Knowledge Graph Enhanced Transformers for Diagnosis Generation of Chinese Medicine / 中国结合医学杂志

Chinese medicine (CM) diagnosis intellectualization is one of the hotspots in the research of CM modernization. The traditional CM intelligent diagnosis models transform the CM diagnosis issues into classification issues, however, it is difficult to solve the problems such as excessive or similar categories. With the development of natural language processing techniques, text generation technique has become increasingly mature. In this study, we aimed to establish the CM diagnosis generation model by transforming the CM diagnosis issues into text generation issues. The semantic context characteristic learning capacity was enhanced referring to Bidirectional Long Short-Term Memory (BILSTM) with Transformer as the backbone network. Meanwhile, the CM diagnosis generation model Knowledge Graph Enhanced Transformer (KGET) was established by introducing the knowledge in medical field to enhance the inferential capability. The KGET model was established based on 566 CM case texts, and was compared with the classic text generation models including Long Short-Term Memory sequence-to-sequence (LSTM-seq2seq), Bidirectional and Auto-Regression Transformer (BART), and Chinese Pre-trained Unbalanced Transformer (CPT), so as to analyze the model manifestations. Finally, the ablation experiments were performed to explore the influence of the optimized part on the KGET model. The results of Bilingual Evaluation Understudy (BLEU), Recall-Oriented Understudy for Gisting Evaluation 1 (ROUGE1), ROUGE2 and Edit distance of KGET model were 45.85, 73.93, 54.59 and 7.12, respectively in this study. Compared with LSTM-seq2seq, BART and CPT models, the KGET model was higher in BLEU, ROUGE1 and ROUGE2 by 6.00-17.09, 1.65-9.39 and 0.51-17.62, respectively, and lower in Edit distance by 0.47-3.21. The ablation experiment results revealed that introduction of BILSTM model and prior knowledge could significantly increase the model performance. Additionally, the manual assessment indicated that the CM diagnosis results of the KGET model used in this study were highly consistent with the practical diagnosis results. In conclusion, text generation technology can be effectively applied to CM diagnostic modeling. It can effectively avoid the problem of poor diagnostic performance caused by excessive and similar categories in traditional CM diagnostic classification models. CM diagnostic text generation technology has broad application prospects in the future.

The Value Generation of College Students’ Responsibility Ethics in Major Public Emergencies / 中国医学伦理学

The outbreak of major public emergencies is an important practical issue that affects social development and human survival and security. In the face of major public emergencies, college students in the new era must have a strong sense of responsibility and mission. This paper took the formation value of college students’ responsibility ethics as a logical clue, deeply analyzed the subject-object function relationship of college students’ responsibility ethics in major public emergencies, and combined the philosophy of subjectivity to reveal the contradictory connotations of college students’ subjects, that is, the contradictory relationship between spontaneity and consciousness, selfishness and dedication, passivity and initiative, and relyed on the connotation logic of responsibility ethics to promote the sense of responsibility and mission of college students in major public emergencies, so that they can develop to a higher level, thus realizing the ultimate goal of generating the value of responsibility ethics.

Application of metagenomic next-generation sequencing in prevention and control of infection in solid organ transplantation / 器官移植

Organ transplantation has become an effective treatment for multiple end-stage diseases. However, the recipients of organ transplantation need to take immunosuppressive drugs for a long time after operation, which leads to low immune function and relatively high incidence of bacterial, viral and fungal infections. Traditional microbial detection methods, such as pathogen culture, immunological detection and polymerase chain reaction, have been widely applied in infection detection, whereas these methods may cause problems, such as long detection time and presumed pathogens. Metagenomic next-generation sequencing has been widely adopted in infection prevention and control in organ transplantation in recent years due to high detection rate and comprehensive detection of pathogen spectrum. In this article, the application of metagenomic next-generation sequencing in the prevention and control of infection in solid organ transplantation was reviewed, aiming to provide reference for the diagnosis and treatment of transplantation-related infection.

Potencial transmisión congénita de la enfermedad de Chagas en la segunda generación de jóvenes embarazadas que asistieron a su control prenatal en el departamento de Cordillera, Paraguay

Trypanosoma cruzi es el agente causal de la enfermedad de Chagas. En Paraguay se estima que existen 165.000 personas infectadas y actualmente la principal vía de transmisión es la congénita, con una prevalencia del 5% y con alrededor de 400 niños infectados nacidos por año. El departamento de Cordillera es área endémica de la Región Oriental del país, donde se implementó el Programa de Control Prenatal de Chagas en el año 1995. El objetivo de este estudio fue inferir sobre la potencial transmisión congénita de la enfermedad de Chagas en jóvenes embarazadas de segunda generación de Cordillera que asistieron a su control prenatal en el período 2010-2012, 15 años después de la implementación del Programa de Control Prenatal. De 9.588 embarazadas; 482 fueron seropositivas (5%); 2,74% en el grupo de 12 a 19 años, 4,93% de 20 a 30 años, 8,03% de 31 a 40 años y 16,11% de 41 a 48 años. Para estimar el origen de la transmisión congénita de segunda generación se tuvo en cuenta a las 72 seropositivas de 12 a 19 años y según la base de datos de las respectivas madres 61 eran seropositivas. Con esta información se estima que la transmisión a embarazadas de segunda generación de 12 a 19 años fue congénita en un 85% indicando una transmisión congénita muy significativa en la población de estudio. Esta información ayudaría al Programa Nacional de Chagas en el fortalecimiento del control de la transmisión congénita de la enfermedad de Chagas en el país.

Trypanosoma cruzi is the causative agent of Chagas disease. In Paraguay, it is estimated that 165,000 people are infected and currently the main route of transmission is the congenital one, with a prevalence of 5% and about 400 infected children are born per year. The Department of Cordillera is an endemic area of the Eastern Region of the country, where the Chagas Prenatal Control Program was implemented in 1995. The aim of this study was to infer the potential congenital transmission of Chagas disease towards second generation pregnant women from the Department of Cordillera who attended their prenatal control in the period 2010-2012, 15 years after the implementation of the Prenatal Control Program. Of 9,588 pregnant women; 482 were seropositive (5%); 2.74% in the group aged 12 to 19 years, 4.93% aged 20 to 30 years, 8.03% aged 31 to 40 years, and 16.11% aged 41 to 48 years. To estimate the origin of second generation congenital transmission, the 72 seropositive women aged 12 to 19 years were taken into account and according to the database of their respective mothers, 61 mothers of the 72 were seropositive. With this información, it can be estimated that 85% of the transmission to second generation pregnant women aged 12 to 19 years was congenital showing a very significant congenital transmission in the study population. This information could help the National Chagas Program in strengthening the control of congenital transmission of Chagas disease in the country.

Investigation of the molecular genetic causes of non-syndromic primary ovarian ınsufficiency by next generation sequencing analysis

ABSTRACT Objective: The aim of this study is to investigate the molecular genetic causes of non-syndromic primary ovarian insufficiency (POI) cases with the gene panel based on next generation sequencing analysis and to establish the relationship between genotype and phenotype. Subjects and methods: Twenty three cases aged 14-40 years followed up with POI were included. Patients with a karyotype of 46, XX, primary or secondary amenorrhea before the age of 40, with elevated FSH (>40 IU/mL) and low AMH levels (<0.03 ng/mL) were included in the study. Molecular genetic analyzes were performed by the next generation sequencing analysis method targeted with the TruSightTM Exome panel. Results: Median age of the cases was 17.8 (14.0-24.3) years, and 12 (52%) cases admitted before the age of 18. Fifteen (65%) patients had consanguineous parents. In 2 (8.6%) cases, variants detected were in genes that have been previously proven to cause POI. One was homozygous variant in FIGLA gene and the other was homozygous variant in PSMC3IP gene. Heterozygous variants were detected in PROK2, WDR11 and CHD7 associated with hypogonadotropic hypogonadism, but these variants are insufficient to contribute to the POI phenotype. Conclusion: Genetic panels based on next generation sequencing analysis technologies can be used to determine the molecular genetic diagnosis of POI, which has a highly heterogeneous genetic basis.

Tessituras de memórias: o Instituto Fernandes Figueira pelo olhar geracional / Interweaving memories: the Fernandes Figueira Institute through a generational perspective

Resumo Recuperamos memórias do Instituto Fernandes Figueira via o cuidado que reúne crianças doentes e suas mães. A categoria analítica geração sustenta o argumento do instituto como espaço de experiências e memórias. Interpretamos três fontes de memórias: (1) a pesquisa de Marismary Horsth De Seta com a geração que chegou no instituto na década de 1940; (2) o relatório de atividades do instituto de 1973; (3) três entrevistas com trabalhadores admitidos na década de 1980. Concluímos que o cuidado com as crianças e, por conseguinte, um olhar para as mulheres nessa relação se dão em sintonia com a transição epidemiológica global, complexificando o perfil da atenção do instituto.

Abstract Memories of care involving sick children and their mothers at the Fernandes Figueira Institute (Instituto Fernandes Figueira) are retrieved. The analysis using a generational perspective reveals the institute as a space of experiences and memories. Three sources of memories are analysed: (1) the research by Marismary Horsth De Seta with the generation that reached the institute in the 1940s; (2) the institute's 1973 activity report; (3) three interviews with workers admitted in the 1980s. It is concluded that care for children, and therefore interest in their mothers, is aligned with the global epidemiological transition, increasing the complexity of the profile of care given at the institute.

Effects of environmental stability and phycoperiphyton structure on the macroinvertebrate community of regulated Andean rivers / Efectos de la estabilidad ambiental y estructura del ficoperifiton en la comunidad de macroinvertebrados en ríos andinos regulados

Introduction: The variability in the structure of aquatic communities is frequently attributed to environmental changes; however, in stable environments such as regulated rivers, trophic interactions could be another key environmental factor determining the structure of these communities. These alterations could cause a greater growth of algae, and in turn, changes in the functional groups and in the composition of the macroinvertebrate community favoring the dominance of certain groups of organisms. Objective: To identify the effects of environmental variations and changes in the structure of the phycoperiphyton on the macroinvertebrate community of regulated Andean rivers. Methods: We analyzed environmental and biological data collected in quarterly samples carried out between 2010 and 2018 in two rivers of the Central Andes (Antioquia - Colombia), for a total of 27 samples. Sample collections used standardized methods. Different statistical models were used to establish spatial and temporal patterns of the environmental variables, of the abundance and/or density and diversity of phycoperiphyton and macroinvertebrates, as well as the trophic relationships that exists between them. Results: We found that regulated rivers present relatively little environmental variability. The environmental parameters with the greatest variation were temperature, turbidity, and orthophosphates; these last two were the abiotic variables with the greatest contribution to benthic instability. Conclusion: The presence of scraping and foraging macroinvertebrates was more affected by the stability of the phycoperiphyton density than by environmental variables, showing the importance of trophic interactions in regulated rivers and the bottom up control in these ecosystems.

Introducción: La variabilidad en la estructura de las comunidades acuáticas se atribuye frecuentemente a cambios ambientales, no obstante, en ambientes estables como ríos regulados, las interacciones tróficas podrían ser otro factor ambiental clave determinante de la estructura de estas comunidades. Estas alteraciones podrían provocar un mayor crecimiento de algas y, a su vez, cambios en los grupos funcionales y en la composición de la comunidad de macroinvertebrados favoreciendo la dominancia de determinados grupos de organismos. Objetivo: Identificar el efecto de los cambios ambientales y de la estructura del ficoperifiton sobre la comunidad de macroinvertebrados de ríos Andinos regulados. Métodos: Se analizaron datos ambientales y biológicos recolectados en muestreos trimestrales realizados entre 2010 y 2018 en dos ríos de los Andes Centrales (Antioquia - Colombia), para un total de 27 muestras. La recolección de muestras empleó métodos estandarizados. Se utilizaron diferentes modelos estadísticos para establecer patrones espaciales y temporales de las variables ambientales, de la abundancia y/o densidad y diversidad de ficoperifiton y de los macroinvertebrados, así como las relaciones tróficas que existen entre ellos. Resultados: Se encontró que los ríos regulados presentan relativamente poca variabilidad ambiental. Los parámetros ambientales con mayor variación fueron: temperatura, turbidez y ortofosfatos; las dos últimas variables abióticas fueron las que más aportaron a la inestabilidad bentónica. Conclusión: La presencia de macroinvertebrados raspadores y recolectores fue más afectada por la estabilidad de la densidad del ficoperifiton que por las variables ambientales, evidenciando la importancia de las interacciones tróficas en ríos regulados y el control bottoom up en estos ecosistemas.

Silage quality and bacterial diversity of silages inoculated with Listeria monocytogenes and Lacticaseibacillus paracasei_6714

Introduction: King grass (Cenchrus purpureus (Schumach.) Morrone, syn. Pennisetum purpuphoides) and pineapple peel (Ananas comosus) silages are food alternatives for livestock in conditions of feed shortage. Objective: To describe the dynamics of the microbiota present in king grass and pineapple silage during the fermentation process using next generation sequencing (NGS) and to evaluate the protective effect of Lacticaseibacillus paracasei_6714 as a silage inoculum against Listeria monocytogenes. Methods: We used an unrestricted randomized design to characterize the microbiota present in silages made from king grass harvested 70 days after regrowth and pineapple peel. We inoculated mixtures of grass and peel with L. paracasei_6714 or L. monocytogenes, or both, with a non-inoculated treatment as control. The nutritional and fermentative profile was evaluated after 30 days. After 15 and 30 days of fermentation, we used 16S rRNA analysis to determine the dynamics and diversity of the microbiota in the inoculated and control silages. Result: Dry matter content and digestibility did not differ significantly; however, there were differences in crude protein, pH and organic acids. We obtained 4432 amplicon sequence variants of Proteobacteria, Firmicutes, Bacterioidetes, Actinobacteria, Verrucomicrobia, Planctomycetes and Patescibacteria. The relative abundance of each phylum varied depending on the material and fermentation period. Phylum similarity was over 70 % (but not greater than 50 % with Bray-Curtis at the species level). Conclusion: These bacterial communities seem to have an important role during silage fermentation. Proper management of silage processing can reduce or eliminate pathogenic bacteria.

Introducción: Los ensilajes del pasto king grass (Cenchrus purpureus (Schumach.) Morrone, syn. Pennisetum purpuphoides) y cáscaras de piña (Ananas comosus) son alternativas de alimento para ganado en condiciones de escasez alimentaria. Objetivo: Describir las dinámicas de la microbiota presente en los ensilajes de king grass y piña durante el proceso de fermentación usando secuenciación de próxima generación (NGS) y evaluar el efecto de protección de Lacticaseibacillus paracasei_6714 como inoculante de ensilaje ante Listeria monocytogenes. Métodos: Usamos un diseño aleatorio no restringido para caracterizar la microbiota presente en ensilajes de king Grass cosechados 70 días después de rebrote y de cáscaras de piña. Inoculamos mezclas de pasto y cáscara con L. paracasei_6714 o L. monocytogenes, o ambos, con un tratamiento control sin inocular. El perfil nutricional y de fermentación fue evaluado luego de 30 días. Después de 15 y 30 días de fermentación, usamos un análisis de para determinar la dinámicas y diversidad de la microbiota en los ensilajes inoculados y control. Resultados: Los contenidos de materia seca y digestibilidad, no difirieron significativamente; sin embargo, hubo diferencias en proteína cruda, pH y ácidos orgánicos. Obtuvimos 4 432 secuencias variantes de amplicon de Proteobacteria, Firmicutes, Bacterioidetes, Actinobacteria, Verrucomicrobia, Planctomycetes y de Patescibacteria. La abundancia relativa de cada filo vario dependiendo del material y periodo de fermentación. Similitudes de filo fueron mayores al 70 % (pero no mayor que 50 % con Bray-Curtis a nivel de especie). Conclusión: Estas comunidades bacterianas parecen cumplir un papel importante durante la fermentación del ensilaje. Un manejo apropiado del proceso de ensilaje puede reducir o eliminar baterías patogénicas.

Clinicopathological and molecular analyses of uterine carcinosarcomas using next-generation sequencing: A single-center experience

Background: Uterine carcinosarcomas (UCS) constitute 3–4% of all uterine malignancies and 16% of deaths caused due to uterine neoplasms. Aim: In this study, we aimed to perform DNA-based mutation analysis in 12 genes (KRAS, NRAS, EGFR, C-KIT, BRAF, PDGFRA, ALK, ERBB2, ERBB3, ESR1, RAF1, PIK3CA) to determine the molecular subtypes of UCS using next-generation sequencing (NGS) in patients with aggressive UCS and poor prognosis. We aimed to compare the results of our analysis with clinicopathological data to contribute to the development of targeted therapy approaches related to the molecular changes of UCS. Materials and Methods: In this study, we included 12 cases diagnosed with uterine carcinosarcomas and examined the changes in oncogenes that play a role in UCS pathogenesis. For the analysis of mutation, the clinicopathological data were compared with the variations in the DNA-based gene panel consisting of 12 genes and 1237 variants in the UCS using the NGS method. Results: EGFR mutation was found in 91.7% of the cases, mutation in 41.7%, PDGFRA mutation in 25%, KRAS and PIK3CA mutation in 16.7%, and C-KIT mutation in 8.3% of the cases. Although no statistical significance was found between the detected mutation and clinicopathological data, it was concluded that PDGFRA mutation might be associated with advanced-stage disease development. Conclusion: This study's findings regarding different molecular types of UCS and information on oncogenesis of UCS can provide inferences for targeted therapies in the future by identifying targetable mutations representing early oncogenic events and thereby contribute toward further studies on this subject.

Next-generation sequencing-based genetic testing and phenotype correlation in retinitis pigmentosa patients from India

Purpose: Inherited retinal dystrophies (IRD) are a heterogeneous group of retinal diseases leading to progressive loss of photoreceptors through apoptosis. Retinitis pigmentosa (RP) is considered the most common form of IRD. Panel?based testing in RP has proven effective in identifying the causative genetic mutations in 70% and 80% of the patients. This is a retrospective, observational, single?center study of 107 RP patients who had undergone next?generation sequencing?based targeted gene panel testing for IRD genes. These patients were inspected for common phenotypic features to arrive at meaningful genotype–phenotype correlation. Methods: Patients underwent complete ophthalmic examination, and blood was collected from the proband for DNA extraction after documenting the pedigree. Targeted Next Generation Sequencing (NGS) was done by panel?based testing for IRD genes followed by co?segregation analysis wherever applicable. Results: Of the 107 patients, 72 patients had pathogenic mutations. The mean age of onset of symptoms was 14 ± 12 years (range: 5–55). Mean (Best Corrected Visual Acuity) BCVA was 6/48 (0.9 logMAR) (range 0.0–3.0). At presentation, over one?third of eyes had BCVA worse than 6/60 (<1 logMAR). Phenotype analysis with the gene defects showed overlapping features, such as peripheral well?defined chorioretinal atrophic patches in patients with CERKL, PROM1, and RPE65 gene mutations and large macular lesions in patients with RDH12 and CRX gene mutations, respectively. Nummular or clump?like pigmentation was noted in CRB1, TTC8, PDE6A, and PDE6B. Conclusion: NGS?based genetic testing can help clinicians to diagnose RP more accurately, and phenotypic correlations can also help in better patient counselling with respect to prognosis and guidance regarding ongoing newer gene?based therapies.

Implementación asistencial de estudios genómicos aplicados al diagnóstico molecular / Implementation of genomic studies applied to molecular diagnostics

El Hospital Garrahan ha sido pionero en el diagnóstico molecular de patologías pediátricas en Argentina. Los avances tecnológicos de las últimas décadas en el área de la biología molecular, sentaron las bases para la optimización y ampliación del diagnóstico molecular a partir de la secuenciación masiva en paralelo de múltiples genes. El presente trabajo describe el proceso de implementación de los estudios de secuenciación de nueva generación y el desarrollo de la Unidad de Genómica en un hospital público pediátrico de alta complejidad, así como su impacto en las capacidades diagnósticas de enfermedades poco frecuentes de origen genético. La creación del Grupo Interdisciplinario de Estudios Genómicos constituyó la vía institucional para la toma de decisiones que implican la implementación de nuevos estudios genómicos y el establecimiento de prioridades diagnósticas, extendiendo la disponibilidad del diagnóstico molecular a más disciplinas. La Unidad de Genómica trabaja en diseñar las estrategias que permitan la mayor optimización de los recursos con los que cuenta el hospital, teniendo en cuenta el equipamiento disponible, las prioridades establecidas y la frecuencia de las distintas patologías. Se demuestra el salto significativo operado en nuestras capacidades diagnósticas, tanto en la variedad de enfermedades como en el número de genes analizados, habiendo estudiado a la fecha alrededor de 2.000 pacientes, muchos de los cuales ven de este modo finalizada su odisea diagnóstica. Los estudios de NGS se han convertido en una herramienta de la práctica diaria para la atención de un número importante de pacientes de nuestro hospital. Continuaremos trabajando para ampliar su aplicación a la mayor cantidad de patologías, a través de los mecanismos institucionales ya existentes (AU)

The Garrahan Hospital has been a pioneer in the molecular diagnosis of pediatric diseases in Argentina. The technological advances of the last decades in the area of molecular biology have laid the foundations for the optimization and expansion of molecular diagnostics through massive parallel sequencing of multiple genes. This study describes the process of implementation of next-generation sequencing studies and the development of the Genomics Unit in a public pediatric tertiary hospital, and its impact on the capacity to diagnose rare diseases of genetic origin. The creation of the Interdisciplinary Group of Genomic Studies constituted the institutional pathway for decision-making involving the implementation of new genomic studies and the establishment of diagnostic priorities, extending the availability of molecular diagnostics to additional disciplines. The Genomics Unit is working to design strategies that allow for optimization of the resources available to the hospital, taking into account the equipment available, the priorities established, and the frequency of the different diseases. It demonstrates the significant leap in our diagnostic capabilities, both in the variety of diseases and in the number of genes analyzed. To date, around 2,000 patients have been studies, many of whom have thus completed their diagnostic odyssey. NGS studies have become a tool in daily practice for the care of a significant number of patients in our hospital. We will continue working to expand its application to as many diseases as possible, through the existing institutional mechanisms (AU)

IMPACT OF EMOTIONAL INTELLIGENCE ON ACADEMIC STRESS: A QUALITATIVE STUDY

Modern technology has become an integral part of the daily lives of the new generation in the fast- changing 21st century. As a result of instant access to digital information and communication technologies via mobile phones and the internet, this generation is called the 'Digital Generation'. Without understanding real love and association with family and friends, they con?ne themselves to the digital world. People with high emotional intelligence (EI) feel a sense of association and belongingness. A person's emotional intelligence is their ability to comprehend and cope with dif?cult and complex situations in life. By overcoming stress, EI can enhance productivity. An analysis of the relationship between Emotional Intelligence and Academic Stress is presented in this paper

Characterization of third generation cephalosporin-resistant Escherichia coli clinical isolates from Ushuaia, Argentina / Caracterización de aislamientos clínicos de Escherichia coli resistente a cefalosporinas de tercera generación de Ushuaia, Argentina

Abstract Escherichia coli is one of the main human pathogens causing different hospital- and community-acquired infections. During the period from January 2013 to March 2015, 1.96% (32/1632) of E. coli isolates recovered at the Hospital Regional de Ushuaia, Tierra del Fuego province, were resistant to third-generation cephalosporins (TGCs). These isolates were resistant to cefotaxime (91%) and/or ceftazidime (28%). No resistance to carbapenems was detected. Twenty-six isolates were positive for blaCTX-M gene, grouped as CTX-M-1/15 (54%); CTX-M-9/14 (25%); CTX-M-2 (17%); and CTX-M-1/15 plus CTX-M-9/14 (4%). Five TGC-resistant strains were positive for blaCMY gene, while one strain harbored TEM-19 ESBL. Twelve isolates were identified as ST131 E. coli hyperepidemic clone, and one as ST69. Genome sequence analysis of seven blaCTX-M-15 E. coli selected isolates confirm the circulation of ST131, ST617 and ST405 international high-risk clones in the city of Ushuaia.

Resumen Escherichia coli es uno de los principales patógenos humanos causantes de diferentes infecciones de inicio hospitalario y comunitario. Se determinó que el 1,96% (32/1.632) de los aislamientos de E. coli recuperados entre enero de 2013 y marzo de 2015 en el Hospital Regional de Ushuaia, provincia de Tierra del Fuego, fueron resistentes a cefalosporinas de tercera generación (CTG). Estos aislamientos fueron resistentes a cefotaxima (91%) y/o a ceftazidima (28%). No se detectó resistencia a los carbapenemes. Veintiséis aislamientos fueron positivos para el gen blaCTX-M, agrupados como CTX-M-1/15 (54%), CTX-M-9/14 (25%), CTX-M-2 (17%) y CTX-M-1/15 más CTX-M-9/14 (4%). Cinco cepas resistentes a CTG dieron positivo para el gen blaCMY, mientras que un aislamiento presentó la BLEE TEM-19. Doce aislamientos se identificaron como clon hiperepidémico E. coli ST131 y uno como ST69. El análisis de las secuencias del genoma de siete aislamientos seleccionados de E. coli blaCTX-M-15 confirmó la circulación de los clones internacionales de alto riesgo ST131, ST617 y ST405 en la ciudad de Ushuaia.

Molecular characterization & recombination analysis of complete enterovirus-88 isolated from acute flaccid paralysis cases in India

Background & objectives: Focus on non-polio enteroviruses (NPEVs) causing acute flaccid paralysis (AFP) due to myelitis has increased with the containment of the poliovirus. Enterovirus-B88 (EV-B88) has been associated with the AFP cases in Bangladesh, Ghana, South Africa, Thailand and India. In India, EV-B88 infection was linked to AFP a decade ago; however, to date, no complete genome has been made available. In this study, the complete genome sequence of EV-B88 was identified and reported from two different States (Bihar and Uttar Pradesh) in India using the next-generation sequencing technique. Methods: Virus isolation was performed on the three AFP suspected cases as per the WHO-recommended protocol. Samples showing cytopathic effects in the human Rhabdocarcinoma were labelled as NPEVs. Next-generation sequencing was performed on these NPEVs to identify the aetiological agent. The contiguous sequences (contigs) generated were identified, and reference-based mapping was performed. Results: EV-B88 sequences retrieved in our study were found to be 83 per cent similar to the EV-B88 isolate from Bangladesh in 2001 (strain: BAN01-10398; Accession number: AY843306.1). Recombination analyses of these samples demonstrate recombination events with sequences from echovirus-18 and echovirus-30. Interpretation & conclusions: Recombination events in the EV-B serotypes are known, and this work reconfirms the same for EV-B88 isolates also. This study is a step in increasing the awareness about EV-B88 in India and emphasizes future studies to be conducted in the identification of other types of EV present in India.

ON-CHIP PLANER WAVEGUIDES FOR SUPERCONTINUUM GENERATION IN THE MID-IR REGION OF ELECTROMAGNETIC SPECTRUM: A REVIEW

On-chip planer optical waveguide-based sources for supercontinuum (SC) generation have become highly attractive devices in the twenty-first century. Mid-IR SC sources in the 2-20 ?m wavelength region are advantageously used for gas sensing, high-sensitivity molecular detection, security, and industrial applications. These integrated photonic devices are cost-effective, scalable, and robust, and also offer more flexibility in tailoring the dispersion characteristics relative to other SC generation techniques. This article reviews the evolution of SC sources from fiber-based devices to optical waveguide-based devices and presents a historical as well as recent progress in various types of on-chip optical waveguides with physical mechanisms involved in generating coherent SC sources.

Clinical Application of the Next Generation Sequencing for Molecular Classification in Endometrial Carcinomas / 中山大学学报(医学科学版)

ObjectiveTo explore the clinical application of molecular classification in endometrial cancers with the next generation sequencing （NGS）. MethodsTotally 112 cases of endometrial carcinoma diagnosed by pathology in The Sun Yat-sen University Cancer Center were collected. All of them were tested by hybridized-capture second-generation sequencing based on 1，021 gene panel. The molecular variation spectrum of each subtype and its relationship between the clinicopathological features were analyzed. ResultsThe cases were distributed as follows： 8 （7.1%） POLE mutation， 34 （30.4%） mismatch repair deficient， 26 （23.2%） TP53 mutation， 44 （39.3%） non-specific molecular profile. The median tumor mutation burden was respectively 252.0， 38.4， 5.8 and 5.4 Muts/Mb. There were no significantly differences among four subtypes in clinicopathological features such as age， histological grade， lymph node metastasis and clinical stage. PTEN （75.5%）， PIK3CA （66.7%）， ARID1A （55.9%）， TP53 （40.2%）， NF1 （29.4%） were the most common mutations in endometrial cancers. ConclusionsThe utilization of NGS in endometrial cancers can simultaneously identify molecular subgroups， screen Lynch syndrome and obtain molecular variation spectrum， which can provide guidance for immunotherapy and targeted therapy， contribute to further accumulation and exploration of molecular genetic characteristics.

Clinical Characteristics and Diagnostic Methods of Pulmonary Mucormycosis / 中山大学学报(医学科学版)

ObjectiveTo summarize the clinical features and prognosis of pulmonary mucormycosis （PM） in southern China， and to explore the diagnostic value of metagenomic next generation sequencing （mNGS） in PM. MethodsThe clinical manifestations， diagnosis， treatment and prognosis of patients diagnosed with PM in The First Affiliated Hospital of Sun Yat-sen University from January 1， 2019 to January 31， 2022 who had undergone mNGS detection in lung tissue or alveolar lavage fluid were collected retrospectively. A total of 14 patients with PM were included， including 4 patients with confirmed diagnosis and 10 patients with clinical diagnosis. ResultsAll patients had underlying medical conditions， with hematological malignancies and diabetes being the most common. The most common symptoms were fever （n = 10）， cough （n = 9） and shortness of breath （n = 9）. Consolidation was the most common sign of chest CT， followed by mass， mostly with cavity. On laboratory tests， decreased CD4+T lymphocytes， elevated CD8+T lymphocytes， and decreased CD4+/CD8+ ratio， and presentation with pleural effusion indicate poor prognosis. The positive rate of mNGS diagnosis was 78.5%， which was significantly higher than that of histopathology （50%）， fungus rapid fluorescence staining （61.5%） and fungal culture （23.1%） of bronchoalveolar lavage fluid. ConclusionsPulmonary mucormycosis is more likely to occur in patients with underlying diseases or who are immunocompromised. The clinical manifestations lack specificity. The low CD4/CD8 ratio and presentation of pleural effusion on CT imaging indicate poor prognosis of patients. mNGS is a rapid， convenient and sensitive method for the diagnosis of PM， which has advantages in the diagnosis of pulmonary mucormycosis.

Research Progress of Lung Cancer Vaccines / 中国肺癌杂志

With the development of medical technology, tumor vaccines as a novel precise immunotherapy approach have gradually received attention in clinical applications. Against the backdrop of the global corona virus disease 2019 (COVID-19) outbreak, vaccine technology has further advanced. Depending on the types of antigens, tumor vaccines can be divided into whole-cell vaccines, peptide vaccines, messenger ribonucleic acid (mRNA) vaccines, recombinant virus vaccines, etc. Although some tumor vaccines have been marketed and achieved certain therapeutic effects, the results of tumor vaccines in clinical trials have been unsatisfactory in the past period. With the maturation of next-generation sequencing (NGS) technology and the continuous development of bioinformatics, dynamic monitoring of the entire process of tumor subpopulation development has become a reality, which has laid a solid foundation for personalized, neoantigen-centered therapeutic tumor vaccines. This article reviews the recent developments of tumor vaccines of different types, starts with lung cancer and summarizes the achievements of tumor vaccines in clinical applications, and provides an outlook for the future development of antigen-centered tumor vaccines.
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Analysis of CSF3R Gene Mutations and Clinical Characteristics in Patients with t(8;21) Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the occurrence of CSF3R mutation in patients with t(8;21) acute myeloid leukemia (AML) and its correlation with some clinical parameters.@*METHODS@#The clinical and laboratory data of 167 newly diagnosed AML patients with t(8;21) translocation were analyzed retrospectively. High-throughput DNA sequencing technology combined with Sanger sequencing method was used to detect 112 gene mutations. The occurrence of CSF3R gene mutation and its influence on the remission rate after chemotherapy were analyzed.@*RESULTS@#Among 167 patients with t(8;21) AML, 15 patients (9.0%) carried CSF3R mutations, including 6 cases of membrane proximal region mutations and 9 cases of truncation mutations in the cytoplasmic tail. The most common coexisting mutations of CSF3R were KIT (40.0%), TET2 (33.3%), DNMT3A (26.7%), FLT3 (20.0%), CBL (20.0%), IDH1 (13.3%), etc. Compared with the wild type, the CSF3R mutant group had a higher mutation rate of DNA methylation-related genes（P <0.001）. The median peripheral white blood cell (WBC) count of patients with CSF3R gene mutation was 5.80 (3.20-8.56)×109/L at initial diagnosis, which was significantly lower than 8.80 (5.26-19.92)×109/L of the CSF3R wild-type patients (P =0.017). There was no significant difference between the two groups in sex, median age, FAB classification, hemoglobin level, platelet count, etc. (P >0.05). The CR rate of the CSF3R gene mutation group (100%) was significantly higher than that of the wild-type group (86.8%), but the difference was not statistically significant (P >0.05). The CSF3R gene mutation group had a significantly higher CD19 positive rate and a higher -X rate than the wild group (86.7% vs 47.4%, P =0.004; 33.3% vs 13.2%, P =0.037).@*CONCLUSION@#There is a high incidence of CSF3R mutation in t (8;21) AML patients. The clinical characteristics and coexisting mutation genes of CSF3R mutation-positive patients are different from those of wild-type patients.

High-Throughput Sequencing Technology for Detection of Gene Mutations in Myeloid Malignancies and Its Clinical Prognostic Significance / 中国实验血液学杂志

OBJECTIVE@#To detect the gene mutations in patients with myeloid malignancies by high-throughput sequencing and explore the correlation between gene mutations and prognosis.@*METHODS@#A retrospective analysis was performed on 56 patients with myeloid malignancies who were hospitalized in the department of hematology, Peking University International Hospital from January 2020 to May 2021. The genetic mutations of the patients were detected by next-generation sequencing technology, and the correlation between the genetic mutations and prognosis of myeloid malignancies was analyzed.@*RESULTS@#In 56 patients, the number of mutated genes detected in a single patient is 0-9, with a median of 3. Sequencing results showed that the most common mutated genes were RUNX1(21.4%), TET2(17.9%), DNMT3A(17.9%), TP53(14.3%) and ASXL1(14.3%), among which the most common mutations occurred in the signaling pathway-related genes (23.3%) and the transcription factor genes (18.3%). 84% of the patients carried multiple mutated genes (≥2), and correlation analysis showed there were obvious co-occurring mutations between WT1 and FLT3, NPM1 and FLT3-ITD, and MYC and FLT3. TP53 mutation was more common in MDS patients.The overall survival time of patients with NRAS mutation was significantly shortened (P =0.049). The prognosis of patients with TP53 mutation was poor compared with those without TP53 mutation, but the difference wasn't statistically significant (P =0.08).@*CONCLUSION@#The application of next-generation sequencing technology is of great significance in myeloid malignancies, which is helpful to better understand the pathogenesis of the disease, to judge the prognosis and to find possible therapeutic targets.