Extrinsic and intrinsic effects setting viscosity in complex fluids and life processes: the role of fundamental physical constants.

Understanding the values and origin of fundamental physical constants, one of the grandest challenges in modern science, has been discussed in particle physics, astronomy and cosmology. More recently, it was realized that fundamental constants have a biofriendly window set by life processes involving motion and flow. This window is related to intrinsic fluid properties such as energy and length scales in condensed matter set by fundamental constants.

The Landmark Series: Neoadjuvant Radiotherapy in Extremity Soft Tissue Sarcoma-The Way to Hypofractionation.

For patients with nonmetastatic soft tissue sarcoma (STS) who are at high risk of local recurrence, the standard of care for limb-conserving local management is combined radiotherapy and surgery. Radiotherapy for STS entails 5 weeks of conventionally fractionated radiotherapy (25 × 2 Gy) preoperatively or 6 or more weeks postoperatively. There is growing interest in the use of preoperative hypofractionated regimes, viz.

Laser speckle contrast imaging with principal component and entropy analysis: a novel approach for depth-independent blood flow assessment.

Current study presents an advanced method for improving the visualization of subsurface blood vessels using laser speckle contrast imaging (LSCI), enhanced through principal component analysis (PCA) filtering. By combining LSCI and laser speckle entropy imaging with PCA filtering, the method effectively separates static and dynamic components of the speckle signal, significantly improving the accuracy of blood flow assessments, even in the presence of static scattering layers located above and below the vessel. Experiments conducted on optical phantoms, with the vessel depths ranging from 0.

Ureteral access sheath or percutaneous nephrostomy during flexible ureteroscopy: which is better?

Studies in literature discussed the drawbacks of the ureteral access sheath use in flexible ureteroscopy and in the same time mentioned the benefits of ureteral access sheath in decreasing the incidence of urosepsis and better stone free rate. In the current study we aim to compare between percutaneous nephrostomy tube (PCN) insertion before flexible ureteroscopy and conventional ureteral access sheath (UAS) flexible ureteroscopy in terms of safety, efficacy and perioperative outcomes. In all, 100 Patients aged 20 to 67 years with upper ureteric stones and mild hydronephrosis or renal pelvic stones less than 20 mm with mild hydronephrosis were randomized into 2 groups; patients undergoing PCN insertion before flexible ureteroscopy, and patients undergoing the conventional UAS flexible ureteroscopy.

Modelling the Impact of HIF on Metabolism and the Extracellular Matrix: Consequences for Tumour Growth and Invasion.

The extracellular matrix (ECM) is a complex structure involved in many biological processes with collagen being the most abundant protein. Density of collagen fibers in the matrix is a factor influencing cell motility and migration speed. In cancer, this affects the ability of cells to migrate and invade distant tissues which is relevant for designing new therapies.

Method to define recommended portion sizes for consumer guidance.

Purpose: Provision of nutrition information is mandated for packaged foods, but few countries regulate serving sizes. Our objective was to develop a methodology to establish globally consistent portion size recommendations for both nutrient-dense and discretionary foods.

Methods: A stepwise systematic approach incorporated portion values from serving size regulations (n = 10), food-based dietary guidelines (FBDG; n = 90, aggregated into 6 regions), and reported food intakes from Europe and Australia.

A morphometric study of posterior tibial slope differences by sex and ethnicity in a South African population.

Purpose: Posterior tibial slope (PTS) influences knee kinetics and kinematics. The purpose of this study was to investigate morphology and variation within a sample of the black and white male and female population.

Method: 480 randomly selected lateral knee radiographs were included.

Identification of biomarkers for chronic lymphocytic leukemia risk: a proteome-wide Mendelian randomization study.

Background: Chronic lymphocytic leukemia (CLL) is a common hematologic malignancy. Although previous research has explored associations between plasma proteins and CLL, the causal relationships remain unclear. This study used Mendelian randomization (MR) to investigate the causal relationship between 7156 plasma proteins and CLL risk.

Health state utilities associated with invasive pneumococcal disease, pneumonia, and recurrent acute otitis media in young children.

Purpose: Cost-utility analyses examining the value of new vaccines for pneumococcal disease will require health state utilities as inputs. Existing utilities for pneumococcal infections in young children are limited. The purpose of this study was to estimate health state utilities associated with pneumococcal infections in young children.

Base of Skull & Spinal Canal Narrowing in an Adolescent with Autosomal Recessive Hypophosphatemic Rickets Type 2.

Autosomal recessive hypophosphatemic rickets type 2 (ARHR2) is an uncommon hereditary form of rickets characterised by chronic renal phosphate loss and impaired bone mineralisation. This results from compound heterozygous or homozygous pathogenic variants in ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), a key producer of extracellular inorganic pyrophosphate (PPi) and an inhibitor of fibroblast growth factor23 (FGF23). ENPP1 deficiency impacts FGF23 and increases its activity.

The Association between Social Support and Musculoskeletal Health in Community-Dwelling Older Adults: Findings from the Hertfordshire Cohort Study.

Previous studies suggest social support is associated with musculoskeletal health in later life. We explored this relationship further in community-dwelling older adults, by considering associations between different aspects of social support and musculoskeletal health in community-dwelling adults. Participants from the Hertfordshire Cohort Study reported level of confiding/emotional, practical, and negative support using the Close Persons Questionnaire.

Critical comparison of BMD and TD methods for the calculation of acceptable intakes for N-nitroso compounds.

The tumorigenic dose 50 (TD) is a widely used measure of carcinogenic potency which has historically been used to determine acceptable intake limits for carcinogenic compounds. Although broadly used, the TD model was not designed to account for important biological factors such as DNA repair and cell compensatory mechanisms, changes in absorption, etc., leading to the development of benchmark dose (BMD) approaches, which use more flexible dose-response models that are better able to account for these processes.

Understanding the Scale and Nature of Parent/Guardian Telephone Calls to a Tertiary Children's Cardiac Centre: A Service Evaluation.

Heart defects are the second most common congenital anomaly in babies born in the UK and standards state families should have access to a children's cardiac nurse specialist telephone advice service. However, there is little published information to describe the nature of calls and the workload associated with telephone support. We conducted a prospective service evaluation of telephone calls received at one UK specialist children's cardiac surgical center from parents/carers (April-June 2019).

Multi-trait Genome-Wide Analysis Identified 20 Novel Loci for Sarcopenia-Related Traits in UK Biobank.

This study aims to identify novel loci associated with sarcopenia-related traits in UK Biobank (UKB) through multi-trait genome-wide analysis. To identify novel loci associated with sarcopenia, we integrated the genome-wide association studies (GWAS) of usual walking pace (UWP) and hand grip strength (HGS) to conduct a joint association study known as multi-trait analysis of GWAS (MTAG). We performed a transcriptome-wide association study (TWAS) to analyze the results of MTAG in relation to mRNA expression data for genes identified in skeletal muscle.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD), characterized by significant brain volume reduction, is influenced by genetic predispositions related to brain volumetric phenotypes. While genome-wide association studies (GWASs) have linked brain imaging-derived phenotypes (IDPs) with AD, existing polygenic risk scores (PRSs) based models inadequately capture this relationship. We develop BrainNetScore, a network-based model enhancing AD risk prediction by integrating genetic associations between multiple brain IDPs and AD incidence.

Quality-by-design principles applied to the development and optimisation of lidocaine-loaded dissolving microneedle arrays - a proof-of-concept.

The use of dissolving microneedle arrays (dMNA) for intradermal and transdermal drug delivery has been a growing trend in the field for the past decades. However, a lack of specific regulatory standards still hinders their clinical development and translation to market. It is also well-known that dMNA composition significantly impacts their performance, with each new formulation potentially presenting a challenge for developers, manufacturers and regulatory agencies.

Basic Science and Pathogenesis.

Background: White matter hyperintensities (WMH) are commonly observed on MRI in Alzheimer's disease (AD), but the molecular pathways underlying their relationships with the ATN biomarkers remain unclear. The aim of this study was to identify genetic variants that may modify the relationship between WMH and the ATN biomarkers.

Method: This genome-wide interaction study (GWIS) included individuals with AD, MCI, and normal cognition from ADNI (n = 1012).

Complex genetic interactions affect susceptibility to Alzheimer's disease risk in the BIN1 and MS4A6A loci.

Genetics is the second strongest risk factor for Alzheimer's disease (AD) after age. More than 70 loci have been implicated in AD susceptibility so far, and the genetic architecture of AD entails both additive and nonadditive contributions from these loci. To better understand nonadditive impact of single-nucleotide polymorphisms (SNPs) on AD risk, we examined individual, joint, and interacting (SNPxSNP) effects of 139 and 66 SNPs mapped to the BIN1 and MS4A6A AD-associated loci, respectively.

SNP rs6543176 is associated with extreme human longevity but increased risk for cancer.

Using whole-genome sequencing (WGS) might offer insights into rare genetic variants associated with healthy aging and extreme longevity (EL), potentially pointing to useful therapeutic targets. In this study, we conducted a genome-wide association study using WGS data from the Long Life Family Study and identified a novel longevity-associated variant rs6543176 in the SLC9A2 gene. This SNP also showed a significant association with reduced hypertension risk and an increased, though not statistically significant, cancer risk.

A Dynamical Analysis of the Alignment Mechanism Between Two Interacting Cells.

In this work we analytically investigate the alignment mechanism of self-propelled ellipse-shaped cells in two spatial dimensions interacting via overlap avoidance. By considering a two-cell system and imposing certain symmetries, we obtain an analytically tractable dynamical system, which we mathematically analyse in detail. We find that for elongated cells there is a half-stable steady state corresponding to perfect alignment between the cells.

Basic Science and Pathogenesis.

Background: Recent research reported that cancer patients had lower risk of Alzheimer's disease (AD). Common signaling pathways, hormonal systems, and genetic predispositions have been hypothesized as important factors contributing to this inverse association. However, the exact mechanisms are still unknown.

Basic Science and Pathogenesis.

Background: Microglia are key players in Alzheimer's disease (AD): Genetic risk for AD is enriched in microglial enhancers, and microglial gene regulatory networks have been shown to be disrupted in AD. Here, we studied polygenic and variant-specific (APOE) risk burden for AD in a xenotransplantation model of AD and human post-mortem brain tissue.

Method: We profiled gene regulation by RNA-seq and ATAC-seq in human iPS-derived microglia, xenotransplanted into the APPNL-G-F mouse model of AD.

Basic Science and Pathogenesis.

Background: Possession of the APOE4 allele is the strongest genetic risk factor for developing the sporadic form of Alzheimer's disease (AD). Studies investigating APOE4's associated AD risk have largely centered on APOE4's propensity to regulate the deposition of extracellular amyloid beta plaques. More recent attempts to characterize APOE4's role in AD have brought into question the role APOE4 may possess in modulating the pathogenesis of intracellular tau tangles.