Isolation and genome-wide analysis of the novel Acinetobacter baumannii bacteriophage vB_AbaM_AB3P2.

A lytic Acinetobacter baumannii phage, isolate vB_AbaM_AB3P2, was isolated from a sewage treatment plant in China. A. baumannii phage vB_AbaM_AB3P2 has a dsDNA genome that is 44,824 bp in length with a G + C content of 37.75%. Ninety-six open reading frames were identified, and no genes for antibiotic resistance or virulence factors were found. Genomic and phylogenetic analysis of this phage revealed that it represents a new species in the genus Obolenskvirus. Phage vB_AbaM_AB3P2 has a short latent period (10 min) and high stability at 30-70°C and pH 2-10 and is potentially useful for controlling multi-drug-resistant A. baumannii.

Single-cell RNA sequencing reveals the role of mitochondrial dysfunction in the cardiogenic toxicity of perfluorooctane sulfonate in human embryonic stem cells.

Perfluorooctane sulfonate (PFOS), an endocrine-disrupting chemical pollutant, affects embryonic heart development; however, the mechanisms underlying its toxicity have not been fully elucidated. Here, Single-cell RNA sequencing (scRNA-seq) was used to investigate the overall effects of PFOS on myocardial differentiation from human embryonic stem cells (hESCs). Additionally, apoptosis, mitochondrial membrane potential, and ATP assays were performed. Downregulated cardiogenesis-related genes and inhibited cardiac differentiation were observed after PFOS exposure in vitro. The percentages of cardiomyocyte and cardiac progenitor cell clusters decreased significantly following exposure to PFOS, while the proportion of primitive endoderm cell was increased in PFOS group. Moreover, PFOS inhibited myocardial differentiation and blocked cellular development at the early- and middle-stage. A Gene Ontology analysis and pseudo-time trajectory illustrated that PFOS disturbed multiple processes related to cardiogenesis and oxidative phosphorylation in the mitochondria. Furthermore, PFOS decreased mitochondrial membrane potential and induced apoptosis. These results offer meaningful insights into the cardiogenic toxicity of PFOS exposure during heart formation as well as the adverse effects of PFOS on mitochondria.

Noninvasive Detection of Salt Stress in Cotton Seedlings by Combining Multicolor Fluorescence-Multispectral Reflectance Imaging with EfficientNet-OB2.

Salt stress is considered one of the primary threats to cotton production. Although cotton is found to have reasonable salt tolerance, it is sensitive to salt stress during the seedling stage. This research aimed to propose an effective method for rapidly detecting salt stress of cotton seedlings using multicolor fluorescence-multispectral reflectance imaging coupled with deep learning. A prototyping platform that can obtain multicolor fluorescence and multispectral reflectance images synchronously was developed to get different characteristics of each cotton seedling. The experiments revealed that salt stress harmed cotton seedlings with an increase in malondialdehyde and a decrease in chlorophyll content, superoxide dismutase, and catalase after 17 days of salt stress. The Relief algorithm and principal component analysis were introduced to reduce data dimension with the first 9 principal component images (PC1 to PC9) accounting for 95.2% of the original variations. An optimized EfficientNet-B2 (EfficientNet-OB2), purposely used for a fixed resource budget, was established to detect salt stress by optimizing a proportional number of convolution kernels assigned to the first convolution according to the corresponding contributions of PC1 to PC9 images. EfficientNet-OB2 achieved an accuracy of 84.80%, 91.18%, and 95.10% for 5, 10, and 17 days of salt stress, respectively, which outperformed EfficientNet-B2 and EfficientNet-OB4 with higher training speed and fewer parameters. The results demonstrate the potential of combining multicolor fluorescence-multispectral reflectance imaging with the deep learning model EfficientNet-OB2 for salt stress detection of cotton at the seedling stage, which can be further deployed in mobile platforms for high-throughput screening in the field.

Isoliquiritigenin suppresses the progression of malignant melanoma via targeting H2A.Z.1-E2F1 pathway.

Cutaneous melanoma is one of the most prevalent tumors, and it is still a huge challenge in the current clinical treatment. Isoliquiritigenin (ISL), which is isolated from Glycyrrhiza uralensis Fisch., has been reported for its anti-tumor effect. However, the underlying mechanism and targets of ISL are still not be revealed clearly. In this study, differentiallyexpressedproteins were identified bylabel-free quantitative mass spectrometry. Two isoforms of the histone variant H2A.Z, including H2A.Z.1 and H2A.Z.2, were significantly down regulated after administration of ISL in melanoma. H2A.Z.1 was highly expressed in melanoma and correlated with poor prognosis of melanoma. The expression of H2A.Z was inhibited by ISL in a concentration-dependent manner. Overexpression of H2A.Z.1 in melanoma cell lines partly restored the repressed cell proliferation and cell cycle by ISL. Moreover, E2F1 was identified as one downstream target of H2A.Z.1, which was also highly expressed in melanoma and correlated with poor prognosis of melanoma. Furthermore, in vivo assays validated the inhibitory role of ISL in melanoma proliferation and the expression of H2A.Z.1 and E2F1.Aboveall,it is indicated that ISL inhibit melanoma proliferation via targeting H2A.Z.1-E2F1 pathway. These findings explain the anti-tumor mechanism of ISL and provide potential therapeutic targets for melanoma.

Fatal Necrotizing Enterocolitis in Neonate Caused by Cronobacter sakazakii Sequence Type 64 Strain of CRISPR Sublineage b.

We report fatal neonatal necrotizing enterocolitis in China caused by Cronobacter sakazakii capsular profile K1:CA1, sequence type 64, and CRISPR type 197. Phylodynamic analyses indicated that the strain originated from the ancient, widespread, and antimicrobial drug-sensitive CRISPR sublineage b. Enhanced surveillance and pathogenesis research on this organism are required.

Occurrence, molecular characterization and antibiotic resistance of Cronobacter spp. isolated from wet rice and flour products in Guangdong, China.

This study explored the prevalence of Cronobacter spp. in wet rice and flour products from Guangdong province, China, the molecular characteristics and antimicrobial susceptibility profiles of the isolates were identified. Among 249 samples, 100 (40.16%) were positive for Cronobacter spp., including 77 wet rice and 23 wet flour products. Eleven serotypes were characterized among 136 isolates with C. sakazakii O2 (n = 32) predominating. Forty-nine MLST patterns were assigned, 15 of which were new. C. sakazakii ST4 (n = 17) was the dominant ST, which is previously reported to have caused three deaths; followed by C. malonaticus ST7 (n = 15), which is connected to adult infections. All strains presented susceptibility to ampicillin/sulbactam, imipenem, aztreonam and trimethoprim/sulfamethoxazole. The isolates showed maximum resistance to cephalothin, and the resistance and intermediate rates were 91.91% and 3.68%, each. Two strains, croM234A1 and croM283-1, displayed resistance to three antibiotics. High contamination level and predominant number of pathogenic STs of Cronobacter in wet rice and flour products implied a potential risk to public healthiness. This survey could provide comprehensive information for establishing more targeted control methods for Cronobacter spp.

Self-Reported Cognitive Function and Quality of Life in Patients With SCLC in the Hippocampal Avoidance Prophylactic Cranial Irradiation Versus Prophylactic Cranial Irradiation Randomized Phase 3 Trial (NCT01780675).

Introduction: In the randomized controlled trial in patients with SCLC comparing standard prophylactic cranial irradiation (PCI) with hippocampal avoidance PCI (HA-PCI), we did not observe beneficial effects of HA-PCI on tested cognition. Here, we report findings on self-reported cognitive functioning (SRCF) and quality of life (QoL). Methods: Patients with SCLC were randomized to receive PCI with or without HA (NCT01780675) and assessed at baseline (82 HA-PCI and 79 PCI patients) and at 4, 8, 12, 18, and 24 months of follow-up, using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and EORTC QLQ-brain cancer module (BN20). SRCF was assessed with the cognitive functioning scale of the EORTC QLQ-C30 and the Medical Outcomes Study questionnaire. A change of 10 points was used for minimal clinically important differences. Percentages of patients classified with having improved, stable, or deteriorated SRCF were compared between groups using chi-square tests. Changes in mean scores were analyzed using linear mixed models. Results: There was no significant difference in the percentage of patients with deteriorated, stable, or improved SRCF between the treatment arms. Depending on the evaluated time point, 31% to 46% and 29% to 43% of patients in the HA-PCI and PCI arm, respectively, reported a deteriorated SRCF on the basis of the EORTC QLQ-C30 and Medical Outcomes Study. QoL outcomes were not significantly different between the study arms, except for physical functioning at 12 months (p = 0.019) and motor dysfunction at 24 months (p = 0.020). Conclusions: Our trial did not find beneficial effects of HA-PCI over PCI on SRCF and QoL. The cognitive benefit of sparing the hippocampus in the context of PCI is still a subject of debate.

The Association of Gross Tumor Volume and Its Radiomics Features with Brain Metastases Development in Patients with Radically Treated Stage III Non-Small Cell Lung Cancer.

PURPOSE: To identify clinical risk factors, including gross tumor volume (GTV) and radiomics features, for developing brain metastases (BM) in patients with radically treated stage III non-small cell lung cancer (NSCLC). METHODS: Clinical data and planning CT scans for thoracic radiotherapy were retrieved from patients with radically treated stage III NSCLC. Radiomics features were extracted from the GTV, primary lung tumor (GTVp), and involved lymph nodes (GTVn), separately. Competing risk analysis was used to develop models (clinical, radiomics, and combined model). LASSO regression was performed to select radiomics features and train models. Area under the receiver operating characteristic curves (AUC-ROC) and calibration were performed to assess the models' performance. RESULTS: Three-hundred-ten patients were eligible and 52 (16.8%) developed BM. Three clinical variables (age, NSCLC subtype, and GTVn) and five radiomics features from each radiomics model were significantly associated with BM. Radiomic features measuring tumor heterogeneity were the most relevant. The AUCs and calibration curves of the models showed that the GTVn radiomics model had the best performance (AUC: 0.74; 95% CI: 0.71-0.86; sensitivity: 84%; specificity: 61%; positive predictive value [PPV]: 29%; negative predictive value [NPV]: 95%; accuracy: 65%). CONCLUSION: Age, NSCLC subtype, and GTVn were significant risk factors for BM. GTVn radiomics features provided higher predictive value than GTVp and GTV for BM development. GTVp and GTVn should be separated in clinical and research practice.

Co-occurrence of blaNDM-1, rmtC, and mcr-9 in multidrug-resistant Enterobacter kobei strain isolated from an infant with urinary tract infection.

OBJECTIVES: The co-emergence of mcr and carbapenem resistance genes in Gram-negative bacteria is a serious problem. This study aims to clarify the genetic characteristic of one novel multidrug-resistant Enterobacter kobei EC1382 with mcr-9 causing urinary tract inflammation in an infant. METHODS: Antimicrobial drug susceptibility testing was performed for this isolate using the broth microdilution method. Whole-genome sequencing was performed using the Illumina PacBio RS II platform and HiSeq platform, and the antimicrobial resistance genes, mobile elements, and plasmid replicon types were identified. Conjugation analysis was performed using Escherichia coli C600 as recipients. RESULTS: Enterobacter kobei EC1382 was resistant to carbapenem, aminoglycoside, and cephalosporin. Twenty-five antimicrobial resistance genes were identified, including genes conferring resistance to carbapenem (blaNDM-1), colistin (mcr-9), and aminoglycosides (rmtC). The blaNDM-1 gene, accompanied by bleMBL and rmtC located downstream of an ISCR14 element, was detected in the IncFII(Yp) type plasmid pEC1382-2. Interestingly, although E. kobei EC1382 was susceptible to colistin, it had three identical mcr-9 genes (two in the chromosome and one in the IncHI2-type plasmid pEC1382-1). The backbone (∼12.2-kb genetic fragment) of these mcr-9 (flanked by IS903B and IS481-IS26) regions were conserved in this strain, and they were found to be present in various bacteria as three types, implying a silent distribution. CONCLUSIONS: To the best of our knowledge, this is the first study to demonstrate the coexistence of blaNDM-1, rmtC, and mcr-9 in E. kobei. The silent prevalence of mcr-9 in bacteria may be a threat to public health.

Metabolomics-based response of Salmonella to desiccation stress and skimmed milk powder storage.

The strong survival ability of Salmonella in low-moisture foods (LMFs) has been of public concern, and is considered a threat to people's health. Recently, the development of omics technology has promoted research on the molecular mechanisms of the desiccation stress response of pathogenic bacteria. However, multiple analytical aspects related to their physiological characteristics remain unclear. We explored the physiological metabolism changes of S. enterica Enteritidis exposed to a 24 h-desiccation treatment and a subsequent 3-month desiccation storage in skimmed milk powder (SMP) with an approach of gas chromatography-mass spectrometry (GC-MS) and ultra-performance liquid chromatography-Q Exactive-mass spectrometry (UPLC-QE-MS). A total of 8,292 peaks were extracted, of which 381 were detected by GC-MS and 7,911 peaks were identified by LC-MS/MS, respectively. Through analyses of differentially expressed metabolites (DEMs) and key pathways, a total of 58 DEMs emerged from the 24 h-desiccation treatment, which exhibited the highest relevance for five metabolic pathways, involving glycine, serine, and threonine metabolism, pyrimidine metabolism, purine metabolism, vitamin B6 metabolism, and pentose phosphate pathway. After 3-month SMP storage, 120 DEMs were identified, which were related to several regulatory pathways including arginine and proline metabolism, serine and threonine metabolism, ß-alanine metabolism, glycerolipid metabolism, and glycolysis. The analyses of key enzyme activities of XOD, PK, and G6PDH and ATP content provided further evidence that supported the metabolic responses such as nucleic acid degradation, glycolysis, and ATP production played an important role in Salmonella's adaptation to desiccation stress. This study enables a better understanding of metabolomics-based responses of Salmonella at the initial stage of desiccation stress and the following long-term adaptive stage. Meanwhile, the identified discriminative metabolic pathways may serve as potentially useful targets in developing strategies for the control and prevention of desiccation-adapted Salmonella in LMFs.

Risk factors for cognitive impairment in radically treated stage III NSCLC: Secondary findings of the NVALT-11 study.

AIM: To identify risk factors for self-reported cognitive impairment in radically treated stage III non-small cell lung cancer (NSCLC). METHODS: Cognitive functioning was assessed using the EORTC-QLQ-C30 at seven pre-specified time points in the phase III NVALT-11 trial (observation versus prophylactic cranial irradiation [PCI] in stage III NSCLC treated with chemo-radiotherapy ± surgery). Cognition was analyzed as binary (impairment or not) and continuous outcome, respectively, using generalized estimating equation (GEE) before and after multiple imputation. A score < 75 was defined as cognitive impairment. A mean difference by < 10, 10-<20, ≥ 20 points was regarded as of no, moderate, and large clinical effect, respectively. We categorized the cognitive impairment into four types based on changes over time: sustained, reversible, recurring, and alternating. RESULTS: In the no-PCI arm, 43/84 [51.2%] reported cognitive impairment at least once, of which 31.4% were sustained, 25.7% reversible, 28.6% recurring, and 14.3% alternating. Results were similar in the PCI arm. Cognitive functioning at baseline was comparable in two arms and a score < 75 was a significant risk factor with large effect for subsequent cognitive impairment (no-PCI: ß = -23.30, p < 0.001; PCI arm: ß = -22.34, p < 0.001; All: ß = -23.47, p < 0.001). Younger age (≤60y), squamous histology, and PCI were risk factors without clinical relevance (ß > -10, p < 0.05). Cognitive functioning declined over time (ß = -0.26, p = 0.001) except for patients with cognitive impairment at baseline (ß = 0.141, p = 0.33). CONCLUSION: Cognitive impairment is dynamic over time with four types. Baseline cognitive impairment (score < 75) is the most important risk factor for subsequent cognitive impairment in stage III NSCLC. Note: This work has been partly reported as an oral presentation at the ESTRO 2021 meeting (OC-0176).

Analysis of Factors Affecting Psychological Resilience of Emergency Room Nurses Under Public Health Emergencies.

Resilience is essential for frontline health workers to cope with the unfavorable situations, especially under public health emergencies. Emergency room (ER) nurses are a special cohort of health professionals that may present moderate level of resilience. This study aimed to identify factors that are correlated with resilience in this special cohort to provide directions for intervention and management. ER nurses that have encountered a public health emergency within 3 months were recruited using purposive sampling and snowball technique for the study. Questionnaires, including Connor-Davidson Resilience Scale (CD-RISC), Zung Self-Rating Depression Scale (SDS), and Maslach Burnout Inventory-Human Services Survey (MBI-HSS) were established, followed by an in-depth interview to identify different clusters of themes. Thirteen ER nurses were recruited, and the average CD-RISC score was 66 ± 21. Resilience was negatively correlated with SDS index, and positively correlated with personal accomplishment. Five clusters of themes were identified from in-depth interviews, including physical tolerability, psychological tolerability, tenacity of internal drive, institutional implementation, and external adjustment. This study identified factors associated with resilience in ER nurses under public health emergencies, providing useful information for future directions for intervention.

The identification and preliminary study of lncRNA TUG1 and its related genes in hepatocellular carcinoma.

Introduction: Hepatocellular carcinoma (HCC) is a common malignant tumour of the digestive system, which is a threat to public health. The purpose of this study was to investigate the featured genes and pathways of HCC from a bioinformatics database, and verify their correlation with diagnosis and prognosis of HCC. Material and methods: We downloaded the gene expression profile on HCC from the Gene Expression Omnibus (GEO), and software R was used to identify differentially expressed lncRNA (DEL). The target genes of the lncRNA were further predicted by using a cluster database and molecular interaction database. Subsequently, a combined interaction network of target genes was constructed using the Cytoscape platform with preliminary verification at the level of different databases, cell lines, and tissues. Finally, we explored the effectiveness of TUG1 and its target genes on the diagnosis and prognosis of HCC by univariate Cox analysis and survival analysis. Results: A total of four DELs were identified and the most remarkably up-regulated lncRNA was TUG1, which included 12 high-confidence target genes. Moreover, we found that the expression changes of TUG1 and its target genes in different databases, cell lines, and liver cancer tissues were consistent with the prediction. The high expression of TUG1 and its target genes could significantly predict the shorter survival time of HCC patients, among which NCAPG, MCM6, PIGC, PEA15, and RACGAP1 have significant diagnostic value for HCC (AUC > 0.9). Conclusions: This study provides a starting point for the screening of therapeutically relevant targets in HCC. Further experiment should be conducted to verify our findings.

Effectivity of involved-field radiotherapy for recurrent brain metastasis in patients with small-cell lung cancer.

Objectives: To investigate the outcome difference of whole brain radiotherapy (WBRT) and involved-field radiotherapy (IFRT) in limited-stage small-cell lung cancer (LS-SCLC) patients with recurrent brain metastases (BMs) after prophylactic cranial irradiation (PCI). Methods: A retrospective analysis was carried out in 68 LS-SCLC patients who underwent WBRT or IFRT owing to the occurrence of recurrent BMs after PCI from 2009 to 2020. Results: The median overall survival (OS) of all patients was 11.43 months [95% confidence interval (CI) 9.39-13.48 months]. In the paired comparison of OS, the IFRT group had a significantly longer survival time than the WBRT group in all patients [17.80 months vs. 8.47 months; hazard ratio (HR), 0.393, 95% CI, 0.213-0.728; P = 0.002] and 46 matched patients (18.23 months vs. 8.73 months; HR, 0.411, 95% CI, 0.195-0.865; P = 0.019). In terms of the intra-cranial progression-free survival (iPFS), there was no significant difference between the WBRT group and IFRT group before matching (5.93 months vs. 7.30 months; HR, 0.644, 95% CI, 0.373-1.112; P = 0.111); similarly, no statistical difference was detected between the WBRT group and IFRT group after matching (5.33 months vs. 8.10 months; HR, 0.623, 95% CI, 0.323-1.199; P = 0.152). Meanwhile, of the 41 patients with symptoms, 27 cases (65.9%) had symptom relief, showing tolerable toxicity without unexpected toxicity during the observation. Conclusions: Compared with WBRT, IFRT exhibits better survival benefits for LS-SCLC patients with recurrent BMs after PCI. Re-irradiation for BMs exhibits advantages of symptom relief and tolerable side effects.

Investigation of the added value of CT-based radiomics in predicting the development of brain metastases in patients with radically treated stage III NSCLC.

Introduction: Despite radical intent therapy for patients with stage III non-small-cell lung cancer (NSCLC), cumulative incidence of brain metastases (BM) reaches 30%. Current risk stratification methods fail to accurately identify these patients. As radiomics features have been shown to have predictive value, this study aims to develop a model combining clinical risk factors with radiomics features for BM development in patients with radically treated stage III NSCLC. Methods: Retrospective analysis of two prospective multicentre studies. Inclusion criteria: adequately staged [18F-fluorodeoxyglucose positron emission tomography-computed tomography (18-FDG-PET-CT), contrast-enhanced chest CT, contrast-enhanced brain magnetic resonance imaging/CT] and radically treated stage III NSCLC, exclusion criteria: second primary within 2 years of NSCLC diagnosis and prior prophylactic cranial irradiation. Primary endpoint was BM development any time during follow-up (FU). CT-based radiomics features (N = 530) were extracted from the primary lung tumour on 18-FDG-PET-CT images, and a list of clinical features (N = 8) was collected. Univariate feature selection based on the area under the curve (AUC) of the receiver operating characteristic was performed to identify relevant features. Generalized linear models were trained using the selected features, and multivariate predictive performance was assessed through the AUC. Results: In total, 219 patients were eligible for analysis. Median FU was 59.4 months for the training cohort and 67.3 months for the validation cohort; 21 (15%) and 17 (22%) patients developed BM in the training and validation cohort, respectively. Two relevant clinical features (age and adenocarcinoma histology) and four relevant radiomics features were identified as predictive. The clinical model yielded the highest AUC value of 0.71 (95% CI: 0.58-0.84), better than radiomics or a combination of clinical parameters and radiomics (both an AUC of 0.62, 95% CIs of 0.47-076 and 0.48-0.76, respectively). Conclusion: CT-based radiomics features of primary NSCLC in the current setup could not improve on a model based on clinical predictors (age and adenocarcinoma histology) of BM development in radically treated stage III NSCLC patients.

Single Blind Randomized Controlled Trial of Modified Constraint-Induced Movement Therapy in Infants With the Sequelas of Unilateral Brachial Plexus Injury.

Objective: To explore the effect of modified constraint-induced movement therapy (mCIMT) on upper limbs residual dysfunction for infancy with the sequelas of unilateral brachial plexus injury (uBPI). Methods: Single blind randomized controlled trial of mCIMT vs. standard care. An enrolling 31 infants with a uBPI exhibiting residual dysfunction of the affected upper limb for over 6 months was conducted. And functional outcomes pertaining to the affected upper limb were assessed via AMS, GRES, RHS, and MSS at 0, 3, and 6 months after treatment. Results: No differences were found in baseline (acquisition phase) AMS, MSS, GRES, or RHS between the control and mCIMT groups [F(1, 14) = 0.062, P = 0.086; F(1, 14) = 0.483, P = 0.499; F(1, 14) = 0.272, P = 0.610; Z = -0.336, P = 7.373]. At the 3- and 6-month follow-up time points, AMS, MSS, and GRES scores were significantly improved over baseline in both groups [mCIMT: F(2, 30) = 183.750, 128.614, 110.085, P < 0.05; Control: F(2, 28) = 204.007, 75.246, 51.070, P < 0.05]. No significant differences were found between two treatment groups at the 3-month follow-up time point [F(1, 14) = 0.565, P = 0.465; F(1, 14) = 0.228, P = 0.641; F(1, 14) = 0.713, P = 0.413; Z = -0.666, P = 0.505]. However, at the 6-month follow-up time point, AMS and MSS scores were significantly improved in the mCIMT group relative to the control group [F(1, 14) = 8.077, P = 0.013; F(1, 14) = 18.692, P = 0.001]. Conclusion: mCIMT may benefit the rehabilitation of residual upper limb dysfunction associated with a uBPI in infants. Clinical Trial Registration: [www.chictr.org.cn], identifier [ChiCTR1900022119].

Risk Factors for Brain Metastases in Patients With Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

The use of prophylactic cranial irradiation (PCI) for small cell lung cancer (SCLC) patients is controversial. Risk factors for brain metastasis (BM) development are largely lacking, hampering personalized treatment strategies. This study aimed to identify the possible risk factors for BM in SCLC.We systematically searched the Pubmed database (1 January 1995 to 18 January 2021) according to the PRISMA guidelines. Eligibility criteria: studies reporting detailed BM data with an adequate sample size (randomized clinical trials [RCTs]: N ≥50; non-RCTs: N ≥100) in patients with SCLC. We summarized the reported risk factors and performed meta-analysis to estimate the pooled hazard ratios (HR) if enough qualified data (i.e., two or more studies; the same study type; the same analysis method; and HRs retrievable) were available. In total, 61/536 records were eligible (18 RCTs and 39 non-RCTs comprising 13,188 patients), in which 57 factors were reported. Ten factors qualified BM data for meta-analysis: Limited stage disease (LD) (HR = 0.34, 95% CI: 0.17-0.67; P = 0.002) and older age (≥65) (HR = 0.70, 95% CI: 0.54-0.92; P = 0.01) were associated with less BM; A higher T stage (≥T3) (HR = 1.72, 95% CI: 1.16-2.56; P = 0.007) was a significant risk factor for BM. Male sex (HR = 1.24, 95% CI: 0.99-1.54; P = 0.06) tended to be a risk factor, and better PS (0-1) (HR = 0.66, 95% CI: 0.42-1.02; P = 0.06) tended to have less BM. Smoking, thoracic radiotherapy dose were not significant (P >0.05). PCI significantly decreased BM (P <0.001), but did not improve OS in ED-SCLC (P = 0.81). A higher PCI dose did not improve OS (P = 0.11). The impact on BM was conflicting between Cox regression data (HR = 0.59, 95% CI: 0.26-1.31; P = 0.20) and competing risk regression data (HR = 0.74, 95% CI: 0.55-0.99; P = 0.04). Compared to M0-M1a, M1b was a risk factor for OS (P = 0.01) in ED-SCLC, but not for BM (P = 0.19). As regular brain imaging is rarely performed, high-quality data is lacking. Other factors such as N-stage and blood biomarkers had no qualified data to perform meta-analysis. In conclusion, younger age, higher T stage, and ED are risk factors for BM, suggesting that PCI should be especially discussed in such cases. Individual patient data (IPD) meta-analysis and well-designed RCTs are needed to better identify more risk factors and further confirm our findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021228391, identifier CRD42021228391.

A novel Bacillus cereus bacteriophage DLn1 and its endolysin as biocontrol agents against Bacillus cereus in milk.

Bacillus cereus is a common foodborne pathogen that causes vomiting and diarrheal symptoms. Due to its spore-forming ability, B. cereus can resist physical sterilization and possess a relatively high contamination level in dairy products; therefore, it is necessary to develop an efficient strategy to control the growth of B. cereus. In this study, a novel bacteriophage, named DLn1, was isolated and characterized, and its endolysin was expressed. Morphological and genomic analyses revealed that the phage is a new species belonging to the Northropvirinae subfamily of the Salasmaviridae family. The life cycle and stability assays showed that the phage DLn1 exhibited a short latent period (15 min) and high burst size (618 plaque-forming units (PFU)/cell) and was tolerant to a wide range of pH (4-10) and temperature (4-55 °C) conditions. This lytic phage had narrow but specific host range to B. cereus strains, and could effectively reduce the number of B. cereus in milk within 6 h. More interestingly, the purified endolysin of phage DLn1 had a much wider lytic range and the inhibitory effect against B. cereus in milk was more efficient. Taken together, the new phage DLn1 and its endolysin could be promising biocontrol agents against B. cereus in dairy products.

Lung cancer diagnosis using deep attention-based multiple instance learning and radiomics.

BACKGROUND: Early diagnosis of lung cancer is a key intervention for the treatment of lung cancer in which computer-aided diagnosis (CAD) can play a crucial role. Most published CAD methods perform lung cancer diagnosis by classifying each lung nodule in isolation. However, this does not reflect clinical practice, where clinicians diagnose a patient based on a set of images of nodules, instead of looking at one nodule at a time. Besides, the low interpretability of the output provided by these methods presents an important barrier for their adoption. METHOD: In this article, we treat lung cancer diagnosis as a multiple instance learning (MIL) problem, which better reflects the diagnosis process in the clinical setting and provides higher interpretability of the output. We selected radiomics as the source of input features and deep attention-based MIL as the classification algorithm. The attention mechanism provides higher interpretability by estimating the importance of each instance in the set for the final diagnosis. To improve the model's performance in a small imbalanced dataset, we propose a new bag simulation method for MIL. RESULTS AND CONCLUSION: The results show that our method can achieve a mean accuracy of 0.807 with a standard error of the mean (SEM) of 0.069, a recall of 0.870 (SEM 0.061), a positive predictive value of 0.928 (SEM 0.078), a negative predictive value of 0.591 $0.591$ (SEM 0.155), and an area under the curve (AUC) of 0.842 (SEM 0.074), outperforming other MIL methods. Additional experiments show that the proposed oversampling strategy significantly improves the model's performance. In addition, experiments show that our method provides a good indication of the importance of each nodule in determining the diagnosis, which combined with the well-defined radiomic features, to make the results more interpretable and acceptable for doctors and patients.

A novel multiplex PCR method for simultaneous identification of hypervirulent Listeria monocytogenes clonal complex 87 and CC88 strains in China.

Listeria monocytogenes is an important foodborne pathogen worldwide, with 20-30% fatality rate in vulnerable persons. The hypervirulent L. monocytogenes clonal complex (CC) 87 strains have emerging both in food production environments and clinic cases. The objective of this study was to develop a multiplex PCR to simultaneously detect L. monocytogenes CC87 and CC88 strains based on pan-genome analysis. A novel multiplex PCR comprised of genes A6K41_13255 (specific for CC87 and 88), BCW_4260_01987 group_8135 (specific for CC88) and 02-1103_01073 group_5869 (specific for L. monocytogenes) were designed. The specificity of this multiplex PCR was robust verified with other CCs of L. monocytogenes and other species strains. The detection limit of this multiplex PCR for CC87 and CC88 were 1.7 × 104 cfu/mL and 2.1 × 104 cfu/mL, respectively. This multiplex PCR could accurately detect CC87 and CC88 strains with the interference of different ratios of L. monocytogenes CC8, CC9, CC121, CC155, and L. innocua strains. Furthermore, this multiplex PCR method could successfully detect 1.9 × 104 cfu/mL of L. monocytogenes CC87 and 1.7 × 104 cfu/mL CC88 strains in artificially contaminated milk after 9 h enrichment, respectively. In addition, this multiplex PCR could accurately detect CC87 isolates in food samples within 48 h, which was faster than the routine MLST analysis. In conclusion, this novel multiplex PCR offers a promising approach for accurate, inexpensive, and rapid detection of L. monocytogenes CC87 and CC88 strains simultaneously, which could apply to surveillance the prevalence of CC87 and CC88 strains in both food and food production environments and to evaluate the effect of disinfection measures for controlling the persistent L. monocytogenes contamination.