The value of cell-free circulating tumour DNA profiling in advanced non-small cell lung cancer (NSCLC) management

Liquid biopsy (LB) has boosted a remarkable change in the management of cancer patients by contributing to tumour genomic profiling. Plasma circulating cell-free tumour DNA (ctDNA) is the most widely searched tumour-related element for clinical application. Specifically, for patients with lung cancer, LB has revealed valuable to detect the diversity of targetable genomic alterations and to detect and monitor the emergence of resistance mechanisms. Furthermore, its non-invasive nature helps to overcome the difficulty in obtaining tissue samples, offering a comprehensive view about tumour diversity. However, the use of the LB to support diagnostic and therapeutic decisions still needs further clarification. In this sense, this review aims to provide a critical view of the clinical importance of plasma ctDNA analysis, the most widely applied LB, and its limitations while anticipating concepts that will intersect the present and future of LB in non-small cell lung cancer patients

On O(1) contributions to the free energy in Bethe Ansatz systems: the exact g-function

We investigate the sub-leading contributions to the free energy of Bethe Ansatz solvable (continuum) models with different boundary conditions. We show that the Thermodynamic Bethe Ansatz approach is capable of providing the O(1) pieces if both the density of states in rapidity space and the quadratic fluctuations around the saddle point solution to the TBA are properly taken into account. In relativistic boundary QFT the O(1) contributions are directly related to the exact g-function. In this paper we provide an all-orders proof of the previous results of P. Dorey et al. on the g-function in both massive and massless models. In addition, we derive a new result for the g-function which applies to massless theories with arbitrary diagonal scattering in the bulk.Comment: 28 pages, 2 figures, v2: minor corrections, v3: minor corrections and references adde

Economic History and History of Economics: Complementary Approaches to Portuguese Economic Development

This chapter focuses on how the problems of economic development were addressed by the Portuguese historiography of the late nineteenth and twentieth centuries. The ensuing discussion benefits from the simultaneous consideration of two historiographical domains that complement each other: economic history and the history of economics. On the one hand, there are the authors and texts of economic history that seek to describe the facts and circumstances related to the functioning and dynamics of economic reality, for a given period or succession of periods, in order to establish evolutionary trends. On the other hand, there are the authors and texts of the history of economics that seek to adopt analytical forms (principles and laws) and doctrinal and programmatic frameworks (visions and ideologies) aimed at providing explanatory meaning to the observed economic changes, phenomena and regularities. A true understanding of the important issues pertaining to Portuguese economic development is to be found, however, in the intersection of these distinct but complementary historiographical perspectives.info:eu-repo/semantics/publishedVersio

A Novel TRAF3IP2 Mutation Causing Chronic Mucocutaneous Candidiasis

Inborn errors of the IL-17-mediated signaling have been associated with chronic mucocutaneous candidiasis (CMC). We describe a patient with CMC, atopic dermatitis, enamel dysplasia, and recurrent parotitis harboring a novel compound heterozygous mutation of TRAF3IP2, leading to autosomal recessive ACT1 deficiency and deficient IL-17 signaling.info:eu-repo/semantics/publishedVersio

The Mechanical Behavior of a 25Cr Super Duplex Stainless Steel at Elevated Temperature

Peer reviewedPostprin

Mutational mechanism for DAB1 (ATTTC) n insertion in SCA37: ATTTT repeat lengthening and nucleotide substitution

Dynamic mutations by microsatellite instability are the molecular basis of a growing number of neuromuscular and neurodegenerative diseases. Repetitive stretches in the human genome may drive pathogenicity, either by expansion above a given threshold, or by insertion of abnormal tracts in nonpathogenic polymorphic repetitive regions, as is the case in spinocerebellar ataxia type 37 (SCA37). We have recently established that this neurodegenerative disease is caused by an (ATTTC)n insertion within an (ATTTT)n in a noncoding region of DAB1. We now investigated the mutational mechanism that originated the (ATTTC)n insertion within an ancestral (ATTTT)n . Approximately 3% of nonpathogenic (ATTTT)n alleles are interspersed by AT-rich motifs, contrarily to mutant alleles that are composed of pure (ATTTT)n and (ATTTC)n stretches. Haplotype studies in unaffected chromosomes suggested that the primary mutational mechanism, leading to the (ATTTC)n insertion, was likely one or more T>C substitutions in an (ATTTT)n pure allele of approximately 200 repeats. Then, the (ATTTC)n expanded in size, originating a deleterious allele in DAB1 that leads to SCA37. This is likely the mutational mechanism in three similar (TTTCA)n insertions responsible for familial myoclonic epilepsy. Because (ATTTT)n tracts are frequent in the human genome, many loci could be at risk for this mutational process.We are grateful to the families and individuals who participated in this work. We thank Patricia Ribeiro for technical assistance. This study was financed by Fundo Europeu de Desenvolvimento Regional (FEDER), through the COMPETE 2020 Operational Pro- gram for Competitiveness and Internationalization (POCI) of Portugal 2020, and by the Fundacão para a Ciência e a Tecnologia (FCT) and Ministério da Ciência, Tecnologia e Ensino Superior (Portugal), in the framework of the project POCI-01-0145-FEDER-029255; (PTDC/MED-GEN/29255/2017) to I.S. J.R.L. and C.L.O. were sup- ported by scholarships from PEst-C/SAU/LA0002/2013. S.M. is funded by the project IF/00930/2013/ CP1184/CT0002 from FCT. This work was also funded by the Porto Neurosciences and Neurologic Disease Research Initiative at the Instituto de Investigação e Inovação em Saúde (Norte-01-0145-FEDER- 000008), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTU- GAL 2020 Partnership Agreement with FEDER

Implementation of COGNIVITRA, an Information- and Communications-Technology-Based Solution for Dual-Task Training, in Patients at Risk of Cognitive Impairment

Mild cognitive impairment (MCI) is characterized by a modest decline in cognitive function that, while noticeable, does not severely impact daily life, allowing individuals to maintain their independence—a key factor distinguishing it from dementia. Currently, there are no treatments available that can modify the course of the disease, although cognitive and physical activities have shown potential in slowing its progression. In response to the need for more accessible cognitive care, COGNIVITRA, an information- and communications-technology-based solution, was developed to extend cognitive training into the home environment. This platform not only facilitates communication between patients and care providers but also holds promise for enhancing cognitive care accessibility and potentially influencing the economic aspects of healthcare institutions. To evaluate the usability, impact, and effectiveness of COGNIVITRA, a 12-week (6 mandatory + 6 voluntary) multicenter study was conducted, with an expected total sample size of 20 professionals, 90 patients and 20 caregivers and involving two settings (clinical and home settings) and the collection of various data types at baseline and after 6 or 12 weeks of training, including sociodemographic information, cognitive assessments, and usability metrics. These metrics included the System Usability Scale (SUS), the International Classification of Functioning-Based Usability Scales (ICF-US I and II), the Unified Theory of Acceptance and Use of Technology (UTAUT), health-related quality of life measures such as the EQ-5D-5L, cognitive domain assessments via the Montreal Cognitive Assessment (MoCA), and physical assessments such as the Timed 25-Foot Walk (T25-FW) test. The study included 22 patients, 2 caregivers, and 24 professionals. The usability evaluation revealed that patients, particularly those participating in the home study, showed improved SUS scores, suggesting an enhanced user experience with the platform. The ICF-US I results further supported this finding by indicating that COGNIVITRA was particularly effective as a supportive tool in terms of satisfaction and ease of learning. Despite a higher incidence of errors during the home study, the observational grid questionnaire demonstrated high success rates for task completion. Professionals involved in the study also reported high SUS scores and provided positive feedback regarding device usability. Overall, the participants expressed increased satisfaction with the platform, as reflected in their responses. The UTAUT analysis confirmed a generally positive attitude toward the use of COGNIVITRA. However, when assessing effectiveness, the analysis revealed a noninferiority positive trend in the EQ-5D-5L, T25-FW, and MoCA scores, indicating that while there were positive changes, they were not statistically significant. © 2024 by the authors.This project has received funding from the European Union under the AAL programme through project CogniViTra (Grant No. AAL-2018-5-115-CP), with national funding support from Fundação para a Ciência e a Tecnologia (FCT), Instituto de Salud Carlos III (ISCIII) and Luxembourg National Research Fund (FNR). This presentation reflects the authors’ views and neither AAL nor the National Funding Agencies are responsible for any use that may be made of the information

Silicon-based spin and charge quantum computation

Silicon-based quantum-computer architectures have attracted attention because of their promise for scalability and their potential for synergetically utilizing the available resources associated with the existing Si technology infrastructure. Electronic and nuclear spins of shallow donors (e.g. phosphorus) in Si are ideal candidates for qubits in such proposals due to the relatively long spin coherence times. For these spin qubits, donor electron charge manipulation by external gates is a key ingredient for control and read-out of single-qubit operations, while shallow donor exchange gates are frequently invoked to perform two-qubit operations. More recently, charge qubits based on tunnel coupling in P$_2^+$ substitutional molecular ions in Si have also been proposed. We discuss the feasibility of the building blocks involved in shallow donor quantum computation in silicon, taking into account the peculiarities of silicon electronic structure, in particular the six degenerate states at the conduction band edge. We show that quantum interference among these states does not significantly affect operations involving a single donor, but leads to fast oscillations in electron exchange coupling and on tunnel-coupling strength when the donor pair relative position is changed on a lattice-parameter scale. These studies illustrate the considerable potential as well as the tremendous challenges posed by donor spin and charge as candidates for qubits in silicon.Comment: Review paper (invited) - to appear in Annals of the Brazilian Academy of Science

Bridging Time Scales in Cellular Decision Making with a Stochastic Bistable Switch

Cellular transformations which involve a significant phenotypical change of the cell's state use bistable biochemical switches as underlying decision systems. In this work, we aim at linking cellular decisions taking place on a time scale of years to decades with the biochemical dynamics in signal transduction and gene regulation, occuring on a time scale of minutes to hours. We show that a stochastic bistable switch forms a viable biochemical mechanism to implement decision processes on long time scales. As a case study, the mechanism is applied to model the initiation of follicle growth in mammalian ovaries, where the physiological time scale of follicle pool depletion is on the order of the organism's lifespan. We construct a simple mathematical model for this process based on experimental evidence for the involved genetic mechanisms. Despite the underlying stochasticity, the proposed mechanism turns out to yield reliable behavior in large populations of cells subject to the considered decision process. Our model explains how the physiological time constant may emerge from the intrinsic stochasticity of the underlying gene regulatory network. Apart from ovarian follicles, the proposed mechanism may also be of relevance for other physiological systems where cells take binary decisions over a long time scale.Comment: 14 pages, 4 figure