CAR T-cell treatment during the COVID-19 pandemic: Management strategies and challenges.

The pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly across the world. Currently, the COVID-19 pandemic is affecting the continuity of essential routine healthcare services and procedures, including chimeric antigen receptor T-cell (CAR-T) therapy, a life-saving option for patients with relapsed/refractory (R/R) hematologic malignancies. Due to the rapid disease progression of hematological malignancies, there is an urgent need to manufacture and utilize CAR T-cells. However, CAR-T treatment has become extraordinarily challenging during this COVID-19 pandemic. Thus, many medical and technical factors must now be taken into consideration before, during, and after CAR-T therapy. The purpose of this review is to provide brief suggestions for rational decision-making strategies in evaluating and selecting CAR T-cell treatment and appropriate CAR T-cell products, and protective strategies for medical staff and patients to prevent infection in the midst of the current COVID-19 pandemic.

Image quality assessment of a photon counting detector in x-ray projection imaging.

The recent advancements in the photon counting detection have created a significant growing research interest in the x-ray imaging. It is essential to objectively understand the image quality parameters of a photon counting detector before developing imaging applications. In this work, we have assessed the imaging quality of a cadmium telluride (CdTe) based PCD in projection imaging mode. The detector is 70.4 mm × 6.6 mm dimensions. The detector has a pixel array of 64×4 with a pixel pitch of 1.1 mm×1.65 mm. With each pixel having 4 channels in its corresponding ASIC, this PCD can create three bin images from a single projection. With a microfocus x-ray source, the imaging quality in each bin image was measured in terms of the spatial resolution, noise, and contrast to noise ratio (CNR). We used 70 kV, 50µA, 10 s (0.5mAs) with 0.5mm thick aluminum (Al) filter for the acquisition of each image. The MTF curves indicated that the spatial resolution for the bin-1, bin-2, and bin-3 was almost identical. The NNPS curves indicated that the noise in bin 1 and bin 2 images was almost the same for all frequencies while bin 3 image had relatively less noise. The CNR analyses showed that the bin-1 image had the highest CNR. As the flux was increased from 0.5 to 1 mAs, the number of detected counts also increased that resulted in the CNR increase. Beyond this flux, the pulse pileup occurred due to which multiple counts were read as single that resulted in few detected counts and lower CNR. The knowledge of the spatial resolution, noise, and CNR in terms of energy binning allows the determination and optimization of imaging techniques necessary for various applications.

Assessment of Feng-Liao-Chang-Wei-Kang as a potential inducer of cytochrome P450 3A4 and pregnane X receptors.

Feng-Liao-Chang-Wei-Kang (FLCWK), a traditional Chinese patent medicine, consists primarily of Polygonum hydropiper and Daphniphyllum calycinum roots. As a complex containing several kinds of flavonoids, FLCWK has the potential to impact the drug metabolism enzyme P450 3A4 (CYP3A4) and nuclear receptors. The purpose of this research was to probe the effects of FLCWK on CYP3A1, the homolog of CYP3A4 in rats, and to confirm whether FLCWK interferes with PXR and CAR-mediated transactivation of CYP3A4. The effects of FLCWK on Cyp3a1 mRNA, catalytic activity levels, and protein expression in Sprague-Dawley (SD) rat liver tissues were examined using real-time PCR, western blotting, and high-performance liquid chromatography (HPLC) assays, respectively. The efficacy of PXR and CAR on CYP3A4 transcriptional activity were detected using luciferase reporter assays and further research of the impact of FLCWK on CYP3A4 gene expression mediated by the PXR pathway was examined by transient transfection of PXR siRNA. FLCWK significantly increased Cyp3a1 mRNA, CYP3A1 activity, and protein expression levels in SD rats. FLCWK highly induced CYP3A4 luciferase activity mediated by PXR in PXRCYP3A4 co-transfected cells. A siRNA-mediated drop-off in PXR expression greatly cut the effect of FLCWK on CYP3A4 mRNA expression in HepG2 cells. These findings show that FLCWK up-regulates CYP3A4 levels via the PXR pathway. This effect should be considered being applied in clinical use as FLCWK has the potential to interact with other drugs.

Detecting Wash Trade in Financial Market Using Digraphs and Dynamic Programming.

A wash trade refers to the illegal activities of traders who utilize carefully designed limit orders to manually increase the trading volumes for creating a false impression of an active market. As one of the primary formats of market abuse, a wash trade can be extremely damaging to the proper functioning and integrity of capital markets. The existing work focuses on collusive clique detections based on certain assumptions of trading behaviors. Effective approaches for analyzing and detecting wash trade in a real-life market have yet to be developed. This paper analyzes and conceptualizes the basic structures of the trading collusion in a wash trade by using a directed graph of traders. A novel method is then proposed to detect the potential wash trade activities involved in a financial instrument by first recognizing the suspiciously matched orders and then further identifying the collusions among the traders who submit such orders. Both steps are formulated as a simplified form of the knapsack problem, which can be solved by dynamic programming approaches. The proposed approach is evaluated on seven stock data sets from the NASDAQ and the London Stock Exchange. The experimental results show that the proposed approach can effectively detect all primary wash trade scenarios across the selected data sets.

Adaptive hidden Markov model with anomaly States for price manipulation detection.

Price manipulation refers to the activities of those traders who use carefully designed trading behaviors to manually push up or down the underlying equity prices for making profits. With increasing volumes and frequency of trading, price manipulation can be extremely damaging to the proper functioning and integrity of capital markets. The existing literature focuses on either empirical studies of market abuse cases or analysis of particular manipulation types based on certain assumptions. Effective approaches for analyzing and detecting price manipulation in real time are yet to be developed. This paper proposes a novel approach, called adaptive hidden Markov model with anomaly states (AHMMAS) for modeling and detecting price manipulation activities. Together with wavelet transformations and gradients as the feature extraction methods, the AHMMAS model caters to price manipulation detection and basic manipulation type recognition. The evaluation experiments conducted on seven stock tick data from NASDAQ and the London Stock Exchange and 10 simulated stock prices by stochastic differential equation show that the proposed AHMMAS model can effectively detect price manipulation patterns and outperforms the selected benchmark models.

Risk factors of indoor fall injuries in community-dwelling older women: a prospective cohort study.

The aims of the study were to explore the characteristics and the potential risk factors of indoor fall injuries in community-dwelling older women, and to provide evidence for the future intervention strategy. A prospective cohort of 3043 women aged 60 years old and above from 3 selected counties in Shanghai was followed up on the outcomes of indoor fall injuries for up to 1 year. Demographic and health data were collected during admission; the physical function, balance ability and home-living environment were examined by a structured questionnaire when admitted. The outcome of indoor fall injury was investigated by a visit in month 3, month 6 and month 12 after baseline survey. Univariate analysis and Multiple Logistic Regression Model were used to examine the associations between potential risk factors and outcomes of indoor fall injuries. Two hundred and thirty-one of the 3043 women (7.6%) eventually suffered indoor fall injuries at least once during the 1-year follow-up. The injurious falls of women were significantly associated with age, educational level, marital status, health status, balance ability, physical activity and home-living environment in the univariate analyses. Women who worried about falls and restrained activities for it were more likely to suffer fall injury. Younger women, with less chronic disease, with good balance ability and living in good corridor environment, were less likely to receive fall injury in multiple logistic regression analyses. Multidimensional factors were associated with indoor fall injuries for community-dwelling older women. Proper clinical treatment of chronic disease and improvement of women's balance ability, as well as reducing the risk factor of indoor environment, which will play vital roles in preventing indoor fall injuries, should be prioritized for the intervention strategy.

A low-cost exon capture method suitable for large-scale screening of genetic deafness by the massively-parallel sequencing approach.

Current major barriers for using next-generation sequencing (NGS) technologies in genetic mutation screening on an epidemiological scale appear to be the high accuracy demanded by clinical applications and high per-sample cost. How to achieve high efficiency in enriching targeted disease genes while keeping a low cost/sample is a key technical hurdle to overcome. We validated a cDNA-probe-based approach for capturing exons of a group of genes known to cause deafness. Polymerase chain reaction amplicons were made from cDNA clones of the targeted genes and used as bait probes in hybridization for capturing human genomic DNA (gDNA) fragments. The cDNA library containing the clones of targeted genes provided a readily available, low-cost, and regenerable source for producing capture probes with standard molecular biology equipment. Captured gDNA fragments by our method were sequenced by the Illumina NGS platform. Results demonstrated that targeted exons captured by our approach achieved specificity, multiplexicity, uniformity, and depth of coverage suitable for accurate sequencing applications by the NGS systems. Reliable genotype calls for various homozygous and heterozygous mutations were achieved. The results were confirmed independently by conventional Sanger sequencing. The method validated here could be readily expanded to include all-known deafness genes for applications such as genetic hearing screening in newborns. The high coverage depth and cost benefits of the cDNA-probe-based exon capture approach may also facilitate widespread applications in clinical practices beyond screening mutations in deafness genes.

Fractional anisotropy for assessment of white matter tracts injury in methylmalonic acidemia.

BACKGROUND: Methylmalonic acidemia (MMA) is a multifactorial autosomal recessive inborn error of organic acid metabolism, often presenting with neurological symptoms. As neurological disorders are often related to white matter injury, diffusion tensor imaging (DTI) is an excellent tool for assessment of white matter injury and possibly for diagnosing this disorder. METHODS: We retrospectively analyzed DTI images of 12 patients with MMA (7 males, 5 females, age range: 7 - 12 months, mean age: 9.25 +/- 1.70 months) with negative MRI findings. And another 12 age-matched and gender-matched infants were enrolled as control subjects. Fractional anisotropy (FA) of different white matter tracts of the brain was measured in both groups. RESULTS: For patients with negative MRI findings, compared with healthy infants, a statistically significant reduction in DTI FA value of the frontal white matter, temporal white matter, and occipital white matter was observed (P < 0.01). CONCLUSIONS: In addition to conventional T1W and T2W MR Image, Brain DTI presents a useful, sensitive and complementary tool for the assessment of brain damage in patients with MMA.