Analyzing RNA posttranscriptional modifications to decipher the epitranscriptomic code.

The discovery of RNA silencing has revealed that non-protein-coding sequences (ncRNAs) can cover essential roles in regulatory networks and their malfunction may result in severe consequences on human health. These findings have prompted a general reassessment of the significance of RNA as a key player in cellular processes. This reassessment, however, will not be complete without a greater understanding of the distribution and function of the over 170 variants of the canonical ribonucleotides, which contribute to the breathtaking structural diversity of natural RNA. This review surveys the analytical approaches employed for the identification, characterization, and detection of RNA posttranscriptional modifications (rPTMs). The merits of analyzing individual units after exhaustive hydrolysis of the initial biopolymer are outlined together with those of identifying their position in the sequence of parent strands. Approaches based on next generation sequencing and mass spectrometry technologies are covered in depth to provide a comprehensive view of their respective merits. Deciphering the epitranscriptomic code will require not only mapping the location of rPTMs in the various classes of RNAs, but also assessing the variations of expression levels under different experimental conditions. The fact that no individual platform is currently capable of meeting all such demands implies that it will be essential to capitalize on complementary approaches to obtain the desired information. For this reason, the review strived to cover the broadest possible range of techniques to provide readers with the fundamental elements necessary to make informed choices and design the most effective possible strategy to accomplish the task at hand.

Detection of Marchiafava Bignami disease using distinct deep learning techniques in medical diagnostics.

PURPOSE: To detect the Marchiafava Bignami Disease (MBD) using a distinct deep learning technique. BACKGROUND: Advanced deep learning methods are becoming more crucial in contemporary medical diagnostics, particularly for detecting intricate and uncommon neurological illnesses such as MBD. This rare neurodegenerative disorder, sometimes associated with persistent alcoholism, is characterized by the loss of myelin or tissue death in the corpus callosum. It poses significant diagnostic difficulties owing to its infrequency and the subtle signs it exhibits in its first stages, both clinically and on radiological scans. METHODS: The novel method of Variational Autoencoders (VAEs) in conjunction with attention mechanisms is used to identify MBD peculiar diseases accurately. VAEs are well-known for their proficiency in unsupervised learning and anomaly detection. They excel at analyzing extensive brain imaging datasets to uncover subtle patterns and abnormalities that traditional diagnostic approaches may overlook, especially those related to specific diseases. The use of attention mechanisms enhances this technique, enabling the model to concentrate on the most crucial elements of the imaging data, similar to the discerning observation of a skilled radiologist. Thus, we utilized the VAE with attention mechanisms in this study to detect MBD. Such a combination enables the prompt identification of MBD and assists in formulating more customized and efficient treatment strategies. RESULTS: A significant breakthrough in this field is the creation of a VAE equipped with attention mechanisms, which has shown outstanding performance by achieving accuracy rates of over 90% in accurately differentiating MBD from other neurodegenerative disorders. CONCLUSION: This model, which underwent training using a diverse range of MRI images, has shown a notable level of sensitivity and specificity, significantly minimizing the frequency of false positive results and strengthening the confidence and dependability of these sophisticated automated diagnostic tools.

16S rRNA based metagenomic analysis unveils unique oral microbial signatures in oral squamous cell carcinoma cases from Coastal Karnataka, India.

Oral Squamous cell carcinoma (OSCC) is the 14th most frequent cancer with 300,000 new cases and 100,000 deaths reported annually. Even with advanced therapy, the treatment outcomes are poor at advanced stages of the disease. The diagnosis of early OSCC is of paramount clinical value given the high mortality rate associated with the late stages of the disease. Recently, the role of microbiome in the disease manifestation, including oral cancer, has garnered considerable attention. But, to establish the role of bacteria in oral cancer, it is important to determine the differences in the colonization pattern in non-tumour and tumour tissues. In this study, 16S rRNA based metagenomic analyses of 13 tumorous and contralateral anatomically matched normal tissue biopsies, obtained from patients with advanced stage of OSCC were evaluated to understand the correlation between OSCC and oral microbiome. In this study we identified Fusobacterium, Prevotella, Capnocytophaga, Leptotrichia, Peptostreptococcus, Parvimonas and Bacteroidetes as the most significantly enriched taxa in OSCC lesions compared to the non-cancerous tissues. Further, PICRUSt2 analysis unveiled enhanced expression of metabolic pathways associated with L-lysine fermentation, pyruvate fermentation, and isoleucine biosynthesis in those microbes associated with OSCC tissues. These findings provide valuable insights into the distinctive microbial signatures associated with OSCC, offering potential biomarkers and metabolic pathways underlying OSCC pathogenesis. While our focus has primarily centred on microbial signatures, it is essential to recognize the pivotal role of host factors such as immune responses, genetic predisposition, and the oral microenvironment in shaping OSCC development and microbiome composition.

Exploring microtubule dynamics in Alzheimer's disease: Longitudinal assessment using [11C]MPC-6827 PET imaging in rodent models of Alzheimer's-related pathology.

INTRODUCTION: Microtubule (MT) stability is crucial for proper neuronal function. Understanding MT dysregulation is critical for connecting amyloid beta (Aß) and tau-based degenerative events and early changes in presymptomatic Alzheimer's disease (AD). Herein we present positron emission tomography (PET) imaging properties of our MT-PET radiotracer, [11C]MPC-6827, in multiple established AD mouse models. METHODS: Longitudinal PET, biodistribution, autoradiography, immunohistochemistry, and behavioral studies were conducted at multiple time points in APPswe/PSEN1dE9 (APP/PS1), P301S-PS19 (P301S), 5xFAD, and age-matched control mice. RESULTS: Longitudinal [11C]MPC-6827 brain imaging showed significant increases in APP/PS1, P301S, and 5xFAD mice compared to controls. Longitudinal MT-PET correlated positively with biodistribution, autoradiography, and immunohistochemistry results and negatively with behavior data. DISCUSSION: Our study demonstrated significant longitudinal [11C]MPC-6827 PET increases in multiple AD mouse models for the first time. Strong correlations between PET and biomarker data underscored the interplay of MT destabilization, amyloid, and tau pathology in AD. These results suggest [11C]MPC-6827 PET as a promising tool for monitoring MT dysregulation early in AD progression. HIGHLIGHTS: Longitudinal positron emission tomography (PET) imaging studies using [11C]MPC-6827 in multiple established Alzheimer's disease (AD) mouse models revealed an early onset of microtubule dysregulation, with significant changes in brain radiotracer uptake evident from 2 to 4 months of age. Intra-group analysis showed a progressive increase in microtubule dysregulation with increasing AD burden, supported by significant correlations between PET imaging data and biodistribution, autoradiography, and molecular pathological markers. [11C]MPC-6827 PET imaging demonstrated its efficacy in detecting early microtubule alterations preceding observable behavioral changes in AD mouse models, suggesting its potential for early AD imaging. The inclusion of the 5xFAD mouse model further elucidated the impact of amyloid beta (Aß) toxicity on inducing tau hyperphosphorylation-mediated microtubule dysregulation, highlighting the versatility of [11C]MPC-6827 in delineating various aspects of AD pathology. Our study provides immediate clarity on high uptake of the microtubule-based radiotracer in AD brains in a longitudinal setting, which directly informs clinical utility in Aß/tau-based studies.

Sustainable approach for the expulsion of metaldehyde: risk, interactions, and mitigation: a review.

All pests can be eliminated with the help of pesticides, which can be either natural or synthetic. Because of the excessive use of pesticides, it is harmful to both ecology and people's health. Pesticides are categorised according to several criteria: their chemical composition, method of action, effects, timing of use, source of manufacture, and formulations. Many aquatic animals, birds, and critters live in danger owing to hazardous pesticides. Metaldehyde is available in various forms and causes significant impact even when small amounts are ingested. Metaldehyde can harm wildlife, including dogs, cats, and birds. This review discusses pesticides, their types and potential environmental issues, and metaldehyde's long-term effects. In addition, it examines ways to eliminate metaldehyde from the aquatic ecosystem before concluding by anticipating how pesticides may affect society. The metal-organic framework and other biosorbents have been appropriately synthesized and subsequently represent the amazing removal of pesticides from effluent as an enhanced adsorbent, such as magnetic nano adsorbents. A revision of the risk assessment for metaldehyde residuals in aqueous sources is also attempted.

Volumetric Analysis of Hand and Rotary Instrumentation, Root Canal Filling Techniques, and Obturation Materials in Primary Teeth Using Spiral CT.

AIM AND BACKGROUND: To compare the root canal volume in primary teeth using hand and rotary instruments and to evaluate root canal filling techniques and flow of root canal obturation materials in the postinstrumented root canal volume using spiral computed tomography (SCT). MATERIALS AND METHODS: Freshly extracted 16 primary molars were randomly divided into two groups and subjected to SCT analysis before and after instrumentation. For the manual technique (group I) with eight teeth were prepared using K files, and rotary (group II) eight teeth preparation was performed with ProTaper files. The filled volume in each canal was measured using SCT, and the percentage of obturated volume was calculated. The data were statistically analyzed using the Mann-Whitney U test. RESULTS: There was a statistically significant difference in both groups' volume of root canals enlarged. Even though both K files and the ProTaper system brought about enlarged canals after instrumentation, there was a statistically significant increase in volume after using K files in two canals. In three canals, there was a statistically significant increase in volume after using ProTaper. Irrespective of the obturation technique and materials used, there is no statistically significant difference in the volume after obturation. CONCLUSION: From the results of this study, the ProTaper file system shows suitable volumetric enlargement up to an optimum level, which is needed in primary root canal walls, and is better in canal shaping, as evidenced by good postobturation volume. CLINICAL SIGNIFICANCE: The traditional method of cleaning and shaping the root canals in permanent teeth using manual stainless-steel files can lead to undesirable curvatures in root canal morphology, making correctly filling the root canals difficult. It is also time-consuming and sometimes leads to iatrogenic errors. Rotary nickel-titanium (Ni-Ti) instrumentation techniques have been developed to overcome these problems. How to cite this article: Yadav DBUC, Varma RB, Kumar JS, et al. Volumetric Analysis of Hand and Rotary Instrumentation, Root Canal Filling Techniques, and Obturation Materials in Primary Teeth Using Spiral CT. J Contemp Dent Pract 2024;25(3):250-259.

Genetic and Epigenetic Basis of Drug-Induced Liver Injury.

Drug-induced liver injury (DILI) is a rare but severe adverse drug reaction seen in pharmacotherapy and a major cause of postmarketing drug withdrawals. Advances in genome-wide studies indicate that genetic and epigenetic diversity can lead to inter-individual differences in drug response and toxicity. It is necessary to identify how the genetic variations, in the presence of environmental factors, can contribute to development and progression of DILI. Studies on microRNA, histone modification, DNA methylation, and single nucleotide polymorphisms related to DILI were retrieved from databases and were analyzed for the current research and updated to develop this narrative review. We have compiled some of the major genetic, epigenetic, and pharmacogenetic factors leading to DILI. Many validated genetic risk factors of DILI, such as variants of drug-metabolizing enzymes, HLA alleles, and some transporters were identified. In conclusion, these studies provide useful information in risk alleles identification and on implementation of personalized medicine.

Factors associated with pathologic complete response following neoadjuvant chemoradiation and esophagectomy for carcinoma of esophagus and gastroesophageal junction.

BACKGROUND AND OBJECTIVES: The aim of this study was to analyze factors associated with pathologic complete response (pCR) following neoadjuvant chemoradiation (NCRT) and esophagectomy for carcinoma of the esophagus (EC) and gastroesophageal junction (GEJ). METHODS: Patients with EC and GEJ tumors who received NCRT and underwent esophagectomy between January 2010 to March 2021 were included. Univariate and multivariate analyses were performed to evaluate the factors associated with pCR by comparing the patients who achieved pCR (pCR group) with those who did not achieve pCR (non-pCR group). RESULTS: A total of 321 patients were included in the study, with squamous cell carcinoma (SCC) accounting for the majority of cases (76%). One hundred and sixty (49.8%) patients had pCR. SCC histology and pretreatment radiographic node-negative status (cN0) were associated with pCR. Patients in the pCR group had significantly better overall and disease-free survival compared with patients in the non-pCR group. CONCLUSIONS: SCC histology and pretreatment radiographic node-negative status were associated with pCR. For patients with tumors of EC and GEJ who received NCRT and underwent esophagectomy, pCR was associated with improved prognosis compared with those not achieving pCR.

Unveiling the molecular identity of the diminutive cyprinid, Horadandia brittani (Teleostei: Cyprinidae), a species endemic to Southern India.

BACKGROUND: Horadandia brittani is a small cyprinid fish species initially discovered in the coastal floodplains of southern India. For almost 50 years, the genus Horadandia was monotypic with a single species confined to Sri Lanka. In 1992, a new species H. brittani was described from south-western India. Despite being described as a separate species, H. brittani was later considered a synonym of H. atukorali, but in 2013, researchers recognized it as a distinct species based on morphological differences. Despite this clarification, there was still a need to validate the identity of H. brittani and determine its evolutionary relationship with its closely related species using DNA sequences. METHODS: To address the uncertainties surrounding the identity of H. brittani, the present study utilized molecular techniques to generate DNA sequences. Sample collection involved obtaining specimens of H. brittani from their natural habitats. Subsequently, DNA was extracted from the collected samples, and the mitochondrial cytochrome C oxidase (COI) gene was amplified using appropriate methods. RESULTS: The analysis of DNA sequences obtained from the COI gene revealed significant genetic distinctions between H. brittani and H. atukorali. The genetic distance values between these two species ranged from 3.21 to 3.63%, clearly indicating that these two species are genetically separate entities. The study successfully established the phylogenetic relationships between H. brittani and H. atukorali based on the COI gene sequences, further confirming the validity of H. brittani as a distinct and separate species. CONCLUSION: The findings of this study conclusively demonstrate that H. brittani is a valid and separate species, distinct from H. atukorali. The genetic analysis based on mitochondrial COI gene sequences provided strong evidence for the differentiation between these two species. The molecular data generated in this research can be used to identify H. brittani quickly and accurately in the future.

Identifying potential immuno-oncology targets in salivary gland mucoepidermoid carcinoma based on inflammatory status and treatment response.

BACKGROUND: Mucoepidermoid carcinoma is a rare salivary gland malignant tumour. This study aimed to investigate inflammatory and immune signatures of mucoepidermoid carcinoma by identifying potential proteo-transcriptomic biomarkers towards the development of precision immuno-oncology treatment strategies. METHODS: A total of 30 biopsies obtained from patients diagnosed with mucoepidermoid carcinoma between 2013 and 2022 were analysed after H&E staining for scoring of histological inflammatory stroma subtypes and inflammatory hotspots with QuPath. Multiplex immunofluorescence staining and NanoString nCounter PanCancer IO 360™ panel were used to assess stroma and tumour inflammation signatures in high grade mucoepidermoid carcinoma cases in the tumour microenvironment via proteomics and transcriptomics, respectively. RESULTS: Inflammatory cells within the histological inflammatory stroma inflammatory (HIS-INF/hot) tumour neighbourhoods were greater compared to the histological inflammatory stroma-immune desert (HIS-ID/cold) (p = 0.001). A similar trend was observed between treatment non-responders and responders in stroma neighbourhoods (p = 0.0625) and in stroma-to-interface inflammatory hotspots (p = 0.0081), indicating an augmented inflammatory response in hot tumours and non-responders. Furthermore, there were striking differences in the expression of pan-immune leukocyte marker CD45 between responders and non responders particularly in the tumour neighbourhoods (p = 0.0341), but such were not robust for PD-1 and macrophage fractions. Additionally, transcriptomic analysis revealed key differences in leukocyte activation profiles between responders and non-responders. CONCLUSION: This preliminary report unveils the importance of assessing immune leukocyte cellular fractions and pathways for future prognostic biomarker discoveries in mucoepidermoid carcinoma as per the involvement of CD45-driven inflammatory and immune mediators in high grade mucoepidermoid carcinoma in non-responders to treatment. These findings will potentially contribute to the development of novel personalised immunotherapies.

Bio-waste mediated synthesis of zirconium nanoparticle fuel: Energy management strategy for performance evaluation in a diesel engine.

The impact of biosynthesized zirconium nanoparticles originated from biological waste, blended in diesel fuel processed through bio-refining strategy and its combustion, emissions, and overall diesel engine performance towards safety has been examined. Different weight fractions of zirconia nanoparticles were combined with crude diesel at 10, 20, and 30 mg/L values. According to the engine tests, Zirconia (20 nm) added to pure diesel at a concentration of 30 parts per million incremented thermal efficiencies by 4.9% compared to regular diesel fuel. The average reduction in specific fuel consumption for clean diesel fuel when the engine was operating at full power was 2.9%, 3.9%, and 4.9%. Diesel smoke, hydrocarbon, CO, and NOx emissions were reduced by 13%, 20%, 25%, and 29%, respectively, when nano additives were used at a concentration of 30 ppm.Nanoparticles enhance fuel stability, overcome detonation difficulties, and avoid fouling spark plugs. The pressure within cylinder, the temperature, and the rate at which heat is released was improved when alumina nanoparticles were appended to diesel fuel. However, both the length of the combustion and further delay in ignition were cut down. The ideal concentration of zirconia nanoparticles for improving combustion, efficiency, and emissions along with safety attainment in an internal combustion engine is recorded at 30 ppm.

Adsorptive removal of acid blue dye 113 using three agricultural waste biomasses: The possibility of valorization by activation and carbonization - A comparative analysis.

The presence of various organic and inorganic contaminants in wastewater leads to serious health effects on humans and ecosystems. Industrial effluents have been considered as noticeable sources of contaminating water streams. These effluents directly liberate the pollutants such as dye molecules and heavy metal ions into the environment. In the present study, three biowaste materials (groundnut shell powder, coconut coir powder and activated corn leaf carbon) were utilized and compared for the removal of acid blue dye 113 from aqueous solutions. The characterization study of newly prepared sorbent material (H3PO4-activated corn leaf carbon) and the other utilized sorbents was carried out by Scanning Electron Microscope (SEM) and Fourier Transform Infrared Spectrophotometer (FTIR), along with Energy Dispersive X-Ray (EDX) Analysis. The influence of experimental conditions such as pH, initial dye concentration, temperature, contact time, and sorbent dosage on the removal efficiency of the dye were appraised. The adsorption isotherm and kinetic result of acid blue dye 113 adsorption onto the sorbents best obeyed from Sips and pseudo-second-order kinetic model. Overall, the outcomes confirmed that the newly synthesized sorbent material (carbonized H3PO4-activated corn leaf) has superior adsorption capacity, rapid adsorption, and higher suitability for the removal of toxic dyes from the contaminated waters.

Deep insights into kinetics, optimization and thermodynamic estimates of methylene blue adsorption from aqueous solution onto coffee husk (Coffee arabica) activated carbon.

In the current study, an attempt was made to synthesize coffee husk (CH) activated carbon by chemical modification approach (sulphuric acid-activated CH (SACH) activated carbon) and was used as a valuable and economical sorbent for plausible remediation of Methylene blue (MB) dye. Batch mode trials were carried out by carefully varying the batch experimental variables: SACH activated carbon (SACH AC) dosage, pH, initial dye concentration, temperature, and contact time. The optimum equilibrium time for adsorption by SACH activated carbon was obtained as 60 min, and the maximum adsorption took place at 30 °C. Morphological and elemental composition, crystallinity behaviour, functional groups, and thermal stability were examined using SEM with EDX, XRD, FTIR, BET, TGA, and DTA and these tests showed successful production of activated carbon. The outcomes showed that chemical activation enhanced the number of pores and roughness which possibly maximized the adsorptive potential of coffee husk. The Box-Benken design (BBD) was used to optimize the MB dye adsorption studies and 99.48% MB dye removed at SACH AC dosage of 4.83 g/L at 30 °C for 60 min and pH 8.12, and the maximum adsorption was yielded for sulphuric acid-activated coffee husk carbon carbon with 88.1 mg/g maximum MB adsorption capacity. Langmuir- Freundlich model deliberately provided a better fit to the equilibrium data. The SACH AC-MB dye system kinetics showed a high goodness-of-fit with pseudo second order model, compared to other studied models. Change in Gibbs's free energy (ΔGo) of the system indicated spontaneity whereas low entropy value (ΔSo) suggested that the removal of MB dye on the SACH activated carbon was an enthalpy-driven process. The exothermic nature of the sorption cycle was affirmed by the negative enthalpy value (ΔHo). The adsorptive-desorptive studies reveal that SACH AC could be restored with the maximum adsorption efficiency being conserved after the fifth cycles. Overall, the outcomes revealed that sulphuric acid-activated coffee husk activated carbon (SACH AC) can be used as prompt alternative for low-cost sorbent for treating dye-laden synthetic wastewaters.

Evaluation of effects of temperature and humidity on the secondary structure of Ganirelix in an injectable formulation and comparison with Orgalutran® using circular dichroism spectroscopy.

Ganirelix, a drug used in in vitro fertilization (IVF), prevents ovulation in women who are not ready to have children by inhibiting a gene that produces gonadotropin. Peptides are macromolecules that are able to preserve a predetermined shape while carrying out the structural and regulatory roles for which they were originally intended. Peptide structures can be altered in the production and storage processes. Therapeutic peptides' biological activity can be drastically altered by even small modifications in their primary and secondary structures. The molecules' secondary structures can be monitored by subjecting them to different processing or storage conditions. In our investigation, we used circular dichroism (CD) spectroscopy with two different software programs for secondary structure evaluation to look at how environmental factors like temperature and humidity affected the secondary structure of Ganirelix in an injectable formulation. The CD results revealed that the alpha-helical (regular and distorted), beta-sheet, beta-strands (regular and distorted), beta-turn, and random coil structures of temperature and humidity stressed generic drug products are comparable to reference-listed drug.

A Radiative Chemical Process for the Methylene Blue Degradation by Natural Convective Nanofluid Flow over an Upright Cone.

An upstraight cone with nonisothermal surface velocity, temperature, and concentration was investigated using a numerical solution approach to simulate MHD, MB dye, and various nanofluid flows. Numerical evaluation of the flow field equation was carried out using an excellent finite difference method after it has been converted into a dimensionless form. Different heat transfer occurrences were observed depending on temperature, velocity, and concentration when using several types of nanofluids (TiO, Ag, Cu, and Al2O3Z3). The amount of MB dye that was degraded by the synthesized nanofluids under the influence of sunlight irradiation was 81.40 percent as a catalyst (carbon nanodots). The parametric analysis of various features of flow fields has been shown using graphs. It was observed that heat is generated from the cone during the sun light irradiation reaction, heat is transferred to MB dye containing nanofluids, and heat interacts with nanofluids and is involved in the chemical reaction with the assistance of electrons. As MB dye degrades in the absence of catalysts (carbon nanodots), it is only 52 percent effective. MB dye is degraded at 81.40 percent, then becomes stable, and takes 120 minutes to degrade in nanofluids containing MB dye with catalysts (carbon nanodots).

Imaging of central nervous system emergencies in oncology.

Central nervous system (CNS) may be predisposed to devastating complications in cancer patients which may add to morbidity and mortality in this group. Majority of the complications are vascular in nature due to the altered coagulation profile and pro-inflammatory state in these patients. However, there are a host of other conditions which may affect the clinical course of these patients including metabolic and toxic encephalopathies, infections, and paraneoplastic syndromes. Moreover, multimodality management of these patients, which is often used in majority of the cancers, exposes them to treatment related complications. This pictorial review aims to enlighten the reader regarding the various complications affecting the CNS as seen at our tertiary cancer care institute. We aim to highlight the emergent nature of these complications and the need to identify them quickly and accurately on imaging which helps to institute early appropriate management and prevents further morbidity and mortality.

EUS versus MRCP to perform ERCP in patients with intermediate likelihood of choledocholithiasis: a randomised controlled trial.

OBJECTIVE: In patients with an intermediate likelihood of choledocholithiasis, European Society of Gastrointestinal Endoscopy (ESGE) guidelines recommend endoscopic ultrasound (EUS) or magnetic resonance cholangiopancreatography (MRCP) to diagnose choledocholithiasis to make the indication for endoscopic retrograde cholangiopancreatography (ERCP) treatment; there is no randomised control trial to compare both in this setting. DESIGN: Patients with suspected choledocholithiasis satisfying ESGE guideline's intermediate likelihood were screened for this single-centre randomised controlled trial between November 2019 and May 2020. The enrolled patients were randomised to either EUS or MRCP. ERCP was performed in stone positive cases or if clinical suspicion persisted during follow-up. Negative cases underwent a further 6-month clinical follow-up. Main outcome was accuracy (sensitivity/specificity) of both tests to diagnose choledocholithiasis, with ERCP or follow-up as a gold standard. RESULTS: Of 266 patients, 224 patients (mean age: 46.77±14.57 years; 50.9 % female) were enrolled; overall prevalence of choledocholithiasis was 49.6%, with a higher frequency in the MRCP group (63/112 vs 46/112 for EUS). Both sensitivity of EUS and MRCP were similarly high (92%-98%), without significant differences between the two groups. The negative predictive value and likelihood ratio + were significantly higher in EUS arm (p<0.05). The percentage of ERCPs either incorrectly halted back (false negatives: EUS: 2 vs MRCP: 5) or performed unnecessarily (false positives: EUS: 1 vs MRCP: 2) was low in both groups. CONCLUSION: The performance parameters of both EUS and MRCP are comparable for detecting choledocholithiasis in the intermediate-risk group of choledocholithiasis and the choice of a test should be based on local expertise, availability of resources and patient preference. TRIAL REGISTRATION NUMBER: NCT04173624.

Radiosynthesis and evaluation of [11C]AG-488, a dual anti-angiogenetic and anti-tubulin PET ligand.

Combinations of antiangiogenic and cytotoxic agents show promising results in the treatment of cancer. However, there is a lack of single agent with both antiangiogenic and cytotoxic activities for clinical application. AG-488 aka FLAG-003 is a novel ligand with established antiangiogenetic properties via activation of receptor thymidine kinase (RTK) and anti-tubulin properties in tumor cells. AG-488 is also reported to reduce tumor volume and prolong survival in preclinical animal models of glioblastoma multiforme, breast cancer and is in clinical stage. Higher expression of RTKs and tubulins is reported in various cancers. This study reveals the development of [11C]AG-488, a high affinity dual target inhibitor binding to RTK and anti-tubulin activities. We rationale that antiangiogenic RTK and anti-tubulin activity of [11C]AG-488 may enhance the tumor to tissue ratio, assisting in cancer drug development. [11C]AG-488 was synthesized in 35 ± 5 % radiochemical yield by radiomethylating the corresponding phenolate using [11C]CH3I. MicroPET studies in mice indicated blood-brain barrier penetration of [11C]AG-488 and retention in the brain. However, blocking studies with antitubulin and RTK agent HD-800 and microtubule depolymerizing agent MPC-6827 show increased binding of [11C]AG-488 in brain. The pattern of tracer binding in blocking conditions is similar to the baseline conditions. The higher binding may be due to the increased plasma uptake of radiotracer or the formation of more free tubulins due to microtubule dynamic instability during the blocking conditions.

Geometrical picture of the electron-electron correlation at the large-D limit.

In electronic structure calculations, the correlation energy is defined as the difference between the mean field and the exact solution of the non relativistic Schrödinger equation. Such an error in the different calculations is not directly observable as there is no simple quantum mechanical operator, apart from correlation functions, that correspond to such quantity. Here, we use the dimensional scaling approach, in which the electrons are localized at the large-dimensional scaled space, to describe a geometric picture of the electronic correlation. Both, the mean field, and the exact solutions at the large-D limit have distinct geometries. Thus, the difference might be used to describe the correlation effect. Moreover, correlations can be also described and quantified by the entanglement between the electrons, which is a strong correlation without a classical analog. Entanglement is directly observable and it is one of the most striking properties of quantum mechanics and bounded by the area law for local gapped Hamiltonians of interacting many-body systems. This study opens up the possibility of presenting a geometrical picture of the electron-electron correlations and might give a bound on the correlation energy. The results at the large-D limit and at D = 3 indicate the feasibility of using the geometrical picture to get a bound on the electron-electron correlations.

Surface treated Phoenix sylvestris for bioadsorption of oil from aqueous solution: Isotherms and kinetic studies.

Biosorption is a versatile technique of removing the oil spill - one of the major toxicants that causes water pollution, which threatens the ecological balance of the aquatic ecosystem. The proposed research aims in developing a viable adsorbent from discarded agricultural waste, Phoenix sylvestris, which was surface altered, assessed and utilised as a biosorbent for the effective removal of diesel from aqueous solution in batch adsorption trials. Waste palm leaves, Phoenix sylvestris (RPS)was physically (PMPS) and chemically modified (CMPS) to adsorb diesel in the emulsion. The synthesised materials were characterised by FTIR, SEM, and EDS, confirming a well-defined microporous structure consisting of ionisable groups. The studies indicated optimised conditions of 10 g, 4.5 g and 2 g of RPS, PMPS and CMPS respectively at 303K for an optimised adsorption time of 60 min. Freundlich isotherm agreed well with experimental data, and the kinetic mechanism claimed better results with RPS, PMPS and CMPS for Pseudo first-order model. The adsorbents could be reused five times without much loss of efficiency. From the performed studies, it can be inferred that good adsorption capacities at optimised conditions followed the order of CMPS > PMPS > RPS. Thermodynamic analysis proved the feasibility of such biosorption with exothermic nature predicting spontaneous attraction of oil components to the surface of PMPS and CMPS. Moreover, the density of the CMPS layer rendered proven results for such biosorption displaying a hyperbolic dependency assuring its efficacy. Hence, it can be concluded that the prepared adsorbent from Phoenix sylvestris, an agricultural waste, possess good adsorptive properties.