Viral kinetics of sequential SARS-CoV-2 infections.

The impact of a prior SARS-CoV-2 infection on the progression of subsequent infections has been unclear. Using a convenience sample of 94,812 longitudinal RT-qPCR measurements from anterior nares and oropharyngeal swabs, we identified 71 individuals with two well-sampled SARS-CoV-2 infections between March 11, 2020, and July 28, 2022. We compared the SARS-CoV-2 viral kinetics of first vs.

Prediction of cancer treatment response from histopathology images through imputed transcriptomics.

Advances in artificial intelligence have paved the way for leveraging hematoxylin and eosin (H&E)-stained tumor slides for precision oncology. We present ENLIGHT-DeepPT, an approach for predicting response to multiple targeted and immunotherapies from H&E-slides. In difference from existing approaches that aim to predict treatment response directly from the slides, ENLIGHT-DeepPT is an indirect two-step approach consisting of (1) DeepPT, a new deep-learning framework that predicts genome-wide tumor mRNA expression from slides, and (2) ENLIGHT, which predicts response based on the DeepPT inferred expression values.

KCNQ potassium channels modulate Wnt activity in gastro-oesophageal adenocarcinomas.

Voltage-sensitive potassium channels play an important role in controlling membrane potential and ionic homeostasis in the gut and have been implicated in gastrointestinal (GI) cancers. Through large-scale analysis of 897 patients with gastro-oesophageal adenocarcinomas (GOAs) coupled with in vitro models, we find family genes are mutated in ∼30% of patients, and play therapeutically targetable roles in GOA cancer growth. and mediate the WNT pathway and MYC to increase proliferation through resultant effects on cadherin junctions.

Geographical distribution of scrub typhus and risk of Orientia tsutsugamushi infection in Indonesia: Evidence mapping.

Background: Scrub typhus is a potentially fatal acute febrile illness caused by bacteria in the genus Orientia. Though cases have been documented, a comprehensive body of evidence has not previously been compiled to give an overview of scrub typhus in Indonesia. This study aimed to address this key knowledge gap by mapping and ranking geographic areas based on existing data on the presence or absence of the pathogen in humans, vectors, and host animals.

Dual-modality imaging of immunofluorescence and imaging mass cytometry for whole-slide imaging and accurate segmentation.

Imaging mass cytometry (IMC) is a powerful technique capable of detecting over 30 markers on a single slide. It has been increasingly used for single-cell-based spatial phenotyping in a wide range of samples. However, it only acquires a rectangle field of view (FOV) with a relatively small size and low image resolution, which hinders downstream analysis.

Genic constraint against nonsynonymous variation across the mouse genome.

Background: Selective constraint, the depletion of variation due to negative selection, provides insights into the functional impact of variants and disease mechanisms. However, its characterization in mice, the most commonly used mammalian model, remains limited. This study aims to quantify mouse gene constraint using a new metric called the nonsynonymous observed expected ratio (NOER) and investigate its relationship with gene function.

Integrating Artificial Intelligence Tools in the Clinical Research Setting: The Ovarian Cancer Use Case.

Artificial intelligence (AI) methods applied to healthcare problems have shown enormous potential to alleviate the burden of health services worldwide and to improve the accuracy and reproducibility of predictions. In particular, developments in computer vision are creating a paradigm shift in the analysis of radiological images, where AI tools are already capable of automatically detecting and precisely delineating tumours. However, such tools are generally developed in technical departments that continue to be siloed from where the real benefit would be achieved with their usage.

Response to anti-IL17 therapy in inflammatory disease is not strongly impacted by genetic background.

Response to the anti-IL17 monoclonal antibody secukinumab is heterogeneous, and not all participants respond to treatment. Understanding whether this heterogeneity is driven by genetic variation is a key aim of pharmacogenetics and could influence precision medicine approaches in inflammatory diseases. Using changes in disease activity scores across 5,218 genotyped individuals from 19 clinical trials across four indications (psoriatic arthritis, psoriasis, ankylosing spondylitis, and rheumatoid arthritis), we tested whether genetics predicted response to secukinumab.

Characterising personal, household, and community PM exposure in one urban and two rural communities in China.

Background: Cooking and heating in households contribute importantly to air pollution exposure worldwide. However, there is insufficient investigation of measured fine particulate matter (PM) exposure levels, variability, seasonality, and inter-spatial dynamics associated with these behaviours.

Methods: We undertook parallel measurements of personal, household (kitchen and living room), and community PM in summer (May-September 2017) and winter (November 2017-Janauary 2018) in 477 participants from one urban and two rural communities in China.

Pregnancy-Associated Bleeding and Genetics: Five Sequence Variants in the Myometrium and Progesterone Signaling Pathway are associated with postpartum hemorrhage.

Bleeding in early pregnancy and postpartum hemorrhage (PPH) bear substantial risks, with the former closely associated with pregnancy loss and the latter being the foremost cause of maternal death, underscoring the severity of these complications in maternal-fetal health. Here, we investigated the genetic variation underlying aspects of pregnancy-associated bleeding and identified five loci associated with PPH through a meta-analysis of 21,512 cases and 259,500 controls. Functional annotation analysis indicated candidate genes, , , and / at three loci and showed that at each locus, associated variants were located within binding sites for progesterone receptors (PGR).

Diagnostic performance of Strongyloides-specific IgG4 detection in urine for diagnosis of human strongyloidiasis.

Background: Detection of parasite-specific IgG in urine is a sensitive method for diagnosis of strongyloidiasis and gives similar accuracy to serum IgG. However, there are no data concerning detection of IgG subclass in urine. To further explore the utility of diagnosis from urine samples, we evaluated the diagnostic performance of IgG4 in urine compared with parasitological and other immunological methods.

Neuroscience Needs Network Science.

The brain is a complex system comprising a myriad of interacting neurons, posing significant challenges in understanding its structure, function, and dynamics. Network science has emerged as a powerful tool for studying such interconnected systems, offering a framework for integrating multiscale data and complexity. To date, network methods have significantly advanced functional imaging studies of the human brain and have facilitated the development of control theory-based applications for directing brain activity.

Topic modeling identifies novel genetic loci associated with multimorbidities in UK Biobank.

Many diseases show patterns of co-occurrence, possibly driven by systemic dysregulation of underlying processes affecting multiple traits. We have developed a method (treeLFA) for identifying such multimorbidities from routine health-care data, which combines topic modeling with an informative prior derived from medical ontology. We apply treeLFA to UK Biobank data and identify a variety of topics representing multimorbidity clusters, including a healthy topic.

A modelling analysis of a new multi-stage pathway for classifying achievement of public health milestones for leprosy.

Several countries have come close to eliminating leprosy, but leprosy cases continue to be detected at low levels. Due to the long, highly variable delay from infection to detection, the relationship between observed cases and transmission is uncertain. The World Health Organization's new technical guidance provides a path for countries to reach elimination.

Modelling morbidity for neglected tropical diseases: the long and winding road from cumulative exposure to long-term pathology.

Reducing the morbidities caused by neglected tropical diseases (NTDs) is a central aim of ongoing disease control programmes. The broad spectrum of pathogens under the umbrella of NTDs lead to a range of negative health outcomes, from malnutrition and anaemia to organ failure, blindness and carcinogenesis. For some NTDs, the most severe clinical manifestations develop over many years of chronic or repeated infection.

Plasmids pick a bacterial partner before committing to conjugation.

Bacterial conjugation was first described by Lederberg and Tatum in the 1940s following the discovery of the F plasmid. During conjugation a plasmid is transferred unidirectionally from one bacterium (the donor) to another (the recipient), in a contact-dependent manner. Conjugation has been regarded as a promiscuous mechanism of DNA transfer, with host range determined by the recipient downstream of plasmid transfer.

Genome-wide association studies reveal novel loci associated with pyrethroid and organophosphate resistance in Anopheles gambiae and Anopheles coluzzii.

Resistance to insecticides in Anopheles mosquitoes threatens the effectiveness of malaria control, but the genetics of resistance are only partially understood. We performed a large scale multi-country genome-wide association study of resistance to two widely used insecticides: deltamethrin and pirimiphos-methyl, using sequencing data from An. gambiae and An.