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Since 2021, the emergence of variants of concern (VOC) has led Brazil to experience record numbers of in COVID-19 cases and deaths. The expanded spread of the SARS-CoV-2 combined with a low vaccination rate has contributed to the emergence of new mutations that may enhance viral fitness, leading to the persistence of the disease. Due to limitations in the real-time genomic monitoring of new variants in some Brazilian states, we aimed to investigate whether genomic surveillance, coupled with epidemiological data and SARS-CoV-2 variants spatiotemporal spread in a smaller region, can reflect the pandemic progression at a national level. Our findings revealed three SARS-CoV-2 variant replacements from 2021 to early 2022, corresponding to the introduction and increase in the frequency of Gamma, Delta, and Omicron variants, as indicated by peaks of the Effective Reproductive Number (Reff). These distinct clade replacements triggered two waves of COVID-19 cases, influenced by the increasing vaccine uptake over time. Our results indicated that the effectiveness of vaccination in preventing new cases during the Delta and Omicron circulations was six and eleven times higher, respectively, than during the period when Gamma was predominant, and it was highly efficient in reducing the number of deaths. Furthermore, we demonstrated that genomic monitoring at a local level can reflect the national trends in the spread and evolution of SARS-CoV-2.
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Mycoplasma hyopneumoniae is the causative bacterium of porcine enzootic pneumonia and one of the primary etiologic agents of the porcine respiratory disease complex. Most Brazilian commercial pig farms are positive for this pathogen. However, the prevalence of the pathogen in backyard pig farms has not been described, to our knowledge. Therefore, we aimed to determine the prevalence of M. hyopneumoniae in backyard pig farms in the state of Paraná, Brazil. In January-March 2020, we collected 585 serum samples from pigs in 187 non-vaccinated herds. We tested the sera with an indirect ELISA for anti-M. hyopneumoniae antibodies and found that 182 of 585 (31.1%) samples were positive, and were found in 109 of 187 (58.3%) herds assessed.
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Bladder cancer is the tenth most frequently diagnosed cancer globally. Classification of high- or low-grade tumors is based on cytological differentiation and is an important prognostic factor. LncRNAs regulate gene expression and play critical roles in the occurrence and development of cancer, however, there are few reports on their diagnostic value and co-expression levels with genes, which may be useful as specific biomarkers for prognosis and therapy in bladder cancer. Thus, we performed a marker lesion study to investigate whether gene/lncRNA expression in urothelial carcinoma tissues may be useful in differentiating low-grade and high-grade tumors. RT-qPCR was used to evaluate the expression of the JHDM1D gene and the lncRNAs CTD-2132N18.2, SBF2-AS1, RP11-977B10.2, CTD-2510F5.4, and RP11-363E7.4 in 20 histologically diagnosed high-grade and 10 low-grade tumors. A protein-to-protein interaction network between genes associated with JHDM1D gene was constructed using STRING website. The results showed a moderate (positive) correlation between CTD-2510F5.4 and CTD2132N18.2. ROC curve analyses showed that combined JHDM1D and RP11-363E7.4 predicted tumor grade with an AUC of 0.826, showing excellent accuracy. In conclusion, the results indicated that the combined expression of JHDM1D and RP11-363E7.4 may be a prognostic biomarker and a promising target for urothelial tumor therapy.
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Background: People with a chronic condition such as Parkinson's disease (PD) struggle with acceptance and finding meaning in life. Consciousness coaching could be a valuable addition in addressing these issues. Objective: We aim to evaluate the user experiences and potential effectiveness of consciousness coaching for people with PD (PwPD). Methods: We performed a pilot randomized controlled trial including PwPD in Hoehn & Yahr stage 1-3. People with cognitive impairments, severe psychiatric disorders, or those who did not have a clear issue to address with consciousness coaching, were excluded. PwPD were randomly allocated to either receiving 6 months of consciousness coaching in addition to usual care or to usual care alone. To explore experiences we performed semi-structured qualitative interviews with all PwPD in the intervention group. Potential effects were explored using questionnaires on quality of life, activities of daily life, self-management and non-motor symptoms at baseline and after 6 months. Results: We included 39 PwPD, 19 participants in the intervention group and 20 in the control group. Based on the interviews, we identified a number of themes and codes. In general PwPD experienced consciousness coaching as confronting but supportive in reaching their goals and in taking more responsibility for their lives. Quantitatively, we did not find a difference between groups for any of the outcomes. Conclusions: Consciousness coaching was considered valuable by most participants in this study and may be an interesting addition to PD treatment. We did not find any effects of the intervention on PD symptoms or quality of life.
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Due to events related to the urbanization process, specimens of Saimiri collinsi are often referred to veterinarians specializing in the treatment of wild animals. With these professionals and the oral health of this species in mind, we evaluated the skull and the exact location of the infraorbital, mentual and mandibular foramens, with the aim of supporting the anesthetic block for dental procedures in Saimiri collinsi. The infraorbital foramen was located in the maxillary bone and was arranged with one on each side, except in one individual, with a pair in each antimer. The mentual foramen was located in the diastema between the canine tooth and the lateral incisor. The mandibular foramen was located medially on the ramus of the mandible, close to the mandibular incisure. The distances between the foramina and the main reference points, were greater in females than in males (p < 0.05). For access purposes, in the foramens investigated we suggest using a Gingival Needle 30G 21 mm Short, positioned externally at 15º to the maxillary bone to access the infraorbital foramen. Externally, perpendicular to the chin, in the diastema between the lower lateral incisor tooth and the canine tooth, to approach the mentual foramen, and ventral to the edge of the mandibular body, at a 90º angle, to access the mandibular foramen.
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The majority of people with dementia live in low or middle-income countries (LMICs) where resources that play a crucial role in brain health, such as quality education, are still not widely available. In Brazil, illiteracy remains a prevalent issue, especially in communities with lower socioeconomic status (SES). The PROAME study set out to explore basic education in illiterate adults as a means to improve cognitive reserve. Objective: This manuscript aims to explore the relationship between SES and learning, as well as cognitive outcomes, in an older illiterate population. Methods: This six-month clinical trial (NCT04473235) involved 108 participants, of which 77 concluded all assessments, enrolled in late-life basic education. SES assessments included Quality of Urban Living Index, Municipal Human Development Index and Household SES calculated for each participant. Cognitive assessments encompassed the Free and Cued Selective Reminding Test (FCSRT), a word list to assess reading, and the Beta III matrix. Results: The sample consisted primarily of women, with a mean age of 58.5. Participants improved their reading (p=0.01) and their FCSRT (p=0.003). Regarding episodic memory, women outperformed men (p=0.007) and younger participants improved more than their older counterparts (p=0.001). There was no association observed between SES and cognitive outcomes. Conclusion: Irrespective of SES, participants demonstrated positive outcomes after attending basic education. These findings highlight that late life education could be an important non-pharmacologic preventative measure, especially in LMICs.
A maioria das pessoas com demência vive em países de baixa/média renda, onde recursos essenciais para a saúde cerebral, como educação de qualidade, ainda não são amplamente acessíveis. No Brasil, o analfabetismo ainda é frequente, especialmente em comunidades de baixo nível socioeconômico. O estudo PROAME teve como objetivo explorar a educação básica tardia em pessoas analfabetas como ferramenta para o aumento da reserva cognitiva. Objetivo: Investigar a relação entre nível socioeconômico com aprendizado e com desempenho em testes cognitivos, em adultos analfabetos. Métodos: Este estudo clínico de seis meses (NCT04473235) contou com 108 participantes inscritos no projeto Educação para Jovens e Adultos (EJA), dos quais 77 completaram os testes. O nível socioeconômico de cada participante foi medido usando-se: o Índice de Qualidade de Vida Urbana, o Índice de Desenvolvimento Humano Municipal e o nível socioeconômico doméstico. Avaliações cognitivas incluíram: o Teste de Recordação Seletiva Livre e Guiada (TRSLG), uma lista de palavras para avaliar leitura e a matriz Beta III. Resultados: A amostra era predominantemente feminina, com idade média de 58,5. Os participantes melhoraram a leitura (p=0,01) e o TRSLG (p=0,003). Com relação à memoria episódica, as mulheres tiveram resultados superiores aos dos homens (p=0,007) e participantes mais jovens melhoraram mais que seus colegas mais velhos (p=0,001). Não foi observada nenhuma relação entre o nível socioeconômico e o desempenho cognitivo. Conclusão: Independentemente do nível socioeconômico, participantes obtiveram resultados positivos após frequentar a educação básica. Isso sugere que a educação tardia pode ser uma medida preventiva não farmacológica importante, especialmente em países de baixa/média renda.
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Cryptomeria japonica wood industry generates large amounts of foliage biomass residues. Due to the increasing applications and markets for essential oils (EOs), fresh Azorean C. japonica foliage (Az-CJF) residues are used for local EO production. Hydrodistillation (HD), a common process for obtaining EOs, also provides the possibility to fractionate them. Thus, this study evaluated the in vitro antimicrobial and antioxidant activities of six Az-CJF EO fractions (Frs. 1-6), collected at sequential HD timeframes (HDTs: 0-2, 2-10, 10-30, 30-60, 60-120, and 120-240 min), in comparison to the crude EO, obtained from a non-fractionated HD (0-240 min HDT). Antimicrobial activities were assessed via disc diffusion method against seven bacteria (foodborne and/or human pathogens) and two Penicillium spp. (phytopathogenic fungi), and antioxidant activity was estimated using DPPH and ABTS assays. Concerning the antibacterial activity, all the EO samples were effective only toward Gram-positive bacteria. Fractions 1-3 (<30 min HDT) were the most active, with growth inhibition zones (GIZ) of 7.0-23.3 mm (1.4-2.2 times higher than those of the crude EO), being Bacillus spp. (B. licheniformis and B. subtilis) the most sensitive, followed by Staphylococcus aureus and Micrococcus luteus. Regarding the antifungal activity, Frs. 1-3 also displayed the best activities, but only against P. italicum (GIZ around 9.0 mm), while the crude EO showed no antifungal activity. Overall, the best antimicrobial properties of Frs. 1-3 could be attributed, at least in part, to their highest content in α-pinene and bornyl acetate. On the other hand, Frs. 4-6 (>30 min HDT) exhibited the strongest antioxidant activities (EC50 values: 1.5-2.3 and 1.0-1.7 mg mL-1 for DPPH and ABTS, respectively), being at least 1.3-fold higher than those of the crude EO. The presence of nezukol, elemol, and eudesmol isomers could strongly contribute to the best free radical scavenging properties of Frs. 4-6. In conclusion, HD was found to be an efficient process for obtaining new Az-CJF EO fractions with variable and enhanced bioactivities due to their differential composition, as assessed using GC-MS. Hence, these findings could contribute to increasing the commercial potential of the C. japonica EO industry, namely, the Fr2 and Fr6, which presented the most significant activities and can have potential applications in the food, medical, and agriculture sectors.
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Spermatogenesis is a complex process that can be disrupted by genetic and epigenetic changes, potentially leading to male infertility. Recent research has rapidly increased the number of protein coding mutations causally linked to impaired spermatogenesis in humans and mice. However, the role of non-coding mutations remains largely unexplored. As a case study to evaluate the effects of non-coding mutations on spermatogenesis, we first identified an evolutionarily conserved topologically associated domain (TAD) boundary near two genes with important roles in mammalian testis function: Dmrtb1 and Lrp8 . We then used CRISPR-Cas9 to generate a mouse line where 26kb of the boundary was removed including a strong and evolutionarily conserved CTCF binding site. ChIP-seq and Hi-C experiments confirmed the removal of the CTCF site and a resulting increase in the DNA-DNA interactions across the domain boundary. Mutant mice displayed significant changes in testis gene expression, abnormal testis histology, a 35% drop in the estimated efficiency of spermatogenesis and a 28% decrease in daily sperm production compared to littermate controls. Despite these quantitative changes in testis function, mutant mice show no significant changes in fertility. This suggests that non-coding deletions affecting testis gene regulation may have smaller effects on fertility compared to coding mutations of the same genes. Our results demonstrate that disruption of a TAD boundary can have a negative impact on sperm production and highlight the importance of considering non-coding mutations in the analysis of patients with male infertility.
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Choloepus didactylus (two-toed sloth) is a Xenarthran mammal whose morphology has so far been little studied. Given the increasing number of sloths requiring clinical and surgical interventions, this lack of clarity regarding anatomical features and landmarks has had a negative impact on veterinary decision-making for this species. We therefore sought to describe the topography of the medullary cone (MC) of Choloepus didactylus in order to provide guidance to qualified professionals on the ideal access for locoregional anesthesia. In evaluating four specimens, radiographs and dissections revealed that Choloepus didactylus has three lumbar vertebrae and five sacral vertebrae. The lumbar intumescence is located between T14 and the cranial half of L2, the medullary cone is located between the caudal half of L2 and L3, with an average length of 2.26 cm, and the cauda equina extends from S1 to S5. Based on these anatomical findings, we propose that the lumbosacral region would be the most suitable target for epidural anesthesia in Choloepus didactylus.
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The fruit juice industry generates a significant amount of waste, with a strong impact on the environment and the economy. Therefore, researchers have been focusing on the characterization of resources considered as food waste. This work provides information about the lipophilic and polar metabolites of pear pomace flours (PPFs) as a tool that can shed more light on the bioactive potential of this residue. Using UPLC-PDA, UPLC-FLR, and GC-MS, the study identified and quantified PPF's polar and non-polar metabolites. Essential, conditional, and non-essential amino acids were found, with asparagine being the most abundant. Isoprenoids, including lutein, zeaxanthin, and carotene isomers, ranged from 10.8 to 22.9 mg/100 g dw. Total flavonoids and phenolic compounds were 520.5-636.4 mg/100 g dw and 536.9-660.1 mg/100 g dw, respectively. Tocotrienols and tocopherols were identified, with concentrations of 173.1-347.0 mg/100 g dw and 468.7-913.4 mg/100 g dw. Fatty acids were the major non-polar compounds. All fractions significantly reduced matrix metalloproteinase-9 (MMP-9) activity. Although PPF had lower antioxidant potential (3-6 mmol Trolox/100 g dw), it inhibited AChE and BuChE by 23-30% compared to physostigmine salicylate. These findings suggest that pear pomace waste can be repurposed into functional products with valuable bioactive properties by re-introducing it in the food chain.
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Background: Infectious keratitis secondary to fungus or acanthamoeba often has a poor outcome despite receiving the best available medical therapy. In vitro Rose Bengal Photodynamic therapy (RB-PDT) appears to be effective against fungal and acanthamoeba isolates.22,23 In one published series RB-PDT reduced the need for therapeutic penetrating keratoplasty in severe bacterial, fungal, and acanthameoba keratitis not responsive to medical therapy. Methods: This international, randomized, sham and placebo controlled 2-arm clinical trial, randomizes patients with smear positive fungal and acanthameoba and smear negative corneal ulcers in a 1:1 fashion to one of two treatment arms: 1) Topical antimicrobial plus sham RB-PDT or 2) Topical antimicrobial plus RB-PDT. Discussion: We anticipate that RB-PDT will improve best spectacle corrected visual acuity and also reduce complications such as corneal perforation and the need for therapeutic penetrating keratoplasty. This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Our results will be disseminated via clinicaltrials.gov website, meetings, and journal publications. Our data will also be available upon reasonable request. Trial Registration: NCT, NCT05110001, Registered November 5, 2021. https://www.clinicaltrials.gov/study/NCT05110001.
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BACKGROUND: Evidence from randomized studies support complete over culprit-only revascularization for patients with acute coronary artery syndrome (ACS) and multivessel coronary artery diseases (MVD). Whether these findings extend to elderly patients, however, has not been thoroughly explored. METHODS: We conducted a systematic review and meta-analysis comparing clinical outcomes of elderly individuals (defined as age ≥75â years) with ACS and MVD submitted to complete vs partial-only percutaneous coronary intervention (PCI). PubMed, Embase, and Cochrane were searched. We computed pooled hazard ratios with 95% confidence intervals (CI) to preserve time time-to-event data. RESULTS: We included 7 studies, of which 2 were RCT and 5 were multivariable adjusted cohorts, comprising a total 10â 147, of whom 43.8% underwent complete revascularization. As compared with partial-only PCI, complete revascularization was associated with a lower all-cause mortality (hazard ratio 0.71; 95% CI 0.60-0.85; Pâ <â 0.01), cardiovascular mortality (hazard ratio 0.64; 95% CI 0.52-0.79; Pâ <â 0.01), and recurrent myocardial infarction (hazard ratio 0.65; 95% CI 0.50-0.85; Pâ <â 0.01). There was no significant difference between groups regarding the risk of revascularizations (hazard ratio 0.80; 95% CI 0.53-1.20; Pâ =â 0.28). CONCLUSION: Among elderly patients with ACS and multivessel CAD, complete revascularization is associated with a lower risk of all-cause mortality, cardiovascular mortality, and recurrent myocardial infarction.
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The species Cuniculus paca is highly subject to predation, whether natural or anthropogenic, and the ability of species to withstand different levels of depredation depends directly on their reproductive dynamics. However, there is little literature on the developmental biology of this species, and so the aim of this paper was to describe the fetal development of the urinary tract of C. paca through morphological analysis. Twelve specimens with estimated gestational ages of between 75 and 157 days were used, divided into 3 groups. We found the urinary tract in pelvic-abdominal topography with macroscopic differentiation between the organs already present in the first ages studied; in addition, the microscopic structural pattern changed little between the groups. This evidence reinforces the precocial development of these individuals. RESEARCH HIGHLIGHTS: With the results obtained for development of urinary tract in Cuniculus paca reinforces the precocial development of these individuals. The urinary tract had pelvic-abdominal topography with macroscopic differentiation between the organs already present in the first ages studied. The microscopic structural pattern changed little between the groups. At all analyzed fetal ages, the cortical region of kidney was characterized by the presence of glomeruli arranged throughout the region, formed by capillary plexuses surrounded by a glomerular capsule. In addition, the cortical region also presented convoluted tubules with cubic epithelial tissue cells and a brush border. The presence of a developed macula densa was observed next to the glomeruli, suggesting the initial formation of the fetal juxtaglomerular apparatus.
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In the Azores archipelago (Portugal), forest operations and wood industry generate large amounts of Cryptomeria japonica biomass residues (CJBR), which can be used to produce valuable essential oils (EOs). In this study, we evaluated the chemical composition and antioxidant activities of EOs from Azorean C. japonica sawdust (CJS) and resin-rich bark (CJRRB). The CJS and CJRRB EOs, obtained via hydrodistillation, showed different yield values (0.27% vs. 0.80% v/w, dry weight) and also different chemical profiles, as assessed using GC/MS. A total of 64 and 85 components were identified in CJS and CJRRB EOs, representing 95.7% and 96.9% of the total composition, respectively. The major components in CJS EO were oxygenated sesquiterpenes (mainly α+ß-eudesmol, 1-epicubenol, and cubebol), while in CJRRB EO, the major components were monoterpene hydrocarbons, including α-pinene, δ-3-carene, and limonene (66.6% vs. 6.4% for oxygenated sesquiterpenes and 0% vs. 64% for monoterpene hydrocarbons, respectively). Antioxidant activity was estimated using (i) two radical-based assays, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity, and (ii) a lipid model assay, ß-carotene-linoleic acid bleaching activity (BCBA). Both CJS and CJRRB EOs exhibited concentration-dependent antioxidant activities, and their DPPH, ABTS, and BCBA EC50 values were 1107 vs. 1275 µg/mL, 260 vs. 498 µg/mL, and 1764 vs. 662 µg/mL, respectively. The results indicate that both EOs were able to exert antioxidant activity via different mechanisms of action. Therefore, Azorean CJS and CJRRB may be sustainable sources for antioxidant compounds. This study expands the chemical and biological knowledge of CJBR EOs and, consequently, adds more value to the C. japonica EO industry.
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Osteomyelitis caused by non-Candida species is rare and often neglected, and current recommendations are based on primarily clinical experience and expert opinion. The objective of this study was to describe a case series of non-Candida fungal osteomyelitis. This retrospective study included 10 patients with non-Candida fungal osteomyelitis. Patients with osteomyelitis and microbiologically confirmed non-Candida species from bone fragment cultures were selected from the institution Infection Control Board database. Fusarium spp. were the most commonly isolated fungus from bone fragment cultures in five patients (50%). The majority did not present immunosuppression. The most common etiology was post-traumatic (n = 7, 70%), particularly open fractures. All patients were treated with antifungals associated with surgery. The antifungals used were itraconazole in five patients (50%), and voriconazole in another five patients (50%), with a median duration of antifungal therapy of four weeks (range: 3-25). There were no observed deaths within 30 days and one year. An antifungal approach combined with surgical treatment demonstrated favorable clinical outcomes, including low mortality rates and effective remission.
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Artificial intelligence has revolutionized many sectors with unparalleled predictive capabilities supported by machine learning (ML). So far, this tool has not been able to provide the same level of development in pharmaceutical nanotechnology. This review discusses the current data science methodologies related to polymeric drug-loaded nanoparticle production from an innovative multidisciplinary perspective while considering the strictest data science practices. Several methodological and data interpretation flaws were identified by analyzing the few qualified ML studies. Most issues lie in following appropriate analysis steps, such as cross-validation, balancing data, or testing alternative models. Thus, better-planned studies following the recommended data science analysis steps along with adequate numbers of experiments would change the current landscape, allowing the exploration of the full potential of ML.
[Box: see text].
Assuntos
Inteligência Artificial , Ciência de Dados , Aprendizado de Máquina , Nanopartículas , Nanopartículas/química , Humanos , Ciência de Dados/métodos , Nanotecnologia/métodos , Polímeros/químicaAssuntos
Leucemia Mieloide Aguda , Proteína Tumoral p73 , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/genética , Prognóstico , Proteína Tumoral p73/genética , Proteína Tumoral p73/metabolismo , Feminino , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Idoso , Regulação Leucêmica da Expressão Gênica , AdultoRESUMO
Anti-CD19 CAR-T cell therapy represents a breakthrough in the treatment of B-cell malignancies, and it is expected that this therapy modality will soon cover a range of solid tumors as well. Therefore, a universal cheap and sensitive method to detect CAR expression is of foremost importance. One possibility is the use of epitope tags such as c-Myc, HA or FLAG tags attached to the CAR extracellular domain, however, it is important to determine whether these tags can influence binding of the CAR with its target molecule. Here, we conducted in-silico structural modelling of an FMC63-based anti-CD19 single-chain variable fragment (scFv) with and without a c-Myc peptide tag added to the N-terminus portion and performed molecular dynamics simulation of the scFv with the CD19 target. We show that the c-Myc tag presence in the N-terminus portion does not affect the scFv's structural equilibrium and grants more stability to the scFv. However, intermolecular interaction potential (IIP) analysis reveals that the tag can approximate the complementarity-determining regions (CDRs) present in the scFv and cause steric impediment, potentially disturbing interaction with the CD19 protein. We then tested this possibility with CAR-T cells generated from human donors in a Nalm-6 leukemia model, showing that CAR-T cells with the c-Myc tag have overall worse antitumor activity, which was also observed when the tag was added to the C-terminus position. Ultimately, our results suggest that tag addition is an important aspect of CAR design and can influence CAR-T cell function, therefore its use should be carefully considered.
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The yellow fever (YF) vaccine is one of the safest and most effective vaccines currently available. Still, its administration in people living with HIV (PLWH) is limited due to safety concerns and a lack of consensus regarding decreased immunogenicity and long-lasting protection for this population. The mechanisms associated with impaired YF vaccine immunogenicity in PLWH are not fully understood, but the general immune deregulation during HIV infection may play an important role. To assess if HIV infection impacts YF vaccine immunogenicity and if markers of immune deregulation could predict lower immunogenicity, we evaluated the association of YF neutralization antibody (NAb) titers with the pre-vaccination frequency of activated and exhausted T cells, levels of pro-inflammatory cytokines, and frequency of T cells, B cells, and monocyte subsets in PLWH and HIV-negative controls. We observed impaired YF vaccine immunogenicity in PLWH with lower titers of YF-NAbs 30 days after vaccination, mainly in individuals with CD4 count <350 cells/mm3. At the baseline, those individuals were characterized by having a higher frequency of activated and exhausted T cells and tissue-like memory B cells. Elevated levels of those markers were also observed in individuals with CD4 count between 500 and 350 cells/mm3. We observed a negative correlation between the pre-vaccination level of CD8+ T cell exhaustion and CD4+ T cell activation with YF-NAb titers at D365 and the pre-vaccination level of IP-10 with YF-NAb titers at D30 and D365. Our results emphasize the impact of immune activation, exhaustion, and inflammation in YF vaccine immunogenicity in PLWH.
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BACKGROUND Evidence from randomized studies support complete over culprit-only revascularization for patients with acute coronary artery syndrome (ACS) and multivessel coronary artery diseases (MVD). Whether these findings extend to elderly patients, however, has not been thoroughly explored. METHODS We conducted a systematic review and meta-analysis comparing clinical outcomes of elderly individuals (defined as age ≥75 years) with ACS and MVD submitted to complete vs partial-only percutaneous coronary intervention (PCI). PubMed, Embase, and Cochrane were searched. We computed pooled hazard ratios with 95% confidence intervals (CI) to preserve time time-to-event data. RESULTS We included 7 studies, of which 2 were RCT and 5 were multivariable adjusted cohorts, comprising a total 10 147, of whom 43.8% underwent complete revascularization. As compared with partial-only PCI, complete revascularization was associated with a lower all-cause mortality (hazard ratio 0.71; 95% CI 0.600.85; P < 0.01), cardiovascular mortality (hazard ratio 0.64; 95% CI 0.520.79; P < 0.01), and recurrent myocardial infarction (hazard ratio 0.65; 95% CI 0.500.85; P < 0.01). There was no significant difference between groups regarding the risk of revascularizations (hazard ratio 0.80; 95% CI 0.531.20; P = 0.28). CONCLUSION Among elderly patients with ACS and multivessel CAD, complete revascularization is associated with a lower risk of all-cause mortality, cardiovascular mortality, and recurrent myocardial infarction.