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The case for precision medicine in the prevention, diagnosis, and treatment of cardiometabolic diseases in low-income and middle-income countries

Cardiometabolic diseases are the leading preventable causes of death in most geographies. The causes, clinical presentations, and pathogenesis of cardiometabolic diseases vary greatly worldwide, as do the resources and strategies needed to prevent and treat them. Therefore, there is no single solution and health care should be optimised, if not to the individual (ie, personalised health care), the

Understanding diabetes heterogeneity : key steps towards precision medicine in diabetes

Diabetes is a highly heterogeneous condition; yet, it is diagnosed by measuring a single blood-borne metabolite, glucose, irrespective of aetiology. Although pragmatically helpful, disease classification can become complex and limit advances in research and medical care. Here, we describe diabetes heterogeneity, highlighting recent approaches that could facilitate management by integrating three d

Human Genetic Variation at rs10071329 Correlates with Adiposity-related Traits, Modulates PPARGC1B Expression, and Alters Brown Adipocyte Function

Human genetic variation in PPARGC1B has been associated with adiposity, but the genetic variants that affect PPARGC1B expression have not been experimentally determined. Here, guided by previous observational data, we used CRISPR/Cas9 to scarlessly edit the alleles of the candidate causal genetic variant rs10071329 in a human brown adipocyte cell line (hBAs). Switching the rs10071329 genotype from

Microwave power harvesting using resonator-coupled double quantum dot photodiode

We demonstrate a microwave power-to-electrical energy conversion in a resonator-coupled double quantum dot. The system, operated as a photodiode, converts individual microwave photons to electrons tunneling through the double dot, resulting in an electrical current flowing against the applied voltage bias at input powers down to 1 fW. The device attains a maximum power harvesting efficiency of 2%,

DNA digestion and formation of DNA-network structures with Holliday junction-resolving enzyme Hjc_15-6 in conjunction with polymerase reactions

The recently identified novel Holliday junction-resolving enzyme, termed Hjc_15-6, activity investigation results imply DNA cleavage by Hjc_15-6 in a manner that potentially enhances the molecular self-assembly that may be exploited for creating DNA-networks and nanostructures. The study also demonstrates Pwo DNA polymerase acting in combination with Hjc_15-6 capability to produce large amounts of

Inflammation-related proteins in blood after dermal exposure to some common chemicals depend on the skin barrier gene filaggrin - a human experimental study

Filaggrin (FLG), a skin barrier protein, is associated with higher dermal uptake of some chemicals in carriers of loss-of-function (null) mutations. This study investigates FLG mutations and systemic effects following dermal exposure to chemicals. Individuals (n = 23 FLG null, n = 31 FLG wt) were simultaneously exposed to pyrimethanil, pyrene, oxybenzone, and nickel ions for 4 h. Pre- and post-exp

Persistent pain and its predictors after starting anti-tumour necrosis factor therapy in psoriatic arthritis : what is the role of inflammation control?

Objective: While considerable focus has been placed on pain due to inflammation in psoriatic arthritis (PsA), less is reported on pain despite inflammation control. Here, we aimed to investigate the occurrence/predictors of persistent pain, including non-inflammatory components, after starting anti-tumour necrosis factor (anti-TNF) therapy. Method: Bionaïve PsA patients starting a first anti-TNF t

On the influence of carbides in laser-cladded coating on friction, wear, and airborne particle emissions of disc brakes

Recently, it has become a focus to reduce non-exhaust aerosol emissions from the transport sector. One possible way to decrease brake particle emissions is by laser-cladding coatings onto brake discs. This work tested five different laser-cladding coated brake discs against a non-asbestos organic brake pad. The performance of these coatings was compared to a commercial grey cast iron brake disc te

Cationic Polymer Brushes Functionalized with Carbon Dots and Boronic Acids for Bacterial Detection and Inactivation

Drug-resistant bacterial infections are among the most severe physiological challenges facing human health. Therefore, the detection and inactivation of pathogenic bacteria remains a crucial therapeutic goal in modern society. In this study, we design multifunctional nanocomposites aimed at bacterial binding, fluorescence labeling, and synergistic antibacterial treatment. These nanocomposites are

Increased prevalence of osteopenia and osteoporosis in systemic sclerosis patients, including in men and young women—a case–control study

ObjectivesTo investigate bone mineral density (BMD), osteoporosis prevalence and SSc-specific associations of BMD in SSc patients compared with background population.MethodsIn total, 211 SSc patients (182 women, 29 men; mean age 61.3 and 62.2 years, respectively) and 505 age- and sex-matched controls from the same geographic area participated. BMD and T-score at total hip and lumbar spine was meas

Cyanobacterial Argonautes and Cas4 family nucleases cooperate to interfere with invading DNA

Prokaryotic Argonaute proteins (pAgos) from the long-A clade are stand-alone immune systems that use small interfering DNA (siDNA) guides to recognize and cleave invading plasmid and virus DNA. Certain long-A pAgos are co-encoded with accessory proteins with unknown functions. Here, we show that cyanobacterial long-A pAgos act in conjunction with Argonaute-associated Cas4 family enzyme 1 (ACE1). S

PIONEER big data platform for prostate cancer: lessons for advancing future real-world evidence research

Prostate Cancer Diagnosis and Treatment Enhancement through the Power of Big Data in Europe (PIONEER) is a European network of excellence for big data in prostate cancer. PIONEER brings together 34 private and public stakeholders from 9 countries in one multidisciplinary research consortium with the aim of positively transforming the field of prostate cancer clinical care by answering pressing que

Translation and Linguistic Validation of the Multidimensional Dyspnoea Profile into Telugu in a Palliative Care Setting

Objectives: Dyspnea, or breathlessness, is a frequent and distressing symptom among patients with heart and lung diseases, particularly in advanced cancer stages, where it affects up to 90% of lung cancer cases. This symptom considerably diminishes quality of life, leading to physical deconditioning, increased levels of anxiety and depression, repeated hospitalizations, and elevated mortality rate

Methodologies for velocimetry and flow visualization in supersonic flows enabled by CO2 seeding

A high spatiotemporal resolution technique for instantaneous flow field measurement has been developed, enabling one-dimensional velocimetry and flow field visualization within a converging–diverging nozzle. By employing femtosecond laser-induced long-lived, high-intensity plasma emission in a CO2/N2 gas flow, coupled with an ICCD camera, we achieved instantaneous one-dimensional velocity measurem

Transport of Dipolar Excitons at the Type-II Polytype Interface of InP Platelets

The pursuit of high charge carrier mobility in nanostructures is crucial for advancing both device development and exploring fundamental physics. This study focuses on minimizing scattering to achieve high mobility, employing a polytype type-II interface formed between wurtzite and zincblende InP. On the zincblende side, electrons accumulate, while holes gather on the wurtzite side, resulting in t

Peripherally administered TNF inhibitor is not protective against α-synuclein-induced dopaminergic neuronal death in rats

The underlying cause of neuronal loss in Parkinson's disease (PD) remains unknown, but evidence implicates neuroinflammation in PD pathobiology. The pro-inflammatory cytokine soluble tumor necrosis factor (TNF) seems to play an important role and thus has been proposed as a therapeutic target for modulation of the neuroinflammatory processes in PD. In this regard, dominant-negative TNF (DN-TNF) ag

Temporal artery biopsy in giant cell arteritis : clinical perspectives and histological patterns

Although its role has been debated, temporal artery biopsy (TAB) remains the gold standard for the diagnosis of cranial giant cell arteritis (GCA). The specificity of TAB is excellent and the sensitivity, albeit lower, is comparable with other diagnostic modalities used for the diagnosis of GCA. This outpatient procedure has a low rate of complications and is well integrated in the majority of hea