Sign Reversal of Spin-Transfer Torques.

Spin-transfer torque (STT) and spin-orbit torque (SOT) form the core of spintronics, allowing for the control of magnetization through electric currents. While the sign of SOT can be manipulated through material and structural engineering, it is conventionally understood that STT lacks a degree of freedom in its sign. However, this study presents the first demonstration of manipulating the STT sign by engineering heavy metals adjacent to magnetic materials in magnetic heterostructures. Spin torques are quantified through magnetic domain-wall speed measurements, and subsequently, both STT and SOT are systematically extracted from these measurements. The results unequivocally show that the sign of STT can be either positive or negative, depending on the materials adjacent to the magnetic layers. Specifically, Pd/Co/Pd films exhibit positive STT, while Pt/Co/Pt films manifest negative STT. First-principle calculations further confirm that the sign reversal of STT originates from the sign reversal of spin polarization of conduction electrons.

Novel yellowish-green single-phased spinel Mg1-xBaxAl2O4:Mn2+ phosphor(s) for color rendering white-light-emitting diodes.

For white light-rendering research activities, interpretation by using colored emitting materials is an alternative approach. But there are issues in designing the white color emitting materials. Particularly, differences in thermal and decay properties of discrete red, green, and blue emitting materials led to the quest for the search of a single-phased material, able to emit primary colors for white light generation. The current study is an effort to design a simple, single-phase, and cost-effective material with the tunable emission of primary colors by a series of Mg1-xBaxAl2O4:Mn2+ nanopowders. Doping of manganese ion (Mn2+) in the presence of the larger barium cation (Ba2+) at tetrahedral-sites of the spinel magnesium aluminate (MgAl2O4) structure led to the creation of antisite defects. Doped samples were found to have lower bandgaps compared with MgAl2O4, and hybridization of 3d-orbitals of Mn2+ with O(2p), Mg(2s)/Al(2s3p) was found to be responsible for narrowing the bandgap. The distribution of cations at various sites at random results in a variety of electronic transitions between the valance band and oxygen vacancies as well as electron traps produced the antisite defects. The suggested compositions might be used in white light applications since they have three emission bands with centers at 516 nm (green), 464 nm (blue) and 622 nm (red) at an excitation wavelength of 380 nm. A detailed discussion to analyze the effects of the larger cationic radius of Ba2+ on the lattice strain, unit cell parameters, and cell volumes using X-ray diffraction analysis is presented.

Hydrochemical, hydrogeological, and cancer health risk analysis of groundwater due to anthropogenic activities, Hasilpur, Pakistan.

Drinking water quality deteriorates rapidly due to anthropogenic activities and rapid population growth. These activities, in developing countries, will lead to water scarcity. In Pakistan, 70% of the population has no access to safe water, and people use canal water to drink. This study performed hydrochemical, hydrogeological, and cancer risk analyses on Tahsil Hasilpur, Bahawalpur, Pakistan. Thirteen tube wells were selected for groundwater and borehole log study. Twenty-two drinking water quality parameters were analyzed using standard methods and quality checks. The borehole data (2D and 3D) shows the abundance of sand (fine and coarse) with some uniformities, which changes the groundwater quality. The results of water quality parameters show that the concentration of TDS (2064-11,159 mg/L), Cl-1 (213-4917 mg/L), As+3 (0.048-0.158 mg/L), Pb+2 (1.294-1.673 mg/L), and Cd+2 (0.008-0.053 mg/L) were beyond guideline values. The statistical analysis showed that the parameters have a moderate to strong correlation (Pearson correlation), which may be due to the same origin (ANOVA). The principal component analysis and cluster analysis confirm the multiple sources of pollutants in the groundwater of the study area. The Piper, Durov, Stiff, and Scholler diagrams confirm that the groundwater system has an abundance of Ca+2 and Mg+2 with Cl-1. The Gibbs diagram showed that the groundwater is not saturated and tends to dissolve more minerals. The hazard quotient values are above 1.0, which indicates noncancer risk severity. The HQ trend was As+3 > Pb+2 > Cd+2 > Ni+2 > Cu+2 > Cr+2 > Zn+2 > Fe+2. The cancer risk values showed that 3-5 people/100 population were exposed to cancer risk. The trend of CR was As+3 > Cd+2 > Cr+2 > Pb+2 > Ni+2. The GIP mapping of pollutants showed that the concentration of pollutants near the canals was high compared to the locations away from the canal. The overall groundwater quality is alarming and needs immediate government attention.

Evaluation of polyherbal gel for musculoskeletal injuries in industrial workers.

BACKGROUND: Industrial workers often have musculoskeletal disorders due to the nature of their work. OBJECTIVE: The goal was to investigate the scientific use of polyherbal gel in relieving pain and stiffness due to musculoskeletal injuries and improving activities of daily living (ADLs) in industrial workers. METHODS: A pragmatic, single-blinded, randomized control study divided 200 musculoskeletal injury patients into four parallel groups (n = 50). Groups 1 and 2 were applied polyherbal gel via phonophoresis with therapeutic ultrasound and superficial massage. Groups 3 and 4 received diclofenac diethyl-ammonium 1% gel by phonophoresis and superficial massage. The Global Pain Relief Scale, Numeric Pain Rating Scale (NPRS), and Western Ontario and McMaster Universities Arthritis Index (WOMAC) were used to measure pain, stiffness, and ADLs. Data was analyzed using one-way analysis of variance (ANOVA) and paired t-test to compare mean±SD of four independent groups before and after gel application. The confidence interval was 95%, with p <  0.05 considered significant. RESULTS: The results revealed that polyherbal gel reduced pain (NPRS, WOMAC and Global pain relief scales) more efficiently (p≤0.000) when applied with phonophoresis as compared to applied with massage and standard diclofenac (p≤0.005), furthermore, polyherbal gel when applied with phonophoresis showed more efficient results. CONCLUSION: Industrial workers with musculoskeletal injuries benefited from the use of polyherbal gel for pain and inflammation relief. The polyherbal gel is natural, cost-effective, and easy to formulate.

QbD-Based Fabrication of Biomimetic Hydroxyapatite Embedded Gelatin Nanoparticles for Localized Drug Delivery against Deteriorated Arthritic Joint Architecture.

Biomaterials such as nanohydroxyapatite and gelatin are widely explored to improve damaged joint architecture associated with rheumatoid arthritis (RA). Besides joint damage, RA is associated with inflammation of joints and cartilage, which potentiates the need for both bone nucleation and therapeutic intervention. For such purpose, a modified nanoprecipitation method is used herein to fabricate tofacitinib (Tofa)-loaded nanohydroxyapatite (nHA) embedded gelatin (GLT) nanoparticles (NPs) (Tofa-nHA-GLT NPs). The quality by design (QbD) approach is chosen to assess the key parameters that determine the efficiency of the NPs, and are further optimized via Box-Behnken design of experiment. The particle size, polydispersity, zeta potential, and encapsulation efficiency (EE) of the prepared NPs are found to be 269 nm, 0.18, -20.5 mV, and 90.7%, respectively. Furthermore, the NPs have improved stability, skin permeability, and a sustained drug release pattern at pH 6.5 (arthritic joint pH). Moreover, rhodamine-B loaded nHA-GLT NPs demonstrates considerably higher cellular uptake by the murine-derived macrophages than free rhodamine-B solution. In vitro, cell-based experiments confirm the good cell biocompatibility with insignificant toxicity. Thus, QbD-based approach has successfully led to the development of Tofa-nHA-GLT NPs with the potential to target inflamed arthritic joint.

Synthesis of 2-amino-terephthalic acid crosslinked chitosan/bentonite hydrogel; an efficient adsorbent for anionic dyes and laccase.

This research article presents the fabrication of NH2-terephthalic acid crosslinked chitosan-bentonite composite, which adopted a facile synthesis approach and offered efficient adsorption capacity for organic dyes. A novel hydrogel material named CB 5:1 demonstrated remarkable adsorption for anionic dyes (Congo red (CR) and brilliant blue (BB)) while showing a negligible affinity for cationic dyes. Adsorption isotherm studies revealed the adsorption capacity of 4950 mg/g and 2053 mg/g (per g of composite's dry weight) for CR and BB following the Langmuir adsorption model. Kinetics and thermodynamic studies were also conducted while the adsorption of anionic dyes in the presence of metal ions, cationic dyes, anionic dyes, and in simulated water remained unaffected. Laccase, an industrially important enzyme, was also immobilized on CB 5:1 to achieve enzyme stability and reusability, resulting in a staggering immobilization capacity (4782 mg/g) at pH 6.0. Laccase immobilized product was employed to perform dye degradation (> 90 % for CR and > 75 % for BB), and the reusability was tested. Overall, our crosslinked product proved appealing for removing high concentrations of anionic organic dyes from polluted water and could be envisaged for practical use.

Towards sustainable electrochemistry: green synthesis and sintering aid modulations in the development of BaZr0.87Y0.1M0.03O3-δ (M = Mn, Co, and Fe) IT-SOFC electrolytes.

In this study, BaZr0.87Y0.1M0.03O3-δ perovskite electrolytes with sintering aids (M = Mn, Co, and Fe) were synthesized by a sustainable approach using spinach powder as a chelating agent and then compared with chemically synthesized BaZr0.87Y0.1M0.03O3-δ (M = Mn, Co, and Fe) electrolytes for intermediate temperature SOFCs. This is the first example of such a sustainable synthesis of perovskite materials with sintering aids. Structural analysis revealed the presence of a cubic perovskite structure in BaZr0.87Y0.1M0.03O3-δ (M = Mn, Co, and Fe) samples synthesized by both green and conventional chemical methods. No significant secondary phases were observed in the samples synthesized by a sustainable approach. The observed phenomena of plane shift were because of the disparities between ionic radii of the dopants, impurities, and host materials. The surface morphology analysis revealed a denser microstructure for the electrolytes synthesized via green routes due to metallic impurities in the organic chelating agent. The absence of significant impurities was also observed by compositional analysis, while functional groups were identified through Fourier-transform infrared spectroscopy. Conductivity measurements showed that BaZr0.87Y0.1M0.03O3-δ (M = Mn, Co, and Fe) electrolytes synthesized by oxalic acid have higher conductivities compared to BaZr0.87Y0.1M0.03O3-δ (M = Mn, Co, and Fe) electrolytes synthesized by the green approach. The button cells employing BaZr0.87Y0.1Co0.03O3-δ electrolytes synthesized by the chemical and green routes achieved peak power densities 344 and 271 mW·cm-2 respectively, suggesting that the novel green route can be applied to synthesize SOFC perovskite materials with minimal environmental impact and without significantly compromising cell performance.

Mitigative potential of rhoifolin against cisplatin prompted testicular toxicity: biochemical, spermatogenic and histological based analysis.

Rhoifolin (ROF) is a naturally occurring flavonoid compound with diverse pharmacological and therapeutic benefits. The current investigation was designed to evaluate the curative potential of Rhoifolin (ROF) against Cisplatin (CP) induced testicular damage. Mature male albino rats (n = 48) were randomly distributed into 4 equal groups: control, CP (10 mg/kg), CP + ROF (10 mg/kg + 20 mg/kg) and ROF (20 mg/kg) supplemented group. Following 56 days of the trial, biochemical, inflammatory markers, spermatogenic, steroidogenic, hormonal, apoptotic, anti-apoptotic, and histopathological parameters were evaluated. The exposure to CP markedly (p < 0.05) lowered the activities of anti-oxidant enzymes, glutathione reductase (GSR), catalase (CAT), and glutathione peroxidase (GPx) as well as superoxide dismutase (SOD) in testicular tissues of male albino rats. Besides the levels of reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) were considerably augmented in CP exposed rats. The administration of CP also increased the level of inflammatory cytokines i.e. IL-6, TNF-α, 1L-1ß and NF-κß as well as COX-2 activity. Additionally, a notable (p < 0.05) upsurge was observed in dead sperms count, abnormality in the tail, midpiece as well as head of sperms along with a notable decline in sperm motility in CP treated rats. Moreover, the expressions of steroidogenic enzymes were also lowered in CP administered group. The levels of follicle stimulating hormone (FSH) and plasma testosterone as well as luteinizing hormone (LH) were decreased in CP treated group. Moreover, the expression of Bax as well as Caspase-3 (apoptotic markers) were increased. On the other hand, Bcl-2 expression (anti-apoptotic marker) was reduced. Furthermore, the histopathological analysis showed that CP considerably (p < 0.05) damaged the testicular tissues. However, the administration of ROF significantly reduced the damaging effects of CP in testicular tissues. The results of our study suggested that ROF can potentially alleviate CP-induced testicular damages due to its androgenic, anti-oxidant and anti-inflammatory as well as anti-apoptotic nature.

Knowledge, Attitude, and Practices Regarding Vitamin D in Middle-Aged Pakistani Population and the Impact of Sun Exposure on Their Serum Vitamin D Levels.

OBJECTIVE: This study aimed to assess the knowledge, attitude, and practices regarding vitamin D (D-KAP) among middle-aged individuals in Pakistan and examine the impact of sun exposure on their serum vitamin D levels. METHODOLOGY: A cross-sectional study was conducted, involving 80 middle-aged individuals from Lahore, Pakistan. Data on demographics, sun exposure, and D-KAP were collected. Serum vitamin D levels were measured using enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: The study revealed inadequate knowledge and awareness of vitamin D among the participants. There was a positive correlation between sun exposure duration and serum vitamin D levels, indicating the importance of sun exposure for maintaining optimal vitamin D status. However, there was no significant difference in practice scores between groups, highlighting the need for interventions to bridge the gap between knowledge and practice. CONCLUSION: The study emphasizes the need to improve D-KAP in the middle-aged Pakistani population. Public health initiatives should focus on promoting accurate information, addressing cultural beliefs, and encouraging responsible sun exposure practices. Collaborative efforts are crucial to address vitamin D deficiency and its associated health consequences.

Rhamnazin ameliorates 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin-evoked testicular toxicity by restoring biochemical, spermatogenic and histological profile in male albino rats.

2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) is a potential environmental toxin that has the ability to affect male reproductive tract. Rhamnazin is a naturally present flavone that displays multiple medicinal properties. Therefore, the current study was designed to determine the mitigative role of rhamnazin against TCDD induced reproductive damage. 48 adult male albino rats were randomly separated into four groups: control, TCDD (10 µgkg-1), TCDD + rhamnazin (10 µgkg-1 + 5 mgkg-1 respectively) and rhamnazin (5 mgkg-1). The trial was conducted for 56 days. TCDD intoxication notably affected superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GSR) and catalase (CAT) activities, besides reactive oxygen species (ROS) and malondialdehyde (MDA) concentrations were augmented. TCDD administration also lowered sperm motility, viability, sperm number, while it augmented the sperm morphological (tail, neck/midpiece and head) anomalies. Moreover, it decreased the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and plasma testosterone. Moreover, TCDD reduced steroidogenic enzymes i.e., 17-beta hydroxysteroid dehydrogenase (17ß-HSD), steroidogenic acute regulatory protein (StAR) and 3-beta hydroxysteroid dehydrogenase (3ß-HSD) as well as B-cell lymphoma 2 (Bcl-2) expressions, but increased the expressions of Bcl-2-associated X protein (Bax) and cysteine-aspartic acid protease (Caspase-3). Furthermore, TCDD exposure also induced histopathological anomalies in testicular tissues. However, the supplementation of rhamnazin recovered all the mentioned damages in the testicles. The outcomes revealed that rhamnazin can ameliorate TCDD induced reproductive toxicity due to its anti-oxidant, anti-apoptotic and androgenic nature.

Design and Evaluation of Continentalic Acid Encapsulated Transfersomal Gel and Profiling of its Anti-arthritis Activity.

Rheumatoid arthritis restricts the physical ability of patients and increases the disease burden; therefore, research has always been focused on evaluating better therapeutic options. The present research aimed to design Continentalic acid (CA)-loaded transfersomes (CA-TF) embedded in Carbopol gel containing permeation enhancer (PE) for the treatment of rheumatoid arthritis. CA-TF was developed via a modified thin film hydration method and incorporated into Carbopol 934 gel containing Eucalyptus oil (EO) as PE. The fabricated CA-TF showed particle size of < 140 nm with spherical geometry, optimal encapsulation efficiency (EE), and sustained drug release pattern. CA-TF-gel along with PE (CA-TF-PE-gel) showed better ex vivo skin penetration than plain CA gel and CA-TF-gel without PE. In vivo evaluation supported improved therapeutic outcomes of CA-TF-PE-gel in terms of behavioral findings, arthritic index, and histological findings whereas biochemical assays and pro-inflammatory cytokines (TNF-α and IL-1ß) showed a significant decrease in their levels. Furthermore, immunohistochemistry assay for Nrf2 and HO-1 signaling pathways showed significant improvement in the expression of the Nrf2, and HO-1 proteins to depict improvement in arthritic condition in the animal model. CA-TF-PE-gel significantly delivered CA to the diseased target site via a topical route with promising therapeutic outcomes displayed in the CFA-induced arthritic model.

Dual pH and microbial-sensitive galactosylated polymeric nanocargoes for multi-level targeting to combat ulcerative colitis.

Ulcerative colitis (UC) is a type of inflammatory bowel disease characterized by inflammation, ulcers and irritation of the mucosal lining. Oral drug delivery in UC encounters challenges because of multifaceted barriers. Dexamethasone-loaded galactosylated-PLGA/Eudragit S100/pullulan nanocargoes (Dexa-GP/ES/Pu NCs) have been developed with a dual stimuli-sensitive coating responsive to both colonic pH and microbiota, and an underneath galactosylated-PLGA core (GP). The galactose ligand of the GP preferentially binds to the macrophage galactose type-lectin-C (MGL-2) surface receptor. Therefore, both stimuli and ligand-mediated targeting facilitate nanocargoes to deliver Dexa specifically to the colon with enhanced macrophage uptake. Modified emulsion method coupled with a solvent evaporation coating technique was employed to prepare Dexa-GP/ES/Pu NCs. The nanocargoes were tested using in vitro, ex vivo techniques and dextran sodium sulfate (DSS) induced UC model. Prepared nanocargoes had desired physicochemical properties, drug release, cell uptake and cellular viability. Investigations using a DSS-colitis model showed high localization and mitigation of colitis with downregulation of NF-ĸB and COX-2, and restoration of clinical, histopathological, biochemical indices, antioxidant balance, microbial alterations, FTIR spectra, and epithelial junctions' integrity. Thus, Dexa-GP/ES/Pu NCs found to be biocompatible nanocargoes capable of delivering drugs to the inflamed colon with unique targeting properties for prolonged duration.

Phytochemical, antioxidant, antipyretic and anti-inflammatory activities of aqueous-methanolic leaf extract of Mangifera indica.

OBJECTIVE: Plant-based natural antioxidants have a wide variety of biological activities with significant therapeutic value. Mangifera indica has been used traditionally to treat a variety of ailments in animals and human, but little is defined about its biological or pharmacological effects. Therefore, the objective of the present study was to evaluate phytochemical, antioxidant, antipyretic and anti-inflammatory activities of aqueous-methanolic leaf extract of M. indica. METHODS: To investigate the possible impact of aqueous-methanolic leaf extract of M. indica on oxidative stress, inflammation, and pyrexia, we used a combined in vitro and in vivo series of experiments on laboratory animals. RESULTS: Results revealed significant antioxidant potential in 2,2-diphenylpicrylhydrazyl (DPPH) and nitric oxide (NO) scavenging assay, while significant but dose dependent antipyretic potential was documented in typhoid-paratyphoid A and B (TAB) vaccine and prostaglandin E (PGE) induced pyrexia models. Significant anti-inflammatory effects were observed in both acute and chronic inflammatory models of arachidonic acid and formalin. Phytochemical screening and high-performance liquid chromatography (HPLC) analysis of M. Indica confirmed the presence of mangiferin, quercetin, and isoquercetin. These phytoconstituents likely play a role in the observed biological activities. Our results show that M. indica has antioxidant, anti-inflammatory, and antipyretic effects, lending credence to its traditional use and advocating for its utilization as a viable contender in treating oxidative stress-associated ailments. CONCLUSION: It is concluded that Magnifera indica has various properties in the treatment of various diseases.

Privacy-Aware Collaborative Learning for Skin Cancer Prediction.

Cancer, including the highly dangerous melanoma, is marked by uncontrolled cell growth and the possibility of spreading to other parts of the body. However, the conventional approach to machine learning relies on centralized training data, posing challenges for data privacy in healthcare systems driven by artificial intelligence. The collection of data from diverse sensors leads to increased computing costs, while privacy restrictions make it challenging to employ traditional machine learning methods. Researchers are currently confronted with the formidable task of developing a skin cancer prediction technique that takes privacy concerns into account while simultaneously improving accuracy. In this work, we aimed to propose a decentralized privacy-aware learning mechanism to accurately predict melanoma skin cancer. In this research we analyzed federated learning from the skin cancer database. The results from the study showed that 92% accuracy was achieved by the proposed method, which was higher than baseline algorithms.

Exploring the multifunctional roles of quantum dots for unlocking the future of biology and medicine.

With recent advancements in nanomedicines and their associated research with biological fields, their translation into clinically-applicable products is still below promises. Quantum dots (QDs) have received immense research attention and investment in the four decades since their discovery. We explored the extensive biomedical applications of QDs, viz. Bio-imaging, drug research, drug delivery, immune assays, biosensors, gene therapy, diagnostics, their toxic effects, and bio-compatibility. We unravelled the possibility of using emerging data-driven methodologies (bigdata, artificial intelligence, machine learning, high-throughput experimentation, computational automation) as excellent sources for time, space, and complexity optimization. We also discussed ongoing clinical trials, related challenges, and the technical aspects that should be considered to improve the clinical fate of QDs and promising future research directions.

Multifunctional analysis and antimicrobial activity of Adhatoda vasica: a traditional medicinal plant.

OBJECTIVES: Antibiotic resistance is rising, prompting innovative strategies for eradicating the epidemic. This study investigated the antibacterial properties of the leaves of a widely used medicinal plant, Adhatoda vasica. METHODS: The plant's polar (water, methanol) and non-polar (hexane) extracts were tested against several different bacterial strains using the disc diffusion technique. RESULTS: In a study, it was found that the water extract had the greatest inhibitory effect on Staphylococcus simulans and Staphylococcus aureus, with minimum inhibitory concentrations of 16.444 and 19.315 g/mL, respectively. Gram-negative strains were more susceptible to plant extracts than Gram-positive strains. The phytochemical analysis indicated the presence of secondary metabolites such as alkaloids, saponins, flavonoids, tannins, and steroids, where absorbance was recorded at 415 nm. The water extract had the highest amount of phenolics, with a total phenolic content of 53.92 0.47 mg and a total flavonoid content of 7.25 0.08 mg. Results suggest that the extract may have potential therapeutic applications for antimicrobial properties. CONCLUSIONS: The study concluded that the extract's phenolic group of secondary metabolites were responsible for its antibacterial activity. The study highlights A. vasica as a promising source for discovering new and effective antibacterial compounds.

Differential expression of SLITRK6 gene as a potential therapeutic target for urothelial carcinoma in particular upper tract cancer.

BACKGROUND: Urinary bladder urothelial carcinoma (UBUC) and upper tract urothelial carcinoma (UTUC) harbor analogous morphology with comparable cytogenetic changes as well as prognostic factors but their similar biological activities still remain controversial. SLITRK6 gene has been demonstrated to have distinct role in urothelial cancers with a distinction between UTUC and UBUC. METHOD: The study included a total of 80 patients of urothelial carcinoma including 60 UBUC and 20 UTUC cases. The tumor tissues from both the groups were evaluated for gene expression at mRNA level by qRT-PCR, and protein expression by immunohistochemistry (IHC) and western blot. RESULTS: Significantly more than 4-fold high mRNA expression of SLITRK6 was observed in UTUC against 1.2-fold in UBUC (p < 0.0001). The overall SLITRK6 expression by IHC was observed in 80% of the UBUC cases in comparison to 100% strong expression in UTUC patients and among two groups expression exhibited a significant difference for moderate to strong expression (p = 0.0005). The protein expression by western blot analysis in UTUC samples was considerably higher as compared to UBUC samples (1.64 vs. 0.76 respectively: p = 0.01). A strong concordance exhibited for the higher mRNA and protein expression in both UTUC and UBUC cases (∼75%) wherein 80%, 75% and 70% higher expression of SLITRK6 was detected by qRT-PCR, Western blot and IHC respectively. CONCLUSION: To conclude, although SLITRK6 exhibits a strong expression in both UTUC and UBUC but was considerably observed higher in majority of UTUC cases. Therefore, SLITRK6 appears as a promising novel possible gene target for urothelial carcinoma in particular UTUC.

Fifth Generation Quality Control of Immunoassay Parameters by Six Sigma Value.

OBJECTIVE: To determine the sigma value of immunoassay parameters which are within the 2Z score on external quality control (EQC). STUDY DESIGN: A cross-sectional study. Place and Duration of the Study: Department of Chemical Pathology and Endocrinology (AFIP),non-ability ity consecutive  from June to November 2022. METHODOLOGY: Ten immunoassay parameters were selected on the basis of the internal quality control (IQC) and external quality control (EQC) programs. The Clinical Laboratory Improvement Amendments (CLIA) is used for Total Allowable Error (TEa). Sigma value was calculated from coefficient of variation (CV) and bias, which was determined by IQC and EQC, observed for 6 subsequent months. If the sigma values are ≥6, between 3 and 5, and <3, they are classified as good, acceptable or unacceptable, respectively. RESULTS: T4, prolactin, Vitamin B12 at >3 ó at IQC level 1. TSH, T3, T4, and Vitamin B12 showed that on level 2 IQC at >3 ó T3, Vitamin D at 4-5 ó level, Prolactin, FSH, and LH at 6 ó level in level 2 IQC. In the EQC program, the sigma level calculated for ten assays found that almost all parameters were at sigma >3 ó level except TSH which was at 5.8 Ï­ level during June to August 2022. From September to November 2022, all parameters at >3 ó level except for TSH, growth hormone, FSH, LH, and Vitamin b12 which showed at 4.4 ó level. CONCLUSION: Most of the immunoassay parameters show good performance in the EQC program and at both levels of IQC level with sigma value 4-5. KEY WORDS: Bias, Six sigma, Key performance indicators, External quality control.

Predicting the effects of rare genetic variants on oncogenic signaling pathways: A computational analysis of HRAS protein function.

The HRAS gene plays a crucial role in regulating essential cellular processes for life, and this gene's misregulation is linked to the development of various types of cancers. Nonsynonymous single nucleotide polymorphisms (nsSNPs) within the coding region of HRAS can cause detrimental mutations that disrupt wild-type protein function. In the current investigation, we have employed in-silico methodologies to anticipate the consequences of infrequent genetic variations on the functional properties of the HRAS protein. We have discovered a total of 50 nsSNPs, of which 23 were located in the exon region of the HRAS gene and denoting that they were expected to cause harm or be deleterious. Out of these 23, 10 nsSNPs ([G60V], [G60D], [R123P], [D38H], [I46T], [G115R], [R123G], [P11OL], [A59L], and [G13R]) were identified as having the most delterious effect based on results of SIFT analysis and PolyPhen2 scores ranging from 0.53 to 69. The DDG values -3.21 kcal/mol to 0.87 kcal/mol represent the free energy change associated with protein stability upon mutation. Interestingly, we identified that the three mutations (Y4C, T58I, and Y12E) were found to improve the structural stability of the protein. We performed molecular dynamics (MD) simulations to investigate the structural and dynamic effects of HRAS mutations. Our results showed that the stable model of HRAS had a significantly lower energy value of -18756 kj/mol compared to the initial model of -108915 kj/mol. The RMSD value for the wild-type complex was 4.40 Å, and the binding energies for the G60V, G60D, and D38H mutants were -107.09 kcal/mol, -109.42 kcal/mol, and -107.18 kcal/mol, respectively as compared to wild-type HRAS protein had -105.85 kcal/mol. The result of our investigation presents convincing corroboration for the potential functional significance of nsSNPs in augmenting HRAS expression and adding to the activation of malignant oncogenic signalling pathways.