Genomic insights unveil the plasmid transfer mechanism and epidemiology of hypervirulent Klebsiella pneumoniae in Vietnam.

Hypervirulent Klebsiella pneumoniae (hvKp) is a significant cause of severe invasive infections in Vietnam, yet data on its epidemiology, population structure and dynamics are scarce. We screened hvKp isolates from patients with bloodstream infections (BSIs) at a tertiary infectious diseases hospital in Vietnam and healthy individuals, followed by whole genome sequencing and plasmid analysis. Among 700 BSI-causing Kp strains, 100 (14.3%) were hvKp. Thirteen hvKp isolates were identified from 350 rectal swabs of healthy adults; none from 500 rectal swabs of healthy children. The hvKp isolates were genetically diverse, encompassing 17 sequence types (STs), predominantly ST23, ST86 and ST65. Among the 113 hvKp isolates, 14 (12.6%) carried at least one antimicrobial resistance (AMR) gene, largely mediated by IncFII, IncR, and IncA/C plasmids. Notably, the acquisition of AMR conjugative plasmids facilitated horizontal transfer of the non-conjugative virulence plasmid between K. pneumoniae strains. Phylogenetic analysis demonstrated hvKp isolates from BSIs and human carriage clustered together, suggesting a significant role of intestinal carriage in hvKp transmission. Enhanced surveillance is crucial to understand the factors driving intestinal carriage and hvKp transmission dynamics for informing preventive measures. Furthermore, we advocate the clinical use of our molecular assay for diagnosing hvKp infections to guide effective management.

A bibliometric literature review of stock price forecasting: From statistical model to deep learning approach.

We introduce a comprehensive analysis of several approaches used in stock price forecasting, including statistical, machine learning, and deep learning models. The advantages and limitations of these models are discussed to provide an insight into stock price forecasting. Traditional statistical methods, such as the autoregressive integrated moving average and its variants, are recognized for their efficiency, but they also have some limitations in addressing non-linear problems and providing long-term forecasts. Machine learning approaches, including algorithms such as artificial neural networks and random forests, are praised for their ability to grasp non-linear information without depending on stochastic data or economic theory. Moreover, deep learning approaches, such as convolutional neural networks and recurrent neural networks, can deal with complex patterns in stock prices. Additionally, this study further investigates hybrid models, combining various approaches to explore their strengths and counterbalance individual weaknesses, thereby enhancing predictive accuracy. By presenting a detailed review of various studies and methods, this study illuminates the direction of stock price forecasting and highlights potential approaches for further studies refining the stock price forecasting models.

Product Attributes of CAR T-cell Therapy Differentially Associate with Efficacy and Toxicity in Second-line Large B-cell Lymphoma (ZUMA-7).

Treatment resistance and toxicities remain a risk following chimeric antigen receptor (CAR) T-cell therapy. Herein, we report pharmacokinetics, pharmacodynamics, and product and apheresis attributes associated with outcomes among patients with relapsed/refractory large B-cell lymphoma (LBCL) treated with axicabtagene ciloleucel (axi-cel) in ZUMA-7. Axi-cel peak expansion associated with clinical response and toxicity, but not response durability. In apheresis material and final product, a naive T-cell phenotype (CCR7+CD45RA+) expressing CD27 and CD28 associated with improved response durability, event-free survival, progression-free survival, and a lower number of prior therapies. This phenotype was not associated with high-grade cytokine release syndrome (CRS) or neurologic events. Higher baseline and postinfusion levels of serum inflammatory markers associated with differentiated/effector products, reduced efficacy, and increased CRS and neurologic events, thus suggesting targets for intervention. These data support better outcomes with earlier CAR T-cell intervention and may improve patient care by informing on predictive biomarkers and development of next-generation products. SIGNIFICANCE: In ZUMA-7, the largest randomized CAR T-cell trial in LBCL, a naive T-cell product phenotype (CCR7+CD45RA+) expressing CD27 and CD28 associated with improved efficacy, decreased toxicity, and a lower number of prior therapies, supporting earlier intervention with CAR T-cell therapy. In addition, targets for improvement of therapeutic index are proposed. This article is featured in Selected Articles from This Issue, p. 4.

Axicabtagene Ciloleucel in Combination with the 4-1BB Agonist Utomilumab in Patients with Relapsed/Refractory Large B-Cell Lymphoma: Phase 1 Results from ZUMA-11.

PURPOSE: Chimeric antigen receptor (CAR) T-cell therapies have shown clinical benefit for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL), yet approximately 60% of patients do not respond or eventually relapse. We investigated the safety and feasibility of the CD19-directed CAR T-cell therapy axicabtagene ciloleucel (axi-cel) in combination with the 4-1BB agonist antibody utomilumab as an approach to improve efficacy of CAR T-cell therapy. PATIENTS AND METHODS: In phase 1 of the single-arm ZUMA-11 trial, patients with R/R LBCL received a single axi-cel infusion (target dose, 2 × 106 cells/kg) plus utomilumab 10 to 200 mg intravenously every 4 weeks for up to 6 months in a dose-escalation design. The primary endpoint was incidence of dose-limiting toxicities (DLT) with utomilumab. Key secondary endpoints were safety, antitumor activity, pharmacokinetics, and pharmacodynamics. RESULTS: No DLTs were observed among patients treated with axi-cel and utomilumab (n = 12). Grade ≥3 adverse events occurred in 10 patients (83%); none were Grade ≥3 cytokine release syndrome or neurologic events. The objective response rate was 75% and seven patients (58%) had a complete response. Peak CAR T-cell levels increased in a utomilumab dose-dependent manner up to 100 mg. Patients who received utomilumab 100 mg had persistently increased CAR T cells on days 57 to 168 compared with other dose levels. Utomilumab was associated with dose-dependent increases in IL2, IFNγ, and IL10. CONCLUSIONS: Utomilumab-mediated 4-1BB agonism combined with axi-cel therapy had a manageable safety profile. Dual 4-1BB and CD28 costimulation is a feasible therapeutic approach that may enhance CAR T-cell expansion in patients with LBCL.

Leaf Recognition Based on Joint Learning Multiloss of Multimodel Convolutional Neural Networks: A Testing for Vietnamese Herb.

A new modification of multi-CNN ensemble training is investigated by combining multiloss functions from state-of-the-art deep CNN architectures for leaf image recognition. We first apply the U-Net model to segment leaf images from the background to improve the performance of the recognition system. Then, we introduce a multimodel approach based on a combination of loss functions from the EfficientNet and MobileNet (called as multimodel CNN (MMCNN)) to generalize a multiloss function. The joint learning multiloss model designed for leaf recognition allows each network to perform its task and cooperate with the others simultaneously, where knowledge from various trained deep networks is shared. This cooperation-proposed multimodel is forced to deal with more complicated problems rather than a simple classification. Therefore, the network can learn much rich information and improve its generalization capability. Furthermore, a multiloss trade-off strategy between two deep learning models can reduce the effect of redundancy problems in ensemble classifiers. The performance of our approach is evaluated by our custom Vietnamese herbal leaf species dataset, and public datasets such as Flavia, Leafsnap, and Folio are used to build test cases. The results confirm that our approach enhances the leaf recognition performance and outperforms the current standard single networks while having less low computation cost.

Coronary Vessel Segmentation by Coarse-to-Fine Strategy Using U-nets.

Each level of the coronary artery has different sizes and properties. The primary coronary arteries usually have high contrast to the background, while the secondary coronary arteries have low contrast to the background and thin structures. Furthermore, several small vessels are disconnected or broken up vascular segments. It is a challenging task to use a single model to segment all coronary artery sizes. To overcome this problem, we propose a novel segmenting method for coronary artery extraction from angiograms based on the primary and secondary coronary artery. Our method is a coarse-to-fine strategic approach for extracting coronary arteries in many different sizes. We construct the first U-net model to segment the main coronary artery extraction and build a new algorithm to determine the junctions of the main coronary artery with the secondary coronary artery. Using these junctions, we determine regions of the secondary coronary arteries (rectangular regions) for a secondary coronary artery-extracted segment with the second U-net model. The experiment result is 76.40% in terms of Dice coefficient on coronary X-ray datasets. The proposed approach presents its potential in coronary vessel segmentation.

Importance of anatomical dominance in the evaluation of coronary dilatation in Kawasaki disease.

Introduction In Kawasaki disease, although coronary dilatation is attributed to vasculitis, the effect of myocardial inflammation is underestimated. Coronary dilatations are determined by Z-scores, which do not take into account dominance. The aim of the present study was to describe the impact of coronary dominance on dilatation in Kawasaki disease. METHODS: We performed a retrospective analysis of coronary dilatations according to angiography categorisation of dominance. RESULTS: Of 28 patients (2.6 [0.2-10.1] years), right dominance was present in 15 patients and left in 13. Early dilatation was present in all patients, of whom 11 were ipsilateral to the dominant segment and 17 contralateral. Ipsilateral dilatations were present at diagnosis (9/11 versus 6/17, p=0.02) compared with contralateral dilatations, which developed 2 weeks after diagnosis (9/11 versus 16/17, p=0.29). Coronary artery Z-scores of patients with contralateral dilatation increased at 2 weeks, before returning to baseline values (2.0±2.2 at diagnosis, 4.1±1.8 at 2 weeks, 1.8±1.2 at 3-6 months, p=0.001), compared with patients with ipsilateral dilatation in whom Z-scores were maximal at diagnosis and remained stable (3.0±0.9, 2.7±1.1 and 2.6±1.5, respectively, p=0.13). Dominant coronary artery Z-scores were higher compared with non-dominant segments at diagnosis (3.0±0.9 versus 1.0±0.8, p<0.001) and at late follow-up (2.6±1.5 versus 0.4±1.4, p=0.002) in patients with ipsilateral dilatation. CONCLUSION: Progression of coronary dilatation after diagnosis may be a sign of dilatation secondary to vasculitis, as opposed to regression of Z-scores in ipsilateral dilatations, probably related to physiological vasodilatation in response to carditis. This needs to be validated in larger studies against vasculitic and myocardial inflammatory markers.

The epidemiology, prevention, and detection of melanoma.

We are seeing a record number of newly diagnosed skin cancers worldwide, with the incidence of melanoma increasing at a faster rate than almost all other cancers. As clinicians, we will have, by far, the greatest impact on reducing this incidence through better methods of early detection of melanoma and proven prevention methods and techniques. The medical community must enhance its efforts to increase its training of new health care personnel who are capable of diagnosing and treating this record number of patients with skin cancer. We must also try to increase the access to our limited number of dermatologists and provide novel ways of patient education such as through skin self-examinations, total body photography, and improved education for our children. By providing easier access to skin examinations, we will increase our chances of detecting melanoma in its earliest and most curable form. The dangers of indoor tanning beds and salons must be transparent to those that use them, focusing on expanding the oversight of such facilities by our local and federal governmental agencies while establishing legislation in several states to further limit their use to our youth, who are especially at high risk for developing melanoma in the future. This review will focus on the epidemiology, prevention, and detection of melanoma.

Intrinsic versus environmental influences on T-cell responses in aging.

A decline in T-cell responses and a switch to memory T-cell predominance occur with aging. We have used the T-cell receptor (TCR) transgenic mouse model to study age-associated changes in T-cell responses that are a consequence of shifts in subset representation versus changes intrinsic to T cells versus changes in the 'aged' microenvironment. We found that naive transgene-expressing (Tg(+)) CD4(+) T cells from aged mice respond to antigen with reduced interleukin-2 (IL-2) production, decreased cell expansion, and limited differentiation to effectors. Comparable to the characteristic accumulation of memory phenotype T cells in aged humans and conventional rodents, Tg(+) CD4(+) T cells from old OTII and 6.5 TCR transgenic mice acquire a memory phenotype without immunization and become hyporesponsive. The naive Tg(+) CD8(+) T cells from aged 2C mice expressed activation markers, produced IL-2, proliferated, and differentiated into cytotoxic T lymphocytes as efficiently as their young counterparts. Responses by adoptive transferred Tg(+) cells from young mice, immunized in young and old conventional hosts, indicated that the host age influences the onset of cell division, level of cell expansion, and number of cytokine-producing cells. Co-transfer of dendritic cells (DCs) from young and less so from aged conventional mice partially restored responses. Furthermore, DCs and T-cell migration to draining lymphoid organs was reduced due to deficiencies intrinsic to aged cells and the aged environment. Thus, alterations in T-cell responses in aging are attributable to intrinsic and environmental influences.