Distinct virologic trajectories in chronic hepatitis B identify heterogeneity in response to nucleos(t)ide analogue therapy.

Background & Aims: The dynamics of HBV viral load (VL) in patients with chronic hepatitis B (CHB) on nucleos(t)ide analogue (NA) treatment and its relationship with liver disease are poorly understood. We aimed to study longitudinal VL patterns and their associations with CHB clinical outcomes.

Methods: Utilising large scale, routinely collected electronic health records from six centres in England, collated by the National Institute for Health and Care Research Health Informatics Collaborative (NIHR HIC), we applied latent class mixed models to investigate VL trajectory patterns in adults receiving NA treatment.

Footprint of sustained poleward warm water flow within East Antarctic submarine canyons.

The intrusion of relatively warm water onto the continental shelf is widely recognized as a threat to Antarctic ice shelves and glaciers grounded below sea level, as enhanced ocean heat increases their basal melt. While the circulation of warm water has been documented on the East Antarctic continental shelf, the modes of warm water transport from the deep ocean onto the shelf are still uncertain. This makes predicting the future responses of major East Antarctic marine-grounded glaciers, such as Totten and Ninnis glaciers, particularly challenging.

KLF4 in smooth muscle cell-derived progenitor cells is essential for angiotensin II-induced cardiac inflammation and fibrosis.

Cardiac fibrosis is defined by the excessive accumulation of extracellular matrix (ECM) material resulting in cardiac tissue scarring and dysfunction. While it is commonly accepted that myofibroblasts are the major contributors to ECM deposition in cardiac fibrosis, their origin remains debated. By combining lineage tracing and RNA sequencing, our group made the paradigm-shifting discovery that a subpopulation of resident vascular stem cells residing within the aortic, carotid artery, and femoral aartery adventitia (termed AdvSca1-SM cells) originate from mature vascular smooth muscle cells (SMCs) through an reprogramming process.

Challenges and solutions to system-wide use of precision oncology as the standard of care paradigm.

The personalised oncology paradigm remains challenging to deliver despite technological advances in genomics-based identification of actionable variants combined with the increasing focus of drug development on these specific targets. To ensure we continue to build concerted momentum to improve outcomes across all cancer types, financial, technological and operational barriers need to be addressed. For example, complete integration and certification of the 'molecular tumour board' into 'standard of care' ensures a unified clinical decision pathway that both counteracts fragmentation and is the cornerstone of evidence-based delivery inside and outside of a research setting.

Cell Cycle-Dependent TICRR/TRESLIN and MTBP Chromatin Binding Mechanisms and Patterns.

The selection of replication origins is a defining characteristic of DNA replication in eukaryotes, yet its mechanism in humans has not been well-defined. In this study, we use Cut&Run to examine genomic binding locations for TICRR/TRESLIN and MTBP, the human orthologs for the yeast DNA replication initiation factors Sld3 and Sld7. We mapped TRESLIN and MTBP binding in HCT116 colorectal cancer cells using asynchronous and G1 synchronized populations.

Smooth muscle-derived adventitial progenitor cells direct atherosclerotic plaque composition complexity in a Klf4-dependent manner.

We previously established that vascular smooth muscle-derived adventitial progenitor cells (AdvSca1-SM) preferentially differentiate into myofibroblasts and contribute to fibrosis in response to acute vascular injury. However, the role of these progenitor cells in chronic atherosclerosis has not been defined. Using an AdvSca1-SM cell lineage tracing model, scRNA-Seq, flow cytometry, and histological approaches, we confirmed that AdvSca1-SM-derived cells localized throughout the vessel wall and atherosclerotic plaques, where they primarily differentiated into fibroblasts, smooth muscle cells (SMC), or remained in a stem-like state.

Confounding Effects of Tamoxifen: Cautionary and Practical Considerations for the Use of Tamoxifen-Inducible Mouse Models in Atherosclerosis Research-Brief Report.

Background: In recent years, fate-mapping lineage studies in mouse models have led to major advances in vascular biology by allowing investigators to track specific cell populations in vivo. One of the most frequently used lineage tracing approaches involves tamoxifen-inducible Cre-LoxP systems. However, tamoxifen treatment can also promote effects independent of Cre recombinase activation, many of which have not been fully explored.

Smooth muscle-derived adventitial progenitor cells promote key cell type transitions controlling plaque stability in atherosclerosis in a Klf4-dependent manner.

We previously established that vascular smooth muscle-derived adventitial progenitor cells (AdvSca1-SM) preferentially differentiate into myofibroblasts and contribute to fibrosis in response to acute vascular injury. However, the role of these progenitor cells in chronic atherosclerosis has not been defined. Using an AdvSca1-SM lineage tracing model, scRNA-Seq, flow cytometry, and histological approaches, we confirmed that AdvSca1-SM cells localize throughout the vessel wall and atherosclerotic plaques, where they primarily differentiate into fibroblasts, SMCs, or remain in a stem-like state.

Demographic history and distinct selection signatures of two domestication genes in mungbean.

Domestication is the long and complex process underlying the evolution of crops, in which artificial directional selection transformed wild progenitors into the desired form, affecting genomic variation and leaving traces of selection at targeted loci. However, whether genes controlling important domestication traits follow the same evolutionary pattern expected under the standard selective sweep model remains unclear. With whole-genome resequencing of mungbean (Vigna radiata), we investigated this issue by resolving its global demographic history and targeted dissection of the molecular footprints of genes underlying 2 key traits representing different stages of domestication.

Environment as a limiting factor of the historical global spread of mungbean.

While the domestication process has been investigated in many crops, the detailed route of cultivation range expansion and factors governing this process received relatively little attention. Here, using mungbean ( var. ) as a test case, we investigated the genomes of more than 1000 accessions to illustrate climatic adaptation's role in dictating the unique routes of cultivation range expansion.

The role of virtual reality as adjunctive therapy to spinal cord stimulation in chronic pain: A feasible concept?

Spinal cord stimulation and virtual reality therapy are established and promising techniques, respectively, for managing chronic pain, each with its unique advantages and challenges. While each therapy has been the subject of significant research interest, the prospect of combining the two modalities to offer a synergistic effect in chronic pain therapy is still in its infancy. In this narrative review, we assess the state of the field combining virtual reality as an adjunctive therapy to spinal cord stimulation in chronic pain.

Intensification of Penaeid Shrimp Culture: An Applied Review of Advances in Production Systems, Nutrition and Breeding.

Intensification of the shrimp sector, also referred to as vertical expansion, has been predominately driven by consecutive incidences of global disease outbreaks, which have caused enormous economic loss for the main producer countries. A growing segment of the shrimp farming industry has opted to use production systems with higher density, biosecurity, and operating control to mitigate the risks posed by disease. However, successful super-intensive shrimp production is reliant on an advanced understanding of many important biological and economic parameters in the farming system, coupled with effective monitoring, to maintain optimal production.

A Narrative Analysis of the Progression in the Top 100 Marathon, Half-Marathon, and 10-km Road Race Times from 2001 to 2019.

Purpose: This study aimed to characterize and describe finishing time trends of the fastest 100 performers in the men's and women's marathon, half-marathon, and road 10-km each year from 2001 to 2019 and assess the underlying basis for recent performance improvements.

Methods: The top 100 performers for each sex, event, and year were partitioned into four arbitrary ranking groups: 1-10, 11-25, 26-50, and 51-100. The percent improvement in mean performance time for each year beyond 2001 was calculated for each ranking group, event, and sex.

Impact of COVID-19 on mobility and participation of older adults living in Hamilton, Ontario, Canada: a multimethod cohort design protocol.

Introduction: The novel COVID-19 required many countries to impose public health measures that likely impacted the participation and mobility of community-dwelling older adults. This protocol details a multimethod cohort design undertaken to describe short-term and medium-term changes to the mobility and participation of older Canadians living in the community rather than retirement facilities during the COVID-19 pandemic.

Methods And Analysis: A longitudinal telephone (or online)-administered survey is being conducted with a random sample of older adults living within 20 km of McMaster University, Hamilton, Ontario, Canada, identified from census dissemination areas.

The CRL4DTL E3 ligase induces degradation of the DNA replication initiation factor TICRR/TRESLIN specifically during S phase.

A DNA replication program, which ensures that the genome is accurately and wholly replicated, is established during G1, before the onset of S phase. In G1, replication origins are licensed, and upon S phase entry, a subset of these will form active replisomes. Tight regulation of the number of active replisomes is crucial to prevent replication stress-induced DNA damage.

Longitudinal Analysis of the Utility of Liver Biochemistry as Prognostic Markers in Hospitalized Patients With Corona Virus Disease 2019.

The association of liver biochemistry with clinical outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is currently unclear, and the utility of longitudinally measured liver biochemistry as prognostic markers for mortality is unknown. We aimed to determine whether abnormal liver biochemistry, assessed at baseline and at repeat measures over time, was associated with death in hospitalized patients with COVID-19 compared to those without COVID-19, in a United Kingdom population. We extracted routinely collected clinical data from a large teaching hospital in the United Kingdom, matching 585 hospitalized patients who were SARS-CoV-2 real-time reverse transcription-polymerase chain reaction (RT-PCR) positive to 1,165 hospitalized patients who were RT-PCR negative for age, sex, ethnicity, and preexisting comorbidities.

Hepatitis B virus (HBV) viral load, liver and renal function in adults treated with tenofovir disoproxil fumarate (TDF) vs. untreated: a retrospective longitudinal UK cohort study.

Background: Current clinical guidelines recommend treating chronic hepatitis B virus (HBV) infection in a minority of cases, but there are relatively scarce data on evolution or progression of liver inflammation and fibrosis in cases of chronic HBV (CHB) that do not meet treatment criteria. We aimed to assess the impact of TDF on liver disease, and the risk of renal impairment in treated CHB patients in comparison to untreated patients.

Methods: We studied a longitudinal ethnically diverse CHB cohort in the UK attending out-patient clinics between 2005 and 2018.

Effect of sample type and the use of high or low fishmeal diets on bacterial communities in the gastrointestinal tract of Penaeus monodon.

In shrimp aquaculture, manufactured diets that include various supplements and alternative fishmeal ingredients are increasingly being used and their effect on the gastrointestinal (GI) microbiota studied. However, dietary effects on different shrimp GI samples are not known. We investigated how a high (HFM) or low (LFM) fishmeal diet affects bacterial communities from different sample types collected from Penaeus monodon gastrointestinal tract.

Transfer learning efficiently maps bone marrow cell types from mouse to human using single-cell RNA sequencing.

Biomedical research often involves conducting experiments on model organisms in the anticipation that the biology learnt will transfer to humans. Previous comparative studies of mouse and human tissues were limited by the use of bulk-cell material. Here we show that transfer learning-the branch of machine learning that concerns passing information from one domain to another-can be used to efficiently map bone marrow biology between species, using data obtained from single-cell RNA sequencing.

A SNP-Based Genome-Wide Association Study to Mine Genetic Loci Associated to Salinity Tolerance in Mungbean ( L.).

Mungbean ( (L.) R. Wilzeck var.

Shrub and vegetation cover predict resource selection use by an endangered species of desert lizard.

Globally, no species is exempt from the constraints associated with limited available habitat or resources, and endangered species in particular warrant critical examination. In most cases, these species are restricted to limited locations, and the relative likelihood of resource use within the space they can access is important. Using Gambelia sila, one of the first vertebrate species listed as endangered, we used resource selection function analysis of telemetry and remotely sensed data to identity key drivers of selected versus available locations for this species in Carrizo Plain National Monument, USA.

Pre-concentration of thorium and neodymium isotopes using Nobias chelating resin: Method development and application to chromatographic separation.

The isotopes of thorium (Th) and neodymium (Nd) are used as tracers in oceanography, and are key parameters in the international GEOTRACES program. The very low concentrations of Th and Nd as well as the reactive nature of Th isotopes makes the analysis of seawater samples a complex process. Analysis requires time-consuming pre-concentration from over 5 L of seawater.