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PubMed2026

Genetic insights into lung squamous cell carcinoma: how TP53 and CSMD3 co-mutations shape prognosis and immune response.

BACKGROUND: Lung squamous cell carcinoma (LUSC) accounts for a significant proportion of lung cancer cases and is often associated with smoking and various environmental factors. The prognostic and immunologic implications of TP53 and CSMD3 co-mutations in LUSC remain poorly understood. This study aimed to investigate the role of TP53/CSMD3 co-mutations in LUSC using comprehensive bioinformatics analyses. METHODS: Data from 487 LUSC patients were obtained from The Cancer Genome Atlas (TCGA) database, with external validation performed using the combined cohort. Patients were stratified into TP53/CSMD3 co-mutation, single-mutation, and wild-type (WT) groups. Prognostic analysis was conducted using Kaplan-Meier survival curves. Tumor mutational burden (TMB) was calculated, and immune cell infiltration was assessed using multiple algorithms. Differentially expressed genes (DEGs) between co-mutated and WT groups were identified, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. A nomogram incorporating mutation status, gender, age, and tumor stage (T stage) was developed for individualized prognostic prediction. RESULTS: The TP53/CSMD3 co-mutated group exhibited significantly better overall survival (OS) compared to single-mutation and WT groups. TMB scores were markedly higher in co-mutated patients, suggesting potential sensitivity to immune checkpoint inhibitors. Immune infiltration analysis revealed distinct profiles, including elevated CD8 T cells and reduced immunosuppressive components, in the co-mutation group. A total of 403 DEGs were identified between co-mutated and WT groups, with significant enrichment in immune-related pathways. Mechanistically, the co-mutation was associated with distinct downregulation of complement negative regulators (CFH/CFI), indicating complement hyperactivation independent of TMB. The constructed nomogram provided accurate individualized prognostic assessments. CONCLUSIONS: The co-mutation of TP53 and CSMD3 identifies a distinct LUSC subtype with favorable survival, marked by high TMB and an immune-activated microenvironment. Beyond TMB-driven neoantigen generation, the significant downregulation of complement negative regulators (CFH/CFI) reveals an independent complement hyperactivation pathway associated with CSMD3 loss. The constructed nomogram provides accurate individualized survival prediction. These findings establish TP53/CSMD3 co-mutation as a promising prognostic biomarker and offer mechanistic insights for personalized immunotherapy strategies. Future prospective cohorts are warranted to validate its predictive value.

Lung squamous cell carcinoma (LUSC)↗
PubMed1990

Pharmacokinetic and pharmacodynamic studies on recombinant human erythropoietin.

In order to optimize the treatment of anemia in uremic patients the pharmacokinetic and pharmacodynamic properties of recombinant erythropoietin (r-Epo) were studied after i.v., s.c. and i.p. administration. Both in healthy volunteers and in patient with chronic renal failure, the half-life of r-Epo after i.v. administration was short (about 6 h) in comparison with the commonly used dosing interval of 3 to 7 days. Hence, the minimum serum concentration during a dosing interval is expected to be less than 1% of the peak concentration. Absorption following a s.c. dose was slow, resulting in a markedly different concentration-time profile in comparison to i.v. dosing. The half-life was about 25 h and only approximately 25% of the given dose reached the systemic circulation. As a result of differences in concentration-time profiles, higher trough concentrations during s.c. dosing intervals may be expected in comparison to those occurring after i.v. dosing. When r-Epo was given i.p. (diluted in dialysate) the extent of systemic absorption depended on the dwell time in the peritoneal cavity. A long administration time was required to absorb an amount of r-Epo predicted from s.c. studies to be adequate to achieve the desired clinical effect. In spite of reduced bioavailability, s.c. treatment did not require higher r-Epo doses than i.v. treatment to maintain the desired hemoglobin concentration. On the contrary, a trend to a requirement for lower doses was detected. The pharmacodynamic and pharmacokinetic results strongly indicate a more efficacious concentration-time profile following s.c. administration. Since s.c. dosing also allows self-administration the use of this administration route is recommended. To simplify the treatment of anemic patients with r-Epo, a model was developed to predict the required weekly s.c. dose. To facilitate the use of this model a nomogram was constructed.

Adult↗
PubMed1989

Predictors of excessive blood use after coronary artery bypass grafting. A multivariate analysis.

One hundred fifty-nine consecutive patients who underwent coronary artery bypass grafting were studied to determine clinical and laboratory predictors of excessive postoperative packed red blood cell transfusion. Consideration of the distribution of packed red blood cells administered revealed that the patients could be divided into two groups: those patients who received 5 units of red blood cells or less (group I, n = 139) and those patients who received more than 5 units of packed red blood cells (group II, n = 20). The Mann-Whitney test or Fisher's exact test was used whenever appropriate to test differences between these two groups with respect to twelve patient variables. Patients in group II were found to have a significantly longer preoperative template bleeding time and decreased preoperative packed red blood cell volume (p less than 0.0008 for both variables). In addition, group II patients were significantly older (p = 0.026), were more likely to have had preoperative heparin therapy (p = 0.049), and contained a greater proportion of women (p = 0.0048). Of interest, variables that did not achieve statistical significance between groups were partial thromboplastin time, prothrombin time, platelet count, preoperative hematocrit level, urgency of operation, recent ingestion of aspirin, and recent heparin administration. All of the measured variables were used in a stepwise logistic regression analysis to identify the best predictors of the need for more than 5 units of packed red blood cells after operation. Of the variables examined, bleeding time (p less than 0.001; chi 2 improvement = 15.1) and red blood cell volume (p = 0.009; chi 2 improvement = 6.8) were the best predictors of excessive postoperative packed red blood cell use. On the basis of a 50% logistic probability level, the specificity and sensitivity of these two variables in predicting greater than a 5-unit transfusion requirement were 85% and 99%, respectively. A clinically useful nomogram based on this logistic model is presented. This nomogram suggests that a ratio of bleeding time to red blood cell volume of 0.0071 or greater is associated with a greater than 70% chance of requiring more than 5 units of packed red blood cells. We conclude that preoperative bleeding time and red blood cell volume are useful predictors of excessive postoperative blood transfusion. These results suggest that factors other than aspirin therapy may be associated with bleeding time prolongation leading to excessive postoperative transfusion.

Aged↗
PubMed1996

Predicting duration of sleep from the three process model of regulation of alertness.

OBJECTIVES: Irregular working hours severely disturb sleep and wakefulness. This paper presents a modification of the quantitative (computerised) three process model of regulation of alertness to predict duration of sleep in connection with irregular sleep patterns. METHODS: The model uses a circadian "C" (sinusoidal) and homeostatic "S" (exponential) component (the duration of previous periods awake and asleep), which are summed to yield predicted alertness (on a scale of 1-16). It assumes that waking from sleep will occur at a given alertness level (S' + C') when recuperation is complete. Variables of electroencephalographic duration of sleep from two studies of irregular sleep were used to model the S and C variables in a regression approach to maximise prediction. The model performance was cross validated against published field and laboratory data. RESULTS: The model parameters were defined with a high degree of precision R2 = 0.99 and the validation yielded similar values R2 = 0.98-0.95, depending on the acrophase. The paper also describes a simplified graphical version of the computation model seen as a two dimensional duration of sleep nomogram. CONCLUSION: The model seems to predict group means for duration of sleep with high precision and may serve as a tool for evaluating work and rest schedules to reduce risks of sleep disturbances.

Adult↗
PubMed1984

[Quantification (by nomograms) of physiopathological parameters in an experimental model of passive anaphylaxis caused by immune complexes].

Pharmacological changes in a model of passive anaphylaxis by immune complexes in mice have been studied. The results have been evaluated by nomograms to overcome the difficulties observed when using classical criteria as 50% lethal dosis or 50% infective dosis in experimental models which do not allow serial dilutions of the reagents. Mean lethal time, maximal pathogenic capacity and relative survival time can be easily determined, allowing the comparison of the immunopharmacologic protection for each administration schedule. By these criteria, we have observed a different degree of anaphylactic reaction depending on the genetic background of the hosts as well as a protection against anaphylactic shock using the antiserotoninic cyproheptadine and, to a lesser extent, by the platelet antiaggregant ticlopidine.

Anaphylaxis↗
PubMed2026

Construction of a new predictive model in head and neck squamous cell carcinoma based on the investigation of extracellular matrix-associated genes.

A key aspect influencing immune cell infiltration is the composition of the extracellular matrix (ECM). Therefore, investigating the association between ECM-associated proteins and immune cell infiltration is key for the identification of new biomarkers to distinguish 'immune-hot' solid tumors and predict patient prognosis. A total of 513 head and neck squamous cell carcinoma (HNSCC) cases as training samples from The Cancer Genome Atlas and an additional 270 as testing samples from the Gene Expression Omnibus were obtained for use in the present study. Using a single-sample Gene Set Enrichment Analysis method, the 513 training samples were divided into Cluster 1 and Cluster 2. Subsequently, the present analysis uncovered 1,573 differentially expressed genes distinguishing the two clusters. After performing an intersection analysis with 751 ECM-associated genes, 103 differentially expressed ECM-associated genes were identified. Least absolute shrinkage and selection operator-Cox and multivariate Cox regression analyses were employed to identify candidate ECM risk genes (P<0.05) and to construct a predictive model. Finally, a nomogram and a three gene (cerebellin 2, galectin-10 and cathepsin G) predictive model were developed. Therefore, the present prognostic risk score model can evaluate the immune infiltration, predict the prognosis of HNSCC, and potentially guide more personalized immunotherapy interventions.

extracellular matrix↗
PubMed1995

Nomograms for determining the probability of axillary node involvement in women with breast cancer.

We have previously reported that a history of pregnancy is independently associated with axillary node involvement in breast cancer patients. We have now studied additional women with breast cancer and have used our data and the logistic model to produce nomograms for determining the risk of axillary node involvement, based on tumor size, age, and number of pregnancies. There was an increase in the incidence of axillary node involvement in women with a history of pregnancy. To exclude the confounding effect that tumor size or age might have on node involvement, logistic regression was performed. Pregnancy, tumor size, and age were the three independent variables. History of pregnancy had a significant effect on node involvement (P = 0.036) that was independent of tumor size and age. Nomograms were constructed from these data. Surgeons do not perform an axillary dissection in every breast cancer patient. If the axilla is clinically negative and the tumor small, the surgeon, medical oncologist, and radiation oncologist may decide that a dissection need not be done. The nomograms in this article may allow for a more methodical choice of patients for axillary dissection. Moreover, a radiation oncologist might use the nomograms to help decide whether to irradiate an undissected axilla.

Adult↗
PubMed2026

A Dynamic Nomogram to Predict Metabolic Dysfunction-Associated Fatty Liver Disease in Patients with Metabolic Syndrome.

BACKGROUND: Metabolic syndrome (MetS) involves multiple metabolic disorders. This study aimed to identify high-risk populations for metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with MetS and to establish a dynamic predictive nomogram. METHODS: A total of 627 patients with MetS from six regions in Zhejiang Province were enrolled and categorized into MAFLD and non-MAFLD groups, then randomly assigned to training and validation sets at a ratio of 7:3. Independent predictors of MAFLD were identified using least absolute shrinkage and selection operator regression and multivariable logistic regression analyses. These predictors were then used to construct a dynamic nomogram. RESULTS: A total of 627 patients with MetS were included in the final analysis, of whom 77.0% (483/627) were diagnosed with MAFLD. Multivariable logistic regression analysis identified body mass index (BMI), waist circumference (WC), total cholesterol (TC), alanine aminotransferase (ALT), MetS-defined dysglycemia, and education level as independent risk factors for MAFLD. MetS-defined dysglycemia showed the highest odds ratio (OR) for MAFLD development [OR = 1.87, 95% confidence interval (CI): 1.07-3.29]. Although the number of MetS components and the metabolic syndrome score were significantly associated with MAFLD in univariate analysis, they were not independently associated with MAFLD in the multivariate model. A dynamic nomogram for predicting MAFLD risk in patients with MetS was developed and internally validated. The area under the receiver operating characteristic curve was 0.834 (95% CI: 0.787-0.880) in the training set and 0.839 (95% CI: 0.771-0.899) in the validation set, indicating strong predictive performance. Bootstrap internal validation demonstrated good agreement between predicted and observed outcomes in calibration curves. Decision curve analysis further indicated favorable clinical applicability of the nomogram. CONCLUSION: BMI, WC, TC, ALT, MetS-defined dysglycemia, and education level are independent risk factors for MAFLD. A dynamic nomogram for predicting MAFLD risk in patients with MetS was successfully developed and validated.

Humans↗
PubMed1979

Studies of the effect of peroral fenylpropanolamin on the functional size of the human maxillary ostium.

The effect of peroral fenylpropanolamin on the functional size of the human maxillary ostium was studied in 20 patients suffering from acute rhino-sinusitis. The size of the maxillary ostium was measured by a manometric procedure over a 2-hour period. During the introduction of a known airflow into the sinus for a short while, the pressure increase was compared with a nomogram obtained by model experiments. The introduction of the cannulas into the maxillary sinus caused a swelling of the mucosa in the ostium in the placebo group and initially also in the group receiving fenylpropanolamin, but, after 60 minutes, the latter group had a mean functional ostial size greater than the initial one. These differences were not statistically significant. This seems to be the first objective study of the size of the ostia in the human paranasal sinuses during treatment with a peroral decongestant.

Acute Disease↗
PubMed1986

Controversies in antimicrobial therapy: pitfalls in monitoring aminoglycoside therapy.

Efficacy, safety, and cost factors related to aminoglycoside therapy, which is the treatment of choice for mixed infections of the skin, respiratory tract, and abdominal cavity, are reviewed. The cost of therapy must include all measurable costs of drug preparation, administration, monitoring, and potential toxicity or treatment failure. These costs are often difficult to quantify, as are potential differences in efficacy. Aminoglycosides are usually given by injection and are excreted unchanged by the kidneys. They are concentrated in the renal cortex, leading some investigators to assess the correlation of this uptake with renal toxicity. An increase in serum aminoglycoside concentrations serves as a retrospective, nonspecific marker of the renal toxicity that occurs in up to 35% of patients receiving these drugs. Pharmacokinetic monitoring of aminoglycoside therapy is used to assure therapeutic drug concentrations. Blood samples for aminoglycoside assays must be drawn, stored, separated, and assayed correctly, and the timing and labeling of the sample is of utmost importance. Nomograms and pharmacokinetic models, which can be used with computers and hand-held calculators, are useful for predicting initial doses and modifying subsequent doses. Aminoglycoside therapy is important in selected patients, but the comparative efficacy and safety of these drugs remains insufficiently assessed. Pharmacokinetic monitoring is helpful in assuring safe and effective dosing of aminoglycosides.

Aminoglycosides↗
PubMed2026

Artificial Intelligence for Diagnosis, Risk Stratification, and Prognosis of Neuroblastoma - A Systematic Review and Meta-Analysis.

PURPOSE: To synthesizes evidence on artificial intelligence (AI) performance in neuroblastoma (NB) diagnosis, risk stratification, prognosis, and genomic characterization. MATERIALS AND METHODS: A systematic review and meta-analysis was conducted following PRISMA 2020 guidelines (PROSPERO: CRD42024539475) across five databases. Meta-analyses used random-effects models with logit-transformed Area Under the Curve (AUCs) and cluster-robust standard errors. AI models were classified as Machine Learning Models (MLM) or Hybrid Nomograms (HN) based on their construction methodology. RESULTS: Of 3,742 articles identified, 53 were included. MLMs demonstrated higher point estimates than radiologists in differential diagnosis (AUC: 0.87 vs. 0.83), though this difference was not statistically significant and carried substantial uncertainty. HNs achieved stronger performance in risk stratification (AUC: 0.87). AI-derived nomograms (AUC: 0.9) and gene signatures (AUC: 0.8) outperformed conventional prognostic markers descriptively. Chemotherapy response prediction remained below clinical utility thresholds across all model types. Only 33.9% of models reported calibration and 24.5% underwent external validation. CONCLUSIONS: AI demonstrates proof-of-concept across multiple NB clinical domains. However, clinical adoption remains premature given persistent gaps in external validation, calibration, dataset size, and pediatric-specific model development. Future studies should test these models prospectively in multicenter pediatric cohorts, ideally through COG or SIOPEN, using shared definitions for diagnosis, risk group, treatment response, and survival outcomes.

Humans↗
PubMed1991

[Comparative multifactorial analysis of combined administration of injection and peroral forms of an antibiotic with a microbial immunomodulator in experimental anthrax].

Comparative efficacy of the use of injection and oral dosage forms of rifampicin in the subtherapeutic doses in combination with peptidoglycan , an immunomodulator of microbial origin, was studied in respect to experimental anthracic infection with application of multifactorial analysis. It was shown that the antibiotic and immunomodulator had a pronounced synergistic effect. Polynomial statistic models were developed and nomograms or equal level curves defining the survival rate and average life-span (ALS) of the experimental animals within a wide range of the antibiotic and immunomodulator doses and the peptidoglycan dosing time were plotted. The combined use of the injection rifampicin in the subtherapeutic doses and the immunomodulator provided a significant increase in the survival rate and ALS, whereas the use of the oral antibiotic in combination with the immunomodulator increased only the ALS and not the survival rate. Multifactorial analysis proved to be an optimal methodical approach to comparative study of various antibiotic dosage forms used in combination with immunomodulators under experimental conditions.

Adjuvants, Immunologic↗
PubMed2025

Comprehensive investigation identifies CPSF3 as a novel prognostic and oncogenic biomarker in bladder cancer.

BACKGROUND: Bladder cancer (BC) remains a prevalent malignancy worldwide, with rising incidence rates each year. Despite progress in therapeutic strategies, many patients suffer recurrence or progression, emphasizing the urgent need for novel prognostic biomarkers and therapeutic targets. This research evaluated the prognostic relevance and functional role of Cleavage and Polyadenylation Specificity Factor 3 (CPSF3) in BC. METHODS: We analyzed CPSF3 expression using The Cancer Genome Atlas data and immunohistochemistry on a cohort of 203 BC patients. A nomogram incorporating CPSF3 expression was developed based on CPSF3 expression for prediction of overall survival and disease-free survival. Immune infiltration analyses and transcriptome sequencing were performed to explore underlying biological mechanisms. In vitro and in vivo experiments were utilized to examine the results of CPSF3 silencing on bladder cancer cell growth, colony-forming ability and cell cycle transitions. RESULTS: Elevated CPSF3 expression was significantly linked to unfavorable overall survival and disease-free survival both in TCGA datasets and our cohort. The CPSF3-based nomogram outperformed conventional prognostic models. CPSF3 expression was associated with tumor-infiltrating immune cells and immune checkpoint markers. Enrichment analysis revealed CPSF3 enrichment in cell cycle-related pathways. Suppression of CPSF3 expression led to marked reductions in cell proliferation, colony formation, tumor growth in animal models and inhibited G1 to S phase progression. CONCLUSION: CPSF3 is a promising prognostic biomarker for BC and may play a crucial role in BC progression. Incorporating CPSF3 into clinical prognostic models may enhance prediction of patient outcomes. CPSF3 may represent a promising therapeutic target for BC management.

Bladder cancer↗
PubMed1976

Correction of stereological parameters from biased samples on nucleated particle phases. I. Nuclear volume fraction.

Stereologists are aware that the experimental evaluation of component volume fractions and surface-to-volume ratios are subject to systematic errors whenever the requirements for cell identification impose the necessity for component-biased sectioning. Mathematical corrections of biased volume proportion data have recently been published; these corrections assume that the components under analysis are spherical, and that the nucleated particle phase is monodispersed. In this report, general methods for obtaining corrections of biased nuclear volume fraction data are set out for polydispersed phases of nucleated particles, in terms of the relevant shapes and joint size distribution of nucleus and cell; the scope and limitations of these methods are thereby discussed. Explicit corrections of an immediate applicability are obtained, together with their standard errors, for monodispersed phases where nucleus and cell are two dissimilar biaxial ellipsoids (spheroids). When nucleus and cell are two concentric and similar convex bodies of a certain class--to which triaxial ellipsoids belong--the corrections are shown to be very simple. The corrections for the spheroid-spheroid systems are easily accessible with the aid of a small programmable calculator, whereas those for the sphere-spheroid models are directly obtainable from two nomograms.

Cell Nucleus↗
PubMed1995

Validation of the S and C components of the three-process model of alertness regulation.

This paper summarizes work to validate and develop further the homeostatic and circadian component of a quantitative (computerized) three-process model for predicting alertness/sleepiness in daily living. The model uses sleep data as input and contains circadian and homeostatic components (amount of prior wake and amount of prior sleep), which are summed to yield predicted alertness on a scale between 1 and 16. The present validation was carried out using regression analysis, with sleepiness-related electroencephalographic parameters (alpha power density) from field and laboratory studies as criteria. The results showed that variations in alpha-power density in truck drivers, train drivers and laboratory subjects could be predicted with considerable accuracy (r2 > 0.70) from the model, as could subjective alertness. Levels < or = 7 on the 16-point scale were defined as critically low alertness. The paper also describes a simplified, graphic, paper version of the computation model, visualized as a two-dimensional "alertness nomogram". It is suggested that the studied components of the model may serve as tools for evaluating work/rest schedules in terms of sleep-related safety risks.

Adult↗
PubMed1995

A nomogram for predicting optimal dosage of cyclosporine in renal transplant patients: taking physiological factors into consideration for regimen during immunosuppressive therapy.

We constructed a nomogram for determining the optimal regimen of cyclosporine (CyA), based on physiological changes that occur during immunosuppressive therapy. The nomogram consists of a fixed model and a variable model. In the fixed model, the oral dose of CyA (D, mg/kg) is given by the multiple linear function of logarithmic CyA trough level (TL, ng/ml), the surrogate apparent total body clearance of CyA (CL/fsu, l/h/kg, being equal to D/TL/12), and the erythrocyte-to-plasma distribution ratio of CyA (CyA-EP), as defined by: D = 4.938 x log(TL) + 1.5037 x CL/fsu - 0.0326 x CyA-EP - 10.7156. In the variable model, the CL/fsu is given by the CyA-EP and the patient's intrinsic parameters (P1, P2), using a nonlinear equation: CL/fsu = P1 x exp(P2 x CyA-EP)/CyA-EP. An optimal CyA dose to maintain a desired trough level was calculated, and the validity of the nomogram was found satisfactory for clinical use. This offers a very concise and practical method for the therapeutic monitoring of CyA. Because the pharmacokinetics of CyA depends on physiological changes due to several disease states, and because the CyA-EP reflects the pharmacokinetics of CyA and the patient's disease state, the proposed nomogram is believed to provide an optimal dosage adjustment, taking physiological factors into consideration.

Adolescent↗
PubMed1997

Screening and treatment of bacterial vaginosis during pregnancy: a model for determining benefit.

Bacterial vaginosis is associated with an increased risk of preterm birth. The treatment of bacterial vaginosis has recently been shown to decrease the risk of preterm delivery, especially in high-risk populations. However, the benefit of routine screening and treatment in the general population is uncertain. Using the information from several recent studies, a graph and nomogram generated from a mathematical model allow the obstetrician to determine the benefit of routine screening and treatment of bacterial vaginosis in his or her obstetrical population, depending on the prevalence of bacterial vaginosis and the total preterm delivery rate in that obstetrician's practice. If the prevalence of bacterial vaginosis and the incidence of preterm delivery are low, then routine screening would be expected to prevent small numbers of preterm births, and therefore may not be cost-effective.

Cost-Benefit Analysis↗
PubMed1991

Nomogram for dosing warfarin at steady state.

The predictive performance of a nomogram for dosing warfarin was compared with that of a computer program. The nomogram and the computer program were developed from the log-linear model describing warfarin pharmacodynamics at steady state. The nomogram's dose-response curves were generated by using previously reported pharmacodynamic and pharmacokinetic values for an outpatient population receiving warfarin. The series of dose-response curves were plotted by altering the pharmacodynamic values over a range of 3 standard deviations. The ability of the nomogram to predict the steady-state prothrombin time ratio (PTR) after an adjustment in the dosage of warfarin was evaluated, and the results were compared with those of a commercially available program involving Bayesian regression. Data for 65 outpatients were evaluated. The mean +/- S.D. nomogram-predicted, computer-predicted, and measured PTRs were 1.63 +/- 0.27, 1.64 +/- 0.24, and 1.66 +/- 0.23, respectively. The mean prediction errors for the nomogram and the computer program were -0.037 and -0.026, respectively, and the mean percent absolute prediction errors were 11.6% and 11.0%, respectively. Neither method was biased, and differences between the results for the two methods were not significant. The predictive performance of the warfarin dosing nomogram was comparable to that of the computer program.

Bayes Theorem↗