Progression-free survival estimation of docetaxel-based second-line treatment for advanced non-small cell lung cancer: a pooled analysis from 18 randomized control trials.

Background: Lung cancer is the foremost cause of cancer-related death globally, with non-small cell lung cancer (NSCLC) accounting for 85-90% of cases. Targeted therapy is the most essential therapeutic option for NSCLC, other common treatments include radiation therapy, surgery, chemotherapy, and immunotherapy. Objective: Our study objective was to estimate whether progression-free survival (PFS) is an outcome of NSCLC extracted from 18 randomized control trials (RCTs) with docetaxel as experimental group and antineoplastic agent, kinase inhibitor, and monoclonal antibodies as a control group. Methods: We selected relevant studies published between 2011 and 2022 using Google Scholar, PubMed, Scopus, Science Direct, and Cochrane Library. Advanced NSCLC, chemotherapy, RCT, docetaxel, and second-line treatment were the terms included in the search. A total of 9738 patients were evaluated from the 18 identified studies. We used the meta package of R Studio to perform the meta-analysis. Graphical funnel plots were used to evaluate publication bias visually. Results: Patients who underwent docetaxel-based therapy had a considerably longer PFS than those who got antineoplastic agents, kinase inhibitors, or monoclonal antibodies-based treatment. Patients in the standard treatment arm had a slightly longer PFS than those in the experimental therapy arm in the overall meta-analysis. Conclusion: Docetaxel outperformed monoclonal antibodies, antineoplastic agents, and kinase inhibitors in the second-line therapy of advanced NSCLC since PFS was extensively utilized.

Shifting to machine supervision: annotation-efficient semi and self-supervised learning for automatic medical image segmentation and classification.

Advancements in clinical treatment are increasingly constrained by the limitations of supervised learning techniques, which depend heavily on large volumes of annotated data. The annotation process is not only costly but also demands substantial time from clinical specialists. Addressing this issue, we introduce the S4MI (Self-Supervision and Semi-Supervision for Medical Imaging) pipeline, a novel approach that leverages advancements in self-supervised and semi-supervised learning. These techniques engage in auxiliary tasks that do not require labeling, thus simplifying the scaling of machine supervision compared to fully-supervised methods. Our study benchmarks these techniques on three distinct medical imaging datasets to evaluate their effectiveness in classification and segmentation tasks. Notably, we observed that self-supervised learning significantly surpassed the performance of supervised methods in the classification of all evaluated datasets. Remarkably, the semi-supervised approach demonstrated superior outcomes in segmentation, outperforming fully-supervised methods while using 50% fewer labels across all datasets. In line with our commitment to contributing to the scientific community, we have made the S4MI code openly accessible, allowing for broader application and further development of these methods. The code can be accessed at https://github.com/pranavsinghps1/S4MI .

The Molecular Twin artificial-intelligence platform integrates multi-omic data to predict outcomes for pancreatic adenocarcinoma patients.

Contemporary analyses focused on a limited number of clinical and molecular biomarkers have been unable to accurately predict clinical outcomes in pancreatic ductal adenocarcinoma. Here we describe a precision medicine platform known as the Molecular Twin consisting of advanced machine-learning models and use it to analyze a dataset of 6,363 clinical and multi-omic molecular features from patients with resected pancreatic ductal adenocarcinoma to accurately predict disease survival (DS). We show that a full multi-omic model predicts DS with the highest accuracy and that plasma protein is the top single-omic predictor of DS. A parsimonious model learning only 589 multi-omic features demonstrated similar predictive performance as the full multi-omic model. Our platform enables discovery of parsimonious biomarker panels and performance assessment of outcome prediction models learning from resource-intensive panels. This approach has considerable potential to impact clinical care and democratize precision cancer medicine worldwide.

Impact of Alcohol and Methamphetamine Use on Burn Resuscitation.

Mortality associated with burn injuries is declining with improved critical care. However, patients admitted with concurrent substance use have increased risk of complications and poor outcomes. The impact of alcohol and methamphetamine use on acute burn resuscitation has been described in single-center studies; however, has not been studied since implementation of computerized decision support for resuscitation. Patients were evaluated based presence of alcohol, with a minimum blood alcohol level of 0.10, or positive methamphetamines on urine drug screen. Fluid volumes and urine output were examined over 48 hours. A total of 296 patients were analyzed. 37 (12.5%) were positive for methamphetamine use, 50 (16.9%) were positive for alcohol use, and 209 (70.1%) with negative for both. Patients positive for methamphetamine received a mean of 5.30 ± 2.63 cc/kg/TBSA, patients positive for alcohol received a mean of 5.41 ± 2.49 cc/kg/TBSA, and patients with neither received a mean of 4.33 ± 1.79 cc/kg/TBSA. Patients with methamphetamine or alcohol use had significantly higher fluid requirements. In the first 6 hours patients with alcohol use had significantly higher urinary output (UO) in comparison to patients with methamphetamine use which had similar output to patients negative for both substances. This study demonstrated that patients with alcohol and methamphetamine use had statistically significantly greater fluid resuscitation requirements compared to patients without. The effects of alcohol as a diuretic align with previous literature. However, patients with methamphetamine lack the increased UO as a cause for their increased fluid requirements.

Evaluating the Antimicrobial and Anti-Hemolytic Activity of Synthesized Pseudopeptide against Leptospiral Species: In Silico and In Vitro Approach.

Bacterial infections are one of the leading causes of morbidity, mortality, and healthcare complications in patients. Leptospirosis is found to be the most prevalent, re-emergent, and neglected tropical zoonotic disease worldwide. The adaptation to various environmental conditions has made Leptospira acquire a large genome (~4.6 Mb) and a complex outer membrane, making it unique among bacteria that mimic the symptoms of jaundice and hemorrhage. Sph2 is another important virulence factor that enhances hemolytic sphingomyelinase-capable of moving inside mitochondria-which increases the ROS level and decreases the mitochondrial membrane potential, thereby leading to cell apoptosis. In the present study, 25 suspected bovine serum samples were subjected to the Microscopic Agglutination Test (MAT) across the Mysuru region. Different samples, such as urine, serum, and aborted materials from the confirmed MAT-positive animals, were used for isolation and genomic detection by conventional PCR targeting virulence gene, Lipl32, using specific primers. Further, in vitro and in silico studies were performed on isolated cultures to assess the anti-leptospiral, anti-hemolytic, and sphingomyelinase enzyme inhibition using novel pseudopeptides. The microdilution technique (MDT) and dark field microscope (DFM) assays revealed that at a concentration of 62.5 µg/mL, the pseudopeptide inhibited 100% of the growth of Leptospira spp., suggesting its efficiency in the treatment of leptospirosis. The flow cytometry analyses show the potency of the pseudopeptide against sphingomyelinase enzymes using human umbilical vein endothelial cells (HUVECs). Thus, the present study demonstrated the efficacy of the pseudopeptide in the inhibition of the growth of Leptospira, and therefore, this can be used as an alternative drug for the treatment of leptospirosis.

Evaluation of codon usage patterns and molecular evolution dynamics in Japanese encephalitis virus: An integrated bioinformatics approach.

In the recent survey, Japanese encephalitis (JE) is one of the most common mosquito-borne diseases, accounting for ∼30% of fatalities. The outbreaks of the JE virus (JEV) suggests that exhaustive study is essential for the prevention and management of the disease. The disease mainly spreads in humans and pigs by the vector: mosquito; as this is a major concern, this study had employed various bioinformatics tools to investigate the codon usage bias, evolutionary inference and selection pressure analysis of the Japanese encephalitis virus disease. The results indicated that the JE virus was biased and natural selection was the main factor shaping the codon usage that was determined and confirmed with the Nc, neutrality, PR2 plots and correlation analysis. The evolutionary analysis revealed that the virus had a substitution rate of 1.54 × 10-4 substitution/site/year and the tMRCA was found to be in 1723. The transmission of the virus in the map found transmissions mostly from China and transmitted across Asia and Africa. The selection pressure analysis employed three methods which had 969th codon site as diversifying site and had many purifying sites that shows the virus had evolved rapidly. The inferences from this study would aid people to employ this methodology on various diseases and also perform insilico studies in the field of vaccinology and immunoinformatics.

Adaptive optimal control of entangled qubits.

Developing fast, robust, and accurate methods for optimal control of quantum systems comprising interacting particles is one of the most active areas of current science. Although a valuable repository of algorithms is available for numerical applications in quantum control, the high computational cost is somewhat overlooked. Here, we present a fast and accurate optimal control algorithm for systems of interacting qubits, QOALA (quantum optimal control by adaptive low-cost algorithm), which is predicted to offer [Formula: see text](M2) speedup for an M-qubit system, compared to the state-of-the-art exact methods, without compromising overall accuracy of the optimal solution. The method is general and compatible with diverse Hamiltonian structures. The proposed approach uses inexpensive low-accuracy approximations of propagators far from the optimum, adaptively switching to higher accuracy, higher-cost propagators when approaching the optimum. In addition, the utilization of analytical Lie algebraic derivatives that do not require computationally expensive matrix exponential brings even better performance.

Preparation, Characterization and In Vitro Biological Activities of New Diphenylsulphone Derived Schiff Base Ligands and Their Co(II) Complexes.

The present work describes the chemical preparation of Schiff bases derived from 4,4'-diaminodiphenyl sulfone (L1-L5) and their Co(II) metal complexes. The evaluation of antimicrobial and anticancer activities against MCF-7 cell line and human lung cancer cell line A-549 was performed. The aforementioned synthesized compounds are characterized by spectroscopic techniques and elemental analysis confirms successful synthesis. The results from the above analytical techniques revealed that the complexes are in an octahedral geometry. The antimicrobial activity of the synthesized Schiff base ligands and their metal complexes under study was carried out by using the agar well diffusion method. The ligand and complex interactions for biological targets were predicted using molecular docking and high binding affinities. Further, the anticancer properties of the synthesized compounds are performed against the MCF-7 cell line and human lung cancer cell line A-549 using adriamycin as the standard drug.

Vagal paraganglioma clinically presenting as a persistent dry cough.

Vagal paragangliomas (VPs) are a rare subset of neuroendocrine tumour derived from paraganglia located in the head/neck that are usually indolent in nature. Typical clinical presentations include pulsatile tinnitus or hoarseness associated with a neck mass. Surgery and radiation therapy remain the primary treatment modalities but come with significant morbidity including cranial nerve damage. We describe a unique case of VP in which cough was the only presenting symptom, that was exacerbated by enlargement of the tumour. Symptoms improved following radiation treatment.

Evaluation and Comparison of Self-applied Remineralizing Agents Using Confocal Microscopy: An In Vitro Study.

AIM AND OBJECTIVE: The study was conducted to assess and compare the remineralization ability of fluoride varnish, casein phosphopeptide amorphous calcium phosphate fluoride (CPP-ACPF), bioactive glass-ceramic, and nanohydroxyapatite crystals using a confocal microscope. MATERIALS AND METHODS: Eighty premolars and 80 deciduous central incisors were included in this study. Two windows of approximately 3 × 3 mm were created on the labial surface of the premolars and 2 × 2 mm on deciduous maxillary incisors. Artificial caries like lesions was created by demineralizing the sample windows. The teeth sections were then randomly assigned into four groups (n = 20). Specimens of the first group were once painted with fluoride varnish, while those in CPP-ACPF, bioactive glass-ceramic, and nanohydroxyapatite were brushed twice daily for 2 minutes each for 40 days, respectively. 150-200 µm longitudinal sections were obtained and were photographed under a confocal laser scanning microscope. They were quantified using a computerized imaging system for demineralization and later for remineralization. The recorded values were tabulated and analyzed using Fisher's test, analysis of variance (ANOVA), and post hoc Bonferroni's test. RESULTS: All the materials used in the study showed remineralization potential at the end of 40 days in both permanent and deciduous teeth. The highest remineralization potential was observed in the fluoride varnish group followed by bioactive glass, CPP-ACFP, and nanohydroxyapatite in both permanent and deciduous teeth. In permanent teeth, the difference in the remineralization potential of fluoride varnish and bioactive glass was not statistically significant. CONCLUSION: The present study showed that self-applied bioactive glass has similar remineralization potential to fluoride varnish in permanent teeth. Therefore, bioactive glass can be used for the management of incipient caries lesions daily. HOW TO CITE THIS ARTICLE: Goel T, Singhal A, Singh I, et al. Evaluation and Comparison of Self-applied Remineralizing Agents Using Confocal Microscopy: An In Vitro Study. Int J Clin Pediatr Dent 2020;13(S-1):S34-S39.

Alignment-free filtering for cfNA fusion fragments.

MOTIVATION: Cell-free nucleic acid (cfNA) sequencing data require improvements to existing fusion detection methods along multiple axes: high depth of sequencing, low allele fractions, short fragment lengths and specialized barcodes, such as unique molecular identifiers. RESULTS: AF4 was developed to address these challenges. It uses a novel alignment-free kmer-based method to detect candidate fusion fragments with high sensitivity and orders of magnitude faster than existing tools. Candidate fragments are then filtered using a max-cover criterion that significantly reduces spurious matches while retaining authentic fusion fragments. This efficient first stage reduces the data sufficiently that commonly used criteria can process the remaining information, or sophisticated filtering policies that may not scale to the raw reads can be used. AF4 provides both targeted and de novo fusion detection modes. We demonstrate both modes in benchmark simulated and real RNA-seq data as well as clinical and cell-line cfNA data. AVAILABILITY AND IMPLEMENTATION: AF4 is open sourced, licensed under Apache License 2.0, and is available at: https://github.com/grailbio/bio/tree/master/fusion.

Sixth-order schemes for laser-matter interaction in the Schrödinger equation.

Control of quantum systems via lasers has numerous applications that require fast and accurate numerical solution of the Schrödinger equation. In this paper, we present three strategies for extending any sixth-order scheme for the Schrödinger equation with time-independent potential to a sixth-order method for the Schrödinger equation with laser potential. As demonstrated via numerical examples, these schemes prove effective in the atomic regime as well as the semiclassical regime and are a particularly appealing alternative to time-ordered exponential splittings when the laser potential is highly oscillatory or known only at specific points in time (on an equispaced grid, for instance). These schemes are derived by exploiting the linear in space form of the time dependent potential under the dipole approximation (whereby commutators in the Magnus expansion reduce to a simpler form), separating the time step of numerical propagation from the issue of adequate time-resolution of the laser field by keeping integrals intact in the Magnus expansion and eliminating terms with unfavorable structure via carefully designed splittings.

A predictive model for the diffusion of a highly non-ideal ternary system.

Diffusion plays a central part in many unit operations. The Maxwell-Stefan model is the dominant model for both gaseous and liquid diffusion. However, it was developed from the kinetic theory of gases, raising the question of whether it can be extended to non-ideal liquid systems. The dynamic fluctuation model is an alternative model based on the Cussler theory and predicts a smaller thermodynamic influence relative to the linear influence of the Maxwell-Stefan model due to dynamic concentration fluctuations. Since the dynamic fluctuation model, which uses the scaling factor α, had improved performance relative to the Maxwell-Stefan model for a wide range of binary systems, it is postulated that this improved performance should also be observed for a ternary system. In this work, the dynamic molecular fluctuation model was extended to a highly non-ideal ternary system, using the same scaling factor α, through matrix manipulation. Using self-diffusion data measured by NMR, mutual diffusion predictions of the developed model and the Maxwell-Stefan model were compared to experimental mutual diffusion data of the partially miscible system ethanol/toluene/n-decane. It is demonstrated that the dynamic fluctuation model gives improved predictions relative to the Maxwell-Stefan approach, consistent with previous observations on binary systems, showing that the reduced thermodynamic influence of the dynamic fluctuation model is an improvement. In addition, we show that the use of local mole fractions, to account for molecular association, in both the dynamic fluctuation and Maxwell-Stefan models, results in improved diffusion predictions for the ternary system. The results confirm that the dynamic fluctuation model improves predictions of mutual diffusion in liquid mixtures, suggesting a non-linear correction to the thermodynamic correction factor. The results also suggest that that the key assumptions in the Maxwell-Stefan model and its derivation, rooted in the kinetic theory of gases, are not entirely accurate for highly non-ideal liquid systems. The optimum α for the ternary system studied here is approximately 0.45, similarly to the optimum α of 0.40 to 0.80 for a range of binary systems previously studied, suggesting that the use of the α scaling factor, which is grounded in scaling laws theory, is of general validity.

RNA-seq analysis identifies key long non-coding RNAs connected to the pathogenesis of alcohol-associated head and neck squamous cell carcinoma.

Alcohol consumption has been implicated in the pathogenesis of head and neck squamous cell carcinoma (HNSCC), although its mechanism is poorly understood. Recent advances in the identification and understanding of long non-coding RNAs (lncRNAs) have indicated that these molecules have a profound effect on numerous biological processes, including tumorigenesis and oncogenesis. The present authors hypothesize that alcohol-mediated dysregulation of lncRNAs is a key event in HNSCC pathogenesis. An in silico differential expression analysis utilizing RNA sequencing (RNA-seq) data from 34 HNSCC patients, which included alcohol drinkers and non-alcohol drinkers, identified a panel of lncRNAs that were dysregulated due to alcohol consumption. Normal oral keratinocytes were then exposed to ethanol and acetaldehyde to validate the RNA-seq results. Two lncRNAs that were differentially expressed due to alcohol consumption were identified from RNA-seq analysis of the clinical data: lnc-PSD4-1 and lnc-NETO-1. Oral keratinocytes exposed to alcohol and acetaldehyde demonstrated dysregulation of these two lncRNAs, thus validating the results of RNA-seq analysis. In addition, low expression of the lnc-PSD4-1 isoform, lnc-PSD4-1:14, exhibited a strong correlation with high survival rates in a Cox proportional hazards regression model. Therefore, these lncRNAs may play a key role in the early pathogenesis of HNSCC, since they are dysregulated in both clinical data and in vitro experiments mimicking the effects of alcohol use.

Soft tissue development around pontic site: A case series.

An ideal emergence profile is vital for maintaining gingival health and developing esthetics. The ovate pontic which mimics a natural tooth gives the most appropriate emergence profile. For a successful ovate pontic restoration, an alveolar ridge of sufficient height and width is necessary to enhance the deficient ridge and to achieve an esthetic emergence profile. Interpositional graft was carried out along with ovate pontic to achieve an ideal esthetic restoration. After three months of the postoperative period, there was an increased horizontal dimension in the deficient ridge and an esthetic emergence profile. Interpositional graft technique is a simpler and predictable technique for pontic site development in moderate cases of bucco-lingual ridge deficiency.

The non-coding landscape of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is an aggressive disease marked by frequent recurrence and metastasis and stagnant survival rates. To enhance molecular knowledge of HNSCC and define a non-coding RNA (ncRNA) landscape of the disease, we profiled the transcriptome-wide dysregulation of long non-coding RNA (lncRNA), microRNA (miRNA), and PIWI-interacting RNA (piRNA) using RNA-sequencing data from 422 HNSCC patients in The Cancer Genome Atlas (TCGA). 307 non-coding transcripts differentially expressed in HNSCC were significantly correlated with patient survival, and associated with mutations in TP53, CDKN2A, CASP8, PRDM9, and FBXW7 and copy number variations in chromosomes 3, 5, 7, and 18. We also observed widespread ncRNA correlation to concurrent TP53 and chromosome 3p loss, a compelling predictor of poor prognosis in HNSCCs. Three selected ncRNAs were additionally associated with tumor stage, HPV status, and other clinical characteristics, and modulation of their expression in vitro reveals differential regulation of genes involved in epithelial-mesenchymal transition and apoptotic response. This comprehensive characterization of the HNSCC non-coding transcriptome introduces new layers of understanding for the disease, and nominates a novel panel of transcripts with potential utility as prognostic markers or therapeutic targets.

Enhancing the zone of keratinized tissue around implants.

Presence or absence of a minimal zone of keratinized tissue around dental implants has been a matter of controversy. However, a consensus exists that a thick zone of keratinized zone around implants provides a prosthetic friendly environment, facilitates precise prosthetic procedures, allows oral hygiene maintenance, resists recession, and enhances esthetic blending. The aim of the present case series was to increase the zone of keratinized soft tissue around dental implants supporting overdentures. Three different surgical techniques modified palatal roll technique with and without apical positioning and connective tissue graft (CTG) were used to achieve this goal. There was a significant gain of keratinized soft tissue with all the three techniques, which remained stable over a period of 6 months. Modified palatal roll technique with and without apical positioning and CTG are simpler surgical techniques, which can be successfully and predictably used for increasing the zone of keratinized tissue around implants.

Assessment of the effectiveness of sustained release Bupropion and intensive physician advice in smoking cessation.

BACKGROUND: Tobacco use is the cause of immense burden on our nation in terms of mortality and morbidity, being the single leading cause of preventable illnesses and death. Smoking cessation interventions in our country will be the most cost effective of all interventions considering that the cost incurred on the three main tobacco related illnesses (COPD, CAD, and Cancer) being around Rs 27,761 crore in the year 1999. MATRIALS AND METHODS: A double blind placebo controlled trial was conducted to see the efficacy of Bupropion in smoking cessation. Smokers with current depression were excluded. The subjects (n = 30) were randomly assigned to receive Bupropion SR 300 mg/day or placebo for seven weeks. Target quit date was preferentially 8(th) day of starting the treatment. Intensive counseling was provided by the physician at the baseline and brief counseling at every visit weekly during the treatment phase and at weeks 12 and 16. Self reported abstinence was confirmed by a carbon monoxide concentration in expired air of less than 10 ppm. RESULTS: The seven-day point prevalence abstinence rate at the end of week 2 and week 16 in the drug group was 46.67% and 53.33 % respectively and in the placebo group was 13.33% and 20% respectively with the 'P' value of 0.04 and 0.05 respectively. Rates of continuous abstinence at weeks 4, 7 and 16 were 46.67%, 40% and 33.33% in the drug group and 13.33%, 13.33% and 13.33% in the placebo group respectively. The rates were significantly higher in the drug group till week 4 starting from week 2 of the treatment phase. The mean weight gain in drug group was found to be significant less as compared to the placebo at week 16 (P = 0.025) The mean change of depression scores from the baseline was not significantly different between the two groups at any point of time. The withdrawal symptom score increase from the baseline was not significantly higher at any point of time in the drug group but in the placebo group the increase was significantly higher for seven days after target quit date and at weeks 3 and 4 (P < 0.05). The most common adverse events in the drug group were insomnia, which was seen in 6 (40%) patients and dry mouth and/or altered taste in 4 (26.67%) patients, which was significantly higher as compared to placebo. PREDICTORS OF OUTCOME: The univariate predictors of a successful outcome were the point prevalence abstinence at week 16 were older age (>40 years), (P = 0.044) and quitter status at week 2 (P = 0.001). Multivariate predictors in order of importance were Quit status at 2nd week (P = 0.002) and Age >40 years (P = 0.031). The combined predictive value of these two variables was found to be 86.3%. CONCLUSIONS: Bupropion helps in smoking cessation. This has been proved by three large multicenter randomized controlled trials. This study has also reflected the same result in the form of significantly high seven-day point prevalence abstinence at week 16 in the Bupropion group as compared to placebo. Bupropion has a beneficial effect on weight gain and withdrawal symptoms and the benign adverse effects of insomnia and dry mouth or altered taste make it a very effective and cheap treatment for nicotine addiction in smokers.