Attention-Guided Partial Domain Adaptation for Automated Pneumonia Diagnosis From Chest X-Ray Images.

Deep neural networks (DNN) supported by multicenter large-scale Chest X-Ray (CXR) datasets can efficiently perform tasks such as disease identification, lesion segmentation, and report generation. However, the non-ignorable inter-domain heterogeneity caused by different equipment, ethnic groups, and scanning protocols may lead to dramatic degradation in model performance. Unsupervised domain adaptation (UDA) methods help alleviate the cross-domain discrepancy for subsequent analysis. Nevertheless, they may be prone to: 1) spatial negative transfer: misaligning non-transferable regions which have inadequate knowledge, and 2) semantic negative transfer: failing to extend to scenarios where the label spaces of the source and target domain are partially shared. In this work, we propose a classification-based framework named attention-guided partial domain adaptation (AGPDA) network for overcoming these two negative transfer challenges. AGPDA is composed of two key modules: 1) a region attention discrimination block (RADB) to generate fine-grained attention value via lightweight region-wise multi-adversarial networks. 2) a residual feature recalibration block (RFRB) trained with class-weighted maximum mean discrepancy (MMD) loss for down-weighing the irrelevant source samples. Extensive experiments on two publicly available CXR datasets containing a total of 8598 pneumonia (viral, bacterial, and COVID-19) cases, 7163 non-pneumonia or healthy cases, demonstrate the superior performance of our AGPDA. Especially on three partial transfer tasks, AGPDA significantly increases the accuracy, sensitivity, and F1 score by 4.35%, 4.05%, and 1.78% compared to recently strong baselines.

Testosterone biosensor in sports doping / Biossensor de testosterona no doping esportivo / Biosensor de testosterona en el dopaje deportivo

ABSTRACT Introduction: Testosterone is a steroid that can help with blood disorders, sexual dysfunctions, connective tissue diseases, some malignancies, intractable pain, and other serious diseases. However, it must be prescribed under medical supervision because of the risk of major adverse effects such as liver disease, heart disease, stroke, blood clots, and cancer. There is an urgent need for research on developing an electrochemical sensor to detect testosterone as a doping substance in sports. Objective: Develop an electrochemical sensor of poly(ionic liquid)-graphene oxide molecularly printed polymers (PIL/MIs/GO) to detect testosterone as a doping substance in sports. Methods: Morphological characterization of modified electrodes was performed by field emission scanning electron microscopy (FESEM), allowing the GO to be surface-mounted with fragments and apertures. Due to the holes generated by the agglomeration of PIL and MIs molecules on the wavy edges of the GO nanosheets, the surface morphology of PIL/MIs/GO/GCE also revealed a high porosity structure. Results: Compared to other synergistic influences of GO nanosheets with PIL and MIs molecules, electrochemical investigations using a differential pulse voltammetry approach indicated high selectivity, good stability, appropriate linear range, lower detection limit, and higher selectivity. Conclusion: In pharmaceutical samples and human biological fluids, the validity and accuracy of PIL/MIs/GO/GCE for the determination of testosterone demonstrated practical application. PIL/MIs/GO/GCE can thus be used as an accurate and reliable sensor for detecting testosterone as a doping agent in sports. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A testosterona é um esteróide que pode ajudar com distúrbios sanguíneos, disfunções sexuais, doenças do tecido conjuntivo, algumas malignidades, dores intratáveis e outras doenças graves. No entanto, devido ao risco de grandes efeitos adversos como doenças hepáticas, doenças cardíacas, derrames, coágulos sanguíneos e câncer, ela deve ser prescrita sob supervisão médica. Há uma necessidade urgente da pesquisa sobre o desenvolvimento de um sensor eletroquímico para detectar a testosterona como substância dopante nos esportes. Objetivo: Desenvolver um sensor eletroquímico de poli-(líquido iônico)-polímeros impressos molecularmente em óxido de grafeno (PIL/MIs/GO) para detectar a testosterona como substância dopante nos esportes. Métodos: Efetuou-se a caracterização morfológica de eletrodos modificados por microscopia eletrônica de varredura de emissão de campo (FESEM) permitindo que o GO fosse em superfície com fragmentos e aberturas. Devido aos orifícios gerados pela aglomeração das moléculas de PIL e MIs nas bordas onduladas das nano folhas de GO, a morfologia da superfície de PIL/MIs/GO/GCE também revelou uma estrutura de alta porosidade. Resultados: Em comparação com outras influências sinergéticas das nanoquetas GO com as moléculas PIL e MIs, os resultados das investigações eletroquímicas utilizando a abordagem de voltametria de pulso diferencial indicaram alta seletividade, boa estabilidade, faixa linear apropriada, limite de detecção mais baixo e seletividade mais alta. Conclusão: Em amostras farmacêuticas e fluidos biológicos humanos, a validade e a precisão do PIL/MIs/GO/GCE para a determinação de testosterona demonstraram aplicação prática. O PIL/MIs/GO/GCE pode assim ser utilizado como um sensor preciso e confiável para a detecção de testosterona como agente dopante no esporte. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: La testosterona es un esteroide que puede ayudar en los trastornos sanguíneos, la disfunción sexual, las enfermedades del tejido conectivo, algunos tumores malignos, el dolor intratable y otras enfermedades graves. Sin embargo, debido al riesgo de que se produzcan efectos adversos importantes, como enfermedades hepáticas, cardíacas, accidentes cerebrovasculares, coágulos sanguíneos y cáncer, debe prescribirse bajo supervisión médica. Es urgente investigar el desarrollo de un sensor electroquímico para detectar la testosterona como sustancia dopante en el deporte. Objetivo: Desarrollar un sensor electroquímico de polímeros impresos molecularmente de poli(líquido iónico)-óxido de grafeno (PIL/MIs/GO) para detectar la testosterona como sustancia dopante en el deporte. Métodos: La caracterización morfológica de los electrodos modificados se llevó a cabo mediante microscopía electrónica de barrido de emisión de campo (FESEM) permitiendo que el GO estuviera en la superficie con fragmentos y aberturas. Debido a los agujeros generados por la aglomeración de moléculas de PIL y MIs en los bordes ondulados de las nanohojas de GO, la morfología superficial de PIL/MIs/GO/GCE también reveló una estructura de alta porosidad. Resultados: En comparación con otras influencias sinérgicas de las nanohojas de GO con las moléculas PIL y MIs, los resultados de las investigaciones electroquímicas utilizando el enfoque de la voltamperometría diferencial de impulsos indicaron una alta selectividad, una buena estabilidad, un rango lineal apropiado, un límite de detección más bajo y una mayor selectividad. Conclusión: En muestras farmacéuticas y fluidos biológicos humanos, la validez y precisión de PIL/MIs/GO/GCE para la determinación de testosterona demostró su aplicación práctica. Así pues, PIL/MIs/GO/GCE puede utilizarse como un sensor preciso y fiable para la detección de la testosterona como agente dopante en el deporte. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Transcriptional adaptation of Shigella flexneri during adherence to epithelial cells.

Shigella adhesion to host cells is a transitional stage from an extracellular to an intracellular environment. However, the dynamic adaptations of Shigella during adhesion are poorly understood. To address this, we performed the first transcriptome analysis of Shigella flexneri 2457T during adhesion. A total of 1,757 genes were differentially regulated (>twofold). The majority of plasmid-borne ipa-mxi-spa locus genes were downregulated, indicating these virulence genes were strictly regulated after successful adhesion. Altered expression of genes involved in stress response indicates that adherent S. flexneri encountered envelope stress and oxidative stress. Shigella flexneri also experienced reduced energy production during adherence. Transcript profiling and cell culture assays using glpD and glpK mutants showed that enhancement of glycerol catabolism were related with adhesion ability of S. flexneri. In addition, regulation of expression of some ionic transport system may be required for S. flexneri adhesion. Expression levels of 26 genes were further examined using qRT-PCR, which were congruent with transcriptome data. A comparison with expression profile during intracellular growth revealed major differences in genes involved in translation, surface modification, and utilization of carbon and iron. These results contribute to the knowledge of the adaptation mechanisms of S. flexneri during adhesion.

Loss of the lac operon contributes to Salmonella invasion of epithelial cells through derepression of flagellar synthesis.

Salmonella, a genus that is closely related to Escherichia coli, includes many pathogens of humans and other animals. A notable feature that distinguishes Salmonella from E. coli is lactose negativity, because the lac operon is lost in most Salmonella genomes. Here, we expressed the lac operon in Salmonella enterica serovar Typhimurium and compared the virulence of the Lac(+) strain to that of the wild-type strain in a murine model, invasion assays, and macrophage replication assays. We showed that the Lac(+) strain is attenuated in vivo and the attenuation of virulence is caused by its defect in epithelial cell invasion. However, the invasion-defective phenotype is unrelated to lactose utilization. Through sequencing and the comparison of the transcriptome profile between the Lac(+) and wild-type strains during invasion, we found that most flagellar genes were markedly downregulated in the Lac(+) strain, while other genes associated with invasion, such as the majority of genes encoded in Salmonella pathogenicity island 1, were not differentially expressed. Moreover, we discovered that lacA is the major repressor of flagellar gene expression in the lac operon. In conclusion, these data demonstrate that the lac operon decreases Salmonella invasion of epithelial cells through repression of flagellar biosynthesis. As the ability to invade epithelial cells is a critical virulence determinant of Salmonella, our results provide important evidence that the loss of the lac operon contributes to the evolution of Salmonella pathogenicity.

Structure and gene cluster of the O-antigen of Escherichia coli O109; chemical and genetic evidences of the presence of L-RhaN3N derivatives in the O-antigens of E. coli O109 and O119.

O-antigen representing the O-polysaccharide chain of the lipopolysaccharide is the most variable constituent on the cell surface of Gram-negative bacteria and a player in their pathogenicity. The O-polysaccharide of Escherichia coli O109 was studied by sugar analysis and nuclear magnetic resonance spectroscopy and found to contain a rarely occurring monosaccharide, 2,3-diacetamido-2,3,6-trideoxy-l-mannose (l-RhaNAc3NAc). The following structure of the tetrasaccharide repeating unit of the O-polysaccharide was established, which is closely related to that of Proteus penneri O66: Ac--4-ß-L-RhapNAc3NAc -->4)-α-D-Glcp-(1-->3)-α-L-6dTalp-(1-->3)-ß-D-GlcpNAc-(1-->. The O-antigen gene cluster of E. coli O109 was sequenced and all 14 genes found were assigned functions based on their similarity to genes from the available databases. Putative genes for synthesis of l-RhaN3N were found in E. coli O109 and their homologues in E. coli O119, whose O-antigen has been reported earlier to contain 2-acetamido-2,3,6-trideoxy-3-formamido-d-mannose (d-RhaNAc3NFo). Analysis by GLC of the (S)-2-octyl glycosides confirmed that the absolute configuration of RhaN3N in E. coli O119 should be revised from D TO L.