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Kashif Asghar,1 Shaarif Bashir,2 Iftikhar Ali Rana,2 Muhammad Abu Bakar,3 Asim Farooq,1 Muhammad Hassan,1 Zukhruf Asif,1 Mahnoor Afzal,1 Iqra Masood,4 Muhammad Ishaq,2 Muhammad Tahseen,2 Sundus Bilal,5 Shafqat Mehmood,5 Nosheen Kanwal,6 Islah Ud Din,6 Asif Loya2 1Department of Basic Sciences Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Punjab, Pakistan; 2Department of Pathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Punjab, Pakistan; 3Department of Cancer Registry and Clinical Data Management, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Punjab, Pakistan; 4Department of Clinical Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Punjab, Pakistan; 5Department of Internal Medicine (Gastroenterology), Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Punjab, Pakistan; 6Department of Radiology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Punjab, PakistanCorrespondence: Kashif Asghar, Department of Basic Sciences Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre, 7-A Block R-3, Johar Town, Lahore, Punjab, 54000, Pakistan, Tel +92-42-35905000, Fax +92-42-35945206, Email kashifasghar@skm.org.pkBackground/Aim: Hepatocellular carcinoma (HCC) is one of the most common forms of liver cancer that is modulated by the immune system. Programmed cell death ligand-1 (PD-L1) has emerged as a novel therapeutic target in various cancers. Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme that is associated with poor prognoses in various cancer types. The aim of this study was to investigate the PD-L1 expression, and clinicopathological features of non-HCV and non-HBV-associated HCC patients, including IDO expression.Patients and Methods: In this study, immunohistochemical analysis was performed to analyze the expression of PD-L1 and IDO. Formalin-fixed paraffin-embedded HCC tumor tissues (n=50) were obtained from the pathology department, at Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC) in Lahore, Pakistan between 2005 and 2022. All the patients were HBV and HCV negative. Furthermore, it was a rare group of patients with no previous history of any viral hepatitis. In addition, for categorical and continuous variables chi-square or Fisher exact test and Mann–Whitney U-test was performed.Results: Of 50 tissue specimens, PD-L1+ was observed in 21 [high: 12 (24%), low: 9 (18%)] and PD-L1- was observed in 29 HCC patients. IDO+ was observed in all 50 specimens [high: 42 (84%), low: 8 (16%)]. Additionally, both PD-L1 and IDO had high expression in 11 (22%) patients. While both PD-L1 and IDO had low expression in 2 (4%) patients. Furthermore, in IDO+/PD-L1- group, 20 (69%) out of 29 patients died while in the IDO+/PD-L1+ group, 9 (43%) out of 21 patients died.Conclusion: Evaluation of IDO and PD-L1 expression may add therapeutic advantage in non-HCV and non-HBV-associated HCC patients that overexpress IDO. Further validation in a larger cohort is warranted.Keywords: programmed cell death ligand-1, indoleamine 2, 3-dioxygenase, non-HCV HCC, non-HBV HCC, immune checkpoint molecules

In this work, the electro-optical and magnetic characteristics of Be1-xCrxS (x = 6.25%, 12.5% and 25%) are brought into investigation by employing full potential linearized augmented plane wave (FP-LAPW) scheme designed within density functional theory (DFT). The stability of the Be1-xCrxS alloy is justified by the negative values of formation energy. The band structures and density of states are examined by using GGA functional. Be1-xCrxS compound demonstrates the half-metallic (HM) ferromagnetic behavior for all doping concentrations; spin-up channel reveals the metallic character and other spin version displays the semiconductor (SC) behavior. The values of total magnetic moment (µB) are recorded as 4.0 8.0 and 16.0 µB for corresponding 6.25%, 12.5% and 25%, which mainly arises owing to Cr-3d state. Moreover, optical features including dielectric function ε(ω), reflectivity, refraction, and absorption are explored within range of 0-10 eV. The maximum absorption of incident photons was found in ultraviolet (UV) span which implies their importance for optoelectronic applications. Results reveal that the studied alloy has potential applications in magnetic and optoelectronic gadgets. [ABSTRACT FROM AUTHOR]

Objective. To examine the association between insomnia and obesity in Mexican adults aged 50 and older. Materials and methods. We used data from the Mexican Health and Aging Study (2015-2018). Self-reported insomnia was measured using the modified insomnia severity index with scores ranging from zero to six. Obesity was categorized using body mass index (BMI = 30 kg/m2). We used generalized estimating equations to assess the association between insomnia and obesity over three years. Results. Insomnia was associated with obesity (odds ratio [OR]: 1.06, 95% confidence interval [CI]: 1.01,1.11), among those with no obesity at baseline. Among those with obesity, insomnia was not associated with changes in BMI. Lastly, obesity was not associated with changes in insomnia symptoms. Conclusion. This work highlights the association between insomnia and obesity among older Mexican adults and demonstrates the importance of further studies on the effects of insomnia within this population. [ABSTRACT FROM AUTHOR]

This study explored the effect of Morus nigra fruit extract (MFE) on microanatomical and physiological parameters of cryopreserved bovine sperms. Three ejaculates were collected on weekly basis, from five fertile bulls. Each semen sample was mixed with dilution medium (DM) (1:2 v/v), centrifuged (32 g) for 10 minutes to pore away the upper-half of the mixture. The remaining material was then extended (1:4 ratios) with standard cryopreservation extender (SCE). Three aliquots (0.3 mL) from this extended sample were further extended with 0.7 mL pure SCE (control group), 0.7 mL SCE containing 3% MFE (MFE-3 group) and 0.7 mL SCE containing 6% MFE (MFE-6 group) respectively to attain final dilutions (25 times dilution of fresh semen ejaculate, containing approximately 1836.5 ± 85.23 million sperms per mL). From each final dilution (0.1 mL) sample was directly analyzed for semen quality parameters (SQPs) and rest of the material was placed in liquid nitrogen for 24 hrs for post thaw study of the SQPs and in-vitro fertilizability. Results revealed substantial improvement in sperm membrane integrity, motility, and fertilizability in MFE-3 and MFE-6 against SCE group. Likewise, significantly high mean percent number of progressively motile sperms and sperms showing 20 µ/sec or above velocity both before and after cryopreservation, were observed in MFE-6 and MFE-3 groups as compared to SCE. These findings show protective effects of MFE for bovine spermatozoa against cryoinjuries and the post thawed oxidative stress. [ABSTRACT FROM AUTHOR]

Polymer-based zinc oxide/titanium dioxide (ZnO/TiO2) nanocomposites flexible sheets with high dielectric permittivity and low loss factor have numerous applications in light emitting and energy storage devices. In this work, polymer-based ZnO/TiO2 nanocomposites are synthesized by co-precipitation technique and their structural, morphological, elemental composition, dielectric and electrical properties are studied. The XRD analysis shows the development of diffraction planes related to TiO2 and ZnO phases confirming the synthesis of polycrystalline polymer-based ZnO/TiO2 nanocomposites. The crystallinity of various phases is associated with increasing ZnO nanofillers. The SEM analysis reveals the formation of nanoparticles of different shapes and dimensions associated with increasing amount of ZnO nanofillers. The EDX analysis confirms the presence of Zn, O and Ti in the synthesized nanocomposites. Dielectric measurements demonstrate the sharp increase in dielectric permittivity with relatively low dissipation factor of the nanocomposites. The observed AC conductivity of the nanocomposites at 3.0 × 105 and 1.0 × 106 Hz is ranged from 3.7–9.8 and 15.6–42.7 S/m respectively. The decreasing complex impedance and increasing electric modulus further confirm that the synthesized polymer-based ZnO/TiO2 nanocomposites flexible sheets are the promising candidates for better capacitive performance showing high strength and flexibility. [ABSTRACT FROM AUTHOR]

This study examines internal labour migration in Thailand to study the stress level of workers who have to care of and look after their ageing parents. A cross-sectional survey was administered to 300 Thai migrant labourers who continuously have to attend to their ageing parents. Thai Job Content Questionnaire (Thai-JCQ) was used to gather information on job stress level using the Job Demand Control (JDC) model developed by Karasek. Findings show that distance, wages, and working conditions have a direct effect on job stress. Wages had the most direct relationship with job stress with a standardised regression weight of 0.400 (p-value<0.01). In conclusion, distance, wages, and working conditions, each directly impacts job stress. However, caring for ageing parents is a mediator and a moderator of job stress levels. [ABSTRACT FROM AUTHOR]

Research evaluated various nitrogen sources, and a supplementary foliar fertilizer or biochar on cabbage. It was conducted from July to October 2014 in Poncokusumo, Malang ca. 600 meters above sea level. The experiment used a randomized block design with four replications. The treatments were fertilized with different concentrations of urea, goat manure and selected substances i.e. 100% N urea (controls); 75% N urea + 25% N goat manure; 50% N urea + 50% N goat manure; 75% N urea + 25% N goat manure + foliar fertilizer (6-30-30), 50% N urea + 50% N goat manure + foliar fertilizer (6-30-30); 75% N urea + 25% N manure + biochar; and 50% N urea + 50% N goat manure + biochar. The dose of N fertilizer used was 69 kg ha-1. The results showed that a higher yield was recorded in the application of 75% N urea + 25% N goat manure and 50% N urea + 50% N manure with an addition of foliar fertilizer that was not significant with the application of 75% N urea + 25% N goat manure with the addition of biochar, resulting in a marketable yield of 68.84, 66.5 and 64.75 t ha-1, respectively. [ABSTRACT FROM AUTHOR]

The present research was conducted to investigate the influence of different processing methods and ingredient mixing techniques to judge storage stability and consumer acceptability of guava jam. In the present study four treatments of guava jam were prepared at laboratory scale using two processing methods (open kettle, T1 and T2; double jacketed steam kettle, T3 and T4) and different ingredient mixing technique (dry mixing, T1 and T3; wet mixing or pre solution, T2 and T4). After preliminary analysis of guava fruit, all the four treatments were analyzed for physico-chemical, phytochemical and sensory analysis for an interval of 15 days during 2 month storage period. The results indicated that pH, water activity, color, firmness, ascorbic acid, non-reducing sugars, total phenolic contents, antioxidant activity and overall acceptability (sensory evaluation) showed a decreasing trend during storage. Opposite is the case with acidity, total soluble solids, total sugars as well as reducing sugars. Sensory analysis indicated that the order of preference for guava jam treatments was T4>T3>T2>T1. There was no significant effect of adding sugar and pectin in dry form or by making their pre solution for all the studied traits except for sensory parameters. As good sensory characteristics were shown by the treatments in which pectin and sugar was added by making their pre-solution, so it is recommended that for having superior sensory characteristics pectin and sugar should be added in pre-solution form. Study suggests that losses in fresh guava fruit can be curtailed by processing it into jam. It further suggests that losses in vitamin C, antioxidants and total phenolic contents during processing can be minimized by giving preference to double jacketed steam kettle over open kettle. [ABSTRACT FROM AUTHOR]

Plants produced large number of small proteins which help the plant against pathogen attack and environmental stresses. These proteins are called deadly for pathogens and can play important role in drug development and crop production. Seeds (TS) and young leaves (TYL) of Solanum lycopersicum (tomato) plants were subjected under investigation for bioactive proteins. Crude proteins of tomato seeds and young leaves were extracted by phenol extraction method and assessed for antioxidant, thrombolytic, mutagenesis and DNA damage protection assays. SDS-PAGE of protein samples showed that tomato seeds contain higher protein profiles (1.23 µg/µl) as compared to tomato leaves extract (0.015 µg/µl). Results also showed that tomato-young leaves produced more anti-scavenging proteins (27.49%) as compared to tomato seeds (11.81%). The thrombolytic activities of TS and TYL were 38.88 and 51.02% which showed that tomato leaves might be good source for the treatment of heart diseases. TYL has also protected plasmid DNA damage induced by H2O2 and FeSO4. Results of the Ames test showed that TYL and TS protein extracts are non-mutagenic. From the results it is concluded that tomato young leaves produced bioactive proteins which possess antioxidant and thrombolytic activities while tomato seeds have proteins related to storage and structural proteins. [ABSTRACT FROM AUTHOR]

Classification of digital image content is mainly done by identifying low level image features such as corners and edges. The literature shows variety of algorithms for the identification of corner and non-corner pixels, important for objects' identification and image segmentation. However, all of these algorithms produce different results for same data and therefore, suitable for limited applications. This paper proposes a hybrid solution of combining complementary corner detection algorithms to improve image pixels' classification. This has been done by identifying the best detection algorithm for corner points with small and large angles and producing a hybrid algorithm by combining the latter two. Results have shown that Harris detector combined with Global and Local Curvature Points (GLC) improved the detection rate by 28% in synthetic images, but 50% in real images whereas, the combination of Shi's detection algorithm with GLC enhanced the detection rate by 25.9% in synthetic images and 123% in real images, showing a significant improvement. [ABSTRACT FROM AUTHOR]

Performance characterization of algorithms has been commonly performed using parametric methods such as Precision-Recall, Repeatability, and detection rate etc. These methods assume that the data to be normally distributed, and therefore, the results became data specific. The main objective of this analytical study was to employ non-parametric statistical tests, for this purpose two tests Wilcoxon Signed Rank test and McNemar's test were applied to characterize the performance of corner detection algorithms. The results showed that the use of sufficiently large amount of data and correct testing framework using different non-parametric statistical tests yielded similar results, which was not observed with conventional parametric tests. Both Wilcoxon Signed Rank test and McNemar's test produced a similar ranking of corner detection algorithms, as both tests suggested Harris and Stephens at the top position then SUSAN, FAST, GLC and finally KLT. Hence, these non-parametric test were recommended to be used for the evaluation of vision algorithm due to their simplicity and reliability. [ABSTRACT FROM AUTHOR]

Machine learning algorithms have been widely used for classification purposes in a number of research domains; however, very few researches paid any attention to statistically validate the performance of these algorithms for different data. This paper attempted to study the Naïve Bayes algorithm's performance for dataset of different sizes. Furthermore, a known theory has also been investigated, that building multiple models such as Bagging, Boosting and Stacking tend to improve a classifier's performance. The analysis has been performed using McNemar's test; a well known nonparametric statistical test in the medical analysis domain. Results showed that not all ensemble methods work as expected and therefore, needs to be selected carefully. Moreover, the use of McNemar's test appeared to be simple, but gave statistically valid results. [ABSTRACT FROM AUTHOR]

Xylanases are essential hydrolytic enzymes which break down the plant cell wall polysaccharide, xylan composed of D-xylose monomers. Surface-enhanced Raman Spectroscopy (SERS) was utilized for the characterization of interaction of xylanases with xylan at varying concentrations. The study focuses on the application of SERS for the characterization of enzymatic activity of xylanases causing hydrolysis of Xylan substrate with increase in its concentration which is substrate for this enzyme in the range of 0.2% to 1.0%. SERS differentiating features are identified which can be associated with xylanases treated with different concentrations of xylan. SERS measurements were performed using silver nanoparticles as SERS substrate to amplify Raman signal intensity for the characterization of xylan treated with xylanases. Principal Component Analysis (PCA) and Partial Least Square Discriminant Analysis (PLS-DA) were applied to analyze the spectral data to analyze differentiation between the SERS spectra of different samples. Mean SERS spectra revealed significant differences in spectral features particularly related to carbohydrate skeletal mode and O-C-O and C-C-C ring deformations. PCA scatter plot effectively differentiates data sets, demonstrating SERS ability to distinguish treated xylanases samples and the PC-loadings plot highlights the variables responsible for differentiation. PLS-DA was employed as a quantitative classification model for treated xylanase enzymes with increasing concentrations of xylan. The values of sensitivity, specificity, and accuracy were found to be 0.98%, 0.99%, and 100% respectively. Moreover, the AUC value was found to be 0.9947 which signifies the excellent performance of PLS-DA model. SERS combined with multivariate techniques, effectively characterized and differentiated xylanase samples as a result of interaction with different concentrations of the Xylan substrate. The identified SERS features can help to characterize xylanases treated with various concentrations of xylan with promising applications in the bio-processing and biotechnology industries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Edible oils and fats are crucial components of everyday cooking and the production of food products, but their purity has been a major issue for a long time. High-quality edible oils are contaminated with low- and cheap-quality edible oils to increase profits. The adulteration of edible oils and fats also produces many health risks. Detection of main and minor components can identify adulterations using various techniques, such as GC, HPLC, TLC, FTIR, NIR, NMR, direct mass spectrometry, PCR, E-Nose, and DSC. Each detection technique has its advantages and disadvantages. For example, chromatography offers high precision but requires extensive sample preparation, while spectroscopy is rapid and non-destructive but may lack resolution. Direct mass spectrometry is faster and simpler than chromatography-based MS, eliminating complex preparation steps. DNA-based oil authentication is effective but hindered by laborious extraction processes. E-Nose only distinguishes odours, and DSC directly studies lipid thermal properties without derivatization or solvents. Mass spectrometry-based techniques, particularly GC-MS is found to be highly effective for detecting adulteration of oils and fats in food and non-food samples. This review summarizes the benefits and drawbacks of these analytical approaches and their use in conjunction with chemometric tools to detect the adulteration of animal fats and vegetable oils. This combination provides a powerful technique with enormous chemotaxonomic potential that includes the detection of adulterations, quality assurance, assessment of geographical origin, assessment of the process, and classification of the product in complex matrices from food and non-food samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

In this study, UV-vis spectroscopy was employed to investigate the interaction between formylphenoxyacetic acid (FPAA) and its derivatives (chalcone and flavones) with ionic surfactants (SDS, CTAB, and DTAB) in different physiological environments. Changes in the physiochemical properties of FPAA chalcone and flavones including binding constants, partitioning constants, and Gibbs free energy were observed which were influenced by the presence of ionic surfactants computed using mathematical models. The solubilization of the targeted compounds in the ionic surfactants was determined through the binding constant (Kb). The results of the present study indicated that electrostatic interactions played a significant role in the solubilization of the targeted compounds in SDS, CTAB, and DTAB. At pH 4.1, FPAA chalcone exhibited stronger binding affinity with SDS compared to CTAB and DTAB. However, at pH 7.4, chalcone showed stronger binding with DTAB compared to SDS, while negligible interaction with CTAB was observed at pH 7.4. The flavones demonstrated stronger binding with DTAB at pH 7.4 compared to SDS and CTAB and it exhibited strong bonding with CTAB at pH 4.1. The negative values of the Gibbs free energy for binding (ΔGb˚) and partitioning (ΔGp˚) constants displayed the spontaneity of the process. However, FPAA chalcone with SDS and FPAA flavones with DTAB furnished positive ΔGb˚, indicating a non-spontaneous process., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Artemisinin, artemether, artesunate, and dihydroartemisinin are renowned for their antimalarial potential. The current study aims to repurpose the above-mentioned artemisinic compounds (ACs) by conducting an intercomparison to evaluate their antiinflammatory potential (AIP). In order to develop potential candidates for the evaluation of AIP of ACs (50 and 100 mg/kg BW), carbon tetrachloride (1ml/kg body weight (BW)) was administered intraperitoneally to BALB/c mice. Alterations in animal behavior were assessed weekly through tail suspension test, force swim test, open field test, Y-maze test, inverted screen analysis, and weight lifting test. Aberrations in hematological, serological, endogenous antioxidants, and oxidative stress marker profiles were assessed in all twelve groups. Histological alterations were read using hematoxylin and eosin staining. Levels of inflammatory markers including nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), were determined using immunohistochemical analysis (IHCA). Antioxidant markers i.e., nuclear factor erythroid-2-related factor (Nrf-2) and thioredoxin (TRX) were also quantified through IHCA. Comet assay was performed to quantify DNA damage. Oral administration of ACs to mice significantly alleviated the carbon tetrachloride induced inflammation in comparison with silymarin. Reduced levels of several inflammatory markers including nitric oxide, thiobarbituric acid reactive substances, interleukin-1 beta, NF-κB, TNF-α, and NLRP3, underscore the substantial AIP of ACs. IHCA depicted the revitalized percent relative expression of Nrf-2 and TRX in groups treated with ACs. Behavioral analysis revealed that ACs-treated groups significantly (p<0.05) attenuated the memory deficit, anxiety, and depressive-like behavior. Moreover, histopathological, hematological, serological, and endogenous antioxidant profiles indicated substantial AIP of ACs. Findings of comet assay further bolstered the compelling evidence as DNA damage was significantly (p<0.05) curbed down after ACs (100 mg/kg) treatment. All these outcomes implied that ACs exhibited AIP in a dose-dependent manner with maximal AIP imparted by artemisinin (100 mg/kg). This pre-clinical investigation avers the tremendous AIP of ACs targeting key molecular pathways. The current study divulges artemisinin as the most potent antiinflammatory agent among the tested compounds., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kazmi, Fatima, Naz, Kanwal and Haq.)

In the current research study, zinc oxide nanoparticles (ZnO-NPs) were synthesized via a green synthesis technique using the seed extract of Citrullus lanatus . The study further intended to evaluate the potential synergistic effects of ZnO-NPs with antibiotics against multidrug resistant (MDR) bacteria. It was observed that C. lanatus seed extracts obtained by n -hexane and methanolic solvents revealed the presence of constituents, such as tannins, flavonoids, and terpenoids. Furthermore, the extract of n -hexane displayed the strongest antibacterial activity against Yersinia species (17 ± 1.2 mm) and Escherichia coli (17 ± 2.6 mm), while the methanolic extract showed the maximum antibacterial activity against E. coli (17 ± 0.8 mm). Additionally, the ZnO-NP synthesis was confirmed by ultraviolet-visible analysis with a characteristic absorption peak at 280 nm. The Fourier transform infrared spectroscopy analysis suggested the absorption peaks in the 500-3800 cm -1 range, which corresponds to various groups of tertiary alcohol, aldehyde, amine, ester, aromatic compounds, thiol, amine salt, and primary amine. The scanning electron microscopy spectra of ZnO-NPs demonstrated the presence of zero-dimensional spherical particles with well-dispersed character. Moreover, encapsulation with ZnO-NPs improved the antimicrobial activity of antibiotics against the panel of MDR bacteria, and the increases in the effectiveness of particular antibiotics against MDR bacteria were significant ( P = 0.0005). In essence, the synthesized ZnO-NPs have the potential as drug carriers with powerful bactericidal properties that work against MDR bacterial strains. These outcomes are an indication of such significance in pharmaceutical science, giving possibilities for further research and development in this field., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

In this study, surface-enhanced Raman spectroscopy (SERS) technique, along with principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA), is used as a simple, quick, and cost-effective analysis method for identifying biochemical changes occurring due to induced mutations in the Aspergillus niger fungus strain. The goal of this study is to identify the biochemical changes in the mutated fungal cells (cell mass) as compared to the control/nonmutated cells. Furthermore, multivariate data analysis tools, including PCA and PLS-DA, are used to further confirm the differentiating SERS spectral features among fungal samples. The mutations are caused in A. niger by the clustered regularly interspaced palindromic repeat CRISPR-Cas9 genomic editing method to improve their biotechnological potential for the production of cellulase enzyme. SERS was employed to detect the changes in the cells of mutated A. niger fungal strains, including one mutant producing low levels of an enzyme and another mutant producing high levels of the enzyme as a result of mutation as compared with an unmutated fungal strain as a control sample. The distinctive features of SERS corresponding to nucleic acids and proteins appear at 546, 622, 655, 738, 802, 835, 959, 1025, 1157, 1245, 1331, 1398, and 1469 cm -1 . Furthermore, PLS-DA is used to confirm the 89% accuracy, 87.7% precision, 87% sensitivity, and 88.9% specificity of this method, and the value of the area under the curve (AUROC) is 0.67. It has been shown that surface-enhanced Raman spectroscopy is an effective method for identifying and differentiating biochemical changes in genome-modified fungal samples., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Modern cancer diagnostics involves extracting tissue specimens from suspicious areas and conducting histotechnical procedures to prepare a digitized glass slide, called Whole Slide Image (WSI), for further examination. These procedures frequently introduce different types of artifacts in the obtained WSI, and histological artifacts might influence Computational Pathology (CPATH) systems further down to a diagnostic pipeline if not excluded or handled. Deep Convolutional Neural Networks (DCNNs) have achieved promising results for the detection of some WSI artifacts, however, they do not incorporate uncertainty in their predictions. This paper proposes an uncertainty-aware Deep Kernel Learning (DKL) model to detect blurry areas and folded tissues, two types of artifacts that can appear in WSIs. The proposed probabilistic model combines a CNN feature extractor and a sparse Gaussian Processes (GPs) classifier, which improves the performance of current state-of-the-art artifact detection DCNNs and provides uncertainty estimates. We achieved 0.996 and 0.938 F1 scores for blur and folded tissue detection on unseen data, respectively. In extensive experiments, we validated the DKL model on unseen data from external independent cohorts with different staining and tissue types, where it outperformed DCNNs. Interestingly, the DKL model is more confident in the correct predictions and less in the wrong ones. The proposed DKL model can be integrated into the preprocessing pipeline of CPATH systems to provide reliable predictions and possibly serve as a quality control tool., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Regulation of RNA helicase activity, often accomplished by protein cofactors, is essential to ensure target specificity within the complex cellular environment. The largest family of RNA helicase cofactors are the G-patch proteins, but the cognate RNA helicases and cellular functions of numerous human G-patch proteins remain elusive. Here, we discover that GPATCH4 is a stimulatory cofactor of DHX15 that interacts with the DEAH box helicase in the nucleolus via residues in its G-patch domain. We reveal that GPATCH4 associates with pre-ribosomal particles, and crosslinks to the transcribed ribosomal DNA locus and precursor ribosomal RNAs as well as binding to small nucleolar- and small Cajal body-associated RNAs that guide rRNA and snRNA modifications. Loss of GPATCH4 impairs 2'-O-methylation at various rRNA and snRNA sites leading to decreased protein synthesis and cell growth. We demonstrate that the regulation of 2'-O-methylation by GPATCH4 is both dependent on, and independent of, its interaction with DHX15. Intriguingly, the ATPase activity of DHX15 is necessary for efficient methylation of DHX15-dependent sites, suggesting a function of DHX15 in regulating snoRNA-guided 2'-O-methylation of rRNA that requires activation by GPATCH4. Overall, our findings extend knowledge on RNA helicase regulation by G-patch proteins and also provide important new insights into the mechanisms regulating installation of rRNA and snRNA modifications, which are essential for ribosome function and pre-mRNA splicing., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Drug-resistant pathogenic bacteria are a major cause of infectious diseases in the world and they have become a major threat through the reduced efficacy of developed antibiotics. This issue can be addressed by using bacteriophages, which can kill lethal bacteria and prevent them from causing infections. Surface-enhanced Raman spectroscopy (SERS) is a promising technique for studying the degradation of infectious bacteria by the interaction of bacteriophages to break the vicious cycle of drug-resistant bacteria and help to develop chemotherapy-independent remedial strategies. The phage (viruses)-sensitive Staphylococcus aureus ( S. aureus ) bacteria are exposed to bacteriophages (Siphoviridae family) in the time frame from 0 min (control) to 50 minutes with intervals of 5 minutes and characterized by SERS using silver nanoparticles as SERS substrate. This allows us to explore the effects of the bacteriophages against lethal bacteria ( S. aureus ) at different time intervals. The differentiating SERS bands are observed at 575 (C-C skeletal mode), 620 (phenylalanine), 649 (tyrosine, guanine (ring breathing)), 657 (guanine (COO deformation)), 728-735 (adenine, glycosidic ring mode), 796 (tyrosine (C-N stretching)), 957 (C-N stretching (amide lipopolysaccharides)), 1096 (PO 2 (nucleic acid)), 1113 (phenylalanine), 1249 (CH 2 of amide III, N-H bending and C-O stretching (amide III)), 1273 (CH 2 , N-H, C-N, amide III), 1331 (C-N stretching mode of adenine), 1373 (in nucleic acids (ring breathing modes of the DNA/RNA bases)) and 1454 cm -1 (CH 2 deformation of saturated lipids), indicating the degradation of bacteria and replication of bacteriophages. Multivariate data analysis was performed by employing principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) to study the biochemical differences in the S. aureus bacteria infected by the bacteriophage. The SERS spectral data sets were successfully differentiated by PLS-DA with 94.47% sensitivity, 98.61% specificity, 94.44% precision, 98.88% accuracy and 81.06% area under the curve (AUC), which shows that at 50 min interval S. aureus bacteria is degraded by the replicating bacteriophages., Competing Interests: The authors have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)