various risk factors.
  • The study analyzed data from 3,829 HCV-positive patients in England and Scotland to identify significant risk factors for severe liver disease, including age, sex, body mass index (BMI), diabetes, HCV genotype, and route of infection.
  • Findings indicate that older age, male sex, high BMI, and specific HCV genotypes are associated with higher risks, while an unexpected lower risk is noted among black patients compared to white patients, implying the need for targeted public health strategies.
  • This research establishes a baseline for understanding historical risk factors and highlights the importance of monitoring geographical differences in healthcare access and disease burden related to H
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Unlabelled: BACKGROUND AND AIMS: The newly developed direct-acting antivirals have revolutionized the treatment of chronic hepatitis C virus (HCV), with cure rates as high as 98% in some cohorts. Although genome sequencing has demonstrated that some subtypes of HCV naturally harbor drug resistance associated substitutions (RAS), these are often overlooked as "rarities." Furthermore, commercial subtyping assays and associated epidemiological findings are skewed towards Western cohorts and whole-genome sequencing can be problematic to deploy without significant infrastructure and training support.

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Natural hepatitis C virus (HCV) infection is restricted to humans, whereas other primates such as rhesus macaques are non-permissive for infection. To identify human and rhesus macaque genes that differ or share the ability to inhibit HCV replication, we conducted a medium-throughput screen of lentivirus-expressed host genes that disrupt replication of HCV subgenomic replicon RNA expressing secreted Gaussia luciferase. A combined total of >800 interferon-stimulated genes (ISGs) were screened.

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Hepatitis C virus (HCV) genotype 3 (GT-3) represents 22-30% of all infections and is the second most common genotype among all HCV genotypes. It has two main subtypes, GT-3a and GT-3b, that present epidemiological differences in transmission groups. This report generated 56 GT-3a and 64 GT-3b whole-genome sequences to conduct an evolutionary kinetics and selective force analysis with reference sequences from various countries.

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Article Synopsis
  • Hepatitis C virus (HCV) shows high genetic diversity, particularly among strains found in the Li ethnic group on Hainan Island, China, where new strains of HCV genotype 6 (gt6) were identified.
  • Researchers sequenced 33 complete HCV genomes and found three new clades and 30 unassigned strains of gt6, showing a long history of HCV presence, dating back to roughly 2767 BCE.
  • The study indicates that the HCV gt6 strains were likely introduced to the Li community through multiple independent transmission events, shedding light on the evolutionary history of this virus.
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Introduction: Risk-stratifying patients with hepatitis C virus (HCV) cirrhosis according to medium-term prognosis will inform clinical decision-making. It is unclear which biomarkers/models are optimal for this purpose. We quantified the discriminative ability of 14 diverse biomarkers for prognosis prediction over a 4-year time.

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The host genetic background for hepatocellular carcinoma (HCC) is incompletely understood. We aimed to determine if four germline genetic polymorphisms, rs429358 in apolipoprotein E (APOE), rs2642438 in mitochondrial amidoxime reducing component 1 (MARC1), rs2792751 in glycerol-3-phosphate acyltransferase (GPAM), and rs187429064 in transmembrane 6 superfamily member 2 (TM6SF2), previously associated with progressive alcohol-related and nonalcoholic fatty liver disease, are also associated with HCC. Four HCC case-control data sets were constructed, including two mixed etiology data sets (UK Biobank and FinnGen); one hepatitis C virus (HCV) cohort (STOP-HCV), and one alcohol-related HCC cohort (Dresden HCC).

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Interferon lambdas (IFNλ) (also known as type III IFNs) are critical cytokines that combat infection predominantly at barrier tissues, such as the lung, liver, and gastrointestinal tract. Humans have four IFNλs (1-4), where IFNλ1-3 show ~80%-95% homology, and IFNλ4 is the most divergent displaying only ~30% sequence identity. Variants in IFNλ4 in humans are associated with the outcome of infection, such as with hepatitis C virus.

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Persistent hepatitis C virus (HCV) infection is a major cause of chronic liver disease, worldwide. With the development of direct-acting antivirals, treatment of chronically infected patients has become highly effective, although a subset of patients responds less well to therapy. Sofosbuvir is a common component of current de novo or salvage combination therapies, that targets the HCV NS5B polymerase.

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Background: The present study explored the influence of romantic love on the expression of several obsessive-compulsive disorder (OCD) characteristics, including symptom severity, symptom dimensions, age at onset, sensory phenomena (SP), and developmental course, as well as other related comorbid disorders. It was hypothesized that love-precipitated OCD would be associated with a set of distinct characteristics and exhibit greater rates of comorbid disorders.

Methods: The analyses were performed using a large sample (n = 981) of clinical patients with a primary diagnosis of OCD (Females = 67.

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Sustained viral response (SVR) rates for direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection routinely exceed 95%. However, a small number of patients require retreatment. Sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) is a potent DAA combination primarily used for the retreatment of patients who failed by DAA therapies.

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Background: Chronic hepatitis C virus (HCV) infection affects 71 million individuals, mostly residing in low- and middle-income countries (LMICs). Direct-acting antivirals (DAAs) give high rates of sustained virological response (SVR) in high-income countries where a restricted range of HCV genotypes/subtypes circulate.

Methods: We studied United Kingdom-resident patients born in Africa to examine DAA effectiveness in LMICs where there is far greater breadth of HCV genotypes/subtypes.

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Host haplotype status contributes to the development of chronic hepatitis C virus (HCV) infection in individuals who are acutely infected with the virus. studies revealed that specific amino acid variants at multiple sites on the HCV polyprotein correlate with functional single-nucleotide polymorphisms (SNPs) in the locus. Thus, SNPs at the locus may select variants that influence virus replication and thereby the outcome of infection.

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Article Synopsis
  • The study investigates the persistent infection mechanisms of hepatitis C virus (HCV) and how its RNA structure contributes to liver disease, highlighting that the genomic RNA has specific ordered structures linked to viral persistence.
  • Using new methods to analyze HCV's RNA structure, researchers found that while certain regions were conserved, variability existed in non-coding areas, particularly between different HCV subtypes, indicating evolutionary changes influenced by the host's genetics.
  • Findings showed that the host's genetic factors, like the rs12979860 SNP genotype, impact the virus's RNA structure and response to treatment, suggesting a complex interaction between HCV and the host's immune system that affects disease progression and viral adaptation.
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IFNs, produced during viral infections, induce the expression of hundreds of IFN-stimulated genes (ISGs). Some ISGs have specific antiviral activity, whereas others regulate the cellular response. Besides functioning as an antiviral effector, ISG15 is a negative regulator of IFN signaling, and inherited ISG15 deficiency leads to autoinflammatory IFNopathies, in which individuals exhibit elevated ISG expression in the absence of pathogenic infection.

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The treatment of hepatitis C virus (HCV) infection has been revolutionised by the advent of oral, well-tolerated, direct acting antiviral therapies (DAA), with high cure rates. However, in some scenarios, HCV resistance to antiviral therapies may have an impact on treatment success. Public Health England's HCV Resistance Group was established to support clinicians treating people with HCV, where the issue of resistance may be a factor in clinical decision-making, and this review includes the Group's current recommendations on the use of HCV resistance testing.

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Hepatitis C virus (HCV) is a highly variable pathogen that frequently establishes chronic infection. This genetic variability is affected by the adaptive immune response but the contribution of other host factors is unclear. Here, we examined the role played by interferon lambda-4 (IFN-λ4) on HCV diversity; IFN-λ4 plays a crucial role in spontaneous clearance or establishment of chronicity following acute infection.

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Hepatitis C virus (HCV) genotype 3 is very prevalent in Europe and Asia and is associated with worst outcomes than other genotypes. Genetic factors have been associated with HCV infection; however, no extensive genome-wide study has been performed among HCV genotype 3 patients. In this study, using a large cohort of 1,759 patients infected with HCV genotype 3, we explore the role of genetic variants on the response to interferon (IFN) and direct-acting antiviral (DAA) regimens and viremia in a combined candidate gene and genome-wide analysis.

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Background & Aims: Sofosbuvir is a frequently used pan-genotype inhibitor of hepatitis C virus (HCV) polymerase. This drug eliminates most chronic HCV infections, and resistance-associated substitutions in the polymerase are rare. However, HCV genotype 3 responds slightly less well to sofosbuvir-based therapies than other genotypes.

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Article Synopsis
  • Deep sequencing technologies, like Illumina, allow researchers to analyze viral RNA populations and uncover the diversity of viral genomes within individual hosts.
  • Various software and pipelines can convert raw sequencing data into Sequence Alignment Mapping (SAM) files, enabling analysis of viral variants.
  • The samReporter tool effectively processes these SAM files by translating reads into amino acids, leading to more accurate interpretations of viral resistance mutations compared to methods that don't maintain linkage, as demonstrated in a study of HCV patients.
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