AI powered quantification of nuclear morphology in cancers enables prediction of genome instability and prognosis.

While alterations in nucleus size, shape, and color are ubiquitous in cancer, comprehensive quantification of nuclear morphology across a whole-slide histologic image remains a challenge. Here, we describe the development of a pan-tissue, deep learning-based digital pathology pipeline for exhaustive nucleus detection, segmentation, and classification and the utility of this pipeline for nuclear morphologic biomarker discovery. Manually-collected nucleus annotations were used to train an object detection and segmentation model for identifying nuclei, which was deployed to segment nuclei in H&E-stained slides from the BRCA, LUAD, and PRAD TCGA cohorts. Interpretable features describing the shape, size, color, and texture of each nucleus were extracted from segmented nuclei and compared to measurements of genomic instability, gene expression, and prognosis. The nuclear segmentation and classification model trained herein performed comparably to previously reported models. Features extracted from the model revealed differences sufficient to distinguish between BRCA, LUAD, and PRAD. Furthermore, cancer cell nuclear area was associated with increased aneuploidy score and homologous recombination deficiency. In BRCA, increased fibroblast nuclear area was indicative of poor progression-free and overall survival and was associated with gene expression signatures related to extracellular matrix remodeling and anti-tumor immunity. Thus, we developed a powerful pan-tissue approach for nucleus segmentation and featurization, enabling the construction of predictive models and the identification of features linking nuclear morphology with clinically-relevant prognostic biomarkers across multiple cancer types.

Influence of brassinosteroid and silicon on growth, antioxidant enzymes, and metal uptake of leafy vegetables under wastewater irrigation.

Vegetable cultivation under sewage irrigation is a common practice mostly in developing countries due to a lack of freshwater. Long-term usage provokes heavy metals accumulation in soil and ultimately hinders the growth and physiology of crop plants and deteriorates the quality of food. A study was performed to investigate the role of brassinosteroid (BRs) and silicon (Si) on lettuce, spinach, and cabbage under lead (Pb) and cadmium (Cd) contaminated sewage water. The experiment comprises three treatments (control, BRs, and Si) applied under a completely randomized design (CRD) in a growth chamber. BRs and Si application resulted in the highest increase of growth, physiology, and antioxidant enzyme activities when applied under canal water followed by distilled water and sewage water. However, BRs and Si increased the above-determined attributes under the sewage water by reducing the Pb and Cd uptake as compared to the control. It's concluded that sewerage water adversely affected the growth and development of vegetables by increasing Pb and Cd, and foliar spray of Si and BRs could have great potential to mitigate the adverse effects of heavy metals and improve the growth. The long-term alleviating effect of BRs and Si will be evaluated in the field conditions at different ecological zones.

Long-term efficacy of spinal cord stimulation for chronic primary neuropathic pain in the contemporary era: a systematic review and meta-analysis.

INTRODUCTION: Spinal cord stimulation (SCS) is a modern neuromodulation technique extensively proven to be an effective modality for treatment of chronic neuropathic pain. It has been mainly studied for complex regional pain syndrome (CRPS) and failed back surgery syndrome (FBSS) and recent data almost uniformly establishes its statistically significant positive therapeutic results. It has also been compared with other available treatment modalities across various studies. However, long term data on maintenance of its efficacious potential remains less explored. Few studies have reported data on long follow-up times (>= 12 months) and have compared its efficacy with other treatment options for chronic pain, respectively. Our study pools and analyzes the available data and compares SCS with other treatment options. It also analyzes the efficacy of SCS in long term management of patients with chronic pain. EVIDENCE ACQUISITION: We reviewed all the data available on MEDLINE, Embase and Cochrane CENTRAL using a search strategy designed to fit our pre-set inclusion and exclusion criteria. Both single-arm and double-arm studies were included. The primary outcome was defined as decrease of visual analogue scale (VAS) by >50% at 6, 12 and/or 24 months after SCS. EVIDENCE SYNTHESIS: According to the pooled data of double-arm studies, SCS has unanimously proven its superiority over other treatment options at 6 months follow-up; however it fails to prove statistically significant difference in results at longer treatment intervals. Dorsal root ganglion stimulation, a relatively recent technique with the same underlying physiologic mechanisms as SCS, showed far more promising results than SCS. Single-arm studies show around 70% patients experiencing greater than 50% reduction in their VAS scores at 6 and 12 months. CONCLUSIONS: SCS is a viable option for management of chronic neuropathic pain secondary to FBSS and CRPS. However, data available for its long term efficacy remains scarce and show no further statistically significant results.

Plant growth-promoting bacterial consortia improved the physiology and growth of maize by regulating osmolytes and antioxidants balance under salt-affected field conditions.

This study was undertaken to see how microbial consortia influenced maize development and yield under salt-affected conditions. The efficacy of the pre-isolated bacterial strains Burkholderia phytofirmans, Bacillussubtilis, Enterobacter aerogenes, and Pseudomonas syringae and Pseudomonas fluorescens to decrease the detrimental effects of salt on maize was tested in four distinct combinations using Randomized Complete Block Design with three replicates. The results revealed that these strains were compatible and collaborated synergistically, with an 80% co-aggregation percentage under salt-affected conditions. Following that, these strains were tested for their ability to increase maize growth and yield under salt-affected field conditions. The photosynthetic rate (11-50%), relative water content (10-34%), and grain yield (13-21%) of maize were all increased by these various combinations. However, when Burkholderia phytofirmans, Enterobacter aerogenes and Pseudomonas fluorescens were combined, the greatest increase was seen above the un-inoculated control. Furthermore, as compared to the un-inoculated control, the same combination resulted in a 1.5-fold increase in catalase and a 2.0-fold increase in ascorbate concentration. These findings showed that a multi-strain consortium might boost maize's total yield response as a result of better growth under salt stress.

Therapeutic and safety outcomes of intracoronary nicardipine in coronary artery disease patients: a systematic review.

Aim: This systematic review aimed to shed light on the efficacy of intracoronary (IC) nicardipine in treating no reflow with CAD undergoing revascularization. Methods: Literature search was performed on databases with following eligibility criteria: adult patients with CAD; clinical trials or observational studies; IC nicardipine as intervention; therapeutic and safety outcome reported. Results: A total of 1249 papers were yielded during the literature search. Of these, 11 studies were finalized for this systematic review. Complete restoration of TIMI 3 flow was observed in 98.6% of the patients receiving IC nicardipine. A significant increase in the CBF after infusion of IC nicardipine (p < 0.05) was also observed. Conclusion: IC nicardipine significantly increases CBF and decreases coronary vascular resistance.

Coronary artery disease (CAD) is a condition that results in the narrowing or blockage of heart arteries. Arteries are blood vessels that bring oxygen-rich blood from your heart to the rest of your body's cells. We aimed to evaluate the effects of intracoronary (IC) nicardipine, a drug that blocks calcium from entering the muscle cells and blood vessels of the heart, which causes the vessels to relax and widen, allowing for blood to flow more easily, on a phenomenon known as coronary slow flow (CSF). CSF is defined as a delayed widening of the blood vessels of the heart. CSF or the no reflow phenomenon is a major negative complication associated with surgical procedures such as percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), both of which are used to open up blocked arteries. The systematic search identified studies that evaluated the effect of IC nicardipine in patient during CAD treatment, undergoing PCI, CABG, or having confirmed or suspected narrowing of the aortic valve or one of the four valves of the heart, which results in restricted blood flow from the heart to the body. From the results of studies discussed in the review, it can be concluded that IC nicardipine significantly increases blood flow to the heart and can help prevent the no reflow phenomenon in patients undergoing PCI. Nicardipine proved to be a safe and effective option in the management of complications such as no reflow in patients receiving therapies to restore blood flow following CAD.

Mechanical Response of Glass-Epoxy Composites with Graphene Oxide Nanoparticles.

Graphene-based fillers possess exceptional properties that encourage researchers toward their incorporation in glass-epoxy (GE) polymer composites. Regarding the mechanical and wear properties of glass-epoxy composites, the effect of graphene oxide (GO) reinforced in glass-epoxy was examined. A decrease in tensile modulus and increase in tensile strength was reported for 1 wt. % of GO. A shift in glass transition temperature Tg was observed with the addition of GO. The cross-link density and storage modulus of the composite decreased with the addition of GO. The decrease in dissipation energy and wear rate was reported with the increase in GO concentration. A simple one-dimensional damage model of nonlinear nature was developed to capture the stress-strain behavior of the unfilled and filled glass-epoxy composite. Tensile modulus E, Weibull scale parameter σo, and Weibull shape parameter ß were considered to develop the model. Finally, to understand the failure mechanisms in GO-filled composites, a scanning electron microscopic (SEM) examination was carried out for tensile fractured composites.

Evaluating CNC Milling Performance for Machining AISI 316 Stainless Steel with Carbide Cutting Tool Insert.

The present study investigates the CNC milling performance of the machining of AISI 316 stainless steel using a carbide cutting tool insert. Three critical machining parameters, namely cutting speed (v), feed rate (f) and depth of cut (d), each at three levels, are chosen as input machining parameters. The face-centred central composite design (FCCCD) of the experiment is based on response surface methodology (RSM), and machining performances are measured in terms of material removal rate (MRR) and surface roughness (SR). Analysis of variance, response graphs, and three-dimensional surface plots are used to analyse experimental results. Multi-response optimization using the data envelopment analysis based ranking (DEAR) approach is used to find the ideal configuration of the machining parameters for milling AISI 316 SS. The variables v = 220 m/min, f = 0.20 mm/rev and d = 1.2 mm were obtained as the optimal machine parameter setting. Study reveals that MRR is affected dominantly by d followed by v. For SR, f is the dominating factor followed by d. SR is found to be almost unaffected by v. Finally, it is important to state that this work made an attempt to successfully machine AISI 316 SS with a carbide cutting tool insert, to investigate the effect of important machining parameters on MRR and SR and also to optimize the multiple output response using DEAR method.

Assessment of Destructive and Nondestructive Analysis for GGBS Based Geopolymer Concrete and Its Statistical Analysis.

Geopolymer is the alternative to current construction material trends. In this paper, an attempt is made to produce a sustainable construction composite material using geopolymer. Ground granulated blast furnace slag (GGBS)-based geopolymer concrete was prepared and tested for different alkaline to binder ratios (A/B). The effect of various temperatures on compressive strength properties was assessed. The cubes were exposed to temperature ranging from 50 to 70 °C for a duration ranging from 2 to 10 h, and the compressive strength of the specimens was analyzed for destructive and non-destructive analysis and tested for 7, 28, and 90 days. The obtained compressive strength (CS) results were analyzed employing the probability plot (PP) curve, distribution overview curve (DOC), probability density function (PDF), Weibull, survival, and hazard function curve. Maximum compressive strength was achieved for the temperature of 70 °C and an A/B of 0.45 for destructive tests and non-destructive tests with 44.6 MPa and 43.56 MPa, respectively, on 90 days of testing. The survival and hazard function curves showed incremental distribution characteristics for 28 and 90 days of testing results with a probability factor ranging from 0.8 to 1.0.

Optimization of Alkaline Activator on the Strength Properties of Geopolymer Concrete.

This study investigates the effects of red mud on the performance of geopolymer concrete in regard to fresh and mechanical properties. Red mud was used as a binder, and GGBS replaced the binder. Different proportions of red mud ranging from 0 to 30% with an interval of 2% and activator agents such as KOH and K2SiO3 for various alkaline-to-binder ratios such as 0.30, 0.40, and 0.50 were used; their effect on the fresh and mechanical properties of geopolymer concrete were the focusing parameter on the current study. Fresh properties such as setting time, slump, compaction factor, and vee-bee consistometer test, and mechanical properties such as compressive strength, split tensile strength, flexural strength, modulus of elasticity, and impact energy were studied. ANOVA and radar plot analysis were studied for various alkaline to binder (A/B) compressive strength results tested for 7 to 90 days. The increase of red mud quantity caused the decline of workability, but there was continuous enhancement of mechanical properties of GPC up to a specific limit. An alkaline-to-binder ratio of 0.4 shows excellent results compared with other ratios at ambient conditions for strength properties. ANOVA and radar plot reveal that A/B of 0.40 for 90 days shows excellent results compared with other ratios, and CS values vary in a linear manner.

Polio amidst COVID-19 in Pakistan: Ongoing efforts, challenges, and recommendations.

Poliomyelitis is a crippling viral disease caused by poliovirus, a positive-stranded RNA virus that is a serotype of Enterovirus C. Pakistan remains one of the countries in the world where poliomyelitis is still prevalent, posing an obstacle to global poliomyelitis eradication. With the commencement of the COVID-19 pandemic, polio eradication campaigns have proven less feasible, resulting in an increase in polio cases across the country. Pakistan's healthcare system and socio-economic framework are incapable of dealing with two deadly viruses at the same time. As a result, effective measures for combating the destruction caused by the spread of the poliovirus are required.

Transfusion Transmitted Infections: A Present-Day Danger for Pakistan.

Over 1.5 million units of blood are collected in Pakistan each year, with around 65% of this donation coming from replacement donors-relatives or close friends of the affected who willingly donate blood to support the patient. Although blood transfusion is a life-saving therapy, it also involves the danger of spreading blood-borne illnesses if not appropriately screened. It has been extensively discussed that the precise number of transfusion transmitted infections (TTIs) in the Pakistani population is still unclear, and the estimates reported by the Sindh Blood Transfusion Authority may be a major underestimation because of the country's lack of inexpensive and effective screening tests. Regular blood transfusions are the mainstay of treatment of patients with blood diseases such as thalassemia and anemia. They are also commonly used to handle acute injuries, surgery, bleeding, and birthing difficulties. However, the risk of getting a TTI results in an increased hesitancy among blood transfusion recipients. Hence, to reduce the occurrence of TTIs, effective and vigorous measures must be implemented.

Interactive effect of different salinity sources and their formulations on plant growth, ionic homeostasis and seed quality of maize.

Soil salinity is one of the most pernicious environmental hazards affecting crop growth and productivity in arid and semi-arid climates. In saline soils, the crop plants encounter nutrients deficient conditions mainly due to antagonistic affinity of sodium (Na+) and chloride (Cl-). The accumulation of salts in the rhizosphere restricts plant growth, the severity of which depends on the source and concentration of the salt. Therefore, we hypothesized that sodium containing salts could have toxic effects on maize plants either in a single or in combined form. To evaluate the interactive effect of sodium salts on plant growth, ionic homeostasis, and seed quality attributes, a pot study was performed using maize as a test plant at the research area of the College of Agriculture, University of Sargodha. Selected salts including, NaCl, Na2SO4 and their combination (NaCl + Na2SO4), were applied in equal ratio for different salinity levels (7, 10, 13 and 16 dS m-1) and the untreated control. The results show that all the measured growth, yield, biochemical and quality attributes of maize were negatively affected with increasing concentration of all the salt sources; however, severity of these effects were more intense when NaCl was applied at all salinity levels. It is concluded that all salts (NaCl, Na2SO4 and NaCl + Na2SO4) had negative effects on biochemical, qualitative, growth and yield characteristics of maize plant. Most importantly, NaCl was found to be more harmful compared to Na2SO4 and mixtures of both salts due to the dominance of Na+ and Cl-ions. Among all salinity levels, the more detrimental effects of NaCl occurred at salinity level of 16 dS m-1.

Robust p53 recovery using chattering free sliding mode control and a gain-scheduled modified Utkin observer.

p53 protein plays an essential role in protecting the genomic integrity of mammalian cells. A drastic decrease in the amount of p53 protein has been observed in cancerous cells. By using Nutlin-based small molecule drugs, the concentration of p53 can be restored to the desired level. This paper presents the drug-dosage design for p53 pathway, based on a control-oriented nonlinear model. A chattering free sliding mode control (CFSMC) strategy is employed to track the desired trajectory of p53 concentration for both of its dynamic behaviors, i.e., sustained and oscillatory responses. A gain-scheduled modified Utkin observer (GSMUO) is designed for robust state reconstruction and disturbance estimation. The simulation results show that CFSMC and GSMUO exhibit desired robustness and performance properties in the presence of parametric variations, an input disturbance and measurement noise. Moreover, a comprehensive simulation study, along with a detailed quantitative analysis is performed to compare CFSMC-GSMUO with four different techniques: a sliding mode control (SMC) with an equivalent control based sliding mode observer (SMO) and GSMUO, respectively, and a dynamic sliding mode control (DSMC) with SMO and GSMUO, respectively. The analysis demonstrates that the tracking error and utilization of the control energy is the least in the case of CFSMC-GSMUO as compared to its counterparts.

Comparing SPEED and OSDI Questionnaires in a Non-Clinical Sample.

PURPOSE: To compare the performance of OSDI and SPEED questionnaires in a non-clinical sample in Pakistan. METHODS: SPEED and OSDI questionnaires were simultaneously administered to a sample of 600 participants in Pakistan with an average age of 31.0 ± 10.1 years. RESULTS: Mean SPEED scores were calculated according to the OSDI categories and were found to be 3.33 ± 3.44, 5.45 ± 3.77, 7.86 ± 4.33, and 9.39 ± 4.56 for the normal, mild, moderate, and severe groups, respectively. Using Cronbach's alpha, the total OSDI and SPEED scores were calculated to be 0.924 and 0.879, respectively. A receiver operating curve was plotted, and the area under the curve (AUC) was estimated to be 0.791. Using this curve, the cutoff score for the SPEED questionnaire was found to be 4.00 (P < 0.001). CONCLUSION: The SPEED questionnaire can be used as an effective alternative to the OSDI.

Development of artificial neural network model for prediction of post-streptococcus mutans in dental caries.

BACKGROUND AND OBJECTIVE: Streptococcus mutans is the primary initiator and most common organism associated with dental caries. Prediction of post-Streptococcus mutans favours in the selection of appropriate caries excavation method which eventually results in meliorate caries-free cavity preparation for restoration. The objective of this study is to predict the post-Streptococcus mutans prior to dental caries excavation based on pre- Streptococcus mutans using iOS App developed on Artificial Neural Network (ANN) model. METHODS: For the current research work, children with occlusal dentinal caries lesion were chosen, 45 primary molar teeth cases were studied. Caries excavation was done with carbide bur, polymer bur and spoon excavator. The colony forming units for pre and post-Streptococcus mutans were recorded, data emanating from clinical trials was employed to develop the ANN models. ANN models were trained, validated and tested with the registered clinical data using different ANN architectures. RESULTS: Feedforward backpropagation ANN model with an architecture of 4-5-1, predicts post-Streptococcus mutans with an efficiency of 0.99033, mean squared error and mean absolute percentage error for testing cases were 0.2341 and 4.967 respectively. CONCLUSIONS: Caries excavation methods and pre-Streptococcus mutans are feed as inputs, while post-Streptococcus mutans as targets to develop ANN model. Based on the developed ANN model, an ingenious iOS App was developed, the global clinician may utilize the App to meticulously predict post-Streptococcus mutans on iPhone based on pre-Streptococcus mutans, which in turn aids in decision making for the selection of caries excavation method. This study manifests the potential application of iOS App with built-in ANN model in efficiently predicting the post-Streptococcus mutans. Also, the study extends scope for applications of iOS App with built-in ANN models in clinical medicine.

Can-CSC-GBE: Developing Cost-sensitive Classifier with Gentleboost Ensemble for breast cancer classification using protein amino acids and imbalanced data.

Early prediction of breast cancer is important for effective treatment and survival. We developed an effective Cost-Sensitive Classifier with GentleBoost Ensemble (Can-CSC-GBE) for the classification of breast cancer using protein amino acid features. In this work, first, discriminant information of the protein sequences related to breast tissue is extracted. Then, the physicochemical properties hydrophobicity and hydrophilicity of amino acids are employed to generate molecule descriptors in different feature spaces. For comparison, we obtained results by combining Cost-Sensitive learning with conventional ensemble of AdaBoostM1 and Bagging. The proposed Can-CSC-GBE system has effectively reduced the misclassification costs and thereby improved the overall classification performance. Our novel approach has highlighted promising results as compared to the state-of-the-art ensemble approaches.