Search

Abstract This paper presents Multi-view Leap2 Hand Pose Dataset (ML2HP Dataset), a new dataset for hand pose recognition, captured using a multi-view recording setup with two Leap Motion Controller 2 devices. This dataset encompasses a diverse range of hand poses, recorded from different angles to ensure comprehensive coverage. The dataset includes real images with the associated precise and automatic hand properties, such as landmark coordinates, velocities, orientations, and finger widths. This dataset has been meticulously designed and curated to maintain a balance in terms of subjects, hand poses, and the usage of right or left hand, ensuring fairness and parity. The content includes 714,000 instances from 21 subjects of 17 different hand poses (including real images and 247 associated hand properties). The multi-view setup is necessary to mitigate hand occlusion phenomena, ensuring continuous tracking and pose estimation required in real human-computer interaction applications. This dataset contributes to advancing the field of multimodal hand pose recognition by providing a valuable resource for developing advanced artificial intelligence human computer interfaces.

PURPOSE: The surrogacy of biochemical recurrence (BCR) for overall survival (OS) in localized prostate cancer remains controversial. Herein, we evaluate the surrogacy of BCR using different surrogacy analytic methods. MATERIALS AND METHODS: Individual patient data from 11 trials evaluating radiotherapy dose escalation, androgen deprivation therapy (ADT) use, and ADT prolongation were obtained. Surrogate candidacy was assessed using the Prentice criteria (including landmark analyses) and the two-stage meta-analytic approach (estimating Kendalls tau and the R2). Biochemical recurrence-free survival (BCRFS, time from random assignment to BCR or any death) and time to BCR (TTBCR, time from random assignment to BCR or cancer-specific deaths censoring for noncancer-related deaths) were assessed. RESULTS: Overall, 10,741 patients were included. Dose escalation, addition of short-term ADT, and prolongation of ADT duration significantly improved BCR (hazard ratio [HR], 0.71 [95% CI, 0.63 to 0.79]; HR, 0.53 [95% CI, 0.48 to 0.59]; and HR, 0.54 [95% CI, 0.48 to 0.61], respectively). Adding short-term ADT (HR, 0.91 [95% CI, 0.84 to 0.99]) and prolonging ADT (HR, 0.86 [95% CI, 0.78 to 0.94]) significantly improved OS, whereas dose escalation did not (HR, 0.98 [95% CI, 0.87 to 1.11]). BCR at 48 months was associated with inferior OS in all three groups (HR, 2.46 [95% CI, 2.08 to 2.92]; HR, 1.51 [95% CI, 1.35 to 1.70]; and HR, 2.31 [95% CI, 2.04 to 2.61], respectively). However, after adjusting for BCR at 48 months, there was no significant treatment effect on OS (HR, 1.10 [95% CI, 0.96 to 1.27]; HR, 0.96 [95% CI, 0.87 to 1.06] and 1.00 [95% CI, 0.90 to 1.12], respectively). The patient-level correlation (Kendalls tau) for BCRFS and OS ranged between 0.59 and 0.69, and that for TTBCR and OS ranged between 0.23 and 0.41. The R2 values for trial-level correlation of the treatment effect on BCRFS and TTBCR with that on OS were 0.563 and 0.160, respectively. CONCLUSION: BCRFS and TTBCR are prognostic but failed to satisfy all surrogacy criteria. Strength of correlation was greater when noncancer-related deaths were considered events.

Introduction: Diffuse intrinsic pontine glioma (DIPG) is the most common malignant brainstem tumour in children. Despite advances in understanding its biology, current treatments have shown minimal impact on overall survival in this fatal disease. Focal radiotherapy (RT) is the only treatment proven to improve symptoms and extend progression-free survival. Albeit palliative, re-irradiation (rRT) has emerged as the best alternative for progressive disease. This study presents the Spanish experience with re-irradiation in DIPG. Results: Between April 2015 and December 2023, 44 paediatric patients with progressive DIPG underwent rRT in 16 Spanish institutions. Median time from diagnosis to progression was 9.9 months (range, 4.2–24.3 months). Median dose of rRT was 20 Gy (range, 18–40 Gy) in 2 Gy fractions (range, 1.3–4 Gy). Twenty-two patients (50 %) received other treatments besides RT. Clinical improvement was seen in 77.3 %, and radiological improvement in 60 %. Treatment was well tolerated (1 case toxicity >grade 2 related to rRT). Median overall survival was 15.5 months (range, 8.2–63.2 months), with a median time from rRT to death of 4.2 months (range, 0.6–10.3 months). Longer time between diagnosis and rRT (>10 months) and dose of rRT >20 Gy were statistically significantly correlated with better overall survival. There was no survival benefit in patients receiving additional treatments. Conclusions: Re-irradiation is safe and effective in progressive DIPG patients, not only improving symptoms but also prolonging survival. However, the ideal candidates for rRT remain undefined, as well as the best irradiation scheme. Prospective studies are needed.

PurposeThe sequencing of androgen-deprivation therapy (ADT) with radiotherapy (RT) may affect outcomes for prostate cancer in an RT-field size-dependent manner. Herein, we investigate the impact of ADT sequencing for men receiving ADT with prostate-only RT (PORT) or whole-pelvis RT (WPRT).Materials and methodsIndividual patient data from 12 randomized trials that included patients receiving neoadjuvant/concurrent or concurrent/adjuvant short-term ADT (4-6 months) with RT for localized disease were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate consortium. Inverse probability of treatment weighting (IPTW) was performed with propensity scores derived from age, initial prostate-specific antigen, Gleason score, T stage, RT dose, and mid-trial enrollment year. Metastasis-free survival (primary end point) and overall survival (OS) were assessed by IPTW-adjusted Cox regression models, analyzed independently for men receiving PORT versus WPRT. IPTW-adjusted Fine and Gray competing risk models were built to evaluate distant metastasis (DM) and prostate cancer-specific mortality.ResultsOverall, 7,409 patients were included (6,325 neoadjuvant/concurrent and 1,084 concurrent/adjuvant) with a median follow-up of 10.2 years (interquartile range, 7.2-14.9 years). A significant interaction between ADT sequencing and RT field size was observed for all end points (P interaction < .02 for all) except OS. With PORT (n = 4,355), compared with neoadjuvant/concurrent ADT, concurrent/adjuvant ADT was associated with improved metastasis-free survival (10-year benefit 8.0%, hazard ratio [HR], 0.65; 95% CI, 0.54 to 0.79; P < .0001), DM (subdistribution HR, 0.52; 95% CI, 0.33 to 0.82; P = .0046), prostate cancer-specific mortality (subdistribution HR, 0.30; 95% CI, 0.16 to 0.54; P < .0001), and OS (HR, 0.69; 95% CI, 0.57 to 0.83; P = .0001). However, in patients receiving WPRT (n = 3,049), no significant difference in any end point was observed in regard to ADT sequencing except for worse DM (HR, 1.57; 95% CI, 1.20 to 2.05; P = .0009) with concurrent/adjuvant ADT.ConclusionADT sequencing exhibits a significant impact on clinical outcomes with a significant interaction with field size. Concurrent/adjuvant ADT should be the standard of care where short-term ADT is indicated in combination with PORT.

Summary: Single-cell microcultures (SCMs) form a monosynaptic circuit that allows stimulation and recording of postsynaptic responses using a single electrode. Here, we present a protocol to establish autaptic cultures from rat superior cervical ganglion neurons. We describe the steps for preparing SCMs, recording synaptic currents, and identifying and processing the recorded neurons for electron microscopy. We then detail procedures for visualizing synapses. This protocol is illustrated by correlating evoked and spontaneous neurotransmitter release with the ultrastructural features of synapses recorded.For complete details on the use and execution of this protocol, please refer to Velasco et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Background Focal brain lesions following a stroke of the middle cerebral artery induce large-scale network disarray with a potential to impact multiple cognitive and behavioral domains. Over the last 20 years, non-invasive brain neuromodulation via electrical (tCS) stimulation has shown promise to modulate motor deficits and contribute to recovery. However, weak, inconsistent, or at times heterogeneous outcomes using these techniques have also highlighted the need for novel strategies and the assessment of their efficacy in ad hoc controlled clinical trials. Methods We here present a double-blind, sham-controlled, single-center, randomized pilot clinical trial involving participants having suffered a unilateral middle cerebral artery (MCA) stroke resulting in motor paralysis of the contralateral upper limb. Patients will undergo a 10-day regime (5 days a week for 2 consecutive weeks) of a newly designed high-definition transcranial direct current stimulation (HD-tDCS) protocol. Clinical evaluations (e.g., Fugl Meyer, NIHSS), computer-based cognitive assessments (visuo-motor adaptation and AX-CPT attention tasks), and electroencephalography (resting-state and task-evoked EEG) will be carried out at 3 time points: (I) Baseline, (II) Post-tDCS, and (III) Follow-up. The study consists of a four-arm trial comparing the impact on motor recovery of three active anodal tDCS conditions: ipsilesional DLPFC tDCS, contralesional cerebellar tDCS or combined DLPFC + contralesional cerebellar tDCS, and a sham tDCS intervention. The Fugl-Meyer Assessment for the upper extremity (FMA-UE) is selected as the primary outcome measure to quantify motor recovery. In every stimulation session, participants will receive 20 min of high-density tDCS stimulation (HD-tDCS) (up to 0.63 mA/ $${\mathrm{cm}}^{2}$$ cm 2 ) with $${\mathrm{\pi cm}}^{2}$$ π cm 2 electrodes. Electrode scalp positioning relative to the cortical surface (anodes and cathodes) and intensities are based on a biophysical optimization model of current distribution ensuring a 0.25 V/m impact at each of the chosen targets. Discussion Our trial will gauge the therapeutic potential of accumulative sessions of HD-tDCS to improve upper limb motor and cognitive dysfunctions presented by middle cerebral artery stroke patients. In parallel, we aim at characterizing changes in electroencephalographic (EEG) activity as biomarkers of clinical effects and at identifying potential interactions between tDCS impact and motor performance outcomes. Our work will enrich our mechanistic understanding on prefrontal and cerebellar contributions to motor function and its rehabilitation following brain damage. Trial registration ClinicalTrials.gov NCT05329818. April 15, 2022.

Foot-and-mouth disease (FMD) is globally recognized as a highly economically devastating and prioritized viral disease affecting livestock. Vaccination remains a crucial preventive measure against FMD. The improvement of current vaccine platforms could help control outbreaks, leading to the potential eradication of the disease. In this review, we describe the variances in virulence and immune responses among FMD-susceptible host species, specifically bovines and pigs, highlighting the details of host–pathogen interactions and their impact on the severity of the disease. This knowledge serves as an important foundation for translating our insights into the rational design of vaccines and countermeasure strategies, including the use of interferon as a biotherapeutic agent. Ultimately, in this review, we aim to bridge the gap between our understanding of FMDV biology and the practical approaches to control and potentially eradicate FMD.

Foot-and-mouth disease (FMD) is a vesicular disease of cloven-hoofed animals with devastating economic implications. The current FMD vaccine, routinely used in enzootic countries, requires at least 7 days to induce protection. However, FMD vaccination is typically not recommended for use in non-enzootic areas, underscoring the need to develop new fast-acting therapies for FMD control during outbreaks. Interferons (IFNs) are among the immune system’s first line of defense against viral infections. Bovine type III IFN delivered by a replication defective adenovirus (Ad) vector has effectively blocked FMD in cattle. However, the limited duration of protection—usually only 1–3 days post-treatment (dpt)—diminishes its utility as a field therapeutic. Here, we test whether polyethylene glycosylation (PEGylation) of recombinant bovine IFNλ3 (PEGboIFNλ3) can extend the duration of IFN-induced prevention of FMDV infection in both vaccinated and unvaccinated cattle. We treated groups of heifers with PEGboIFNλ3 alone or in combination with an adenovirus-based FMD O1Manisa vaccine (Adt-O1M) at either 3 or 5 days prior to challenge with homologous wild type FMDV. We found that pre-treatment with PEGboIFNλ3 was highly effective at preventing clinical FMD when administered at either time point, with or without co-administration of Adt-O1M vaccine. PEGboIFNλ3 protein was detectable systemically for >10 days and antiviral activity for 4 days following administration. Furthermore, in combination with Adt-O1M vaccine, we observed a strong induction of FMDV-specific IFNγ+ T cell response, demonstrating its adjuvanticity when co-administered with a vaccine. Our results demonstrate the promise of this modified IFN as a pre-exposure prophylactic therapy for use in emergency outbreak scenarios.

Cabbage (Brassica oleracea), a crop of major economic importance worldwide, is affected by numerous diseases, which are caused by a wide range of microorganisms, including fungi, oomycetes, bacteria, and viruses, which lead to important losses in yield and quality. The increasing availability of reference genomes of plant-associated microbes together with recent advances in metagenomic approaches provide new opportunities to identify microbes linked to distinct symptomatology in Brassica leaves. In this study, shotgun metagenomics was used to investigate the microbial community in leaves of B. oleracea plants from agricultural farmlands. Compared with conventional techniques based on culture-based methods, whole-genome shotgun sequencing allows the reliable identification of the microbial population inhabiting a plant tissue at the species level. Asymptomatic and symptomatic leaves showing different disease symptoms were examined. In the asymptomatic leaves, Xanthomonas species were the most abundant taxa. The relative abundance of bacterial and fungal communities varied depending on disease symptoms on the leaf. The microbiome of the leaves showing mild to severe levels of disease was enriched in bacterial populations (Sphingomonas, Methylobacterium, Paracoccus) and to a lesser degree in some fungal taxa, such as Alternaria and Colletotrichum (e.g., in leaves with high levels of necrotic lesions). Sclerotinia species were highly abundant in severely damaged leaves (S. sclerotium, S. trifolium, S. bolearis), followed by Botrytis species. The common and specific bacterial and fungal species associated to disease symptoms were identified. Finally, the analysis of the gene functions in the metagenomic data revealed enrichment in carbohydrate-active enzymes potentially involved in pathogenicity, whose distribution also varied among disease severity groups. Understanding the B. oleracea leaf microbiome in agricultural ecosystems will pave the way for the efficient management of diseases in this crop.

Immunocompromised individuals, particularly autologous hematopoietic stem cell transplant (auHSCT) recipients, are at high risk for herpes zoster (HZ). We provide an in-depth description of humoral and cell-mediated immune (CMI) responses by age (protocol-defined) or underlying disease (post-hoc) as well as efficacy by underlying disease (post-hoc) of the adjuvanted recombinant zoster vaccine (RZV) in a randomized observer-blind phase III trial (ZOE-HSCT, NCT01610414). 1846 adult auHSCT recipients were randomized to receive a first dose of either RZV or placebo 50-70 days post-auHSCT, followed by the second dose at 1-2 months (M) later. In cohorts of 114-1721 participants, at 1 M post-second vaccine dose: Anti-gE antibody geometric mean concentrations (GMCs) and median gE-specific CD4[2+] T-cell frequencies (CD4 T cells expressing ≥2 of four assessed activation markers) were similar between 18-49 and ≥50-year-olds. Despite lower anti-gE antibody GMCs in non-Hodgkin B-cell lymphoma (NHBCL) patients, CD4[2+] T-cell frequencies were similar between NHBCL and other underlying diseases. The proportion of polyfunctional CD4 T cells increased over time, accounting for 79.6% of gE-specific CD4 T cells at 24 M post-dose two. Vaccine efficacy against HZ ranged between 42.5% and 82.5% across underlying diseases and was statistically significant in NHBCL and multiple myeloma patients. In conclusion, two RZV doses administered early post-auHSCT induced robust, persistent, and polyfunctional gE-specific immune responses. Efficacy against HZ was also high in NHBCL patients despite the lower humoral response.

The Eighteenth Century witnessed the emergence of an extensive array of artifacts. These artifacts took on diverse forms such as boxes, wagons, rooms, or a monumental infrastructure. They provided a wide range of visual experiences, including immersive illusions in spatial perspective, three-dimensionality, and the sensation of movement. Accompanied by an explanatory commentary or music, these optical devices toured fairs and squares, or found installations in halls and buildings. They evoked landscapes, urban vistas, and contemporary events. This exploratory work advance into the identification and analysis of documentary evidence related to immersive visual media located in Spain. The timeframe examined spans from 1734 to 1908, encompassing the period between the introduction of the term “mundinovi” in the Dictionary of the Royal Spanish Academy and the premiere of Cinefluo. The purpose of this text is to present a historical approach that aims to enrich our understanding of the archaeology of visual communication media in Spain.

Rice is one of the most important crops in the world and a staple food for more than half of the world’s population. At present, the blast disease caused by the fungus Magnaporthe oryzae poses a severe threat to food security through reduction of rice yields worldwide. High phosphate fertilization has previously been shown to increase blast susceptibility. At present, however, our knowledge on the mechanisms underpinning phosphate-induced susceptibility to M. oryzae infection in rice is limited. In this work, we conducted live cell imaging on rice sheaths inoculated with a M. oryzae strain expressing two fluorescently-tagged M. oryzae effectors. We show that growing rice under high phosphate fertilization, and subsequent accumulation of phosphate in leaf sheaths, promotes invasive growth of M. oryzae. Consistent with this, stronger expression of M. oryzae effectors and Pathogenicity Mitogen-activated Protein Kinase (PMK1) occurs in leaf sheaths of rice plants grown under high a phosphate regime. Down-regulation of fungal genes encoding suppressors of plant cell death and up-regulation of plant cell death-inducing effectors also occurs in sheaths of phosphate over-accumulating rice plants. Treatment with high Pi causes alterations in the expression of fungal phosphate transporter genes potentially contributing to pathogen virulence. From the perspective of the plant, Pi accumulation in leaf sheaths prevents H2O2 accumulation early during M. oryzae infection which was associated to a weaker activation of Respiratory Burst Oxidase Homologs (RBOHs) genes involved in reactive oxygen species (ROS) production. Further, a weaker activation of defense-related genes occurs during infection in rice plants over-accumulating phosphate. From these results, it can be concluded that phosphate fertilization has an effect on the two interacting partners, pathogen and host. Phosphate-mediated stimulation of fungal effector genes (e.g., potentiation of fungal pathogenicity) in combination with repression of pathogen-inducible immune responses (e.g., ROS accumulation, defense gene expression) explains higher colonization by M. oryzae in rice tissues accumulating phosphate. Phosphate content can therefore be considered as an important factor in determining the outcome of the rice/M. oryzae interaction. As fertilizers and pesticides are commonly used in rice cultivation to maintain optimal yield and to prevent losses caused by pathogens, a better understanding of how phosphate impacts blast susceptibility is crucial for developing strategies to rationally optimize fertilizer and pesticide use in rice production.

Multiple myeloma is a malignancy characterized by the accumulation of malignant plasma cells in bone marrow and the production of monoclonal immunoglobulin. A hallmark of cancer is the evasion of immune surveillance. Histone deacetylase inhibitors have been shown to promote the expression of silenced molecules and hold potential to increase the anti-MM efficacy of immunotherapy. The aim of the present work was to assess the potential effect of tinostamustine (EDO-S101), a first-in-class alkylating deacetylase inhibitor, in combination with daratumumab, an anti-CD38 monoclonal antibody (mAb), through different preclinical studies. Tinostamustine increases CD38 expression in myeloma cell lines, an effect that occurs in parallel with an increment in CD38 histone H3 acetylation levels. Also, the expression of MICA and MICB, ligands for the NK cell activating receptor NKG2D, augments after tinostamustine treatment in myeloma cell lines and primary myeloma cells. Pretreatment of myeloma cell lines with tinostamustine increased the sensitivity of these cells to daratumumab through its different cytotoxic mechanisms, and the combination of these two drugs showed a higher anti-myeloma effect than individual treatments in ex vivo cultures of myeloma patients’ samples. In vivo data confirmed that tinostamustine pretreatment followed by daratumumab administration significantly delayed tumor growth and improved the survival of mice compared to individual treatments. In summary, our results suggest that tinostamustine could be a potential candidate to improve the efficacy of anti-CD38 mAbs.

The meiotic recombination checkpoint reinforces the order of events during meiotic prophase I, ensuring the accurate distribution of chromosomes to the gametes. The AAA+ ATPase Pch2 remodels the Hop1 axial protein enabling adequate levels of Hop1-T318 phosphorylation to support the ensuing checkpoint response. While these events are localized at chromosome axes, the checkpoint activating function of Pch2 relies on its cytoplasmic population. In contrast, forced nuclear accumulation of Pch2 leads to checkpoint inactivation. Here, we reveal the mechanism by which Pch2 travels from the cell nucleus to the cytoplasm to maintain Pch2 cellular homeostasis. Leptomycin B treatment provokes the nuclear accumulation of Pch2, indicating that its nucleocytoplasmic transport is mediated by the Crm1 exportin recognizing proteins containing Nuclear Export Signals (NESs). Consistently, leptomycin B leads to checkpoint inactivation and impaired Hop1 axial localization. Pch2 nucleocytoplasmic traffic is independent of its association with Zip1 and Orc1. We also identify a functional NES in the non-catalytic N-terminal domain of Pch2 that is required for its nucleocytoplasmic trafficking and proper checkpoint activity. In sum, we unveil another layer of control of Pch2 function during meiosis involving nuclear export via the exportin pathway that is crucial to maintain the critical balance of Pch2 distribution among different cellular compartments.

Abstract Background Rice is one of the most salt sensitive crops at seedling, early vegetative and reproductive stages. Varieties with salinity tolerance at seedling stage promote an efficient growth at early stages in salt affected soils, leading to healthy vegetative growth that protects crop yield. Saltol major QTL confers capacity to young rice plants growing under salt condition by maintaining a low Na+/K+ molar ratio in the shoots. Results Marker-assisted backcross (MABC) procedure was adopted to transfer Saltol locus conferring salt tolerance at seedling stage from donor indica IR64-Saltol to two temperate japonica varieties, Vialone Nano and Onice. Forward and background selections were accomplished using polymorphic KASP markers and a final evaluation of genetic background recovery of the selected lines was conducted using 15,580 SNP markers obtained from Genotyping by Sequencing. Three MABC generations followed by two selfing, allowed the identification of introgression lines achieving a recovery of the recurrent parent (RP) genome up to 100% (based on KASP markers) or 98.97% (based on GBS). Lines with highest RP genome recovery (RPGR) were evaluated for agronomical-phenological traits in field under non-salinized conditions. VN1, VN4, O1 lines were selected considering the agronomic evaluations and the RPGR% results as the most interesting for commercial exploitation. A physiological characterization was conducted by evaluating salt tolerance under hydroponic conditions. The selected lines showed lower standard evaluation system (SES) scores: 62% of VN4, and 57% of O1 plants reaching SES 3 or SES 5 respectively, while only 40% of Vialone Nano and 25% of Onice plants recorded scores from 3 to 5, respectively. VN1, VN4 and O1 showed a reduced electrolyte leakage values, and limited negative effects on relative water content and shoot/root fresh weight ratio. Conclusion The Saltol locus was successfully transferred to two elite varieties by MABC in a time frame of three years. The application of background selection until BC3F3 allowed the selection of lines with a RPGR up to 98.97%. Physiological evaluations for the selected lines indicate an improved salinity tolerance at seedling stage. The results supported the effectiveness of the Saltol locus in temperate japonica and of the MABC procedure for recovering of the RP favorable traits.

Abstract Iron is an essential nutrient required for plant growth and development. The availability of iron might also influence disease resistance in plants. However, the molecular mechanisms involved in the plant response to iron availability and immunity have been investigated separately from each other. In this work, we found that exposure of rice plants to high iron enhances resistance to infection by the fungal pathogen Magnaporthe oryzae, the causal agent of blast disease. RNA-Seq analysis revealed that blast resistance in iron-treated rice plants was associated with superinduction of defense-related genes during pathogen infection, including Pathogenesis-Related genes. The expression level of genes involved in the biosynthesis of phytoalexins, both diterpene phytoalexins and the flavonoid phytoalexin sakuranetin, was also higher in iron-treated plants compared with control plants, which correlated well with increased levels of phytoalexins in these plants during M. oryzae infection. Upon pathogen infection, lipid peroxidation was also higher in iron-treated plants compared with non-treated plants. We also show that M. oryzae infection modulates the expression of genes that play a pivotal role in the maintenance of iron homeostasis. Histochemical analysis of M. oryzae-infected leaves revealed colocalization of iron and reactive oxygen species in cells located in the vicinity of fungal penetration sites (e.g. appressoria) in rice plants that have been exposed to iron. Together these findings support that ferroptosis plays a role in the response of iron-treated rice plants to infection by virulent M. oryzae. Understanding interconnected regulations between iron signaling and immune signaling in rice holds great potential for developing novel strategies to improve blast resistance in rice.

Background. Lung transplantation remains the treatment of choice for end-stage lung diseases, and recipient selection is currently based on clinical urgency, ABO compatibility, and donor size. The risk of allosensitization is classically based on HLA mismatch, but eplet mismatch load is increasingly seen to be important in long-term outcomes in solid organ transplantation. Chronic lung allograft dysfunction (CLAD) is relatively common and relevant, affecting almost 50% of patients 5 y after transplantation and being the first cause of death from the first year after transplantation. The overall class-II eplet mismatch load has been associated with CLAD development. Methods. Based on clinical data, 240 lung transplant recipients were eligible for CLAD, and HLA and eplet mismatch was analyzed using the HLAMatchmaker 3.1 software. Results. A total of 92 (38.3%) lung transplant recipients developed CLAD. The time free-of-CLAD was significantly decreased in patients with presence of DQA1 eplet mismatches (P = 0.015). Furthermore, when other previously described CLAD risk factors were studied in a multivariate analysis, the presence of DQA1 eplet mismatches was found to be independently associated with the early onset of CLAD. Conclusions. The concept of epitope load has arisen as a new tool to better define donor–recipient immunologic compatibility. The presence of DQA1 eplet mismatches potentially would increase the likelihood of developing CLAD.

Abstract Background Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. Methods This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. Results A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR = 1.022, 95%CI 1.007‒1.038 and OR = 1.025, 95%CI 1.001‒1.051, respectively), while thromboprophylaxis use was protective (OR = 0.199, 95%CI 0.061‒0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR = 1.062, 95%CI 1.017–1.109 and OR = 2.438, 95%CI 1.023–5.813, respectively). Conclusions Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration.

Abstract Different reports have shown the clinical and serologic response to the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) messenger RNA (mRNA) vaccines in preventing coronavirus disease 2019 (COVID‐19) in the general population, but few studies have examined these responses in transplant recipients. We assessed the vaccine immunogenicity of two doses (100 μg) of the mRNA‐1273 vaccine (Moderna) administered with a 28‐day interval in liver transplant recipients (LTRs) at follow‐up at the Marques de Valdecilla University Hospital. LTRs without a history of COVID‐19 infection were tested for SARS‐CoV‐2 immunoglobulin G (IgG) antibodies directed against the spike protein (S) a median of 43 days after receiving the second Moderna vaccine dose. Clinical data, including immunosuppressive regimen and routine laboratory data, were obtained from the medical record of each patient up to 3 months before the date of the first vaccination. Factors associated with serologic response were evaluated through logistic regression. In total, 129 LTRs who had anti‐S results were included. Most patients were men (n = 99; 76.7%) with a median age of 63 years (interquartile range, 56–68). Alcohol (43.4%) and chronic hepatitis C (18.6%) were the most frequent causes of liver transplantation. A positive anti‐S IgG response was observed in 113 LTRs (87.6%; 95% confidence interval [CI], 80.8–92.2). A strong inverse relationship between mycophenolate mofetil use and serologic response was found (odds ratio, 0.07; 95% CI, 0.02–0.26; p = 0.001). Conclusion: Most LTRs develop an immunological response to the Moderna SARS‐CoV‐2 mRNA‐based vaccine. An immunosuppressive regimen that includes mycophenolate predicts a weak serologic response.

Presynaptic terminals of the central nervous system can support univesicular and multivesicular synchronous release of neurotransmitters, however, the functional implications of the prevalence of one mechanism over the other are yet unresolved. Here, we took advantage of the expression of SF-iGluSnFR.S72A in the astrocytic feeder layer of autaptic hippocampal neuronal cultures to associate the liberation of glutamate to excitatory postsynaptic currents. The presence of the glutamate sensor in glial cells avoided any interference with the function of endogenous postsynaptic receptors. It was possible to optically detect changes in neurotransmitter release probability, which was heterogeneous among synaptic boutons studied. For each neuron investigated, the liberation of neurotransmitters occurred through a predominant mechanism. The prevalence of multivesicular over univesicular release increased synaptic strength and enhanced short-term synaptic depression. These results show that the preference of hippocampal boutons to synchronously release one or more vesicles determines the strength and low pass filtering properties of the synapses established.

Este trabajo revisa de manera crítica el ámbito de la lingüística aplicada conocido como fonética forense. Desde el propio nombre de esta disciplina, existen algunas controversias terminológicas, no solo acerca de cómo referirse a esta rama del saber, sino también sobre cuáles son –y cómo denominar– sus principales campos de actuación. Gracias a una pormenorizada revisión bibliográfica, describimos las cinco grandes áreas de aplicación de la fonética forense, haciendo énfasis en desmitificar posibles ideas erróneas sobre el alcance de esta disciplina. Asimismo, se ha hecho un esfuerzo por presentar los resultados de las investigaciones más recientes, sobre todo en el ámbito de la comparación forense de hablantes, que es la tarea más conocida y encargada con más frecuencia al perito forense. Para esta subárea nos centraremos en explicar las aproximaciones metodológicas actuales, así como los parámetros fonéticos más utilizados.

Introduction Patients with mental disorders have a decreased life expectancy, being the main reason the cardiovascular disease. An important proportion of patients present a comorbid drug consumption. Amongst drugs, alcohol is the most frequent, and it is associated with a higher cardiovascular risk. The metabolic syndrome is one of the most employed tools to assess cardiovascular risk. Objectives - To describe the demographic characteristics of the patients with an active alcohol consumption that were admitted to the hospital during the period of study. - To describe the prevalence of metabolic syndrome in the sample, according to the Adult Treatment Panel III (ATP-III) criteria. Methods Retrospective observational study of three months duration. Data was collected from all patients admitted to the hospital during the period of study, with no specific exclusion criteria. Descriptive statistics were performed. Results During the period of study 172 patients were admitted to the hospital (56.4% women and 43.6% men). A 44.8% presented alcohol consumption (25% sporadically, 6.4% weekly and 13.4% daily). Amongst women, 1% presented daily and 1% weekly consumption. Amongst men, 21.3% presented daily and 5.3% weekly consumption. The prevalence of metabolic syndrome in the study sample was 29.11%. In the alcohol consumption group, the prevalence was 24.7% and differed according to the pattern of consumption: 43.5% in the daily consumption group, 27.3% in the weekly and 14% in the sporadically consumption group. Conclusions On the one hand, in the sample of study a higher percentage of men present an active alcohol consumption, compared to women. It is remarkable the high percentage of daily alcohol consumption amongst men in our sample. On the other hand, the prevalence of metabolic syndrome in our sample is similar to the one found in scientific literature regarding patients with mental disorders. It is noteworthy in our sample the increased prevalence of metabolic syndrome found in patients with a daily alcohol consumption, and a decreased prevalence in those with a sporadic pattern. Disclosure of Interest None Declared

Introduction In the last decade, the prevalence of THC use is increasing among adolescents and adults. There is also strong evidence to suggest that cannabis use is associated with psychiatric comorbidities. The strongest evidence is found between cannabis use and psychotic disorder. However, the literature shows that those who have used cannabis in the past or for a large part of their lives are at higher risk of mood disorders, anxiety, personality disorder or other drug use than those who do not use cannabis in a harmful way. Objectives To provide an overview of the association between cannabis use and the different mental pathologies presented by the patients admitted during the study period. To describe the prevalence of THC use in the study according to the mental pathology presented by the patient. Methods A retrospective observational descriptive study was developed for 3 months, of all patients admitted to the acute unit of the psychiatric hospital. No exclusion criteria were included. Results During the period of study 172 patients were admitted to the hospital, classified according to the main diagnosis we have: 49 patients suffer from schizophrenia, 26 bipolar affective disorder, 20 with depressive disorder, 20 with personality disorder, 19 with substance use disorder, 18 with other unspecified disorders and 20 patients with no known previous diagnosis. The prevalence of THC use in the study sample according to diagnosis, would be schizophrenia 16%, Bipolar affective disorder 19%, Depressive disorder 5%, Personality disorder 45%, Substance use disorder 21%, Unspecified disorders 11% and patients with no known previous diagnosis 10%. Conclusions The results obtained in the study in terms of THC use are in agreement with those obtained in the literature. In our study, we observed that cannabis use is associated with psychotic disorders as well as with mood, personality and substance abuse disorders. Given that the frequency of use has increased and there is a strong association with different comorbid psychiatric diagnoses, guidance on modifications in medication strategies might be necessary. Disclosure of Interest None Declared

Introduction Thyroid disorders can present with psychiatric symptons similar to depression, and, at the same time, certain treatments, like litio, can cause changes in thyroid function. Given, therefore, the importance for the treatment and care of patients, the study of thyroid function is one of the parametres that should be requested in patients with psychiatric pathology. Objectives To study the frequency of thyroid disorders in patients who where admitted to a psychiatric short stay unit. Methods Retrospective descriptive observational study is carried out in the acute stay unit of a psychiatric hospital. As a sample, all patients admitted to the unit over a period of three months. During admission, their sociodemographic data, the treatment they receive and their diagnosis are recorded. Secondly, blood test are performed whith differents parameters, including TSH values. Results In the total sample of 172 patients, 8 of them have TSH abnormalities. 7 of them, all women, present hypothyroidism values. A single male patient presented values of hyperthryroidism. Conclusions According to the present study, 4,6% of the patients present alterations at the TSH at admission, although except in one case, the values were not markedly altered. The thyroid study at admission allows detecting cases of altered TSH that are amenable to treatment and monitoring. Disclosure of Interest None Declared

Introduction Patients with mental disorders frequently become non-adherent during their long term prescribed treatment. This situation frequently triggers clinical worsening and hospital admission. Therefore, non-adherence may result in poorer long term clinical outcomes and has economic implications for health-care providers (Carlos De las Cuevas et al. Neuropsychopharmacol Hung 2021; 23(4):347-362). Objectives - To describe the adherence to oral and long acting injectable treatment in the sample of patients that were admitted to the short stay hospital unit during the period of study. - To describe the adherence to treatment amongst psychiatric diagnosis in the sample of study. Methods It was a retrospective observational study with a duration of three months. Data was collected from all patients admitted to the short stay hospital unit during the period of study and there were no specific exclusion criteria. Descriptive statistics were performed. To assess the adherence to pharmachological treatment the patient report, the family report and the pharmacy dispensation according to the existent informatic prescription platform was considered. Regarding the long acting injectable treatment the formulary of administration in the clinical history was checked. Results During the period of study 172 patients were admitted to the short stay hospital unit. Of those, 146 patients had a previous pharmacologic prescription. Data of treatment was not possible to obtain in 7 patients. In the sample of study, 83.5% were on oral and 16.5% on long acting injectable treatment. The general adherence to treatment in the sample was 61.87%. In the oral treatment group the adherence was 58.4% and in the long acting injectable treatment group was 65.2%. Amongst the different psychiatric diagnoses the outcomes of adherence to treatment were: 60.4% in schizophrenia and related psychosis, 62.5% in bipolar disorder, 78.6% in depression, 58.3% in personality disorders and 62% in addictive disorders. Conclusions In our descriptive study adherence to treatment was higher in the long acting injectable treatment group, agreeing with the existent scientific literature. The results of adherence for schizophrenia and bipolar disorder are similar to the ones found in scientific literature but differ from the ones for depression, being higher in our sample (Judit Lazary et al. Neuropsychopharmacol Hung 2021;23(4): 347-362). Moreover, in scientific literature it is found a similar prevalence of adherence across diagnosis (for schizophrenia, bipolar disorder and depression) whereas in our sample patients with depression showed a different and higher adherence to treatment (Judit Lazary et al. Neuropsychopharmacol Hung 2021;23(4): 347-362). In our sample, patients with personality disorders had the lowest adherence to treatment. Disclosure of Interest None Declared

Introduction Patients affected by mental disorders are known to have a decreased life expectancy. One of the main reasons are cardiovascular diseases. It is known that tobacco and hypertension are risk factors to develop them. WHO estimates that hypertension is diagnosed and treated in less than half of adults with hypertension, and even less in patients with severe mental illness. Objectives To describe the demographic characteristics of patients with tobacco comsumption and hypertension admitted to a short-term hospitalization unit. Methods A three-month retrospective observational study. Data were collected by interviewing incoming patients and performing a blood pressure measurement, with no exclusion criteria. Results Of 172 patients admitted, 100 were smokers of whom 49 were men and 51 were women. Among the smokers, a total of 18 patients were diagnosed with hypertension and 79 were not diagnosed. Within the group of patients not diagnosed with hypertension, elevated blood pressure was recorded in 5 of them. A total of 67 patients were non-smokers, 23 of whom were male and 44 female. Among the non-smokers, 19 were diagnosed with hypertension and 48 were not, despite which elevated blood pressure levels were recorded in 4 of them. No data were collected from 5 patients. Conclusions The prevalence of smokers in our sample was 58%. The prevalence of patients diagnosed with hypertension was 21,51% which is coherent with the existent literature. We did not find a higher percentage of hypertensive patients among the smokers admitted. There were patients who suffered from hypertension and were not diagnosed or treated previously. Disclosure of Interest None Declared

Hand pose recognition presents significant challenges that need to be addressed, such as varying lighting conditions or complex backgrounds, which can hinder accurate and robust hand pose estimation. This can be mitigated by employing MediaPipe to facilitate the efficient extraction of representative landmarks from static images combined with the use of Convolutional Neural Networks. Extracting these landmarks from the hands mitigates the impact of lighting variability or the presence of complex backgrounds. However, the variability of the location and size of the hand is still not addressed by this process. Therefore, the use of processing modules to normalize these points regarding the location of the wrist and the zoom of the hands can significantly mitigate the effects of these variabilities. In all the experiments performed in this work based on American Sign Language alphabet datasets of 870, 27,000, and 87,000 images, the application of the proposed normalizations has resulted in significant improvements in the model performance in a resource-limited scenario. Particularly, under conditions of high variability, applying both normalizations resulted in a performance increment of 45.08%, increasing the accuracy from 43.94 ± 0.64% to 89.02 ± 0.40%.

Several sign language datasets are available in the literature. Most of them are designed for sign language recognition and translation. This paper presents a new sign language dataset for automatic motion generation. This dataset includes phonemes for each sign (specified in HamNoSys, a transcription system developed at the University of Hamburg, Hamburg, Germany) and the corresponding motion information. The motion information includes sign videos and the sequence of extracted landmarks associated with relevant points of the skeleton (including face, arms, hands, and fingers). The dataset includes signs from three different subjects in three different positions, performing 754 signs including the entire alphabet, numbers from 0 to 100, numbers for hour specification, months, and weekdays, and the most frequent signs used in Spanish Sign Language (LSE). In total, there are 6786 videos and their corresponding phonemes (HamNoSys annotations). From each video, a sequence of landmarks was extracted using MediaPipe. The dataset allows training an automatic system for motion generation from sign language phonemes. This paper also presents preliminary results in motion generation from sign phonemes obtaining a Dynamic Time Warping distance per frame of 0.37.

This paper proposes, analyzes, and evaluates a deep learning architecture based on transformers for generating sign language motion from sign phonemes (represented using HamNoSys: a notation system developed at the University of Hamburg). The sign phonemes provide information about sign characteristics like hand configuration, localization, or movements. The use of sign phonemes is crucial for generating sign motion with a high level of details (including finger extensions and flexions). The transformer-based approach also includes a stop detection module for predicting the end of the generation process. Both aspects, motion generation and stop detection, are evaluated in detail. For motion generation, the dynamic time warping distance is used to compute the similarity between two landmarks sequences (ground truth and generated). The stop detection module is evaluated considering detection accuracy and ROC (receiver operating characteristic) curves. The paper proposes and evaluates several strategies to obtain the system configuration with the best performance. These strategies include different padding strategies, interpolation approaches, and data augmentation techniques. The best configuration of a fully automatic system obtains an average DTW distance per frame of 0.1057 and an area under the ROC curve (AUC) higher than 0.94.

Rice is one of the most important crops in the world, and its production is severely affected by the rice blast disease caused by the fungus Magnaporthe oryzae. Several major blast resistance genes and QTLs associated with blast resistance have been described and mostly identified in indica rice varieties. In this work, we report the obtention of a blast-resistant rice breeding line derived from crosses between the resistant indica variety CT13432 and the japonica elite cultivar JSendra (highly susceptible to blast). The breeding line, named COPSEMAR9, was found to exhibit resistance to leaf blast and panicle blast, as demonstrated by disease assays under controlled and field conditions. Furthermore, a high-quality genome sequence of the blast-resistant breeding line was obtained using a strategy that combines short-read sequencing (Illumina sequencing) and long-read sequencing (Pacbio sequencing). The use of a whole-genome approach allowed the fine mapping of DNA regions of indica and japonica origin present in the COPSEMAR9 genome and the identification of parental gene regions potentially contributing to blast resistance in the breeding line. Rice blast resistance genes (including Pi33 derived from the resistant parent) and defense-related genes in the genome of COPSEMAR9 were identified. Whole-genome analyses also revealed the presence of microRNAs (miRNAs) with a known function in the rice response to M. oryzae infection in COPSEMAR9, which might also contribute to its phenotype of blast resistance. From this study, the genomic information and analysis methods provide valuable knowledge that will be useful in breeding programs for blast resistance in japonica rice cultivars.

Kidney transplantation is the preferred therapeutic option for end-stage renal disease; however, the alloimmune response is still the leading cause of renal allograft failure. To better identify immunologic disparities in order to evaluate HLA compatibility between the donor and the recipient, the concept of eplet load has arisen. Regular kidney function monitoring is essential for the accurate and timely diagnosis of allograft rejection and the appropriate treatment. Donor-derived cell-free DNA (dd-cfDNA) has been proposed as a potential biomarker of acute rejection and graft failure in kidney transplantation. The proportion of plasma dd-cfDNA was determined in forty-two kidney patients at 1 month after transplantation. A total of eleven (26.2%) patients had a dd-cfDNA proportion of ≥1.0%. The only pretransplant variable related to dd-cfDNA > 1.0% was the HLA class II eplet mismatch load, mainly the HLA-DQB1 eplet mismatch load. Furthermore, dd-cfDNA was able to discriminate the patients with antibody-mediated rejection (AbMR) (AUC 87.3%), acute rejection (AUC 78.2%), and troubled graft (AUC 81.4%). Increased dd-cfDNA levels were associated with kidney allograft deterioration, particularly rejection, as well as a greater HLA class II eplet mismatch load. Consequently, combining dd-cfDNA determination and HLA eplet mismatch load calculation should improve the assessment of the risk of short- and long-term allograft damage.

In recent years, numerous investigations have focused on voice quality (VQ) for forensic purposes. These studies notwithstanding, we lack an international picture of how VQ is generally understood by forensic practitioners and how it contrasts with the practices of voice therapists. To fill this gap, a survey was designed and sent to both cohorts: forensicists and clinicians. A total of 45 responses from 20 countries were received. Important differences were found between groups, particularly regarding perceptual assessment. One conclusion to be drawn is that more emphasis should be placed on calibration and error measurement in forensic approaches to VQ. Further collaborations with clinicians should also be encouraged.

El presente artículo reflexiona sobre el desarrollo de Medianautas, una acción que fomenta la coeducación y el pensamiento crítico en materia de conocimiento histórico a partir del álbum fotográfico doméstico del alumnado de enseñanza superior. Medianautas se integra en la experiencia de investigación e innovación responsable FotoC3: ciudadanía, creatividad y cuidado, una iniciativa que promueve la coeducación en el contexto de la enseñanza superior mediante el uso sistemático de la fotografía colaborativa, la innovación docente, la indagación autoetnográfica, la creación cultural y la educación patrimonial. A partir de una metodología expositiva, el texto describe cómo Medianautas se renueva cada curso académico en el contexto socioeducativo de la Facultad de Ciencias Sociales de la Universidad de Salamanca (USAL), apoyándose en tres prácticas de investigación-acción participativa –Fotovoz, el Aprendizaje Basado en Proyectos y el Aprendizaje-Servicio– y adoptando la norma ISO 9001:2015 para la mejora continua de sus procesos de gestión. El trabajo enumera los resultados obtenidos por Medianautas en tres dimensiones específicas: la puesta en marcha de buenas prácticas en innovación docente y responsabilidad social; la creación de contenidos visuales de carácter colectivo para su difusión mediante Di(ver)sium, y el desarrollo de la Colección Medianautas como una colección universitaria de etnofotografía implementada en un repositorio web de carácter institucional y de acceso público integrado en la Red de Colecciones Científicas de la Universidad de Salamanca. Finalmente, el ensayo pone énfasis en cómo la experiencia formativa que impulsa Medianautas –y que explora la construcción de la identidad visual y de la diversidad afectivo-sexual desde una perspectiva mediática e histórica–, fortalece las prácticas coeducativas en la enseñanza superior.

Immunocompromised individuals, particularly autologous hematopoietic stem cell transplant (auHSCT) recipients, are at high risk for herpes zoster (HZ). We provide an in-depth description of humoral and cell-mediated immune (CMI) responses by age (protocol-defined) or underlying disease (post-hoc) as well as efficacy by underlying disease (post-hoc) of the adjuvanted recombinant zoster vaccine (RZV) in a randomized observer-blind phase III trial (ZOE-HSCT, NCT01610414). 1846 adult auHSCT recipients were randomized to receive a first dose of either RZV or placebo 50–70 days post-auHSCT, followed by the second dose at 1–2 months (M) later. In cohorts of 114–1721 participants, at 1 M post-second vaccine dose: Anti-gE antibody geometric mean concentrations (GMCs) and median gE-specific CD4[2+] T-cell frequencies (CD4 T cells expressing ≥2 of four assessed activation markers) were similar between 18–49 and ≥50-year-olds. Despite lower anti-gE antibody GMCs in non-Hodgkin B-cell lymphoma (NHBCL) patients, CD4[2+] T-cell frequencies were similar between NHBCL and other underlying diseases. The proportion of polyfunctional CD4 T cells increased over time, accounting for 79.6% of gE-specific CD4 T cells at 24 M post-dose two. Vaccine efficacy against HZ ranged between 42.5% and 82.5% across underlying diseases and was statistically significant in NHBCL and multiple myeloma patients. In conclusion, two RZV doses administered early post-auHSCT induced robust, persistent, and polyfunctional gE-specific immune responses. Efficacy against HZ was also high in NHBCL patients despite the lower humoral response.