Using multi-label ensemble CNN classifiers to mitigate labelling inconsistencies in patch-level Gleason grading.

This paper presents a novel approach to enhance the accuracy of patch-level Gleason grading in prostate histopathology images, a critical task in the diagnosis and prognosis of prostate cancer. This study shows that the Gleason grading accuracy can be improved by addressing the prevalent issue of label inconsistencies in the SICAPv2 prostate dataset, which employs a majority voting scheme for patch-level labels. We propose a multi-label ensemble deep-learning classifier that effectively mitigates these inconsistencies and yields more accurate results than the state-of-the-art works. Specifically, our approach leverages the strengths of three different one-vs-all deep learning models in an ensemble to learn diverse features from the histopathology images to individually indicate the presence of one or more Gleason grades (G3, G4, and G5) in each patch. These deep learning models have been trained using transfer learning to fine-tune a variant of the ResNet18 CNN classifier chosen after an extensive ablation study. Experimental results demonstrate that our multi-label ensemble classifier significantly outperforms traditional single-label classifiers reported in the literature by at least 14% and 4% on accuracy and f1-score metrics respectively. These results underscore the potential of our proposed machine learning approach to improve the accuracy and consistency of prostate cancer grading.

Zinc and nitrogen mediate the regulation of growth, leading to the upregulation of antioxidant aptitude, physio-biochemical traits, and yield in wheat plants.

An ample amount of water and soil nutrients is required for economic wheat production to meet the current food demands. Nitrogen (N) and zinc (Zn) fertigation in soils can produce a substantial wheat yield for a rapidly increasing population and bring a limelight to researchers. The present study was designed to ascertain N and Zn's synergistic role in wheat growth, yield, and physio-biochemical traits. A pot experiment was laid out under a complete randomized design with four N levels (N1-0, N2-60, N3- 120, and N4-180 kg ha-1), Zn (T1-0, T2-5, T3-10, and T4-15 kg ha-1) with four replications. After the emergence of the plants, N and Zn fertigation was applied in the soil. The growth traits were considerably increased by combined applications as compared to the sole applications of the N and Zn. The photosynthetic pigments were found maximum due to combined applications of N and Zn, which were positively associated with biomass, growth, yield, and wheat grain quality. The combined application also substantially enhances the antioxidant enzyme activities to scavenge the ROS as H2O2 and reduce lipid peroxidation to protect the permeability of the biologic membranes. The combined higher applications of N and Zn were more responsive to ionic balance in a shoot by maintaining the Na+ for osmotic adjustments, accumulating more Ca2+ for cellular signaling; but, combined applications resulted in K+ reduction. Our present results suggest that appropriate sole or combined applications of N and Zn improve wheat's growth, yield, and antioxidant mechanisms. Previous studies lack sufficient information on N and Zn combined fertigation. We intend to investigate both the sole and combined roles of N and Zn to exploit their potential synergistic effects on wheat.

Diffusion MRI Metrics Characterize Postoperative Clinical Outcomes After Surgery for Cervical Spondylotic Myelopathy.

BACKGROUND AND OBJECTIVES: Advanced diffusion-weighted MRI (DWI) modeling, such as diffusion tensor imaging (DTI) and diffusion basis spectrum imaging (DBSI), may help guide rehabilitation strategies after surgical decompression for cervical spondylotic myelopathy (CSM). Currently, however, postoperative DWI is difficult to interpret, owing to signal distortions from spinal instrumentation. Therefore, we examined the relationship between postoperative DTI/DBSI-extracted from the rostral C3 spinal level-and clinical outcome measures at 2-year follow-up after decompressive surgery for CSM. METHODS: Fifty patients with CSM underwent complete clinical and DWI evaluation-followed by DTI/DBSI analysis-at baseline and 2-year follow-up. Clinical outcomes included the modified Japanese Orthopedic Association score and comprehensive patient-reported outcomes. DTI metrics included apparent diffusion coefficient, fractional anisotropy, axial diffusivity, and radial diffusivity. DBSI metrics evaluated white matter tracts through fractional anisotropy, fiber fraction, axial diffusivity, and radial diffusivity as well as extra-axonal pathology through restricted and nonrestricted fraction. Cross-sectional Spearman's correlations were used to compare postoperative DTI/DBSI metrics with clinical outcomes. RESULTS: Twenty-seven patients with CSM, including 15, 7, and 5 with mild, moderate, and severe disease, respectively, possessed complete baseline and postoperative DWI scans. At 2-year follow-up, there were 10 significant correlations among postoperative DBSI metrics and postoperative clinical outcomes compared with 3 among postoperative DTI metrics. Of the 13 significant correlations, 7 involved the neck disability index (NDI). The strongest relationships were between DBSI axial diffusivity and NDI (r = 0.60, P < .001), DBSI fiber fraction and NDI (rs = -0.58, P < .001), and DBSI restricted fraction and NDI (rs = 0.56, P < .001). The weakest correlation was between DTI apparent diffusion coefficient and NDI (r = 0.35, P = .02). CONCLUSION: Quantitative measures of spinal cord microstructure after surgery correlate with postoperative neurofunctional status, quality of life, and pain/disability at 2 years after decompressive surgery for CSM. In particular, DBSI metrics may serve as meaningful biomarkers for postoperative disease severity for patients with CSM.

Proteomic Profiling of Small-Cell Lung Cancer: A Systematic Review.

The accurate diagnosis of small-cell lung cancer (SCLC) is crucial, as treatment strategies differ from those of other lung cancers. This systematic review aims to identify proteins differentially expressed in SCLC compared to normal lung tissue, evaluating their potential utility in diagnosing and prognosing the disease. Additionally, the study identifies proteins differentially expressed between SCLC and large cell neuroendocrine carcinoma (LCNEC), aiming to discover biomarkers distinguishing between these two subtypes of neuroendocrine lung cancers. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive search was conducted across PubMed/MEDLINE, Scopus, Embase, and Web of Science databases. Studies reporting proteomics information and confirming SCLC and/or LCNEC through histopathological and/or cytopathological examination were included, while review articles, non-original articles, and studies based on animal samples or cell lines were excluded. The initial search yielded 1705 articles, and after deduplication and screening, 16 articles were deemed eligible. These studies revealed 117 unique proteins significantly differentially expressed in SCLC compared to normal lung tissue, along with 37 unique proteins differentially expressed between SCLC and LCNEC. In conclusion, this review highlights the potential of proteomics technology in identifying novel biomarkers for diagnosing SCLC, predicting its prognosis, and distinguishing it from LCNEC.

Recent Advances in Microbial-Assisted Remediation of Cadmium-Contaminated Soil.

Soil contamination with cadmium (Cd) is a severe concern for the developing world due to its non-biodegradability and significant potential to damage the ecosystem and associated services. Industries such as mining, manufacturing, building, etc., rapidly produce a substantial amount of Cd, posing environmental risks. Cd toxicity in crop plants decreases nutrient and water uptake and translocation, increases oxidative damage, interferes with plant metabolism and inhibits plant morphology and physiology. However, various conventional physicochemical approaches are available to remove Cd from the soil, including chemical reduction, immobilization, stabilization and electro-remediation. Nevertheless, these processes are costly and unfriendly to the environment because they require much energy, skilled labor and hazardous chemicals. In contrasting, contaminated soils can be restored by using bioremediation techniques, which use plants alone and in association with different beneficial microbes as cutting-edge approaches. This review covers the bioremediation of soils contaminated with Cd in various new ways. The bioremediation capability of bacteria and fungi alone and in combination with plants are studied and analyzed. Microbes, including bacteria, fungi and algae, are reported to have a high tolerance for metals, having a 98% bioremediation capability. The internal structure of microorganisms, their cell surface characteristics and the surrounding environmental circumstances are all discussed concerning how microbes detoxify metals. Moreover, issues affecting the effectiveness of bioremediation are explored, along with potential difficulties, solutions and prospects.

Biogenic Fabrication of Iron Oxide Nanoparticles from Leptolyngbya sp. L-2 and Multiple In Vitro Pharmacogenetic Properties.

Metallic nanoparticles have received a significant amount of reflection over a period of time, attributed to their electronic, specific surface area, and surface atom properties. The biogenic synthesis of iron oxide nanoparticles (FeONPs) is demonstrated in this study. The green synthesis of metallic nanoparticles (NPs) is acquiring considerable attention due to its environmental and economic superiorities over other methods. Leptolyngbya sp. L-2 extract was employed as a reducing agent, and iron chloride hexahydrate (FeCl3·6H2O) was used as a substrate for the biogenic synthesis of FeONPs. Different spectral methods were used for the characterization of the biosynthesized FeONPs, ultraviolet-visible (UV-Vis) spectroscopy gave a surface plasmon resonance (SPR) peak of FeONPs at 300 nm; Fourier transform infrared (FTIR) spectral analysis was conducted to identify the functional groups responsible for both the stability and synthesis of FeONPs. The morphology of the FeONPs was investigated using scanning electron microscopy (SEM), which shows a nearly spherical shape, and an X-ray diffraction (XRD) study demonstrated their crystalline nature with a calculated crystallinity size of 23 nm. The zeta potential (ZP) and dynamic light scattering (DLS) measurements of FeONPs revealed values of -8.50 mV, suggesting appropriate physical stability. Comprehensive in-vitro pharmacogenetic properties revealed that FeONPs have significant therapeutic potential. FeONPs have been reported to have potential antibacterial and antifungal properties. Dose-dependent cytotoxic activity was shown against Leishmania tropica promastigotes (IC50: 10.73 µg/mL) and amastigotes (IC50: 16.98 µg/mL) using various concentrations of FeONPs. The cytotoxic potential was also investigated using brine shrimps, and their IC50 value was determined to be 34.19 µg/mL. FeONPs showed significant antioxidant results (DPPH: 54.7%, TRP: 49.2%, TAC: 44.5%), protein kinase (IC50: 96.23 µg/mL), and alpha amylase (IC50: 3745 µg/mL). The biosafety of FeONPs was validated by biocompatibility tests using macrophages (IC50: 918.1 µg/mL) and red blood cells (IC50: 2921 µg/mL). In conclusion, biogenic FeONPs have shown potential biomedical properties and should be the focus of more studies to increase their nano-pharmacological significance for biological applications.

Biosorption of Cadmium and Lead by Dry Biomass of Nostoc sp. MK-11: Kinetic and Isotherm Study.

Cadmium (Cd) and lead (Pb) are global environmental pollutants. In this study, Nostoc sp. MK-11 was used as an environmentally safe, economical, and efficient biosorbent for the removal of Cd and Pb ions from synthetic aqueous solutions. Nostoc sp. MK-11 was identified on a morphological and molecular basis using light microscopic, 16S rRNA sequences and phylogenetic analysis. Batch experiments were performed to determine the most significant factors for the removal of Cd and Pb ions from the synthetic aqueous solutions using dry Nostoc sp. MK1 biomass. The results indicated that the maximum biosorption of Pb and Cd ions was found under the conditions of 1 g of dry Nostoc sp. MK-11 biomass, 100 mg/L of initial metal concentrations, and 60 min contact time at pH 4 and 5 for Pb and Cd, respectively. Dry Nostoc sp. MK-11 biomass samples before and after biosorption were characterized using FTIR and SEM. A kinetic study showed that a pseudo second order kinetic model was well fitted rather than the pseudo first order. Three isotherm models Freundlich, Langmuir, and Temkin were used to explain the biosorption isotherms of metal ions by Nostoc sp. MK-11 dry biomass. Langmuir isotherm, which explains the existence of monolayer adsorption, fitted well to the biosorption process. Considering the Langmuir isotherm model, the maximum biosorption capacity (qmax) of Nostoc sp. MK-11 dry biomass was calculated as 75.757 and 83.963 mg g-1 for Cd and Pb, respectively, which showed agreement with the obtained experimental values. Desorption investigations were carried out to evaluate the reusability of the biomass and the recovery of the metal ions. It was found that the desorption of Cd and Pb was above 90%. The dry biomass of Nostoc sp. MK-11 was proven to be efficient and cost-effective for removing Cd and especially Pb metal ions from the aqueous solutions, and the process is eco-friendly, feasible, and reliable.

Alleviation of cadmium toxicity in Zea mays L. through up-regulation of growth, antioxidant defense system and organic osmolytes under calcium supplementation.

Calcium (Ca) is a macronutrient and works as a modulator to mitigate oxidative stress induced by heavy metals. In this study, we investigated the role of Ca to ameliorate the Cd toxicity in Zea mays L. by modulating the growth, physio-biochemical traits, and cellular antioxidant defense system. Maize genotype Sahiwal-2002 was grown under a controlled glasshouse environment with a day/night temperature of 24 ± 4°C/14 ± 2°C in a complete randomized design with three replications and two Cd levels as (0 and 150 µM) and six regimes of Ca (0, 0.5, 1, 2.5, 5, and 10 mM). Maize seedlings exposed to Cd at 150 µM concentration showed a notable decrease in growth, biomass, anthocyanins, chlorophylls, and antioxidant enzymes activities. A higher level of Cd (150 µM) also caused an upsurge in oxidative damage observed as higher electrolyte leakage (increased membrane permeability), H2O2 production, and MDA accumulation. Supplementation of Ca notably improved growth traits, photosynthetic pigments, cellular antioxidants (APX, POD, and ascorbic acid), anthocyanins, and levels of osmolytes. The significant improvement in the osmolytes (proteins and amino acids), and enzymatic antioxidative defense system enhanced the membrane stability and mitigated the damaging effects of Cd. The present results concluded that exogenously applied Ca potentially improve growth by regulating antioxidants and enabling maize plants to withstand the Cd toxicity.

Cadmium Phytotoxicity, Tolerance, and Advanced Remediation Approaches in Agricultural Soils; A Comprehensive Review.

Cadmium (Cd) is a major environmental contaminant due to its widespread industrial use. Cd contamination of soil and water is rather classical but has emerged as a recent problem. Cd toxicity causes a range of damages to plants ranging from germination to yield suppression. Plant physiological functions, i.e., water interactions, essential mineral uptake, and photosynthesis, are also harmed by Cd. Plants have also shown metabolic changes because of Cd exposure either as direct impact on enzymes or other metabolites, or because of its propensity to produce reactive oxygen species, which can induce oxidative stress. In recent years, there has been increased interest in the potential of plants with ability to accumulate or stabilize Cd compounds for bioremediation of Cd pollution. Here, we critically review the chemistry of Cd and its dynamics in soil and the rhizosphere, toxic effects on plant growth, and yield formation. To conserve the environment and resources, chemical/biological remediation processes for Cd and their efficacy have been summarized in this review. Modulation of plant growth regulators such as cytokinins, ethylene, gibberellins, auxins, abscisic acid, polyamines, jasmonic acid, brassinosteroids, and nitric oxide has been highlighted. Development of plant genotypes with restricted Cd uptake and reduced accumulation in edible portions by conventional and marker-assisted breeding are also presented. In this regard, use of molecular techniques including identification of QTLs, CRISPR/Cas9, and functional genomics to enhance the adverse impacts of Cd in plants may be quite helpful. The review's results should aid in the development of novel and suitable solutions for limiting Cd bioavailability and toxicity, as well as the long-term management of Cd-polluted soils, therefore reducing environmental and human health hazards.

Morphogenetic variation and assorted biological activities in true branching Nostocales strains of Cholistan oasis, Pakistan.

From the oasis of Cholistan, true branching heterocystous cyanobacterial strains were studied for, the cell arrangement in primary branches being mono- or bi-seriate; the shape of cells in main filament large and irregular; profused secondary branching emerging on one or both sides and tapering along their length. In these observed traits, two clear morphological taxa were recognized, both well-assorted from the previously described species of the genus Westiellopsis. Both strains showed culturing responses and were studied for antibacterial, cytotoxic, and anticancer potentials. The strain derived from the site B-10 provenance exhibited antibacterial activity against Pseudomonas (18 mm), Klebsiella (15 mm), Staphylococcus (22 mm). On the contrary, the strain of site A-44 showed no activity against any of the above-mentioned bacterial strains. The cytotoxicity assay for the strain of the B-10 site showed 36% larval mortality, whereas strain A-44 showed 24% larval mortality. Performance of the strain B-10 in MTT assay (assessed on HCT-116 cell lines) revealed a dose-dependent activity: at 200, 100, 50, and 25 µg/ml; achieving a growth inhibition of 50.15%, 40.22%, 33.72%, and 10.21%, respectively; and the strain of A-44 could only exhibit a 30.06% growth inhibition at 200 µg/ml. The 16S rRNA sequencing revealed the sequence homology with Neowestiellopsis. Based on data presented here we report two diverse taxa of true branching Nostocales from Cholistan oasis, Pakistan.

Evaluation of Antimicrobial and Anticancer Activities of Selected Medicinal Plants of Himalayas, Pakistan.

Medicinal plants are known for their diverse use in the traditional medicine of the Himalayan region of Pakistan. The present study is designed to investigate the anticancer and antimicrobial activities of Prunus cornuta and Quercus semicarpifolia. The anticancer activity was performed using cancerous human cell lines (HepG2, Caco-2, A549, MDA-MB-231, and NCI-H1437 carcinoma cells), while the antimicrobial activity was conducted with the agar-well diffusion method. Furthermore, toxicity studies were performed on alveolar and renal primary epithelial cells. Initially, different extracts were prepared by maceration techniques using n-hexane, chloroform, ethyl acetate, butanol, and methanol. The preliminary phytochemical screening showed the presence of secondary metabolites such as alkaloids, tannins, saponins, flavonoids, glycosides, and quinones. The chloroform extract of P. cornuta (PCC) exhibited significant inhibitory activity against Acinetobacter baumannii (16 mm) and Salmonella enterica (14.5 mm). The A. baumannii and S. enterica strains appeared highly susceptible to n-hexane extract of P. cornuta (PCN) with an antibacterial effect of 15 mm and 15.5 mm, respectively. The results also showed that the methanolic extracts of Quercus semecarpifolia (QSM) exhibited considerable antibacterial inhibitory activity in A. baumannii (18 mm), Escherichia coli (15 mm). The QSN and QSE extracts also showed good inhibition in A. baumannii with a 16 mm zone of inhibition. The Rhizopus oryzae strain has shown remarkable mycelial inhibition by PCM and QSN with 16 mm and 21 mm inhibition, respectively. Furthermore, the extracts of P. cornuta and Q. semicarpifolia exhibited prominent growth inhibition of breast (MDA-MB-231) and lung (A549) carcinoma cells with 19-30% and 22-39% cell viabilities, respectively. The gut cell line survival was also significantly inhibited by Q. semicarpifolia (24-34%). The findings of this study provide valuable information for the future development of new antibacterial and anticancer medicinal agents from P. cornuta and Q. semicarpifolia extracts.

Microwave-assisted synthesis and in vitro osteogenic analysis of novel bioactive glass fibers for biomedical and dental applications.

Glass fiber-based materials have gained interest for use in biomedical and dental applications. The aim of this study was to make E-glass fiber bioactive by a novel method using the microwave irradiation technique. Industrial E-glass fibers were used after surface activation with the hydrolysis method. The ratio of calcium and phosphorous precursors was set at 1.67. After maintaining the pH of the calcium solution, E-glass fibers in two ratios, i.e. 30% (nHA/E30) and 50% (nHA/E50) wt/wt, were added. The phosphorous precursor was added later and the solution was irradiated in a microwave to obtain nano-hydroxyapatite (nHA) particles on E-glass fibers. The structural, physical and in vitro biocompatibility analyses of the resulting materials were conducted. The expression of osteopontin (OPN) and collagen (Col) type 1 was measured by reverse transcription polymerase chain reaction (RT-PCR) and comparison was made between all the groups. Fourier transform infrared spectroscopy and x-ray diffraction showed characteristic peaks of nHA, and a change in the peak intensities was observed with an increase in the concentration of E-glass fibers. Scanning electron microscopic (SEM) images confirmed the homogenous adhesion of nHA spherical particles all over the fibers. Cell viability with mesenchymal stem cells showed growth, proliferation, and adhesion. All the materials were able to upregulate the expression of the OPN and Col, where gene expression was highest in nHA followed by nHA/E30 and nHA/E50. The bioactive glass fibers were synthesized in the shortest time and showed osteogenic properties. These materials have the potential for use in bone tissue engineering, dental prosthesis, and tooth restoration.

Cardio-protective and anti-cancer therapeutic potential of Nigella sativa.

Nigella sativa is the miraculous plant having a lot of nutritional and medicinal benefits, and attracts large number of nutrition and pharmacological researchers. N. sativa seed composition shows that it is the blessing of nature and it contains and many bioactive compounds like thymoquinone, α-hederin, alkaloids, flavonoids, antioxidants, fatty acids many other compounds that have positive effects on curing of different diseases. Several medicinal properties of N. sativa like its anti-cancer, anti-inflammatory, anti-diabetic, antioxidant activities and many others are well acknowledged. However, this article focuses on activity of N. sativa against cardiovascular diseases and cancer. For gathering required data the authors went through vast number of articles using search engines like Science direct, ELSEVIER, Pub Med, Willey on Line Library and Google scholar and the findings were classified on the basis of relevance of the topic and were reviewed in the article. N. sativa is rich source of different biologically active compounds and is found effective in controlling number of cardiovascular diseases and various cancers both in vivo and in vitro studies.