Mutations in the TP53, VEGFA, and CTH Genes as Key Molecular Markers for the Diagnosis of Glioblastoma.

Background Brain cancer, particularly glioblastoma (GBM), is a global health problem. Despite therapy advances, GBM patients have a poor prognosis. The progression and etiology of GBM may be linked to gene polymorphisms in the VEGFA, TP53, and CTH genes, among others. However, the genetic variations and their interaction in GBM are not fully understood. This study examines the effects of mutations in the VEGFA, TP53, and CTH genes on GBM. Methodology Tissue and blood samples were obtained for hematological, biochemical, and genetic analysis from 18 patients diagnosed with GBM as well as 28 healthy individuals. Standard methods were adopted to perform hematological and biochemical analyses, whereas mutational landscape and expression profiles were obtained from publicly accessible databases. Tissue samples were processed for genomic DNA extraction, and genotype determination was carried out through conventional polymerase chain reaction (PCR) and Sanger sequencing. Results The study involved 18 patients with grade IV GBM before treatment and 28 healthy individuals. The patients consisted of 11 men (61%) and seven females (39%), while healthy individuals included 14 (50%) males and 14 (50%) females. Sixty-seven percent of patients were under 50, 17% between 51 and 60, and 17% over 61, compared to healthy individuals who were 61% under 50, 7% between 51 and 60, and 32% over 60. GBM patients showed higher neutrophil and monocyte counts (median 81% (63.9, 83.5) and 4.2% (3.8-7.3)), respectively, and lower lymphocyte counts (median 13.4% (8.8, 28.40)) compared to controls. The median values of aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) showed no significant differences between the control and GBM groups. GBM patients had significantly higher median CRP levels of 2.55 (1.6, 98) than controls. Analysis of databases revealed a high prevalence of mutations in TP53, with splice region variants, missense variants, and intron variants being the most common. VEGFA and CTH also displayed mutations, primarily missense and intron variants. Gene expression analysis showed significantly higher levels of TP53 and VEGFA in GBM patients compared to controls. CTH expression also exhibited a slight increase in GBM patients. Sanger sequencing identified three mutations in the TP53 gene, including a novel mutation (11915C>A) not previously reported in external databases. Additionally, novel mutations were found in the VEGFA (841G>GA, 919T>TG) and CTH (28398A>AC, 28399A>AT) genes. Conclusions This study highlights the immune dysregulation, inflammation, and genetic variations in GBM. The findings emphasize the potential importance of the TP53, VEGFA, and CTH genes as targets for therapies and diagnostic biomarkers of GBM. Further study is necessary to comprehend these genetic variations' functional implications and their use in personalized GBM treatment.

Organic Geochemistry and 1-D Basin Modeling of the Late Triassic Baluti Formation: Implication of Shale Oil Potential in the Kurdistan Region of Iraq.

This investigation looks at the Late Triassic Baluti Formation's organic geochemical, mineralogical, and petrographical characteristics from a single exploration well (TT-22) near the Taq Taq oilfield in northern Iraq. The Baluti Formation shale samples that were studied in the studied well have high total organic carbon (TOC %) values up to 4.92 wt % and mostly hydrogen-rich types I and II kerogen with a minor gradient to types II/III and III kerogen, indicating a good oil-source rock. The hydrogen-rich kerogen was also confirmed by various organic matter (OM) origins and depositional environment-related biomarkers. The biomarker indicators demonstrate that the Baluti shale was deposited under anoxic conditions and contains a variety of OM generated mostly from algae marine and other aqueous organic materials, along with some terrigenous land plants. The geochemical and optical maturity indicators show that most of the examined Baluti shale samples, with a deep burial depth of more than 4000 m, are thermally mature, thus defining peak-mature to late-mature stages of the oil generation window. According to the basin models, from the late Miocene to the present, between 10 and 59% of the kerogen in the Baluti shale source rock has been transformed into oil, which is consistent with the VR values between 0.77 and 1.08%. The presence of the oil crossover in these shale rocks with an oil saturation index of more than 100 mg HC/g rock supports the maximal oil generation from the Baluti source rock system. Additionally, there was little oil expulsion from the Baluti source rock system at the end of the late Miocene, with transformation ratio values below 60% (59%). Considering the more significant oil generation and little expulsion, a high pressure was generated and forced the brittle minerals of the Baluti shales (mainly quartz), creating a natural fracture system as recognized and observed in the thin section. This natural fracture system enhances the porosity system of tight shale rocks of the Baluti Formation, giving rise to a high probability of oil production using hydraulic fracturing stimulation.

Correction: Theoretical prediction of the electronic structure, optical properties and photocatalytic performance of type-I SiS/GeC and type-II SiS/ZnO heterostructures.

[This corrects the article DOI: 10.1039/D3RA01061A.].

Theoretical prediction of the electronic structure, optical properties and photocatalytic performance of type-I SiS/GeC and type-II SiS/ZnO heterostructures.

Nowadays, it would be ideal to develop high-performance photovoltaic devices as well as highly efficient photocatalysts for the production of hydrogen via photocatalytic water splitting, which is a feasible and sustainable energy source for addressing the challenges related to environmental pollution and a shortage of energy. In this work, we employ first-principles calculations to investigate the electronic structure, optical properties and photocatalytic performance of novel SiS/GeC and SiS/ZnO heterostructures. Our results indicate that both the SiS/GeC and SiS/ZnO heterostructures are structurally and thermodynamically stable at room temperature, suggesting that they are promising materials for experimental implementation. The formation of SiS/GeC and SiS/ZnO heterostructures gives rise to reduction of the band gaps as compared to the constituent monolayers, enhancing the optical absorption. Furthermore, the SiS/GeC heterostructure possesses a type-I straddling gap with a direct band gap, while the SiS/ZnO heterostructure forms a type-II band alignment with indirect band gap. Moreover, a red-shift (blue-shift) has been observed in SiS/GeC (SiS/ZnO) heterostructures as compared with the constituent monolayers, enhancing the efficient separation of photogenerated electron-hole pairs, thereby making them promising candidates for optoelectronic applications and solar energy conversion. More interestingly, significant charge transfers at the interfaces of SiS-ZnO heterostructures, have improved the adsorption of H, and the Gibbs free energy ΔH* becomes close to zero, which is optimal for the hydrogen evolution reaction to produce hydrogen. The findings pave the path for the practical realization of these heterostructures for potential applications in photovoltaics and photocatalysis of water splitting.

Overt visual attention and between-limb asynchrony for bimanual reaching movements.

Although synchrony between the limbs is an often-cited feature of bimanual coordination, recent studies have also highlighted the small asynchronies that can occur. The visuo-motor demands of any bimanual task are considered central to the emergence of asynchrony, but the relationship between the two remains largely unexplored. This study aimed to address this issue. Hand and eye movements were measured in 19 participants, while they made either unimanual or bimanual reach-to-point (aiming) movements to targets presented on a touchscreen. Bimanual movements were either congruent (same-sized targets) or incongruent (different-sized targets). Resulting hand data showed many of the typical patterns of movement previously reported. While temporal coupling between the limbs remained largely evident for bimanual movements, small between-limb asynchronies were apparent and demonstrated clear associations with the competing precision requirements of the targets and related visual attention. Participants mainly directed their gaze towards the more difficult target with corresponding reaching movements demonstrating greater precision than for the easier target. Additionally, there was a reliable tendency for the hand reaching towards the more difficult target to lead. Importantly, it was the competing visuo-motor demands of individual movements rather than overall difficulty that resulted in greater between-limb asynchrony; accordingly, where both targets were small (i.e., the most difficult condition), asynchrony was significantly less pronounced than for incongruent bimanual conditions. The results show how the visuo-motor system balances its apparent drive for synchrony in coordinating bimanual movements with the competing demands that characterise the constituent unimanual movements.

A first principles study of a van der Waals heterostructure based on MS2 (M = Mo, W) and Janus CrSSe monolayers.

The strategy of stacking two-dimensional materials for designing van der Waals heterostructures has gained tremendous attention in realizing innovative device applications in optoelectronics and renewable energy sources. Here, we performed the first principles calculations of the geometry, optoelectronic and photocatalytic performance of MS2-CrSSe (M = Mo, W) vdW heterostructures. The mirror asymmetry in the Janus CrSSe system allows the designing of two models of the MS2-CrSSe system by replacing S/Se atoms at opposite surfaces in CrSSe. The feasible configurations of both models of the MS2-CrSSe system are found energetically, dynamically and thermally stable. The studied heterobilayers possess an indirect type-I band alignment, indicating that the recombination of photogenerated electrons and holes in the CrSSe monolayer is hence crucial for photodetectors and laser applications. Remarkably, a red-shift in the optical absorption spectra of MS2-CrSSe makes them potential candidates for light harvesting applications. More interestingly, all heterobilayers (except W(Mo)S2-CrSSe of model-I(II)) reveal appropriate band edge positions of the oxidation and reduction potentials of the photocatalysis of water dissociation into H+/H2 and O2/H2O at pH = 0. These results shed light on the practical design of the MS2-CrSSe system for efficient optoelectronic and photocatalytic water splitting applications.

Clinical and echocardiographic characteristics associated with evolution of patent ductus arteriosus in preterm neonates: A prospective cohort study.

BACKGROUND: In preterm infants, persistence of ductus arteriosus is an important medical condition. Functional echocardiography for patent ductus arteriosus (PDA) may guide clinical decision-making regarding treatment requirement strategies. Objectives of the study were to assess the trends of clinical and functional echocardiographic parameters with evolution of ductus arteriosus in babies≤1250 gm of birth weight and to evaluate whether there is any association of these parameters with persistence of ductus. METHODS: In this prospective observational study, recruited babies were assessed serially for clinical events and functional echocardiography. Babies were classified into three groups: without PDA, with PDA but PDA spontaneously closed (within 7 days) and persistent PDA. RESULT: We included 143 infants (Birth weight 1017±179 g, gestational age 30.8±2.7 weeks). Out of 60 babies with PDA, PDA failed to close spontaneously in first week in 32 (53.4 %) infants. PDA Doppler flow pattern on day 3 was found to be one of the most significant markers for future ductus. The highest frequency of growing pattern (37.5%) and pulsatile pattern (59.4%) was seen in persistence ductus group. PDA diameter and LA/Ao ratio were found strongly correlated with all other variables except E/A ratio. CONCLUSION: We noticed persistence of ductus in preterm infants had significant clinical and echocardiographic association. PDA doppler flow pattern on day 3 was found to be a significant marker for future behaviour of ductus. Significant correlation was found among individual functional echocardiographic parameters in babies with PDA. This would guide judicious treatment of PDA in preterm neonates.

A randomized controlled trial of restricted versus standard fluid management in late preterm and term infants with transient tachypnea of the newborn.

BACKGROUND: Transient tachypnea of the newborn(TTNB) is the most common respiratory morbidity in late preterm and term babies and is pathophysiologically related to delayed lung fluid clearance after birth. Mimicking low physiological fluid intake in the initial period of life may accelerate the recovery from TTNB. In a randomized controlled trial, we compared the roles of restricted versus standard fluid management in babies with TTNB requiring respiratory support. METHODS: This parallel group,non-blinded, stratified randomized controlled trial was conducted in a level III neonatal unit of eastern India. Late preterm and term babies with TTNB requiring continuous positive airway pressure (CPAP) were randomly allocated to standard and restricted fluid arms for the first 72 hours (hrs). Primary outcome was CPAP duration. RESULTS: In total, 100 babies were enrolled in this study with 50 babies in each arm. CPAP duration was significantly less in the restricted arm (48[42, 54] hrs vs 54[48,72] hrs, p = 0.002). However, no difference was observed in the incidence of CPAP failure between the two arms. In the subgroup analysis, the benefit of reduced CPAP duration persisted in late preterm but not in term infants. However, the effect was not significant in the late preterm babies exposed to antenatal steroid. CONCLUSION: This trial demonstrated the safety and effectiveness of restrictive fluid strategy in reducing CPAP duration in late preterm and term babies with TTNB. Late preterm babies, especially those not exposed to antenatal steroid were the most benefitted by this strategy.

Prediction of ductus closure and development of adverse clinical outcome by functional echocardiography in very low birth weight newborn.

OBJECTIVE: To evaluate the role of functional echocardiography for prediction of patent ductus arteriosus (PDA) closure and development of adverse outcome in very low birth weight newborn. METHODS AND STUDY DESIGN: Functional echocardiography was done in 143 neonates with birth weight less than 1250 g on day 3. Nine echocardiographic parameters were analyzed for babies with PDA for prediction of spontaneous closure and development of one or more adverse outcomes (bronchopulmonary dysplasia, necrotizing enterocolitis≥stage 2 and intraventricular hemorrhage > grade 2) during hospital stay. RESULT: The mean (±SD) birthweight and gestational age of the cohort were 1017 (±17) g and 30.8 (±2.7) weeks. PDA was found in 60 (41.9%) babies on day 3 among the recruited babies. Binary logistic regression model showed strong prediction ability of early (day 3) functional echocardiography markers in predicting future spontaneous closure of PDA and development of one or more adverse clinical outcome. In multivariate analysis, abnormal flow pattern (growing or pulsatile) was found to have increased risk for persistence of PDA (adjusted OR 22.9, CI 1.97-269) in comparison to PDA with closing/bidirectional pattern. CONCLUSION: Early functional echocardiography, especially the flow pattern, is useful for prediction of PDA closure. Adverse clinical outcome prediction is possible with functional echocardiography markers when combined with gestational age and PDA closure status.

Tissue Paper as a Substrate for Electronic Biosensing.

In the presented work, we combine a commonplace commodity, tissue paper, with biosensing capabilities to provide on-the-go detection of biomarkers. We developed a simple light-weight sensor using single walled carbon nanotubes (SWCNT) on commercially available tissue paper. As a proof of concept, we show that these sensors can be used to quantify Interleukin-6 protein concentration. Detection is carried out by examining the modulation in electrical properties of the substrate induced by addition of protein on these sensors. Our results show that these sensors can provide the foundation for development of tissue paper based portable sensors for biomarkers relevant to on-the-go testing.

Antioxidant associated chemoprevention by selenomethionine in murine tumor model.

Effectiveness of selenium in different forms like sodium selenite, selenocysteine and selenomethionine has been compared in four different doses, namely 4, 6, 8 and 10 ppm of each, in terms of their bioavailability and prolongation of survival of Dalton's lymphoma (DL) bearing mice. Selenomethionine, at a dose of 8 ppm, was found to be the most bioavailable and least-cytotoxic form that was capable of increasing the life span of the tumour bearing hosts maximally (almost two-fold). Beneficiality of selenomethionine has also been studied by observing continuous changes brought about by this compound on the glutathione (GSH) level, glutathione peroxidase (GPx) activity and extent of lipid peroxidation in the hepatic tissue of the tumour bearing hosts, which are indispensable for a cell to function normally and are found to exhibit significantly altered behaviour in neoplastic cells. Selenomethionine caused the maintenance of high steady state GSH level and a normal GPx activity during the fist phase of tumour growth. It also controlled lipid peroxidation during the first 15-20 days following tumour transplantation. These conditions helped in the maintenance of intracellular redox balance, cellular integrity and metabolic rhythms of cells in DL bearing mice receiving selenomethionine.

Lack of evidence from HPLC 32P-post-labelling for tamoxifen-DNA adducts in the human endometrium.

Tamoxifen is associated with an increased incidence of endometrial cancer in women. It is also a potent carcinogen in rat liver and forms covalent DNA adducts in this tissue. A previous study exploring DNA adducts in human endometria, utilizing thin layer chromatography 32P-postlabelling, found no evidence for adducts in tamoxifen-treated women [Carmichael,P.L., Ugwumadu,A.H.N., Neven,P., Hewer,A.J., Poon,G.K. and Phillips,D.H. (1996) Cancer Res., 56, 1475-1479]. However, subsequent work utilizing HPLC 32P-post-labelling [Hemminki,K., Ranjaniemi,H., Lindahl,B. and Moberger,B. (1996) Cancer Res., 56, 4374-4377] suggested that very low levels could be detected. We have sought to investigate this question further by reproducing the HPLC methodology at two centres, and analysing endometrial DNA from 20 patients treated with 20 mg/day tamoxifen for between 22 and 65 months. Liver DNA isolated from tamoxifen-treated rats was used as a positive control. We found no convincing evidence for tamoxifen-derived DNA adducts in human endometrium. HPLC elution profiles of post-labelled DNA from tamoxifen-treated women were indistinguishable from those obtained with DNA from 14 untreated women and from six women taking toremifene, an analogue of tamoxifen.

Role of vitamin D3 on the activity patterns of hepatic drug metabolizing enzymes in transplantable murine lymphoma.

Vitamin D3 (D3) has been found to exert varied pharmacological actions including restriction of cell growth of a number of malignant cell lines in vitro and inhibition of the promotion of chemical carcinogenesis in mouse skin. In an attempt to confirm the efficacy of D3 as an antineoplastic agent, the present investigation aims at characterizing the importance of D3 in modulating hepatic drug metabolizing enzymes, namely, cytosolic glutathione S-transferase (GSHT), microsomal UDP glucuronyl transferase (UDPGT), and cytochrome P-450, which have been reported by us in recent literature as significant neoplastic markers in mice bearing Dalton's lymphoma (DL). Results show that D3 causes a 150% elevation of GSHT activity and the maintenance of normal, near-control UDPGT activity and cytochrome P-450 content, up to almost 30 days following tumor transplantation, along with bringing about a twofold increase in survival of the host mice. In conclusion, we confirm the definite and significant antitumorigenic role of D3 and its involvement with the discussed hepatic tumor markers in monitoring the processes that lead to cell survival.

Selenomethionine in the inhibition of a transplantable murine lymphoma: reflection on hepatic drug metabolizing enzymes.

This study attempts to determine whether selenomethionine treatment can improve the survival time of mice inoculated with Dalton's lymphoma (DL) and thereby to identify phase/phases of the neoplastic processes at which selenium exerts its maximal action as an anticancer agent. Accordingly, a maximum of 30.76 and 143% increase in survival was brought about by treatment of selenomethionine prior to lymphoma transplantation, in comparison to mice receiving selenomethione supplementation concurrently with inoculation of DL, and those tumor-bearing mice receiving no supplementation, respectively. Beneficiality of selenomethionine has also been studied by monitoring the continuous changes brought about by this compound on hepatic total cytochrome P-450 and b5 content, NADPH cytochrome c reductase, UDP glucuronyl transferase and glutathione S-transferase (GST) activities. These are important biotransformation enzymes and are altered significantly in neoplasia. The drastic increase in all the markers studied, excepting GST, was effectively counteracted by selenomethionine treatment (more before than concurrently), which sufficiently delayed and controlled the increase in those xenobiotic indices. The 112 and 78.78% induction in GST activity brought about by prior and concurrent treatment of selenomethionine, respectively, confirms the fact that inducers of GSTs are often antitumorigenic.

Comparative effectiveness of vitamin D3 and dietary vitamin E on peroxidation of lipids and enzymes of the hepatic antioxidant system in Sprague--Dawley rats.

The vitamin D-endocrine system has mostly been studied for its role in calcium and phosphorus metabolism and its possible role as an antioxidant has been neglected. This study attempts to elucidate the antioxidative properties of the prohormone with respect to vitamin E, a membrane antioxidant. Results herein show that D3 treatment brought about similar reduction in the extent of lipid peroxidation and induction in superoxide dismutase (SOD) activity, as with vitamin E supplementation. While selenium dependent glutathione peroxidase (Sedep. GPx) activity reflected no change with vitamin D3 treatment, total GPx activity was more significantly influenced by vitamin D3 than by vitamin E. The glutathione (GSH) content in the experimental rats also reflected similar changes. Vitamin E supplementation caused 8.57% increase in glutathione reductase (GR) activity, while vitamin D3 decreased the concerned enzymes activity by 11.11%. Vitamin D3 treatment also caused 25% increase in glucose 6-phosphate dehydrogenase (G6PD) activity. These data thus suggest that vitamin D3 may function as an antioxidant in the liver in vivo and illustrate an effectiveness higher than that observed with vitamin E supplementation.

Role of beta-carotene on the changes in activity patterns and levels of biotransforming enzymes in transplantable murine lymphoma.

The differential levels of induction of hepatic microsomal cytochrome P-450 (cyt. P-450), UDP-glucuronyl transferase (UDPGT) and cytosolic glutathione-S-transferase (GST) activities were evaluated over various periods of time, following tumor transplantation in male Swiss albino mice in the presence and absence of beta-carotene supplementation in their basal diet (100 mg/kg). An increase in the total hepatic microsomal cytochrome P-450 and UDP-glucuronyl transferase and cytosolic GSH-transferase activities (1.5 to 2 fold) occurred during the later stage of tumor progression (22 +/- 2 days onwards). However, beta-carotene supplementation throughout the study increased or decreased the random activity trends of the above markers significantly (P < 0.05- < 0.01). Finally, beta-carotene supplementation could enhance the survival of the host bearing lymphoma by almost 2-fold (50-60 days) over and above the lymphoma controls (30-35 days).

Protective role of vanadium in the survival of hosts during the growth of a transplantable murine lymphoma and its profound effects on the rates and patterns of biotransformation.

Vanadium, as ammonium mononium monovanadate, has been found to have anticarcinogenic effect in host mice bearing a transplantable ascitic lymphoma. The potentiating effect of vanadium was supported by biochemical analysis of autopsies relating to markers like microsomal cytochrome P-450, UDP glucuronyl transferase (UDPGT) and cytosolic glutathione-S-transferase (GSHT) in the hepatic tissue of the hosts, which showed substantial alterations in the extent of tumor regression as compared to their lymphoma and normal counterparts, prolonging the survival of the hosts.