Bayes Factors for Mixed Models: a Discussion

van Doorn et al. (2021) outlined various questions that arise when conducting Bayesian model comparison for mixed effects models. Seven response articles offered their own perspective on the preferred setup for mixed model comparison, on the most appropriate specification of prior distributions, and on the desirability of default recommendations. This article presents a round-table discussion that aims to clarify outstanding issues, explore common ground, and outline practical considerations for any researcher wishing to conduct a Bayesian mixed effects model comparison

Infinitesimal sulfur fusion yields quasi-metallic bulk silicon for stable and fast energy storage

A fast-charging battery that supplies maximum energy is a key element for vehicle electrification. High-capacity silicon anodes offer a viable alternative to carbonaceous materials, but they are vulnerable to fracture due to large volumetric changes during charge???discharge cycles. The low ionic and electronic transport across the silicon particles limits the charging rate of batteries. Here, as a three-in-one solution for the above issues, we show that small amounts of sulfur doping (<1 at%) render quasi-metallic silicon microparticles by substitutional doping and increase lithium ion conductivity through the flexible and robust self-supporting channels as demonstrated by microscopy observation and theoretical calculations. Such unusual doping characters are enabled by the simultaneous bottom-up assembly of dopants and silicon at the seed level in molten salts medium. This sulfur-doped silicon anode shows highly stable battery cycling at a fast-charging rate with a high energy density beyond those of a commercial standard anode

Giant regular polyhedra from calixarene carboxylates and uranyl

Self-assembly of large multi-component systems is a common strategy for the bottom-up construction of discrete, well-defined, nanoscopic-sized cages. Icosahedral or pseudospherical viral capsids, built up from hundreds of identical proteins, constitute typical examples of the complexity attained by biological self-assembly. Chemical versions of the so-called 5 Platonic regular or 13 Archimedean semi-regular polyhedra are usually assembled combining molecular platforms with metals with commensurate coordination spheres. Here we report novel, self-assembled cages, using the conical-shaped carboxylic acid derivatives of calix[4]arene and calix[5]arene as ligands, and the uranyl cation UO22+ as a metallic counterpart, which coordinates with three carboxylates at the equatorial plane, giving rise to hexagonal bipyramidal architectures. As a result, octahedral and icosahedral anionic metallocages of nanoscopic dimensions are formed with an unusually small number of components

Phage therapy is effective against infection by Mycobacterium ulcerans in a murine footpad model

Author Summary: Buruli Ulcer (BU), caused by Mycobacterium ulcerans, is a necrotizing disease of the skin, subcutaneous tissue and bone. Standard treatment of BU patients consists of a combination of the antibiotics rifampicin and streptomycin for 8 weeks. However, in advanced stages of the disease, surgical resection of the destroyed skin is still required. The use of bacterial viruses (bacteriophages) for the control of bacterial infections has been considered as an alternative or a supplement to antibiotic chemotherapy. By using a mouse model of M. ulcerans footpad infection, we show that mice treated with a single subcutaneous injection of the mycobacteriophage D29 present decreased footpad pathology associated with a reduction of the bacterial burden. In addition, D29 treatment induced increased levels of IFN-γ and TNF in M. ulcerans -infected footpads, correlating with a predominance of a mononuclear infiltrate. These findings suggest the potential use of phage therapy in BU, as a novel therapeutic approach against this disease, particularly in advanced stages where bacteria are found primarily in an extracellular location in the subcutaneous tissue, and thus immediately accessible by lytic phages.This work was supported by a grant from the Health Services of Fundacao Calouste Gulbenkian, and the Portuguese Science and Technology Foundation (FCT) fellowships SFRH/BPD/64032/2009, SFRH/BD/41598/2007, and SFRH/BPD/68547/2010 to GT, TGM, and AGF, respectively. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Clinical research evidence of cupping therapy in China: a systematic literature review

<p>Abstract</p> <p>Background</p> <p>Though cupping therapy has been used in China for thousands of years, there has been no systematic summary of clinical research on it.</p> <p>This review is to evaluate the therapeutic effect of cupping therapy using evidence-based approach based on all available clinical studies.</p> <p>Methods</p> <p>We included all clinical studies on cupping therapy for all kinds of diseases. We searched six electronic databases, all searches ended in December 2008. We extracted data on the type of cupping and type of diseases treated.</p> <p>Results</p> <p>550 clinical studies were identified published between 1959 and 2008, including 73 randomized controlled trials (RCTs), 22 clinical controlled trials, 373 case series, and 82 case reports. Number of RCTs obviously increased during past decades, but the quality of the RCTs was generally poor according to the risk of bias of the Cochrane standard for important outcome within each trials. The diseases in which cupping was commonly employed included pain conditions, herpes zoster, cough or asthma, etc. Wet cupping was used in majority studies, followed by retained cupping, moving cupping, medicinal cupping, etc. 38 studies used combination of two types of cupping therapies. No serious adverse effects were reported in the studies.</p> <p>Conclusions</p> <p>According to the above results, quality and quantity of RCTs on cupping therapy appears to be improved during the past 50 years in China, and majority of studies show potential benefit on pain conditions, herpes zoster and other diseases. However, further rigorous designed trials in relevant conditions are warranted to support their use in practice.</p

Molecular mechanisms of severe acute respiratory syndrome (SARS)

Severe acute respiratory syndrome (SARS) is a new infectious disease caused by a novel coronavirus that leads to deleterious pulmonary pathological features. Due to its high morbidity and mortality and widespread occurrence, SARS has evolved as an important respiratory disease which may be encountered everywhere in the world. The virus was identified as the causative agent of SARS due to the efforts of a WHO-led laboratory network. The potential mutability of the SARS-CoV genome may lead to new SARS outbreaks and several regions of the viral genomes open reading frames have been identified which may contribute to the severe virulence of the virus. With regard to the pathogenesis of SARS, several mechanisms involving both direct effects on target cells and indirect effects via the immune system may exist. Vaccination would offer the most attractive approach to prevent new epidemics of SARS, but the development of vaccines is difficult due to missing data on the role of immune system-virus interactions and the potential mutability of the virus. Even in a situation of no new infections, SARS remains a major health hazard, as new epidemics may arise. Therefore, further experimental and clinical research is required to control the disease

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe