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Phage therapy is still in its infancy, but it is increasingly promising as a future alternative for treating antibiotic-resistant bacteria. To investigate the effect of phages on Mycobacterium abscessus complex (MABC), we isolated 113 environmental phages, grown them to high titres, and assayed them on MABC clinical strains through the spot test. Of all the phages, only 16 showed killing activity. Their activity was so temperate to MABC that they could not generate any plaque-forming units (PFUs). The Appelmans method of directed evolution was carried out to evolve these 16 phages into more lytic ones. After only 11 of 30 rounds of evolution, every single clinical strain in our collection, including those that were unsusceptible up to this point, could be lysed by at least one phage. The evolved phages were able to form PFUs on the clinical strains tested. Still, they are temperate at best and require further training. The genomes of one random parental phage and three random evolved phages from Round 13 were sequenced, revealing a diversity of clusters and genes of a variety of evolutionary origins, mostly of unknown function. These complete annotated genomes will be key for future molecular characterisations.

Mycobacterium abscessus complex infections are ever on the rise. To curb their increasing evolution, we performed an in-depth study of 43 clinical isolates of cystic fibrosis patients obtained from 2009 to 2020. We identified their subspecies, uncovered their genotypic resistance profiles, characterised their antibiotic-resistant genes, and assessed their phenotypic antibiotic susceptibilities. The phenotypic and genotypic methods showed total agreement in terms of resistance to clarithromycin and amikacin. Of the 43 clinical strains, 28 belonged to M. abscessus subsp. abscessus (65.1%), 13 to M. abscessus subsp. massiliense (30.2%), and 2 to M. abscessus subsp. bolletii (4.6%). The resistant rates for clarithromycin and amikacin, the two main drugs against M. abscessus complex pulmonary infections, were 64.2% and 14.2%, respectively. We found three strains of M. abscessus subsp. abscessus that showed heteroresistance in the rrl and rrs genes, and these strains also presented double-resistance since they were macrolide- and aminoglycoside-resistant. M. abscessus subsp. abscessus showed a high minimum inhibitory concentration (MIC) and a resistant percentage larger than or equal to 88% to cefoxitin, ciprofloxacin, moxifloxacin, doxycycline, imipenem, and trimethoprim-sulfamethoxazole. These results show a panorama of the high resistance of Mycobacterium abscessus complex to current drugs for cystic fibrosis patients. Thus, other treatment methods are urgently needed.

ObjectiveTo explore the application values of deep-learning based artificial intelligence (AI) automatic classification system, on the differential diagnosis of non-lactating mastitis (NLM) and malignant breast tumors, via its comparation with traditional ultrasound interpretations and the following interpretation conclusions made by the sonographers with various seniorities.MethodsA total of 707 patients suffering from breast lesions (475 malignant breast tumors and 232 NLM), were selected from the following three medical centers, including Zhejiang Cancer Hospital, Hebei Province Hospital of Traditional Chinese Medicine, and Yantai Affiliated Hospital of Binzhou Medical University, and the time period was set from April 2020 to September 2021. All selected cases firstly accepted the routine breast ultrasound diagnosis, followed by the interpretations from a senior sonographer with more than 15 years of work experience, and an intermediate-aged sonographer with more than 5 years of work experience, independently. Meanwhile, a third physician also interpreted the same ultrasound images by deep learning–based AI automatic classification system, independent of the interpretation results from the previous two physicians. The kappa test was performed to evaluate the consistency between the conventional ultrasound interpretation results and pathological results interpreted from physicians with different working experiences.ResultsIn total, 475 cases of malignant breast tumors (512 nodules) and 232 cases of NLM (255 nodules) were pathologically diagnosed. The accuracy, sensitivity, and specificity of conventional ultrasound interpretations vary from different sonographers with different working experiences. The accuracy, sensitivity, and specificity for intermediate-aged sonographers and senior sonographers were 76.92% (590/767), 84.71% (216/255), and 73.95% (374/512) and 87.35% (670/767), 86.27% (220/255), and 87.89% (450/512), respectively (P

Ground-based remote observation systems are vulnerable to atmospheric turbulence, which can lead to image degradation. While some methods can mitigate this turbulence distortion, many have issues such as long processing times and unstable restoration effects. Furthermore, the physics of turbulence is often not fully integrated into the image reconstruction algorithms, making their theoretical foundations weak. In this paper, we propose a method for atmospheric turbulence mitigation using optical flow and convolutional neural networks (CNN). We first employ robust principal component analysis (RPCA) to extract a reference frame from the images. With the help of optical flow and the reference frame, the tilt can be effectively corrected. After correcting the tilt, the turbulence mitigation problem can be simplified as a deblurring problem. Then, we use a trained CNN to remove blur. By utilizing (i) a dataset that conforms to the turbulence physical model to ensure the restoration effect of the CNN and (ii) the efficient parallel computing of the CNN to reduce computation time, we can achieve better results compared to existing methods. Experimental results based on actual observed turbulence images demonstrate the effectiveness of our method. In the future, with further improvements to the algorithm and updates to GPU technology, we expect even better performance.

To find novel and effective anti-cancer agents, sixteen novel imamine-1,3,5-triazine derivatives were firstly designed and synthesized using a molecular hybridization strategy and nucleophilic substitution reaction. The structures of imamine-1,3,5-triazine derivatives were characterized by 1H NMR, 13C NMR, IR, HR-MS and single crystal X-ray diffraction. These compounds were tested using the methyl thiazolyl tetrazolium (MTT) assay for their antiproliferative properties against MDA-MB-231 (breast cancer cells), HeLa (cervical cancer cells) and A498 (kidney cancer cells) cells with imatinib as the positive control which is the parent compound of imamine. The data revealed that some of the imamine-1,3,5-triazine derivatives possessed better anticancer activity than imatinib. The imamine-1,3,5-triazine derivatives were selective against triple-negative MDA-MB-231 breast cancer cells. Compound 4f (N2-allyl-6-chloro-N2-methyl-N4-(4-methyl-3-((4-(pyridin-3-yl) pyrimidin-2-yl) amino) phenyl)-1,3,5-triazine-2,4-diamine) and 4k (6-chloro-N2-cyclohexyl-N2-methyl-N4-(4-methyl-3-((4-(pyridin-3-yl) pyrimidin-2-yl) amino) phenyl)-1,3,5-triazine-2,4-diamine) demonstrated potent anti-proliferative activity against MDA-MB-231 cells with IC50 of 6.25 μM and 8.18 μM respectively surpassing that of imatinib (IC50 = 35.50 μM). Further studies have shown that compound 4f not only inhibits the migration, invasion, adhesion, and proliferation of MDA-MB-231 cells, but also has a strong inhibitory effect on the proliferation of MDA-MB-231 tumor xenografts in vivo. In addition, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties suggest that these compounds may have the properties of drug candidates. Thus, compound 4f may be a promising drug candidate for the treatment of cancer. [ABSTRACT FROM AUTHOR]

Phage therapy is still in its infancy, but it is increasingly promising as a future alternative for treating antibiotic-resistant bacteria. To investigate the effect of phages on Mycobacterium abscessus complex (MABC), we isolated 113 environmental phages, grown them to high titres, and assayed them on MABC clinical strains through the spot test. Of all the phages, only 16 showed killing activity. Their activity was so temperate to MABC that they could not generate any plaque-forming units (PFUs). The Appelmans method of directed evolution was carried out to evolve these 16 phages into more lytic ones. After only 11 of 30 rounds of evolution, every single clinical strain in our collection, including those that were unsusceptible up to this point, could be lysed by at least one phage. The evolved phages were able to form PFUs on the clinical strains tested. Still, they are temperate at best and require further training. The genomes of one random parental phage and three random evolved phages from Round 13 were sequenced, revealing a diversity of clusters and genes of a variety of evolutionary origins, mostly of unknown function. These complete annotated genomes will be key for future molecular characterisations. [ABSTRACT FROM AUTHOR]

Mycobacterium abscessus complex infections are ever on the rise. To curb their increasing evolution, we performed an in-depth study of 43 clinical isolates of cystic fibrosis patients obtained from 2009 to 2020. We identified their subspecies, uncovered their genotypic resistance profiles, characterised their antibiotic-resistant genes, and assessed their phenotypic antibiotic susceptibilities. The phenotypic and genotypic methods showed total agreement in terms of resistance to clarithromycin and amikacin. Of the 43 clinical strains, 28 belonged to M. abscessus subsp. abscessus (65.1%), 13 to M. abscessus subsp. massiliense (30.2%), and 2 to M. abscessus subsp. bolletii (4.6%). The resistant rates for clarithromycin and amikacin, the two main drugs against M. abscessus complex pulmonary infections, were 64.2% and 14.2%, respectively. We found three strains of M. abscessus subsp. abscessus that showed heteroresistance in the rrl and rrs genes, and these strains also presented double-resistance since they were macrolide- and aminoglycoside-resistant. M. abscessus subsp. abscessus showed a high minimum inhibitory concentration (MIC) and a resistant percentage larger than or equal to 88% to cefoxitin, ciprofloxacin, moxifloxacin, doxycycline, imipenem, and trimethoprim-sulfamethoxazole. These results show a panorama of the high resistance of Mycobacterium abscessus complex to current drugs for cystic fibrosis patients. Thus, other treatment methods are urgently needed. [ABSTRACT FROM AUTHOR]

Background: Several epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI) have been approved for first‐line (1L) treatment of EGFR‐mutated metastatic non‐small cell lung cancer (mNSCLC) in the United States (US). Real‐world analyses of 1L treatment patterns with EGFR TKIs, including the third‐generation EGFR TKI osimertinib which was most recently approved in 2018, are still sparse. Methods: This retrospective observational study used data from IQVIA's prescription claims (LRx) and medical claims (Dx) databases. mNSCLC patients newly treated with any EGFR TKI in the 1L setting were identified from January 1, 2015 to April 30, 2020; the first date of EGFR TKI (third‐generation osimertinib, first‐generation [erlotinib, gefitinib], or second‐generation [afatinib, dacomitinib]) was the index date. Treatment patterns were reported in the cohorts stratified by 1L EGFR TKI. Results: A total of 2505 patients were included in the study (982 osimertinib, 1060 first‐generation, and 463 second‐generation EGFR TKI). Beginning in 2018, osimertinib became the most common 1L EGFR TKI (66.7%) and in early 2020, it accounted for 90.6% of 1L EGFR TKIs. Nearly all patients (>97%) were treated with 1L EGFR TKI monotherapy. Patients with 1L osimertinib had longer treatment duration compared to patients with 1L first‐ or second‐generation EGFR TKI (median months: 17.8 vs. 8.7 vs. 10.5, respectively; log‐rank test for comparisons with osimertinib p < 0.0001) over median follow‐up times of 9.8, 20.5, and 19.3 months. 32.5% and 36.3% of the first‐ and second‐generation EGFR TKI cohorts, respectively, had evidence of 2L treatment. Osimertinib monotherapy accounted for the majority of 2L treatments (58.3%/60.7%) and 11.3%/8.9% had 2L chemotherapy or immuno‐oncology therapy following 1L first‐ or second‐generation EGFR TKI. Conclusion: In this real‐world study of a US claims database, 1L treatment duration was longer with osimertinib compared with other EGFR TKIs. Future studies with longer follow‐up are recommended to understand treatment patterns after progression on EGFR TKIs. [ABSTRACT FROM AUTHOR]