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Genome sequencing has revealed over 300 million genetic variations in human populations. Over 90% of variants are single nucleotide polymorphisms (SNPs), the remainder include short deletions or insertions, and small numbers of structural variants. Hundreds of thousands of these variants have been associated with specific phenotypic traits and diseases through genome wide association studies which link significant differences in variant frequencies with specific phenotypes among large groups of individuals. Only 5% of disease-associated SNPs are located in gene coding sequences, with the potential to disrupt gene expression or alter of the function of encoded proteins. The remaining 95% of disease-associated SNPs are located in non-coding DNA sequences which make up 98% of the genome. The role of non-coding, disease-associated SNPs, many of which are located at considerable distances from any gene, was at first a mystery until the discovery that gene promoters regularly interact with distal regulatory elements to control gene expression. Disease-associated SNPs are enriched at the millions of gene regulatory elements that are dispersed throughout the non-coding sequences of the genome, suggesting they function as gene regulation variants. Assigning specific regulatory elements to the genes they control is not straightforward since they can be millions of base pairs apart. In this review we describe how understanding 3D genome organization can identify specific interactions between gene promoters and distal regulatory elements and how 3D genomics can link disease-associated SNPs to their target genes. Understanding which gene or genes contribute to a specific disease is the first step in designing rational therapeutic interventions.

Objective: Breast cancer has a strong impact on the mental state of those affected. Cognitive behavioral therapy (CBT) is one effective approach to reduce disease burden. This randomized controlled pilot trial aimed to assess the effect of the digital CBT‐based application Living Well on psychological outcomes in a German female breast cancer population. Methods: Female breast cancer patients (n = 70) with ongoing or finished oncological treatment that is who were receiving or had received any type of oncological treatment were included in the study and randomized to an intervention group (IG, n = 32) receiving Living Well in addition to care as usual, and a control group (CG, n = 38) receiving care as usual only. Participants completed standardized questionnaires at baseline and after 2, 4, 8, and 12 weeks to assess anxiety and depression (HADS) as primary outcomes, distress (DT), health‐related quality of life (HRQoL, AQoL‐8D), and illness perception (B‐IPQ) as secondary outcomes. Results: After 12 weeks, significant (p < 0.05) higher improvements in the IG could be observed in anxiety levels, HRQoL, and illness perception, when compared to the CG. Age and time since diagnosis were found to be relevant covariates for anxiety levels. In distress levels, the IG showed a clinically relevant and nearly significant reduction compared to the CG (p = 0.057). No effects could be observed in depression levels. Conclusions: The results demonstrate the potential of Living Well to improve psychological outcomes of female breast cancer patients and encourage further studies evaluating the effectiveness of the digital application. Trial Registration: The trial has been registered in the German Clinical Trials Register (DRKS00029918) [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion Basic therapy is an integral part of the treatment of chronic skin diseases. However, the formulation of skin products should be analysed with respect to the physical stability and tolerance by the patients before applying them to diseased skin. In particular, the suitability of the formulation for use on damaged skin should be taken into consideration so that no exacerbation of the condition is caused.The following approach investigated two formulations with the emulsifier sorbitan monostearate and one with the addition of polyethylene glycol 100 stearyl ether. The characterization included rheology, macroscopic and microscopic cream analysis compared to marketed products for basic therapy. Pyranine staining of stratum corneum (SC) and trans‐epidermal water loss (TEWL) measurements were performed with ex vivo porcine SC to asses skin barrier function.The rheological characterization showed a gel‐like, viscoelastic behaviour of the formulations and a viscosity in the same order of magnitude as the marketed products. Staining with pyranine revealed that skin damage caused by sodium lauryl sulfate was compensated by treatment with the developed formulations. Following the same trend, TEWL results clearly showed decreasing values, which evidence improved skin barrier function.In conclusion, the developed sorbitan monostearate formulations can potentially improve deficient skin barrier function as a part of basic therapy of skin diseases and act as a superior alternative to market products comprising a minimum of well‐chosen ingredients. [ABSTRACT FROM AUTHOR]

The role of transcriptional enhancers and 3D chromatin organisation in coordinating the transition from naive to primed pluripotency remains poorly understood. Here the authors generate a high-resolution atlas of gene regulatory interactions, chromatin profiles and transcription factor occupancy in naive and primed human pluripotent stem cells to provide insights into these developmental processes.

Abstract Background Since operating rooms are a major bottleneck resource and an important revenue driver in hospitals, it is important to use these resources efficiently. Studies estimate that between 60 and 70% of hospital admissions are due to surgeries. Furthermore, staffing cannot be changed daily to respond to changing demands. The resulting high complexity in operating room management necessitates perpetual process evaluation and the use of decision support tools. In this study, we evaluate several management policies and their consequences for the operating theater of the University Hospital Augsburg. Methods Based on a data set with 12,946 surgeries, we evaluate management policies such as parallel induction of anesthesia with varying levels of staff support, the use of a dedicated emergency room, extending operating room hours reserved as buffer capacity, and different elective patient sequencing policies. We develop a detailed simulation model that serves to capture the process flow in the entire operating theater: scheduling surgeries from a dynamically managed waiting list, handling various types of schedule disruptions, rescheduling and prioritizing postponed and deferred surgeries, and reallocating operating room capacity. The system performance is measured by indicators such as patient waiting time, idle time, staff overtime, and the number of deferred surgeries. Results We identify significant trade-offs between expected waiting times for different patient urgency categories when operating rooms are opened longer to serve as end-of-day buffers. The introduction of parallel induction of anesthesia allows for additional patients to be scheduled and operated on during regular hours. However, this comes with a higher number of expected deferrals, which can be partially mitigated by employing additional anesthesia teams. Changes to the sequencing of elective patients according to their expected surgery duration cause expectable outcomes for a multitude of performance indicators. Conclusions Our simulation-based approach allows operating theater managers to test a multitude of potential changes in operating room management without disrupting the ongoing workflow. The close collaboration between management and researchers in the design of the simulation framework and the data analysis has yielded immediate benefits for the scheduling policies and data collection efforts at our practice partner.

Senescence is a state of stable proliferative arrest. Here, the authors perform Hi-C analysis on oncogenic RAS-induced senescence in human fibroblasts and characterize the changes in the 3D genome folding associated with the senescence-specific gene expression profile, which are mediated in part through cohesin redistribution on chromatin.

Photoelasticity is considered a useful measurement tool for the non-destructive and contactless determination of mechanical stresses or strains in the production of silicon wafers. It describes a change in the indices of refraction of a material when the material is mechanically loaded. As silicon has a diamond lattice structure, the stress-dependent change in the refractive indices varies with the loading direction. In this work, an anisotropic stress-optic law is derived, and the corresponding stress-optical parameters are measured using a Brazilian disc test. The parameters were determined to be (π11-π12)=14.4⋅10-7 MPa−1 and π44=9.4⋅10-7 MPa−1. The results of this work are compared to previous works found in the literature, and the deviations are discussed.

Measures of stepping volume and rate are common outputs from wearable devices, such as accelerometers. It has been proposed that biomedical technologies, including accelerometers and their algorithms, should undergo rigorous verification as well as analytical and clinical validation to demonstrate that they are fit for purpose. The aim of this study was to use the V3 framework to assess the analytical and clinical validity of a wrist-worn measurement system of stepping volume and rate, formed by the GENEActiv accelerometer and GENEAcount step counting algorithm. The analytical validity was assessed by measuring the level of agreement between the wrist-worn system and a thigh-worn system (activPAL), the reference measure. The clinical validity was assessed by establishing the prospective association between the changes in stepping volume and rate with changes in physical function (SPPB score). The agreement of the thigh-worn reference system and the wrist-worn system was excellent for total daily steps (CCC = 0.88, 95% CI 0.83–0.91) and moderate for walking steps and faster-paced walking steps (CCC = 0.61, 95% CI 0.53–0.68 and 0.55, 95% CI 0.46–0.64, respectively). A higher number of total steps and faster paced-walking steps was consistently associated with better physical function. After 24 months, an increase of 1000 daily faster-paced walking steps was associated with a clinically meaningful increase in physical function (0.53 SPPB score, 95% CI 0.32–0.74). We have validated a digital susceptibility/risk biomarker—pfSTEP—that identifies an associated risk of low physical function in community-dwelling older adults using a wrist-worn accelerometer and its accompanying open-source step counting algorithm.