Total serum N-glycans associate with response to immune checkpoint inhibition therapy and survival in patients with advanced melanoma.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of melanoma and other cancers. However, no reliable biomarker of survival or response has entered the clinic to identify those patients with melanoma who are most likely to benefit from ICIs. Glycosylation affects proteins and lipids' structure and functions.

Escape from X-inactivation in twins exhibits intra- and inter-individual variability across tissues and is heritable.

X-chromosome inactivation (XCI) silences one X in female cells to balance sex-differences in X-dosage. A subset of X-linked genes escape XCI, but the extent to which this phenomenon occurs and how it varies across tissues and in a population is as yet unclear. To characterize incidence and variability of escape across individuals and tissues, we conducted a transcriptomic study of escape in adipose, skin, lymphoblastoid cell lines and immune cells in 248 healthy individuals exhibiting skewed XCI.

Rare and common genetic determinants of metabolic individuality and their effects on human health.

Garrod's concept of 'chemical individuality' has contributed to comprehension of the molecular origins of human diseases. Untargeted high-throughput metabolomic technologies provide an in-depth snapshot of human metabolism at scale. We studied the genetic architecture of the human plasma metabolome using 913 metabolites assayed in 19,994 individuals and identified 2,599 variant-metabolite associations (P < 1.

Circulating inflammatory proteins associate with response to immune checkpoint inhibition therapy in patients with advanced melanoma.

Background: Inflammation can modulate tumour growth and progression, and influence clinical response to treatment. We investigated the potential of circulating inflammatory proteins for response stratification of immune checkpoint inhibitor (ICI) therapy for advanced melanoma.

Methods: Study subjects were 87 patients with unresectable stage III or IV cutaneous melanoma from the multiple centres across the United Kingdom (UK) and the Netherlands (NL) who received ipilimumab, nivolumab, or pembrolizumab, or a combination of ipilimumab and nivolumab.

Cutaneous manifestations of SARS-CoV-2 infection during the Delta and Omicron waves in 348 691 UK users of the UK ZOE COVID Study app.

Background: Symptoms of SARS-CoV-2 infection have differed during the different waves of the pandemic but little is known about how cutaneous manifestations have changed.

Objectives: To investigate the diagnostic value, frequency and duration of cutaneous manifestations of SARS-CoV-2 infection and to explore their variations between the Delta and Omicron waves of the pandemic.

Methods: In this retrospective study, we used self-reported data from 348 691 UK users of the ZOE COVID Study app, matched 1 : 1 for age, sex, vaccination status and self-reported eczema diagnosis between the Delta and Omicron waves, to assess the diagnostic value, frequency and duration of five cutaneous manifestations of SARS-CoV-2 infection (acral, burning, erythematopapular and urticarial rash, and unusual hair loss), and how these changed between waves.

miRNAs as Molecular Biomarkers for Prostate Cancer.

miRNAs are short noncoding RNAs able to regulate specific mRNA stability, thus influencing target gene expression. Disrupted levels of several miRNAs have been associated with prostate cancer (PC), the leading cause of cancer death among men and the fifth leading cause of death worldwide. Herein, we investigated whether miR-145, miR-148, and miR-185 circulating levels in plasma could be used as molecular biomarkers, to allow distinguishing between individuals with benign prostatic hyperplasia, precancerous lesions, and PC.

Immune Trait Shifts in Association With Tobacco Smoking: A Study in Healthy Women.

Tobacco smoking is known to impact circulating levels of major immune cells populations, but its effect on specific immune cell subsets remains poorly understood. Here, using high-resolution data from 223 healthy women (25 current and 198 never smokers), we investigated the association between smoking status and 35,651 immune traits capturing immune cell subset frequencies. Our results confirmed that active tobacco smoking is associated with increased frequencies of circulating CD8+ T cells expressing the CD25 activation marker.

Ethnic-specific association of amylase gene copy number with adiposity traits in a large Middle Eastern biobank.

Studies assessing the impact of amylase genes copy number (CN) on adiposity report conflicting findings in different global populations, likely reflecting the impact of ancestral and ethnic-specific environment and lifestyle on selection at the amylase loci. Here, we leverage population size and detailed adiposity measures from a large population biobank to resolve confounding effects and determine the relationship between salivary (AMY1) and pancreatic (AMY2A) amylase genes CN and adiposity in 2935 Qatari individuals who underwent whole-genome sequencing (WGS) as part of the Qatar Genome Programme. We observe a negative association between AMY1 CNs and trunk fat percentage in the Qatari population (P = 7.

Current smoking and COVID-19 risk: results from a population symptom app in over 2.4 million people.

Background: The association between current tobacco smoking, the risk of developing symptomatic COVID-19 and the severity of illness is an important information gap.

Methods: UK users of the Zoe COVID-19 Symptom Study app provided baseline data including demographics, anthropometrics, smoking status and medical conditions, and were asked to log their condition daily. Participants who reported that they did not feel physically normal were then asked by the app to complete a series of questions, including 14 potential COVID-19 symptoms and about hospital attendance.

Interplay between the human gut microbiome and host metabolism.

The human gut is inhabited by a complex and metabolically active microbial ecosystem. While many studies focused on the effect of individual microbial taxa on human health, their overall metabolic potential has been under-explored. Using whole-metagenome shotgun sequencing data in 1,004 twins, we first observed that unrelated subjects share, on average, almost double the number of metabolic pathways (82%) than species (43%).