Deep learning for computational cytology: A survey.

Computational cytology is a critical, rapid-developing, yet challenging topic in medical image computing concerned with analyzing digitized cytology images by computer-aided technologies for cancer screening. Recently, an increasing number of deep learning (DL) approaches have made significant achievements in medical image analysis, leading to boosting publications of cytological studies. In this article, we survey more than 120 publications of DL-based cytology image analysis to investigate the advanced methods and comprehensive applications. We first introduce various deep learning schemes, including fully supervised, weakly supervised, unsupervised, and transfer learning. Then, we systematically summarize public datasets, evaluation metrics, versatile cytology image analysis applications including cell classification, slide-level cancer screening, nuclei or cell detection and segmentation. Finally, we discuss current challenges and potential research directions of computational cytology.

Rethinking Annotation Granularity for Overcoming Shortcuts in Deep Learning-based Radiograph Diagnosis: A Multicenter Study.

Purpose: To evaluate the ability of fine-grained annotations to overcome shortcut learning in deep learning (DL)-based diagnosis using chest radiographs. Materials and Methods: Two DL models were developed using radiograph-level annotations (disease present: yes or no) and fine-grained lesion-level annotations (lesion bounding boxes), respectively named CheXNet and CheXDet. A total of 34 501 chest radiographs obtained from January 2005 to September 2019 were retrospectively collected and annotated regarding cardiomegaly, pleural effusion, mass, nodule, pneumonia, pneumothorax, tuberculosis, fracture, and aortic calcification. The internal classification performance and lesion localization performance of the models were compared on a testing set (n = 2922); external classification performance was compared on National Institutes of Health (NIH) Google (n = 4376) and PadChest (n = 24 536) datasets; and external lesion localization performance was compared on the NIH ChestX-ray14 dataset (n = 880). The models were also compared with radiologist performance on a subset of the internal testing set (n = 496). Performance was evaluated using receiver operating characteristic (ROC) curve analysis. Results: Given sufficient training data, both models performed similarly to radiologists. CheXDet achieved significant improvement for external classification, such as classifying fracture on NIH Google (CheXDet area under the ROC curve [AUC], 0.67; CheXNet AUC, 0.51; P < .001) and PadChest (CheXDet AUC, 0.78; CheXNet AUC, 0.55; P < .001). CheXDet achieved higher lesion detection performance than CheXNet for most abnormalities on all datasets, such as detecting pneumothorax on the internal set (CheXDet jackknife alternative free-response ROC [JAFROC] figure of merit [FOM], 0.87; CheXNet JAFROC FOM, 0.13; P < .001) and NIH ChestX-ray14 (CheXDet JAFROC FOM, 0.55; CheXNet JAFROC FOM, 0.04; P < .001). Conclusion: Fine-grained annotations overcame shortcut learning and enabled DL models to identify correct lesion patterns, improving the generalizability of the models.Keywords: Computer-aided Diagnosis, Conventional Radiography, Convolutional Neural Network (CNN), Deep Learning Algorithms, Machine Learning Algorithms, Localization Supplemental material is available for this article © RSNA, 2022.

A novel homozygous mutation in DNAJB13-a gene associated with the sperm axoneme-leads to teratozoospermia.

PURPOSE: To evaluate the unknown genetic causes of teratozoospermia, and determine the pathogenicity of candidate variants. METHODS: A primary infertile patient and his family members were recruited in the West China Second University Hospital of Sichuan University. Whole-exome sequencing was performed to identify causative genes in a man with teratozoospermia. Immunofluorescence staining and western blotting were applied to assess the pathogenicity of the identified variant. Intracytoplasmic sperm injection (ICSI) was used to assist fertilization for the patient with teratozoospermia. RESULTS: We performed whole-exome sequencing (WES) and detected a novel homozygous frameshift mutation of c.335_336del [p.E112Vfs*3] in DNAJB13 on a primary infertile male patient. Intriguingly, we identified abnormal sperm morphology in this patient, with recurrent respiratory infections and chronic cough. Furthermore, we confirmed that this mutation resulted in negative effects on DNAJB13 expression in the spermatozoa of the affected individual, causing ultrastructural defects in his sperm. Remarkably, our staining revealed that DNAJB13 was expressed in the cytoplasm of primary germ cells and in the flagella of spermatids during spermiogenesis in humans and mice. Finally, we are the first group to report a favorable prognosis using ICSI for a patient carrying this DNAJB13 mutation. CONCLUSION: Our study revealed a novel homozygous frameshift mutation of c.335_336del [p.E112Vfs*3] in DNAJB13 involved in teratozoospermia phenotype. Our study greatly expands the spectrum of limited DNAJB13 mutations, and is expected to provide a better understanding of genetic counseling diagnoses and subsequent treatment of male infertility.

Ring-shaped traveling wave ultrasonic motor for high-output power density with suspension stator.

A ring-shaped traveling wave ultrasonic motor with a suspension stator is proposed for improving output power density. Piezoelectric stacks working in d33 mode are involved in the stator, whereas piezoelectric plates employed in classic ring-shaped traveling wave motors often work in d31 mode. Spring-mass systems are used to suspend the stator from the base that supports the motor and provide preload force. The volume of piezoelectric material and the power density of the motor can be easily increased through the suspension structure. Large vibration amplitude of the stator can be generated on the coupling surface. Simulink analysis and finite element analysis are conducted to verify the theory and determine the optimum parameters of the suspension stator with four piezoelectric stacks. The maximum free vibration amplitude of 4.25 µm of the stator is observed, which is nearly 4.7 times of that without suspension. The prototype can work at a maximum no-load speed of 62 rpm and produce a stall torque of 49.5 mN m under a driving signal of 30 Vpp when the mass block is 0.30 g. Furthermore, the higher output power can be expected because more extra stacks can be added in this suspension structure.

A Multi-Organ Nucleus Segmentation Challenge.

Generalized nucleus segmentation techniques can contribute greatly to reducing the time to develop and validate visual biomarkers for new digital pathology datasets. We summarize the results of MoNuSeg 2018 Challenge whose objective was to develop generalizable nuclei segmentation techniques in digital pathology. The challenge was an official satellite event of the MICCAI 2018 conference in which 32 teams with more than 80 participants from geographically diverse institutes participated. Contestants were given a training set with 30 images from seven organs with annotations of 21,623 individual nuclei. A test dataset with 14 images taken from seven organs, including two organs that did not appear in the training set was released without annotations. Entries were evaluated based on average aggregated Jaccard index (AJI) on the test set to prioritize accurate instance segmentation as opposed to mere semantic segmentation. More than half the teams that completed the challenge outperformed a previous baseline. Among the trends observed that contributed to increased accuracy were the use of color normalization as well as heavy data augmentation. Additionally, fully convolutional networks inspired by variants of U-Net, FCN, and Mask-RCNN were popularly used, typically based on ResNet or VGG base architectures. Watershed segmentation on predicted semantic segmentation maps was a popular post-processing strategy. Several of the top techniques compared favorably to an individual human annotator and can be used with confidence for nuclear morphometrics.

[Nicotinamide-adenine dinucleotide phosphate oxidase p22phox expression in induced sputum cells for patients with obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: the aim of the study was to observe the change of NADPH oxidase p22phox expression in the induced sputum cells for patients with obstructive sleep apnea hypopnea syndrome (OSAHS), and its relationship with the severity of OSAHS. METHODS: thirty OSAHS patients and 23 healthy controls were recruited in the study. Before sleep and in the next morning sputum induction was performed twice for each subject, cell numbers and differentials in induced sputum were counted. NADPH oxidase p22phox mRNA expression was measured in induced sputum cells by RT-PCR and the protein was measured by immunocytochemistry. RESULTS: the OSAHS group showed a significant higher percentage of neutrophils and a lower percentage of macrophages in the induced sputum compared to the control group (P < 0.05). Macrophages and neutrophils represented the main cell types expressing NADPH oxidase p22phox in induced sputum cells by immunocytochemistry. In the control group, level of NADPH oxidase p22phox mRNA and percentages of NADPH oxidase p22phox positive neutrophils and macrophages in sputum samples collected both in the morning and before sleep was significantly lower than in OSAHS group (P < 0.05). In OSAHS group, higher levels of NADPH oxidase p22phox mRNA and percentages of NADPH oxidase p22phox positive neutrophils and macrophages were found in the morning than at pre-sleep. A negative correlation was found between levels of NADPH oxidase p22phox mRNA and percentage of NADPH oxidase p22phox positive neutrophils and macrophages in the morning sputum were negatively associated with LspO(2), but positively associated with AHI. CONCLUSION: these findings suggest that there are changes of NADPH oxidase p22phox expression in induced sputum cells of OSAHS patients, and these changes are related to the severity of OSAHS.

Relationship between reduced nicotinamide adenine dinucleotide phosphate oxidase subunit p22phox gene polymorphism and obstructive sleep apnea-hypopnea syndrome in the Chinese Han population.

BACKGROUND: Increased production of reactive oxygen species (ROS) is thought to play a major role in the pathogenesis of obstructive sleep apnea-hypopnea syndrome (OSAHS). The reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex is an important source of ROS. The p22phox subunit is polymorphic with a C242T variant that changes histidine-72 for a tyrosine in the potential heme binding site. This study aimed to investigate the relationship between NADPH oxidase subunit p22phox gene polymorphism and OSAHS. METHODS: The genotypes of p22phox polymorphism were determined by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) assay in 176 unrelated subjects of the Han population in southern region of China (including 107 OSAHS subjects and 69 non-OSAHS subjects), while the plasma concentration of superoxide dismutase (SOD) was detected in the two groups, and p22phox mRNA expression in peripheral blood mononuclear cell (PBMC) was determined with reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The phagocyte NADPH oxidase subunit p22phox mRNA expression was significantly increased in the OSAHS group than that in the non-OSAHS group (P < 0.01). Compared with the non-OSAHS control group ((85.31 +/- 9.23) U/ml), the levels of SOD were lower in patients with OSAHS ((59.65 +/- 11.61) U/ml (P < 0.01). There were significant differences in genotypes distribution in p22phox polymorphism between the two groups (P = 0.02). Compared with the non-OSAHS control group, the OSAHS group had a significantly higher T allele frequency in p22phox polymorphism (P = 0.03). There were independent effects of p22phox polymorphism on body mass index (BMI), neck circumference (NC), waist-to-hip ratio (WHR) in the OSAHS group, and the carriers of the T allele of p22phox polymorphism had greater NC, WHR, systolic blood pressure (SBP), diastolic blood pressure (DBP) and apnea-hypopnea index (AHI) (P < 0.05), but the carriers of the T allele had lower SOD (P < 0.01) and lowest SaO(2) (P = 0.04). There was no significant difference in p22phox mRNA expression between the OSAHS groups with or without T allele (P = 0.45). CONCLUSIONS: The NADPH oxidase subunit p22phox gene polymorphism may be associated with susceptibility to OSAHS, and it may be an important candidate gene for OSAHS.

[Effect of NADPH oxidase activity inhibitor apocynin on blood pressure in rats exposed to chronic intermittent hypoxia and the possible mechanisms].

OBJECTIVE: To investigate the effect of NADPH oxidase activity inhibitor apocynin on the blood pressure of rats exposed to chronic intermittent hypoxia (CIH). METHODS: Thirty healthy male SD rats were randomly divided into 3 groups of 10 each, a CIH group, an apocynin treatment group and a control group. The systolic blood pressure (SBP) was measured with tail-cuff method. RT-PCR and Western blot were used to examine mRNA and protein expression of NADPH oxidase subunit p22phox. The level of MDA, SOD, NO and .O(2)(-) were detected by colorimetric method. RESULTS: Compared to the normal group, the expression of p22phox mRNA and protein were significantly increased in CIH group (q = 3.202, 6.522, P < 0.05). There were no statistic difference of p22phox mRNA and protein expression between CIH group and apocynin treatment group (P > 0.05). Compared with those of CIH group, the levels of MDA, .O(2)(-) and the systolic blood pressure decreased significantly (P < 0.05), while SOD and NO activity increased significantly (q = 6.960, 4.385, P < 0.05) in apocynin treatment group. CONCLUSIONS: These results indicate that NADPH oxidase up-expression is closely associated with hypertension in OSAHS. Inhibition of NADPH oxidase activity may be hopefully served as a useful strategy for prevention and treatment of OSAHS-induced hypertension.

Modes of regulation of RpoS by H-NS.

Regulated degradation of RpoS requires RssB and ClpXP protease. Mutations in hns increase both RpoS synthesis and stability, causing a twofold increase in synthesis and almost complete stabilization of RpoS, independent of effects on synthesis and independent of phosphorylation of RssB. This suggests that H-NS regulates an RssB inhibitor or inhibitors.

Analysis of the Escherichia coli Alp phenotype: heat shock induction in ssrA mutants.

The major phenotypes of lon mutations, UV sensitivity and overproduction of capsule, are due to the stabilization of two substrates, SulA and RcsA. Inactivation of transfer mRNA (tmRNA) (encoded by ssrA), coupled with a multicopy kanamycin resistance determinant, suppressed both lon phenotypes and restored the rapid degradation of SulA. This novel protease activity was named Alp but was never identified further. We report here the identification, mapping, and characterization of a chromosomal mutation, faa (for function affecting Alp), that leads to full suppression of a Deltalon ssrA::cat host and thus bypasses the requirement for multicopy Kan(r); faa and ssrA mutants are additive in their ability to suppress lon mutants. The faa mutation was mapped to the C terminus of dnaJ(G232); dnaJ null mutants have similar effects. The identification of a lon suppressor in dnaJ suggested the possible involvement of heat shock. We find that ssrA mutants alone significantly induce the heat shock response. The suppression of UV sensitivity, both in the original Alp strain and in faa mutants, is reversed by mutations in clpY, encoding a subunit of the heat shock-induced ClpYQ protease that is known to degrade SulA. However, capsule synthesis is not restored by clpY mutants, probably because less RcsA accumulates in the Alp strain and because the RcsA that does accumulate is inactive. Both ssrA effects are partially relieved by ssrA derivatives encoding protease-resistant tags, implicating ribosome stalling as the primary defect. Thus, ssrA and faa each suppress two lon mutant phenotypes but by somewhat different mechanisms, with heat shock induction playing a major role.