Congress of Neurological Surgeons Systematic Review and Evidence-based Guidelines Update on the Role of Neuropathology in the Management of Progressive Glioblastoma in Adults

Target population These recommendations apply to adult patients with progressive or recurrent glioblastoma (GBM).QuestionFor adult patients with progressive glioblastoma does testing for Isocitrate Dehydrogenase (IDH) 1 or 2 mutations provide new additional management or prognostic information beyond that derived from the tumor at initial presentation?RecommendationLevel III: Repeat IDH mutation testing is not necessary if the tumor is histologically similar to the primary tumor and the patient’s clinical course is as expected. Question For adult patients with progressive glioblastoma does repeat testing for MGMT promoter methylation provide new or additional management or prognostic information beyond that derived from the tumor at initial presentation and what methods of detection are optimal?Recommendation Level III: Repeat MGMT promoter methylation is not recommended. Question For adult patients with progressive glioblastoma does EGFR amplification or mutation testing provide management or prognostic information beyond that provided by histologic analysis and if performed on previous tissue samples, does it need to be repeated?RecommendationLevel III: In cases that are difficult to classify as glioblastoma on histologic features EGFR amplification testing may help in classification. If a previous EGFR amplification was detected, repeat testing is not necessary. Repeat EGFR amplification or mutational testing may be recommended in patients in which target therapy is being considered.Question For adult patients with progressive glioblastoma does whole genome or large panel sequencing provide management or prognostic information beyond that derived from histologic analysis?RecommendationLevel III: Primary or repeat whole genome or large panel sequencing may be considered in patients who are eligible or interested in molecularly guided therapy or clinical trials.QuestionFor adult patients with progressive glioblastoma should immune checkpoint biomarker testing be performed to provide management and prognostic information beyond that obtained from histologic analysis?RecommendationLevel III: The current evidence does not support making PD-L1 or mismatch repair (MMR) enzyme activity a component of standard testing.QuestionFor adult patients with progressive glioblastoma are there meaningful biomarkers for bevacizumab responsiveness and does their assessment provide additional information for tumor management and prognosis beyond that learned by standard histologic analysis?RecommendationLevel III: No established Bevacizumab biomarkers are currently available based upon the inclusion criteria of this guideline.

Competition between Entrainment Phenomenon and Chaos in a Quantum-Cascade Laser under Strong Optical Reinjection

The topic of external optical feedback in quantum-cascade lasers is relevant for stability and beam-properties considerations. Albeit less sensitive to external optical feedback than other lasers, quantum-cascade lasers can exhibit several behaviors under such feedback, and those are relevant for a large panel of applications, from communication to ranging and sensing. This work focused on a packaged Fabry–Perot quantum-cascade laser under strong external optical feedback and shows the influence of the beam-splitter characteristics on the optical power properties of this commercially available laser. The packaged quantum-cascade laser showed extended conditions of operation when subject to strong optical feedback, and the maximum power that can be extracted from the external cavity was also increased. When adding a periodic electrical perturbation, various non-linear dynamics were observed, and this complements previous efforts about the entrainment phenomenon in monomode quantum-cascade lasers, with the view of optimizing private communication based on mid-infrared quantum-cascade lasers. Overall, this work is a step forward in understanding the behavior of the complex quantum-cascade-laser structure when it is subjected to external optical feedback.

Genetic Potential of Dissulfurimicrobium hydrothermale, an Obligate Sulfur-Disproportionating Thermophilic Microorganism

The biochemical pathways of anaerobic sulfur disproportionation are only partially deciphered, and the mechanisms involved in the first step of S0-disproportionation remain unknown. Here, we present the results of sequencing and analysis of the complete genome of Dissulfurimicrobium hydrothermale strain Sh68T, one of two strains isolated to date known to grow exclusively by anaerobic disproportionation of inorganic sulfur compounds. Dissulfurimicrobium hydrothermale Sh68T is a motile, thermophilic, anaerobic, chemolithoautotrophic microorganism isolated from a hydrothermal pond at Uzon caldera, Kamchatka, Russia. It is able to produce energy and grow by disproportionation of elemental sulfur, sulfite and thiosulfate. Its genome consists of a circular chromosome of 2,025,450 base pairs, has a G + C content of 49.66% and a completion of 97.6%. Genomic data suggest that CO2 assimilation is carried out by the Wood–Ljungdhal pathway and that central anabolism involves the gluconeogenesis pathway. The genome of strain Sh68T encodes the complete gene set of the dissimilatory sulfate reduction pathway, some of which are likely to be involved in sulfur disproportionation. A short sequence protein of unknown function present in the genome of strain Sh68T is conserved in the genomes of a large panel of other S0-disproportionating bacteria and was absent from the genomes of microorganisms incapable of elemental sulfur disproportionation. We propose that this protein may be involved in the first step of elemental sulfur disproportionation, as S0 is poorly soluble and unable to cross the cytoplasmic membrane in this form.

The Problem of Densification of Large-Panel Housing Estates upon the Example of Cracow

The paper focuses on the phenomenon of intense, uncontrolled densification of large-panel housing estates in Poland. Despite the fact that such housing estates as a legacy of the Modernist concept of segregation of functions are often burdened with problems, they still have considerable potential, which results predominantly from their urban advantages, such as functional and spatial logic, large amounts of open public space, and abundance of greenery. Unfortunately, this potential is being destroyed by introducing new buildings, ignoring the existing urban layout of the housing estate along with its original compositional assumptions. This type of densification results from—without limitations—the pressure exerted by developers in the free-market economy, and it often leads to problems such as the devastation of urban layouts of these housing estates, breaking the continuity of public spaces, appropriation of green areas, strengthening of monofunctionality, etc. This problem is becoming noticeable in the scientific debate, although it is still difficult to obtain reliable data illustrating the densifications of such housing estates. The goal of this paper is to present the scales and character of such densifications of the large-panel housing estates, which pose a threat of devastation of their urban layouts often considered as urban heritage. The paper proposes a method of a quantitative analysis of the housing estates with reference to the increase in the built-up area and a qualitative analysis of the character of development with reference to its distribution. This method comprises a sequence of subsequent steps with relevant criteria. In the results, it demonstrates the scale of the problem, which in many cases is already big and still growing. The resultant threat of devastation of the urban layout and its consequences are presented upon selected examples of housing estates in Cracow, Poland. This paper is a voice in a discussion devoted to the current status, but most of all to the future of large-panel housing estates, particularly in terms of their protection as valuable achievements of urban planning of the second half of the 20th century, and to stopping unfavorable tendencies of urban destruction.

Receptor binding and escape from Beta antibody responses drive Omicron-B.1.1.529 evolution

On the 24th November 2021 the sequence of a new SARS CoV-2 viral isolate spreading rapidly in Southern Africa was announced. Omicron contains a total of 30 substitutions plus deletions and an insertion in Spike, far more than any previously reported variant. The mutations include those previously identified by In-vitro evolution to contribute to high-affinity binding to ACE2, including mutations Q498R and N501Y critical in forming additional interactions in the interface. Together with increased charge complementarity between the RBD and ACE2, these substantially increase affinity and potentially virus transmissibility through increased syncytia formation. Further mutations promote immune evasion. We have studied the binding of a large panel of potent monoclonal antibodies generated from early pandemic or Beta infected cases. Mutations in Omicron will likely compromise the binding of many of these and additionally, the binding of antibodies under commercial development, however residual binding should provide protection from severe disease.

A Computational Journey across Nitroxide Radicals: From Structure to Spectroscopic Properties and Beyond

Nitroxide radicals are characterized by a long-lived open-shell electronic ground state and are strongly sensitive to the chemical environment, thus representing ideal spin probes and spin labels for paramagnetic biomolecules and materials. However, the interpretation of spectroscopic parameters in structural and dynamic terms requires the aid of accurate quantum chemical computations. In this paper we validate a computational model rooted into double-hybrid functionals and second order vibrational perturbation theory. Then, we provide reference quantum chemical results for the structures, vibrational frequencies and other spectroscopic features of a large panel of nitroxides of current biological and/or technological interest.

Add, Transform, and Utilize. Possibilities of Applying Druot, Lacaton, and Vassal’s Modernization Strategies and Solutions in Polish Large-Panel Housing Estates

In 2004, in response to France’s 1960s and 1970s urban regeneration program proposing the demolition and redevelopment of large scale social housing developments, Frédérik Druot, Anne Lacaton, and Jean-Philippe Vassal created their PLUS theory (PLUS—Les grands ensembles de logements–Territoires d’exception). Its main aim was to modernize the existing buildings, and to add extra living space, functional freedom, and comfort. This essay examines the PLUS strategy and two of the architects’ projects: the Bois le Prêtre Tower in Paris and the Grand Parc housing estate in Bordeaux. Its aim is to examine the tools used by the architects and investigate the purposefulness and potential of using their solutions in Polish large-scale prefabricated housing estates. Combining the categories of luxury and saving in redevelopment of housing estates paves the way for a new outlook. Maximizing living space, quality, and freedom of living in housing facilities that are not part of the commercial luxury segment of the housing market may prevent potential gentrification and homogenization of the social structure in individual city districts.

Community oncologists’ perceptions and utilization of large-panel genomic tumor testing

Purpose Large-panel genomic tumor testing (GTT) is an emerging technology with great promise but uncertain clinical value. Previous research has documented variability in academic oncologists’ perceptions and use of GTT, but little is known about community oncologists’ perceptions of GTT and how perceptions relate to clinicians' intentions to use GTT. Methods Community oncology physicians (N = 58) participating in a statewide initiative aimed at improving access to large-panel GTT completed surveys assessing their confidence in using GTT, attitudes regarding the value of GTT, perceptions of barriers to GTT implementation, and future intentions to use GTTs. Descriptive and multivariable regression analyses were conducted to characterize these perceptions and to explore the relationships between them. Results There was substantial variability in clinicians’ perceptions of GTT. Clinicians generally had moderate confidence in their ability to use GTT, but lower confidence in patients’ ability to understand test results and access targeted treatment. Clinicians had positive attitudes regarding the value of GTT. Clinicians’ future intentions to use GTT were associated with greater confidence in using GTT and greater perceived barriers to implementing GTT, but not with attitudes about the value of GTT. Conclusions Community oncologists’ perceptions of large-panel genomic tumor testing are variable, and their future intentions to use GTT are associated with both their confidence in and perceived barriers to its use, but not with their attitudes towards GTT. More research is needed to understand other factors that determine how oncologists perceive and use GTT in clinical practice.

Transcriptomic evidence for versatile metabolic activities of mercury cycling microorganisms in brackish microbial mats

Methylmercury, biomagnifying through food chains, is highly toxic for aquatic life. Its production and degradation are largely driven by microbial transformations; however, diversity and metabolic activity of mercury transformers, resulting in methylmercury concentrations in environments, remain poorly understood. Microbial mats are thick biofilms where oxic and anoxic metabolisms cooccur, providing opportunities to investigate the complexity of the microbial mercury transformations over contrasted redox conditions. Here, we conducted a genome-resolved metagenomic and metatranscriptomic analysis to identify putative activity of mercury reducers, methylators and demethylators in microbial mats strongly contaminated by mercury. Our transcriptomic results revealed the major role of rare microorganisms in mercury cycling. Mercury methylators, mainly related to Desulfobacterota, expressed a large panel of metabolic activities in sulfur, iron, nitrogen, and halogen compound transformations, extending known activities of mercury methylators under suboxic to anoxic conditions. Methylmercury detoxification processes were dissociated in the microbial mats with methylmercury cleavage being carried out by sulfide-oxidizing Thiotrichaceae and Rhodobacteraceae populations, whereas mercury reducers included members of the Verrucomicrobia, Bacteroidetes, Gammaproteobacteria, and different populations of Rhodobacteraceae. However most of the mercury reduction was potentially carried out anaerobically by sulfur- and iron-reducing Desulfuromonadaceae, revising our understanding of mercury transformers ecophysiology.

Integrating Digital Twin Technology Into Large Panel System Estates Retrofit Projects

As sustainability is now a standard for the proposed developments, the focus ought to be shifted towards the existing buildings and, among them, the worldwide stock of large panel system (LPS) buildings. Major upgrades and retrofits were done to some of the LPS estates in Germany and France, but a leading sustainable way must still be developed for LPS buildings in Eastern European countries, where apartments in those half-a-century-old estates are privately owned. Both sustainability and ownership issues make the demolition option redundant, and therefore the method for deep thermal retrofit and urban intervention is being developed with the use of BIM simulation tools. Digital twin (DT) technology allows for calibration to intertwine with the Internet of Things applications that reward the inhabitants for sustainable behaviour while feeding the relevant data back to the DT. Thanks to this, smart technology can be used to raise the level of social participation in the projects and thus help educate the end-users, which is paramount in establishing and maintaining good ecological habits, and as such, also for the efficacy and viability of the final endeavour. This article proposes a procedure of creating a 3D model typology repository for facilitating DT technology to provide a good analytical tool for community consultation and enable virtual testing of technical and urban solutions before implementation. It aims to determine the method for virtual technology to give deteriorating estates a new lease of life and improve their perception in the wider community while being a conduit for the adaptation of CEE to the digital revolution.