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PMS2, a Lynch Syndrome gene, presents challenges in genetic testing due to the existence of multiple pseudogenes. This study aims to describe a series of cases harboring a variant in the PMS2CL pseudogene that has been incorrectly assigned to PMS2 with different nomenclatures. We reviewed data from 647 Brazilian patients who underwent multigene genetic testing at a single center to identify those harboring the PMS2 V1:c.2186_2187delTC or V2:c.2182_2184delACTinsG variants, allegedly located at PMS2 exon 13. Gene-specific PCR and transcript sequencing was performed. Among the 647 individuals, 1.8% (12) carried the investigated variants, with variant allele frequencies ranging from 15 to 34%. By visually inspecting the alignments, we confirmed that both V1 and V2 represented the same variant and through gene-specific PCR and PMS2 transcript analysis, we demonstrated that V1/V2 is actually located in the PMS2CL pseudogene. Genomic databases (ExAC and gnomAD) report an incidence of 2.5 - 5.3% of this variant in the African population. Currently, V1 is classified as "uncertain significance" and V2 as "conflicting" in ClinVar, with several laboratories classifying them as "pathogenic". We identified a frequent African PMS2CL variant in the Brazilian population that is misclassified as a PMS2 variant. It is likely that V1/V2 have been erroneously assigned to PMS2 in several manuscripts and by clinical laboratories, underscoring a disparity-induced matter. Considering the limitations of short-read NGS differentiating between certain regions of PMS2 and PMS2CL, using complementary methodologies is imperative to provide an accurate diagnosis.

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The transition to a low-carbon economy is one of the main challenges of our time. In this context, solar energy, along with many other technologies, has been developed to optimize performance. For example, solar trackers follow the sun's path to increase the generation capacity of photovoltaic plants. However, several factors need consideration to further optimize this process. Important variables include the distance between panels, surface reflectivity, bifacial panels, and climate variations throughout the day. Thus, this paper proposes an artificial intelligence-based algorithm for solar trackers that takes all these factors into account-mainly weather variations and the distance between solar panels. The methodology can be replicated anywhere in the world, and its effectiveness has been validated in a real solar plant with bifacial panels located in northeastern Brazil. The algorithm achieved gains of up to 7.83% on a cloudy day and obtained an average energy gain of approximately 1.2% when compared to a commercial solar tracker algorithm.

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The classification of carbapenemases can help guide therapy. The present study evaluated the performance of the CPO detection test, included in the BD Phoenix™ NMIC-501 panel for the detection and classification of carbapenemases on the representative molecularly characterized strains collection from Mexico. Carbapenem non-susceptible isolates collected in Mexico were included. The clinical isolates (n = 484) comprised Klebsiella pneumoniae (n = 154), Escherichia coli (n = 150), and P. aeruginosa (n = 180). BD Phoenix CPO NMIC-504 and NMIC-501 panels were used for the identification of species, antimicrobial susceptibility tests, and detection of CPOs. For the detection of carbapenemase-encoding genes, E. coli and K. pneumoniae were evaluated using PCR assays for blaNDM-1, blaKPC, blaVIM, blaIMP, and blaOXA-48-like. For P. aeruginosa, blaVIM, blaIMP, and blaGES were detected using PCR. Regarding E. coli, the CPO panels had a sensitivity of 70% and specificity of 83.33% for the detection of a class B carbapenemase (blaNDM in the molecular test). Regarding K. pneumoniae, the panels had a sensitivity of 75% and specificity of 100% for the detection of a class A carbapenemase (blaKPC in the molecular test). The Phoenix NMIC-501 panels are reliable for detecting class B carbapenemases in E. coli. The carbapenemase classification in K. pneumoniae for class A carbapenemases has a high specificity and PPV; thus, a positive result is of high value.

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Next-generation sequencing (NGS), comprising targeted panels (TP), exome sequencing (ES), and genome sequencing (GS) became robust clinical tools for diagnosing hereditary ataxia (HA). Determining their diagnostic yield (DY) is crucial for optimal clinical decision-making. We conducted a comprehensive systematic literature review on the DY of NGS tests for HA. We searched PubMed and Embase databases for relevant studies between 2016 and 2022 and manually examined reference lists of relevant reviews. Eligible studies described the DY of NGS tests in patients with ataxia as a significant feature. Data from 33 eligible studies showed a median DY of 43% (IQR = 9.5-100%). The median DY for TP and ES was 46% and 41.9%, respectively. Higher DY was associated with specific phenotype selection, such as episodic ataxia at 68.35% and early and late onset of ataxia at 46.4% and 54.4%. Parental consanguinity had a DY of 52.4% (p = 0.009), and the presumed autosomal recessive (AR) inheritance pattern showed 62.5%. There was a difference between the median DY of studies that performed targeted sequencing (tandem repeat expansion, TRE) screening and those that did not (p = 0.047). A weak inverse correlation was found between DY and the extent of previous genetic investigation (rho = - 0.323; p = 0.065). The most common genes were CACNA1A and SACS. DY was higher for presumed AR inheritance pattern, positive family history, and parental consanguinity. ES appears more advantageous due to the inclusion of rare genes that might be excluded in TP.

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BACKGROUND: Ventilator-Associated pneumonia (VAP) is one of the leading causes of morbidity and mortality in critically ill COVID-19 patients in lower-and-middle-income settings, where timely access to emergency care and accurate diagnostic testing is not widely available. Therefore, rapid microbiological diagnosis is essential to improve effective therapy delivery to affected individuals, preventing adverse outcomes and reducing antimicrobial resistance. METHODS: We conducted a cross-sectional study of patients with suspected VAP and COVID-19, evaluating the diagnostic performance of the BioFire® FilmArray® Pneumonia Panel (FA-PP). Respiratory secretion samples underwent standard microbiological culture and FA-PP assays, and the results were compared. RESULTS: We included 252 samples. The traditional culture method detected 141 microorganisms, and FA-PP detected 277, resulting in a sensitivity of 95% and specificity of 60%, with a positive predictive value of 68% and negative predictive value of 93%. In samples with high levels of genetic material (> 10^5 copies/mL), the panel had a sensitivity of 94% and specificity of 86%. In addition, 40% of the culture-negative samples had positive FA-PP® results, of which 35% had > 10^5 copies/mL of genetic material. The most prevalent bacteria were Gram-negative bacilli, followed by Gram-positive cocci. The panel identified 98 genes associated with antimicrobial resistance, predominantly extended-spectrum beta-lactamases (28%). CONCLUSION: The FA-PP is a sensitive assay for identifying bacteria causing VAP in patients with COVID-19, with a greater capacity to detect bacteria than the conventional method. The timely microbiological recognition offered by this panel could lead to optimized decision-making processes, earlier tailored treatment initiation, and improved antibiotic stewardship practices.

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Hereditary breast cancer (BC) corresponds to 5% of all BC and a larger parcel of early-onset disease. The incorporation of next-generation sequencing (NGS) techniques reduced the cost of molecular testing and allowed the inclusion of additional cancer predisposition genes in panels that are more comprehensive. This enabled the identification of germline pathogenic variants in carriers and the introduction of risk-reducing strategies. It also resulted in the identification of the co-occurrence of more than one germline pathogenic variant in BC genes in some families. This is a rare event, and there are few reports on its impact on cancer risk. We conducted a single-institution retrospective study in which 1,156 women with early onset BC and/or a family history of cancer were tested by a germline multi-gene hereditary cancer panel. Germline pathogenic variants in high- and/or moderate-penetrance BC genes were identified in 19.5% of the individuals (n = 226). The most frequent variants were found in TP53 (69 of 226; 55 of them represented by p.R337H), BRCA1 (47 of 226), and BRCA2 (41 of 226). Double heterozygous (DH) variants were detected in 14 cases, representing 1.2% of all individuals assessed. There were no significant differences in age of BC onset and risk for bilateral BC in DH carriers when compared with those with one germline variant.

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Sandwich panels (SP) are very promising components for structures as they ally high levels of specific stiffness and strength. Civil, marine and automotive industries are some examples of the sectors that use SPs frequently. This work demonstrates the potential of manufacturing Z-pin-reinforced foam core SPs, using a design strategy that indicated optimal values for both pin position and angle, keeping the same pin diameter as determined in a previous study. A simple search algorithm was applied to optimize each design, ensuring maximum flexural stiffness. Designs using optimal pin position, optimal pin angle and optimal values for both parameters are herein investigated using numerical and experimental approaches. The optimal pin position yielded an increase in flexural stiffness of around 8.0% when compared to the non-optimized design. In this same comparison, the optimal pin angle by itself increased the flexural stiffness by about 63.0%. Besides, the highest increase in the maximum load was found for those composites, molded with optimized levels of pin position and pin angle, which synergistically contributed to this result. All results were demonstrated with numerical and experimental results and there was a good agreement between them.

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Sandwich composites are widely used in the manufacture of aircraft cabin interior panels for commercial aircraft, mainly due to the light weight of the composites and their high strength-to-weight ratio. Panels are used for floors, ceilings, kitchen walls, cabinets, seats, and cabin dividers. The honeycomb core of the panels is a very light structure that provides high rigidity, which is considerably increased with fiberglass face sheets. The panels are manufactured using the compression molding process, where the honeycomb core is crushed up to the desired thickness. The crushed core breaks fiberglass face sheets and causes other damage, so the panel must be reworked. Some damage is associated with excessive build-up of resin in localized areas, incomplete curing of the pre-impregnated fiberglass during the manufacturing process, and excessive temperature or residence time during the compression molding. This work evaluates the feasibility of using rigid polyurethane foams as a substitute for the honeycomb core. The thermal and viscoelastic behavior of the cured prepreg fiberglass under different manufacturing conditions is studied. The first part of this work presents the influence of the manufacturing parameters and the feasibility of using rigid foams in manufacturing flat panels oriented to non-structural applications. The conclusion of the article describes the focus of future research.

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The manufacturing process of the aircraft cabin interior panels is expensive and time-consuming, and the resulting panel requires rework due to damages that occurred during their fabrication. The aircraft interior panels must meet structural requirements; hence sandwich composites of a honeycomb core covered with two layers of pre-impregnated fiberglass skin are used. Flat sandwich composites are transformed into panels with complex shapes or geometries using the compression molding process, leading to advanced manufacturing challenges. Some aircraft interior panels are required for non-structural applications; hence sandwich composites can be substituted by cheaper alternative materials and transformed using disruptive manufacturing techniques. This paper evaluates the feasibility of replacing the honeycomb and fiberglass skin layers core with rigid polyurethane foams and thermoplastic polymers. The results show that the structural composites have higher mechanical performances than the proposed sandwich composites, but they are compatible with non-structural applications. Sandwich composite fabrication using the vacuum forming process is feasible for developing non-structural panels. This manufacturing technique is fast, easy, economical, and ecological as it uses recyclable materials. The vacuum forming also covers the entire panel, thus eliminating tapestries, paints, or finishes to the aircraft interior panels. The conclusion of the article describes the focus of future research.

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BACKGROUND: Several species of Costa Rican wildlife are suffering terrible injuries along the power lines in rural areas of the country due to the increasing human development in rural areas, but this has also brought the problem of poorly designed electric infrastructure, where arboreal mammals find their normal tree routes cut down so that the only way for them to cross is on the power lines where they can get electrocuted. METHODS: Blood samples for complete blood count (CBC) and biochemistry panels (alkaline phosphatase, aspartate aminotransferase, amylase, total bilirubin, plasma urea, Ca, P, creatinine, glucose, Na, K, total protein, globulins, and albumin) were collected from 34 electrocuted mantled howler monkeys (Alouatta palliata) individuals that arrived at the Nosara Refuge for Wildlife between May 2018 and May 2019. RESULTS: From the total sample, 18 were males (11 juveniles and eight adults), and 16 were females (six juveniles and 10 adults). From those individuals, 13 animals survived: five females (three juveniles and two adults) and eight males (six juveniles and two adults). Then, 22 animals died after the event from 1 to 102 days (22.41 ± 31.17) after they arrived at the center. Of these 22 animals, 11 were females (three juveniles and eight adults), and 11 were males (six juveniles and five adults). CONCLUSIONS: The preliminary results showed significant differences in the plasma glucose, with adults being significantly higher than the juveniles, and there was also a significant difference in the plasma urea with the deceased ones being higher than the ones that survived the incident. These results may provide a better way to understand and predict the possible outcome of an electrical accident with these primates and assist with returning them back to their natural environment in the least time possible.

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Gene/s sequencing in hereditary breast/ovary cancer (HBOC) in routine diagnosis is challenged by the analysis of panels. We aim to report a retrospective analysis of BRCA1/2 and non-BRCA gene sequencing in patients with breast/ovary cancer (BOC), including triple-negative breast cancer (TNBC), in our population. In total 2155 BOC patients (1900 analyzed in BRCA1/2 and 255 by multigenic panels) gave 372 (17.2.6%) and 107 (24.1%) likely pathogenic/pathogenic variants (LPVs/PVs), including BRCA and non-BRCA genes, for the total and TNBC patients, respectively. When BOC was present in the same proband, a 51.3% rate was found for LPVs/PVs in BRCA1/2. Most of the LPVs/PVs in the panels were in BRCA1/2; non-BRCA gene LPVs/PVs were in CDH1, CHEK2, CDKN2A, MUTYH, NBN, RAD51D, and TP53. TNBC is associated with BRCA1/2 at a higher rate than the rest of the breast cancer types. The more prevalent PVs in BRCA1/2 genes (mostly in BRCA1) do not rule out the importance to panels of genes, although they are certainly far from shedding light on the gap of the 85% predicted linkage association of BOC with BRCA1/2 and are still not elucidated.

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The quality of plywood depends on factors such as the forest species and the adhesive used in their production, and understanding the interferences of these factors in the final properties of the plywood is of fundamental importance. The study aimed to develop multilayer plywood with two forest species and two types of adhesive and to evaluate the influences of these factors (forest species and adhesive) on the physical and mechanical properties of the plywood. The panels were produced with wood veneers of parica and pine with two types of adhesives, urea-formaldehyde and phenol-formaldehyde, with a weight of 150 g.m2. Then, each set was pressed for 10 min under a specific pressure of 0.98 MPa at a temperature of 150 °C. Three panels were produced for each type of veneer and adhesive, totaling four treatments. The plywood was evaluated for physical properties (moisture content, bulk density, and water absorption) and mechanical properties (parallel and perpendicular static bending strength and shear strength). The results showed that the forest species had a greater influence on physical and mechanical properties, with the best results being observed for plywood produced with pine and PF adhesive. The specific mass of the panels should be considered as it positively influenced the mechanical properties and negatively impacted water absorption. The PCA was used to reduce the dimensionality of the data from 9 dependent variables to 2 main components, explaining 76.70% of the total variance of the data. The multivariate analyzes of the differentiated independent factors showed that both the species and the adhesive affected as properties of the plywood and both independent variables must be taken into account in the production of the plywood. It is concluded that the porosity and specific mass of the paricá veneers contributed to a greater penetration of the adhesives, resulting in lower physical and mechanical properties than the pine veneers. However, in general, it is concluded that the plywoods produced can be used for internal and external applications. However, it is not indicated for structural purposes as it did not meet the requirements of the NBR 31.000.001/2:2001.

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In this work, the production of biologically synthesized silica nanoparticles was proposed to prepare a nanosuspension as a thermal fluid in parabolic solar panels at the laboratory level. Silica nanoparticles were produced from construction sand in two stages. Biosynthesis broth was produced by Aspergillus niger aerated fermentation in a 1 L bioreactor for 9 days. Each supernatant was contacted with 18% construction sand in a 500 L reactor with mechanical agitation, at a temperature of 25 °C, and a contact time of 30 min. Subsequently, the separation process was carried out. For day 9, a pH value of 1.71 was obtained as well as acid concentrations of 15.78 g/L for citrus and 4.16 g/L for malic. The metal extraction efficiency of Si nanoparticles was 19%. The vibration peaks in the FTIR were characteristic of the presence of silica nanoparticles in wavenumbers 1020 cm-1 and 1150 cm-1. Finally, a prototype solar radiation test bench for parabolic systems was built and provided with a radiation source that falls on a translucent pipe that transports the nanoparticles, which has a pump and a series of thermocouples. The heat capacity of the biotechnologically produced silica nanoparticle suspension was 0.72 ± 0.05 kJ/kgK, using material and energy balances in the flow circuit.

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As the use of photovoltaic installations becomes extensive, it is necessary to look for recycling processes that mitigate the environmental impact of damaged or end-of-life photovoltaic panels. There is no single path for recycling silicon panels, some works focus on recovering the reusable silicon wafers, others recover the silicon and metals contained in the panel. In the last few years, silicon solar cells are thinner, and it becomes more difficult to separate them from the glass, so the trend is towards the recovery of silicon. In this paper, we investigate the experimental conditions to delaminate and recovery silicon in the recycling process, using a combination of mechanical, thermal, and chemical methods. The conditions of thermal treatment to remove the ethylene-vinyl acetate (EVA) layer were optimized to 30 min at 650 °C in the furnace. To separate silicon and metals, the composition of HF/HNO3 solution and the immersion time were adjusted considering environmental aspects and cost. Under the selected conditions, panels from different manufacturers were tested, obtaining similar yields of recovered silicon but differences in the metal concentrations.

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Current Genome-Wide Association Studies (GWAS) rely on genotype imputation to increase statistical power, improve fine-mapping of association signals, and facilitate meta-analyses. Due to the complex demographic history of Latin America and the lack of balanced representation of Native American genomes in current imputation panels, the discovery of locally relevant disease variants is likely to be missed, limiting the scope and impact of biomedical research in these populations. Therefore, the necessity of better diversity representation in genomic databases is a scientific imperative. Here, we expand the 1,000 Genomes reference panel (1KGP) with 134 Native American genomes (1KGP + NAT) to assess imputation performance in Latin American individuals of mixed ancestry. Our panel increased the number of SNPs above the GWAS quality threshold, thus improving statistical power for association studies in the region. It also increased imputation accuracy, particularly in low-frequency variants segregating in Native American ancestry tracts. The improvement is subtle but consistent across countries and proportional to the number of genomes added from local source populations. To project the potential improvement with a higher number of reference genomes, we performed simulations and found that at least 3,000 Native American genomes are needed to equal the imputation performance of variants in European ancestry tracts. This reflects the concerning imbalance of diversity in current references and highlights the contribution of our work to reducing it while complementing efforts to improve global equity in genomic research.

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As more uses for biomarkers are sought after for an increasing number of disease targets, single-target biomarkers are slowly giving way for biomarker panels. These panels incorporate various sources of biomolecular and clinical data to guarantee a higher robustness and power of separation for a clinical test. Multifactorial diseases such as psychiatric disorders show great potential for clinical use, assisting medical professionals during the analysis of risk and predisposition, disease diagnosis and prognosis, and treatment applicability and efficacy. More specific tests are also being developed to assist in ruling out, distinguishing between, and confirming suspicions of multifactorial diseases, as well as to predict which therapy option may be the best option for a given patient's biochemical profile. As more complex datasets are entering the field, involving multi-omic approaches, systems biology has stepped in to facilitate the discovery and validation steps during biomarker panel generation. Filtering biomolecules and clinical data, pre-validating and cross-validating potential biomarkers, generating final biomarker panels, and testing the robustness and applicability of those panels are all beginning to rely on machine learning and systems biology and research in this area will only benefit from advances in these approaches.

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This work was focused on evaluating the effects of polycarboxylic acid addition and retrogradation phenomenon on tribological performance, thermal, and mechanical properties of both, bioadhesives and sustainable panels. The rheological behavior of adhesives was affected by retrogradation, exhibiting formulations containing CA higher elastic modulus than those with BTCA, regardless of the acid concentration. With regard to tribomechanical properties, panels formulated with CA20 and BTCA80 adhesives presented the lower friction coefficient and wear degree. Thermocompression process induced a crosslinking reaction between wood fibers and starch-based adhesives, leading to more hydrophobic and thermally stable matrices in the presence of BTCA. The selection of the adhesive formulation depends on the moment of its use, since retrogradation limits its performance and that of the derived sustainable panels, being the adhesive CA20 more appropriate in freshly prepared formulations. Meanwhile, when the storage of the adhesive prepared in batch is required, the BTCA80 formulation would be more suitable. Thus, bioinspired materials can provide a valuable insight towards incorporating starch-based adhesives for wood applications.

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BACKGROUND: Gender disparities exist worldwide related to female representation in digital health initiatives especially in low and middle income countries (LMICs). Upstream approaches and policy implementation has been effective in some countries to reduce the gender gap in the areas of political and sector leadership. At an international digital health conference in Bolivia, all-male expert panels presented their research and innovations to audiences from the Bolivian national and regional health departments and private and non-governmental organization heath leaders. METHODS: An in-depth qualitative analysis of participant perspectives related to the absence of female presenters at this digital health conference in Bolivia was performed. Using a cross-sectional research design, the questionnaire rated the respondents' satisfaction using Likert scales and their perspectives using open-ended questions. A multidisciplinary team of coders reviewed the respondents' responses in detail and developed general themes. RESULTS: The sample consisted of 80 respondents who completed the questionnaire from the 115 people attending the conference, giving a 70% response rate (80/115). Respondents were broadly represented in terms of gender, age, occupation and experience using digital health tools. The code structure contained five primary codes each reflecting sets of ideas and possible solutions for gender equality in science and health technology in Bolivia. The five recurrent themes, ranked from the most common mentioned to the least common, were: (I) opportunities and incentives (38%); (II) indifference (23%); (III) role models (18%); (IV) capacity strengthening and empowerment (15%); (V) norms and policies (7%). CONCLUSIONS: The results of this study can be useful for preparing a more representative digital health field in Bolivia overtime. Conference respondents provide key recommendations to reduce gender inequality at digital health conferences and in the field. This study provides evidence from Bolivian health workers and officials on their perspectives related to the absence of female presenters at an international digital health conference and their suggestions for optimizing female participation and leadership at conferences and in the digital health field going forward.

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RESUMEN Los nódulos tiroideos representan un problema clínico a nivel mundial debida a su alta prevalencia. La importancia clínica de su estudio radica en excluir malignidad, que ocurre entre el 7-15% de los mismos. El método estándar de oro para el diagnóstico de los mismos es el análisis citológico de la punción aspiración con aguja fina. Sin embargo, hasta un 30% de estos presentan citologías indeterminadas (Bethesda III o IV). Con un resultado histopatológico benigno en, aproximadamente tres de cada cuatro de estos casos, la cirugía diagnóstica (tiroidectomía parcial o lobectomía) resulta en un inconveniente ya que expone al paciente a innecesarios riesgos quirúrgicos. En el caso de lesiones malignas, una tiroidectomía en una segunda etapa es a menudo indicada, lo que se asocia con costos adicionales y mayores riesgos de complicaciones quirúrgicas. Es por esto que se requiere de una herramienta con mayor precisión para determinar la benignidad o malignidad de un nódulo tiroideo con citología indeterminada. En este contexto el análisis molecular del tejido tiroideo se convierte en un poderoso complemento para el diagnóstico preoperatorio de los nódulos tiroideos con citología indeterminada, ya que entre el 60 al 70% de los cánceres de tiroides albergan al menos una mutación genética conocida.

ABSTRACT Thyroid nodules represent a clinical problem worldwide due to its high prevalence. The clinical importance lies in excluding malignancy, which occurs between 7-15% of them. The cytological analysis is the gold standard for the diagnosis. However, up to 30% of these have indeterminate cytologies (Bethesda III or IV). In these patients, diagnostic surgeries are performed. With a benign histopathological result in approximately three out of four of these cases, surgery results in an inconvenience since it exposes the patient to unnecessary surgical risks. In the case of malignant lesions, a thyroidectomy in a second stage is often indicated, which is associated with additional costs and increased risks of surgical complications. A more precise method is needed to determine the benignity or malignancy of a thyroid nodule with indeterminate cytology. In this context, molecular analysis of thyroid tissue becomes a powerful complement for the preoperative diagnosis of thyroid nodules with indeterminate cytology, since between 60 to 70% of thyroid cancers harbor at least one known genetic mutation.

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Omics technologies have revolutionised fundamental and medical research. Oncology is perhaps the field where these technologies have been most rapidly adopted and where they have had their biggest impact, dramatically transforming clinical practice guidelines over a very short period of time. Along with this transformation has come an even larger array of technologies, tools and jargon, that make following the most recent developments in the field a truly daunting task for those not involved in it. This chapter is intended to provide a general overview of evolving topics in oncology research in the era of big data analysis and precision medicine, with a specific focus on the use of tumour biomarkers, tumour biomarker tests, targeted drugs and the changing landscape of clinical trial designs.

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