Prediction of patient's neurological recovery from cervical spinal cord injury through XGBoost learning approach.

Due to the diversity of patient characteristics, therapeutic approaches, and radiological findings, it can be challenging to predict outcomes based on neurological consequences accurately within cervical spinal cord injury (SCI) entities and based on machine learning (ML) technique. Accurate neurological outcomes prediction in the patients suffering with cervical spinal cord injury is challenging due to heterogeneity existing in patient characteristics and treatment strategies. Machine learning algorithms are proven technology for achieving greater prediction outcomes. Thus, the research employed machine learning model through extreme gradient boosting (XGBoost) for attaining superior accuracy and reliability followed with other MI algorithms for predicting the neurological outcomes. Besides, it generated a model of a data-driven approach with extreme gradient boosting to enhance fault detection techniques (XGBoost) efficiency rate. To forecast improvements within functionalities of neurological systems, the status has been monitored through motor position (ASIA [American Spinal Injury Association] Impairment Scale [AIS] D and E) followed by the method of prediction employing XGBoost, combined with decision tree for regression logistics. Thus, with the proposed XGBoost approach, the enhanced accuracy in reaching the outcome is 81.1%, and from other models such as decision tree (80%) and logistic regression (82%), in predicting outcomes of neurological improvements within cervical SCI patients. Considering the AUC, the XGBoost and decision tree valued with 0.867 and 0.787, whereas logistic regression showed 0.877. Therefore, the application of XGBoost for accurate prediction and decision-making in the categorization of pre-treatment in patients with cervical SCI has reached better development with this study.

External control arms in oncology: current use and future directions.

Although randomized control trials allow for a comparison of treatment arms with minimal concern for confounding by known and unknown factors, a randomized study is not feasible in certain disease settings. When a randomized design is not possible, incorporating external control data into the study design can be an effective way to expand the interpretability of the results of an experimental arm by introducing the ability to carry out a formal or an informal comparative analysis. This paper provides an introduction to the concepts of external controls in oncology trials, followed by a review of relevant and current research on this topic. The paper also focuses on general considerations for designing a trial that may incorporate external control data, followed by case studies of the marketing applications submitted to the Food and Drug Administration that included external control data.

Analysis of time-to-treatment discontinuation of targeted therapy, immunotherapy, and chemotherapy in clinical trials of patients with non-small-cell lung cancer.

BACKGROUND: Pragmatic end points, such as time-to-treatment discontinuation (TTD), defined as the date of starting a medication to the date of treatment discontinuation or death has been proposed as a potential efficacy end point for real-world evidence (RWE) trials, where imaging evaluation is less structured and standardized. PATIENTS AND METHODS: We studied 18 randomized clinical trials of patients with metastatic non-small-cell lung cancer (mNSCLC), initiated after 2007 and submitted to U.S. Food and Drug Administration. TTD was calculated as date of randomization to date of discontinuation or death and compared to progression-free survival (PFS) and overall survival (OS) across all patients, as well as in treatment-defined subgroups [EGFR mutation-positive treated with tyrosine kinase inhibitor (TKI), EGFR wild-type treated with TKI, ALK-positive treated with TKI, immune checkpoint inhibitor (ICI), chemotherapy doublet with maintenance, chemotherapy monotherapy]. RESULTS: Overall across 8947 patients, TTD was more closely associated with PFS (r = 0.87, 95% CI 0.86-0.87) than with OS (0.68, 95% CI 0.67-0.69). Early TTD (PFS-TTD ≥ 3 months) occurred in 7.7% of patients overall, and was more common with chemo monotherapy (15.0%) while late TTD (TTD-PFS ≥ 3 months) occurred in 6.0% of patients overall, and was more common in EGFR-positive and ALK-positive patients (12.4% and 22.9%). In oncogene-targeted subgroups (EGFR positive and ALK positive), median TTDs (13.4 and 14.1 months) exceeded median PFS (11.4 and 11.3 months). CONCLUSIONS: At the patient level, TTD is associated with PFS across therapeutic classes. Median TTD exceeds median PFS for biomarker-selected patients receiving oncogene-targeted therapies. TTD should be prospectively studied further as an end point for pragmatic randomized RWE trials only for continuously administered therapies.

Efficacy of Curcumin as an Adjunct to Scaling and Root Planing in Chronic Periodontitis Patients: A Randomized Controlled Clinical Trial.

AIM: The aim of the present study is to evaluate the efficacy of curcumin gel as local drug delivery post-scaling and root planing and its effect on clinical parameters like plaque, gingival scores, pocket depth, and clinical attachment level (CAL). MATERIALS AND METHODS: Ten patients with two sites in the contralateral quadrants having probing pocket depths (PPDs) of ≥5 mm were selected. Full-mouth scaling and root planing (SRP) was performed followed by the application of curcumin gel on a single side. Assessment of plaque index (PI), gingival index (GI), PPD, and CALs were done at the baseline and at the 4th week. RESULTS: The results revealed that there was a statistically significant reduction in PI and probing depth in the test group when compared with the control group. CAL was improved but the results were not statically significant. CONCLUSION: The local application of curcumin gel when used in conjunction with SRP showed a significant improvement in periodontal parameters and has a beneficial effect in patients with chronic periodontitis. CLINICAL SIGNIFICANCE: Curcumin gel as an adjunct to SRP showed a marked improvement in restoring gingival health by an improvement in clinical parameters. It has proven properties like anti-inflammatory, antioxidant, antimicrobial, hepatoprotective, immunostimulant, antiseptic, antimutagenic, and it also accelerates wound healing. It may be a more acceptable and viable option for the common man. Curcumin can be used as an effective alternative local drug delivery agent.

Complex-compound Odontome with 526 Denticles: A Unique Case Report.

Aim: To report a unique case presentation of a complex-compound odontome with 526 denticles. Background: Odontoma is a hamartoma of the jaws that has both epithelial and mesenchymal components differentiating to form enamel and dentin. It is of compound and complex types. Rarely, the features of both the types are present together in what is called the compound-complex type of odontoma. Case description: The case report discussed here is that of a 7-year-old boy who presented with a compound-complex odontoma in the right posterior mandibular region. Conclusion: Timely diagnosis and prompt surgical treatment aid in preventing complications and bony expansion. Thus, proper histopathological examination is essential for the confirmation of odontoma. Recurrence of odontoma is rare and usually has a favorable prognosis if diagnosed early. Clinical significance: The odontome contained 526 denticles, the maximum reported in the literature so far, making this a case of extreme clinical significance. How to cite this article: Marimuthu M, Prabhu AR, Kalyani P, et al. Complex-compound Odontome with 526 Denticles: A Unique Case Report. Int J Clin Pediatr Dent 2022;15(6):789-792.

The impact of using weight estimated from mammographic images vs self-reported weight on breast cancer risk calculation.

Personalised breast screening requires assessment of individual risk of breast cancer, of which one contributory factor is weight. Self-reported weight has been used for this purpose, but may be unreliable. We explore the use of volume of fat in the breast, measured from digital mammograms. Volumetric breast density measurements were used to determine the volume of fat in the breasts of 40,431 women taking part in the Predicting Risk Of Cancer At Screening (PROCAS) study. Tyrer-Cuzick risk using self-reported weight was calculated for each woman. Weight was also estimated from the relationship between self-reported weight and breast fat volume in the cohort, and used to re-calculate Tyrer-Cuzick risk. Women were assigned to risk categories according to 10 year risk (below average <2%, average 2-3.49%, above average 3.5-4.99%, moderate 5-7.99%, high ≥8%) and the original and re-calculated Tyrer-Cuzick risks were compared. Of the 716 women diagnosed with breast cancer during the study, 15 (2.1%) moved into a lower risk category, and 37 (5.2%) moved into a higher category when using weight estimated from breast fat volume. Of the 39,715 women without a cancer diagnosis, 1009 (2.5%) moved into a lower risk category, and 1721 (4.3%) into a higher risk category. The majority of changes were between below average and average risk categories (38.5% of those with a cancer diagnosis, and 34.6% of those without). No individual moved more than one risk group. Automated breast fat measures may provide a suitable alternative to self-reported weight for risk assessment in personalized screening.

Conjugation of ampicillin and enrofloxacin residues with bovine serum albumin and raising of polyclonal antibodies against them.

AIM: The aim of this study is to test the potency of bovine serum albumin (BSA) conjugated ampicillin (AMP) and enrofloxacin (ENR) antigens in eliciting an immune response in rats using indirect competitive enzyme-linked immunosorbent assay (icELISA). MATERIALS AND METHODS: AMP and ENR antibiotics were conjugated with BSA by carbodiimide reaction using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) as a cross-linker. The successful conjugation was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Sprague-Dawley rats were immunized with the conjugates and blood samples were collected serially at 15 days time interval after first immunization plus first booster, second booster, third booster, and the fourth sampling was done 1½ month after the third booster. The antibody titres in the antisera of each antibiotic in all the four immunization cycles (ICs) were determined by an icELISA at various serum dilutions ranging from 1/100 to 1/6400. RESULTS: Analysis of antibiotic-BSA conjugates by sodium dodecyl sulfate polyacrylamide gel electrophoresis and coomassie blue staining revealed high molecular weight bands of 85 kDa and 74 kDa for AMP-BSA and ENR-BSA respectively when compared to 68 kDa band of BSA. Both the antibiotic conjugates elicited a good immune response in rats but comparatively the response was more with AMP-BSA conjugate than ENR-BSA conjugate. Maximum optical density 450 value of 2.577 was recorded for AMP-BSA antisera, and 1.723 was recorded for ENR-BSA antisera at 1/100(th) antiserum dilution in third IC. CONCLUSION: AMP and ENR antibiotics proved to be good immunogens when conjugated to BSA by carbodiimide reaction with EDC as crosslinker. The polyclonal antibodies produced can be employed for detecting AMP and ENR residues in milk and urine samples.

NADH oxidation is stimulated by an intermediate formed during vanadyl-H2O2 interaction.

Addition of NADH decreased the oxygen release that accompanied oxidation of vanadyl by H2O2. The added NADH was oxidized rapidly and oxygen was consumed with a stoichiometry of 1:1 for NADH/O2. Small concentrations of H2O2 were sufficient to trigger this oxygen-consuming NADH oxidation which terminated on exhaustion of either NADH or vanadyl. The oxidation of NADH increased proportionately with concentration of NADH and vanadyl. The oxidation products of vanadyl were found to be a mixture of vanadate oligomers and peroxovanadates. The reaction was sensitive to catalase, SOD, histidine and EDTA. Using ESR spectroscopy with DMPO as the spin trap, an adduct corresponding to DMPO-OH was detected in these phosphate-buffered reaction mixtures. Participation of hydroxyl radicals in NADH oxidation, however, seems doubtful because even high concentrations of ethanol, methanol, mannitol, formate and benzoate, known to scavenge these radicals, did not block the reaction. The results indicate that peroxovanadate intermediates formed during vanadyl oxidation by H2O2 play a key role in the oxidation of NADH.

A study on biochemical facet of anemia in cancers: A strong link between erythropoietin and tumor necrosis factor alpha in anemic cancer patients.

BACKGROUND: The three direct factors that could lead cancer patients to anemia, apart from therapy are iron deficiency, inflammatory cytokines surge and decreased erythropoietin (Epo). Our aim was to quantify biochemical and hematologic markers serum Epo, ferritin (Fe) and tumor necrosis factor-alpha (TNF-α) along with hemoglobin (Hb) to understand the associations between these factors, patient characteristics and anemia. MATERIALS AND METHODS: The study group consisted of 100 anemic cancer patients and 80 controls. Biochemical marker levels were determined by the enzyme linked immunosorbent assay on an autoanalyser. Univarient analysis, t-test, ANOVA, Bonferroni test, linear regression was performed to find correlations and associations among various factors. RESULTS: The baseline serum Epo (153.07 ± 173.88 vs. 23.607 ± 36.462) and Fe levels (233.53 ± 257.12 vs. 23.06 ± 20.04) were adequately high in cases compared with that controls (P ≤ 0.001). Considerable raise in TNF-α levels was also observed (16.26 ± 13.44 vs. 11.2375 ± 4.84) (P = 0.001). TNF-α correlated positively (P = 0.022) with Epo and Fe (P = 0.000), which was also evident from large effect size of Epo (r2 = 0.414), TNF-α (r2 = 0.369), Hb (r2 = 0.226). Epo and Hb were negatively correlated (ß = -0.375, P = 0.001) and Epo production was found to be appropriate for the degree of anemia (O/P ratio of 3.51 ± 1.26 vs. 1.43 ± 0.47). A strong association was seen between Hb, Epo and TNF-α in hematological and gynecological malignancies for different grades of anemia. Men were more prone to life-threatening anemia (13%) than women (9%). CONCLUSION: Anemia in cancers was not because of inadequate Epo or Fe levels, but because of improper Epo response. Further studies on molecular analysis of Epo, biochemical and molecular interplay between Epo and TNF-α could explain a rationale for anemia in cancers.

Polyvanadate-stimulated NADH oxidation by plasma membranes--the need for a mixture of deca and meta forms of vanadate.

Polyvanadate solutions obtained by extracting vanadium pentoxide with dilute alkali over a period of several hours contained increasing amounts of decavanadate as characterized by NMR and ir spectra. Those solutions having a metavanadate:decavanadate ratio in the range of 1-5 showed maximum stimulation of NADH oxidation by rat liver plasma membranes. Reduction of decavanadate, but not metavanadate, was obtained only in the presence of the plasma membrane enzyme system. High simulation of activity of NADH oxidation was obtained with a mixture of the two forms of vanadate and this further increased on lowering the pH. Addition of increasing concentrations of decavanadate to metavanadate and vice versa increased the stimulatory activity, reaching a maximum when the metavanadate:decavanadate ratio was in the range of 1-5. Increased stimulatory activity can also be obtained by reaching these ratios by conversion of decavanadate to metavanadate by alkaline phosphate degradation, and of metavanadate to decavanadate by acidification. These studies show for the first time that both deca and meta forms of vanadate present in polyvanadate solutions are needed for maximum activity of NADH oxidation.

A novel phenomenon of burst of oxygen uptake during decavanadate-dependent oxidation of NADH.

Oxidation of NADH by decavanadate, a polymeric form vanadate with a cage-like structure, in presence of rat liver microsomes followed a biphasic pattern. An initial slow phase involved a small rate of oxygen uptake and reduction of 3 of the 10 vanadium atoms. This was followed by a second rapid phase in which the rates of NADH oxidation and oxygen uptake increased several-fold with a stoichiometry of NADH: O2 of 1:1. The burst of NADH oxidation and oxygen uptake which occurs in phosphate, but not in Tris buffer, was prevented by SOD, catalase, histidine, EDTA, MnCl2 and CuSO4, but not by the hydroxyl radical quenchers, ethanol, methanol, formate and mannitol. The burst reaction is of a novel type that requires the polymeric structure of decavanadate for reduction of vanadium which, in presence of traces of H2O2, provides a reactive intermediate that promotes transfer of electrons from NADH to oxygen.

Characterization of oxygen free radicals generated during vanadate-stimulated NADH oxidation.

The oxidation of NADH and accompanying reduction of oxygen to H2O2 stimulated by polyvanadate was markedly inhibited by SOD and cytochrome c. The presence of decavanadate, the polymeric form, is necessary for obtaining the microsomal enzyme-catalyzed activity. The accompanying activity of reduction of cytochrome c was found to be SOD-insensitive and therefore does not represent superoxide formation. The reduction of cytochrome c by vanadyl sulfate was also SOD-insensitive. In the presence of H2O2, all the forms of vanadate were able to oxidize reduced cytochrome c, which was sensitive to mannitol, tris and also catalase, indicating H2O2-dependent generation of hydroxyl radicals. Using ESR and spin trapping technique only hydroxyl radicals, but not superoxide anion radicals, were detected during polyvanadate-dependent NADH oxidation.

Decavanadate possesses alpha-adrenergic agonist activity and a structural motif common with trans-beta form of noradrenaline.

Decavanadate, an inorganic polymer of vanadate, produced contraction of rat aortic rings at a relatively high concentration compared to phenylephrine, an agonist of alpha-adrenergic receptor. This effect was blocked by two known alpha-adrenergic receptor antagonists, prazosin and phenoxybenzamine. Decavanadate, formed by possible dimerization of V5 under acid conditions, possessed a structural feature of two pairs of unshared oxygen atoms at a distance of 3.12 A, not found in its constituents of V4 or V5. A structural motif of O..O..O using such oxygen atoms is recognized in decavanadate. This matches with a similar motif of N..O..O that uses the essential amino and hydroxyl groups of the side-chain and the m-hydroxyl group in trans-beta form of noradrenaline. The interaction of such a structural motif with the membrane receptor is likely to be the basis of the unusual noradrenaline-mimic action of decavanadate.