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Higher education opens doors to job enhancement and economic benefits to adult learners. Despite facing multiple barriers such as life-work-school time conflicts and financial constraints, adult learners continue to seek higher education and certifications. Rural employers also benefit from supporting degree completion or job-specific certifications because it allows them to attract and retain highly skilled employees. The goal of the current study was to qualitatively analyze data gathered from focus group interviews of senior managers. The results provide insights into how rural employers in the United States use employee education programs to reduce barriers to adult learner success. The importance of a bilateral relationship between institutions of higher education and employers to support adult learners is discussed.

Abstract Nuclear metabolism and DNA damage response are intertwined processes, but the precise molecular links remain elusive. Here, we explore this crosstalk using triple-negative breast cancer (TNBC) as a model, a subtype often prone to DNA damage accumulation. We show that the de novo purine synthesis enzyme IMPDH2 is enriched on chromatin in TNBC compared to other subtypes. IMPDH2 chromatin localization is DNA damage dependent, and IMPDH2 repression leads to DNA damage accumulation. On chromatin, IMPDH2 interacts with and modulates PARP1 activity by controlling the nuclear availability of NAD+ to fine-tune the DNA damage response. However, when IMPDH2 is restricted to the nucleus, it depletes nuclear NAD+, leading to PARP1 cleavage and cell death. Our study identifies a non-canonical nuclear role for IMPDH2, acting as a convergence point of nuclear metabolism and DNA damage response.

Abstract Many cellular processes are governed by protein–protein interactions that require tight spatial and temporal regulation. Accordingly, it is necessary to understand the dynamics of these interactions to fully comprehend and elucidate cellular processes and pathological disease states. To map de novo protein–protein interactions with time resolution at an organelle-wide scale, we developed a quantitative mass spectrometry method, time-resolved interactome profiling (TRIP). We apply TRIP to elucidate aberrant protein interaction dynamics that lead to the protein misfolding disease congenital hypothyroidism. We deconvolute altered temporal interactions of the thyroid hormone precursor thyroglobulin with pathways implicated in hypothyroidism pathophysiology, such as Hsp70-/90-assisted folding, disulfide/redox processing, and N-glycosylation. Functional siRNA screening identified VCP and TEX264 as key protein degradation components whose inhibition selectively rescues mutant prohormone secretion. Ultimately, our results provide novel insight into the temporal coordination of protein homeostasis, and our TRIP method should find broad applications in investigating protein-folding diseases and cellular processes.

Abstract Multiple-choice test generation is one of the most complex NLP problems, especially in languages other than English, where there is a lack of prior research. After a review of the literature, it has been verified that some methods like the usage of rule-based systems or primitive neural networks have led to the application of a recent architecture, the Transformer architecture, in the tasks of Answer Extraction (AE) and Question Generation (QG). Thereby, this study is centred in searching and developing better models for the AE and QG tasks in Spanish, using an answer-aware methodology. For this purpose, three multilingual models (mT5-base, mT0-base and BLOOMZ-560 M) have been fine-tuned using three different datasets: a translation to Spanish of the SQuAD dataset; SQAC, which is a dataset in Spanish; and their union (SQuAD + SQAC), which shows slightly better results. Regarding the models, the performance of mT5-base has been compared with that found in two newer models, mT0-base and BLOOMZ-560 M. These models were fine-tuned for multiple tasks in literature, including AE and QG, but, in general, the best results are obtained from the mT5 models trained in our study with the SQuAD + SQAC dataset. Nonetheless, some other good results are obtained from mT5 models trained only with the SQAC dataset. For their evaluation, the widely used BLEU1-4, METEOR and ROUGE-L metrics have been obtained, where mT5 outperforms some similar research works. Besides, CIDEr, SARI, GLEU, WER and the cosine similarity metrics have been calculated to present a benchmark within the AE and QG problems for future work.

The biotransformation of poultry (PSW) and swine (SSW) slaughterhouse waste might provide protein feedstuffs, ensuring efficient ruminant systems while safeguarding the environment. The present study aimed to evaluate the potential of PSW and SSW as alternative protein feed for ruminant animals. A total of 24 lambs [25.4 ± 3.13 kg of body weight (BW), mean ± SD] were randomly allocated to one of three groups (n = 8): a control diet formulated with typical protein ingredients (CTRL) and two diets formulated with PSW or SSW meal as a protein source. Dietary inclusion of PSW or SSW did not alter (p = 0.05) dry matter intake or final BW. However, animals fed SSW showed the highest average daily gain (ADG, p = 0.04). In addition, substituting PSW and SSW improved the feed conversation ratio (FCR, p = 0.05). There were no diet effects (p = 0.05) on N intake, while fecal N excretion increased (p = 0.03) with SSW feeding. Compared to CTRL and PSW, ingestion of SSW decreased (p = 0.001) and retained N. The digestibility of crude protein and organic matter remained unchanged (p = 0.05). Additionally, there were no differences (p = 0.05) in potential microbial protein synthesis based on either protein content (SPMp) or energy content (SPMe). Similarly, potential metabolizable protein by protein (PMp) and potential metabolizable energy by protein (PMe) were not affected (p = 0.05). Overall, both PSW and SSW positively influenced the growth performance of ewe lambs. However, further studies are warranted to explore the impact of PWS or SSW feeding on rumen function, nitrogen pollution, and protein escaping the rumen into the intestine in ruminants.

Abstract: Introduction: Psychological treatments are becoming an increasingly important component of medical healthcare, as a growing number of people seek treatment for a wide range of mental health problems. While these treatments are known to be effective, much remains to be understood about their mechanisms and reasons for effectiveness. The study of statistical mediators is crucial in psychological research, as it is fundamental to understanding how psychological factors influence health, well-being, and human behavior, and thus to designing effective psychological interventions. Aim: This study investigates the role of resilience as a treatment mediator in PROCARE+, a brief transdiagnostic, personalized protocol for the selective prevention of emotional disorders in adolescents. This approach has proven effective for young people at risk of developing emotional issues. Method: We used simple mediation models in a sample of 153 adolescents to assess the impact of interventions on resilience. Outcome variables included self-reported and parent-reported emotional risk, mood, anxiety symptoms, and quality of life. Discussion: The results of this study provide valuable information on how PROCARE+ works and how to improve its effectiveness, pointing to resilience as a key mediator in reducing the risk of developing emotional disorders and improving quality of life.

Business financial risk-taking usually occurs under conditions of stress. Biologically, the stress response has two components: one linked to the hypothalamic-pituitary-adrenal (HPA) axis and the other to the autonomic nervous system (ANS). The existing literature on financial risk-taking has primarily focused on the effects of cortisol, related to the HPA axis. This article, however, examines the influence of the ANS, as measured by vagally mediated heart rate variability at rest (VMHRV). A total of 121 participants (60 female) were divided based on whether their VMHRV was below the median. Participants were then randomly assigned to either a stress test group (tsst) or a control group. Financial risk preferences were assessed using an incentive-compatible 50-50% Eckel and Grossman task. Participants in the tsst with high VMHRV had a higher probability of choosing riskier lotteries compared to the other participants (P = 0,0189). This finding suggests that greater parasympathetic modulation enables individuals to make riskier financial decisions when under stress. Thus, the article contributes to the literature by demonstrating that individuals with a higher physiological capacity to cope with external stressors are less risk-averse in financial decisions under social stress conditions.

Summary: Infection is a commonplace, usually self-limiting, condition but can lead to sepsis, a severe life-threatening dysregulated host response. We investigate the individual phenotypic predisposition to developing uncomplicated infection or sepsis in a large cohort of non-infected patients undergoing major elective surgery. Whole-blood RNA sequencing analysis was performed on preoperative samples from 267 patients. These patients developed postoperative infection with (n = 77) or without (n = 49) sepsis, developed non-infectious systemic inflammatory response (n = 31), or had an uncomplicated postoperative course (n = 110). Machine learning classification models built on preoperative transcriptomic signatures predict postoperative outcomes including sepsis with an area under the curve of up to 0.910 (mean 0.855) and sensitivity/specificity up to 0.767/0.804 (mean 0.746/0.769). Our models, confirmed by quantitative reverse-transcription PCR (RT-qPCR), potentially offer a risk prediction tool for the development of postoperative sepsis with implications for patient management. They identify an individual predisposition to developing sepsis that warrants further exploration to better understand the underlying pathophysiology.

Familial Dysautonomia (FD) is an autosomal recessive disorder caused by a splice site mutation in the gene ELP1, which disproportionally affects neurons. While classically characterized by deficits in sensory and autonomic neurons, neuronal defects in the central nervous system have also been described. Although ELP1 expression remains high in the normal developing and adult cerebellum, its role in cerebellar development is unknown. To explore the role of Elp1 in the cerebellum, we knocked out Elp1 in cerebellar granule cell progenitors (GCPs) and examined the outcome on animal behavior and cellular composition. We found that GCP-specific conditional knockout of Elp1 (Elp1cKO) resulted in ataxia by 8 weeks of age. Cellular characterization showed that the animals had smaller cerebella with fewer granule cells. This defect was already apparent as early as 7 days after birth, when Elp1cKO animals also had fewer mitotic GCPs and shorter Purkinje dendrites. Through molecular characterization, we found that loss of Elp1 was associated with an increase in apoptotic cell death and cell stress pathways in GCPs. Our study demonstrates the importance of ELP1 in the developing cerebellum, and suggests that loss of Elp1 in the GC lineage may also play a role in the progressive ataxia phenotypes of FD patients.

BackgroundDue to the slower dissipation of the osmotic gradient, icodextrin-based solutions, compared to glucose-based solutions, can improve water removal. We investigated scenarios where one icodextrin-based long dwell (Extraneal) replaced two glucose-based exchanges.MethodsThe three-pore model with icodextrin hydrolysis was used for numerical simulations of a single exchange to investigate the impact of different peritoneal dialysis schedules on fluid and solute removal in patients with different peritoneal solute transfer rates (PSTRs). We evaluated water removal (ultrafiltration, UF), absorbed mass of glucose (AbsGluc) and carbohydrates (AbsCHO, for glucose and glucose polymers), ultrafiltration efficiency (UFE = UF/AbsCHO) per exchange, and specified dwell time, and removed solute mass for sodium (ReNa), urea (ReU), and creatinine (ReCr) for a single peritoneal exchange with 7.5% icodextrin (Extraneal®) and glucose-based solutions (1.36% and 2.27%) and various dwell durations in patients with fast and average PSTRs.ResultsIntroducing 7.5% icodextrin for the long dwell to replace one of three or four glucose-based exchanges per day leads to increased fluid and solute removal and higher UF efficiency for studied transport groups. Replacing two glucose-based exchanges with one icodextrin exchange provides higher or similar water removal and higher daily sodium removal but slightly lower daily removal of urea and creatinine, irrespective of the transport type present in the case of reference prescription with three and four daily exchanges.ConclusionOne 7.5% icodextrin can replace two glucose solutions. Unlike glucose-based solutions, it resulted only in minor differences between PSTR groups in terms of water and solute removal with UFE remaining stable up to 16 h.

IntroductionOlive cultivation, like other evergreen fruit crops worldwide, is limited by the occurrence of frost episodes in different times of the year, mainly in winter or early spring. Some contradictory results are reported about cultivars’ response to frost, which depends on the physiological stage of the tissues (acclimated or not acclimated) when the cold or frost episode occurs. This work aimed to implement a user-friendly and reliable lab method for discerning frost tolerance.MethodsOur methodology considered both detached leaves and potted plantlets. The optimal temperature at which damage differentiated between cultivars was evaluated, as well as the time of exposure to cold and the recovery time for the correct evaluation of the symptoms. Furthermore, a comparative analysis of damage on both young and mature leaves was conducted. To validate the efficacy of the methodology, assessments were conducted on the cultivars ‘Arbequina’ (tolerant), ‘Picual’ (moderately tolerant), and ‘Frantoio’ (susceptible) under acclimated and non-acclimated conditions.Results and discussionThe results indicated that, when detached leaves were used for frost evaluation, a temperature of -10°C ± 1°C for 30 min and a recovery time at 26°C for 24–48 h after exposure to cold are enough to induce damages on the leaves and discriminate between cultivar susceptibility. Under these conditions, a precise assessment of symptoms can be made, facilitating the categorization of frost tolerance level in various olive cultivars. Notably, no significant differences were observed between young and mature leaves during the evaluation process. On the other hand, the critical temperature to assess damages on potted plantlets was determined to be -7°C ± 1°C. In addition, it was observed that acclimated plants exhibited fewer symptoms compared to non-acclimated ones, with ‘Frantoio’ being the most affected alongside ‘Picual’ and ‘Arbequina’.ConclusionThe implemented methodology will allow the assessment of frost tolerance in several olive cultivars within a short timeframe, and it is proven to be user-friendly and reliable.

The digital competences of university students are developed using a digital learning ecosystem that integrates: 1) virtual learning environments; 2) digital learning tools; and 3) learning methodologies. This research followed the methodology of systematic literature mapping and review, searching the WoS and Scopus databases and obtaining a total of 5,652 articles between 2001 and 2023. Inclusion and exclusion criteria were then applied to reduce the number of selected articles and carry out a systematic literature mapping and review. Among the relevant results of the literature mapping and systematic review, the geographic distribution of scientific publications, the educational areas in which they have been worked on, and the universities were identified. Educational methodologies, technological tools, and virtual learning environments used to develop university students’ digital competences holistically were also determined. This study is useful as it provides a comprehensive, general, and detailed overview of scientific production and its main contributions regarding the methodologies, tools, and environments that contribute to developing students’ the digital competences in higher education.

The SKY130 Process Design Kit (PDK) offers limited options for Static Random-Access Memory (SRAM) configurations, providing only three predefined memory sizes: $8\times 1024$ , $32\times 256$ , and $32\times 512$ , this poses a challenge for designers who require memories with different characteristics, as they must either design an entire memory architecture from scratch or resort to interleaving techniques with the available memory configurations. To address this issue, we present a novel framework that automates the generation of multiple memory arrays with custom floorplans, leveraging the concept of interleaving memory. Our framework enables designers to create various sizes and configurations memories by combining and interleaving the existing SKY130 PDK memories, additionally, the framework allows designers to easily specify their desired memory size, word length, floorplan, and other essential parameters. The framework then automatically generates multiple memory arrays that meet the specified requirements. Furthermore, it provides the files required by OpenLane, facilitating the seamless integration of these memories into the Register Transfer Level (RTL) to Graphic Data System II (GDSII) flow. The key advantage of our framework lies in its ability to streamline the creation of custom memories by automating the interleaving process and offering flexibility in floorplan design. This significantly reduces design time and effort, empowering designers to efficiently create memories with specific characteristics while adhering to the limitations of the SKY130 PDK. The framework thus serves as a valuable tool for memory design in the context of the SKY130 PDK, opening doors for more efficient and optimized chip designs.

In recent years, transformer language models have made a significant impact on automatic text generation. This study focuses on the task of distractor generation in Spanish using a fine-tuned multilingual text-to-text model, namely mT5. Our method outperformed established baselines based on LSTM networks, confirming the effectiveness of Transformer architectures in such NLP tasks. While comparisons with other Transformer-based solutions yielded diverse outcomes based on the metric of choice, our method notably achieved superior results on the ROUGE metric compared to the GPT-2 approach. Although traditional evaluation metrics such as BLEU and ROUGE are commonly used, this paper argues for more context-sensitive metrics given the inherent variability in acceptable distractor generation results. Among the contributions of this research is a comprehensive comparison with other methods, an examination of the potential drawbacks of multilingual models, and the introduction of alternative evaluation metrics. Future research directions, derived from our findings and a review of related works are also suggested, with a particular emphasis on leveraging other language models and Transformer architectures.

Within the field of nanomedicine, which is revolutionizing cancer treatment, solid lipid nanoparticles (SLNs) have shown advantages over conventional chemotherapy when tested on cancer cells in preclinical studies. SLNs have proven to be an innovative strategy for the treatment of triple-negative breast cancer cells, providing greater efficiency than existing treatments in various studies. The encapsulation of antineoplastic drugs in SLNs has facilitated a sustained, controlled, and targeted release, which enhances therapeutic efficiency and reduces adverse effects. Moreover, the surface of SLNs can be modified to increase efficiency. For instance, the coating of these particles with polyethylene glycol (PEG) decreases their opsonization, resulting in a longer life in the circulatory system. The creation of positively charged cationic SLNs (cSLNs), achieved by the utilization of surfactants or ionic lipids with positively charged structural groups, increases their affinity for cell membranes and plasma proteins. Hyaluronic acid has been added to SLNs so that the distinct pH of tumor cells would stimulate the release of the drug and/or genetic material. The current review summarizes the recent research on SLNs, focusing on the encapsulation and transport of therapeutic agents with a cytotoxic effect on triple-negative breast cancer.

Software maintenance is an important and expensive stage during software development. Most of these tasks are done manually with static code analyzers, but this might change if new Artificial Intelligence approaches were used. For this purpose, huge amounts of data are extremely necessary to achieve a good performance by using traditional Data Science and Deep Learning techniques. Accordingly, this paper presents a software capable of creating, automatically, customizable coding error datasets in JSON format by using the SonarQube static analyzer. Consequently, coding error datasets could be easily created, encouraging new maintenance approaches (e.g., automated program repair through Deep Learning Models).

Abstract Significant evidence does exist on the effectiveness of transdiagnostic interventions to improve emotional problems in clinical populations, and their application as universal and indicated prevention programs. However, no randomized controlled trials (RCT) studying selective transdiagnostic prevention intervention have been published. This is the first known RCT to evaluate the efficacy/effectiveness of an evidence-based selective prevention transdiagnostic program for emotional problems in adolescents. The impact of three different interventions was evaluated: (1) PROCARE (Preventive transdiagnostic intervention for Adolescents at Risk for Emotional disorders), which is a group-based, abbreviated version of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents (UP-A), along with adding a booster session to reduce risk of onset of anxiety and depression, (2) PROCARE + , which includes the PROCARE protocol along with personalized add-on modules tailored to match adolescents’ risk factors, and (3) an active control condition (ACC) based on emotional psychoeducation. In total, 208 adolescents (48.5% girls) evidencing high risk and low protective factors were randomized and allocated to PROCARE, PROCARE + or ACC. Data from 153 adolescents who completed all assessments in the different phases of the study were analyzed. Self- and parent-reported measures were taken at baseline, as well as after the intervention, a 6 month follow-up was carried out, together with a 1 month follow-up after the booster session. Differences between conditions were significant on most of the outcome measures, with superior effect sizes for PROCARE + in the short and long term. Interventions were acceptable in terms of acceptability, with good satisfaction rates. Tailored targeted selective transdiagnostic interventions focused on mitigating risk factors and promoting protective factors in vulnerable adolescents are promising.

Rodents are recognized as the main reservoirs of Leptospira spp. Rats, in particular, serve as hosts for the widely predominant Leptospira interrogans serovar Icterohaemorrhagiae, found worldwide. Several studies have shown the importance of other reservoirs, such as mice or hedgehogs, which harbor other leptospires' serovars. Nevertheless, our knowledge of circulating Leptospira spp. in reservoirs other than rats remains limited. In this context, we proposed an eco-health approach to assess the health hazard associated with leptospires in urban green spaces, where contacts between human/small mammals and domestic animals are likely. We studied the prevalence, the diversity of circulating strains, and epidemiology of pathogenic Leptospira species in small terrestrial mammal communities (rodents and shrews), between 2020-2022, in two parks in Lyon metropolis, France. Our study showed a significant carriage of Leptospira spp. in small terrestrial mammals in these parks and unveiled a global prevalence rate of 11.4%. Significant variations of prevalence were observed among the small mammal species (from 0 to 26.1%), with Rattus norvegicus exhibiting the highest infection levels (26.1%). We also observed strong spatio-temporal variations in Leptospira spp. circulation in its reservoirs. Prevalence seems to be higher in the peri-urban park and in autumn in 2021 and 2022. This is potentially due to differences in landscape, abiotic conditions and small mammal communities' composition. Our study suggests an important public health relevance of rats and in a lesser extent of other rodents (Apodemus spp., Clethrionomys glareolus and Mus musculus) as reservoirs of L. interrogans, with rodent species carrying specific serogroups/serovars. We also emphasize the potential hazard associated between the shrew Crocidura russula and L. kirschneri. Altogether, these results improve our knowledge about the prevalence of leptospirosis in an urban environment, which is an essential prerequisite for the implementation of prevention of associated risks.

The management of chronic extensor mechanism injuries represents a significant challenge for orthopaedic surgeons, with numerous options for graft choice and fixation construct, but no clear consensus on which technique achieves optimal outcomes. Although there is little published data regarding outcomes of different fixation methods, small case series have demonstrated modest success using Achilles tendon bone block allografts and transverse patellar screw fixation. In this technical note, we describe a surgical technique for the treatment of a chronic inferior pole patella fracture, with extensor mechanism reconstruction using an Achilles tendon allograft with suture tape augmentation. Our technique describes the use of vertical cannulated screws in the patella for passing tape augmentation sutures, increased construct security by suturing of the Achilles graft directly to the quadriceps tendon, and the use of a post screw in the proximal tibia for suture tape augmentation.

Abstract In peritoneal dialysis, ultrafiltration is achieved by adding an osmotic agent into the dialysis fluid. During an exchange with icodextrin-based solution, polysaccharide chains are degraded by α-amylase activity in dialysate, influencing its osmotic properties. We modelled water and solute removal taking into account degradation by α-amylase and absorption of icodextrin from the peritoneal cavity. Data from 16 h dwells with icodextrin-based solution in 11 patients (3 icodextrin-exposed, 8 icodextrin-naïve at the start of the study) on dialysate volume, dialysate concentrations of glucose, urea, creatinine and α-amylase, and dialysate and blood concentrations of seven molecular weight fractions of icodextrin were analysed. The three-pore model was extended to describe hydrolysis of icodextrin by α-amylase. The extended model accurately predicted kinetics of ultrafiltration, small solutes and icodextrin fractions in dialysate, indicating differences in degradation kinetics between icodextrin-naïve and icodextrin-exposed patients. In addition, the model provided information on the patterns of icodextrin degradation caused by α-amylase. Modelling of icodextrin kinetics using an extended three-pore model that takes into account absorption of icodextrin and changes in α-amylase activity in the dialysate provided accurate description of peritoneal transport and information on patterns of icodextrin hydrolysis during long icodextrin dwells.

Abstract Olive anthracnose, a critical olive fruit disease that adversely impacts oil quality, is caused by Colletotrichum species. A dominant Colletotrichum species and several secondary species have been identified in each olive-growing region. This study surveys the interspecific competition between C. godetiae, dominant in Spain, and C. nymphaeae, prevalent in Portugal, to shed light on the cause of this disparity. When Petri-dishes of Potato Dextrose Agar (PDA) and diluted PDA were co-inoculated with spore mixes produced by both species, C. godetiae displaced C. nymphaeae, even if the percentage of spores in the initial spore mix inoculation was just 5 and 95%, respectively. The C. godetiae and C. nymphaeae species showed similar fruit virulence in separate inoculations in both cultivars, the Portuguese cv. Galega Vulgar and the Spanish cv. Hojiblanca, and no cultivar specialization was observed. However, when olive fruits were co-inoculated, the C. godetiae species showed a higher competitive ability and partially displaced the C. nymphaeae species. Furthermore, both Colletotrichum species showed a similar leaf survival rate. Lastly, C. godetiae was more resistant to metallic copper than C. nymphaeae. The work developed here allows a deeper understanding of the competition between C. godetiae and C. nymphaeae, which could lead to developing strategies for more efficient disease risk assessment.

Defect engineering and doping of semiconductors by ion irradiation are essential in large-scale integration of electronic devices. Here, intense ion pulses from a laser-accelerator, with flux levels up to 1022 ions cm-2 s-1, are used to induce and optimize silicon color centers and photon emitters in the telecom band.

Vascular co-option is a consequence of the direct interaction between perivascular cells, known as pericytes (PCs), and glioblastoma multiforme (GBM) cells (GBMcs). This process is essential for inducing changes in the pericytes’ anti-tumoral and immunoreactive phenotypes. Starting from the initial stages of carcinogenesis in GBM, PCs conditioned by GBMcs undergo proliferation, acquire a pro-tumoral and immunosuppressive phenotype by expressing and secreting immunosuppressive molecules, and significantly hinder the activation of T cells, thereby facilitating tumor growth. Inhibiting the pericyte (PC) conditioning mechanisms in the GBM tumor microenvironment (TME) results in immunological activation and tumor disappearance. This underscores the pivotal role of PCs as a key cell in the TME, responsible for tumor-induced immunosuppression and enabling GBM cells to evade the immune system. Other cells within the TME, such as tumor-associated macrophages (TAMs) and microglia, have also been identified as contributors to this immunomodulation. In this paper, we will review the role of these three cell types in the immunosuppressive properties of the TME. Our conclusion is that the cellular heterogeneity of immunocompetent cells within the TME may lead to the misinterpretation of cellular lineage identification due to different reactive stages and the identification of PCs as TAMs. Consequently, novel therapies could be developed to disrupt GBM-PC interactions and/or PC conditioning through vascular co-option, thereby exposing GBMcs to the immune system.

Abstract Background The development of cancer has been associated with epigenetic alterations such as aberrant histone deacetylase (HDAC) activity. It was recently reported that valproic acid is an effective inhibitor of histone deacetylases and as such induces tumor cell differentiation, apoptosis, or growth arrest. Methods Twelve newly diagnosed patients with cervical cancer were treated with magnesium valproate after a baseline tumor biopsy and blood sampling at the following dose levels (four patients each): 20 mg/kg; 30 mg/kg, or 40 mg/kg for 5 days via oral route. At day 6, tumor and blood sampling were repeated and the study protocol ended. Tumor acetylation of H3 and H4 histones and HDAC activity were evaluated by Western blot and colorimetric HDAC assay respectively. Blood levels of valproic acid were determined at day 6 once the steady-state was reached. Toxicity of treatment was evaluated at the end of study period. Results All patients completed the study medication. Mean daily dose for all patients was 1,890 mg. Corresponding means for the doses 20-, 30-, and 40-mg/kg were 1245, 2000, and 2425 mg, respectively. Depressed level of consciousness grade 2 was registered in nine patients. Ten patients were evaluated for H3 and H4 acetylation and HDAC activity. After treatment, we observed hyperacetylation of H3 and H4 in the tumors of nine and seven patients, respectively, whereas six patients demonstrated hyperacetylation of both histones. Serum levels of valproic acid ranged from 73.6–170.49 μg/mL. Tumor deacetylase activity decreased in eight patients (80%), whereas two had either no change or a mild increase. There was a statistically significant difference between pre and post-treatment values of HDAC activity (mean, 0.36 vs. 0.21, two-tailed t test p < 0.0264). There was no correlation between H3 and H4 tumor hyperacetylation with serum levels of valproic acid. Conclusion Magnesium valproate at a dose between 20 and 40 mg/kg inhibits deacetylase activity and hyperacetylates histones in tumor tissues.

Introduction: The coronavirus 19 disease (COVID-19) increased mortality in organ solid transplant patients due to chronic immunosuppression and significant comorbidity burden. We aim to evaluate patient and graft survival in kidney transplant (KT) recipients who were hospitalized or treated in Intensive Care Units (ICU) after contracting COVID-19. Methods: A retrospective analysis was conducted on adult KT recipients diagnosed with COVID-19 between June 1 and July 31, 2021. The study reported demographics, symptoms, laboratory parameters, and clinical outcomes 30 days after a positive test. Risk factors for mortality were identified through comparisons between hospitalization-in-wards and ICU groups. The Kaplan-Meier method was used to calculate graft and patient survival. Results: 55 KT patients were analysed, recipient age and history of diabetes showed significant differences between groups (p = 0.0124 and p = 0.0506, respectively). Multivariate analysis revealed that diabetes (p = 0.002) and dialysis requirement (p = 0.0006) were significantly associated with mortality risk. The overall mortality rate was 25.5%, with graft loss at 12.7%. Patient survival after 30 days was 74.5%, with significantly higher survival in the hospitalization-in-wards group (p = 0.0001) compared to the ICU group. Conclusions: KT patients diagnosed with COVID-19 are at higher mortality risk than the general population. Our study found that patients in the ICU group experienced worse clinical outcomes and higher mortality rates compared to those in the hospitalization-in-wards group. These findings underscore the importance of closely monitoring COVID-19-implicated KT patients and tailoring treatment plans to minimize risk and improve outcomes.

In the health sector, the reports on delivery of prescriptions and the assignment of medical appointments are generated by the Health Service Provider Institutions and delivered to the Health Service Promoting Entities. These reports usually have an incoherent structure; inconsistencies in the format; non-existent, incomplete, or non-standardized data. These problems affect data quality and hinder the reliability of the information. To address this, it is proposed to adapt Kahn's data quality categories, to these reports, considering that the health sector accepts them categories and contemplates not only the structure and domain of the data but also its completeness and plausibility (credibility). This research followed the methodology of Pratt’s Iterative Research Pattern, studies related to the subject were observed, and the attributes of prescription delivery and appointment assignment were analyzed to understand the problem and its implications in detail. We then adapted the data quality categories proposed by Kahn, taking into account the problems identified in these reports. Subsequently, a group of health experts evaluated the proposed adaptation using the focus group technique. The results, according to their perception, showed that the prescription delivery report obtained 66.7% in the “Completely Agree” category and 33.3% in the “Agree” category; medical appointment assignment had 73.3% in “Completely Agree” and 26.7% in “Agree”, according to the Likert scale. In conclusion, this research contributes to strengthening the data quality of these reports by providing guidelines to improve the reliability of the information.

Audiovisual media are an essential source of information and leisure in our lives, but people with hearing disabilities lose the emotional content that is intended to be transmitted through this channel. Some previous studies have tried to find alternative ways to elicit these emotions using other sensory channels, and some attempts have been made with haptic systems synchronized with rhythms of music and action in movies, but they fail in studying deeply the provoked neural response. In this article, we propose the tactile channel as the alternative to the auditory channel to convey the emotions generated by audiovisual events, measuring the effect of a proprietary system in the emotions by monitoring neural response. We have developed a low-cost system consisting of an Arduino Uno, a pair of gloves with micromotors and a driver. Using EEG, we have measured brain activity generated during audiovisual stimulation of a short film with clearly negative emotional content, with and without synchronized tactile stimuli, in two groups of people, one without hearing impairment and the other with hearing impairment. We have used the Hotelling’s T2 test as a multivariate statistical analysis of EEG measurements. Comparing the difference in brain activation generated in the conditions with and without vibration in both groups, we have found that multimodal stimulation by touch and associated with audiovisual stimuli enhances in a 30% the emotional, attentional, and auditory circuits activation, due to brain reorganization around frontal and parietal structures (all related to emotional responses) in the hearing-impaired group.

The massive integration of distributed renewable energy resources is a reality in the current power system. In this new context with a greater volatility on the generation side it is required to incorporate new assets to provide additional flexibility to the system to accommodate as much renewable resources as possible. Among these new assets, DC or AC flexible links could play a key role in managing the power flows within radial distribution systems. These connected between distribution feeders may regulate the active power flow in a controlled manner and contribute to the network voltage support. However, the power losses of these devices can be a limiting factor of some functionalities. This paper integrates a detailed power loss model of several flexible link topologies for Optimal Power Flow algorithms with the aim of evaluating its impact on the functionalities of these devices. In this way, it is possible to benchmark the performance of different DC and AC flexible links in a quantitative manner by means of some key performance indexes. The paper proposes a case study based on the European MV benchmark with a high penetration of renewable energy sources to evidence the benefits and limitations that flexible links may provide.

Abstract Significant evidence does exist on the effectiveness of transdiagnostic interventions to improve emotional problems in clinical populations, and their application as universal and indicated prevention programs. However, no randomized controlled trials (RCT) studying selective transdiagnostic prevention intervention have been published. This is the first known RCT to evaluate the efficacy/effectiveness of an evidence-based selective prevention transdiagnostic program for emotional problems in adolescents. The impact of three different interventions was evaluated: (1) PROCARE (Preventive transdiagnostic intervention for Adolescents at Risk for Emotional disorders), which is a group-based, online-delivered, abbreviated version of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents (UP-A), along with adding a booster session, to reduce risk of onset of anxiety and depression, (2) PROCARE + , which includes the PROCARE protocol along with personalized add-on modules tailored to match adolescents’ risk factors, and (3) an active control condition (ACC) based on emotional psychoeducation. In total, 286 adolescents (53.3% girls) evidencing high risk and low protective factors were randomized and allocated to PROCARE, PROCARE + or ACC. Self- and parent-reported measures were taken at baseline, as well as after the intervention, a 6-month follow-up was carried out, together with a 1-month follow-up after the booster session. Differences between conditions were significant on most of the outcome measures, with superior effect sizes for PROCARE +. Interventions were excellent in terms of acceptability, with good satisfaction rates. Tailored selective transdiagnostic interventions focused on mitigating risk factors and promoting protective factors in vulnerable adolescents are promising.