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PubMed2026

HIF1A+CSF3R+ neutrophils-dominated hypoxic niche induced metabolic reprogramming for neoadjuvant therapy resistance in NSCLC.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the frequently occurring cancers characterized by molecular heterogeneity and multiple immune cell infiltration patterns, which are associated with treatment sensitivity and resistance. However, the specific microenvironmental cells and their mechanisms that lead to treatment resistance in patients need to be explored in greater depth. METHODS: On the basis of patients receiving neoadjuvant therapy in our center, a multicenter, multicohort NSCLC spatial transcriptome, single-cell transcriptome, T-cell receptor repertoire sequencing, bulk RNA transcriptome, phosphorylated proteome, genome mutation, and clinical data were included for a comprehensive assessment of the therapeutic and prognostic impact of HIF1A+ CSF3R+ neutrophils in NSCLC. In vitro experiments validated the functional phenotype of HIF1A+ CSF3R+ neutrophils and co-localization interactions with other cellular subpopulations. Gradient boosting machine (GBM) constructed region of interest (ROI) models for evaluation. Computer-aided drug design (CADD) was used to predict targeted small molecule drugs, and in vivo mouse models were constructed to assess the effectiveness of the combination treatment regimen. RESULTS: Centered on HIF1A+ CSF3R+ neutrophils, recruited exhausted T cells and stromal cells form a hypoxic niche within the tumor region, which was enriched in non-response patients. ROI composed of these specific cellular subpopulations, associated with senescence and glycolysis, accurately predicting NSCLC progression, prognosis, and microenvironment composition. CADD analysis identified that platycodin-D2 specifically targeted CSF3R, reducing HIF1A expression and inhibiting neutrophil activity. Combining navitoclax, platycodin-D2 with anti-programmed cell death protein 1 (PD-1) significantly suppressed tumor proliferation and improved the immunosuppressive microenvironment. CONCLUSION: Our study emphasized the role of HIF1A+ CSF3R+ neutrophils in immunotherapeutic resistance of NSCLC, constructed a microenvironmental immune dysregulation network in a hypoxic ecological niche with HIF1A+ CSF3R+ neutrophils as the center. Platycodin-D2 specifically targeted HIF1A+ CSF3R+ neutrophils, enhancing the efficacy of anti-PD-1 therapy in NSCLC.

Humans↗
PubMed1992

[A study of the computer aid design for tooth arrangement of full denture].

This paper is to use the power function Simpson's integration formula and some other methods to describe the geometric form of the dentition and edentulous arch in accordance with the theories and principles of tooth arrangement in textbook. The matching equations of artificial dentition and edentulous arch form and size are developed by using the multivariable regression method to analyze and summarize the clinical experiences of prosthodontists. Based on the above facts, a computer program that can be used to aid the dentist to arrange the artificial teeth for full denture is developed with Quick Basic Language and realized them in PC miniprocessors.

Computer-Aided Design↗
PubMedDate not supplied

Using a computer color-matching system in color reproduction of porcelain restorations. Part 1: Application of CCM to the opaque layer.

The reproduction of natural tooth color using porcelain restorations is quite cumbersome, for it is difficult to select, communicate, reproduce, and evaluate color objectively. The present process of color reproduction lacks precision and is primarily dependent on the individual efforts and abilities of the dentist and ceramist. The computer color-matching system, aided by a spectrophotometer and computer, can be an excellent method for reproducing specific colors of various objects. This paper reports application of the system to reproduce various opaque colors used for metal ceramic restorations.

Color↗
PubMed1992

The reality of dental CAD-CAM: hype or hope?

Dental CAD-CAM has become a clinical reality. It holds great promise to help provide a higher level of service to the patient, while allowing the dentist to spend more time on patient needs than on the mechanics of restoration production. Still, this technology is not suited for every dental office. This paper discusses the technique of CAD-CAM, its potential and its limitations so the dentist can better evaluate the appropriateness of this new modality for his or her own office.

Computer-Aided Design↗
PubMedDate not supplied

A computer-aided interactive procedure to improve nurse-training programmes.

Nurses represent the largest single resource in terms of numbers of staff employed as well as the revenue cost within the National Health Service. As trainee nurses constitute about 30% of the nursing staff and in some cases provide more than 60% of the bedside care, the effective design of nurse training programmes must receive considerable analytic attention. A computer-aided interactive procedure is described which enables senior nursing administrators to evaluate and improve, from service point of view, a given nurse training programme.

Computers↗
PubMed1992

Application of computer-aided image interpretation to the diagnosis of periapical bone lesions.

An image analysis system was developed for the computer-aided diagnosis of periapical bone lesions in dental radiographs. The system was designed to (1) identify the periapical region, (2) determine the presence of a periapical lesion and (3) estimate the size of the lesion in cases when a lesion had been found. To initiate the procedure, an observer indicates an arbitrary point on the root in a digitized radiograph. From this initial point, the location of the radiographic projection of the apex of the root is automatically computed. Next, the trabecular bone pattern is detected through texture analysis. A local absence of the trabecular bone pattern in the periapical region is marked as a periapical bone lesion. When a lesion has been identified, its size is estimated based on local edge properties. Observer interaction is only allowed to adjust the result of the apex localization procedure if the apex has not correctly been localized. In an experiment with randomly selected radiographs of 111 mandibular roots, the performance of the system was tested against the consensual diagnosis of four expert observers. The sensitivity of the system to identify a lesion was 83.3%, the specificity 75.6% and the diagnostic accuracy 80.2%. The correlation between the size of the lesions as estimated by the system and by the observers was 0.67 (P < 0.01). When the procedure was repeated, the percentage of correctly reproduced lesion sizes by the system was 92.8%. The determination of the presence of a lesion was reproducible in 98.2% of all the cases.

Alveolar Bone Loss↗
PubMed1977

Evaluation of computer-aided monitoring of patients after heart surgery.

The medical and economic benefits of a computer-aided monitoring system were evaluated in a prospective, randomized study of 810 patients after open-heart surgery. The design of the study separated benefits of systematized postoperative care from benefits unique to the computer system and established measurable criteria by which computer-aided monitoring systems could be objectively evaluated. Criteria for comparison included the rapidity, safety, and smoothness of convalescence and time spent for various nursing activities. The study showed that the computer-aided monitoring system did not provide discernible medical benefits nor favorably affect nursing activities. Downtime of the system averaged 1 day per week. Reliability and accuracy of the system were inadequate and the benefit/cost ratio was low. Future development of computer-aided monitoring systems for open cardiac surgery should stress reliability, accuracy and relevance of the monitored measurements.

Cardiac Surgical Procedures↗
PubMed1992

A second gene (qutH) within the Aspergillus nidulans-quinic-acid utilisation gene cluster encodes a protein with a putative zinc-cluster motif.

A sequence of 3299 nt, contiguous with the previously sequenced quinate permease-encoding (qutD) gene and encompassing the dehydroshikimate dehydratase-encoding (qutC) gene, has been determined. Northern-blot analysis detected (i) a quinate-inducible mRNA of the expected size for the qutC gene, and (ii) a quinate-inducible mRNA of 1.45 kb divergently transcribed away from qutC towards qutD. Computer-aided sequence analysis identified an ORF of 1047 nt corresponding to the qutC gene encoding dehydroshikimate dehydratase. In addition, a genetically uncharacterized 1188-nt gene, designated qutH and containing a putative intron of 61 nt, was identified between qutC and qutD. The inferred protein sequence encoded by qutH contains a putative 'zinc cluster' motif and has a low (16%) but significant similarity with the DNA-directed DNA polymerase of hepatitis B virus. The results are interpreted as being consistent with the view that the qutH gene encodes a DNA-binding protein, possibly involved in the regulation of genes essential for the utilisation of protocatechuic acid.

Alcohol Oxidoreductases↗
PubMed1992

The isolation and characterisation of a cDNA clone encoding L-asparaginase from developing seeds of lupin (Lupinus arboreus).

An L-asparaginase cDNA clone, BR4, was isolated from a Lupinus arboreus Sims developing seed expression library by screening with polyclonal antibodies to the seed asparaginase. The cDNA hybridised with an oligonucleotide probe designed from amino acid sequence data and was found on sequencing to be 947 bp in length. Six polypeptide sequences obtained previously could be placed along the longest open reading frame. Computer-aided codon use analysis revealed that the cDNA sequence was consistent with other plant genes in terms of codon use. The cDNA insert was used to analyse asparaginase transcription in various tissues by northern blot analysis. A transcript size of approximately 1.2 kb was detected in L. arboreus seed total and poly(A)+ RNA. The level of this transcript declined from 30 days after anthesis to an undetectable level by day 55. Furthermore, under the high stringency conditions used, the seed asparaginase cDNA did not hybridise with total or poly(A)+ RNA isolated from root tips, suggesting that the asparaginase known to be present in this tissue may be the product of a different gene. Southern analysis suggested the seed asparaginase is a single-copy gene. The plant asparaginase amino acid sequence did not have any significant homology with microbial asparaginases but was 23% identical and 66% similar (allowing for conservative substitutions) to a human glycosylasparaginase.

Amino Acid Sequence↗
PubMed1978

Preventable anesthesia mishaps: a study of human factors.

A modified critical-incident analysis technique was used in a retrospective examination of the characteristics of human error and equipment failure in anesthetic practice. The objective was to uncover patterns of frequently occurring incidents that are in need of careful prospective investigation. Forty-seven interviews were conducted with staff and resident anesthesiologists at one urban teaching institution, and descriptions of 359 preventable incidents were obtained. Twenty-three categories of details from these descriptions were subjected to computer-aided analysis for trends and patterns. Most of the preventable incidents involved human error (82 per cent), with breathing-circuit disconnections, inadvertent changes in gas flow, and drug-syringe errors being frequent problems. Overt equipment failures constituted only 14 per cent of the total number of preventable incidents, but equipment design was indictable in many categories of human error, as were inadequate experience and insufficient familiarity with equipment or with the specific surgical procedure. Other factors frequently associated with incidents were inadequate communication among personnel, haste or lack of precaution, and distraction. Results from multi-hospital studies based on the methodology developed could be used for more objective determination of priorities and planning of specific investments for decreasing the risk associated with anesthesia.

Accident Prevention↗
PubMed1975

A physiological analysis of walking in the American lobster (Homarus americanus).

The normal, unrestrained, forward walking of the lobster was studied with a closed-circuit television system and a video-tape recorder. A frame-by-frame analysis was undertaken and measurements made of unilateral stepping sequences, contralateral and ipsilateral phase relations between pairs of legs, the movements at the leg joints primarily involved in stepping and their differences in each of the four pereiopods. The order of stepping was expressed in terms of the probability of any leg following any other leg and it was found that while there is a preferred order, there is considerable variation from the dominant pattern. The commonest deviations from the dominant gait are those involving the simplest types of re-ordering of the sequence. Pairs of contralateral legs show a strong tendency to alternate but all phase relations can occur. Similarly, while the ipsilateral legs show preferred phase relations, all possible relations do occur. The four pereiopods from anterior to posterior were found to have respectively, a pulling action, a combined pulling and rowing action, a rowing action and a combined pushing and rowing action. The same parameters of stepping were recorded from animals walking on a transparent, driven treadmill and, as no significant differences were found in comparisons with results from freely moving animals, subsequent results were obtained from animals walking on the treadmill where more detailed study and manipulation could readily be made. The stepping action of the third pereiopod during forwards walking involves major movements about two joints whereas the other pereiopods move about three joints. Detailed study of the intra-leg activity was therefore confined to the third pereiopod where the simpler action considerably simplified the problems involved in collecting and analysing data. Measurements were made of the angles swept out by the joints of the third pereiopod during movement. Electromyograms were recorded from the six muscles primarily responsible for these movements and from movement transducers placed at the joints. The duration of the movements and of the bursts of acitivity in the muscles and the interrelation between different muscle bursts were measured and a computer-aided analysis made to determine the characteristic features of the inter-burst relations during stepping. While there is considerable variability from step to step, the overall activity is relatively phase-constant over a wide range of stepping frequencies. When some of the key parameters of normal walking had been characterized, changes designed to alter the sensory input to the system were imposed.

Animals↗
PubMed1976

[Mechanical studies on the dental bridges by the finite element method. (1)--An abutment tooth model-- (author's transl)].

Biomechanical considerations are very important to design a prosthetic appliance; however, there have been no satisfactory quantitative studies of such problems, mainly because theoretical and experimental models are unable to represent exactly the natural conditions in the mouth. The finite element method has been successfully applied in each field of applied mechanics and found to be effective for the structural analysis of the biological systems, for it has the advantage of greater versatility for modelling. Accordingly, this analytical, computer-aided method was applied to the dental bridges to evaluate the loads transmitted to the abutment tooth and the stress distributions in the supporting tissues. As the preliminary study a two-dimensional model was constructed to simulate the tooth subject to a vertical and a horizontal load and a moment at the coronal portion. The stress distributions in the tooth and the periodontal membrane and the force distributions on the socket wall were calculated for three load conditions. The tooth mobility and the center-of-rotation position were compared with actual data available in some literatures and the characteristics of tooth support were discussed in terms of three spring constants.

Dental Abutments↗
PubMed1992

Molecular modelling of the structures of endothelin antagonists. Identification of a possible structural determinant for ET-A receptor binding.

Computer-aided molecular modelling of the endothelin (ET-A) receptor antagonists, BQ-123 and BE-18257B, shows that they have very similar 3D structures. Parts of their 3D structures are also shown to match closely with that reported for residues 6-8 in endothelin-1. On the basis of these similarities (and with supporting evidence from literature data on endothelin structure-activity relationships) a structural determinant is proposed for ET-A receptor binding, and novel designs of peptide are suggested for providing more potent and selective ET-A receptor antagonists.

Amino Acid Sequence↗
PubMed1975

Computer-aided diagnosis of "dyspepsia".

Experience with computer-aided diagnosis of "dyspepsia" in a consecutive prospective series of 212 patients coming to surgery is described. Analysis is concentrated upon 122 patients who presented to an outpatient clinic de novo for diagnosis. During their first (outpatient) hospital contact, a firm diagnosis was made in just over half of these patients (though where made, it was usually correct). After full investigation, the diagnostic accuracy (prior to operation) was 92.6%. Using data elicited solely from the house surgeon's interview at the time of admission, the computer's overall diagnostic accuracy was 87.7%. The cost of each new computer diagnosis was around 25 new pence ($0.60). and the time taken was about 5 minutes. In a further small series designed to discriminate between organic and functional dyspepsia, the computer correctly assigned all but 1 of 23 patients with organic disease to the correct disease category. However, almost half of 33 patients with x-ray negative dyspepsia were predicted by the computer to have organic lesions. Time alone will tell whether the computer is a better early predictor of eventual organic disease than currently available radiologic methods.

Bayes Theorem↗
PubMedDate not supplied

Bayesian statistics: a guided tour.

An overview of Bayesian statistical decision theory is presented in the tutorial spirit. A section on fundamental principles is followed by selected applications of the Bayesian approach to parameter estimation, pattern recognition, image processing, computer-aided medical diagnosis, optimal diagnostic test selection, and radiotherapy treatment planning.

Decision Making↗