Utilizing 3D Models to Unravel the Dynamics of Myeloma Plasma Cells' Escape from the Bone Marrow Microenvironment.

Recent therapeutic advancements have markedly increased the survival rates of individuals with multiple myeloma (MM), doubling survival compared to pre-2000 estimates. This progress, driven by highly effective novel agents, suggests a growing population of MM survivors exceeding the 10-year mark post-diagnosis. However, contemporary clinical observations indicate potential trends toward more aggressive relapse phenotypes, characterized by extramedullary disease and dominant proliferative clones, despite these highly effective treatments. To build upon these advances, it is crucial to develop models of MM evolution, particularly focusing on understanding the biological mechanisms behind its development outside the bone marrow. This comprehensive understanding is essential to devising innovative treatment strategies. This review emphasizes the role of 3D models, specifically addressing the bone marrow microenvironment and development of extramedullary sites. It explores the current state-of-the-art in MM modelling, highlighting challenges in replicating the disease's complexity. Recognizing the unique demand for accurate models, the discussion underscores the potential impact of these advanced 3D models on understanding and combating this heterogeneous and still incurable disease

The impact of partially missing communities~on the reliability of centrality measures

Network data is usually not error-free, and the absence of some nodes is a very common type of measurement error. Studies have shown that the reliability of centrality measures is severely affected by missing nodes. This paper investigates the reliability of centrality measures when missing nodes are likely to belong to the same community. We study the behavior of five commonly used centrality measures in uniform and scale-free networks in various error scenarios. We find that centrality measures are generally more reliable when missing nodes are likely to belong to the same community than in cases in which nodes are missing uniformly at random. In scale-free networks, the betweenness centrality becomes, however, less reliable when missing nodes are more likely to belong to the same community. Moreover, centrality measures in scale-free networks are more reliable in networks with stronger community structure. In contrast, we do not observe this effect for uniform networks. Our observations suggest that the impact of missing nodes on the reliability of centrality measures might not be as severe as the literature suggests

Clinician's perspectives in using head impulse-nystagmus-test of skew (HINTS) for acute vestibular syndrome: UK experience

Background: Acute vestibular syndrome (AVS) features continuous dizziness and may result from a benign inner ear disorder or stroke. The head impulse-nystagmus-test of skew (HINTS) bedside assessment is more sensitive than brain MRI in identifying stroke as the cause of AVS within the first 24 hours. Clinicians’ perspectives of the test in UK secondary care remains unknown. Here, we explore front-line clinicians’ perspectives of use of the HINTS for the diagnosis of AVS. // Methods: Clinicians from two large UK hospitals who assess AVS patients completed a short online survey, newly designed with closed and open questions. // Results: Almost half of 73 total responders reported limited (n=33), or no experience (n=19), reflected in low rates of use of HINTS (n=31). While recognising the potential utility of HINTS, many reported concerns about subjectivity, need for specialist skills and poor patient compliance. No clinicians reported high levels of confidence in performing HINTS, with 98% identifying training needs. A lack of formalised training was associated with onward specialist referrals and neuroimaging (p=0.044). // Conclusions: Although the low sample size in this study limits the generalisability of findings to wider sites, our preliminary data identified barriers to the application of the HINTS in AVS patients and training needs to improve rapid, cost-effective and accurate clinical diagnosis of stroke presenting with vertigo

Structure and Orientation of MDBA Self-Assembled Monolayers and Their Interaction with Calcite: A Molecular Dynamics Study

We investigate the structure of self-assembled monolayers produced by different mercaptodecyl benzoic acid isomers using molecular dynamics. We examine their interaction with water and calcium carbonate, and analyse the headgroup orientations in each case. We compare our results to experimental findings and propose an explanation for their observed hydrophilicity, as well as for the preferentially oriented growth of calcite on one of the isomers

Crystallisation rates of calcite from an amorphous precursor in confinement

Using molecular dynamics, we simulate the crystallisation of calcite from an amorphous calcium carbonate precursor within the confines of a cylindrical potential. The crystallisation rates of various low-index calcite surfaces are measured. A notable inhibition in the growth of the (00.1) surface is observed and a mechanism relating to the rotation of the carbonate ions is proposed to explain it

Comparison of respondent-reported and sensor-recorded latrine utilization measures in rural Bangladesh: a cross-sectional study.

Background: Health improvements realized through sanitation are likely achieved through high levels of facilities utilization by all household members. However, measurements of sanitation often rely on either the presence of latrines, which does not guarantee use, or respondent-reported utilization of sanitation facilities, which is prone to response bias. Overstatement of sanitation metrics limits the accuracy of program outcome measures, and has implications for the interpretation of related health impact data. Methods: We conducted a cross-sectional study of 213 households in 14 village water, sanitation and hygiene committee clusters throughout rural Bangladesh and used a combined data- and relationship-scale approach to assess agreement between respondent-reported latrine utilization and sensor-recorded measurement. Results: Four-day household-level respondent-reported defecation averaged 28 events (inter-quartile range [IQR] 20-40), while sensor-recorded defecation averaged 17 events (IQR 11-29). Comparative analyses suggest moderately high accuracy (bias correction factor=0.84), but imprecision in the data (broad scatter of data, Pearson's r=0.35) and thus only weak concordance between measures (ρc=0.29 [95% BCa CI 0.15 to 0.43]). Conclusions: Respondent-reported latrine utilization data should be interpreted with caution, as evidence suggests use is exaggerated. Coupling reported utilization data with objective measures of use may aid in the estimation of latrine use

Pilates based core stability training in ambulant individuals with multiple sclerosis: protocol for a multi-centre randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>People with Multiple Sclerosis (MS) frequently experience balance and mobility impairments, including reduced trunk stability. Pilates-based core stability training, which is aimed at improving control of the body's stabilising muscles, is popular as a form of exercise with people with MS and therapists. A replicated single case series study facilitated by the Therapists in MS Group in the United Kingdom (UK) provides preliminary evidence that this approach can improve balance and mobility in ambulant people with MS; further evidence is needed to substantiate these findings to ensure that limited time, energy, finances and resources are used to best effect.</p> <p>This study builds upon the pilot work undertaken in the case series study by implementing a powered randomised controlled study, with the aims of:</p> <p>1 Establishing the effectiveness of core stability training</p> <p>2 Comparing core stability training with standardised physiotherapy exercise</p> <p>3 Exploring underlying mechanisms of change associated with this intervention</p> <p>Methods</p> <p>This is a multi-centre, double blind, block randomised, controlled trial. Eligible participants will be recruited from 4 UK centres. Participants will be randomly allocated to one of three groups: Pilates based core stability training, standardised physiotherapy exercise or contract-relax relaxation sessions (placebo control). All will receive face to face training sessions over a 12 week period; together with a 15 minute daily home programme. All will be assessed by a blinded assessor before training, at the end of the 12 week programme and at 4 week follow-up. The primary outcome measure is the 10 metre timed walk. Secondary outcome measures are the MS walking Scale (MSWS-12), the Functional Reach (forwards and lateral), a 10 point Numerical Rating Scale to determine "Difficulty in carrying a drink when walking", and the Activities-specific Balance Confidence (ABC) Scale. In addition, ultrasound imaging of the abdominal muscles will be performed before and after intervention to assess changes in abdominal musculature at one of the four centres (Plymouth).</p> <p>Discussion</p> <p>This pragmatic trial will assess the effect of these exercise programmes on ambulatory people with MS. It may not be possible to extrapolate the conclusions to those who are non-ambulatory.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01414725">NCT01414725</a></p

Metadynamics simulations of calcite crystallization on self-assembled monolayers

We show that recent developments in the application of metadynamics methods to direct simulations of crystallization make it possible to predict the orientation of crystals grown on self-assembled monolayers. In contrast to previous studies, the method allows for dynamic treatment of the organic component and the inclusion of explicit surface water without the need for computationally intensive interfacial energy calculations or prior knowledge of the interfacial structure. The method is applied to calcite crystallization on carboxylate terminated alkanethiols arrayed on Au (111). We demonstrate that a dynamic treatment of the monolayer is sufficient to reproduce the experimental results without the need to impose epitaxial constraints on the system. We also observe an odd-even effect in the variation of selectivity with organic chain length, reproducing experimentally observed orientations in both cases. Analysis of the ordering process in our simulations suggests a cycle of mutual control in which both the organic and mineral components induce complementary local order across the interface, leading to the formation of a critical crystalline region. The influence of pH, together with some factors that might affect the range of applicability of our method, is discussed

Beyond the culture effect on credibility perception on microblogs

We investigated the credibility perception of tweet readers from the USA and by readers from eight Arabic countries; our aim was to understand if credibility was affected by country and/or by culture. Results from a crowd-sourcing experiment, showed a wide variety of factors affected credibility perception, including a tweet author&#039;s gender, profile image, username style, location, and social network overlap with the reader. We found that culture determines readers&#039; credibility perception, but country has no effect. We discuss the implications of our findings for user interface design and social media systems

Cholesterol and the risk of grade-specific prostate cancer incidence: evidence from two large prospective cohort studies with up to 37 years' follow up

&lt;b&gt;Background&lt;/b&gt; High cholesterol may be a modifiable risk factor for prostate cancer but results have been inconsistent and subject to potential "reverse causality" where undetected disease modifies cholesterol prior to diagnosis.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; We conducted a prospective cohort study of 12,926 men who were enrolled in the Midspan studies between 1970 and 1976 and followed up to 31st December 2007. We used Cox-Proportional Hazards Models to evaluate the association between baseline plasma cholesterol and Gleason grade-specific prostate cancer incidence. We excluded cancers detected within at least 5 years of cholesterol assay.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; 650 men developed prostate cancer in up to 37 years' follow-up. Baseline plasma cholesterol was positively associated with hazard of high grade (Gleason score[greater than or equal to]8) prostate cancer incidence (n=119). The association was greatest among men in the 4th highest quintile for cholesterol, 6.1 to &#60;6.69 mmol/l, Hazard Ratio 2.28, 95% CI 1.27 to 4.10, compared with the baseline of &#60;5.05 mmol/l. This association remained significant after adjustment for body mass index, smoking and socioeconomic status.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; Men with higher cholesterol are at greater risk of developing high-grade prostate cancer but not overall risk of prostate cancer. Interventions to minimise metabolic risk factors may have a role in reducing incidence of aggressive prostate cancer