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Damage to the genetic material of the cell poses a universal threat to all forms of life. The DNA damage response is a coordinated cellular response to a DNA break, key to which is the phosphorylation signalling cascade. Identifying which proteins are phosphorylated is therefore crucial to understanding the mechanisms that underly it. We have used SILAC-based quantitative phosphoproteomics to profile changes in phosphorylation site abundance following double stranded DNA breaks, at two distinct loci in the genome of the single cell eukaryote Trypanosoma brucei. Here, we report on the Trypanosoma brucei phosphoproteome following a single double strand break at either a chromosome internal or subtelomeric locus, specifically the Bloodstream form expression site. We detected >6500 phosphorylation sites, of which 211 form a core set of double strand break responsive phosphorylation sites. Along with phosphorylation of canonical DNA damage factors, we have identified two novel phosphorylation events on Histone H2A and find that in response to a chromosome internal break, proteins are predominantly phosphorylated, while a greater proportion of proteins dephosphorylated following a DNA break at a subtelomeric bloodstream form expression site. Our data represents the first DNA damage phosphoproteome and provides novel insights into repair at distinct chromosomal contexts in Trypanosoma brucei.
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Persistent infection with high-risk human papillomavirus remains the primary factor associated with the progression of cervical squamous intraepithelial lesions and the development of cervical cancer. Nevertheless, a combination of factors, including genetic predisposition, immune response, hormonal influences, and nutritional status, contribute synergistically to the development of cervical cancer. Among the various factors involved in the pathogenesis and therapy of cervical cancer, retinoids have gained considerable attention due to their multifaceted roles in different cellular processes. This review investigates defects within the vitamin A metabolism pathway and their correlation with cervical cancer. Additionally, it integrates epidemiological and experimental findings to discuss the potential utility of retinoid-based therapies, either alone or combined with other therapies, as agents against premalignant lesions and cervical cancer.
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Lesões Pré-Cancerosas , Retinoides , Neoplasias do Colo do Útero , Humanos , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/patologia , Feminino , Retinoides/uso terapêutico , Lesões Pré-Cancerosas/tratamento farmacológico , Lesões Pré-Cancerosas/patologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/tratamento farmacológico , Vitamina A/uso terapêuticoRESUMO
We conducted a multicenter and retrospective study to describe the use of botulinum toxin type A (BoNT-A) to treat post-stroke spasticity (PSS). Data were extracted from free-text in electronic health records (EHRs) in five Spanish hospitals. We included adults diagnosed with PSS between January 2015 and December 2019, stratified into BoNT-A-treated and untreated groups. We used EHRead® technology, which incorporates natural language processing and machine learning, as well as SNOMED CT terminology. We analyzed demographic data, stroke characteristics, BoNT-A use patterns, and other treatments. We reviewed the EHRs of 1,233,929 patients and identified 2190 people with PSS with a median age of 69 years; in total, 52.1% were men, 70.7% had cardiovascular risk factors, and 63.2% had suffered an ischemic stroke. Among the PSS patients, 25.5% received BoNT-A at least once. The median time from stroke to spasticity onset was 205 days, and the time from stroke to the first BoNT-A injection was 364 days. The primary goal of BoNT-A treatment was pain control. Among the study cohort, rehabilitation was the most common non-pharmacological treatment (95.5%). Only 3.3% had recorded monitoring scales. In conclusion, a quarter of patients with PSS received BoNT-A mainly for pain relief, typically one year after the stroke. Early treatment, disease monitoring, and better data documentation in EHRs are crucial to improve PSS patients' care.
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Toxinas Botulínicas Tipo A , Aprendizado de Máquina , Espasticidade Muscular , Processamento de Linguagem Natural , Acidente Vascular Cerebral , Humanos , Espasticidade Muscular/tratamento farmacológico , Espasticidade Muscular/etiologia , Toxinas Botulínicas Tipo A/uso terapêutico , Masculino , Feminino , Idoso , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Estudos Retrospectivos , Pessoa de Meia-Idade , Registros Eletrônicos de Saúde , Fármacos Neuromusculares/uso terapêutico , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Despite being considered a rare disease, Rett syndrome is a leading cause of profound cognitive impairment in females. This study explores game-based cognitive stimulation to enhance attention during learning tasks, offering an alternative treatment perspective. METHODS: Fifteen diagnosed Rett syndrome girls participated in four 24-minute sessions, including a 5-minute initial resting state recording. Primary indicators for analysis included relative power and spectral entropy. RESULTS: Significant findings indicated variations among conditions (resting state, active task, passive task) in response to stimulation. Notably, over four days, evolution occurred, characterized by decreasing delta power and increasing theta and beta power. Topographic maps confirmed these shifts, highlighting affected brain areas. Linear regression emphasized the most significant impact on the first day, with subsequent shifts towards higher frequencies, particularly during the resting state. By the fourth day, resting-state patterns resembled those during cognitive activities. CONCLUSION: Findings suggest cognitive stimulation induces substantial EEG spectral changes, potentially linked to cognitive enhancements in Rett syndrome. The shift towards higher frequency bands and increased spectral entropy align with enhanced brain activation during cognitive sessions, underscoring the potential of cognitive stimulation therapies and calling for further research to optimize abilities in individuals with Rett syndrome. IMPACT: Game-based cognitive stimulation induces substantial EEG changes in individuals with Rett syndrome, enhancing cognitive functions, notably attention during learning. This study conducts a distinctive examination, assessing the habituation paradigm through the combination of game-based cognitive stimulation and learning, providing valuable insights into enhancing attention in Rett syndrome. Impacting understanding of cognitive processes in Rett syndrome, this research reveals significant EEG variations during tasks, emphasizing the potential of cognitive stimulation for attention enhancement and the need for further research in tailored interventions.
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The primary goal of our review was to systematically explore and compare the state-of-the-art methodologies employed in the detection of pesticides, a critical component of global food safety initiatives. New approach methods in the fields of luminescent nanosensors, chromatography, terahertz spectroscopy, and Raman spectroscopy are discussed as precise, rapid, and versatile strategies for pesticide detection in food items and agroecological samples. Luminescent nanosensors emerge as powerful tools, noted for their portability and unparalleled sensitivity and real-time monitoring capabilities. Liquid and gas chromatography coupled to spectroscopic detectors, stalwarts in the analytical chemistry field, are lauded for their precision, wide applicability, and validation in diverse regulatory environments. Terahertz spectroscopy offers unique advantages such as noninvasive testing, profound penetration depth, and bulk sample handling. Meanwhile, Raman spectroscopy stands out with its nondestructive nature, its ability to detect even trace amounts of pesticides, and its minimal requirement for sample preparation. While acknowledging the maturity and robustness of these techniques, our review underscores the importance of persistent innovation. These methodologies' significance extends beyond their present functions, highlighting their adaptability to meet ever-evolving challenges. Environ Toxicol Chem 2024;43:1468-1484. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
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Praguicidas , Análise Espectral Raman , Praguicidas/análise , Monitoramento Ambiental/métodos , Contaminação de Alimentos/análiseRESUMO
HPV vaccination rates remain low among US adolescents, with only 54% completing the series in 2019. The vaccine is recommended at age 11-12 but can be given as early as age 9. Although it has been found that offering the vaccine earlier improves completion rates by age 13, parents remain reluctant to allow their younger children to initiate this vaccine. The purpose of this study was to better understand parental beliefs regarding receipt of the HPV vaccine among their children at ages 9-10. A 40 min phone interview was completed with 21 participants who were asked about their vaccine viewpoints. Even after receiving one-on-one education from a patient navigator, many caretakers expressed inadequate knowledge of the HPV vaccine and limited exposure to both positive and negative influences. The biggest concern was vaccine side effects, often resulting from a lack of medical understanding. Most parents were reluctant to vaccinate their children at a school-based clinic or pharmacy and believed that the government should not mandate HPV vaccination for public school attendance. Our study provides insight into parental beliefs and attitudes about HPV vaccination at age 9-10 years and barriers that need to be addressed.
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Aloina catillum is a variable moss typical of xerophytic environments in the Neotropics, characterized against other closely allied Aloina species with well-differentiated leaf border by its setae twisted to the left throughout. In order to clarify its variability and its relationships with the allied species with differentiated leaf border A. brevirostris, A. obliquifolia, and A. rigida, we performed an integrative study including sequence data from four markers (nuclear ITS, plastid atpB-rbcL, trnG, trnL-F), morphometry, and species assembling by automatic partitioning (ASAP) algorithm. Our data suggest that A. catillum consists of at least three species: A. calceolifolia (an earlier name for A. catillum), and two species described here as a new, A. bracteata sp. nov. and A. limbata sp. nov. This latter species includes the specimens previously identified as A. obliquifolia from South America. Additionally, some morphological and molecular variability was also detected in A. limbata, but was not consistent enough to be recognized taxonomically. The study supports the presence of A. brevirostris in the Neotropics and A. rigida is tentatively excluded from South America. Full descriptions of the A. catillum s.l. species and a diagnostic key to this complex in South America are provided.
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AIM: To assess the value of a prehabilitation program adapted to the current COVID-19 pandemic using a teleprehabilitation modality in a public Latin American hospital. METHODS: The medical records of candidates for elective colorectal cancer surgery (CRC) and who completed a teleprehabiltation program were analyzed. Sociodemographic, clinical, and functional variables were analyzed, such as cardiorespiratory capacity with the sit-to-stand test (STST), independence in activities of daily living with the Barthel index, balance with the five-times STST (FSTST) and fatigue with Brief Inventory Fatigue (BFI). The feasibility of the program was analyzed in terms of recruitment, retention, user satisfaction, and reporting of adverse events. RESULTS: Of 107 people recruited, 57 completed the program (54%, 68.78 ± 12.36 years). There was a significant difference in the BFI, FSTST, and STS 1-min scores after the intervention (p < .01), with an effect size (Cliff's delta) that varied between -.13 and .21. There were no differences in the Barthel index score. In relation to the viability of the program, 99% of patients referred for surgery could be recruited into the program, with 53% retention. Regarding user satisfaction with the program, seven items (77.7%) were rated as "very satisfied," and two items (22.3%) as "satisfied." No adverse events were recorded. CONCLUSION: The structured prehabilitation program adapted to teleprehabilitation for CRC candidates for surgery was effective in optimizing functional results prior to surgery and was feasible to implement in a public hospital with limited resources during the COVID-19 pandemic.
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COVID-19 , Neoplasias Colorretais , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Atividades Cotidianas , Estudos de Viabilidade , Pandemias/prevenção & controle , Neoplasias Colorretais/cirurgiaRESUMO
We aimed to compare rates and characteristics of suicide mortality in formerly incarcerated people with those of the general population in North Carolina. We conducted a retrospective cohort study of 266,400 people released from North Carolina state prisons between January 1, 2000, and March 1, 2020. Using direct and indirect standardization by age, sex, and calendar year, we calculated standardized suicide mortality rates and standardized mortality ratios comparing formerly incarcerated people with the North Carolina general population. We evaluated effect modification by race/ethnicity, sex, age, and firearm involvement. Formerly incarcerated people had approximately twice the overall suicide mortality of the general population for 3 years after release, with the highest rate of suicide mortality being observed in the 2-week period after release. In contrast to patterns in the general population, formerly incarcerated people had higher rates of non-firearm-involved suicide mortality than firearm-involved suicide mortality. Formerly incarcerated female, White and Hispanic/Latino, and emerging adult people had a greater elevation of suicide mortality than their general-population peers compared with other groups. These findings suggest a need for long-term support for formerly incarcerated people as they return to community living and a need to identify opportunities for interventions that reduce the harms of incarceration for especially vulnerable groups. This article is part of a Special Collection on Mental Health.
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Prisioneiros , Suicídio , Adulto , Humanos , Feminino , North Carolina/epidemiologia , Estudos Retrospectivos , Causas de MorteRESUMO
BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy is increasingly used in patients affected by B-cell lymphoma and acute lymphoblastic leukemia. For logistical reasons, initial apheresis products may be cryopreserved for shipment to manufacturing centers. Due to the characteristics of these patients, cells are often collected in large volumes, meaning more bags must be cryopreserved. This requires increased storage, time and monetary costs. In this context, we aimed to evaluate a high cell concentration cryopreservation protocol by centrifugation to standardize the initial CAR-T manufacturing procedure. MATERIALS AND METHODS: Sixty-eight processes of leukapheresis of 57 patients affected by refractory/relapsed B cell lymphoma and 9 patients affected by acute lymphoblastic leukemia who were eligible for anti-CD19 CAR-T cell treatment performed between June 2019 and October 2022 were analyzed. Whole blood count, percentage and number of T cells were assessed on the apheresis final product. The apheresis product, which was alternatively stored overnight at 4°C, was centrifuged, adjusting the volume to approximately 40 mL. The product was immediately cryopreserved to achieve a final cell concentration of 50-200×106 cells/ml for cryopreservation. RESULTS: Leukapheresis volume was reduced by almost fivefold (median: 185 to 40 mL), resulting in a higher product concentration in one bag. In addition, the number of non-target cells (monocytes, platelets and erythrocytes) was also reduced during the development of CAR T cell therapy, thereby maintaining T lymphocyte levels and providing a purer starting material. DISCUSSION: The advantages of the protocol include reducing economic costs, saving storage space, simplifying the manufacturing process, and facilitating shipping logistics. In conclusion, we present a validated, simple, and cost-effective cell enrichment processing protocol that provides high-quality cryopreserved products as starting material for the CAR-T cell manufacturing process.
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Spinal Cord Injury (SCI) is a common disease that usually limits the patient's independence by affecting their motor function. SCI patients usually present neuroplasticity, which allows brain signals transmission through spread pathways. Some innovative rehabilitation therapies, such as functional electrical stimulation (FES) or Brain-computer interfaces (BCIs) jointly with motor neuroprostheses, provide hope for functional restoration. BCIs require the analysis of event-related EEG potentials (ERPs). Movement-related cortical potentials (MRCPs) and event-related desynchroni-zation and synchronization (ERD/ERS) are the most commonly studied ERPs during motor activity. ERPs of healthy subjects may vary from SCI patients. Thus, this study aimed to compare ERPs between healthy subjects and SCI patients during upper-limb movements (forearm supination and pronation, and hand open). Differences between controls and SCI patients were shown in terms of ERPs' amplitude as well as in topographic maps. Changes in amplitude were more substantial in ERD potentials than in MRCPs, while topographic maps showed better localization of all features in healthy patients. The level of SCI injury determines the patients' mobility. A comparison between complete, partial and no motor function subjects showed lower values of feature's amplitudes in the latter group.Clinical Relevance- This demonstrates the existence of significant statistical differences between healthy and SCI subjects, and might be helpful when performing SCI rehabilitation techniques such as designing BCI and neuroprostheses, or analyzing and understanding the brain plasticity process.
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Traumatismos da Medula Espinal , Humanos , Traumatismos da Medula Espinal/reabilitação , Potenciais Evocados/fisiologia , Eletroencefalografia/métodos , Extremidade Superior , MovimentoRESUMO
High-Density Surface Electromyography (HD-sEMG) is a non-invasive technique for measuring the electrical activity of a muscle with multiple, closely spaced electrodes. Estimation of muscle force is one of the applications of HD-sEMG. Usually, validating different EMG-Force models entails simple movements limited to laboratory settings. The validity of these models in more ecological conditions, requesting force production over a wide frequency band, remains unknown. In this study, we, therefore, compare the results of force prediction using four different types of input force profiles that can be representative of daily life activities, and we investigate whether the crest factor of these different input signals affects force prediction. For predicting the force from sEMG signals, we used our real-time and convex methods. HD-sEMG signals were recorded with 144 channels from the biceps brachii, brachioradialis, and triceps (long, lateral, and medial head) muscles of 24 healthy subjects during random signal, random phase, Schroeder phase, and minimum crest factor (crestmin) signal. The correlation and coefficient of determination (R2) between measured and predicted forces were calculated for the different force feedback profiles. The crestmin signal showed significantly better results based on statistical tests (P-value < 0.05), with correlation and R2 equal to 0.92±0.03 and 0.86±0.05, respectively. The results demonstrate that the crest factor of input signals is a crucial parameter that can impact the performance of EMG-Force models and must be considered during training.Clinical Relevance- This study demonstrates that lower crest factor multisine force profiles result in improved fitness for force prediction and can be used as an alternative to random signals.
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Contração Isométrica , Músculo Esquelético , Humanos , Contração Isométrica/fisiologia , Músculo Esquelético/fisiologia , Eletromiografia/métodos , Braço/fisiologia , CotoveloRESUMO
Background: Acute appendicitis (AA) is the most common surgical emergency in children. Assessment scales improve the timely detection of cases. Objective: To evaluate the association of the Pediatric Appendicitis Scale (PAS) with hospital stay (HS) and postoperative complications of appendectomy. Material and methods: Observational, analytical, longitudinal and retrolective study. Patients from 2 months to 15 years of age, without comorbidities, who underwent appendectomy for complicated (CAA) and uncomplicated (UCAA) acute appendicitis were included. PAS score prior to an appendectomy was obtained, and the time of HS and postoperative complications were evaluated. Results: 64 patients were evaluated, age 8 (IQR 8-12) years, PAS score 6 (IQR 4-8). The time from the onset of symptoms to the request for care in the emergency department was shorter (p < 0.0001) and the total neutrophil count was higher (p = 0.001) in the CAA group. No difference was shown in the PAS score between patients with CAA and UCAA (6 [4-7] vs. 7 [4-8], p = 0.087]. A PAS score ≥ 7 was associated with an increased risk of prolonged HE (p = 0.007), but was not associated with postoperative complications. The PAS score alongside the time elapsed from the onset of symptoms until the assistance in the Pediatric Emergency Department, were associated with an increased risk of prolonged HE (R2 = 0.2246, p = 0.003). Conclusions: A PAS score ≥ 7 is associated with prolonged HS, likewise, the PAS score alongside the time elapsed between the onset of symptoms and assistance in emergency care is associated with prolonged HS.
Introducción: la apendicitis aguda (AA) es la patología quirúrgica de urgencia más común en niños. Las escalas de valoración mejoran la detección oportuna de casos. Objetivo: evaluar la asociación de la Escala pediátrica de apendicitis (PAS) con la estancia hospitalaria (EH) y las complicaciones postoperatorias de apendicectomía. Material y métodos: estudio observacional, analítico, longitudinal y retrolectivo. Se incluyeron pacientes de 2 meses a 15 años, sin comorbilidades, intervenidos por apendicectomía por apendicitis aguda complicada (AAC) y no complicada (AANC). Se obtuvo el puntaje PAS previo a apendicectomía y se evaluó la EH y complicaciones postoperatorias. Resultados: se evaluaron 64 pacientes, edad 8 (RIC 8-12) años, puntaje de PAS 6 (RIC 4-8). El tiempo desde el inicio de los síntomas hasta la atención en urgencias fue menor (p < 0.0001) y la cuenta de neutrófilos totales fue mayor (p = 0.001) en el Grupo de AAC. No hubo diferencia en el puntaje PAS entre pacientes con AAC y AANC (6 [4-7] frente a 7 [4-8], p = 0.087). El puntaje PAS ≥ 7 se asoció con incremento del riesgo de EH prolongada (p = 0.007), pero no con complicaciones postoperatorias. El puntaje PAS en conjunto con el tiempo transcurrido desde el inicio de los síntomas hasta la atención en Urgencias Pediátricas se asoció a incremento del riesgo de EH prolongada (R2 = 0.2246, p = 0.003). Conclusiones: el puntaje PAS ≥ 7 se asocia con EH prolongada, y el puntaje PAS en conjunto con el tiempo transcurrido entre el inicio de síntomas y la atención en urgencias se asocia a EH prolongada.
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Apendicite , Laparoscopia , Humanos , Criança , Apendicite/complicações , Apendicite/diagnóstico , Apendicite/cirurgia , Tempo de Internação , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Apendicectomia/efeitos adversos , Contagem de Leucócitos , Doença Aguda , Estudos RetrospectivosRESUMO
Brachybacterium conglomeratum, traditionally considered an environmental bacterium, has recently garnered attention for its potential involvement in human health. While prior research hinted at its pathogenic role in humans, our study aims to determine its prevalence and associations in diverse clinical contexts. We examined vaginal swabs from three distinct patient groups: patients with low-grade squamous intraepithelial lesions (LSIL), patients with cervicovaginal infections, and patients with a history of precancerous lesions undergoing follow-up. B. conglomeratum was present in all three patient groups, with the highest prevalence observed in the LSIL group. Statistically significant associations were primarily identified in the LSIL group, where B. conglomeratum was present in 60% of cases. Notably, the LSIL group exhibited coinfections with multiple high-risk oncogenotypes of human papillomavirus (HPV), suggesting potential synergistic effects, and understanding these microbial relationships and their influence on viral persistence, particularly with HPV, holds promise for mitigating HPV-related carcinogenesis. Furthermore, Gardnerella vaginalis and Atopobium vaginae were frequently detected in this group, along with Ureaplasma parvum as the predominant sexually transmitted bacterium. In all cases, B. conglomeratum was found in association with these microorganisms rather than as a sole pathogen. This coexistence underscores the intricate microbial interactions within cervicovaginal infections and precancerous lesions. This study marks the first report of B. conglomeratum prevalence in women with these clinical conditions.
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The application of an OSMAC (One Strain-Many Compounds) approach on the fungus Pleotrichocladium opacum, isolated from a soil sample collected on the coast of Asturias (Spain), using different culture media, chemical elicitors, and cocultivation techniques resulted in the isolation and identification of nine new compounds (8, 9, 12, 15-18, 20, 21), along with 15 known ones (1-7, 10, 11, 14, 19, 22-25). Compounds 1-9 were detected in fungal extracts from JSA liquid fermentation, compounds 10-12 were isolated from a solid rice medium, whereas compounds 14 and 15 were isolated from a solid wheat medium. Addition of 5-azacytidine to the solid rice medium caused the accumulation of compounds 16-18, whereas adding N-acetyl-d-glucosamine triggered the production of two additional metabolites, 19 and 20. Finally, cocultivation of the fungus Pleotrichocladium opacum with Echinocatena sp. in a solid PDA medium led to the production of five additional natural products, 21-25. The structures of the new compounds were elucidated by HRESIMS and 1D and 2D NMR as well as by comparison with literature data. DP4+ and mix-J-DP4 computational methods were applied to determine the relative configurations of the novel compounds, and in some cases, the absolute configurations were assigned by a comparison of the optical rotations with those of related natural products.
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In ordinary circumstances the highest frequency present in a wave is the highest frequency in its Fourier decomposition. It is however possible for there to be a spatial or temporal region where the wave locally oscillates at a still greater frequency in a phenomenon known as superoscillation. Superoscillations find application in wide range of disciplines, but at present their generation is based upon constructive approaches that are difficult to implement. Here, we address this, exploiting the fact that superoscillations are a product of destructive interference to produce a prescription for generating superoscillations from the superposition of arbitrary waveforms. As a first test of the technique, we use it to combine four quasisinusoidal THz waveforms to produce THz optical superoscillations for the first time. The ability to generate superoscillations in this manner has potential application in a wide range of fields, which we demonstrate with a method we term "superspectroscopy." This employs the generated superoscillations to obtain an observed enhancement of almost an order of magnitude in the spectroscopic sensitivity to materials whose resonance lies outside the range of the component waveform frequencies.
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Race is a social construct, commonly used in epidemiologic research to adjust for confounding. However, adjustment of race may mask racial disparities, thereby perpetuating structural racism. We conducted a systematic review of articles published in Epidemiology and American Journal of Epidemiology between 2020 and 2021 to (1) understand how race, ethnicity, and similar social constructs were operationalized, used, and reported; and (2) characterize good and poor practices of utilization and reporting of race data on the basis of the extent to which they reveal or mask systemic racism. Original research articles were considered for full review and data extraction if race data were used in the study analysis. We extracted how race was categorized, used-as a descriptor, confounder, or for effect measure modification (EMM)-and reported if the authors discussed racial disparities and systemic bias-related mechanisms responsible for perpetuating the disparities. Of the 561 articles, 299 had race data available and 192 (34.2%) used race data in analyses. Among the 160 US-based studies, 81 different racial categorizations were used. Race was most often used as a confounder (52%), followed by effect measure modifier (33%), and descriptive variable (12%). Fewer than 1 in 4 articles (22.9%) exhibited good practices (EMM along with discussing disparities and mechanisms), 63.5% of the articles exhibited poor practices (confounding only or not discussing mechanisms), and 13.5% were considered neither poor nor good practices. We discuss implications and provide 13 recommendations for operationalization, utilization, and reporting of race in epidemiologic and public health research.
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Etnicidade , Saúde Pública , Humanos , Estados Unidos/epidemiologia , Coleta de Dados , Viés , Racismo SistêmicoRESUMO
Resumen La peritonitis por neumococo comprende un pequeno subconjunto de pacientes con enfermedad invasiva (ENI). Durante 15 años (2005-2020) de vigilancia de ENI en un hospital de pediatría, se detectaron 5 casos de peritonitis primaria. Los pacientes, 3 ninas y 2ninos con una media de edad de 5 anos, experimentaron signos y síntomas peritoneales; 3 de ellos presentaban síndrome nefrótico. En coincidencia con los perfiles locales, todos los aislamientos fueron sensibles a betalactámicos, una cepa expresó resistencia a tetraciclina y cotrimoxazol y otra solo a cotrimoxazol. Los serotipos encontrados en 4/5 cepas (una resultó no viable) fueron 1, 19F, 15C y 23A. Los ninos fueron tratados con cefalosporinas de tercera generación o con ampicilina, gentamicina y metronidazol; todos evolucionaron favorablemente. Se destaca la importancia del hallazgo de Streptococcus pneumoniae en peritonitis primarias en niños. Este trabajo contribuye al conocimiento de esta enfermedad en particular y al de la epidemiología local de la ENI.
Abstract Pneumococcal peritonitis represents a small subset of patients suffering from inva-sive pneumococcal disease (IPD). We describe 5 cases of primary peritonitis documented in the pediatric hospital over 15 years (2005-2020) of IPD surveillance. The patients, 3girls and 2boys with a mean age of 5 years, experienced peritoneal signs and symptoms; 3of them suffered from nephrotic syndrome. Based on the local resistance profiles, all isolates were sensitive to beta-lactams, one strain showed resistance to cotrimoxazole and tetracycline while another strain, to cotrimoxazole only. Serotypes found in 4/5 strains (one was non-viable) were: 1, 19F, 15C and 23A. Children were treated with third-generation cephalosporins or ampicillin, gentamicin and metronidazole and all of them evolved favorably. Pneumococcal etiology should be included in the differential diagnosis of acute abdominal pain in children. Our study aims to contribute to the knowledge of this condition and to the local epidemiology of IPD.
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Acyl-CoA-thioesterases, which hydrolyze acyl-CoA-esters and thereby release the respective acid, have essential functions in cellular metabolism and have also been used to produce valuable compounds in biotechnological processes. Thioesterase YciA originating from Haemophilus influenzae has been previously used to produce specific dicarboxylic acids from CoA-bound intermediates of the ethylmalonyl CoA pathway (EMCP) in Methylorubrum extorquens. In order to identify variants of the YciA enzyme with the capability to hydrolyze so far inaccessible CoA-esters of the EMCP or with improved productivity, we engineered the substrate-binding region of the enzyme. Screening a small semi-rational mutant library directly in M. extorquens yielded the F35L variant which showed a drastic product level increase for mesaconic acid (6.4-fold) and 2-methylsuccinic acid (4.4-fold) compared to the unaltered YciA enzyme. Unexpectedly, in vitro enzyme assays using respective M. extorquens cell extracts or recombinantly produced thioesterases could not deliver congruent data, as the F35L variant showed strongly reduced activity in these experiments. However, applied in an Escherichia coli production strain, the protein variant again outperformed the wild-type enzyme by allowing threefold increased 3-hydroxybutyric acid product titers. Saturation mutagenesis of the codon for position 35 led to the identification of another highly efficient YciA variant and enabled structure-function interpretations. Our work describes an important module for dicarboxylic acid production with M. extorquens and can guide future thioesterase improvement approaches. KEY POINTS: ⢠Substitutions at position F35 of YciAHI changed the productivity of YciA-based release of carboxylic acid products in M. extorquens AM1 and E. coli. ⢠YciAHI F35N and F35L are improved variants for dicarboxylic production of 2-methylsuccinic acid and mesaconic acid with M. extorquens AM1. ⢠In vitro enzyme assays did not reveal superior properties of the optimized protein variants.