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Objetivos: Determinar las causas de hemorragia digestiva alta en los pacientes que se sometieron a endoscopía digestiva y el tratamiento realizado en el Servicio de Endoscopía Digestiva del Hospital Nacional de Itauguá en el período comprendido entre marzo del 2020 a diciembre del 2020. Materiales y métodos: estudio retrospectivo, descriptivo y de corte transversal. Resultados: fueron incluidos 251 pacientes, el promedio de edad fue de 61 años con un rango de 18 a 89, 69,7% fueron hombres. Las causa más frecuente de sangrado fue la enfermedad ulceropéptica (27,8%), seguida por las várices esofágicas y gastro-esofágicas (25,8%), las úlceras duodenales (19.5%), las gastritis agudas erosivas (10,3%), y la esofagitis aguda erosiva hemorrágica (9,1%). Causas menos frecuentes fueron las hemorragias por neoplasias intestinales, las úlceras de Cameron, la ectasia vascular antral, el síndrome de Mallory-Weiss y la hemobilia. El tratamiento realizado para las úlceras gástricas y duodenales fueron con sustancias vasoactivas solamente (adrenalina diluida) o combinadas con bipolar; para las várices esofágicas se utilizaron las ligaduras con banding y para las gastroesofágicas sustancias esclerosantes (polidocanol). Presentaron recidivas las úlceras gástricas tratadas con únicamente con adrenalina en 4 pacientes. Conclusiones: La hemorragia digestiva alta es quizá una de las indicaciones más frecuentes para realizar un estudio endoscópico y es también una de las áreas donde la utilización de la misma ha demostrado un mayor impacto. Es también una causa frecuente de consulta de urgencia y en general existen amplias variaciones en cuanto a su etiología y frecuencia por lo que un consenso en su manejo puede tener un gran impacto por su aplicabilidad generalizada.

Hole gases in planar germanium can have high mobilities in combination with strong spin-orbit interaction and electrically tunable g factors, and are therefore emerging as a promising platform for creating hybrid superconductor-semiconductor devices. A key challenge towards hybrid Ge-based quantum technologies is the design of high-quality interfaces and superconducting contacts that are robust against magnetic fields. In this work, by combining the assets of aluminum, which provides good contact to the Ge, and niobium, which has a significant superconducting gap, we demonstrate highly transparent low-disordered JoFETs with relatively large I_{C}R_{N} products that are capable of withstanding high magnetic fields. We furthermore demonstrate the ability of phase-biasing individual JoFETs, opening up an avenue to explore topological superconductivity in planar Ge. The persistence of superconductivity in the reported hybrid devices beyond 1.8 T paves the way towards integrating spin qubits and proximity-induced superconductivity on the same chip.

Abstract Background Metabolic syndrome (MetS) may be associated with knee osteoarthritis (OA), but the association between the individual components and OA are not well-understood. We aimed to study the effect of hypercholesterolemia on synovial inflammation in knee OA. Methods OA was surgically induced in rabbits fed with standard diet (OA group, n = 10) or in rabbits fed with high fat diet (OA-HFD, n = 10). Healthy rabbits receiving standard diet (Control, n = 10) or fed with HFD (HFD, n = 6) were also monitored. Twelve weeks after OA induction, synovial membranes were isolated and processed for studies. Results Animals fed HFD showed higher levels of total serum cholesterol, triglycerides and C-reactive protein than control rabbits. Twelve weeks after OA induction, synovial membrane inflammation and macrophage infiltration were increased in rabbits with OA, particularly in the OA-HFD group. Extensive decrease of synovial adipose tissue area, adipocyte size and perilipin-1A synthesis were observed in the OA-HFD group in comparison to the OA and control groups. The HFD further increased the proinflammatory mediators IL-1β, IL-6 and TNF in the OA synovium. However, the synovial gene expression of adipokines, such as leptin and adiponectin, were markedly decreased in the rabbits with OA, especially in the OA-HFD group, in correlation with adipose tissue loss. However, circulating leptin was upregulated in the HFD and OA-HFD groups. Conclusion Our results indicate that a HFD is an aggravating factor worsening synovial membrane inflammation during OA, guided by increased infiltration of macrophages and removal of the adipose tissue, together with a remarkable presence of proinflammatory factors. Synovial adipocytes and dyslipemia could probably play pivotal roles in OA joint deterioration in patients with MetS, supporting that the link between obesity and OA transcends mechanical loading.

In elite basketball, closely contested games are often decided in the last minute, where a single possession can significantly alter the outcome. The objective of this study was to analyze the offensive patterns and effectiveness of successful play sequences executed during the last minute and overtime periods of the 2022–2023 EuroLeague men’s basketball season. Specifically, we examined how offensive strategies varied based on score conditions and team status (winning, losing, or tied) in games with a score difference of three points or fewer, representing a maximum one-possession margin. The sample consisted of 709 technical–tactical actions performed in one-possession games during the last minute and overtime periods of the men’s EuroLeague 2022–2023 season. An observational methodology was employed using the LINCE PLUS software with a purpose-designed observational instrument. Descriptive analyses and chi-square (χ2) tests were conducted using SPSS 25, and T-Pattern analysis was performed with Theme 6 software. Statistical significance was set at p < 0.05. The results showed that teams leading at the start of the possession executed a higher number of successful actions, primarily through free throws drawn from fouls committed by the opposing team. Additionally, plays involving few or no passes, executed within the first 17 s of possession, and completed by point guards or centers, were associated with higher success rates. While less frequent, fast breaks proved to be more effective than set offenses. Furthermore, the study highlights the role of elite playmakers in late-game situations, as their ability to read defenses and create scoring opportunities plays a crucial role in determining offensive success. The practical implications of this study can assist coaches in optimizing offensive strategies during high-pressure moments in elite men’s basketball by refining late-game decision-making and tactical planning.

Timeouts are a widely supported strategy in the literature, recognized for directly influencing team performance during basketball games. This study aimed to analyze and define the successful patterns of actions after timeouts (ATOs) during critical moments in the 2022/23 EuroLeague season. The sample was drawn from the last two minutes and overtime of 169 games with a final point difference of 10 points or fewer, totaling 365 ATOs. An observational methodology was used, applying the LINCE PLUS software version 2.1.0 and an ad hoc observational instrument. Descriptive analysis and chi-square tests (χ2) were conducted using SPSS 25.0, and T-pattern analysis was performed with Theme 6 software. Statistical significance was set at p < 0.05. Teams in the lead often concluded successful plays through free throws following opponent fouls, while teams trailing behind attempted to close the gap by committing fouls to force free throws in defense and scoring two-point baskets on offense. The findings offer insights into ATOs strategies that can support coaches and technical staff in training and adapting these actions to meet competition demands during critical game moments. These results may assist in enhancing team performance and decision-making under high-stakes conditions.

The growing trend of analyzing all performance factors involved in a game makes identifying offensive patterns a determining factor in improving tactical performance and decision making during a game. The main objective of this research was to analyze the effectiveness and detect successful patterns on offense at critical moments in the men’s EuroBasket 2022 and women’s EuroBasket 2021. The sample was composed of 509 technical–tactical offensive actions obtained from the last 2 min of the final quarters and overtime from the group stage and final round, whose difference in the final score was equal to or less than five points. For this purpose, observational methodology was employed using LINCE PLUS software through an observational instrument designed ad hoc. Descriptive analysis and chi-square (χ2) tests were performed with SPSS 25, and a pattern analysis (T-Patterns) was performed with Theme 5 software. Statistical significance was set at p < 0.05. The teams that were losing when performing the offense finished a greater number of plays and with greater effectiveness. Fastbreaks seem to be more effective in the closing minutes, a play characterized by a maximum of three passes and by finishing with individual play such as 1 × 1. In turn, actions finished near the hoop by inside players seem to be more effective when the possession is finished before 17 s. The practical implications described in this research will enable coaches to tailor their strategies and training to the critical moments of the game.

In Para-judo, the technical actions and tactical situations suitable for scoring in a combat have not been studied. The aim of this research was to determine the technical–tactical patterns of scoring actions in Para-judo, focusing on weight categories. An observational methodology was employed to conduct this study. The sample consisted of all male judokas with visual impairment (n = 172) in the senior category who participated in the World Championships held in Odivelas in 2018. A total of 232 combats and 313 scoring actions were analyzed. To obtain the results, we used different analytical techniques with SPSS: descriptive analysis, chi-square test, and T-pattern analysis. The significance level used was p < 0.05. Key findings show that the majority of scoring actions occurred in the first two minutes of combat, highlighting the importance of early initiative. Techniques such as ashi-waza, te-waza, and sutemi-waza demonstrated particular effectiveness across categories, with a focus on movements like sumi-otoshi, ouchi-gari, and ko-soto-gake. Moreover, the most common grip—lapel-sleeve—proved advantageous, aiding judokas in controlling the bout and achieving scores, especially when coupled with effective transition techniques. The study’s weight-specific analysis further revealed distinct patterns, emphasizing the importance of tailored training approaches. For instance, lighter judokas benefited from countering leg attacks with arm or sacrifice techniques to score waza-ari, while heavier judokas favored leg-to-leg counterattacks, often achieving ippon. The results suggest that judokas and coaches could benefit from a more systematic focus on grip stability, strategic positional work, and transition efficiency, particularly from standing to ground. This research contributes valuable insights into optimal techniques and strategies for visually impaired judokas, providing clear guidelines for training and competition.

Background: Men’s Olympic boxing follows a regulatory temporal structure, but previous studies have shown that this structure varies during competitions. However, these investigations have not thoroughly analyzed the differences in bout development according to weight category. Additionally, most studies have focused on a limited number of categories, leaving gaps in the temporal analysis of various categories. Aim: To determine the temporal structure in the featherweight, lightweight, welterweight, light heavyweight, and heavyweight categories of men’s Olympic boxing, in order to establish models that can help adjust training to meet competitive demands. Methods: An observational approach was used, analyzing 73 bouts involving 80 boxers who competed in the 2020 Tokyo Olympic Games. Results: Most bouts ended after the completion of the full regulation time across all categories. The most common actions were short punching sequences (two to five punches), occurring mainly in the center of the ring. Differences between weight categories were minimal, with the welterweight category showing the most variability. Conclusion: This study presents temporal models that will help coaches and boxers adjust their training with greater precision, improving the efficiency of training sessions according to competitive objectives.

Background: Pickleball is an exponentially growing sport with a lack of notation-based studies. Consequently, this research aimed to conduct a match analysis in men’s singles to enhance the understanding of the game and optimize training practices. Methods: Using observational methodology, a total of 1145 points were analyzed from the semifinal and final rounds of five Professional Pickleball Association Tour tournaments. Data were recorded with LINCE PLUS V.2.1.0 software using the OI-PICKLEBALL-S23 observational instrument. Descriptive statistical analyses were conducted with IBM-SPSS version 25.0, and gameplay patterns were detected using Theme 6.0 Edu. Statistical significance was set at p < 0.05. Results: The data indicated that service faults at the start of the game were minimal (2.4%). The server won fewer points than the returner in the overall set of analyzed points (46.6%). Most points were concluded in short rallies (1–4 shots; 43%) or medium-length rallies (5–8 shots; 44%), with the final shot predominantly occurring from striking zone 2, the area closest to the non-volley line (50.7%). Ground strokes (55.1%) and volleys (38.4%) were the most common final shots. Conclusions: The insights gained from this study can benefit high-performance players and coaches and provide a foundation for future notation-based research in pickleball.

(1) Background: The analysis of women’s tennis performance has not been extensively explored by the scientific community, necessitating further research to understand the tactical actions occurring in matches. This research aimed to examine the chance of winning a point in professional women’s tennis based on the key variables that influence performance in the sport. (2) Methods: Data from 3239 points were examined across three distinct court surfaces, sourced from the final rounds (starting with the quarterfinals) of three Grand Slam tournaments in the 2021 season. An observational methodology was employed, using various analysis techniques: descriptive and chi-square analyses, with a significance level of p < 0.05. (3) Results: The probability of winning a point on the first serve was 61% on clay, 70% on grass, and 69% on hard courts. For second serves, the probability of winning the point varied between 55% and 57%, depending on the court surface. Additionally, the majority of points, ranging from 70% to 71%, concluded with short rallies, involving one to four shots. On clay courts, the server won up to 65% of points with a first serve and a short rally, while the success rate increased to 75% on both grass and hard courts. For medium-length rallies (5–8 shots), the probability of winning the point dropped to 55–57%. The point outcome (winner, forced error, and unforced error) varied according to court surface, serve type, and rally length. (4) Conclusions: Descriptive data from this research on the probability of winning a point could assist coaches and players in developing match strategies.

(1) Background: the penalty kick is an action in football that decides many matches. The aim of this research was to establish the success rate of penalty kicks in Spain between the seasons 2012/2013 and 2019/2020 considering different key performance variables. (2) Methods: A total of 941 penalty kicks were analysed from eight seasons of the first division of the Spanish men’s football league (La Liga). An observational methodology was used and, in order to obtain the results, different analytical techniques were employed: descriptive and chi square with a significance level of p < 0.05. (3) Results: The effectiveness of penalty kicks was 76.7%. Most of the penalties were taken by the home team (60.9%), with a tie on the scoreboard (44.2%) and within the last 30 min of the match (41.9%). The highest success rate was observed for balls kicked to the upper side of the goal (100%), even though the highest number of penalties were taken low, to one of the two sides of the goal (57.0%). Up to 5.6% of the penalties were not kicked inside the goal. (4) Conclusions: Effectiveness does not depend on home–visitor status, player laterality, score or remaining match time, studied independently. A loss of effectiveness is observed when the match scores of both teams are close and in critical moments of the match.

Background—The number of studies on padel has grown significantly in recent years, reflecting the growing importance of the sport. However, more research is still needed on a comprehensive analysis of performance indicators. This study had a double objective: on the one hand, to analyze the probability of winning a point as a function of several variables and, on the other hand, to develop a match analysis. Methods—A total of 980 points from the Menorca 2020 World Padel Tour Master Final Men’s category were examined using observational methodology. The participants were the eight pairs who competed in the final rounds of the tournament. To obtain the results, various analytical techniques were used, such as descriptive analysis and the chi-square test, with a significance level of p < 0.05. Results—The results indicated that most points were initiated on the first serve (88.5%) and were most often won by the serving pair (59.3%). Short rallies predominated (42.2%), with the serving pair most likely to win the point (71%). As the rally became longer, the probability of winning the point decreased, reaching 57% for medium rallies and 47% for long rallies. Almost half of the points were completed in less than 10 s, with an average point duration of 15 s. Most points were finished from the middle area and near the net (41.4% and 36%, respectively), mainly by smashes (25.9%) or volleys (28.9%), with the cross-court trajectory being the most effective. Conclusions—Short rallies (0–6 shots) were the most common, with an average point duration of approximately 15 s. Most points ended with a shot from the middle of the court, using a volley or a smash with a cross-court trajectory. There is a clear relationship between proximity to the net on the final shot and an increased probability of winning the point.

Abstract Objective This study aimed to describe the performance of a next‐generation sequencing (NGS) panel for the detection of precise genomic alterations in cancer in Spanish clinical practice. The impact of tumor characteristics was evaluated on informative NGS and actionable mutation rates. Materials and Methods A cross‐sectional study was conducted at the Fundación Jiménez Díaz University Hospital (May 2021–March 2022) where molecular diagnostic of 537 Formalin‐Fixed Paraffin‐Embedded (FFPE) tissue samples of diverse solid tumors (lung, colorectal, melanoma, gastrointestinal stromal, among others) was performed using AVENIO Tumor Tissue Targeted Kit. A descriptive analysis of the features of all samples was carried out. Multivariable logistic analysis was conducted to assess the impact of sample characteristics on NGS performance defined by informative results rate (for all tumors and for lung tumors), and on actionable mutations rate (for lung tumors only). Results AVENIO performance rate was 75.2% in all tumor samples and 75.3% in lung cancer samples, and the multivariable analysis showed that surgical specimens are most likely to provide informative results than diagnostic biopsies. Regarding the mutational findings, 727 pathogenic, likely pathogenic, or variant of unknown significance mutations were found in all tumor samples. Single nucleotide variant was the most common genomic alteration, both for all tumor samples (85.3% and 81.9% for all solid tumors and lung samples, respectively). In lung tumors, multivariable analysis showed that it is more likely to find actionable mutations from non‐smokers and patients with adenocarcinoma, large cell, or undifferentiated histologies. Conclusion This is the largest cohort‐level study in Spain to profile the analyses of biopsy samples of different tumors using NGS in routine clinical practice. Our findings showed that the use of NGS routinely provides good rates of informative results and can improve tumor characterization and identify a greater number of actionable mutations.

IntroductionFunctional trait-based approaches are extensively applied to the study of mechanisms governing community assembly along environmental gradients. These approaches have been classically based on studying differences in mean values among species, but there is increasing recognition that alternative metrics of trait distributions should be considered to decipher the mechanisms determining community assembly and species coexistence. Under this framework, the main aim of this study is to unravel the effects of environmental conditions as drivers of plant community assembly in sub-Mediterranean ecotones.MethodsWe set 60 plots in six plant communities of a sub-Mediterranean forest in Central Spain, and measured key above- and belowground functional traits in 411 individuals belonging to 19 species, along with abiotic variables. We calculated community-weighted mean (CWM), skewness (CWS) and kurtosis (CWK) of three plant dimensions, and used maximum likelihood techniques to analyze how variation in these functional community traits was driven by abiotic factors. Additionally, we estimated the relative contribution of intraspecific trait variability and species turnover to variation in CWM.Results and discussionThe first three axes of variation of the principal component analyses were related to three main plant ecological dimensions: Leaf Economics Spectrum, Root Economics Spectrum and plant hydraulic architecture, respectively. Type of community was the most important factor determining differences in the functional structure among communities, as compared to the role of abiotic variables. We found strong differences among communities in their CWMs in line with their biogeographic origin (Eurosiberian vs Mediterranean), while differences in CWS and CWK indicate different trends in the functional structure among communities and the coexistence of different functional strategies, respectively. Moreover, changes in functional composition were primarily due to intraspecific variability.ConclusionWe observed a high number of strategies in the forest with the different communities spreading along the acquisitive-conservative axis of resource-use, partly matching their Eurosiberian-Mediterranean nature, respectively. Intraspecific trait variability, rather than species turnover, stood as the most relevant factor when analyzing functional changes and assembly patterns among communities. Altogether, our data support the notion that ecotones are ecosystems where relatively minor environmental shifts may result in changes in plant and functional composition.

In freestyle wrestling, how regulatory breaks and micro pauses affect the efforts during combat has been studied very little. The objective of the study was to determine the temporal structure of fights in male freestyle wrestling in the 65, 86 and 125 kg categories. All wrestlers from the categories (n = 115) who competed in the 2019 senior wrestling world championship (Nur-Sultan, Kazakhstan) participated. Using observational methodology, we analyzed all fights (n = 127). We used different statistical techniques: descriptive, normality tests, Kruskall-Wallis, one-way ANOVA and chi-square. The significance level was ρ

Quantifying the effort of a sport confrontation by determining its temporal structure is of concern to the scientific community. In breaking this has not yet been sufficiently studied. The objectives of the study were to longitudinally analyze the temporal and sequential parameters of male breaking battles to determine the evolution of these parameters and to establish a model of temporal structure. All Red Bull BC One dancers from 2011 to 2021 (n = 152 dancers) participated. By using observational methodology, all battles were analyzed (n = 142). To obtain the results, we employed different analysis techniques: descriptive, normality tests, Student's t-test or Mann-Whitney, one factor ANOVA or Kruskall-Wallis and effect size (Cohen's d or Hedges' g). The significance level established for the study was ρ ≤ 0.05. The results define the temporal and sequential structure of the battles. With these, breaking professionals will be able to develop precise and adequate training for these athletes. We conclude that approaches to dancing and battling have evolved. The effort that the athlete must exert is increasing and will therefore require better preparation to cope with the physical demands required for a sport that will be incorporated into the Olympics program in 2024.

Background: The Iberian Peninsula comprises one of the largest boundaries between Mediterranean and Eurosiberian vegetation, known as sub-Mediterranean zone. This ecotone hosts many unique plant species and communities and constitutes the low-latitude (warm) margin of numerous central European species which co-occur with Mediterranean vegetation. Two of the main species found in this region are the Eurosiberian European beech (Fagus sylvatica L.) and the Mediterranean Pyrenean oak (Quercus pyrenaica Willd.). It remains unclear how the different physiological and adaptive strategies of these two species reflect their niche partitioning within a sub-Mediterranean community and to what extent phenotypic variation (intraspecific variability) is driving niche partitioning across Eurosiberian and Mediterranean species. Methods: We quantified functional niche partitioning, based on the n-dimensional hypervolume to nine traits related to resource acquisition strategies (leaf, stem and root) plus relative growth rate as an additional whole-plant trait, and the environmental niche similarity between Pyrenean oak and European beech. Further, we analyzed the degree of phenotypic variation of both target species and its relationship with relative growth rates (RGR) and environmental conditions. Plant recruitment was measured for both target species as a proxy for the average fitness. Results: Species’ functional space was highly segregated (13.09% overlap), mainly due to differences in niche breadth (59.7%) rather than niche replacement (25.6%), and beech showed higher trait variability, i.e., had larger functional space. However, both species shared the environmental space, i.e., environmental niches were overlapped. Most plant traits were not related to abiotic variables or RGR, neither did RGR to plant traits. Conclusions: Both target species share similar environmental space, however, show notably different functional resource-use strategies, promoting a high complementarity that contributes to maintaining a high functionality in sub-Mediterranean ecosystems. Therefore, we propose that conservation efforts be oriented to preserve both species in these habitats to maximize ecosystem functionality and resilience.

Time-motion analysis has been used to quantify the external load of competition and as a strategy to prevent injuries. The objectives of this study were to determine the external load of competition in breaking, using time-motion analysis, and to establish a battle model to help determine training load and prevent injuries. Using observational methodology, we analysed all the battles of 56 b-boys and 56 b-girls who participated in the Red Bull BC One from 2018 to 2021 (n = 112). To obtain the results we used different analysis techniques. The significance level established was ρ ≤ 0.05. The results show that the time and sequence values have increased in recent years. The total battle time reaches 195 s for bboys and 170 s for bgirls. Men show greater strength and explosiveness, with higher values in total time and sequentiality, using more powermove. Women have higher split time values, showing greater endurance in the movements and using more footwork. The first two rounds have the longest duration for both sexes and the most used categories are also the most injurious in this discipline. Women use less powermove than men and have a lower injury rate. With these results, breaking professionals will be able to elaborate adequate training for their athletes. We conclude that there are significant differences between sexes when it comes to dancing, diminishing as the tournament progresses. We propose a model of temporal and sequential structure individualised by sex. The most damaging elements of breaking (powermove and footwork) should be taken into account when analysing the results and preparing the athletes.

Extensive research efforts are devoted to understand fine root trait variation and to confirm the existence of a belowground root economics spectrum (RES) from acquisitive to conservative root strategies that is analogous to the leaf economics spectrum (LES). The economics spectrum implies a trade-off between maximizing resource acquisition and productivity or maximizing resource conservation and longevity; however, this theoretical framework still remains controversial for roots. We compiled a database of 320 Mediterranean woody and herbaceous species to critically assess if the classic economics spectrum theory can be broadly extended to roots. Fine roots displayed a wide diversity of forms and properties in Mediterranean vegetation, resulting in a multidimensional trait space. The main trend of variation in this multidimensional root space is analogous to the main axis of LES, while the second trend of variation is partially determined by an anatomical trade-off between tissue density and diameter. Specific root area (SRA) is the main trait explaining species distribution along the RES, regardless of the selected traits. We advocate for the need to unify and standardize the criteria and approaches used within the economics framework between leaves and roots, for the sake of theoretical consistency.

Gynecological cancer accounts for an elevated incidence worldwide requiring responsiveness regarding its care. The comprehensive genomic approach agrees with the classification of certain tumor types. We evaluated 49 patients with gynecological tumors undergoing high-throughput sequencing to explore whether identifying alterations in cancer-associated genes could characterize concrete histological subtypes. We performed immune examination and analyzed subsequent clinical impact. We found 220 genomic aberrations mostly distributed as single nucleotide variants (SNV, 77%). Only 3% were classified as variants of strong clinical significance in BRCA1 and BRCA2 of ovarian high-grade serous (HGSC) and uterine endometrioid carcinoma. TP53 and BRCA1 occurred in 72% and 28% of HGSC. Cervical squamous cell carcinoma was entirely HPV-associated and mutations occurred in PIK3CA (60%), as well as in uterine serous carcinoma (80%). Alterations were seen in PTEN (71%) and PIK3CA (60%) of uterine endometrioid carcinoma. Elevated programmed death-ligand 1 (PD-L1) was associated with high TILs. Either PD-L1 augmented in deficient mis-matched repair (MMR) proteins or POLE mutated cases when compared to a proficient MMR state. An 18% received genotype-guided therapy and a 4% immunotherapy. The description of tumor subtypes is plausible through high-throughput sequencing by recognizing clinically relevant alterations. Additional concomitant assessment of immune biomarkers identifies candidates for immunotherapy.

Background Next-generation sequencing (NGS) is a high-throughput technology that has become widely integrated in molecular diagnostics laboratories. Among the large diversity of NGS-based panels, the Trusight Tumor 26 (TsT26) enables the detection of low-frequency variants across 26 genes using the MiSeq platform. Methods We describe the inter-laboratory validation and subsequent clinical application of the panel in 399 patients presenting a range of tumor types, including gastrointestinal (GI, 29%), hematologic (18%), lung (13%), gynecological and breast (8% each), among others. Results The panel is highly accurate with a test sensitivity of 92%, and demonstrated high specificity and positive predictive values (95% and 96%, respectively). Sequencing testing was successful in two-thirds of patients, while the remaining third failed due to unsuccessful quality-control filtering. Most detected variants were observed in the TP53 (28%), KRAS (16%), APC (10%) and PIK3CA (8%) genes. Overall, 372 variants were identified, primarily distributed as missense (81%), stop gain (9%) and frameshift (7%) altered sequences and mostly reported as pathogenic (78%) and variants of uncertain significance (19%). Only 14% of patients received targeted treatment based on the variant determined by the panel. The variants most frequently observed in GI and lung tumors were: KRAS c.35G > A (p.G12D), c.35G > T (p.G12V) and c.34G > T (p.G12C). Conclusions Prior panel validation allowed its use in the laboratory daily practice by providing several relevant and potentially targetable variants across multiple tumors. However, this study is limited by high sample inadequacy rate, raising doubts as to continuity in the clinical setting.

Abstract Inflammatory activity in rheumatoid arthritis may alter the regulation of muscle mass leading to a secondary sarcopenia, commonly termed rheumatoid cachexia (RC). We characterized alterations to muscle structure and various pro-inflammatory, catabolic and regenerative markers in an animal model of RC. Antigen induced arthritis (AiA) was performed in 20 male adult rabbits. AiA animals exhibited significantly less weight gain, a markedly elevated serum C-reactive protein (CRP), lighter muscles with shorter cross-sectional diameter and increased myonuclei when compared to controls. Atrogin-1 and MuRF-1 were up-regulated alongside an increase in IL-1β, active NF-κB and a higher ratio of phosphorylated to inactive p38 MAPK. CCL-2 and TNF levels were reduced and IL-6 was unchanged between groups. We observed decreased pSTAT3, unchanged pSTAT1 and Myf5, but increased Pax7, MyoD and myogenin. AiA rabbits had a reduction in myostatin from gastrocnemii and synovium with a congruent decrease in serum myostatin compared to controls. Chronic arthritis induced an RC-like secondary sarcopenia with increased muscle protein breakdown. Elevated IL-1β may trigger proteolysis via elevated NF-κB and p38 MAPK signaling with a compensatory anabolic response suggested by myonuclear expansion, increased Pax7, MyoD and myogenin, reduced pSTAT3 as well as reduced serum, synovial and muscular myostatin.

Besides its primary function in locomotion, skeletal muscle (SKM), which represents up to half of human's weight, also plays a fundamental homeostatic role. Through the secretion of soluble peptides, or myokines, SKM interacts with major organs involved in metabolic processes. In turn, metabolic cues from these organs are received by muscle cells, which adapt their response accordingly. This is done through an intricate intracellular signaling network characterized by the cross-talking between anabolic and catabolic pathways. A fine regulation of the network is required to protect the organism from an excessive energy expenditure. Systemic inflammation evokes a catabolic reaction in SKM known as sarcopenia. In turn this response comprises several mechanisms, which vary depending on the nature of the insult and its magnitude. In this regard, aging, chronic inflammatory systemic diseases, osteoarthritis and idiopathic inflammatory myopathies can lead to muscle loss. Interestingly, sarcopenia may persist despite remission of chronic inflammation, an issue which warrants further research. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) system stands as a major participant in muscle loss during systemic inflammation, while it is also a well-recognized orchestrator of muscle cell turnover. Herein we summarize current knowledge about models of sarcopenia, their triggers and major mediators and their effect on both protein and cell growth yields. Also, the dual action of the JAK/STAT pathway in muscle mass changes is discussed. We highlight the need to unravel the precise contribution of this system to sarcopenia in order to design targeted therapeutic strategies.