The minor T allele of the MUC5B promoter rs35705950 associated with susceptibility to idiopathic pulmonary fibrosis: a meta-analysis

MUC5B promoter rs35705950 T/G gene polymorphism has been associated with the risk of IPF, but the influence of this relationship varies among different populations. In the past 2 years, there were new clinical studies with different results, but none of them reached unified conclusions. Therefore, this study further included the latest case–control studies, integrated their results and carried out meta-analysis on them to draw reliable conclusions. PubMed, EMBASE, CNKI, Wanfang database and VIP Chinese science were searched by a computer to collect the related literatures of MUC5B gene polymorphism and IPF susceptibility published before June 15, 2021. The first author, year of publication, diagnostic criteria and gene frequency were extracted after screened them. Forest plot was drawn and the trial sequential analysis (TSA) was carried out to confirm the stability of the meta-analysis results. Registration number: CRD42021272940. A total of 24 case–control studies (13 studies on the Caucasian, 7 studies on the Asian and 4 studies on the mixed population), and a total of 6749 IPF patients and 13,898 healthy controls were included in this study. The T vs.G, TT vs. GG, GT vs. GG, GT + TT vs. GG and TT vs. GG + GT genetic models of MUC5B promoter rs35705950 T/G polymorphism were associated with IPF risk in all populations, and the effect values were ([OR] 4.12, 95% CI [3.64, 4.67]), ([OR] 10.12, 95% CI [7.06, 14.49]), ([OR] 4.84, 95% CI [3.85, 6.08]), ([OR] 4.84, 95% CI [3.79, 6.19]) and ([OR] 5.11, 95% CI [4.02, 6.49]), respectively. The results of TSA confirmed the stability of the results. Subgroup analysis showed that T vs.G, TT vs. GG, GT vs. GG, GT + TT vs. GG and TT vs. GG + GT genetic models of MUC5B polymorphism were associated with IPF risk in Caucasian population. The effect values were ([OR] 4.50, 95% CI [3.93, 5.16]), ([OR] 10.98, 95% CI [7.59, 15.89]), ([OR] 6.27, 95% CI [5.37, 7.32]), ([OR] 6.30, 95% CI [5.19, 7.64]) and ([OR] 5.15, 95% CI [4.01, 6.61]), respectively. Similar results were also found in Asian and mixed populations. The association strength of the minor T allele in the Caucasian was more significant than that of the Asian population ([OR] 4.50 vs. [OR] 2.39), and the association strength of all genetic models carrying "T" was more significant than that of the Asian population ([OR] 10.98 vs. [OR] 4.29). In Caucasian, Asian and mixed populations, T minor allele carriers were more likely to be susceptible to pulmonary fibrosis, and TT genotype carriers were more likely to be susceptible to IPF than GT genotype carriers. The association between IPF and Caucasian population with minor T allele and all "T" genetic model was more significant than that of Asian population.

Spatial social dilemmas promote diversity

Cooperative investments in social dilemmas can spontaneously diversify into stably coexisting high and low contributors in well-mixed populations. Here we extend the analysis to emerging diversity in (spatially) structured populations. Using pair approximation, we derive analytical expressions for the invasion fitness of rare mutants in structured populations, which then yields a spatial adaptive dynamics framework. This allows us to predict changes arising from population structures in terms of existence and location of singular strategies, as well as their convergence and evolutionary stability as compared to well-mixed populations. Based on spatial adaptive dynamics and extensive individual-based simulations, we find that spatial structure has significant and varied impacts on evolutionary diversification in continuous social dilemmas. More specifically, spatial adaptive dynamics suggests that spontaneous diversification through evolutionary branching is suppressed, but simulations show that spatial dimensions offer new modes of diversification that are driven by an interplay of finite-size mutations and population structures. Even though spatial adaptive dynamics is unable to capture these new modes, they can still be understood based on an invasion analysis. In particular, population structures alter invasion fitness and can open up new regions in trait space where mutants can invade, but that may not be accessible to small mutational steps. Instead, stochastically appearing larger mutations or sequences of smaller mutations in a particular direction are required to bridge regions of unfavorable traits. The net effect is that spatial structure tends to promote diversification, especially when selection is strong.

Evaluation of Prokaryotic and Eukaryotic Cell

In the “ecosystems-first” approach to the origins of life, networks of noncovalent assemblies of molecules (composomes), rather than individual protocells, evolved under the constraints of molecular complementarity. Composomes evolved into the hyperstructures of modern bacteria. We extend the ecosystems-first approach to explain the origin of eukaryotic cells through the integration of mixed populations of bacteria. We suggest that mutualism and symbiosis resulted in cellular mergers entailing the loss of redundant hyperstructures, the uncoupling of transcription and translation, and the emergence of introns and multiple chromosomes. Molecular complementarity also facilitated integration of bacterial hyperstructures to perform cytoskeletal and movement functions.

What are the effects of teaching Evidence-Based Health Care (EBHC) at different levels of health professions education? An updated overview of systematic reviews

Background Evidence-based healthcare (EBHC) knowledge and skills are recognised as core competencies of healthcare professionals worldwide, and teaching EBHC has been widely recommended as an integral part of their training. The objective of this overview of systematic reviews (SR) was to update evidence and assess the effects of various approaches for teaching evidence-based health care (EBHC) at undergraduate (UG) and postgraduate (PG) medical education (ME) level on changes in knowledge, skills, attitudes and behaviour. Methods and findings This is an update of an overview that was published in 2014. The process followed standard procedures specified for the previous version of the overview, with a modified search. Searches were conducted in Epistemonikos for SRs published from 1 January 2013 to 27 October 2020 with no language restrictions. We checked additional sources for ongoing and unpublished SRs. Eligibility criteria included: SRs which evaluated educational interventions for teaching EBHC compared to no intervention or a different strategy were eligible. Two reviewers independently selected SRs, extracted data and evaluated quality using standardised instrument (AMSTAR2). The effects of strategies to teach EBHC were synthesized using a narrative approach. Previously published version of this overview included 16 SR, while the updated search identified six additional SRs. We therefore included a total of 22 SRs (with a total of 141 primary studies) in this updated overview. The SRs evaluated different educational interventions of varying duration, frequency, and format to teach various components of EBHC at different levels of ME (UG, PG, mixed). Most SRs assessed a range of EBHC related outcomes using a variety of assessment tools. Two SRs included randomised controlled trials (RCTs) only, while 20 reviews included RCTs and various types of non-RCTs. Diversity of study designs and teaching activities as well as aggregated findings at the SR level prevented comparisons of the effects of different techniques. In general, knowledge was improved across all ME levels for interventions compared to no intervention or pre-test scores. Skills improved in UGs, but less so in PGs and were less consistent in mixed populations. There were positive changes in behaviour among UGs and PGs, but not in mixed populations, with no consistent improvement in attitudes in any of the studied groups. One SR showed improved patient outcomes (based on non-randomised studies). Main limitations included: poor quality and reporting of SRs, heterogeneity of interventions and outcome measures, and short-term follow up. Conclusions Teaching EBHC consistently improved EBHC knowledge and skills at all levels of ME and behaviour in UGs and PGs, but with no consistent improvement in attitudes towards EBHC, and little evidence of the long term influence on processes of care and patient outcomes. EBHC teaching and learning should be interactive, multifaceted, integrated into clinical practice, and should include assessments. Study registration The protocol for the original overview was developed and approved by Stellenbosch University Research Ethics Committee S12/10/262. Update of the overview Young T, Rohwer A, Volmink J, Clarke M. What are the effects of teaching evidence-based health care (EBHC)? Overview of systematic reviews. PLoS One. 2014;9(1):e86706. doi: 10.1371/journal.pone.0086706.

Characterisation of Regional Human Meniscal Progenitor Cells

Background The surgical treatment of meniscus injury has represented a clinical challenge for decades. Stimulating meniscus regeneration using transplanted meniscal progenitor cells has been suggested as a promising new strategy. However, there is a lack of studies which decisively identify and characterise progenitor cell populations in human meniscus tissues. Methods In this study, donor-matched progenitor cells were isolated via selective fibronectin adhesion from the avascular (PAvas) and vascular (PVas) regions of the meniscus and chondroprogenitors (PChs) from articular cartilage (n=5 donors). In addition, whole mixed populations of cells (MAvas, MVas, MChs) from the same regions were obtained by standard isolation techniques for comparison. The colony formation efficacy of PAvas, PVas and PChs was monitored using Cell-IQ® live cell imaging. Proliferation rates of progenitors were compared with their mixed population counterparts. Cell surface markers indicative of mesenchymal stromal cells (MSCs) profile and progenitor markers were characterised by flow cytometry in all populations. The chondrogenic capacity was assessed via pellet culture assays and measuring chondrogenic gene expression levels, GAG/DNA content and morphology. Results All meniscal progenitor and chondroprogenitor populations showed colony forming capacity in monolayer culture, whereas mixed populations were distributed randomly at passage 0. PVas had significantly lower population doubling times compare to MVas and proliferated faster than PAvas and PChs based on colony forming efficacy. Progenitor populations showed significantly higher positivity for CD49b and CD49c compared to their mixed population counterparts and PChs had a higher positivity level of CD166 compared to mixed chondrocytes. Collagen types II and X expression was significantly downregulated in pellets formed by progenitor populations. GAG/DNA analysis demonstrated that progenitor cells generally produced more GAG than mixed populations. Conclusions Our study demonstrates that the human meniscus contains meniscal progenitor populations in both the avascular and vascular regions. Meniscal progenitors derived from the vascular region exhibit enhanced proliferative and chondrogenic characteristics compared to those from the avascular region; this may associate with the enhanced meniscal healing potential in the vascular region. These findings build on the body of evidence which suggests that meniscal progenitors represent an attractive cell therapy strategy for meniscal regeneration.

Fast and strong amplifiers of natural selection

Selection and random drift determine the probability that novel mutations fixate in a population. Population structure is known to affect the dynamics of the evolutionary process. Amplifiers of selection are population structures that increase the fixation probability of beneficial mutants compared to well-mixed populations. Over the past 15 years, extensive research has produced remarkable structures called strong amplifiers which guarantee that every beneficial mutation fixates with high probability. But strong amplification has come at the cost of considerably delaying the fixation event, which can slow down the overall rate of evolution. However, the precise relationship between fixation probability and time has remained elusive. Here we characterize the slowdown effect of strong amplification. First, we prove that all strong amplifiers must delay the fixation event at least to some extent. Second, we construct strong amplifiers that delay the fixation event only marginally as compared to the well-mixed populations. Our results thus establish a tight relationship between fixation probability and time: Strong amplification always comes at a cost of a slowdown, but more than a marginal slowdown is not needed.

Crete in the Nineteenth Century

Venizelos was born and brought up in Crete under Ottoman rule, and the island shaped his early career. The author gives an account of Ottoman government of Crete in the 19th century, and how Greek independence attracted the Cretans. Crete's mixed populations of Christians and Muslims developed at different speeds. Uprisings by Christians in 1821, 1866 and later aimed at securing Crete's union (enosis) with Greece. The Great Powers, especially Britain, France, and Russia, had helped secure Greek independence, while delaying Cretan union, so as to preserve the integrity of the Ottoman empire. This was the Cretan Question, part of the wider Eastern Question. The 19th century saw the development of the Great Idea (megali idea) of incorporating in the Greek kingdom as many Greek communities from outside as possible. Civil society was developing in Crete in the second half of the19th century, and as the Cretan Christians increased in wealth and population, the Muslims were largely left behind.

Life Expectancy of the Ethnically Mixed: Register-Based Evidence from Native Finns

As the ethnic composition around the world is becoming more diverse, the need to produce vital statistics for ethnically mixed populations is continuously increasing. Our aim is to provide the first life expectancy estimates for individuals with uniform Finnish, uniform Swedish, and mixed Finnish-Swedish backgrounds, based on individuals in the native population of Finland who can be linked to both their parents. Life expectancy at birth in the period 2005–2015 was calculated from population and mortality numbers at the one-year level based on each person’s sex, year of birth, and the unique ethnolinguistic affiliation of the index person and each parent. Swedish-registered individuals with Swedish-registered parents had the longest life expectancy at birth, or 85.68 years (95% CI: 85.60–85.77) for females and 81.36 for males (95% CI: 81.30–81.42), as compared to 84.76 years (95% CI: 84.72–84.79) and 78.89 years (95% CI: 78.86–78.92) for Finnish-registered females and males with Finnish-registered parents. Persons with mixed backgrounds were found in between those with uniform Finnish and uniform Swedish backgrounds. An individual’s own ethnolinguistic affiliation is nevertheless more important for longevity than parental affiliation. Similar register-based analyses for other countries with mixed populations would be useful.

Origin of diversity in spatial social dilemmas

Cooperative investments in social dilemmas can spontaneously diversify into stably co-existing high and low contributors in well-mixed populations. Here we extend the analysis to emerging diversity in (spatially) structured populations. Using pair approximation we derive analytical expressions for the invasion fitness of rare mutants in structured populations, which then yields a spatial adaptive dynamics framework. This allows us to predict changes arising from population structures in terms of existence and location of singular strategies, as well as their convergence and evolutionary stability as compared to well-mixed populations. Based on spatial adaptive dynamics and extensive individual based simulations, we find that spatial structure has significant and varied impacts on evolutionary diversification in continuous social dilemmas. More specifically, spatial adaptive dynamics suggests that spontaneous diversification through evolutionary branching is suppressed, but simulations show that spatial dimensions offer new modes of diversification that are driven by an interplay of finite-size mutations and population structures. Even though spatial adaptive dynamics is unable to capture these new modes, they can still be under-stood based on an invasion analysis. In particular, population structures alter invasion fitness and can open up new regions in trait space where mutants can invade, but that may not be accessible to small mutational steps. Instead, stochastically appearing larger mutations or sequences of smaller mutations in a particular direction are required to bridge regions of unfavourable traits. The net effect is that spatial structure tends to promote diversification, especially when selection is strong.