Closing the gap: An urgent need for newborn screening of organic acid disorders in developing countries.

Organic acid disorders are rare inherited metabolic disorders of key metabolic pathways. For the identification of specific organic acids, investigation of urinary metabolites and genetic testing are required through newborn screening programmes. Delayed diagnosis leads to complications, such as cardiac attacks, respiratory problems, neuro-developmental disorders, intellectual disability, and even premature death. The burden of such inherited disorders is quite high in developing countries of South Asia due to high rate of consanguinity in the region. Unfortunately, such disorders are left untreated due to the lack of screening facilities in such countries. The current narrative review was planned to highlight the urgent need for closing this gap and implementing effective newborn screening programmes for organic acid disorders in developing countries. The implementation of effective programmes is crucial for reducing morbidity and mortality, and for improving the quality of life for the affected children and of their families, thus promoting global health equity.

Comparison of efficacy and safety of tofacitinib and azathioprine in patients with alopecia areata and variants: a double-blind, randomized controlled trial.

BACKGROUND: Alopecia areata (AA) is an autoimmune pathology manifested by loss of hair. OBJECTIVE: To evaluate and compare the efficacy and safety of tofacitinib and azathioprine in patients with AA and variants. METHODS: In this double-blind randomized controlled trail (RCT) carried out at the Department of Dermatology, Medical Teaching Institute-Lady Reading Hospital (MTI-LRH), Peshawar, Pakistan, patients aged ≥ 12 years diagnosed with AA, alopecia totalis (AT) or alopecia universalis (AU) with minimum 50% scalp hair loss for a period ≥ 06 years were included. Patients were randomly assigned to receive oral tofacitinib 5 mg twice daily (Group I) or oral azathioprine 2 mg/kg body weight once daily (Group II). The primary endpoint was Severity of Alopecia Tool (SALT) score, evaluated at baseline and 06 months follow-up. Safety was consistently assessed during the study. RESULTS: A total of 104 patients underwent random allocation into either the tofacitinib group (n = 52) or the azathioprine group (n = 52). The mean (SD) age of patients was 20.23 (7.14) years and 22.26 (8.07) years, while the mean (SD) disease duration was 6.59 (4.01) years and 7.98 (4.40) years in in Group I and II, respectively. Overall, 40 (38.5%) patients were adolescents while 70 (67.3%) were male. 52 (50%) had AA, 37 (35.5%) had AT and 15 (14.5%) had AU. Mean baseline SALT score in tofacitinib group was 91.02 ± 10.21 and azathioprine group was 91.02 ± 10.63, which at 06 months follow-up improved to 14.1 ± 24.6 and 63.9 ± 33.9, respectively (difference, 11.5 points; 95% confidence interval, 38.3-61.3, p < 0.0001). Overall, no major adverse effects and no difference among the minor adverse effects in the two groups (04 adverse events for tofacitinib group and 08 for azathioprine group: p = 0.23) was observed. CONCLUSIONS: Efficacy of tofacitinib was significantly higher than azathioprine, whilst both drugs were well-tolerated in patients with AA and variants.

Optimizing decision-making with aggregation operators for generalized intuitionistic fuzzy sets and their applications in the tech industry.

Intuitionistic fuzzy sets (IFSs) represent a significant advancement in classical fuzzy set (FS) theory. This study advances IFS theory to generalized intuitionistic fuzzy sets (GIFSBs) and introduces novel operators GIFWAA, GIFWGA, GIFOWAA, and GIFOWGA, tailored for GIFSBs. The primary aim is to enhance decision-making capabilities by introducing aggregation operators within the GIFSB framework that align with preferences for optimal outcomes. The article introduces new operators for GIFSBs characterized by attributes like idempotency, boundedness, monotonicity and commutativity, resulting in aggregated values aligned with GIFNs. A comprehensive analysis of the relationships among these operations is conducted, offering a thorough understanding of their applicability. These operators are practically demonstrated in a multiple-criteria decision-making process for evaluating startup success in the Tech Industry.

Unlocking the Potential of Oleanolic Acid: Integrating Pharmacological Insights and Advancements in Delivery Systems.

The growing interest in oleanolic acid (OA) as a triterpenoid with remarkable health benefits prompts an emphasis on its efficient use in pharmaceutical research. OA exhibits a range of pharmacological effects, including antidiabetic, anti-inflammatory, immune-enhancing, gastroprotective, hepatoprotective, antitumor, and antiviral properties. While OA demonstrates diverse pharmacological effects, optimizing its therapeutic potential requires overcoming significant challenges. In the field of pharmaceutical research, the exploration of efficient drug delivery systems is essential to maximizing the therapeutic potential of bioactive compounds. Efficiently delivering OA faces challenges, such as poor aqueous solubility and restricted bioavailability, and to unlock its full therapeutic efficacy, novel formulation strategies are imperative. This discussion thoroughly investigates different approaches and advancements in OA drug delivery systems with the aim of enhancing the biopharmaceutical features and overall efficacy in diverse therapeutic contexts.

Label free quantitative proteomic profiling of serum samples of intellectually disabled young patients revealed dysregulation of complement coagulation and cholesterol cascade systems.

Intellectual disability is a heterogeneous disorder, diagnosed using intelligence quotient (IQ) score criteria. Currently, no specific clinical test is available to diagnose the disease and its subgroups due to inadequate understanding of the pathophysiology. Therefore, current study was designed to explore the molecular mechanisms involved in disease perturbation, and to identify potential biomarkers for disease diagnosis and prognosis. A total of 250 participants were enrolled in this study, including 200 intellectually disabled (ID) subjects from the subgroups (mild, moderate, and severe) with age and gender matched healthy controls (n = 50). Initially, IQ testing score and biochemical profile of each subject was generated, followed by label-free quantitative proteomics of subgroups of IQ and healthy control group through nano-LC/MS- mass spectrometry. A total of 310 proteins were identified, among them198 proteins were common among all groups. Statistical analysis (ANOVA) of the subgroups of ID showed 142 differentially expressed proteins, in comparison to healthy control group. From these, 120 proteins were found to be common among all subgroups. The remaining 22 proteins were categorized as exclusive proteins found only in disease subgroups. Furthermore, the hierarchical cluster analysis (HCL) of common significant proteins was also performed, followed by PANTHER protein classification and GO functional enrichment analysis. Results provides that the datasets of differentially expressed proteins, belong to the categories of immune / defense proteins, transfer carrier proteins, apolipoproteins, complement proteins, protease inhibitors, hemoglobin proteins etc., they are known to involvein immune system, and complement and coagulation pathway cascade and cholesterol metabolism pathway. Exclusively expressed 22 proteins were found to be disease stage specific and strong PPI network specifically those that have significant role in platelets activation and degranulation, such as Filamin A (FLNA). Furthermore, to validate the mass spectrometric findings, four highly significant proteins (APOA4, SAP, FLNA, and SERPING) were quantified by ELISA in all the study subjects. AUROC analysis showed a significant association of APOA4 (0.830), FLNA (0.958), SAP (0.754) and SERPING (0.600) with the disease. Apolipoprotein A4 (APOA4) has a significant role in cholesterol transport, and in modulation of glucose and lipid metabolism in the CNS. Similarly, FLNA has a crucial role in the nervous system, especially in the functioning of synaptic network. Therefore, both APOA4, and FLNA proteins represent good potential for candidate biomarkers for the diagnosis and prognosis of the intellectual disability. Overall, serum proteome of ID patients provides valuable information of proteins/pathways that are altered during ID progression.

Evaluation of genotoxic effect via expression of DNA damage responsive gene induced by ivermectin on MDBK cell line.

Ivermectin (IVM) is an anti-parasitic drug which is used for treating parasitic infestations. It has been used in humans for treating intestinal strongyloidiasis and onchocerciasis however, currently researchers are investigating its potential for treating coronavirus SARS-CoV-2. Due to its broad-spectrum activities, IVM is being used excessively in animals which has generated an interest for researchers to investigate its toxic effects. Cytotoxic and genotoxic effects have been reported in animals due to excessive usage of IVM. Therefore, this study aims to evaluate the cytotoxic and genotoxic effects of IVM on the Madin-Darby-Bovine-Kidney (MDBK) cell line by examining the expression of a DNA damage-responsive gene (OGG1). Cytotoxicity of IVM was tested using an assay (MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), whereas the genotoxicity was evaluated using comet assay along with micronucleus assay. Moreover, the gene expression of DNA damage response gene (OGG1) was measured by qRT-PCR, after extraction of RNA from the MDBK cell line using the TRIzol method and its conversion to cDNA by reverse-transcriptase PCR. During the experiment, cell viability percentage was measured at different doses of IVM i.e., 25%, 50%, 75%, along with LC50/2, LC50 and LC50*2. It was observed that the gene expression of OGG1 increased as the concentration of IVM increased. It was concluded that IVM has both cytotoxic and genotoxic effects on the MDBK cell line. Furthermore, it is recommended that studies related to the toxic effects of IVM at molecular level and on other model organisms should be conducted to combat its hazardous effects.

GC-MS profiling and biological investigations of Cissampelos pareira L. & Lantana camara L.

The objectives of the study were to conduct phytochemical screening of crude extracts of Cissampelos pareira L. and Lantana camara L. and assessing their biological potentials against protein kinase enzymes, followed by the evaluation of antioxidant and antimicrobial capacities. The n-hexane (A-І, B-І) and ethyl extracts (A-ІІ, B-ІІ) displayed moderate to good antioxidant activity, while the methanol fractions (A-ІІІ, B-ІІІ) showed significant antioxidant activity. Among all the three crude extracts, the ethyl acetate extract (B-II) of L. camara exhibited significant protein kinase inhibitions with remarkable antioxidant potential and was therefore purified through column chromatography. Fraction B-ІІ-2 showed the highest flavonoid contents (735.43), with the most promising protein kinase inhibition exerted by the subtractions B-ІІ-2, B-ІІ-3, B-ІІ-4, and B-ІІ-7. Hence, active fractions were examined through GC-MS for the identification of active constituents, revealing 17 active compounds. In the case of Lantana camara, the ethyl acetate crude extract along with fractions led to the identification of more than thirty compounds, which may be further explored to find a potential lead for drug development.

Surface-Enhanced Raman Spectroscopy for Monitoring the Biochemical Changes Due to DNA Mutations Induced by CRISPR-Cas9 Genome Editing in the Aspergillus niger Fungus.

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.

Rapid Identification and Quantification of Adulteration in Methyl Eugenol using Raman Spectroscopy Coupled with Multivariate Data Analysis.

Identification of adulterants in commercial samples of methyl eugenol is necessary because it is a botanical insecticide, a tephritid male attractant lure that is used to attract and kill invasive pests such as oriental fruit flies and melon flies on crops. In this study, Raman spectroscopy was used to qualitatively and quantitatively assess commercial methyl eugenol along with adulterants. For this purpose, commercial methyl eugenol was adulterated with different concentrations of xylene. The Raman spectral features of methyl eugenol and xylene in liquid formulations were examined, and Raman peaks were identified as associated with the methyl eugenol and adulterant. Principal component analysis (PCA) and partial least-squares regression analysis (PLSR) have been used to qualitatively and quantitatively analyze the Raman spectral features. PCA was applied to differentiate Raman spectral data for various concentrations of methyl eugenol and xylene. Additionally, PLSR has been used to develop a predictive model to observe a quantitative relationship between various concentrations of adulterated methyl eugenol and their Raman spectral data sets. The root-mean-square errors of calibration and prediction were calculated using this model, and the results were found to be 1.90 and 3.86, respectively. The goodness of fit of the PLSR model is found to be 0.99. The proposed approach showed excellent potential for the rapid, quantitative detection of adulterants in methyl eugenol, and it may be applied to the analysis of a range of pesticide products.

The interplay of PTEN and AKT nexus in breast cancer: a molecular perspective.

BACKGROUND: Breast cancer is a highly prevalent and life-threatening ailment that is commonly detected among the females. The downregulation of PTEN in breast cancer is associated with a poor prognosis, aggressive tumor type, and metastasis to lymph nodes, as it activates the pro-survival pathway PI3K/AKT, which is considered the ultimate proliferative pathway. MATERIAL AND METHODS: The mRNA expression of PTEN and AKT genes was investigated using RT-qPCR and TaqMan primer probe chemistry. Moreover DNA was also isolated from the same tissue samples and exonic regions of both genes were amplified for mutational analysis. The proteins expression of PTEN and AKT from seven human breast cancer cell lines was checked through western blot experiments. RESULT: The study revealed a decrease in PTEN expression in 73.3% of the samples, whereas an increase in AKT expression in 40% of samples was observed when compared to the distant normal breast tissue. Conversely, the remaining 60% of samples exhibited a decrease in AKT mRNA expression. There was no observed alteration in the genetic sequence of AKT and PTEN within the targeted amplified regions of breast cancer samples. The high levels of PTEN protein in T-47D and MDA-MB-453 resulted in a lower p-AKT. Two cell lines ZR-75-1 and MDA-MB-468 appeared to be PTEN negative on western blot but mRNA was detected on RT-qPCR. CONCLUSION: In breast cancer the status/expression of PTEN & AKT at mRNA and protein level might be obliging in forecasting the path of disease progression, treatment and prognosis.

An efficient energy management scheme using rule-based swarm intelligence approach to support pulsed load via solar-powered battery-ultracapacitor hybrid energy system.

This work presents an energy management scheme (EMS) based on a rule-based grasshopper optimization algorithm (RB-GOA) for a solar-powered battery-ultracapacitor hybrid system. The main objective is to efficiently meet pulsed load (PL) demands and extract maximum energy from the photovoltaic (PV) array. The proposed approach establishes a simple IF-THEN set of rules to define the search space, including PV, battery bank (BB), and ultracapacitor (UC) constraints. GOA then dynamically allocates power shares among PV, BB, and UC to meet PL demand based on these rules and search space. A comprehensive study is conducted to evaluate and compare the performance of the proposed technique with other well-known swarm intelligence techniques (SITs) such as the cuckoo search algorithm (CSA), gray wolf optimization (GWO), and salp swarm algorithm (SSA). Evaluation is carried out for various cases, including PV alone without any energy storage device, variable PV with a constant load, variable PV with PL cases, and PV with maximum power point tracking (MPPT). Comparative analysis shows that the proposed technique outperforms the other SITs in terms of reducing power surges caused by PV power or load transition, oscillation mitigation, and MPP tracking. Specifically, for the variable PV with constant load case, it reduces the power surge by 26%, 22%, and 8% compared to CSA, GWO, and SSA, respectively. It also mitigates oscillations twice as fast as CSA and GWO and more than three times as fast as SSA. Moreover, it reduces the power surge by 9 times compared to CSA and GWO and by 6 times compared to SSA in variable PV with the PL case. Furthermore, its MPP tracking speed is approximately 29% to 61% faster than its counterparts, regardless of weather conditions. The results demonstrate that the proposed EMS is superior to other SITs in keeping a stable output across PL demand, reducing power surges, and minimizing oscillations while maximizing the usage of PV energy.

Surface-enhanced Raman spectroscopy for the characterization of bacterial pellets of Staphylococcus aureus infected by bacteriophage.

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 (PO2 (nucleic acid)), 1113 (phenylalanine), 1249 (CH2 of amide III, N-H bending and C-O stretching (amide III)), 1273 (CH2, 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 (CH2 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.

Metal pollution in the topsoil of lands adjacent to Sahiwal Coal Fired Power Plant (SCFPP) in Sahiwal, Pakistan.

Coal fly ash from a coal fired power plant is a significant anthropogenic source of various heavy metals in surrounding soils. In this study, heavy metal contamination in topsoil around Sahiwal coal fired power plant (SCFPP) was investigated. Within distance of 0-10, 11-20, 21-30 and 31-40 km of SCFPP, total 56 soil samples were taken, 14 replicate from each distance along with a background subsurface soil sample beyond 60 km. Soil samples were subjected to heavy metals analysis including Fe, Cu and Pb by Atomic Absorption Spectrophotometer (AAS). Composite samples for each distance were analyzed for Al, As, Ba, Cd, Co, Cr, Mn, Mo, Ni, Se, Sr, Zn by Inductively Coupled Plasma (ICP). Pollution indices of exposed soil including Enrichment Factor (EF), Contamination Factor (CF), Geoaccumulation Index (Igeo), and Pollution Load Index (PLI) were calculated. Ecological risk index ([Formula: see text]) of individual metals and the Potential Ecological Risk Index (PERI) for all metals were determined. Soil samples within 40 km of SCFPP were significantly polluted with Pb (mean 2.81 ppm), Cu (mean 0.93 ppm), and Fe (mean 7.93 ppm) compared to their background values (Pb 0.45, Cu 0.3, and Fe 4.9 ppm). Some individual replicates were highly contaminated where Pb, Fe, and Cu values were as high as 6.10, 35.4 and 2.51 ppm respectively. PLI, Igeo, CF, and EF for metals classified the soil around CFPP as "moderate to high degree of pollution", "uncontaminated to moderately contaminated", "moderate to very high contamination", and "moderate to significant enrichment" respectively with average values for Cu as 2.75, 0.82, 3.09, 4.01; Pb 4.79, 1.56, 6.16, 7.76, and for Fe as 1.20, 0.40, 1.62, 3.35 respectively. Average Ecological Risk Index ([Formula: see text]) of each metal and Potential Ecological Risk Index (PERI) for all metals classified the soils as "low risk soils" in all distances. However, ([Formula: see text]) of Pb at a number of sites in all distances have shown "moderate risk". The linear correlation of physico-chemical parameter (EC, pH, Saturation %) and metals have recorded several differential correlations, however, their collective impact on Pb in 0-10 km, has recorded statistically significant correlation (p-value 0.01). This mix of correlations indicates complex interplay of many factors influencing metal concentrations at different sampling sites. The concentration of As, Cr, Co, Cd, and Zn was found within satisfactory limits and lower than in many parts of the world. Although the topsoil around SCFPP is largely recorded at low risk, for complete assessment of its ecological health, further research considering comprehensive environmental parameters, all important trace metals and variety of input pathways is suggested.

A curious case of expanded dengue syndrome.

Dengue fever (DF) primarily presents with fever, headache, malaise, bleeding manifestations and haemoconcentration. World Health Organization (WHO) classifies DF according to levels of severity: (a) without warning signs; (b) with warning signs, such as abdominal pain, persistent vomiting, fluid accumulation, mucosal bleeding, lethargy, liver enlargement, increasing haematocrit and thrombocytopenia; and (c) severe dengue with severe plasma leakage, severe bleeding or organ failure. Atypical clinical presentations of DF are defined as expanded dengue syndrome: this includes renal, cardiac, hepatic or cerebral damage. We report such a severe case where a young man developed acute kidney injury, acute fulminant liver failure and acute pancreatitis secondary to DF, but recovered.

Frequency of Urinary Tract Infection Among Patients Undergoing Implant Fixation for Acute Trauma.

OBJECTIVE: This study aims to determine the frequency of urinary tract infection (UTI), identify the isolated bacteria, and assess antibiotic sensitivity in patients undergoing orthopedic implant fixation for hip fractures. METHODOLOGY: After ethical approval from the institutional review board, this retrospective cross-sectional study was conducted at the Orthopedic Surgery Department of Dow University Hospital Karachi from June 2022 to June 2023. Through non-probability consecutive sampling, 186 patients above 16 years of age, of either gender, presenting with hip fractures such as intracapsular or extracapsular fractures, who underwent surgical fixation, were included in the study. A urine sample for urinalysis of these patients was sent on admission. Patients who presented with open fractures or those treated with conservative management were excluded from the study. The fracture diagnosis was confirmed on radiographs. All other relevant baseline investigations were also performed before surgery, per protocol, and urine-detailed and cultured reports were followed. In addition, each patient was asked about common symptoms of UTI before surgery and then diagnosed with UTI on positive urine culture and sensitivity (CS). RESULTS: Out of 186 hip fracture patients, 98 (52.7%) were males and 88 (47.3%) were females, with a mean age of 61.03 ± 16.43 (16-96) years. Pre-operative UTI symptoms were reported by 79 patients, including dysuria (16; 20.3%), polyuria (19; 24.0%), and burning (44; 55.7%). UTI was diagnosed on culture and sensitivity report in 65 (34.9%) patients with Escherichia coli as commonly diagnosed bacteria 35 (53.8%), followed by Enterococcus 8 (12.4%), Klebsiella 7 (10.9%), Pseudomonas aeruginosa 3 (4.7%), and Acinetobacter 2 (3.1%) patients. E. coli was sensitive to amikacin, amoxicillin/clavulanic acid, ampicillin, cefixime, ceftriaxone, cefuroxime, ciprofloxacin, colistin, cotrimoxazole, fosfomycin, gentamycin, levofloxacin, meropenem, nitrofurantoin, polymyxin B, and piperacillin-tazobactam. CONCLUSION: Urinary tract infection is common in patients undergoing orthopedic implant fixation for hip fractures, which can lead to potentially serious outcomes. Overall, hygiene, prompt treatment, and standard protocol should be utilized to treat those infected and minimize the spread.

Normalized effect size (NES): a novel feature selection model for Urdu fake news classification.

Social media has become an essential source of news for everyday users. However, the rise of fake news on social media has made it more difficult for users to trust the information on these platforms. Most research studies focus on fake news detection in the English language, and only a limited number of studies deal with fake news in resource-poor languages such as Urdu. This article proposes a globally weighted term selection approach named normalized effect size (NES) to select highly discriminative features for Urdu fake news classification. The proposed model is based on the traditional inverse document frequency (TF-IDF) weighting measure. TF-IDF transforms the textual data into a weighted term-document matrix and is usually prone to the curse of dimensionality. Our novel statistical model filters the most discriminative terms to reduce the data's dimensionality and improve classification accuracy. We compare the proposed approach with the seven well-known feature selection and ranking techniques, namely normalized difference measure (NDM), bi-normal separation (BNS), odds ratio (OR), GINI, distinguished feature selector (DFS), information gain (IG), and Chi square (Chi). Our ensemble-based approach achieves high performance on two benchmark datasets, BET and UFN, achieving an accuracy of 88% and 90%, respectively.

Development of low-cost in-house tetra-ARMS-PCR assay for the screening of five CBS mutations found in Pakistani homocystinuria patients.

BACKGROUND: Classical homocystinuria is an inborn amino acid metabolism disorder resulting from mutations in the Cystathionine-ß-Synthase (CBS) gene. These mutations lead to elevated homocysteine and methionine levels and reduced cysteine levels in the blood. Typically, diagnosis occurs after patients display symptoms, and various lab methods confirm it. DNA sequencing is the best option for early detection of genetic variants in asymptomatic suspected individuals. Unfortunately, its high cost can hinder its use, especially in low-income countries like Pakistan. OBJECTIVE: Aim of this study was to devise a robust low-cost diagnostic/screening assay based on Tetra-ARMS-PCR for five prevalent genetic variants found in Pakistani classical homocystinuria patients. MATERIALS AND METHODS: In the current study, T-ARMS-PCR assays were developed for five mutations (c.975G > C, c.770C > T, c.752T > C, c.1039 + 1G > T, c.451 + 1GG > TA), which were characterized previously in classical homocystinuria patients. These low-cost T-ARMS-PCR assays were then used to screen the affected individuals and their family members to identify their genotypes for pathogenic variations in the asymptomatic patients and carriers in their respective families. RESULTS: The outcomes were entirely consistent with those obtained from Sanger DNA sequencing, confirming the sensitivity, specificity, and reliability of the T-ARMS-PCR assay for detecting CBS mutations. CONCLUSION: T-ARMS-PCR has wide applications for low-income countries for the screening and early diagnosis of asymptomatic patients and carriers in the homocystinuria affected families as well as other inherited diseases.

Unlocking therapeutic potential of trigonelline through molecular docking as a promising approach for treating diverse neurological disorders.

Neurological disorders pose significant challenges in terms of treatment options, necessitating the exploration of novel therapeutic approaches. Trigonelline, a naturally occurring alkaloid found in various plants, has emerged as a potential treatment option. It has also been reported that trigonelline is involved in several pathways like; Oxidative Stress and Antioxidant, Inflammatory, Neuroprotection and Neurotrophic, Mitochondrial Function and Energy Metabolism. This study aims to investigate the therapeutic potential of trigonelline for diverse neurological disorders using a molecular docking approach. Molecular docking simulations were performed to predict the binding affinity and interaction between trigonelline and target proteins implicated in neurological disorders. The structural requirements for effective binding were also explored. The molecular docking results revealed strong binding interactions and favorable binding affinities between trigonelline and the target proteins involved in diverse neurological disorders like Alzheimer's disease, Parkinson's disease, epilepsy, and depression etc. The predicted binding modes provided insights into the key molecular interactions governing the ligand-protein complexes. The findings suggest that trigonelline holds promise as a therapeutic approach for several neurological disorders. The molecular docking approach employed in this study provides a valuable tool for rational drug design and optimization of trigonelline-based compounds. Further experimental validation and preclinical studies are warranted to confirm the efficacy and safety of trigonelline as a potential treatment option, paving the way for the development of more effective and targeted therapies for neurological disorders.

Synthesis, Characterization, and Evaluation of Antifungal Activity of 1-Butyl-3-hexyl-1H-imidazol-2(3H)-selenone by Surface-Enhanced Raman Spectroscopy.

In the present research work, a selenium N-heterocyclic carbene (Se-NHC) complex/adduct was synthesized and characterized by using different analytical methods including FT-IR, 1HNMR, and 13CNMR. The antifungal activity of the Se-NHC complex against Aspergillus flavus (A. flavus) fungus was investigated with disc diffusion assay. Moreover, the biochemical changes occurring in this fungus due to exposure of different concentrations of the in-house synthesized compound are characterized by surface-enhanced Raman spectroscopy (SERS) and are illustrated in the form of SERS spectral peaks. SERS analysis yields valuable information about the probable mechanisms responsible for the antifungal effects of the Se-NHC complex. As demonstrated by the SERS spectra, this Se-NHC complex caused denaturation and conformational changes in the proteins as well as decomposition of the fungal cell membrane. The SERS spectra were analyzed using two chemometric tools such as principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA). The fungal samples' SERS spectra were differentiated using PCA, while various groups of spectra were discriminated with ultrahigh sensitivity (98%), high specificity (99.7%), accuracy (100%), and area under the receiver operating characteristic curve (87%) using PLS-DA.