Gender Difference in sidE eFfects of ImmuNotherapy: a possible clue to optimize cancEr tReatment (G-DEFINER): study protocol of an observational prospective multicenter study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have significantly improved outcomes in various cancers. ICI treatment is associated with the incidence of immune-related adverse events (irAEs) which can affect any organ. Data on irAEs occurrence in relation to sex- differentiation and their association with gender-specific factors are limited. AIMS: The primary objective of the G-DEFINER study is to compare the irAEs incidence in female and male patients who undergo ICI treatment. Secondary objectives are: to compare the irAEs incidence in pre- and postmenopausal female patients; to compare the irAEs incidence in female and male patients according to different clinical and gender-related factors (lifestyle, psychosocial, and behavioral factors). Exploratory objectives of the study are to compare and contrast hormonal, gene-expression, SNPs, cytokines, and gut microbiota profiles in relation to irAEs incidence in female and male patients. METHODS AND RESULTS: The patients are recruited from Fondazione IRCCS Istituto Nazionale dei Tumori, Italy, St Vincent's University Hospital, Ireland, Oslo University Hospital, Norway, and Karolinska Insitutet/Karolinska University Hospital, Sweden. The inclusion of patients was delayed due to the Covid pandemic, leading to a total of 250 patients recruited versus a planned number of 400 patients. Clinical and translational data will be analyzed. INTERPRETATION: The expected outcomes are to improve the management of cancer patients treated with ICIs, leading to more personalized clinical approaches that consider potential toxicity profiles. The real world nature of the trial makes it highly applicable for timely irAEs diagnosis.

Validation of Psychometric Instrumentswith Classical Test Theory in Social and Health Sciences: A practical guide / Validación de instrumentos psicométricos en ciencias sociales y de la salud: una guía práctica

Recientemente se ha incrementado significativamente el número de estudios psicométricos junto a avances estadísticos cruciales para evaluar las evidencias defiabilidad y validez de los testsy escalas de medida. Dada la importancia de proporcionar procedimientos más exactos tanto en la metodología como en la interpretación de las puntuaciones, los editores de la revista Anales de Psicología proponen esta guía para abordar los tópicos más relevantes en el campo de la psicometría aplicada. Con esta finalidad, el presente manuscrito analiza los tópicos principales de la TeoríaClásica de Tests (e.g., análisis factorial exploratorio/confirmatorio, fiabilidad, validez, sesgo, etc.) con vistas a sintetizar y clarificarlas aplicaciones prácticas, y mejorar los estándares de publicación de estos trabajos.(AU)

In recent years,there has been a significant rise in the number of psychometric studies, together with crucial statistical advances for validity and reliability measures. Given the importance of providingaccurate procedures both in methodology and score interpretationof tests and/or measurement scales, the editors-in-chie fof the journal Annals of Psychology have draftedthis guide to address the most relevant issues in the field of applied psychometry. To this end, the present manuscript analyses the main topics under the Classical Test Theory framework (e.g., exploratory/confirmatory factor analysis; reliability, bias, etc.) aimingto synthesizeand clarifythe best practical applications;and improve publication standards.(AU)

Leaf hydraulic properties of Antarctic plants: effects of growth temperature and its coordination with photosynthesis.

One of the well-documented effects of regional warming in Antarctica is the impact on flora. Warmer conditions modify several leaf anatomical traits of Antarctic vascular plants, increasing photosynthesis and growth. Given that CO2 and water vapor partially share their diffusion pathways through the leaf, changes in leaf anatomy could also affect the hydraulic traits of Antarctic plants. We evaluated the effects of growth temperature on several anatomical and hydraulic parameters of Antarctic plants and assessed the trait co-variation between these parameters and photosynthetic performance. Warmer conditions promoted an increase in leaf and whole plant hydraulic conductivity, correlating with adjustments in carbon assimilation. These adjustments were consistent with changes in leaf vasculature, where Antarctic species displayed different strategies. At higher temperature, Colobanthus quitensis decreased the number of leaf xylem vessels, but increased their diameter. In contrast, in Deschampsia antarctica the diameter did not change, but the number of vessels increased. Despite this contrasting behavior, some traits such as a small leaf diameter of vessels and a high cell wall rigidity were maintained in both species, suggesting a water-conservation response associated with the ability of Antarctic plants to cope with harsh environments.

Cross-cultural validation and psychometric properties of the Spanish version of the quality of life in Childhood epilepsy Questionnaire (QOLCE-55).

OBJECTIVE: The aims of the present study were to translate and validate the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) into Spanish. METHODS: A backtranslation procedure was used to translate the English version of QOLCE-55 to Spanish, and subsequently, parents of 88 children (aged four to 12 years), completed the Spanish version of three self-reported questionnaires: the QOLCE-55, the Pediatric Quality-of-Life Inventory (PedsQLTM 4.0), and the Pediatric Sleep Questionnaire (PSQ). Seven to 10 days later, parents completed the questionnaires again under the same conditions. RESULTS: Internal consistency was between 0.669 and 0.968 for the four subscales: cognitive (CF), emotional (EF), social (SF) and physical functioning (PF); and 0.954 for the total score. The test-retest reliability assessed with the intraclass correlation coefficient obtained values from 0.683 for SF to 0.962 for CF. The standard error of measurement for the total score was 5.776, and the minimal detectable change was 16.01. Spearman correlations between the total score of the Spanish version of the QOLCE-55 with the subscales was 0.760 for the CF, 0.776 for the EF, 0.799 for the SF, and 0.682 for the PF (p < 0.001). Convergent validity of QOLCE-55 with the PedsQLTM 4.0 scale was -0.962 (p < 0.001), and the discriminant validity of the QOLCE-55 with PSQ was 0.154 (p = 0.272). This version presented a correlation with maximum lifetime consumption of anti-epileptic drugs (0.500; p < 0.001), and current consumption (0.448; p < 0.001). CONCLUSIONS: The Spanish version of the QOLCE-55 has demonstrated adequate psychometric properties, indicating that it can be confidently used to measure the health-related quality-of-life (HRQoL) in children with epilepsy in a Spanish-speaking population. These results corroborate the instrument's cross-cultural validity.

Prognostic Value of BAP1 Protein Expression in Uveal Melanoma.

The prognostic value of the traditional pathologic parameters that form part of the American Joint Committee on Cancer staging system and genetic classifications using monosomy chromosome 3 and structural alterations in chromosome 8 are well established and are part of the diagnostic workup of uveal melanoma (UM). However, it has not been fully clarified whether nuclear protein expression of the tumor suppressor gene BAP1 (nBAP1) by immunohistochemistry alone is as powerful a predictor of overall survival (OS) and/or disease-specific survival (DSS) as chromosome analysis. The protein expression of nBAP1 was evaluated in a retrospective cohort study of 308 consecutive patients treated by primary enucleation between January 1974 and December 2022. We correlated clinical, pathologic, and cytogenetic characteristics to identify the best prognostic indicators for OS and DSS. Loss of nBAP1 was detected in 144/308 (47%) of patients. Loss of nBAP1 expression was significantly associated with poor survival. In patients with disomy chromosome 3, nBAP1 negative is significantly associated with poorer OS but not DSS. We observed that older age (>63 years), presence of metastasis, and nBAP1 negative remained independent prognostic factors in multivariate analysis. nBAP1 protein expression proved to be a more reliable prognostic indicator for OS than the American Joint Committee on Cancer staging, M3 status, or The Cancer Genome Atlas classification in this cohort. This study provides support for accurate prognostication of UM patients in routine histology laboratories by immunohistochemistry for nBAP1 alone.

Short-Chain Fatty Acid Production by Gut Microbiota Predicts Treatment Response in Multiple Myeloma.

PURPOSE: The gut microbiota plays important roles in health and disease. We questioned whether the gut microbiota and related metabolites are altered in monoclonal gammopathies and evaluated their potential role in multiple myeloma and its response to treatment. EXPERIMENTAL DESIGN: We used 16S rRNA sequencing to characterize and compare the gut microbiota of patients with monoclonal gammopathy of undetermined significance (n = 11), smoldering multiple myeloma (n = 9), newly diagnosed multiple myeloma (n = 11), relapsed/refractory multiple myeloma (n = 6), or with complete remission (n = 9). Short-chain fatty acids (SCFA) were quantified in serum and tested in cell lines. Relevant metabolites were validated in a second cohort of 62 patients. RESULTS: Significant differences in alpha- and beta diversity were present across the groups and both were lower in patients with relapse/refractory disease and higher in patients with complete remission after treatment. Differences were found in the abundance of several microbiota taxa across disease progression and in response to treatment. Bacteria involved in SCFA production, including Prevotella, Blautia, Weissella, and Agathobacter, were more represented in the premalignant or complete remission samples, and patients with higher levels of Agathobacter showed better overall survival. Serum levels of butyrate and propionate decreased across disease progression and butyrate was positively associated with a better response. Both metabolites had antiproliferative effects in multiple myeloma cell lines. CONCLUSIONS: We demonstrate that SCFAs metabolites and the gut microbiota associated with their production might have beneficial effects in disease evolution and response to treatment, underscoring its therapeutic potential and value as a predictor.

Improving Sleep Quality, Daytime Sleepiness, and Cognitive Function in Patients with Dementia by Therapeutic Exercise and NESA Neuromodulation: A Multicenter Clinical Trial.

Dementia is a progressive decline in cognitive functions caused by an alteration in the pattern of neural network connections. There is an inability to create new neuronal connections, producing behavioral disorders. The most evident alteration in patients with neurodegenerative diseases is the alteration of sleep-wake behavior. The aim of this study was to test the effect of two non-pharmacological interventions, therapeutic exercise (TE) and non-invasive neuromodulation through the NESA device (NN) on sleep quality, daytime sleepiness, and cognitive function of 30 patients diagnosed with dementia (non-invasive neuromodulation experimental group (NNG): mean ± SD, age: 71.6 ± 7.43 years; therapeutic exercise experimental group (TEG) 75.2 ± 8.63 years; control group (CG) 80.9 ± 4.53 years). The variables were evaluated by means of the Pittsburg Index (PSQI), the Epworth Sleepiness Scale (ESS), and the Mini-Cognitive Exam Test at four different times during the study: at baseline, after 2 months (after completion of the NNG), after 5 months (after completion of the TEG), and after 7 months (after 2 months of follow-up). Participants in the NNG and TEG presented significant improvements with respect to the CG, and in addition, the NNG generated greater relevant changes in the three variables with respect to the TEG (sleep quality (p = 0.972), daytime sleepiness (p = 0.026), and cognitive function (p = 0.127)). In conclusion, with greater effects in the NNG, both treatments were effective to improve daytime sleepiness, sleep quality, and cognitive function in the dementia population.

Corrigendum: Personalized monitoring of circulating tumor DNA with a specific signature of trackable mutations after chimeric antigen receptor T-cell therapy in follicular lymphoma patients.

[This corrects the article DOI: 10.3389/fimmu.2023.1188818.].

High Rate of Inappropriate Antibiotics in Patients with Hematologic Malignancies and Pseudomonas aeruginosa Bacteremia following International Guideline Recommendations.

Optimal coverage of Pseudomonas aeruginosa is challenging in febrile neutropenic patients due to a progressive increase in antibiotic resistance worldwide. We aimed to detail current rates of resistance to antibiotics recommended by international guidelines for P. aeruginosa isolated from bloodstream infections (BSI) in patients with hematologic malignancies. Secondarily, we aimed to describe how many patients received inappropriate empirical antibiotic treatment (IEAT) and its impact on mortality. We conducted a retrospective, multicenter cohort study of the last 20 BSI episodes caused by P. aeruginosa in patients with hematologic malignancies from across 14 university hospitals in Spain. Of the 280 patients with hematologic malignancies and BSI caused by P. aeruginosa, 101 (36%) had strains resistant to at least one of the ß-lactam antibiotics recommended in international guidelines, namely, cefepime, piperacillin-tazobactam, and meropenem. Additionally, 21.1% and 11.4% of the strains met criteria for MDR and XDR P. aeruginosa, respectively. Even if international guidelines were followed in most cases, 47 (16.8%) patients received IEAT and 66 (23.6%) received inappropriate ß-lactam empirical antibiotic treatment. Thirty-day mortality was 27.1%. In the multivariate analysis, pulmonary source (OR 2.22, 95% CI 1.14 to 4.34) and IEAT (OR 2.67, 95% CI 1.37 to 5.23) were factors independently associated with increased mortality. We concluded that P. aeruginosa-causing BSI in patients with hematologic malignancies is commonly resistant to antibiotics recommended in international guidelines, which is associated with frequent IEAT and higher mortality. New therapeutic strategies are needed. IMPORTANCE Bloodstream infection (BSI) caused by P. aeruginosa is related with an elevated morbidity and mortality in neutropenic patients. For this reason, optimal antipseudomonal coverage has been the basis of all historical recommendations in the empirical treatment of febrile neutropenia. However, in recent years the emergence of multiple types of antibiotic resistances has posed a challenge in treating infections caused by this microorganism. In our study we postulated that P. aeruginosa-causing BSI in patients with hematologic malignancies is commonly resistant to antibiotics recommended in international guidelines. This observation is associated with frequent IEAT and increased mortality. Consequently, there is a need for a new therapeutic strategy.

Personalized monitoring of circulating tumor DNA with a specific signature of trackable mutations after chimeric antigen receptor T-cell therapy in follicular lymphoma patients.

Background: CART therapy has produced a paradigm shift in the treatment of relapsing FL patients. Strategies to optimize disease surveillance after these therapies are increasingly necessary. This study explores the potential value of ctDNA monitoring with an innovative signature of personalized trackable mutations. Method: Eleven FL patients treated with anti-CD19 CAR T-cell therapy were included. One did not respond and was excluded. Genomic profiling was performed before starting lymphodepleting chemotherapy to identify somatic mutations suitable for LiqBio-MRD monitoring. The dynamics of the baseline mutations (4.5 per patient) were further analyzed on 59 cfDNA follow-up samples. PET/CT examinations were performed on days +90, +180, +365, and every six months until disease progression or death. Results: After a median follow-up of 36 months, all patients achieved a CR as the best response. Two patients progressed. The most frequently mutated genes were CREBBP, KMT2D and EP300. Simultaneous analysis of ctDNA and PET/CT was available for 18 time-points. When PET/CT was positive, two out of four ctDNA samples were LiqBio-MRD negative. These two negative samples corresponded to women with a unique mesenteric mass in two evaluations and never relapsed. Meanwhile, 14 PET/CT negative images were mutation-free based on our LiqBio-MRD analysis (100%). None of the patients had a negative LiqBio-MRD test by day +7. Interestingly, all durably responding patients had undetectable ctDNA at or around three months after infusion. Two patients presented discordant results by PET/CT and ctDNA levels. No progression was confirmed in these cases. All the progressing patients were LiqBio-MRD positive before progression. Conclusion: This is a proof-of-principle for using ctDNA to monitor response to CAR T-cell therapy in FL. Our results confirm that a non-invasive liquid biopsy MRD analysis may correlate with response and could be used to monitor response. Harmonized definitions of ctDNA molecular response and pinpointing the optimal timing for assessing ctDNA responses are necessary for this setting. If using ctDNA analysis, we suggest restricting follow-up PET/CT in CR patients to a clinical suspicion of relapse, to avoid false-positive results.

Janus kinase inhibitor ruxolitinib in combination with nilotinib and prednisone in patients with myelofibrosis (RuNiC study): A phase Ib, multicenter study.

This phase Ib, non-randomized, open-label study evaluates the safety and tolerability of ruxolitinib in combination with nilotinib and prednisone in patients with naïve or ruxolitinib-resistant myelofibrosis (MF). A total of 15 patients with primary or secondary MF received the study treatment; 13 patients had received prior ruxolitinib treatment (86.7%). Eight patients completed seven cycles (53.3%) and six patients completed twelve cycles of treatment (40%). All the patients experienced at least one adverse event (AE) during the study (the most common AEs were hyperglycemia, asthenia, and thrombocytopenia), and 14 patients registered at least one treatment-related AE (the most common treatment-related AEs were hyperglycemia (22.2%; three grade 3 cases). Five treatment-related serious AEs (SAEs) were reported in two patients (13.3%). No deaths were registered throughout the study. No dose-limiting toxicity was observed. Four out of fifteen (27%) patients experienced a 100% spleen size reduction at Cycle 7, and two additional patients achieved a >50% spleen size reduction, representing an overall response rate of 40% at Cycle 7. In conclusion, the tolerability of this combination was acceptable, and hyperglycemia was the most frequent treatment-related AE. Ruxolitinib in combination with nilotinib and prednisone showed relevant clinical activity in patients with MF. This trial was registered with EudraCT Number 2016-005214-21.

Hemophilic Arthropathy of the Knee and Its Association with Reduced Muscle Strength and Activation and the Pressure Pain Threshold: A Case-Control Study.

(1) Background: Hemophilia is characterized by recurrent hemarthrosis leading to degenerative arthropathy. The aim was to evaluate the differences in muscle strength and activity and the pressure pain threshold between patients with knee arthropathy and their healthy peers; (2) Methods: A case-control study in which 23 adult patients with knee arthropathy and 24 healthy peers matched in terms of characteristics were recruited. The study variables were quadriceps muscle strength, muscle activation and the pressure pain threshold; (3) Results: There were significant differences between the two groups in quadriceps strength on the dominant (CI95%: 64.69, 129.2) and non-dominant (CI95%: 29.95, 93.55) sides and in the pressure pain threshold on the dominant (CI95%: 3.30, 43.54) and non-dominant (CI95%: 3.09, 45.25) sides. There were differences in neuromuscular fatigue on the non-dominant side in the vastus medialis (CI95%: 8.72, 21.51), vastus lateralis (CI95%: 4.84, 21.66) and rectus femoris (CI95%: 6.48, 24.95) muscles; (4) Conclusions: Muscle strength and the pressure pain threshold are lower in patients with hemophilia. Quadriceps muscle activation in patients with hemophilic knee arthropathy does not in any way differ from activation in healthy subjects. However, muscle fatigue is greater in patients with knee arthropathy. Strength training in patients with hemophilia should focus on the activation of the vastus medialis and lateralis muscles.

Prevalence of refractive errors in children of Puerto Rico.

AIM: To determine the prevalence of refractive error in 5- to 17-year-old schoolchildren in Puerto Rico. METHODS: A quantitative descriptive study of 2867 children aged 5 to 17y from all seven educational regions of Puerto Rico was conducted from 2016-2019. Refractive error was determined via static and subjective refraction. Children with distance acuity ≤20/40 or near visual acuity ≤20/32 had a cycloplegic refraction. Data analysis included descriptive statistics, correlation coefficient, Kruskal-Wallis, Chi-square, and t test calculations. RESULTS: Twenty percent of the children had a spherical equivalent refractive error ≤ -0.50 D, 3.2% had a spherical equivalent ≥ +2.00 D, and 10.4% had astigmatism ≥1 D. There was a statistically (but non-clinically) significant myopic change in spherical equivalent refractive error with age (P<0.001). The prevalence of myopia increased with age (P<0.001) but not hyperopia (P=0.59) or astigmatism (P=0.51). Males had a significantly higher hyperopic spherical equivalent than females (P<0.001). Females had a higher prevalence of myopia (P<0.001) than males, but there was no difference in the hyperopia (P=0.74) or astigmatism prevalence (P=0.87). CONCLUSION: The prevalence of a spherical equivalent equal to or less than -0.50 D (myopia, 20.7%) is one of the highest among similar-aged children worldwide. Further studies should explore the rate of myopia progression in children in Puerto Rico. Individual children must be monitored to examine the need for treatment of myopia progression.

Contrasting stem water uptake and storage dynamics of water-saver and water-spender species during drought and recovery.

Drought is projected to occur more frequently and intensely in the coming decades, and the extent to which it will affect forest functioning will depend on species-specific responses to water stress. Aiming to understand the hydraulic traits and water dynamics behind water-saver and water-spender strategies in response to drought and recovery, we conducted a pot experiment with two species with contrasting physiological strategies, Scots pine (Pinus sylvestris L.) and Portuguese oak (Quercus faginea L.). We applied two cycles of soil drying and recovery and irrigated with isotopically different water to track fast changes in soil and stem water pools, while continuously measuring physiological status and xylem water content from twigs. Our results provide evidence for a tight link between the leaf-level response and the water uptake and storage patterns in the stem. The water-saver strategy of pines prevented stem dehydration by rapidly closing stomata which limited their water uptake during the early stages of drought and recovery. Conversely, oaks showed a less conservative strategy, maintaining transpiration and physiological activity under dry soil conditions, and consequently becoming more dehydrated at the stem level. We interpreted this dehydration as the release of water from elastic storage tissues as no major loss of hydraulic conductance occurred for this species. After soil rewetting, pines recovered pre-drought leaf water potential rapidly, but it took longer to replace the water from conductive tissues (slower labeling speed). In contrast, water-spender oaks were able to quickly replace xylem water during recovery (fast labeling speed), but it took longer to refill stem storage tissues, and hence to recover pre-drought leaf water potential. These different patterns in sap flow rates, speed and duration of the labeling reflected a combination of water-use and storage traits, linked to the leaf-level strategies in response to drought and recovery.

Disentangling leaf structural and material properties in relationship to their anatomical and chemical compositional traits in oaks (Quercus L.).

BACKGROUND AND AIMS: The existence of sclerophyllous plants has been considered an adaptive strategy against different environmental stresses. Given that it literally means 'hard-leaved', it is essential to quantify the leaf mechanical properties to understand sclerophylly. However, the relative importance of each leaf trait for mechanical properties is not yet well established. METHODS: Genus Quercus is an excellent system to shed light on this because it minimizes phylogenetic variation while having a wide variation in sclerophylly. We measured leaf anatomical traits and cell wall composition, analysing their relationship with leaf mass per area and leaf mechanical properties in a set of 25 oak species. KEY RESULTS: The upper epidermis outer wall makes a strong and direct contribution to the leaf mechanical strength. Moreover, cellulose plays a crucial role in increasing leaf strength and toughness. The principal component analysis plot based on leaf trait values clearly separates Quercus species into two groups corresponding to evergreen and deciduous species. CONCLUSIONS: Sclerophyllous Quercus species are tougher and stronger owing to their thicker epidermis outer wall and/or higher cellulose concentration. Furthermore, section Ilex species share common traits, although they occupy different climates. In addition, evergreen species living in mediterranean-type climates share common leaf traits irrespective of their different phylogenetic origin.

Genetic Alterations in Members of the Proteasome 26S Subunit, AAA-ATPase (PSMC) Gene Family in the Light of Proteasome Inhibitor Resistance in Multiple Myeloma.

For the treatment of Multiple Myeloma, proteasome inhibitors are highly efficient and widely used, but resistance is a major obstacle to successful therapy. Several underlying mechanisms have been proposed but were only reported for a minority of resistant patients. The proteasome is a large and complex machinery. Here, we focus on the AAA ATPases of the 19S proteasome regulator (PSMC1-6) and their implication in PI resistance. As an example of cancer evolution and the acquisition of resistance, we conducted an in-depth analysis of an index patient by applying FISH, WES, and immunoglobulin-rearrangement sequencing in serial samples, starting from MGUS to newly diagnosed Multiple Myeloma to a PI-resistant relapse. The WES analysis uncovered an acquired PSMC2 Y429S mutation at the relapse after intensive bortezomib-containing therapy, which was functionally confirmed to mediate PI resistance. A meta-analysis comprising 1499 newly diagnosed and 447 progressed patients revealed a total of 36 SNVs over all six PSMC genes that were structurally accumulated in regulatory sites for activity such as the ADP/ATP binding pocket. Other alterations impact the interaction between different PSMC subunits or the intrinsic conformation of an individual subunit, consequently affecting the folding and function of the complex. Interestingly, several mutations were clustered in the central channel of the ATPase ring, where the unfolded substrates enter the 20S core. Our results indicate that PSMC SNVs play a role in PI resistance in MM.

Axicabtagene ciloleucel compared to tisagenlecleucel for the treatment of aggressive B-cell lymphoma.

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-targeted chimeric antigen receptor (CAR) T cells approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We performed a retrospective study to evaluate safety and efficacy of axi-cel and tisa-cel outside the setting of a clinical trial. Data from consecutive patients with R/R LBCL who underwent apheresis for axi-cel or tisa-cel were retrospectively collected from 12 Spanish centers. A total of 307 patients underwent apheresis for axi-cel (n=152) and tisa-cel (n=155) from November 2018 to August 2021, of which 261 (85%) received a CAR T infusion (88% and 82%, respectively). Median time from apheresis to infusion was 41 days for axi-cel and 52 days for tisa-cel (P=0.006). None of the baseline characteristics were significantly different between both cohorts. Both cytokine release syndrome and neurologic events (NE) were more frequent in the axi-cel group (88% vs. 73%, P=0.003, and 42% vs. 16%, P<0.001, respectively). Infections in the first 6 months post-infusion were also more common in patients treated with axi-cel (38% vs. 25%, P=0.033). Non-relapse mortality was not significantly different between the axi-cel and tisa-cel groups (7% and 4%, respectively, P=0.298). With a median follow-up of 9.2 months, median PFS and OS were 5.9 and 3 months, and 13.9 and 11.2 months for axi-cel and tisa-cel, respectively. The 12-month PFS and OS for axi-cel and tisa-cel were 41% and 33% (P=0.195), 51% and 47% (P=0.191), respectively. Factors associated with lower OS in the multivariate analysis were increased lactate dehydrogenase, ECOG ≥2 and progressive disease before lymphodepletion. Safety and efficacy results in our real-world experience were comparable with those reported in the pivotal trials. Patients treated with axi-cel experienced more toxicity but similar non-relapse mortality compared with those receiving tisa-cel. Efficacy was not significantly different between both products.

180-degree immersive VR motion visualization in the treatment of haemophilic ankle arthropathy.

BACKGROUND: Patients with haemophilic arthropathy suffer chronic pain that affects and restricts their quality of life. Visualization of movement through immersive virtual reality is used for pain management. AIM: To evaluate the efficacy of 180-degree immersive VR motion visualization therapy in patients with haemophilic ankle arthropathy. METHODS: Prospective, multicentre pilot study. Fifteen adult patients with bilateral haemophilic ankle arthropathy were recruited (mean age: 42.73 ± 12.36 years). The intervention lasted 4 weeks, with daily home sessions of 180-degree immersive motion visualization. The patients were given virtual reality glasses to use with their smartphones. From the YouTube mobile app® they accessed the recorded video with access from the He-Mirror App®. The study variables were joint state (Haemophilia Joint Health Score), pressure pain threshold (pressure algometer), muscle strength (dynamometry) and range of motion (goniometry). Three evaluations were performed: at baseline (T0), after the intervention (T1) and at the end of a 16-week follow-up period (T2). RESULTS: No patient developed ankle hemarthrosis during the experimental phase. In the repeated measures analysis we found statistically significant differences in joint state (F = 51.38; η2 p = .63), pressure pain threshold of the lateral malleolus (F = 12.34; η2 p = .29) and range of motion (F = 11.7; η2 p = .28). CONCLUSIONS: Therapy using immersive motion visualization does not cause hemarthrosis. This intervention can improve joint condition, pressure pain threshold and range of motion in patients with ankle arthropathy. Changes greater than the MDC were reported in more than 40% of patients for the variables pressure pain threshold, anterior tibialis strength and range of motion, which were considered clinically relevant.

Rock n' Seeds: A database of seed functional traits and germination experiments from Brazilian rock outcrop vegetation.

Advancing functional ecology depends fundamentally on the availability of data on reproductive traits, including those from tropical plants, which have been historically underrepresented in global trait databases. Although some valuable databases have been created recently, they are mainly restricted to temperate areas and vegetative traits such as leaf and wood traits. Here, we present Rock n' Seeds, a database of seed functional traits and germination experiments from Brazilian rock outcrop vegetation, recognized as outstanding centers of diversity and endemism. Data were compiled through a systematic literature search, resulting in 103 publications from which seed functional traits were extracted. The database includes information on 16 functional traits for 383 taxa from 148 genera, 50 families, and 25 orders. These 16 traits include two dispersal, six production, four morphological, two biophysical, and two germination traits-the major axes of the seed ecological spectrum. The database also provides raw data for 48 germination experiments, for a total of 10,187 records for 281 taxa. Germination experiments in the database assessed the effect of a wide range of abiotic and biotic factors on germination and different dormancy-breaking treatments. Notably, 8255 of these records include daily germination counts. This input will facilitate synthesizing germination data and using this database for a myriad of ecological questions. Given the variety of seed traits and the extensive germination information made available by this database, we expect it to be a valuable resource advancing comparative functional ecology and guiding seed-based restoration and biodiversity conservation in tropical megadiverse ecosystems. There are no copyright restrictions on the data; please cite this paper when using the current data in publications; also the authors would appreciate notification of how the data are used in publications.

O avanço da ecologia funcional depende fundamentalmente da disponibilidade de dados sobre traços reprodutivos, incluindo dados de plantas tropicais, que têm sido historicamente subrepresentados em bancos de dados de traços funcionais globais. Embora alguns bancos de dados valiosos tenham sido criados recentemente, eles são restritos principalmente a áreas temperadas e a traços vegetativos, como traços de folhas e madeira. Neste artigo apresentamos Rock n' Seeds, um banco de dados de traços funcionais de sementes e experimentos de germinação de vegetações associadas a afloramentos rochosos do Brasil, os quais são reconhecidos como centros notáveis de diversidade e endemismo. Os dados foram compilados através de uma revisão sistemática na literatura, resultando em 103 publicações das quais foram extraídos os traços funcionais das sementes. O banco de dados inclui informações de 16 traços funcionais para 383 taxa de 148 gêneros, 50 famílias e 25 ordens. Estes dezesseis traços incluem dois traços de dispersão, seis de produção, quatro morfológicos, dois biofísicos e dois germinativos; os eixos principais do espectro ecológico da semente. O banco de dados também fornece os dados brutos para 48 experimentos de germinação para um total de 10.187 registros para 281 taxa. Os experimentos de germinação no banco de dados avaliaram o efeito de uma ampla gama de fatores abióticos e bióticos sobre a germinação e diferentes tratamentos de quebra de dormência. Particularmente, 8.255 desses registros incluem a contagem diária da germinação. Estas informações facilitarão a síntese de dados de germinação e a utilização deste banco de dados para uma grande variedade de questões ecológicas. Dada a variedade de traços das sementes e as amplas informações sobre germinação disponibilizadas por este banco de dados, esperamos que ele seja um recurso valioso para o avanço da ecologia funcional comparativa e para orientar a restauração baseada em sementes e a conservação da biodiversidade em ecossistemas tropicais megadiversos. Não há restrições de direitos autorais sobre os dados; favor citar este artigo ao utilizar os dados nas publicações e os autores agradeceriam uma notificação de como os dados são utilizados nas publicações.

El avance de la ecología funcional depende fundamentalmente de la disponibilidad de datos sobre rasgos reproductivos-incluyendo los de las plantas tropicales-los cuales han estado poco representados en las bases de datos globales de rasgos. Aunque recientemente se han creado algunas bases de datos valiosas, estas se encuentran restringidas principalmente a las zonas templadas y a los rasgos vegetativos, como los de las hojas y la madera. En este artículo presentamos Rock n' Seeds, una base de datos de rasgos funcionales de semillas y experimentos de germinación de la vegetación asociada a afloramientos rocosos de Brasil, los cuales son destacados centros de diversidad y endemismo. Los datos se recopilaron mediante una búsqueda bibliográfica sistemática, que dio como resultado 103 publicaciones de las que se extrajeron los rasgos funcionales de las semillas. La base de datos incluye información de dieciséis rasgos funcionales para 383 taxones de 148 géneros, 50 familias y 25 órdenes. Estos rasgos incluyen dos rasgos de dispersión, seis de producción, cuatro morfológicos, dos biofísicos y dos de germinación; siendo estos los principales ejes del espectro ecológico de las semillas. La base de datos también proporciona los datos brutos de 48 experimentos de germinación, para un total de 10.187 registros de 281 taxones. Dichos experimentos de germinación evaluaron el efecto de una amplia gama de factores abióticos y bióticos sobre la germinación y de diferentes tratamientos para romper la dormancia. En particular, 8.255 de estos registros cuentan con conteos diarios de germinación. Esto facilitará la síntesis de los datos de germinación y el uso de esta base de datos para una gran diversidad de preguntas ecológicas. Dada la variedad de rasgos de las semillas y la amplia información sobre germinación que ofrece esta base de datos, esperamos que sea un recurso valioso para el avance de la ecología funcional comparativa y para orientar la restauración basada en semillas y la conservación de la biodiversidad en ecosistemas tropicales megadiversos. No hay restricciones de derechos de autor sobre los datos; se solicita citar este documento cuando se utilicen los datos en publicaciones y los autores agradecerán ser notificados sobre cómo se utilizan los datos en las publicaciones.

Corrigendum: Personalized monitoring of circulating tumor DNA with a specific signature of trackable mutations after chimeric antigen receptor T-cell therapy in follicular lymphoma patients.

[This corrects the article DOI: 10.3389/fimmu.2023.1188818.].