Cognitive phenotypes in patients with relapsing-remitting multiple sclerosis with different disease duration, applying the international classification of cognitive disorders in MS (IC-CoDiMS).

Objective: Cognitive impairment is experienced by 40-70% of multiple sclerosis patients, with information processing speed and memory most affected. Until now, cognitive results classified patients as impaired and not impaired. With this dichotomous approach, it is difficult to identify, in a heterogeneous group of patients with cognitive impairment, which cognitive domain(s) are most altered. This study aims to identify cognitive phenotypes in a clinical cohort of adult patients with Relapsing-Remitting Multiple Sclerosis (RRMS) using the International Classification of Cognitive Disorders in MS (IC-CoDiMS) and to characterize their clinical features. Methods: Three hundred patients with RRMS underwent neuropsychological assessment with the Brief Repeatable Battery of Neuropsychological Tests (BRBN-T) and the Brief International Cognitive Multiple Sclerosis (BICAMS). Results: In our cohort, the mean age was 41.38 [11.48 SD] years, and 205 [68.3%] were women. At the -1 SD threshold, 49% were cognitively intact, 25% had uni-domain impairment, 17% had bi-domain impairment, and 9% had multi-domain impairment. Processing speed was the most frequent single-domain impairment, followed by memory and verbal fluency. At the -1.5 SD threshold, 74.7% were cognitively intact, 17% had uni-domain impairment, 6% had bi-domain impairment, had bi-domain impairment, and 3.0% had multi-domain impairment. Memory was the most frequent single-domain impairment, followed by processing speed and verbal fluency. Conclusions: This study corroborates the importance of determining cognitive phenotypes through taxonomy (IC-CoDiMS). In addition, it contributes to improving the classification of cognitive phenotypes in patients with RRMS to enhance the development of more effective treatments and cognitive interventions.

Immune response of BALB/c mice infected with two strains of Corynebacterium pseudotuberculosis.

This work evaluated aspects of the immune response of BALB/c mice infected with Corynebacterium pseudotuberculosis (T1 and C57). The fifteen BALB/c mice were euthanized after 70 days of infection and morphologically evaluated, also analyzing the innate and adaptive immune responses. The C57 strain induced more pronounced morphological changes than the T1 strain. There was an increase in CD4+ and CD8+ T cells identified during infection with the C57 strain. Cytokines of the inflammatory profile IL-1α and IL-6 and regulatory IL-13 and IL-10 presented significant differences. Cytokines IL-2, IL-4, INF-γ, IL-22, IL-21, and IL-27 did not differ significantly between groups. The obtained results contribute to a better understanding of the type of response and the immunological mechanisms involved during infection with different strains of C. pseudotuberculosis.

Cotton plants overexpressing the Bacillus thuringiensis Cry23Aa and Cry37Aa binary-like toxins exhibit high resistance to the cotton boll weevil (Anthonomus grandis).

The cotton boll weevil (CBW, Anthonomus grandis) stands as one of the most significant threats to cotton crops (Gossypium hirsutum). Despite substantial efforts, the development of a commercially viable transgenic cotton event for effective open-field control of CBW has remained elusive. This study describes a detailed characterization of the insecticidal toxins Cry23Aa and Cry37Aa against CBW. Our findings reveal that CBW larvae fed on artificial diets supplemented exclusively with Cry23Aa decreased larval survival by roughly by 69%, while supplementation with Cry37Aa alone displayed no statistical difference compared to the control. However, the combined provision of both toxins in the artificial diet led to mortality rates approaching 100% among CBW larvae (LC50 equal to 0.26 PPM). Additionally, we engineered transgenic cotton plants by introducing cry23Aa and cry37Aa genes under control of the flower bud-specific pGhFS4 and pGhFS1 promoters, respectively. Seven transgenic cotton events expressing high levels of Cry23Aa and Cry37Aa toxins in flower buds were selected for greenhouse bioassays, and the mortality rate of CBW larvae feeding on their T0 and T1 generations ranged from 75% to 100%. Our in silico analyses unveiled that Cry23Aa displays all the hallmark characteristics of ß-pore-forming toxins (ß-PFTs) that bind to sugar moieties in glycoproteins. Intriguingly, we also discovered a distinctive zinc-binding site within Cry23Aa, which appears to be involved in protein-protein interactions. Finally, we discuss the major structural features of Cry23Aa that likely play a role in the toxin's mechanism of action. In view of the low LC50 for CBW larvae and the significant accumulation of these toxins in the flower buds of both T0 and T1 plants, we anticipate that through successive generations of these transgenic lines, cotton plants engineered to overexpress cry23Aa and cry37Aa hold promise for effectively managing CBW infestations in cotton crops.

Cellular Immunity of SARS-CoV-2 in the Borriana COVID-19 Cohort: A Nested Case-Control Study.

Our goal was to determine the cellular immune response (CIR) in a sample of the Borriana COVID-19 cohort (Spain) to identify associated factors and their relationship with infection, reinfection and sequelae. We conducted a nested case-control study using a randomly selected sample of 225 individuals aged 18 and older, including 36 individuals naïve to the SARS-CoV-2 infection and 189 infected patients. We employed flow-cytometry-based immunoassays for intracellular cytokine staining, using Wuhan and BA.2 antigens, and chemiluminescence microparticle immunoassay to detect SARS-CoV-2 antibodies. Logistic regression models were applied. A total of 215 (95.6%) participants exhibited T-cell response (TCR) to at least one antigen. Positive responses of CD4+ and CD8+ T cells were 89.8% and 85.3%, respectively. No difference in CIR was found between naïve and infected patients. Patients who experienced sequelae exhibited a higher CIR than those without. A positive correlation was observed between TCR and anti-spike IgG levels. Factors positively associated with the TCR included blood group A, number of SARS-CoV-2 vaccine doses received, and anti-N IgM; factors inversely related were the time elapsed since the last vaccine dose or infection, and blood group B. These findings contribute valuable insights into the nuanced immune landscape shaped by SARS-CoV-2 infection and vaccination.

Routine CSF parameters as predictors of disease course in multiple sclerosis: an MSBase cohort study.

BACKGROUND: It remains unclear whether routine cerebrospinal fluid (CSF) parameters can serve as predictors of multiple sclerosis (MS) disease course. METHODS: This large-scale cohort study included persons with MS with CSF data documented in the MSBase registry. CSF parameters to predict time to reach confirmed Expanded Disability Status Scale (EDSS) scores 4, 6 and 7 and annualised relapse rate in the first 2 years after diagnosis (ARR2) were assessed using (cox) regression analysis. RESULTS: In total, 11 245 participants were included of which 93.7% (n=10 533) were persons with relapsing-remitting MS (RRMS). In RRMS, the presence of CSF oligoclonal bands (OCBs) was associated with shorter time to disability milestones EDSS 4 (adjusted HR=1.272 (95% CI, 1.089 to 1.485), p=0.002), EDSS 6 (HR=1.314 (95% CI, 1.062 to 1.626), p=0.012) and EDSS 7 (HR=1.686 (95% CI, 1.111 to 2.558), p=0.014). On the other hand, the presence of CSF pleocytosis (≥5 cells/µL) increased time to moderate disability (EDSS 4) in RRMS (HR=0.774 (95% CI, 0.632 to 0.948), p=0.013). None of the CSF variables were associated with time to disability milestones in persons with primary progressive MS (PPMS). The presence of CSF pleocytosis increased ARR2 in RRMS (adjusted R2=0.036, p=0.015). CONCLUSIONS: In RRMS, the presence of CSF OCBs predicts shorter time to disability milestones, whereas CSF pleocytosis could be protective. This could however not be found in PPMS. CSF pleocytosis is associated with short-term inflammatory disease activity in RRMS. CSF analysis provides prognostic information which could aid in clinical and therapeutic decision-making.

Comparing ocrelizumab to interferon/glatiramer acetate in people with multiple sclerosis over age 60.

BACKGROUND: Ongoing controversy exists regarding optimal management of disease modifying therapy (DMT) in older people with multiple sclerosis (pwMS). There is concern that the lower relapse rate, combined with a higher risk of DMT-related infections and side effects, may alter the risk-benefit balance in older pwMS. Given the lack of pwMS above age 60 in randomised controlled trials, the comparative efficacy of high-efficacy DMTs such as ocrelizumab has not been shown in older pwMS. We aimed to evaluate the comparative effectiveness of ocrelizumab, a high-efficacy DMT, versus interferon/glatiramer acetate (IFN/GA) in pwMS over the age of 60. METHODS: Using data from MSBase registry, this multicentre cohort study included pwMS above 60 who switched to or started on ocrelizumab or IFN/GA. We analysed relapse and disability outcomes after balancing covariates using an inverse probability treatment weighting (IPTW) method. Propensity scores were obtained based on age, country, disease duration, sex, baseline Expanded Disability Status Scale, prior relapses (all-time, 12 months and 24 months) and prior DMT exposure (overall number and high-efficacy DMTs). After weighting, all covariates were balanced. Primary outcomes were time to first relapse and annualised relapse rate (ARR). Secondary outcomes were 6-month confirmed disability progression (CDP) and confirmed disability improvement (CDI). RESULTS: A total of 248 participants received ocrelizumab, while 427 received IFN/GA. The IPTW-weighted ARR for ocrelizumab was 0.01 and 0.08 for IFN/GA. The IPTW-weighted ARR ratio was 0.15 (95% CI 0.06 to 0.33, p<0.001) for ocrelizumab compared with IFN/GA. On IPTW-weighted Cox regression models, HR for time to first relapse was 0.13 (95% CI 0.05 to 0.26, p<0.001). The hazard of first relapse was significantly reduced in ocrelizumab users after 5 months compared with IFN/GA users. However, the two groups did not differ in CDP or CDI over 3.57 years. CONCLUSION: In older pwMS, ocrelizumab effectively reduced relapses compared with IFN/GA. Overall relapse activity was low. This study adds valuable real-world data for informed DMT decision making with older pwMS. Our study also confirms that there is a treatment benefit in older people with MS, given the existence of a clear differential treatment effect between ocrelizumab and IFN/GA in the over 60 age group.

Effect of photobiomodulation on inflammatory cytokines produced by HaCaT keratinocytes.

Objective: to evaluate the effects of the red and near-infrared wavelength lasers in isolated and simultaneous way on the modulation of inflammatory cytokines produced by human keratinocytes (HaCaT) challenged by cytokines of human monocytes stimulated by lipopolysaccharide from Escherichia coli. Design: HaCaT cells was previously exposed to the laser with wavelengths red (660 nm), near-infrared (808 nm). Then, HaCat cells were stimulated with the supernatant of lipopolysaccharide-challenged peripheral blood cells. The cytokines expressed by HaCat cells were measured using multiplex CBA assay. Results: HaCaT cells increased the production of inflammatory cytokines when stimulated with infrared laser compared to the control group (IFN-α2, IFN-γ, TNF-α, MCP-1, IL-6, IL-8, IL-10, IL -12p70, IL -17A, IL-23, IL-33), the red laser group (IFN-γ and IL-23) and the group of two lasers used simultaneously (IFN-α2, IFN-γ, IL-6 and IL-8, IL-17A, IL-18 and IL-23) (p < 0.05). The red laser also stimulated an increase in the expression of IFN-α2 by HaCaT cells in relation to the control group (p < 0.05). Conclusion: Infrared laser, with an energy density of 5 J/cm2, appear to be able to modulate inflammatory cytokines produced by HaCaT cells challenged by human monocyte cytokines.

Global gene expression profile and functional analysis reveal the conservation of reproduction-associated gene networks in Gossypium hirsutum.

KEY MESSAGE: Lastly, the bZIP gene family encompasses genes that have been reported to play a role in flower development, such as bZIP14 (FD). Notably, bZIP14 is essential for Flowering Locus T (FT) initiation of floral development in Arabidopsis (Abe et al. 2005). Cotton (Gossypium hirsutum L.) is the world's most extensively cultivated fiber crop. However, its reproductive development is poorly characterized at the molecular level. Thus, this study presents a detailed transcriptomic analysis of G. hirsutum at three different reproductive stages. We provide evidence that more than 64,000 genes are active in G. hirsutum during flower development, among which 94.33% have been assigned to functional terms and specific pathways. Gene set enrichment analysis (GSEA) revealed that the biological process categories of floral organ development, pollen exine formation, and stamen development were enriched among the genes expressed during the floral development of G. hirsutum. Furthermore, we identified putative Arabidopsis homologs involved in the G. hirsutum gene regulatory network (GRN) of pollen and flower development, including transcription factors such as WUSCHEL (WUS), INNER NO OUTER (INO), AGAMOUS-LIKE 66 (AGL66), SPOROCYTELESS/NOZZLE (SPL/NZZ), DYSFUNCTIONAL TAPETUM 1 (DYT1), ABORTED MICROSPORES (AMS), and ASH1-RELATED 3 (ASHR3), which are known crucial genes for plant reproductive success. The cotton MADS-box protein-protein interaction pattern resembles the previously described patterns for AGAMOUS (AG), SEEDSTICK (STK), SHATTERPROOF (SHP), and SEPALLATA3 (SEP3) homolog proteins from Arabidopsis. In addition to serving as a resource for comparative flower development studies, this work highlights the changes in gene expression profiles and molecular networks underlying stages that are valuable for cotton breeding improvement.

Optic neuropathy diagnosis in the emergency room - retrospective observational study of the last 18 years.

INTRODUCTION: Optic neuropathies (ON), a broad spectrum of disorders of the optic nerve, are a frequent cause of visual loss, presenting either in isolation or associated to neurological or systemic disorders. They are often first evaluated in the Emergency Room (ER) and a rapid determination of the etiology is imperative for implementing timely and appropriate treatment. We aim to describe ER demographic data and clinical characteristics, as well as the performed imaging exams, of patients subsequently hospitalized and diagnosed with ON. Furthermore, we seek to explore the accuracy of ER discharge diagnosis and evaluate possible predictive factors that may influence it. METHODS: We retrospectively reviewed the medical records of 192 patients admitted to the ward of the Neurology Department of Centro Hospitalar Universitário São João (CHUSJ), with a discharge diagnosis of ON. Subsequently, we selected those admitted from the ER, with clinical, laboratory and imaging data, between January 2004 and December 2021. RESULTS: We included 171 patients. All participants were discharged from the ER and admitted in the ward with a main diagnostic suspicion of ON. Patients were stratified according to suspected etiology at the time of discharge: 99 inflammatory (57.9%), 38 ischemic (22.2%), 27 unspecified (15.8%) and 7 other (4.1%). By comparing with current follow-up diagnosis, 125 patients had an accurate ER diagnosis category (73.1%), 27 had an ON diagnosis of unspecified etiology that was defined only during follow-up (15.8%) and 19 had an inaccurate diagnosis category (11.1%). Diagnostic change was more common with ER ischemic diagnosis (21.1%) compared to inflammatory diagnosis (8.1%) (p = 0.034). CONCLUSIONS: Our study reveals that most patients with ON can be accurately diagnosed in the ER through clinical history neurological and ophthalmological evaluation.

Examining the environmental risk factors of progressive-onset and relapsing-onset multiple sclerosis: recruitment challenges, potential bias, and statistical strategies.

It is unknown whether the currently known risk factors of multiple sclerosis reflect the etiology of progressive-onset multiple sclerosis (POMS) as observational studies rarely included analysis by type of onset. We designed a case-control study to examine associations between environmental factors and POMS and compared effect sizes to relapse-onset MS (ROMS), which will offer insights into the etiology of POMS and potentially contribute to prevention and intervention practice. This study utilizes data from the Primary Progressive Multiple Sclerosis (PPMS) Study and the Australian Multi-center Study of Environment and Immune Function (the AusImmune Study). This report outlines the conduct of the PPMS Study, whether the POMS sample is representative, and the planned analysis methods. The study includes 155 POMS, 204 ROMS, and 558 controls. The distributions of the POMS were largely similar to Australian POMS patients in the MSBase Study, with 54.8% female, 85.8% POMS born before 1970, mean age of onset of 41.44 ± 8.38 years old, and 67.1% living between 28.9 and 39.4° S. The POMS were representative of the Australian POMS population. There are some differences between POMS and ROMS/controls (mean age at interview: POMS 55 years vs. controls 40 years; sex: POMS 53% female vs. controls 78% female; location of residence: 14.3% of POMS at a latitude ≤ 28.9°S vs. 32.8% in controls), which will be taken into account in the analysis. We discuss the methodological issues considered in the study design, including prevalence-incidence bias, cohort effects, interview bias and recall bias, and present strategies to account for it. Associations between exposures of interest and POMS/ROMS will be presented in subsequent publications.

The regeneration conferring transcription factor complex ERF115-PAT1 coordinates a wound-induced response in root-knot nematode induced galls.

The establishment of root-knot nematode (RKN; Meloidogyne spp.) induced galls in the plant host roots likely involves a wound-induced regeneration response. Confocal imaging demonstrates physical stress or injury caused by RKN infection during parasitism in the model host Arabidopsis thaliana. The ERF115-PAT1 heterodimeric transcription factor complex plays a recognized role in wound-induced regeneration. ERF115 and PAT1 expression flanks injured gall cells likely driving mechanisms of wound healing, implying a local reactivation of cell division which is also hypothetically involved in gall genesis. Herein, functional investigation revealed that ectopic ERF115 expression resulted in premature induction of galls, and callus formation adjacent to the expanding female RKN was seen upon PAT1 upregulation. Smaller galls and less reproduction were observed in ERF115 and PAT1 knockouts. Investigation of components in the ERF115 network upon overexpression and knockdown by qRT-PCR suggests it contributes to steer gall wound-sensing and subsequent competence for tissue regeneration. High expression of CYCD6;1 was detected in galls, and WIND1 overexpression resulted in similar ERF115OE gall phenotypes, also showing faster gall induction. Along these lines, we show that the ERF115-PAT1 complex likely coordinates stress signalling with tissue healing, keeping the gall functional until maturation and nematode reproduction.

An ex vitro hairy root system from petioles of detached soybean leaves for in planta screening of target genes and CRISPR strategies associated with nematode bioassays.

MAIN CONCLUSION: The ex vitro hairy root system from petioles of detached soybean leaves allows the functional validation of genes using classical transgenesis and CRISPR strategies (e.g., sgRNA validation, gene activation) associated with nematode bioassays. Agrobacterium rhizogenes-mediated root transformation has been widely used in soybean for the functional validation of target genes in classical transgenesis and single-guide RNA (sgRNA) in CRISPR-based technologies. Initial data showed that in vitro hairy root induction from soybean cotyledons and hypocotyls were not the most suitable strategies for simultaneous performing genetic studies and nematode bioassays. Therefore, an ex vitro hairy root system was developed for in planta screening of target molecules during soybean parasitism by root-knot nematodes (RKNs). Applying this method, hairy roots were successfully induced by A. rhizogenes from petioles of detached soybean leaves. The soybean GmPR10 and GmGST genes were then constitutively overexpressed in both soybean hairy roots and tobacco plants, showing a reduction in the number of Meloidogyne incognita-induced galls of up to 41% and 39%, respectively. In addition, this system was evaluated for upregulation of the endogenous GmExpA and GmExpLB genes by CRISPR/dCas9, showing high levels of gene activation and reductions in gall number of up to 58.7% and 67.4%, respectively. Furthermore, morphological and histological analyses of the galls were successfully performed. These collective data validate the ex vitro hairy root system for screening target genes, using classical overexpression and CRISPR approaches, directly in soybean in a simple manner and associated with nematode bioassays. This system can also be used in other root pathosystems for analyses of gene function and studies of parasite interactions with plants, as well as for other purposes such as studies of root biology and promoter characterization.

Atividades de extensão em enfermagem: Medidas excecionais em tempos de pandemia por COVID-19 / Extension activities in nursing: Exceptional measures during the COVID-19 pandemic / Actividades de extensión en enfermería: medidas excepcionales en tiempos de pandemia por COVID-19

Resumo Enquadramento: A Escola Superior de Enfermagem de Coimbra, ciente do valor das unidades de extensão na articulação do tripé Ensino-Investigação-Extensão tem na sua estrutura a Unidade de Prestação de Serviços à Comunidade e Coordenação das Atividades de Extensão na Comunidade (UPSCCAEC). Objetivo: Descrever o trabalho desenvolvido pela UPSCCAEC em 2019 e 2020, destacando a sua capacidade adaptativa mediante a pandemia pela COVID-19. Principais tópicos em análise: Utilizaram-se como fonte de dados os relatórios de atividades realizadas no contexto da UPSCCAEC nos anos civis de 2019 e 2020, e realizou-se a comparação com achados nos dois anos, os quais foram discutidos à luz do referencial teórico disponível, considerando a pandemia COVID-19 e o impacte a nível das Instituições do Ensino Superior (IES) em seus processos formativos, de investigação e extensão. Conclusão: A atividade da UPSCCAEC nos referidos anos contribuiu para a afirmação da instituição, do desenvolvimento académico, e constituiu recurso de excelência na resposta aos atuais desafios da sociedade, particularmente num período caracterizado por enorme turbulência resultante da pandemia COVID-19.

Abstract Background: The Nursing School of Coimbra knows the importance of extension units in the articulation between teaching, research, and extension. For this reason, the School has a Service Provision and Community Extension Activities Coordination Unit (UPSCCAEC). Objective: To describe the work developed by the UPSCCAEC in 2019 and 2020, highlighting its adaptive capacity in the face of the COVID-19 pandemic. Main topics under analysis: The reports of activities carried out within the scope of the UPSCCAEC in 2019 and 2020 were used as a data source. A comparison was made with findings in the two years, discussed based on the available theoretical framework and considering the COVID-19 pandemic and its impact on Higher Education Institutions' training, research, and extension processes. Conclusion: The UPSCCAEC's activity in those years contributed to the institution's excellence and academic development and successful response to the current societal challenges in a time of great instability due to the COVID-19 pandemic.

Resumen Marco contextual: La Escuela Superior de Enfermería de Coímbra, consciente del valor de las unidades de extensión en la articulación del trípode Enseñanza-Investigación-Extensión, cuenta en su estructura con la Unidad de Prestación de Servicios a la Comunidad y Coordinación de Actividades de Extensión Comunitaria (UPSCCAEC). Objetivo: Describir el trabajo desarrollado por la UPSCCAEC en 2019 y 2020, y destacar su capacidad de adaptación frente a la pandemia por COVID-19. Principales temas en análisis: La fuente de datos utilizada fueron los informes de las actividades realizadas en el marco de la UPSCCAEC en los años civiles de 2019 y 2020, y se realizó una comparación con los hallazgos en ambos años, los cuales se discutieron considerando el marco teórico disponible, la pandemia del COVID-19 y el impacto en las Instituciones de Educación Superior (IES), en sus procesos de formación, investigación y extensión. Conclusión: La actividad de la UPSCCAEC en estos años contribuyó a la afirmación de la institución, al desarrollo académico y constituyó un recurso de excelencia para responder a los desafíos actuales de la sociedad, particularmente en un período caracterizado por enormes turbulencias derivadas de la pandemia del COVID-19.

Identification and expression profile of the SMAX/SMXL family genes in chickpea and lentil provide important players of biotechnological interest involved in plant branching.

MAIN CONCLUSION: SMAX/SMXL family genes were successfully identified and characterized in the chickpea and lentil and gene expression data revealed several genes associated with the modulation of plant branching and powerful targets for use in transgenesis and genome editing. Strigolactones (SL) play essential roles in plant growth, rooting, development, and branching, and are associated with plant resilience to abiotic and biotic stress conditions. Likewise, karrikins (KAR) are "plant smoke-derived molecules" that act in a hormonal signaling pathway similar to SL playing an important role in seed germination and hairy root elongation. The SMAX/SMXL family genes are part of these two signaling pathways, in addition to some of these members acting in a still little known SL- and KAR-independent signaling pathway. To date, the identification and functional characterization of the SMAX/SMXL family genes has not been performed in the chickpea and lentil. In this study, nine SMAX/SMXL genes were systematically identified and characterized in the chickpea and lentil, and their expression profiles were explored under different unstressless or different stress conditions. After a comprehensive in silico characterization of the genes, promoters, proteins, and protein-protein interaction network, the expression profile for each gene was determined using a meta-analysis from the RNAseq datasets and complemented with real-time PCR analysis. The expression profiles of the SMAX/SMXL family genes were very dynamic in different chickpea and lentil organs, with some genes assuming a tissue-specific expression pattern. In addition, these genes were significantly modulated by different stress conditions, indicating that SMAX/SMXL genes, although working in three distinct signaling pathways, can act to modulate plant resilience. Most CaSMAX/SMXL and partner genes such as CaTiE1 and CaLAP1, have a positive correlation with the plant branching level, while most LcSMAX/SMXL genes were less correlated with the plant branching level. The SMXL6, SMXL7, SMXL8, TiE1, LAP1, BES1, and BRC1 genes were highlighted as powerful targets for use in transgenesis and genome editing aiming to develop chickpea and lentil cultivars with improved architecture. Therefore, this study presented a detailed characterization of the SMAX/SMXL genes in the chickpea and lentil, and provided new insights for further studies focused on each SMAX/SMXL gene.

First, Be a Good Citizen: Organizational Citizenship Behaviors, Well-Being at Work and the Moderating Role of Leadership Styles.

The study investigates the effect of organizational citizenship behavior (OCB) on well-being at work. The study further examines the moderating role of people and task-focused leadership styles between OCB on well-being at work. Individual-directed organizational citizenship behaviors (OCBI) and organizational-directed organizational citizenship behaviors (OCBO) will also be analyzed. A quantitative study was conducted and convenient sampling was adopted in selecting respondent workers (n = 200) in different Portuguese organizations. The results show that OCBs positively and significantly influence well-being at work. The strength of individual-directed organizational citizenship behaviors (OCBI) on well-being at work is stronger than that of organization-directed organizational citizenship behaviors (OCBO). Contrary to expectations, the relationship between leadership styles and well-being was not statistically significant, offering possibilities for discussion regarding the central importance usually attributed to leadership in the organizational context. However, leadership styles have a moderating effect between OCB and well-being at work, except when the employee adopts OCBO and the leadership style is people-oriented. The present study is innovative because it positions OCB as an antecedent in the relationship with well-being at work and investigates the moderating role of leadership styles in the relationship between organizational citizenship behavior and well-being.

Long COVID Prevalence and the Impact of the Third SARS-CoV-2 Vaccine Dose: A Cross-Sectional Analysis from the Third Follow-Up of the Borriana Cohort, Valencia, Spain (2020-2022).

BACKGROUND: In March 2020, a COVID-19 outbreak linked to mass gathering dinners at the Falles Festival in Borriana, Spain, resulted in an estimated attack rate of 42.6% among attendees. METHODS: In June 2022, we conducted a cross-sectional follow-up study of 473 adults aged 18 to 64 who attended the dinners at the Falles Festival in 2020, examining the cumulative experience after SARS-CoV-2 infection and vaccination responses. Data included demographic details, lifestyle habits, medical history, infection records, and vaccinations from a population-based vaccine registry. Blood samples were analyzed for SARS-CoV-2 antibodies and cellular immunity. We employed a doubly robust inverse-probability weighting analysis to estimate the booster vaccine dose's impact on long COVID prevalence and symptom count. RESULTS: A total of 28.1% of participants met the WHO criteria for long COVID, with older individuals showing higher rates. Long COVID diagnosis was less likely with factors including O blood group, higher occupational status, physical activity, three vaccine doses, strong SARS-CoV-2-S-reactive IFNγ-producing-CD8+ response, and infection during the Omicron period. Increased age, high or low social activity, underlying health conditions, a severe initial COVID episode, and reinfection were associated with higher long COVID likelihood. A booster dose, compared to one or two doses, reduced long COVID risk by 74% (95% CI: 56% to 92%) and symptom count by 55% (95% CI: 32% to 79%). CONCLUSION: Long COVID was prevalent in a significant portion of those who contracted COVID-19, underscoring the need for sustained follow-up and therapeutic strategies. Vaccinations, notably the booster dose, had a substantial beneficial effect on long-term infection outcomes, affirming the vaccination's role in mitigating SARS-CoV-2 infection consequences.

Elevated CO2 increases biomass of Sorghum bicolor green prop roots under drought conditions via soluble sugar accumulation and photosynthetic activity.

Elevated [CO2 ] (E[CO2 ]) mitigates agricultural losses of C4 plants under drought. Although several studies have described the molecular responses of the C4 plant species Sorghum bicolor during drought exposure, few have reported the combined effects of drought and E[CO2 ] (E[CO2 ]/D) on the roots. A previous study showed that, among plant organs, green prop roots (GPRs) under E[CO2 ]/D presented the second highest increase in biomass after leaves compared with ambient [CO2 ]/D. GPRs are photosynthetically active and sensitive to drought. To understand which mechanisms are involved in the increase in biomass of GPRs, we performed transcriptome analyses of GPRs under E[CO2 ]/D. Whole-transcriptome analysis revealed several pathways altered under E[CO2 ]/D, among which photosynthesis was strongly affected. We also used previous metabolome data to support our transcriptome data. Activities associated with photosynthesis and central metabolism increased, as seen by the upregulation of photosynthesis-related genes, a rise in glucose and polyol contents, and increased contents of chlorophyll a and carotenoids. Protein-protein interaction networks revealed that proliferation, biogenesis, and homeostasis categories were enriched and contained mainly upregulated genes. The findings suggest that the previously reported increase in GPR biomass of plants grown under E[CO2 ]/D is mainly attributed to glucose and polyol accumulation, as well as photosynthesis activity and carbon provided by respiratory CO2 refixation. Our findings reveal that an intriguing and complex metabolic process occurs in GPRs under E[CO2 ]/D, showing the crucial role of these organs in plant drought /tolerance.

Effectiveness of multiple disease-modifying therapies in relapsing-remitting multiple sclerosis: causal inference to emulate a multiarm randomised trial.

BACKGROUND: Simultaneous comparisons of multiple disease-modifying therapies for relapsing-remitting multiple sclerosis (RRMS) over an extended follow-up are lacking. Here we emulate a randomised trial simultaneously comparing the effectiveness of six commonly used therapies over 5 years. METHODS: Data from 74 centres in 35 countries were sourced from MSBase. For each patient, the first eligible intervention was analysed, censoring at change/discontinuation of treatment. The compared interventions included natalizumab, fingolimod, dimethyl fumarate, teriflunomide, interferon beta, glatiramer acetate and no treatment. Marginal structural Cox models (MSMs) were used to estimate the average treatment effects (ATEs) and the average treatment effects among the treated (ATT), rebalancing the compared groups at 6-monthly intervals on age, sex, birth-year, pregnancy status, treatment, relapses, disease duration, disability and disease course. The outcomes analysed were incidence of relapses, 12-month confirmed disability worsening and improvement. RESULTS: 23 236 eligible patients were diagnosed with RRMS or clinically isolated syndrome. Compared with glatiramer acetate (reference), several therapies showed a superior ATE in reducing relapses: natalizumab (HR=0.44, 95% CI=0.40 to 0.50), fingolimod (HR=0.60, 95% CI=0.54 to 0.66) and dimethyl fumarate (HR=0.78, 95% CI=0.66 to 0.92). Further, natalizumab (HR=0.43, 95% CI=0.32 to 0.56) showed a superior ATE in reducing disability worsening and in disability improvement (HR=1.32, 95% CI=1.08 to 1.60). The pairwise ATT comparisons also showed superior effects of natalizumab followed by fingolimod on relapses and disability. CONCLUSIONS: The effectiveness of natalizumab and fingolimod in active RRMS is superior to dimethyl fumarate, teriflunomide, glatiramer acetate and interferon beta. This study demonstrates the utility of MSM in emulating trials to compare clinical effectiveness among multiple interventions simultaneously.

Comparative Effectiveness of Autologous Hematopoietic Stem Cell Transplant vs Fingolimod, Natalizumab, and Ocrelizumab in Highly Active Relapsing-Remitting Multiple Sclerosis.

Importance: Autologous hematopoietic stem cell transplant (AHSCT) is available for treatment of highly active multiple sclerosis (MS). Objective: To compare the effectiveness of AHSCT vs fingolimod, natalizumab, and ocrelizumab in relapsing-remitting MS by emulating pairwise trials. Design, Setting, and Participants: This comparative treatment effectiveness study included 6 specialist MS centers with AHSCT programs and international MSBase registry between 2006 and 2021. The study included patients with relapsing-remitting MS treated with AHSCT, fingolimod, natalizumab, or ocrelizumab with 2 or more years study follow-up including 2 or more disability assessments. Patients were matched on a propensity score derived from clinical and demographic characteristics. Exposure: AHSCT vs fingolimod, natalizumab, or ocrelizumab. Main outcomes: Pairwise-censored groups were compared on annualized relapse rates (ARR) and freedom from relapses and 6-month confirmed Expanded Disability Status Scale (EDSS) score worsening and improvement. Results: Of 4915 individuals, 167 were treated with AHSCT; 2558, fingolimod; 1490, natalizumab; and 700, ocrelizumab. The prematch AHSCT cohort was younger and with greater disability than the fingolimod, natalizumab, and ocrelizumab cohorts; the matched groups were closely aligned. The proportion of women ranged from 65% to 70%, and the mean (SD) age ranged from 35.3 (9.4) to 37.1 (10.6) years. The mean (SD) disease duration ranged from 7.9 (5.6) to 8.7 (5.4) years, EDSS score ranged from 3.5 (1.6) to 3.9 (1.9), and frequency of relapses ranged from 0.77 (0.94) to 0.86 (0.89) in the preceding year. Compared with the fingolimod group (769 [30.0%]), AHSCT (144 [86.2%]) was associated with fewer relapses (ARR: mean [SD], 0.09 [0.30] vs 0.20 [0.44]), similar risk of disability worsening (hazard ratio [HR], 1.70; 95% CI, 0.91-3.17), and higher chance of disability improvement (HR, 2.70; 95% CI, 1.71-4.26) over 5 years. Compared with natalizumab (730 [49.0%]), AHSCT (146 [87.4%]) was associated with marginally lower ARR (mean [SD], 0.08 [0.31] vs 0.10 [0.34]), similar risk of disability worsening (HR, 1.06; 95% CI, 0.54-2.09), and higher chance of disability improvement (HR, 2.68; 95% CI, 1.72-4.18) over 5 years. AHSCT (110 [65.9%]) and ocrelizumab (343 [49.0%]) were associated with similar ARR (mean [SD], 0.09 [0.34] vs 0.06 [0.32]), disability worsening (HR, 1.77; 95% CI, 0.61-5.08), and disability improvement (HR, 1.37; 95% CI, 0.66-2.82) over 3 years. AHSCT-related mortality occurred in 1 of 159 patients (0.6%). Conclusion: In this study, the association of AHSCT with preventing relapses and facilitating recovery from disability was considerably superior to fingolimod and marginally superior to natalizumab. This study did not find evidence for difference in the effectiveness of AHSCT and ocrelizumab over a shorter available follow-up time.