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Treatment of the tumor and dural margin with surgery and sometimes radiation are cornerstones of therapy for meningioma. Molecular classifications have provided insights into the biology of disease; however, response to treatment remains heterogeneous. In this study, we used retrospective data on 2,824 meningiomas, including molecular data on 1,686 tumors and 100 prospective meningiomas, from the RTOG-0539 phase 2 trial to define molecular biomarkers of treatment response. Using propensity score matching, we found that gross tumor resection was associated with longer progression-free survival (PFS) across all molecular groups and longer overall survival in proliferative meningiomas. Dural margin treatment (Simpson grade 1/2) prolonged PFS compared to no treatment (Simpson grade 3). Molecular group classification predicted response to radiotherapy, including in the RTOG-0539 cohort. We subsequently developed a molecular model to predict response to radiotherapy that discriminates outcome better than standard-of-care classification. This study highlights the potential for molecular profiling to refine surgical and radiotherapy decision-making.
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BACKGROUND: Aside from surgical resection, the only standard of care treatment modality for meningiomas is radiotherapy (RT). Despite this, few studies have focused on identifying clinical covariates associated with failure of fractionated RT following surgical resection (fRT), and the timing of fRT following surgery still remains controversial (adjuvant versus salvage fRT). We assessed the outcomes of the largest, multi-institutional cohort of surgically resected meningiomas treated with subsequent adjuvant and salvage fRT to identify factors associated with local freedom from recurrence (LFFR) over 3-10 years post-fRT and to determine the optimal timing of fRT. METHODS: Patients with intracranial meningiomas who underwent surgery and fRT between 1997 and 2018 were included. Primary endpoints were radiographic recurrence/progression and time to progression from the completion of fRT. RESULTS: 404 meningiomas were included for analysis. Of these, 167 (41.3%) recurred post-fRT. Clinical covariates independently associated with worse PFS post-fRT included receipt of previous RT to the meningioma, having a WHO grade 3 meningioma or recurrent meningioma, the meningioma having a higher MIB1-index or brain invasion on pathology, and older patient age at diagnosis. Subgroup analysis identified higher MIB1-index as a histological factor associated with poorer LFFR in WHO grade 2 meningiomas. 179 patients underwent adjuvant RT shortly after surgery whereas 225 patients had delayed, salvage fRT after recurrence/progression. Following propensity score matching, patients that underwent adjuvant fRT had improved LFFR post-fRT compared to those that received salvage fRT. CONCLUSION: There is a paucity of clinical factors that can predict a meningioma's response to fRT following surgery. Adjuvant fRT may be associated with improved PFS post-fRT compared to salvage fRT. Molecular biomarkers of RT-responsiveness are needed to better inform fRT treatment decisions.
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Background: Surgery is the primary treatment for most meningiomas. However, primary fractionated radiotherapy (fRT) remains an option for patients with larger meningiomas in challenging anatomic locations or patients at prohibitively high surgical risk. Outcome prediction for these patients is uncertain and cannot be guided by histopathology without available tumor tissue from surgery. Therefore, we aimed to assess the clinical factors that contribute to treatment failure in a large cohort of meningiomas consecutively treated with fRT as primary therapy, with the goal of identifying predictors of response. Methods: Patients treated with primary fRT for intracranial meningiomas from 1998 to 2017 were reviewed. Those who received primary surgical resection, radiosurgery, previous fRT, or had <6 months of clinical follow-up were excluded. We applied logistic regression and Cox regression modeling to ascertain key predictors of treatment failure, progression-free survival (PFS), and adverse events (AE) following fRT. Results: Our cohort included 137 meningiomas, 21 of which progressed after fRT (median PFS 3.45 years). Progressive meningiomas had a larger median gross tumor volume (GTV) compared to those that remained stable (19.1 cm3 vs 9.6 cm3, p = 2.86 × 10-2). GTV > 11.27 cm3 was independently predictive of progression and larger GTV was associated with higher risk of significant (grades 3/4) AE following fRT. Cavernous sinus and optic nerve sheath meningiomas had overall excellent outcomes post-fRT. Conclusions: We present a large cohort of meningiomas treated with primary fRT and find GTV and anatomic location to be key predictors of outcome, adding to the complex treatment considerations for this heterogeneous disease.
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One of the most widely accepted forms of treatment for coronary artery disease (CAD) is the implementation of stents into the vessel. This area of research is constantly evolving, ranging from bare-metal stents through drug-eluting stents and, more recently, approaching bioresorbable stents and polymer-free stents. This article reviews the evolution of all these devices and emphasizes how they might be further evolved to provide an optimal coronary stent and overcome unsolved challenges in stent development. We thoroughly evaluated a number of published studies in order to advance coronary stent technologies. Additionally, we looked for various literature that highlighted the inadequacies of the coronary stents that are currently available and how they might be modified to create the optimum coronary stent. Coronary stents have significantly improved clinical outcomes in interventional cardiology, but there are still a number of drawbacks, including an persisted risk of thrombosis due to endothelial injury and in-stent restenosis. Gene eluting stents (GES) and customized coronary stents with self-reporting stent sensors are appealing alternatives to existing stent approaches. Considering the adequacy of these gene eluting stents (GES), customized coronary stents produced by novel 4D printing technologies and integrated self-reporting stent sensors should be assumed for anticipating future advancements to optimal coronary stent devices; however, more interventional evidence is required to determine the future prospects of these stent innovations.
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Topic modeling is a machine learning algorithm based on statistics that follows unsupervised machine learning techniques for mapping a high-dimensional corpus to a low-dimensional topical subspace, but it could be better. A topic model's topic is expected to be interpretable as a concept, i.e., correspond to human understanding of a topic occurring in texts. While discovering corpus themes, inference constantly uses vocabulary that impacts topic quality due to its size. Inflectional forms are in the corpus. Since words frequently appear in the same sentence and are likely to have a latent topic, practically all topic models rely on co-occurrence signals between various terms in the corpus. The topics get weaker because of the abundance of distinct tokens in languages with extensive inflectional morphology. Lemmatization is often used to preempt this problem. Gujarati is one of the morphologically rich languages, as a word may have several inflectional forms. This paper proposes a deterministic finite automaton (DFA) based lemmatization technique for the Gujarati language to transform lemmas into their root words. The set of topics is then inferred from this lemmatized corpus of Gujarati text. We employ statistical divergence measurements to identify semantically less coherent (overly general) topics. The result shows that the lemmatized Gujarati corpus learns more interpretable and meaningful subjects than unlemmatized text. Finally, results show that lemmatization curtails the size of vocabulary decreases by 16% and the semantic coherence for all three measurements-Log Conditional Probability, Pointwise Mutual Information, and Normalized Pointwise Mutual Information-from -9.39 to -7.49, -6.79 to -5.18, and -0.23 to -0.17, respectively.
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Intracranial metastatic disease (IMD) complicates the course of nearly 2-4% of patients with systemic cancer. The prevalence of IMD has been increasing over the past few decades. Historically, definitive treatment for brain metastases (BM) has been limited to radiation therapy or surgical resection. Chemotherapies have not typically proven valuable in the treatment of IMD, with the exception of highly chemotherapy-sensitive lesions. Recent data have supported a role for systemic targeted therapies and immune checkpoint inhibitors (ICIs) in the treatment of select patients with IMD. There remains, however, a clear clinical need for further investigation to delineate the role of ICIs in patients with BM. In this review, we outline and describe recent and current efforts to identify the efficacy of ICI therapy in patients with IMD.
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Brain Neoplasms , Immune Checkpoint Inhibitors , Humans , Immune Checkpoint Inhibitors/therapeutic use , Brain Neoplasms/therapy , ImmunotherapyABSTRACT
BACKGROUND: Lipomatous meningiomas are an extremely rare, benign meningioma subtype subcategorized under metaplastic meningioma in the most recent 2021 update to the World Health Organization classification. They make up less than 0.3% of all meningiomas and, to date, less than 70 cases have been reported in the literature, none of which have undergone molecular profiling. This study aims to promote the utility of molecular profiling to better diagnose these rare tumors. OBSERVATIONS: The authors present the first case of a lipomatous meningioma with DNA methylation profiling that both confirmed its benign biology and uncovered unique cytogenetic changes. Molecular characterization of a lipomatous meningioma confirmed its diagnosis as a distinct, benign meningioma subtype and revealed several copy number variations on chromosome 8 and in NF2 and SMARCB1. Here we discuss some of the radiological and histopathological features of lipomatous meningiomas, how they can be used to distinguish from other meningiomas and other similarly presenting tumors, and a brief literature review discussing the pathophysiology and presentation of this rare tumor. LESSONS: This study provides evidence supporting the use of molecular profiling to diagnose lipomatous meningiomas and guide their clinical management more accurately.
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The bank vole (BV) prion protein (PrP) can function as a universal acceptor of prions. However, the molecular details of BVPrP's promiscuity for replicating a diverse range of prion strains remain obscure. To develop a cultured cell paradigm capable of interrogating the unique properties of BVPrP, we generated monoclonal lines of CAD5 cells lacking endogenous PrP but stably expressing either hamster (Ha), mouse (Mo), or BVPrP (M109 or I109 polymorphic variants) and then challenged them with various strains of mouse or hamster prions. Cells expressing BVPrP were susceptible to both mouse and hamster prions, whereas cells expressing MoPrP or HaPrP could only be infected with species-matched prions. Propagation of mouse and hamster prions in cells expressing BVPrP resulted in strain adaptation in several instances, as evidenced by alterations in conformational stability, glycosylation, susceptibility to anti-prion small molecules, and the inability of BVPrP-adapted mouse prion strains to infect cells expressing MoPrP. Interestingly, cells expressing BVPrP containing the G127V prion gene variant, identified in individuals resistant to kuru, were unable to become infected with prions. Moreover, the G127V polymorphic variant impeded the spontaneous aggregation of recombinant BVPrP. These results demonstrate that BVPrP can facilitate cross-species prion replication in cultured cells and that a single amino acid change can override the prion-permissive nature of BVPrP. This cellular paradigm will be useful for dissecting the molecular features of BVPrP that allow it to function as a universal prion acceptor.
Subject(s)
Prion Diseases , Prions , Cricetinae , Animals , Prions/genetics , Prions/metabolism , Prion Proteins/genetics , Prion Proteins/metabolism , Prion Diseases/genetics , Arvicolinae/genetics , Arvicolinae/metabolism , Cells, CulturedABSTRACT
Cryptogenic stroke (CS) represents one-third of all ischaemic strokes. Studies have shown approximately that half of patients with CS have concomitant patent foramen ovale (PFO), with clear data supporting paradoxical embolization as an aetiology of CS. This article is the first of a multi-part review and will detail the history of PFO closure and the clinical trials that have evaluated the efficacy of PFO device closure. Data favour PFO closure in CS for reducing stroke in appropriate patients and should be considered as a treatment modality.
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Bacteriophages, infecting bacterial hosts in every environment on our planet, are a driver of adaptive evolution in bacterial communities. At the same time, the host range of many bacteriophages-and thus one of the selective pressures acting on complex microbial systems in nature-remains poorly characterized. Here, we computationally inferred the putative host ranges of 40 cluster P mycobacteriophages, including members from 6 subclusters (P1-P6). A series of comparative genomic analyses revealed that mycobacteriophages of subcluster P1 are restricted to the Mycobacterium genus, whereas mycobacteriophages of subclusters P2-P6 are likely also able to infect other genera, several of which are commonly associated with human disease. Further genomic analysis highlighted that the majority of cluster P mycobacteriophages harbor a conserved integration-dependent immunity system, hypothesized to be the ancestral state of a genetic switch that controls the shift between lytic and lysogenic life cycles-a temperate characteristic that impedes their usage in antibacterial applications.
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Bacteriophages , Mycobacteriophages , Humans , Mycobacteriophages/genetics , Phylogeny , Host Specificity/genetics , Genome, Viral , Bacteriophages/geneticsABSTRACT
Bacteriophages infecting bacteria of the genus Gordonia have increasingly gained interest in the scientific community for their diverse applications in agriculture, biotechnology, and medicine, ranging from biocontrol agents in wastewater management to the treatment of opportunistic pathogens in pulmonary disease patients. However, due to the time and costs associated with experimental isolation and cultivation, host ranges for many bacteriophages remain poorly characterized, hindering a more efficient usage of bacteriophages in these areas. Here, we perform a series of computational genomic inferences to predict the putative host ranges of all Gordonia cluster DR bacteriophages known to date. Our analyses suggest that BiggityBass (as well as several of its close relatives) is likely able to infect host bacteria from a wide range of genera-from Gordonia to Nocardia to Rhodococcus, making it a suitable candidate for future phage therapy and wastewater treatment strategies.
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Bacteriophages , Gordonia Bacterium , Bacteriophages/genetics , Genome, Viral , Genomics , Gordonia Bacterium/genetics , Humans , Phylogeny , WastewaterABSTRACT
We characterized the complete genome of the cluster P mycobacteriophage Phegasus. Its 47.5-kb genome contains 81 protein-coding genes, 36 of which could be assigned a putative function. Phegasus is most closely related to two subcluster P1 bacteriophages, Mangethe and Majeke, with an average nucleotide identity of 99.63% each.
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Due to the rapid development of the coronavirus disease 2019 (COVID-19) pandemic, the Food and Drug Administration (FDA) expedited the authorization of immunizations to counteract life-threatening COVID-19 effects. COVID-19 immunization was seen as an essential component of surviving endemically with COVID-19. Although there were no major adverse event reports that mandated an early authorization of the mass vaccination approval in initial studies, a few significant adverse events were reported after real-world usage. The most prevalent adverse events are regional reactions, such as discomfort at the injection site. Anaphylactic shock and acute responses were quite infrequent. Current evidence strongly convince the community that the advantages of immunization outweigh the risks. The review investigates the potential adverse reaction in the form of myocarditis caused by the COVID-19 vaccine. Age, sexuality, vaccination type, clinical manifestations, and diagnostic modalities were among the confounding factors associated with vaccine-induced myocarditis. This picture depicts COVID-19 immunization-induced myocarditis and the treatment options available to practitioners. Further evaluation is needed to establish the underlying cause of this association. We compiled the most recent data on SARS-CoV-2 vaccine-induced myocarditis after reviewing available research. Information sources including PubMed and Google Scholar were evaluated retrospectively.
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The coronavirus disease-2019 (COVID-19) pandemic is exacerbating the worldwide healthcare crisis. The pandemic has had an impact on nearly every system of our body. The Food and Drug Administration (FDA) gave immediate authorization of several vaccines to avoid critical COVID-19 outcomes following the rapid spread of the COVID-19. There have only been a few cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination-induced immune thrombocytopenia (ITP) so far. There should be enough information to identify whether some vaccination adverse effects, such as ITP, are caused by the vaccine. This study aims to determine how common ITP occurs after receiving the SARS-CoV-2 vaccine, as well as gender, age, symptoms, biomarkers, predicted outcomes, and sequelae. We looked at a number of research and compiled the best evidence of SARS-CoV-2 vaccine-induced thrombocytopenia currently available. To find the recommended reporting items, the search technique included keywords like "Immune thrombocytopenia," "COVID-19," "SARS-CoV-2," and "Vaccination." The search results were grouped using Boolean operators ("OR," "AND").
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Here, we characterized the complete genome of the Siphoviridae BiggityBass, a lytic subcluster DR bacteriophage infecting Gordonia terrae CAG3. Its 63.2-kb genome contains 84 protein-coding genes, of which 40 could be assigned a putative function. BiggityBass is related most closely to AnClar and Yago84 with 90.61% and 90.52% nucleotide identity, respectively.
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Background: During the COVID-19 pandemic, telemedicine is a quickest expanding service solution to provide improved access to sophisticated healthcare that is efficient, cost-effective, and time-consuming. Methods: This analysis is evaluated on the basis of several studies that look at the history, benefits, various techniques, challenges, uses, and impact of telemedicine in the treatment of heart failure and cardiac rehabilitation as during COVID-19 outbreak. Results: Patients avoided or refused medical treatment during COVID-19 pandemic despite the risk of illness and the threat of infections spreading. Telemedicine has become a non-traditional form of care delivery due to better access and high-end technologies such as virtual consultations, face-to-face video, smartphone visits, two-way text communication, distant patient history, and distal characteristic assessment. Remote monitoring can help manage cardiovascular disease risk factors and increase patient participation in blood pressure, heart failure data, and workout or other activity progress. Conclusion: Based on the findings of past studies, we can infer that telemedicine is still an emerging subject in the treatment and management of cardiovascular disease. Telemedicine and similar technologies will also revolutionize healthcare services by expanding their reach and providing a big pool of database for better research and analysis.
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Increasing municipal solid waste (MSW) generation and environmental concerns have sparked global interest in waste valorization through various waste-to-energy (WtE) to generate renewable energy sources and reduce dependency on fossil-derived fuels and chemicals. These technologies are vital for implementing the envisioned global "bioeconomy" through biorefineries. In light of that, a detailed overview of WtE technologies with their benefits and drawbacks is provided in this paper. Additionally, the biorefinery concept for waste management and sustainable energy generation is discussed. The identification of appropriate WtE technology for energy recovery continues to be a significant challenge. So, in order to effectively apply WtE technologies in the burgeoning bioeconomy, this review provides a comprehensive overview of the existing scenario for sustainable MSW management along with the bottlenecks and perspectives.
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Refuse Disposal , Waste Management , Fossil Fuels , Physical Phenomena , Solid Waste , TechnologyABSTRACT
In recent years, biomass has been reported to obtain a wide range of value-added products. Biochar can be obtained by heating biomass, which aids in carbon sinks, soil amendments, resource recovery, and water retention. Microwave technology stands out among various biomass heating technologies not only for its effectiveness in biomass pyrolysis for the production of biochar and biofuel but also for its speed, volumetrics, selectivity, and efficiency. The features of microwave-assisted biomass pyrolysis and biochar are briefly reviewed in this paper. An informative comparison has been drawn between microwave-assisted pyrolysis and conventional pyrolysis. It focuses mainly on technological and economic scenario of biochar production and environmental impacts of using biochar. This source of knowledge would aid in the exploration of new possibilities and scope for employing microwave-assisted pyrolysis technology to produce biochar.
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Microwaves , Pyrolysis , Biomass , CharcoalABSTRACT
Post-cardiac injury syndrome is a heterogeneous group of conditions that result from autoimmune-mediated inflammation of the pericardium, epicardium, and myocardium. Interventions such as pacemaker lead insertions, percutaneous coronary interventions, radiofrequency ablations, cardiac surgeries, and Swan-Ganz catheterizations can cause myocardial injury leading to post-traumatic pericarditis. This phenomenon can lead to chest pain, recurrent effusions, and fever along with possible complications of heart failure, arrhythmias, conduction abnormalities as well as cardiac tamponade. Herein, we present a case report of a 64-year-old female with a history of sick sinus syndrome managed with a dual-chamber pacemaker who presented with post-cardiac injury syndrome after three months of pacemaker implantation. She developed a recurrent syndrome of fever, chest discomfort, tachycardia with weakness, hemodynamic instability, hemorrhagic serositis, and cardiac tamponade. The mechanism of exudative inflammatory effusions initially remained inconclusive, as the workup for infectious and malignant processes was negative. However, post-cardiac injury syndrome akin to the Dressler syndrome related to screw-in dual-chamber pacemaker implantation remained a possibility. Her condition was acutely managed with a combination of colchicine and glucocorticoid therapy. She was placed on long-term aspirin and colchicine therapy to prevent any recurrences. This article illustrates a case of post-cardiac injury syndrome after dual-chamber pacemaker implantation, including details of evaluation, management, complications and monitoring of patient progress.