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The aim of awake brain surgery is to perform a maximum resection on the one hand, and to preserve cognitive functions, quality of life and personal autonomy on the other hand. Historically, language and sensorimotor functions were most frequently monitored. Over the years other cognitive functions, including music, have entered the operation theatre. Cases about monitoring musical abilities during awake brain surgery are emerging, and a systematic method how to monitor music would be the next step. According to the IDEAL framework for surgical innovations our study aims to present future recommendation based on a systematic literature search (PRISMA) in combination with lessons learned from three case reports from our own clinical practice with professional musicians (n = 3). We plead for structured procedures including individual tailored tasks. By embracing these recommendations, we can both improve clinical care and unravel music functions in the brain. [ABSTRACT FROM AUTHOR]

This work aimed to manufacture scaffolds from a hydrogel composed of a sodium alginate matrix with hydroxyapatite reinforcements using a 3D bioprinter, aiming at application in bone tissue regeneration. The alginate solution was prepared by dissolving sodium alginate at a concentration of 10% (w/v). Hydroxyapatite (HAp) was added to the solution at 2.5% and 5.0% (w/v) concentrations, followed by placing the samples in a container with a 1.0% (w/v) calcium chloride solution. The scaffolds were analyzed for HAp concentration and morphological characteristics, physicochemical properties, and biological response. The scaffolds show reproducibility and spectroscopic analyses confirm hydrogel formation and hydroxyapatite incorporation in the alginate matrix. The hydrophilic properties are compatible with scaffolds obtained through 3D printing made from polysaccharides, and the thermal analysis showed the expected behavior of these same materials. Preliminary findings indicated that scaffolds containing 2.5% (w/v) hydroxyapatite are inside cytotoxicity limit (66.4 ± 7.0%) towards canine E20 lineage cells. In contrast, scaffolds with 0% and 5.0% (w/v) hydroxyapatite were non-cytotoxic. Notably, the latter scaffold demonstrated enhanced cell proliferation, as anticipated, owing to the hydrophilic properties of alginate that enable easy and swift cell seeding, facilitating nutrient transport and cellular growth within the scaffold.

Currently computational tools are helping and improving the processes and testing procedures in several areas of knowledge. Computed tomography (CT) is a diagnostic tool already consolidated and now beginning to be used as a tool for something even more innovative, creating biomodels. Biomodels are anatomical physical copies of human organs and tissues that are used for diagnosis and surgical planning. The use of tomographic images in the creation of biomodels has been arousing great interest in the medical and bioengineering area. In addition to creating biomodels by computed tomography it is also possible, using this process, to create mathematical models to perform computer simulations and analyses of regions of interest. This paper discusses the creation of a biomodel of the skull-mandibular region of a patient from CT for study and evaluation of efforts in the area of the temporomandibular joint (TMJ) aiming at the design and development of a TMJ custom prosthesis. The evaluation of efforts in the TMJ region due to the forces of mastication was made using the finite element method and the results were corroborated by comparison with mandibular models studied in similar works.

The SARS-CoV-2 genome occupies a unique place in infection biology - it is the most highly sequenced genome on earth (making up over 20% of public sequencing datasets) with fine scale information on sampling date and geography, and has been subject to unprecedented intense analysis. As a result, these phylogenetic data are an incredibly valuable resource for science and public health. However, the vast majority of the data was sequenced by tiling amplicons across the full genome, with amplicon schemes that changed over the pandemic as mutations in the viral genome interacted with primer binding sites. In combination with the disparate set of genome assembly workflows and lack of consistent quality control (QC) processes, the current genomes have many systematic errors that have evolved with the virus and amplicon schemes. These errors have significant impacts on the phylogeny, and therefore over the last few years, many thousands of hours of researchers time has been spent in "eyeballing" trees, looking for artefacts, and then patching the tree. Given the huge value of this dataset, we therefore set out to reprocess the complete set of public raw sequence data in a rigorous amplicon-aware manner, and build a cleaner phylogeny. Here we provide a global tree of 4,471,579 samples, built from a consistently assembled set of high quality consensus sequences from all available public data as of June 2024, viewable at https://viridian.taxonium.org. Each genome was constructed using a novel assembly tool called Viridian (https://github.com/iqbal-lab-org/viridian), developed specifically to process amplicon sequence data, eliminating artefactual errors and mask the genome at low quality positions. We provide simulation and empirical validation of the methodology, and quantify the improvement in the phylogeny. We hope the tree, consensus sequences and Viridian will be a valuable resource for researchers., Competing Interests: Conflict of Interest Gavin Screaton sits on the GSK Vaccines Scientific Advisory Board, consults for AstraZeneca, and is a founding member of RQ Biotechnology.

Monkeypox virus (MPXV) is endemic in western and Central Africa, and in May 2022, a clade IIb lineage (B.1) caused a global outbreak outside Africa, resulting in its detection in 116 countries and territories. To understand the global phylogenetics of MPXV, we analyzed all available MPXV sequences, including 10,670 sequences from 65 countries collected between 1958 and 2024. Our analysis reveals high mobility of clade I viruses within Central Africa, sustained human-to-human transmission of clade IIb lineage A viruses within the Eastern Mediterranean region and distinct mutational signatures that can distinguish sustained human-to-human from animal-to-animal transmission. Moreover, distinct clade I sequences from Sudan suggest local MPXV circulation in areas of eastern Africa over the past four decades. Our study underscores the importance of genomic surveillance in tracking spatiotemporal dynamics of MXPV clades and the need to strengthen such surveillance, including in some parts of eastern Africa., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

A globally implemented unified phylogenetic classification for human respiratory syncytial virus (HRSV) below the subgroup level remains elusive. We formulated global consensus of HRSV classification on the basis of the challenges and limitations of our previous proposals and the future of genomic surveillance. From a high-quality curated dataset of 1,480 HRSV-A and 1,385 HRSV-B genomes submitted to GenBank and GISAID (https://www.gisaid.org) public sequence databases through March 2023, we categorized HRSV-A/B sequences into lineages based on phylogenetic clades and amino acid markers. We defined 24 lineages within HRSV-A and 16 within HRSV-B and provided guidelines for defining prospective lineages. Our classification demonstrated robustness in its applicability to both complete and partial genomes. We envision that this unified HRSV classification proposal will strengthen HRSV molecular epidemiology on a global scale.

The major human bacterial pathogen Pseudomonas aeruginosa causes multidrug-resistant infections in people with underlying immunodeficiencies or structural lung diseases such as cystic fibrosis (CF). We show that a few environmental isolates, driven by horizontal gene acquisition, have become dominant epidemic clones that have sequentially emerged and spread through global transmission networks over the past 200 years. These clones demonstrate varying intrinsic propensities for infecting CF or non-CF individuals (linked to specific transcriptional changes enabling survival within macrophages); have undergone multiple rounds of convergent, host-specific adaptation; and have eventually lost their ability to transmit between different patient groups. Our findings thus explain the pathogenic evolution of P. aeruginosa and highlight the importance of global surveillance and cross-infection prevention in averting the emergence of future epidemic clones.

Purpose: Mapping higher-order cognitive functions during awake brain surgery is important for cognitive preservation which is related to postoperative quality of life. A systematic review from 2018 about neuropsychological tests used during awake craniotomy made clear that until 2017 language was most often monitored and that the other cognitive domains were underexposed (Ruis, J Clin Exp Neuropsychol 40(10):1081-1104, 218). The field of awake craniotomy and cognitive monitoring is however developing rapidly. The aim of the current review is therefore, to investigate whether there is a change in the field towards incorporation of new tests and more complete mapping of (higher-order) cognitive functions., Methods: We replicated the systematic search of the study from 2018 in PubMed and Embase from February 2017 to November 2023, yielding 5130 potentially relevant articles. We used the artificial machine learning tool ASReview for screening and included 272 papers that gave a detailed description of the neuropsychological tests used during awake craniotomy., Results: Comparable to the previous study of 2018, the majority of studies (90.4%) reported tests for assessing language functions (Ruis, J Clin Exp Neuropsychol 40(10):1081-1104, 218). Nevertheless, an increasing number of studies now also describe tests for monitoring visuospatial functions, social cognition, and executive functions., Conclusions: Language remains the most extensively tested cognitive domain. However, a broader range of tests are now implemented during awake craniotomy and there are (new developed) tests which received more attention. The rapid development in the field is reflected in the included studies in this review. Nevertheless, for some cognitive domains (e.g., executive functions and memory), there is still a need for developing tests that can be used during awake surgery., (© 2024. The Author(s).)

Left-right orientation, a function related to the parietal lobe, is important for many daily activities. Here, we describe a left-handed patient with a right parietal brain tumour. During awake surgery, electric stimulation of the right inferior parietal lobe resulted in mistakes in his left-right orientation. Postoperatively our patient had no problems in discriminating left right. This case report shows that monitoring of left-right orientation during awake brain tumour surgery is feasible so that this function can be preserved., (© 2023 The Authors. Journal of Neuropsychology published by John Wiley & Sons Ltd on behalf of The British Psychological Society.)

One of the most underdiagnosed and undertreated non-motor symptoms of Parkinson's Disease is chronic pain. This is generally treated with analgesics which is not always effective and can cause several side-effects. Therefore, new ways to reduce chronic pain are needed. Several experimental studies show that CT-optimal touch can reduce acute pain. However, little is known about the effect of CT-optimal touch on chronic pain. The aim of the current study is to investigate whether CT-optimal touch can reduce the chronic pain experience in Parkinson patients. In this intervention study, 17 Parkinson patients underwent three conditions; no touch, CT-optimal touch and CT non-optimal touch with a duration of one week each. During each touch week, participants received touch from their partners twice a day for 15 minutes. Results show that both types of touch ameliorate the chronic pain experience. Furthermore, it appears that it is slightly more beneficial to apply CT-optimal touch also because it is perceived as more pleasant. Therefore, we argue that CT-optimal touch might be used when immediate pain relief is needed. Importantly, this study shows that CT-optimal touch can reduce chronic pain in Parkinson's Disease and can be administered by a partner which makes it feasible to implement CT-optimal touch as daily routine., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Meijer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Recent studies show that CT-optimal touch, gentle slow stroking of the skin, can reduce pain. However, much is unknown regarding the factors influencing its pain-ameliorating effect, such as tactile attention and touch application site. The current study investigates in 36 healthy individuals, whether CT-optimal touch can reduce temporal summation of second pain (TSSP) compared to CT non-optimal touch and tapping the skin. TSSP refers to activation of the C-nociceptors; by stimulating these fibers a burning and/or tingling sensation can be elicited. All participants underwent three conditions on both the contralateral and ipsilateral side of pain induction. The results show that tapping the skin did not reduce TSSP, meaning that pain reduction through touch cannot be explained by tactile attention effects. CT non-optimal touch only reduced TSSP when applied on the ipsilateral side. Importantly, CT-optimal touch effectively reduced TSSP when applied on the contralateral or ipsilateral side. Furthermore, CT-optimal touch was more effective in reducing TSSP compared to CT non-optimal touch and Tapping. This study shows that that CT-optimal touch can reduce TSSP and this effect appears to be independent of touch application site, which is highly relevant for implementing CT-optimal touch as a treatment., (© 2024. The Author(s).)

Pathogen lineage nomenclature systems are a key component of effective communication and collaboration for researchers and public health workers. Since February 2021, the Pango dynamic lineage nomenclature for SARS-CoV-2 has been sustained by crowdsourced lineage proposals as new isolates were sequenced. This approach is vulnerable to time-critical delays as well as regional and personal bias. Here we developed a simple heuristic approach for dividing phylogenetic trees into lineages, including the prioritization of key mutations or genes. Our implementation is efficient on extremely large phylogenetic trees consisting of millions of sequences and produces similar results to existing manually curated lineage designations when applied to SARS-CoV-2 and other viruses including chikungunya virus, Venezuelan equine encephalitis virus complex and Zika virus. This method offers a simple, automated and consistent approach to pathogen nomenclature that can assist researchers in developing and maintaining phylogeny-based classifications in the face of ever-increasing genomic datasets., (© 2024. The Author(s).)

As observed in cancers, individual mutagens and defects in DNA repair create distinctive mutational signatures that combine to form context-specific spectra within cells. We reasoned that similar processes must occur in bacterial lineages, potentially allowing decomposition analysis to detect both disruption of DNA repair processes and exposure to niche-specific mutagens. Here we reconstruct mutational spectra for 84 clades from 31 diverse bacterial species and find distinct mutational patterns. We extract signatures driven by specific DNA repair defects using hypermutator lineages, and further deconvolute the spectra into multiple signatures operating within different clades. We show that these signatures are explained by both bacterial phylogeny and replication niche. By comparing mutational spectra of clades from different environmental and biological locations, we identify niche-associated mutational signatures, and then employ these signatures to infer the predominant replication niches for several clades where this was previously obscure. Our results show that mutational spectra may be associated with sites of bacterial replication when mutagen exposures differ, and can be used in these cases to infer transmission routes for established and emergent human bacterial pathogens., (© 2023. The Author(s).)

Once acquired, hypermutation is unrelenting, and in the long-term, leads to impaired fitness due to its cumulative impact on the genome. This raises the question of why hypermutators arise so frequently in microbial ecosystems. In this work, we explore this problem by examining how the transient acquisition of hypermutability affects inter- and intra-species competitiveness, and the response to environmental insults such as antibiotic challenge. We do this by engineering Pseudomonas aeruginosa to allow the expression of an important mismatch repair gene, mutS, to be experimentally controlled over a wide dynamic range. We show that high levels of mutS expression induce genomic stasis (hypomutation), whereas lower levels of induction lead to progressively higher rates of mutation. Whole-genome sequence analyses confirmed that the mutational spectrum of the inducible hypermutator is similar to the distinctive profile associated with mutS mutants obtained from the airways of people with cystic fibrosis (CF). The acquisition of hypermutability conferred a distinct temporal fitness advantage over the wild-type P. aeruginosa progenitor strain, in both the presence and the absence of an antibiotic selection pressure. However, over a similar time-scale, acquisition of hypermutability had little impact on the population dynamics of P. aeruginosa when grown in the presence of a competing species (Staphylococcus aureus). These data indicate that in the short term, acquired hypermutability primarily confers a competitive intra-species fitness advantage., (© 2023. The Author(s).)

Since SARS-CoV-2 BA.5 (Omicron) emerged and spread in 2022, Omicron lineages have markedly diversified. Here we review the evolutionary trajectories and processes that underpin the emergence of these lineages, and identify the most prevalent sublineages. We discuss the potential origins of second-generation BA.2 lineages. Simple and complex recombination, antigenic drift and convergent evolution have enabled SARS-CoV-2 to accumulate mutations that alter its antigenicity. We also discuss the potential evolutionary trajectories of SARS-CoV-2 in the future., (© 2023. Springer Nature Limited.)

Molnupiravir, an antiviral medication widely used against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), acts by inducing mutations in the virus genome during replication. Most random mutations are likely to be deleterious to the virus and many will be lethal; thus, molnupiravir-induced elevated mutation rates reduce viral load 1,2 . However, if some patients treated with molnupiravir do not fully clear the SARS-CoV-2 infections, there could be the potential for onward transmission of molnupiravir-mutated viruses. Here we show that SARS-CoV-2 sequencing databases contain extensive evidence of molnupiravir mutagenesis. Using a systematic approach, we find that a specific class of long phylogenetic branches, distinguished by a high proportion of G-to-A and C-to-T mutations, are found almost exclusively in sequences from 2022, after the introduction of molnupiravir treatment, and in countries and age groups with widespread use of the drug. We identify a mutational spectrum, with preferred nucleotide contexts, from viruses in patients known to have been treated with molnupiravir and show that its signature matches that seen in these long branches, in some cases with onward transmission of molnupiravir-derived lineages. Finally, we analyse treatment records to confirm a direct association between these high G-to-A branches and the use of molnupiravir., (© 2023. The Author(s).)

Affective touch is gentle slow stroking of the skin, which can reduce experimentally induced pain. Our participant, suffering from Parkinson's Disease and chronic pain, received 1 week of non-affective touch and 1 week of affective touch as part of a larger study. Interestingly, after 2 days of receiving affective touch, the participant started to feel less pain. After 7 days, the burning painful sensations fully disappeared. This suggest that affective touch may reduce chronic pain in clinical populations., (© 2023 The Authors. Journal of Neuropsychology published by John Wiley & Sons Ltd on behalf of The British Psychological Society.)

Exposure to different mutagens leaves distinct mutational patterns that can allow inference of pathogen replication niches. We therefore investigated whether SARS-CoV-2 mutational spectra might show lineage-specific differences, dependent on the dominant site(s) of replication and onwards transmission, and could therefore rapidly infer virulence of emergent variants of concern (VOCs). Through mutational spectrum analysis, we found a significant reduction in G>T mutations in the Omicron variant, which replicates in the upper respiratory tract (URT), compared to other lineages, which replicate in both the URT and lower respiratory tract (LRT). Mutational analysis of other viruses and bacteria indicates a robust, generalizable association of high G>T mutations with replication within the LRT. Monitoring G>T mutation rates over time, we found early separation of Omicron from Beta, Gamma and Delta, while mutational patterns in Alpha varied consistent with changes in transmission source as social restrictions were lifted. Mutational spectra may be a powerful tool to infer niches of established and emergent pathogens.

The SARS-CoV-2 Delta (Pango lineage B.1.617.2) variant of concern spread globally, causing resurgences of COVID-19 worldwide 1,2 . The emergence of the Delta variant in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions. Here we analyse 52,992 SARS-CoV-2 genomes from England together with 93,649 genomes from the rest of the world to reconstruct the emergence of Delta and quantify its introduction to and regional dissemination across England in the context of changing travel and social restrictions. Using analysis of human movement, contact tracing and virus genomic data, we find that the geographic focus of the expansion of Delta shifted from India to a more global pattern in early May 2021. In England, Delta lineages were introduced more than 1,000 times and spread nationally as non-pharmaceutical interventions were relaxed. We find that hotel quarantine for travellers reduced onward transmission from importations; however, the transmission chains that later dominated the Delta wave in England were seeded before travel restrictions were introduced. Increasing inter-regional travel within England drove the nationwide dissemination of Delta, with some cities receiving more than 2,000 observable lineage introductions from elsewhere. Subsequently, increased levels of local population mixing-and not the number of importations-were associated with the faster relative spread of Delta. The invasion dynamics of Delta depended on spatial heterogeneity in contact patterns, and our findings will inform optimal spatial interventions to reduce the transmission of current and future variants of concern, such as Omicron (Pango lineage B.1.1.529)., (© 2022. The Author(s).)

Three lineages (BA.1, BA.2 and BA.3) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern predominantly drove South Africa's fourth Coronavirus Disease 2019 (COVID-19) wave. We have now identified two new lineages, BA.4 and BA.5, responsible for a fifth wave of infections. The spike proteins of BA.4 and BA.5 are identical, and similar to BA.2 except for the addition of 69-70 deletion (present in the Alpha variant and the BA.1 lineage), L452R (present in the Delta variant), F486V and the wild-type amino acid at Q493. The two lineages differ only outside of the spike region. The 69-70 deletion in spike allows these lineages to be identified by the proxy marker of S-gene target failure, on the background of variants not possessing this feature. BA.4 and BA.5 have rapidly replaced BA.2, reaching more than 50% of sequenced cases in South Africa by the first week of April 2022. Using a multinomial logistic regression model, we estimated growth advantages for BA.4 and BA.5 of 0.08 (95% confidence interval (CI): 0.08-0.09) and 0.10 (95% CI: 0.09-0.11) per day, respectively, over BA.2 in South Africa. The continued discovery of genetically diverse Omicron lineages points to the hypothesis that a discrete reservoir, such as human chronic infections and/or animal hosts, is potentially contributing to further evolution and dispersal of the virus., (© 2022. The Author(s).)

Aims of the Study: Since 2014, the Swiss Hepatitis Strategy (SHS) has targeted the elimination of Hepatitis C Virus (HCV) in Switzerland. The epidemiology of HCV is diverse across Swiss cantons, therefore cantonal-level screening and treatment strategies should be developed. This study aimed to identify scenarios to achieve HCV elimination in the canton of Bern by 2030., Methods: A preexisting Markov disease burden model was populated with data for Bern, and used to forecast the current and future prevalence of HCV, annual liver-related deaths (LRDs), and incidence of hepatocellular carcinoma and decompensated cirrhosis until 2030. Scenarios were developed to assess the current standard of care and potential long-term impact of the COVID-19 crisis on the HCV infected population. Additionally, potential scenarios for achieving the WHO 2030 targets and the SHS 2025 and 2030 targets (reduction of new cases of HCV, HCV-related mortality and viremic HCV cases) were identified., Results: In 2019, there were an estimated 4,600 (95% UI: 3,330-4,940) viremic infections in the canton of Bern and 57% (n = 2,600) of viremic cases were diagnosed. This modelling forecasted a 10% increase in LRDs (28 in 2020 to 31 in 2030) with the current standard of care and a 50% increase in LRDs in a scenario assuming long-term delays. To achieve the WHO and SHS targets, the canton of Bern needs to increase the annual number of patients diagnosed (from 90 in 2019 to 250 per year in 2022-2024 [WHO], or 500 per year in 2022-2025 [SHS]) and treated (from 130 in 2019 to 340 per year in 2022-2024 [WHO] or 670 per year in 2022-2025 [SHS])., Conclusions: The SHS goals and the WHO targets for HCV elimination can be achieved in the Swiss canton of Bern by 2030; however, not at the current pace of screening, linkage to care and treatment., Competing Interests: Olivier Schorr was a Master in Public Health university student at the time this work was completed and an employee of Gilead Sciences; This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Although recombination is a feature of coronavirus evolution, previously detected recombinant lineages of SARS-CoV-2 have shown limited circulation thus far. Here, we present a detailed phylogenetic analysis of four SARS-CoV-2 lineages to investigate the possibility of virus recombination among them. Our analyses reveal well-supported phylogenetic differences between the Orf1ab region encoding viral non-structural proteins and the rest of the genome, including Spike (S) protein and remaining reading frames. By accounting for several deletions in NSP6, Orf3a, and S, we conclude that the B.1.628 major cluster, now designated as lineage XB, originated from a recombination event between viruses of B.1.631 and B.1.634 lineages. This scenario is supported by the spatiotemporal distribution of these lineages across the USA and Mexico during 2021, suggesting that the recombination event originated in this geographical region. This event raises important questions regarding the role and potential effects of recombination on SARS-CoV-2 evolution., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Cognitive deficits occur in all different grades of glioma. In a recent study, we found these deficits to be independently, and possibly causally, related to survival in diffuse gliomas. In this study, we investigated whether the relationship between cognition and survival was mediated by three different factors: undertreatment, complications of treatment, and compliance. We hypothesized that patients with cognitive impairment may undergo less intensive treatment, be less compliant, and suffer more from complications, resulting in shortened survival for cognitively impaired patients., Methods: In a retrospective cohort study of patients undergoing awake craniotomy between operative neuropsychological assessments in five cognitive domains. We used Structural Equation Modeling to perform mediation analyses. Mediation analyses are analyses to evaluate whether a variable is a factor in the causal chain, referred to as an intermediate factor., Results: In total 254 patients were included, of whom 111 patients were LGG patients and 143 were HGG patients. The most frequently impaired domain was memory (37.8% ≤-2 SD ) in HGG and attention and executive functioning in LGG (33.3 ≤-1.5 SD). We confirmed the significant association between different cognitive domains and survival. These associations could not be explained by one of the aforementioned intermediate factors., Conclusions: This suggests that other mechanisms should be involved in the relation between cognition and survival. Hypothetically, cognitive functioning can act as a marker for diffuse infiltration of the tumor or cognitive functioning and survival could be determined by overlapping germline and somatic tumoral molecular-genetic factors., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Pain is one of the most common health problems and has a severe impact on quality of life. Yet, a suitable and efficient treatment is still not available for all patient populations suffering from pain. Interestingly, recent research shows that low threshold mechanosensory C-tactile (CT) fibres have a modulatory influence on pain. CT-fibres are activated by slow gentle stroking of the hairy skin, providing a pleasant sensation. Consequently, slow gentle stroking is known as affective touch. Currently, a clear overview of the way affective touch modulates pain, at a neural level, is missing. This review aims to present such an overview. To explain the interaction between affective touch and pain, first the neural basis of the affective touch system and the neural processing of pain will be described. To clarify these systems, a schematic illustration will be provided in every section. Hereafter, a novel model of interactions between affective touch and pain systems will be introduced. Finally, since affective touch might be suitable as a new treatment for chronic pain, possible clinical implications will be discussed., (© 2021 The Authors. Journal of Neuropsychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

Syphilis, which is caused by the sexually transmitted bacterium Treponema pallidum subsp. pallidum, has an estimated 6.3 million cases worldwide per annum. In the past ten years, the incidence of syphilis has increased by more than 150% in some high-income countries, but the evolution and epidemiology of the epidemic are poorly understood. To characterize the global population structure of T. pallidum, we assembled a geographically and temporally diverse collection of 726 genomes from 626 clinical and 100 laboratory samples collected in 23 countries. We applied phylogenetic analyses and clustering, and found that the global syphilis population comprises just two deeply branching lineages, Nichols and SS14. Both lineages are currently circulating in 12 of the 23 countries sampled. We subdivided T. p. pallidum into 17 distinct sublineages to provide further phylodynamic resolution. Importantly, two Nichols sublineages have expanded clonally across 9 countries contemporaneously with SS14. Moreover, pairwise genome analyses revealed examples of isolates collected within the last 20 years from 14 different countries that had genetically identical core genomes, which might indicate frequent exchange through international transmission. It is striking that most samples collected before 1983 are phylogenetically distinct from more recently isolated sublineages. Using Bayesian temporal analysis, we detected a population bottleneck occurring during the late 1990s, followed by rapid population expansion in the 2000s that was driven by the dominant T. pallidum sublineages circulating today. This expansion may be linked to changing epidemiology, immune evasion or fitness under antimicrobial selection pressure, since many of the contemporary syphilis lineages we have characterized are resistant to macrolides., (© 2021. The Author(s).)

Genomic epidemiology, which links pathogen genomes with associated metadata to understand disease transmission, has become a key component of outbreak response. Decreasing costs of genome sequencing and increasing computational power provide opportunities to generate and analyse large viral genomic datasets that aim to uncover the spatial scales of transmission, the demographics contributing to transmission patterns, and to forecast epidemic trends. Emerging sources of genomic data and associated metadata provide new opportunities to further unravel transmission patterns. Key challenges include how to integrate genomic data with metadata from multiple sources, how to generate efficient computational algorithms to cope with large datasets, and how to establish sampling frameworks to enable robust conclusions., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Diffuse gliomas, which are at WHO grade II-IV, are progressive primary brain tumors with great variability in prognosis. Our aim was to investigate whether pre-operative cognitive functioning is of added value in survival prediction in these patients. Methods: In a retrospective cohort study of patients undergoing awake craniotomy between 2010 and 2019 we performed pre-operative neuropsychological assessments in five cognitive domains. Their added prognostic value on top of known prognostic factors was assessed in two patient groups [low- (LGG) and high-grade gliomas (HGG]). We compared Cox proportional hazards regression models with and without the cognitive domain by means of loglikelihood ratios tests (LRT), discriminative performance measures (by AUC), and risk classification [by Integrated Discrimination Index (IDI)]. Results: We included 109 LGG and 145 HGG patients with a median survival time of 1,490 and 511 days, respectively. The domain memory had a significant added prognostic value in HGG as indicated by an LRT ( p -value = 0.018). The cumulative AUC for HGG with memory included was.78 ( SD = 0.017) and without cognition 0.77 ( SD = 0.018), IDI was 0.043 (0.000-0.102). In LGG none of the cognitive domains added prognostic value. Conclusions: Our findings indicated that memory deficits, which were revealed with the neuropsychological examination, were of additional prognostic value in HGG to other well-known predictors of survival., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 van Kessel, Schuit, Huenges Wajer, Ruis, De Vos, Verhoeff, Seute, van Zandvoort, Robe and Snijders.)

Mycobacterium abscessus, a multidrug-resistant nontuberculous mycobacterium, has emerged as a major pathogen affecting people with cystic fibrosis (CF). Although originally thought to be acquired independently from the environment, most individuals are infected with one of several dominant circulating clones (DCCs), indicating the presence of global transmission networks of M. abscessus. How and when these clones emerged and spread globally is unclear. Here, we use evolutionary analyses of isolates from individuals both with and without CF to reconstruct the population history, spatiotemporal spread and recent transmission networks of the DCCs. We demonstrate synchronous expansion of six unrelated DCCs in the 1960s, a period associated with major changes in CF care and survival. Each of these clones has spread globally as a result of rare intercontinental transmission events. We show that the DCCs, but not environmentally acquired isolates, exhibit a specific smoking-associated mutational signature and that current transmission networks include individuals both with and without CF. We therefore propose that the DCCs initially emerged in non-CF populations but were then amplified and spread through the CF community. While individuals with CF are probably the most permissive host, non-CF individuals continue to play a key role in transmission networks and may facilitate long-distance transmission., (© 2021. The Author(s).)

Understanding the causes and consequences of the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern is crucial to pandemic control yet difficult to achieve because they arise in the context of variable human behavior and immunity. We investigated the spatial invasion dynamics of lineage B.1.1.7 by jointly analyzing UK human mobility, virus genomes, and community-based polymerase chain reaction data. We identified a multistage spatial invasion process in which early B.1.1.7 growth rates were associated with mobility and asymmetric lineage export from a dominant source location, enhancing the effects of B.1.1.7's increased intrinsic transmissibility. We further explored how B.1.1.7 spread was shaped by nonpharmaceutical interventions and spatial variation in previous attack rates. Our findings show that careful accounting of the behavioral and epidemiological context within which variants of concern emerge is necessary to interpret correctly their observed relative growth rates., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

The response of the global virus genomics community to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been unprecedented, with significant advances made towards the 'real-time' generation and sharing of SARS-CoV-2 genomic data. The rapid growth in virus genome data production has necessitated the development of new analytical methods that can deal with orders of magnitude of more genomes than previously available. Here, we present and describe Phylogenetic Assignment of Named Global Outbreak Lineages (pangolin), a computational tool that has been developed to assign the most likely lineage to a given SARS-CoV-2 genome sequence according to the Pango dynamic lineage nomenclature scheme. To date, nearly two million virus genomes have been submitted to the web-application implementation of pangolin, which has facilitated the SARS-CoV-2 genomic epidemiology and provided researchers with access to actionable information about the pandemic's transmission lineages., (© The Author(s) 2021. Published by Oxford University Press.)

Although almost all mycobacterial species are saprophytic environmental organisms, a few, such as Mycobacterium tuberculosis , have evolved to cause transmissible human infection. By analyzing the recent emergence and spread of the environmental organism M. abscessus through the global cystic fibrosis population, we have defined key, generalizable steps involved in the pathogenic evolution of mycobacteria. We show that epigenetic modifiers, acquired through horizontal gene transfer, cause saltational increases in the pathogenic potential of specific environmental clones. Allopatric parallel evolution during chronic lung infection then promotes rapid increases in virulence through mutations in a discrete gene network; these mutations enhance growth within macrophages but impair fomite survival. As a consequence, we observe constrained pathogenic evolution while person-to-person transmission remains indirect, but postulate accelerated pathogenic adaptation once direct transmission is possible, as observed for M. tuberculosis Our findings indicate how key interventions, such as early treatment and cross-infection control, might restrict the spread of existing mycobacterial pathogens and prevent new, emergent ones., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: Diffuse gliomas (WHO grade II-IV) are progressive primary brain tumors with great variability in prognosis. Cognitive deficits are of important prognostic value for survival in diffuse gliomas. Until now, few studies focused on domain-specific neuropsychological assessment and rather used MMSE as a measure for cognitive functioning. Additionally, these studies did not take WHO 2016 diagnosis into account. We performed a retrospective cohort study with the aim to investigate the independent relationship between cognitive functioning and survival in treatment-naive patients undergoing awake surgery for a diffuse glioma., Methods: In patients undergoing awake craniotomy between 2010 and 2017, we performed pre-operative neuropsychological assessments in five cognitive domains, with special attention for the domains executive functioning and memory. We evaluated the independent relation between these domains and survival, in a Cox proportional hazards model that included state-of-the-art integrated histomolecular ('layered' or WHO-2016) classification of the gliomas and other known prognostic factors., Results: We included 197 patients. Cognitive impairments (Z-values ≦ - 2.0) were most frequent in the domains memory (18.3%) and executive functioning (25.9%). Impairments in executive functioning and memory were significantly correlated with survival, even after correcting for the possible confounders. Analyses with the domains language, psychomotor speed, and visuospatial functioning yielded no significant results. Extensive domain-specific neuropsychological assessment was more strongly correlated to survival than MMSE., Conclusion: Cognitive functioning is independently related to survival in diffuse glioma patients. Possible mechanisms underlying this relationship include the notion of cognitive functioning as a marker for diffuse infiltration of the tumor and the option that cognitive functioning and survival are determined by overlapping genetic pathways and biomarkers.