Corrigendum to "Rational engineering of an improved adenosine deaminase 2 enzyme for weaponizing T-cell therapies": [Immuno-Oncology and Technology 10 (2023) 100394].

[This corrects the article DOI: 10.1016/j.iotech.2023.100394.].

Rational engineering of an improved adenosine deaminase 2 enzyme for weaponizing T-cell therapies.

Adenosine is a potent immunosuppressive metabolite that accumulates in the extracellular space within solid tumors and inhibits the antitumor function of native immune cell responses as well as chimeric antigen receptor (CAR) T-cell therapies. Here, we show that engineered human cells can degrade extracellular adenosine through secretion of adenosine deaminase (ADA) enzymes-a possible therapeutic enhancement for CAR T cells. We first determine that the high-activity ADA1 isoform is naturally intracellularly restricted and show that the addition of canonical or computationally predicted secretory peptides did not allow for improved secretion. We did, however, determine that the lower-activity ADA2 isoform is naturally secreted. Thus, we utilized phylogenetic-based structural comparisons to guide a mutational survey of ADA2 active site residues, which when coupled with a high-throughput screen for enhanced ADA2-mediated extracellular adenosine rate allowed isolation of the most catalytically efficient ADA2 variant reported to date. When expressed by human cells, this variant exhibits 30× higher extracellular adenosine degradation activity than the wild-type enzyme. Finally, we demonstrate that Jurkat and CAR T cells engineered to express this secreted, high-activity ADA2 variant can degrade significant amounts of extracellular adenosine in vitro.

Mobile Stroke Unit Reduces Time to Image Acquisition and Reporting.

Timely administration of thrombolytic therapy is critical to maximizing the likelihood of favorable outcomes in patients with acute ischemic stroke. Although emergency medical service activation overall improves the timeliness of acute stroke treatment, the time from emergency medical service dispatch to hospital arrival unavoidably decreases the timeliness of thrombolytic administration. Our mobile stroke unit, a new-generation ambulance with on-board CT scanning capability, reduces key imaging time metrics and facilitates in-the-field delivery of IV thrombolytic therapy.

Computer technology: state of the art and future trends.

Computer technology and, more broadly, information technology, are bringing about a fundamental transformation in our society from an industrial economy to an information economy. A review of the short history and present state of information technology identifies two major undercurrents: the miniaturization of computer components, which has produced a millionfold increase in the complexity possible in a single chip of silicon, and the integration of four previously separate areas of information technology: computation, communication, databases and the user interface. Microelectronics, computer networks, data storage and user amenities are the basic technologies that support these four areas and stimulate their progress. Future trends in speech recognition, voice synthesis, artificial intelligence, expert systems, computational imaging and scientific workstations are also examined.

A clinical study comparing marginal and occlusal accuracy of crowns fabricated from double-arch and complete-arch impressions.

BACKGROUND: The double-arch impression technique is widely used in the provision of laboratory fabricated restorations. However, there is little clinical evidence to support or refute its use. The aim of this prospective clinical study was to evaluate the occlusion and marginal fit of posterior full crowns made from double-arch impressions, and to compare these to control crowns fabricated from conventional complete-arch impressions. METHODS: Ten patients requiring single posterior ceramo-metal full crowns had both double-arch and complete-arch impressions taken of the prepared tooth. Two crowns were fabricated for each tooth, using the casts made from both impression methods. Both crowns were tried in and the occlusion and margins evaluated. The results were composed using nonparametric statistical analysis with the probability level for significance at alpha=0.05. RESULTS: The crowns fabricated from the double-arch impression were found to be more accurate in closure to the intercuspal position and had fewer interferences in lateral excursions. There were no significant differences between the two crown groups regarding protrusive interferences and margin quality. CONCLUSIONS: Crowns fabricated from the double-arch impressions were equivalent in marginal accuracy and superior occlusally to crowns fabricated from the complete-arch impressions.

Aminoglycoside antibiotics bound to aminoglycoside-detoxifying enzymes and RNA adopt similar conformations.

Conformations of ribostamycin and isepamicin, aminoglycoside antibiotics, bound to an aminoglycoside antibiotic, 3'-phosphotransferase, were determined by transferred nuclear Overhauser effect spectroscopy and molecular modeling. Two major conformers of enzyme-bound ribostamycin, a neomycin-group aminoglyeoside were observed. The 3'- and 5"-OH groups (reactive hydroxyl groups) in the conformers are placed in approximate locations. One of the conformers is similar to the structure of paromomycin bound to a 27-nucleotide piece of ribosomal RNA that represents the A-site of the small ribosomal subunit, where rings A and C are in an orthogonal arrangement. Isepamicin, a kanamycin-group aminoglycoside antibiotic, also showed two major enzyme-bound conformations. Both conformations were similar to those observed for bound isepamicin in the active site of an aminoglycoside(6')-acetyl transferase-Ii. Conformations of other RNA-bound kanamycin-group aminoglycosides were also similar to the enzyme-bound conformations of isepamicin. These observations suggest that aminoglycosides may adopt similar conformations when bound to RNA and protein targets. This may have significant implications in the design of enzyme inhibitors and/or antibiotics.

Immunoglobulin concentrations in children receiving treatment for acute lymphoblastic leukaemia.

As part of a wider survey of infections and defence mechanisms, concentrations of serum immunoglobulins IgG, IgA, and IgM were measured regularly by single radial immunodiffusion in a group of children receiving treatment for acute lymphoblastic leukaemia while in their first remission. IgM concentrations were often markedly raised at diagnosis, and IgG and IgA concentrations both began falling within one month of diagnosis. Four months after diagnosis all three had fallen significantly, but this tendency stopped after six months. Only IgG partially recovered, and non returned to pretreatment concentrations even in children followed for two years. The results suggest that vincristine and prednisone are the major factors that initiated the fall in IgG and IgA. Lowered IgM concentrations may have been due to cranial irradiation or continuous maintenance treatment, or both.

Anisocytosis and the C-1000 Channelyzer in macrocytic anaemia.

Red cell anisocytosis as assessed using the Coulter Channelyzer C-1000 showed an increase with progressive anaemia in 25 patients with macrocytosis due to B12 and/or folate deficiency. In deficiency of a single factor, the degree of anisocytosis increased with progressive anaemia. In five cases with B12 and folate deficiency combined, anisocytosis was markedly increased out of proportion to the degree of anaemia present. Iron stores were also reduced in four of these cases. It is suggested that objective measurement of anisocytosis is of early diagnostic value in the assessment of multiple haematinic factor deficiency, for example, in macrocytic anaemia associated with malabsorption states and unexpected multiple deficiency states.

Networks for electronic radiology.

Next-generation health care systems must successfully integrate hospital information, laboratory automation, and medical-image management to provide a seamless view of the complete medical record to the primary care physician across a distributed medical enterprise. Broadband networks are an important component of the systems required to achieve this goal. This article provides a brief tutorial on relevant network principles and products, a perspective on the evolution of the field, and a simple view of the network requirements posed by electronic radiology.

Effect of total amygdalectomy upon regulation of salt intake in rats.

Sodium appetite was studied in rats with lesions destroying the entire amygdaloid nuclear complex. The rats were totally aphagic and adipsic for several days following lesioning but regained nearly normal levels of food and water intake about 2 to 3 weeks postoperatively. Intake of 3% saline was observed after induction of sodium appetite by treatment with a mineralocorticoid and a natriuretic agent. Rats with amygdaloid lesions generally manifested severe but not total loss of sodium appetite. Regulation of water intake was also moderately to severely impaired. Suggestive evidence was obtained that recovery of sodium appetite in amygdalectomized rats can be enhanced by postoperative experience with sodium appetite and saline reinforcement.

Progressive coding and transmission of digital diagnostic pictures.

In radiology, as a result of the increased utilization of digital imaging modalities, such as computed tomography (CT) and magnetic resonance imaging (MRI), over a third of the images produced in a typical radiology department are currently in digital form, and this percentage is steadily increasing. Image compression provides a means for the economical storage and efficient transmission of these diagnostic pictures. The level of coding distortion that can be accepted for clinical diagnosis purposes is not yet well-defined. In this paper we introduce some constraints on the design of existing transform codes in order to achieve progressive image transmission efficiently. The design constraints allow the image quality to be asymptotically improved such that the proper clinical diagnoses are always possible. The modified transform code outperforms simple spatial-domain codes by providing higher quality of the intermediately reconstructed images. The improvement is 10 dB for a compression factor of 256:1, and it is as high as 17.5 dB for a factor of 8:1. A novel progressive quantization scheme is developed for optimal progressive transmission of transformed diagnostic images. Combined with a discrete cosine transform, the new approach delivers intermediately reconstructed images of comparable quality twice as fast as the more usual zig-zag sampled approach. The quantization procedure is suitable for hardware implementation.

The complete 1H NMR assignments of aminoglycoside antibiotics and conformational studies of butirosin A through the use of 2D NMR spectroscopy.

The complete proton assignments of the aminoglycoside antibiotics, butirosin A, kanamycin A and kanamycin B, at pH 6.5 have been made through the use of various homonuclear and heteronuclear 2D NMR methods. Butirosin A NOESY experiments suggest a stacking arrangement between the xylose and 2,6-diamino-2,6-dideoxyglucose rings, while the 2-deoxystreptamine ring and its substituent, the (S)-4-amino-2-hydroxybutyryl group, extend away from the stacked rings. Informative long-range NOEs were observed for butirosin A but not with kanamycin A or kanamycin B. Many intra-ring NOEs were observed with all three aminoglycosides that confirm the proton assignments made in this study.

Differences between scorers on selected language measures.

Differences in scores assigned by five speech-language pathologists were determined for 96 language samples utilizing assessments of total words, total sentences, words per sentence, syntax quotient (usage and endings), syntax quotient (structures), and an abstract-concrete scale. Results of the study showed statistically significant interscorer differences for words per sentence, syntax quotient (usage and endings), and the abstract-concrete scale. Although the mean differences between scorers for total words, total sentences, and syntax quotient (structures) were not statistically significant, substantial absolute differences between scorers were found on all six measurement procedures.

The double arch impression technique: a solution to prevent supraocclusion in the indirect restoration.

The literature relating to inaccuracies in the mounting of casts of semi-adjustable articulators and other factors that influence the fabrication of indirect restorations is reviewed. The effects of such discrepancies often result in "high" cast restorations which require considerable adjustment clinically before definitive placement. Some solutions to "high" cast restorations are offered with indications and contraindications for their use.