Performance Status in Cancer: Not Broken, But Time for an Upgrade?
Ontology highlight
ABSTRACT:
SUBMITTER: Scott JM
PROVIDER: S-EPMC7460152 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Most present-day resonant systems, throughout physics and engineering, are characterized by a strict time-reversal symmetry between the rates of energy coupled in and out of the system, which leads to a trade-off between how long a wave can be stored in the system and the system's bandwidth. Any attempt to reduce the losses of the resonant system, and hence store a (mechanical, acoustic, electronic, optical, or of any other nature) wave for more time, will inevitably also reduce the bandwidth of the system. Until recently, this time-bandwidth limit has been considered fundamental, arising from basic Fourier reciprocity. In this work, using a simple macroscopic, fiber-optic resonator where the nonreciprocity is induced by breaking its time-invariance, we report, in full agreement with accompanying numerical simulations, a time-bandwidth product (TBP) exceeding the 'fundamental' limit of ordinary resonant systems by a factor of 30. We show that, although in practice experimental constraints limit our scheme, the TBP can be arbitrarily large, simply dictated by the finesse of the cavity. Our results open the path for designing resonant systems, ubiquitous in physics and engineering, that can simultaneously be broadband and possessing long storage times, thereby offering a potential for new functionalities in wave-matter interactions.
| S-EPMC7519663 | biostudies-literature
Project description:Abstract: Malignant mesothelioma (MM) is a deadly tumor mainly caused by exposure to asbestos. Unfortunately, no current treatment is able to change significantly the natural history of the disease, which has a poor prognosis in the majority of patients. The non-receptor tyrosine kinase SRC and other SRC family kinase (SFK) members are frequently hyperactivated in many cancer types, including MM. Several works have indeed suggested that SFKs underlie MM cell proliferation, survival, motility, and invasion, overall affecting multiple oncogenic pathways. Consistently, SFK inhibitors effectively counteracted MM cancerous features at the preclinical level. Dasatinib, a multi-kinase inhibitor targeting SFKs, was also assessed in clinical trials either as second-line treatment for patients with unresectable MM or, more recently, as a neoadjuvant agent in patients with resectable MM. Here, we provide an overview of the molecular mechanisms implicating SFKs in MM progression and discuss possible strategies for a more successful clinical application of SFK inhibitors. Our aim is to stimulate discussion and further consideration of these agents in better designed preclinical and clinical studies to make the most of another class of powerful antitumoral drugs, which too often are lost in translation when applied to MM.
| S-EPMC7408838 | biostudies-literature
Project description:The development of anticancer immunotherapy is characterized by several approaches, the most recognized of which include cellular vaccines, tumor-associated antigens (TAAs), neoantigens, and chimeric antigen receptor T cells (CAR-T). This paper presents antigenic essence technology as an effective means for the production of new antigen compositions for anticancer vaccination. This technology is developed via proteomics, cell culture technology, and immunological assays. In terms of vaccine development, it does not fit into any of the above-noted approaches and can be considered a new direction. Here we review the development of this technology, its main characteristics, comparison with existing approaches, and the features that distinguish it as a novel approach to anticancer vaccination. This review will also highlight the benefits of this technology over other approaches, such as the ability to control composition, optimize immunogenicity and similarity to target cells, and evade major histocompatibility complex restriction. The first antigenic essence products, presented under the SANTAVAC brand, are also described.
| S-EPMC7917603 | biostudies-literature
Project description:A topological insulator is a material with an insulating interior but time-reversal symmetry-protected conducting edge states. Since its prediction and discovery almost a decade ago, such a symmetry-protected topological phase has been explored beyond electronic systems in the realm of photonics. Electrons are spin-1/2 particles, whereas photons are spin-1 particles. The distinct spin difference between these two kinds of particles means that their corresponding symmetry is fundamentally different. It is well understood that an electronic topological insulator is protected by the electron's spin-1/2 (fermionic) time-reversal symmetry [Formula: see text] However, the same protection does not exist under normal circumstances for a photonic topological insulator, due to photon's spin-1 (bosonic) time-reversal symmetry [Formula: see text] In this work, we report a design of photonic topological insulator using the Tellegen magnetoelectric coupling as the photonic pseudospin orbit interaction for left and right circularly polarized helical spin states. The Tellegen magnetoelectric coupling breaks bosonic time-reversal symmetry but instead gives rise to a conserved artificial fermionic-like-pseudo time-reversal symmetry, Tp ([Formula: see text]), due to the electromagnetic duality. Surprisingly, we find that, in this system, the helical edge states are, in fact, protected by this fermionic-like pseudo time-reversal symmetry Tp rather than by the bosonic time-reversal symmetry Tb This remarkable finding is expected to pave a new path to understanding the symmetry protection mechanism for topological phases of other fundamental particles and to searching for novel implementations for topological insulators.
| S-EPMC4983855 | biostudies-other
Project description:When sound interacts with geometrically asymmetric structures, it experiences coupling between pressure and particle velocity, known as Willis coupling. While in most instances this phenomenon is perturbative in nature, tailored asymmetries combined with resonances can largely enhance it, enabling exotic acoustic phenomena. In these systems, Willis coupling obeys reciprocity, imposing an even symmetry of the Willis coefficients with respect to time reversal and the impinging wave vector, which translates into stringent constraints on the overall scattering response. In this work, we introduce and experimentally observe a dual form of acoustic Willis coupling, arising in geometrically symmetric structures when time-reversal symmetry is broken, for which the pressure-velocity coupling is purely odd-symmetric. We derive the conditions to maximize this effect, we experimentally verify it in a symmetric subwavelength scatterer biased by angular momentum, and we demonstrate the opportunities for sound scattering enabled by odd Willis coupling. Our study opens directions for acoustic metamaterials, with direct implications for sound control, non-reciprocal scattering, wavefront shaping and signal routing, of broad interest also for nano-optics, photonics, elasto-dynamics, and mechanics.
| S-EPMC8110991 | biostudies-literature
Project description:This paper discusses the criteria underlying the design of an innovative X-ray active pixel sensor in CMOS technology. This X-ray detector is used in a Full Field-of-view Digital Mammography (FFDM) camera. The CMOS imager is a three-side buttable 29mm x 119mm, 48 mum active pixel CMOS sensor in 0.18 mum technology. The 1(st) silicon FFDM devices were fabricated at the end of June, 2007. The device suffers a common failure mode of high current and currently is in failure analysis at Bioptics foundry. Current target for revision A1 tape out is at the end of August, 2007.
| S-EPMC2572992 | biostudies-literature
Project description:BackgroundPatients with good performance status (PS) tend to be favored in randomized clinical trials (RCTs), possibly limiting the generalizability of trial findings. We aimed to characterize trial-related factors associated with the use of PS eligibility criteria and analyze patient accrual breakdown by PS.MethodsAdult, therapeutic, multiarm phase III cancer-specific RCTs were identified through ClinicalTrials.gov. PS data were extracted from articles. Trials with a PS restriction ECOG score ≤1 were identified. Factors associated with PS restriction were determined, and the use of PS restrictions was analyzed over time.ResultsIn total, 600 trials were included and 238,213 patients had PS data. Of those trials, 527 studies (87.8%) specified a PS restriction cutoff, with 237 (39.5%) having a strict inclusion criterion (ECOG PS ≤1). Enrollment criteria restrictions based on PS (ECOG PS ≤1) were more common among industry-supported trials (P<.001) and lung cancer trials (P<.001). Nearly half of trials that led to FDA approval included strict PS restrictions. Most patients enrolled across all trials had an ECOG PS of 0 to 1 (96.3%). Even among trials that allowed patients with ECOG PS ≥2, only 8.1% of those enrolled had a poor PS. Trials of lung, breast, gastrointestinal, and genitourinary cancers all included <5% of patients with poor PS. Finally, only 4.7% of patients enrolled in trials that led to subsequent FDA approval had poor PS.ConclusionsUse of PS restrictions in oncologic RCTs is pervasive, and exceedingly few patients with poor PS are enrolled. The selective accrual of healthier patients has the potential to severely limit and bias trial results. Future trials should consider a wider cancer population with close toxicity monitoring to ensure the generalizability of results while maintaining patient safety.
| S-EPMC9671537 | biostudies-literature
Project description:Background Human papillomavirus (HPV) E6/E7 mRNA tests determine the oncogenic activity of the virus and represent a good clinical biomarker for predicting the risk of cervical cancer. So, the present study was conducted to know the role of HPV E6/E7 mRNA as a predictive biomarker for cervical carcinoma. Methodology The present study was conducted on 55 clinical samples of cervical scrapings and biopsy from the clinically suspected cases (based on signs and symptoms) of cervical cancer having abnormal PAP smear. The samples were processed in three steps-(1) HPV DNA detection, (2) HPV E6/E7 mRNA detection, and (3) histopathological analysis. Results Out of a total of 55 patients, 16 (29.09%) were positive for both HPV E6/E7 mRNA and HPV DNA and six were positive for only HPV DNA. So, a total of 22 (40%) patients were positive for HPV DNA. Out of these 22 samples, 10 (45.5%) were of HPV-16, six (27.3%) were of HPV-18, four (18.2%) were of HPV-31, and two (9.1%) were of HPV-45. Out of total 16 patients positive for HPV E6/E7 mRNA, 10 (62.5%) were of genotype 16 and six (37.5%) were of genotype 18. The patients who were found positive for HPV 31 and 45 genotypes did not have E6/E7 mRNA expression. On colposcopic-guided biopsy, among these 16 samples, eight (50%) were diagnosed with invasive squamous cell carcinoma, six (37.5%) with cervical intraepithelial neoplasia grade 3 (CIN3), and two (12.5%) with CIN2. Out of those six patients in whom only HPV DNA was positive, five had normal biopsy findings and one had CIN1. Conclusion The present study suggests that HPV E6/E7 mRNA detection could be more reliable than DNA testing for predicting the risk of progression of HPV-induced cervical lesions to cervical carcinoma and it can be used as a non-invasive tool for triage and patient follow-up.
| S-EPMC9473935 | biostudies-literature
Project description:The realization of quantum spin Hall effect in HgTe quantum wells is considered a milestone in the discovery of topological insulators. Quantum spin Hall states are predicted to allow current flow at the edges of an insulating bulk, as demonstrated in various experiments. A key prediction yet to be experimentally verified is the breakdown of the edge conduction under broken time-reversal symmetry. Here we first establish a systematic framework for the magnetic field dependence of electrostatically gated quantum spin Hall devices. We then study edge conduction of an inverted quantum well device under broken time-reversal symmetry using microwave impedance microscopy, and compare our findings to a non-inverted device. At zero magnetic field, only the inverted device shows clear edge conduction in its local conductivity profile, consistent with theory. Surprisingly, the edge conduction persists up to 9?T with little change. This indicates physics beyond simple quantum spin Hall model, including material-specific properties and possibly many-body effects.
| S-EPMC4455136 | biostudies-literature
Project description:A new class of materials termed topological insulators have been intensively investigated due to their unique Dirac surface state carrying dissipationless edge spin currents. Recently, it has been theoretically proposed that the three dimensional analogue of this type of band structure, the Weyl Semimetal phase, is materialized in pyrochlore oxides with strong spin-orbit coupling, accompanied by all-in-all-out spin ordering. Here, we report on the fabrication and magnetotransport of Eu2Ir2O7 single crystalline thin films. We reveal that one of the two degenerate all-in-all-out domain structures, which are connected by time-reversal operation, can be selectively formed by the polarity of the cooling magnetic field. Once formed, the domain is robust against an oppositely polarised magnetic field, as evidenced by an unusual odd field dependent term in the magnetoresistance and an anomalous term in the Hall resistance. Our findings pave the way for exploring the predicted novel quantum transport phenomenon at the surfaces/interfaces or magnetic domain walls of pyrochlore iridates.
| S-EPMC4426595 | biostudies-literature