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Hepatic angiosarcoma is an uncommon primary malignancy of the liver. It carries a poor prognosis because of very aggressive nature of the tumor. Clinical presentation of hepatic angiosarcoma is variable, most common being hepatomegaly or abdominal mass. Here we report a case of primary hepatic angiosarcoma presented with spontaneous rupture and hemoperitoneum, which was managed successfully by transarterial embolization. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the best non-contrast magnetic resonance imaging (MRI) sequence and role of intravenous contrast administration in preoperative characterization and classification of perianal fistulae, keeping surgery as gold standard. Methods: This prospective study comprised of forty-five consecutive patients with actively draining external perianal opening. MRI was performed on a 1.5 T scanner using non-contrast and contrast enhanced sequences in multiple planes. St. James's University Hospital MRI based classification system was used to classify the fistulae into five grades. Taking surgery as gold standard, association between surgical and MRI findings was statistically analysed. Results: Of the 45 patients recruited, forty were deemed eligible for inclusion. Mean age was 39.7 ± 11.7 years with male preponderance (M: F = 8:1). Commonest type was Grade 1 (40%). The best sequences in terms of overall accuracy were axial & coronal planes of contrast enhanced fat suppressed (FS) T1W turbo spin echo (TSE) (95.7%) followed by FS T2W TSE (94.1%) while sagittal T2W TSE sequence with or without fat suppression had the lowest accuracy (90.13%). The difference in overall diagnostic accuracy of FS T2W TSE and contrast enhanced FS T1W TSE sequence for evaluating perianal fistula was not statistically significant (p = 0.52). However, contrast study had a better accuracy in detecting internal openings and secondary tract of recurrent/ post-operative cases. Conclusion: Best non-contrast MRI sequence is FS T2W TSE (axial and coronal). Non-contrast MRI is equally efficient to contrast study while evaluating primary/previously unoperated cases thereby eliminating the role of contrast in such cases. However, intravenous contrast should be administered for evaluating post-operative cases with recurrence. [ABSTRACT FROM AUTHOR]

• A thermodynamic model has been developed for rare earth elements in the presence of hydroxide, acetate, citrate and oxalate ions. • Speciation and solubility are simultaneously reproduced. • Effects of pH, temperature and complexation on solubility are accurately reproduced. • Effect of crystallinity on REE hydroxide solubility is modeled for limiting cases of crystalline and amorphous hydroxides. A thermodynamic model has been developed for calculating speciation and phase equilibria in aqueous solutions of rare earth elements (REEs) with hydroxide, acetate, citrate, and oxalate anions. The computational framework is based on the Mixed-Solvent Electrolyte (MSE) framework, which has been previously used to establish a systematic treatment of binary and multicomponent systems containing REE sulfates and chlorides up to solid–liquid saturation at temperatures up to 300 °C. The model has been parametrized by performing a multi-property analysis of critically evaluated speciation and solubility data. For rare earth hydroxides, a comprehensive model has been developed for fourteen REEs (i.e., for yttrium and all lanthanides except promethium). The effect of the crystallinity of rare earth hydroxides on their solubility has been analyzed. Model parameters have been determined for two limiting cases, i.e., for crystalline and amorphous hydroxides, while recognizing that the hydroxides may span a range of degrees of crystallinity. For the organic ligands, the model has been established for neodymium with additional analysis for other selected REEs. The model accurately reproduces the effects of pH, temperature, and complexation with organic ligands on the behavior of rare earth elements in aqueous solutions. When coupled with previously developed models for inorganic rare earth salts, it provides a thermodynamic tool for the design and optimization of separation processes for the production and recycling of REEs and for predicting the properties of REEs in geological and biological settings. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • MSE model reproduces properties of multicomponent systems containing REE sulfates. • Phase behavior and caloric properties are predicted for REE 2 (SO 4) 3 and Na 2 REE 2 (SO 4) 4. • SLE phase diagrams elucidate the solubility of both stable and metastable phases. • Regularities in solubilities are identified as a function of the REE cation radius. • REE 2 Na 2 (SO 4) 4 show a V-shaped solubility pattern with a local minimum for Pr. Abstract A thermodynamic model has been developed for calculating the phase behavior and caloric properties of rare earth elements in multicomponent sulfate solutions over wide ranges of temperature (up to 300 °C) at concentrations extending to solid–liquid saturation. The model has been constructed using the previously developed Mixed-Solvent Electrolyte (MSE) framework, which combines the standard-state thermochemical properties of aqueous and solid species with an ion-interaction formulation for the excess Gibbs energy. The model accurately reproduces the properties of binary aqueous rare earth sulfate solutions and multicomponent systems that include sulfuric acid and/or sodium sulfate. Solid-liquid phase diagrams have been constructed to elucidate the solubility of both stable and metastable solid phases. Regularities in the solubility behavior have been identified as a function of the cation radius for rare earth sulfates and double sodium-rare earth sulfate salts. The solubility of rare earth sulfates at ambient conditions shows an s-shape pattern with a local maximum at Pr, followed by a plateau between Sm and Tb and then an increase starting from Tb. On the other hand, the double salts REE 2 Na 2 (SO 4) 4 show a solubility minimum at Pr, followed by a strong increase in solubility for heavier rare earths. For the double sulfate salts for which no experimental data are available, solubilities have been estimated using an analysis of trends in thermochemical properties across the lanthanide series. The model is part of a systematic effort to develop a comprehensive treatment of the properties of rare earth salt solutions to facilitate the design and optimization of processes for the recovery of rare earth elements. [ABSTRACT FROM AUTHOR]

An indole-rich tripodal microtubule inhibitor is designed, which binds at the DCVJ site of tubulin and inhibits its polymerization. It causes apoptotic death of cancer cells without affecting normal cells and inhibits the growth of tumors. Finally, STD-NMR and TR-NOESY experiments reveal that the indole appendages play a crucial role in interacting with tubulin. [ABSTRACT FROM AUTHOR]

We apply the SAFT-VR+DE equation of state to the study of experimental mixed-solvent electrolyte solutions. In the non-primitive model based SAFT-VR+DE approach (Zhao et al., JCP 2007, 126 , 244503) the ions are considered fully dissociated within the solvent that is explicitly treated within the model and the theoretical framework. Typically in the study of electrolyte systems the simpler primitive model is used, which requires knowledge of the experimental dielectric constant. With the non-primitive model the dielectric constant is calculated as part of the theory, which is a particularly attractive feature in the study of mixed-solvent electrolyte systems as data for the experimental dielectric constant of such systems is more scarce. Here for the first time as far as the authors are aware, a non-primitive based equation of state has been used for the study of mixed-solvent electrolytes. The solvents considered (water, methanol and ethanol) are modeled using the SAFT-VR+D approach (Zhao et al., JCP 2007, 127 , 084514; Zhao et al., JCP 2006, 125 , 104504) in which the contribution of the dipole to the thermodynamics and structure of the fluid are explicitly accounted for. The theory is found to accurately predict the vapor-liquid equilibrium, as well as dielectric properties of the salt free alcohol-water mixtures both at room and elevated temperatures. Ternary mixtures of salt/water/alcohol are then studied using the SAFT-VR+DE parameters for the salts determined in earlier work (Das et al., AIChE Journal 2015, 61 , 3053-3072) and a cation-alcohol unlike dispersive energy parameter obtained by fitting to mean ionic activity coefficient data at room temperature and pressure. Thus, with only one adjustable parameter, a predictive SAFT-VR+DE equation to study mixed-solvent electrolyte systems is developed. The SAFT-VR+DE predictions are found to be in good quantitative agreement with mean ionic activity coefficient data for several mixed-solvent electrolyte systems over a wide range of molalities and different solvent ratios. The model is parameterized to allow the molecular level interactions between different cations and the surrounding solvent molecules to be explored. [ABSTRACT FROM AUTHOR]

A model has been developed for calculating thermodynamic properties and phase equilibria in binary and multicomponent aqueous systems containing rare earth element chlorides. Here, the rare earth elements encompass the lanthanides except promethium plus yttrium. The model is based on a comprehensive database of solid-liquid equilibria, osmotic and activity coefficients, enthalpies of dilution and heat capacities of solutions. The computational framework relies on the previously developed Mixed-Solvent Electrolyte (MSE) model. The model accurately reproduces the properties of binary rare earth chloride – water systems and of ternary mixtures that additionally include HCl, NaCl, or CaCl 2 . Solid-liquid phase diagrams have been obtained to provide a convenient summary of the solubility of stable and metastable hydrated solid phases. Analysis of the stability of solid hydrates reveals systematic trends within the rare earth series. At ambient and elevated temperatures, the calculations show an increase in the stability range of rare earth chloride hexahydrates with decreasing cation radius, accompanied by a gradual disappearance of the heptahydrate. At low temperatures, the stable solid phases transition from the decahydrate at higher cation radii to octahydrate in an intermediate range and a combination of pentadeca- and nonahydrates at lower radii. The calculated standard-state enthalpies of formation of the hydrates agree with independently obtained values from calorimetric measurements, thus verifying the internal consistency of the model. [ABSTRACT FROM AUTHOR]

Introduction: Traditional transthoracic oesophagectomy is associated with high perioperative morbidity. Minimally Invasive Oesophagectomy (MIE) techniques have been shown to have a decreased incidence of respiratory complications and an improvement in perioperative outcomes, such as length of hospital stay and wound infection rates. Aim: To evaluate the incidence of postoperative respiratory complications, 30-day mortality, and length of hospital stay among patients with carcinoma of the oesophagus undergoing, Video-Assisted Thoracoscopic Surgery (VATS) oesophagectomy. Materials and Methods: A cross-sectional study was conducted in the Department of Anaesthesiology in a new thoracic oncology unit at a Tertiary Cancer care centre, Dr. B. Borooah Cancer Institute, Guwahati, Assam, India. A total of 67 patients with resectable oesophageal cancer who underwent VATS oesophagectomy from September 2019 to December 2021 were included. Patients who had surgery by open thoracotomy and inoperable cases were excluded. The patients' clinicodemographic profile, intra- and postoperative variables, and complications were studied. Descriptive statistics were used for analysis. A p-value ≤0.05 was considered statistically significant at a 5% level of significance. Results: Out of 67 patients, 45 (67.2%) were male, and 22 (32.8%) were female. The age ranged from 33 to 78 years with a median age of 55 years (IQR 47-61). The median body weight was 45 kg (IQR 42-53). Nineteen (28.4%) patients developed postoperative complications, including respiratory distress in 7 (10.4%) and anastomotic leakage in 5 (7.5%) patients. Other complications included symptomatic Coronavirus Disease 2019 (COVID-19) infection, pneumonia, mediastinitis, Multiorgan Dysfunction Syndrome (MODS) with sepsis, seizure and cardiac arrest, and surgical re-exploration. The 30-day mortality was 2.98%. The median length of hospital stay was 19 days (Interquantile Range (IQR) 16-22), which was higher in those with complications (p<0.001). One-lung ventilation was associated with a higher risk of postoperative respiratory complications (p=0.077). Conclusion: VATS oesophagectomy, even in a new thoracic oncology unit, was associated with lower perioperative complications, a shorter hospital length of stay, and decreased mortality compared to historical controls. [ABSTRACT FROM AUTHOR]

The SAFT-VR+DE approach was developed by combining the statistical associating fluid theory for potentials of variable range (SAFT-VR) with integral equation theory and the generalized mean spherical approximation using a non-primitive model, in order to explicitly describe the solvent in electrolyte solutions. Subsequently, the theory was applied to study nineteen different aqueous electrolyte solutions and a range of thermodynamic properties across different temperatures and salt concentrations were successfully predicted. Here, the theory is applied to study several model mixed dipolar solvent electrolytes in order to validate a simple one-fluid-like approximation that is proposed to describe the interactions between ions and dipolar solvents of arbitrary size and dipole moment. Before application to real fluids the approach is extensively tested through comparison with isothermal-isobaric ensemble (NPT) Monte Carlo simulations for a number of model mixed dipolar solvent electrolyte systems. Simulations have been performed for different ionic concentrations, solvent compositions, cation, anion, and solvent segment diameters, and solvent polarity. The results show that the SAFT-VR+DE equation provides a good description of the PVT behavior of the model mixed solvent electrolyte systems studied, with some over-prediction of the PVT behavior observed only at higher ionic concentrations. Additionally, comparisons are made between predictions from the non-primitive and primitive models for electrolytes and the importance of capturing the effect of ions on the solvent dielectric is demonstrated. [ABSTRACT FROM AUTHOR]

The vapor pressure of four liquidperfluoroalkylalkanes(CF3(CF2)n(CH2)mCH3; n= 3, m= 4,5,7; n= 5, m= 5) was measured as a function of temperature between278 and 328 K. Molar enthalpies of vaporization were calculated fromthe experimental data, and the results were compared with data fromthe literature for the corresponding alkanes and perfluoroalkanes.The heterosegmented statistical associating fluid theory was usedto interpret the results at the molecular level both with and withoutthe explicit inclusion of the dipolar nature of the molecules. Additionally,ab initio calculations were performed for all perfluoroalkylalkanesstudied to determine the dipole moment to be used in the theoreticalcalculations. We demonstrate that the inclusion of a dipolar termis essential for describing the vapor–liquid equilibria ofperfluoroalkylalkanes. It is also shown that vapor–liquidequilibria in these compounds result from a subtle balance betweendipolar interactions, which decrease the vapor pressure, and the relativelyweak dispersive interactions between the hydrogenated and fluorinatedsegments. [ABSTRACT FROM AUTHOR]

Summary Dopaminergic neurons provide value signals in mammals and insects [ 1–3 ]. During Drosophila olfactory learning, distinct subsets of dopaminergic neurons appear to assign either positive or negative value to odor representations in mushroom body neurons [ 4–9 ]. However, it is not known how flies evaluate substances that have mixed valence. Here we show that flies form short-lived aversive olfactory memories when trained with odors and sugars that are contaminated with the common insect repellent DEET. This DEET-aversive learning required the MB-MP1 dopaminergic neurons that are also required for shock learning [ 7 ]. Moreover, differential conditioning with DEET versus shock suggests that formation of these distinct aversive olfactory memories relies on a common negatively reinforcing dopaminergic mechanism. Surprisingly, as time passed after training, the behavior of DEET-sugar-trained flies reversed from conditioned odor avoidance into odor approach. In addition, flies that were compromised for reward learning exhibited a more robust and longer-lived aversive-DEET memory. These data demonstrate that flies independently process the DEET and sugar components to form parallel aversive and appetitive olfactory memories, with distinct kinetics, that compete to guide learned behavior. [ABSTRACT FROM AUTHOR]

Abstract: In recent work, the GC-SAFT-VR equation, which combines the SAFT equation for potentials of variable range (VR) with a group contribution (GC) approach, was proposed. Parameters for key functional groups (such as CH3, CH2, CH, CH2 CH, C O, C6H5, ether, ester, OH, NH2, CH O, COOH) were obtained by fitting to experimental vapor pressure and saturated liquid density data for selected low molecular weight fluids and then used to predict the phase behavior of both pure non-associating and associating fluids and their mixtures, generally without adjusting the group parameters to binary mixture data. In the GC-SAFT-VR approach the benzene ring was modeled as a single group (C6H6 for benzene and C6H5, for alkylbenzenes) however, in common with other group-contribution based SAFT approaches, this approach fails to reproduce the correct curvature seen in the experimental liquid density of alkylbenzenes. In this work, to improve upon the model adopted for ring molecules, the benzene ring is explicitly considered through the connectivity of several smaller groups to more accurately capture the π–π interactions. We demonstrate that the improved model better captures the curvature present in the experimental saturated liquid density data of pure alkylbenzenes. Additionally, mixtures of several non-associating and associating fluids with benzene and alklybenzenes are studied. [Copyright &y& Elsevier]

Background: Maintaining the correct balance of proliferation versus differentiation in retinal progenitor cells (RPCs) is essential for proper development of the retina. The cell cycle regulator cyclin D1 is expressed in RPCs, and mice with a targeted null allele at the cyclin D1 locus (Ccnd1-/ -) have microphthalmia and hypocellular retinas, the latter phenotype attributed to reduced RPC proliferation and increased photoreceptor cell death during the postnatal period. How cyclin D1 influences RPC behavior, especially during the embryonic period, is unclear. Results: In this study, we show that embryonic RPCs lacking cyclin D1 progress through the cell cycle at a slower rate and exit the cell cycle at a faster rate. Consistent with enhanced cell cycle exit, the relative proportions of cell types born in the embryonic period, such as retinal ganglion cells and photoreceptor cells, are increased. Unexpectedly, cyclin D1 deficiency decreases the proportions of other early born retinal neurons, namely horizontal cells and specific amacrine cell types. We also found that the laminar positioning of horizontal cells and other cell types is altered in the absence of cyclin D1. Genetically replacing cyclin D1 with cyclin D2 is not efficient at correcting the phenotypes due to the cyclin D1 deficiency, which suggests the D-cyclins are not fully redundant. Replacement with cyclin E or inactivation of cyclin-dependent kinase inhibitor p27Kip1 restores the balance of RPCs and retinal cell types to more normal distributions, which suggests that regulation of the retinoblastoma pathway is an important function for cyclin D1 during embryonic retinal development. Conclusion: Our findings show that cyclin D1 has important roles in RPC cell cycle regulation and retinal histogenesis. The reduction in the RPC population due to a longer cell cycle time and to an enhanced rate of cell cycle exit are likely to be the primary factors driving retinal hypocellularity and altered output of precursor populations in the embryonic Ccnd1-/- retina. [ABSTRACT FROM AUTHOR]

o‐Aminoazotoluene (OAT), capable of photoisomerization, and o‐vanillin, a potent comutagen, have been used to synthesize a new ligand, HL, [C6H4(CH3)N=NC6H3(CH3)N=CHC6H3(OH)(OCH3)], which, upon complexation with copper(II), results in a new copper(II) complex‐Cu(L)2, [Cu{C6H4(CH3)N=NC6H3(CH3)N=CHC6H3(OCH3)O}2]. Both HL and Cu(L)2 have been characterized by single‐crystal X‐ray diffraction measurements along with other analytical techniques, for example, IR spectroscopy, NMR spectroscopy, UV–Vis spectroscopy, elemental analysis and mass spectrometry. These compounds were tested with different in vitro anticancer assay as well as with in silico studies. A comparative study has been demonstrated on anticancer activity of HL and Cu(L)2 with the ligand HAZ, {C6H5N=NC6H4N=CHC6H3(OH)(OCH3)} and its Cu‐complex, [Cu(AZ)2, Cu{C6H5N=NC6H4N=CHC6H3(OCH3)O}2]. The sensing properties of HAZ, along with the synthesis and structural properties of both HAZ and Cu(AZ)2, have been reported by our group earlier. Cytotoxicity measurements on MCF7 cell lines show that Cu(L)2 and Cu(AZ)2 have higher anticancer activity than their corresponding ligands. The apoptotic effect of Cu‐complex was studied through nuclear fragmentation assay and AO/EB dual‐staining assay on MCF7 cell line. The IC50 value of Cu(L)2 in 0.01% DMSO/water after 24‐h treatment was found 4.2 μM, which is one of the lowest values with this response time compared to the other analogous anticancer compounds. Finally, we have evaluated the expression of hERα protein with respect to Cu‐complexes, and it was observed that Cu(L)2 caused more down‐regulation of hERα as compared to Cu(AZ)2. [ABSTRACT FROM AUTHOR]

Background: Population-based cancer survival is a key indicator for assessing the effectiveness of cancer control by a health care system in a specific geographic area. Breast cancer is the most common cancer among women in India, accounting for over one quarter of all female cancers. The objective of this study was to estimate the 5-year survival of female patients who were diagnosed with breast cancer between 2012 and 2015 from the existing Population-Based Cancer Registries (PBCRs) in India. Methods: In total, 17,331 patients who had breast cancer diagnosed between 2012 and 2015 from 11 PBCRs were followed until June 30, 2021. Active methods were used to track the vital status of registered breast cancer cases. The study conducted survival analysis by calculating the difference between the date of first diagnosis and the date of death or censoring to estimate observed survival and relative survival using the actuarial survival approach and the Ederer-II approach, respectively. Results: The 5-year age-standardized relative survival (95% confidence interval [CI]) of patients with breast cancer was 66.4% (95% CI, 65.5%-67.3%). Mizoram (74.9%; 95% CI, 68.1%-80.8%), Ahmedabad urban (72.7%; 95% CI, 70.3%-74.9%), Kollam (71.5%; 95% CI, 69.2%-73.6%), and Thiruvananthapuram (69.1%; 95% CI, 67.0%-71.2%) had higher survival rates than the national average. Conversely, Pasighat had the lowest survival rate (41.9%; 95% CI, 14.7%-68.6%). The 5-year observed survival rates for localized, regional, and distant metastasis in the pooled PBCRs were 81.0%, 65.5%, and 18.3%, respectively. Conclusions: The overall disparity in survival rates was observed across 11 PBCRs, with lower survival rates reported in Manipur, Tripura, and Pasighat. Therefore, it is imperative to implement comprehensive cancer control strategies widely throughout the country. [ABSTRACT FROM AUTHOR]

Isomerization of aspartate to isoaspartate (isoAsp) on aging causes protein damage and malfunction. Protein- L -isoaspartyl methyltransferase (PIMT) performs a neuroprotective role by repairing such residues. A hexapeptide, Val-Tyr-Pro-(isoAsp)-His-Ala (VA6), a substrate of PIMT, is shown to form fibrils, while the normal Asp-containing peptide does not. Considering the role of PIMT against epileptic seizure, the combined effect of PIMT and two antiepileptic drugs (AEDs) (valproic acid and stiripentol) was investigated for anti-fibrillation activity. Structural/functional modulations due to the binding of AEDs to PIMT were investigated using biophysical techniques. Thioflavin T (ThT) fluorescence assay and microscopic methods were employed to study fibril formation by VA6. In vitro experiments with PC12 cells were carried out with PIMT/AEDs. ThT assay indicated reduction of fibrillation of VA6 by PIMT. AEDs stabilize PIMT, bind close to the cofactor binding site, possibly exerting allosteric effect, increase the enzymatic activity, and anti-fibrillation efficacy. Furthermore, Aβ42, implicated in Alzheimer's disease, undergoes β-sheet to α-helix transition in presence of PIMT. Studies with PC12 derived neurons showed that PIMT and PIMT/AEDs exerted neuroprotective effect against anti-NGF induced neurotoxicity. This was further validated against neurotoxicity induced by Aβ42 in primary rat cortical neurons. The study provides a new perspective to the role isoAsp in protein fibrillation, PIMT in its prevention and AEDs in enhancing the activity of the enzyme. IsoAsp, with an additional C atom in the main-chain of polypeptide chain, may make it more susceptible to fibrillation. PIMT alone, or in association with AEDs prevents this. Unlabelled Image • An isoAsp-containing hexapeptide, but not the corresponding one with Asp, forms fibril. • PIMT, the ubiquitous repair enzyme shows anti-fibrillation property. • Anti-fibrillation activity is enhanced in presence of AEDs. • Neuroprotective role against anti-NGF induced neurotoxicity was shown in PC12 cells. • IsoAsp, a β-amino acid, may be more prone to fibrillation than the α-amino acid. [ABSTRACT FROM AUTHOR]

Malignant tumor cells go through morphological and gene expression alterations, including rearrangement of cytoskeleton proteins that promote invasion and metastasis. Microtubules form a major cytoskeleton component that plays a significant role in regulating multiple cellular activities and function depending on the presence of posttranslational modification (PTM). Acetylation is a type of PTM that generally occurs in the lysine 40 region of α‐tubulin and is known to be critically associated with cancer metastasis. Current evidence demonstrates that noncoding RNAs, such as long noncoding RNA (lncRNA) and microRNA (or miRNA), which are correlated with gene regulation modulate the expression of acetylated tubulin in the development and metastasis of cancer. This review provides an overview about the role of lncRNA and miRNA in regulation of tubulin acetylation in various types of cancer. Significance statement: Tubulin acetylation is one of the primary factors contributing to cancer progression and metastasis. It is commonly observed in various cancers like breast cancer, lung cancer, nasopharyngeal carcinoma, and pancreatic cancer. Through the different courses of cancer development, lncRNA and microRNA regulate the expression of this tubulin acetylation. In spite of a number of research studies reporting relationships of various lncRNAs and microRNAs with Tubulin acetylation, a comprehensive review highlighting their interrelationship has yet not been discussed. Understanding their association in depth will be beneficial in developing new treatments for cancer patients. [ABSTRACT FROM AUTHOR]

Objective: There is increasing adoption of Liver Imaging Reporting and Data System (LI-RADS) treatment response (LR-TR) criteria. However, there is still a relative lack of evidence evaluating the performance of these criteria. We performed this study to assess the diagnostic accuracy of LI-RADS LR-TR criteria. Methods: A thorough search of PubMed, Embase, Scopus, and Cochrane Central Register of Controlled Trials for studies reporting diagnostic accuracy of LI-RADS LR-TR criteria was conducted through 30 June 2020. The meta-analytic summary of sensitivity, specificity, and diagnostic odds ratio of LI-RADS LR-TR criteria was computed using explant histopathology as the reference standard. The quality of the studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Results: Four studies were found eligible for meta-analysis. The total number of LR-TR observations was 462 (240 patients, 82.5% males). Different locoregional therapies (LRTs), including bland embolization, chemoembolization, radiofrequency ablation, and microwave ablation, had been used. The mean time interval between LRT and liver transplantation ranged from 181 to 219 days. There was a moderate to good inter-reader agreement for LR-TR criteria. The pooled sensitivity and specificity of LR-TR criteria for viable disease were 62% (95% CI, 49–74%; I2 = 69%) and 87% (95% CI, 76–93%; I2 = 57%), respectively. The pooled diagnostic odds ratio and area under the curve were 9.83 (95% CI, 5.34–18.08; I2 = 19%) and 0.80. Conclusions: LI-RADS LR-TR criteria have acceptable diagnostic performance for the diagnosis of viable tumor after LRT. Well-designed prospective studies evaluating criteria of equivocal lesions and effect of different LRTs should be performed. Key Points: • The pooled sensitivity and specificity of LI-RADS LR-TR criteria for the diagnosis of viable tumor were 62% and 87%, respectively. • The pooled diagnostic odds ratio and area under the curve were 9.83 and 0.80. • LR-TR criteria had a moderate to good inter-reader agreement. [ABSTRACT FROM AUTHOR]

• New –COOH functionalized POP nanofiber TPDABA was developed via Schieff-based condensation reaction. • POP nanofiber composite UCNPs@TPDABA was synthesized and modified with folic acid for targeted therapy. • High amount of DOX was loaded into UCNPs@TPDABA@FA and shows anticancer effect in lung cancer cells. • Methylene Blue was loaded into UCNPs@TPDABA@FA for singlet oxygen generation upon NIR light excitation via FRET. Covalently linked porous organic polymers featuring a large surface area, low toxicity, and excellent stability is an emerging class of porous material that has drawn immense attention in the area of cancer therapy. However, the development of NIR light excitable nanoscale POP with available surface functional groups for active cancer cell targeting is still a great promise for chemotherapy and PDT. Herein, we have fabricated folic acid (FA) encapsulated upconversion nanoparticle embedded porous organic polymeric nanofiber (POP nanofiber) composite (UCNPs@TPDABA@FA) for cell imaging, targeted drug delivery, and photodynamic therapy. PEI-coated upconversion nanoparticle is attached with imine linked –COOH functionalized POP nanofiber in a single step to achieve highly porous composite UCNPs@TPDABA. Then functionalized folic acid has been attached with the composite which effectively targets cancer cell A549. The composite delivers the anticancer drug DOX and shows significant results for in-vitro lung cancer treatment. Besides the fluorescence imaging property, UCNPs serve as FRET donor to the photosensitizer methylene blue and then generates ROS upon photoexcitation. ROS generation is also detected in A549 cancer cells. So, the smart composite UCNPs@TPDABA@FA could open a new door in serving as an effective carrier for chemotherapeutic drug and PDT. [ABSTRACT FROM AUTHOR]

Identification of key amino acids is required for development of efficient cell-penetrating peptides (CPPs) and has tremendous implications in medicine. Extensive research work has enlightened us about the importance of two amino acids, arginine and tryptophan, in cell penetration. Here, we present a top-down approach to show how spatial positions of two tryptophans regulate the cellular entry and nuclear localization. This enables us to develop short, non-toxic tetrapeptides with excellent potential for cell penetration and nuclear localization. Among them, Glu-Thr-Trp-Trp (ETWW) emerges as the most promising. Results suggest that it enters into cancer cells following an endocytic pathway and binds at the major groove of nuclear DNA, where successive tryptophan plays major role. We subsequently show that it is not a P-glycoprotein substrate and is non-toxic to PC12-derived neurons, suggesting its excellent potential as a CPP. Furthermore, its potential as a CPP is validated in multi-cellular 3D cell culture (spheroid) and in in vivo mice model. This study provides major fundamental insights about the positional importance of tryptophan and opens new avenues toward the development of next-generation CPPs and major-groove-specific anticancer drugs. [ABSTRACT FROM AUTHOR]

Background Approximately 1–2% of all scalp tumours are malignant, but they comprise up to 13% of all malignant cutaneous neoplasms. The current study presents our experience of reconstruction of scalp and forehead for malignant tumours treated at our centre. Methods This is a single institutional observational study conducted at a tertiary cancer centre in North East India. Post-operative outcomes related to quality of life of patients were measured with help of FACE-Q scales. Face-Q –Satisfaction with outcome and FACE-Q- appearance related psychosocial distress scores were analysed. Histograms were used for descriptive statistics. Data were checked for normality using Kolmogorov–Smirnova and Shapiro–Wilk test. For non-normal data Wilcoxon test was used. A p value less than 0.05 was considered as statistically significant at 5% level of significance. Results Mean age of patients was 57.6 ± 14.2 years. The mean defect size was 89.036 ± 81.77 cm2. The mean satisfaction with outcome scores and distress scores at 3-months was 54.9 ± 8.6 and 34.8 ± 8.5 respectively with a statistically significant p value of 0.001.Mean satisfaction scores and psychological distress scores were better at the end of three months when compared to at the time of discharge with a statistical significant p value of < 0.0001. Conclusion Scalp and forehead reconstructions for defects following oncological resections are technically challenging and if chosen carefully with meticulous planning, both local and free tissue transfers give satisfactory outcome in long term follow up. There are lots of reconstruction options for scalp and forehead defects and knowledge of the basic bio-geometry of the each flap is must. [ABSTRACT FROM AUTHOR]

A phenylazo appended ortho‐vanillin Schiff base scaffold (HAZ) has been used for selective colorimetric sensing of Cu2+ in semi‐aqueous medium (methanol–water, 1:1, v/v) in the presence of 16 cations and 20 anions, and the limit of detection is 1.8 × 10−7 M. The structures of HAZ and Cu (II) complex, [Cu(AZ)2], have been characterised by spectroscopic data (UV–Vis, Fourier transform infrared and electron paramagnetic resonance) and established by the single crystal X‐ray diffraction measurement. The Job's plot from the absorption studies has also confirmed the 1:2 stoichiometry of Cu2+:HAZ. The absorption spectrum of [Cu (AZ)2] has returned to the spectrum of HAZ on the addition of Na2EDTA solution which is again recovered upon the addition of Cu2+ solution. Discrete Fourier transform computations were carried out using the coordinates of the X‐ray structures of the compounds, and the molecular functions were used to correlate the solution spectroscopic properties. In addition to this, the probe is treated on MDA‐MB 231 breast cancer cells to check the cytotoxicity. The probe is used for the detection of trace quantity of Cu2+ in the cancer cell. [ABSTRACT FROM AUTHOR]

Ruellia tuberosa L. (Acanthaceae) is a weed plant traditionally used in folklore medicine as a diuretic, anti-hypertensive, anti-pyretic, anti-cancerous, anti-diabetic, analgesic, and gastroprotective agent. It has been previously reported that R. tuberosa L. is enriched with various flavonoids, exhibiting significant cytotoxic potential in various cancer models but a detailed study concerning its molecular mechanism is yet to be explored. Exploring and validating R. tuberosa L. flower methanolic extract (RTME) as an anti-cancerous agent as per traditional usage with special emphasis on multi-drug resistant human triple-negative breast cancer (TNBC) and investigating the possible signaling networks and regulatory pathways involved in it. In this study, RTME was prepared using methanol, and phytochemical analysis was performed through GC-MS. Then, the extract was tested for its anti-cancer potential through in-vitro cytotoxicity assay, clonogenic assay, wound healing assay, ROS generation assay, cell cycle arrest, apoptotic nuclear morphology study, cellular apoptosis study, mitochondrial membrane potential (MMP) alteration study, protein, and gene expressions alteration study. In addition, toxicological status was evaluated in female Balb/C mice, and to check the receptor-ligand interactions, in-silico molecular docking was also conducted. Several phytochemicals were found within RTME through GC-MS, which have been already reported to act as ROS inductive, DNA damaging, cell cycle arresting, and apoptotic agents against cancer cells. Moreover, RTME was found to exhibit significant in-vitro cytotoxicity along with a reduction in colony formation, and inhibition of cell migratory potential. It also induced intracellular ROS, promoted G0/G1 cell cycle arrest, caused mitochondrial membrane potential (MMP) alteration, and promoted cell death. The Western blot and qRT-PCR data revealed that RTME promoted the intrinsic pathway of apoptosis. Furthermore, blood parameters and organ histology on female Balb/C mice disclosed the non-toxic nature of RTME. Finally, an in-silico molecular docking study displayed that the three identified lead phytochemicals in RTME show strong receptor-ligand interactions with the anti-apoptotic Bcl-2 and give a clue to the possible molecular mechanism of the RTME extract. RTME is a potential source of several phytochemicals that have promising therapeutic potential against TNBC cells, and thus could further be utilized for anti-cancer drug development. [Display omitted] • Preparation of methanolic extract of Ruellia tuberosa L. flower (RTME). • Identification of phytochemicals from methanolic extract of Ruellia tuberosa L. flower. • RTME exhibited significant cytotoxicity MDA-MB-231 cells by inducing ROS, G0/G1 cell cycle arrest, and apoptosis. • Toxicological assessments of RTME on female Balb/C mice. • In-silico assessments of lead phytochemicals with the target anti-apoptotic protein, Bcl-2. [ABSTRACT FROM AUTHOR]

Hypericum roeperianum is a medicinal spice traditionally used in West Africa to treat female sterility, fungal infections, and cancer. It has previously been reported that H. roeperianum exhibits cytotoxic potential by reducing the viability of cancer cells involving multidrug-resistant phenotypes, but its underlying molecular mechanism remains unknown. The mechanistic involvement of H. roeperianum methanolic crude extract (HRC) in attenuating breast cancer progression by exploring the effects on mitochondrial apoptosis and epithelial-mesenchymal transition (EMT) was investigated. In the present study, we examined the anticancer properties of HRC through MTT assay, colony formation, wound healing assay, spheroid formation, DNA fragmentation and flow cytometry for cell cycle arrest, apoptosis (Annexin V/PI staining) and mitochondrial membrane potential (MMP) (JC-1) detection. In addition, western blot analysis of various proteins and quantitative real time PCR of various genes involved in apoptosis, EMT and the PI3K/Akt/mToR signal transduction pathway were performed. This study revealed that HRC treatment significantly decreased breast cancer cell viability, colony forming efficiency and reduced the ability of cell migration and spheroid formation. HRC also induced apoptosis in MDA-MB-231 and MCF-7 via promoting G0/G1 cell cycle arrest, disruption of mitochondrial membrane potential and induction of DNA damage. The crude extract induced apoptosis by activating the intrinsic pathway with a stronger effect that relies on the combined potency of associated molecular markers including Bax, Bad, Bcl-2, cytochrome C, caspase-9, and cleaved-PARP. It was also found that HRC regulates the PI3K/Akt/mToR pathway. In addition, HRC inhibited EMT by expressional alteration of Vimentin and E-cadherin, as well as the regulatory transcription factors such as Snail and Slug. The in vitro findings reflected similar mechanistic approach in 4T1 cell induced syngeneic mice model, indicating the reduction of tumor volume along with the significant expressional alteration of EMT and apoptotic markers. Taken together the findings concluded that H. roeperianum is a potential source of cytotoxic phytochemicals that exhibit abortifacient effect on breast cancer, both in vitro and in vivo , thus could further be utilized in breast cancer therapy. [Display omitted] • The anticancer mechanism of action of Hypericum roeperianum crude extract (HRC) was evaluated. • HRC also induced apoptosis in MDA-MB-231 and MCF-7. • HRC causes G0/G1 cell cycle arrest, disruption of mitochondrial membrane potential and DNA damage. • HRC inhibited the epithelial-mesenchymal transition. [ABSTRACT FROM AUTHOR]

Widespread use of gadolinium-based contrast agents in medical imaging has resulted in increased Gd inputs to municipal wastewater treatment plants. Others have reported that typical wastewater treatment does not attenuate Gd, resulting in discharges to natural waters. However, whether elevated Gd impacts the performance of biological treatment has not been investigated. We examined whether gadolinium chloride or Gd chelated with diethylenetriaminepentaacetic acid (DTPA) affected the activity of the model nitrifying bacterium Nitrosomonas europaea. At nominal GdCl 3 additions ranging from 1 to 500 μM, no impact was observed compared to the control. Most (>98%) of the added Gd precipitated, and extracellular GdPO 4 nanoparticles were observed. When chelated with DTPA, Gd remained soluble, but no statistically significant impact on ammonia oxidation was observed until the highest concentrations tested. At 300 and 500 μM Gd-DTPA, a temporary reduction of nitrite production relative to the control (effect size 1.3 mg l−1 and 1.5 mg l−1, respectively, at 24 h) was seen. By itself, DTPA was highly inhibitory. Modeling suggested that DTPA likely chelated other metals, but adjusting the concentrations of the most abundant metals in the medium, calcium and magnesium, indicated that lowering their free ion activities was probably not the cause of inhibition. Complexation of other essential metals was more likely. Our studies indicate that while the low bioavailability of Gd may limit its ecosystem impacts, the role of synthetic ligands used with Gd and other rare earth elements should be considered as the production, use and disposal of these elements increases. Image 1 • Gadolinium additions up to 500 μM did not inhibit N. europaea activity • Thermodynamic modeling suggested phosphate mineral precipitation • Extracellular Gd phosphate nanoparticles were observed • At high Gd-DTPA concentrations (≥300 μM) temporary inhibition occurred • Synthetic ligands used with rare earths may be more problematic than the metals [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Comparison of lixiviants for leaching rare earth elements from synthetic phosphogypsum. • Leaching efficiency: H 2 SO 4 > Biolixiviant > Gluconic Acid > H 3 PO 4 for Ce, Nd, Sm, Eu, and Yb. • Thermodynamic simulations consistent with experimental results. Abstract Leaching of six individual rare earth (yttrium, cerium, neodymium, samarium, europium, and ytterbium) doped synthetic phosphogypsum samples using a suite of lixiviants was conducted. The lixiviants chosen for this study were phosphoric acid, sulfuric acid, gluconic acid, and a "biolixiviant" consisting of spent medium containing organic acids from the growth of the bacterium Gluconobacter oxydans on glucose. The biolixiviant had a pH of 2.1 and the dominant organic acid was determined to be gluconic acid, present at a concentration of 220 mM. The leaching behaviors of the studied lixiviants were compared and rationalized by thermodynamic simulations. The results suggest that at equivalent molar concentrations of 220 mM the biolixiviant was more efficient at rare earth element (REE) extraction than gluconic acid and phosphoric acid but less efficient than sulfuric acid. Unlike the organic acids, at pH 2.1 the mineral acids failed to extract REE, likely due to different complexation and kinetic effects. [ABSTRACT FROM AUTHOR]

A matrix metalloproteinase (MMP) targeted tetrapeptide vesicle has been designed and developed, which strongly binds at a MMP9 enzymatic site. Interestingly, it has a propensity to encapsulate and deliver the doxorubicin drug specifically to the cancer cell, induces superior apoptotic death, and inhibits the metastatic cancer cell migration and growth of multicellular 3D spheroids. [ABSTRACT FROM AUTHOR]

Microtubules regulate eukaryotic cell functions, which have tremendous implication in tumor progression. Thus, the design of novel approaches for controlling microtubule function is extremely important. In this manuscript, a novel tetrapeptide Ser-Leu-Arg-Pro (SLRP) has been designed and synthesized from a small peptide library consisting of 14 tetrapeptides, which perturbs microtubule function through interaction in the "anchor region". We have studied the role of peptides on microtubule function on a chemically functionalized 2D platform. Interestingly, we have found that SLRP binds with tubulin and inhibits the kinesin-driven microtubule motility on a kinesin-immobilized chemically functionalized 2D platform. Further, this peptide modulator interacts with intracellular tubulin/microtubule and depolymerizes the microtubule networks. These interesting findings of perturbation of microtubule function both on engineered platforms and inside the cell by this small peptide modulator inspired us to study the effect of this tetrapeptide on cancer cell proliferation. We found that the novel tetrapeptide modulator causes moderate cytotoxicity to the human breast cancer cell (MCF-7 cell), induces the apoptotic death of MCF-7 cell, and activates the tumor suppressor proteins p53 and cyclin-dependent kinase inhibitor 1 (p21). To the best of our knowledge, this is the shortest peptide discovered, which perturbs microtubule function both on an engineered 2D platform and inside the cell. [ABSTRACT FROM AUTHOR]

[Display omitted] • Dual fluorogenic core of Rhodamine appended chromone Schiff base (RFC) is spectroscopically characterised. • RFC is an efficient sensor to Fe3+, Al3+, Cr3+ at trace level. • LODs are 0.093 μM (Fe3+), 0.11 μM (Al3+) and 0.10 μM (Cr3+) much below the WHO recommended data. • RFC has high anticancer activity to breast cancer MCF-7 cells and IC 50 is 2.53 µM. • RFC shows high growth inhibition efficiency, wound healing capacity and an apoptotic marker. Strategic design of fluorescent probe for the recognition of ions/molecules at very low concentration by fluorescence sensing is one of the stimulating current research topics with reference to health and sustainability. Towards this objective, Rhodamine based chemosensors are playing extraordinary protagonist. In this work, a Rhodamine appended chromone Schiff base (RFC), with two fluorogenic motifs, has been characterized through various spectroscopic techniques. The probe exhibits efficient sensitivity towards Analytical Group IIIA ions (Al3+, Cr3+ and Fe3+) in existence of other competitive analytes. The fluorescent intensity is enhanced by 350 fold (Fe3+), 250 fold (Al3+) and 220 fold (Cr3+), respectively in methanol-water (99:1,v/v; HEPES buffer, pH, 7.2) medium. The limits of detection (LOD) (3σ/M method; σ = standard deviation; M = slope) are 0.0051 ppm (Fe3+), 0.0029 ppm (Al3+) and 0.0052 ppm (Cr3+); which are impressive and much below the WHO recommended data. In addition to this, the compound has been utilized for cell imaging in presence of these three cations. The action of probe on MCF-7 (human breast cancer) cell lines demonstrates IC 50 , 2.53 µM that is far better than activity against WI-38 (normal cell line) (IC 50 , 393.7 µM). The drug (RFC) minimizes the cellular proliferation and has significant wound healing capacity of the infected tissue with MCF-7 cells. The probe shows significant nuclear fragmentation with increase in the expression of apoptotic markers. Growth inhibition analysis in 3D tumor spheroid model showed the inhibition of breast cancer MCF-7 cells. [ABSTRACT FROM AUTHOR]

An antimitotic cell penetrating octapeptide containing single Arg amino acid is discovered, which strongly binds with the exchangeable GTP/GDP binding site of tubulin, inhibits tubulin polymerization, reduces kinesin driven microtubule motility, activates apoptotic and mitotic check point proteins, induces apoptotic death and significantly inhibits the multicellular tumor spheroid growth of HeLa cells. [ABSTRACT FROM AUTHOR]

Dopamine is synonymous with reward and motivation in mammals. However, only recently has dopamine been linked to motivated behaviour and rewarding reinforcement in fruitflies. Instead, octopamine has historically been considered to be the signal for reward in insects. Here we show, using temporal control of neural function in Drosophila, that only short-term appetitive memory is reinforced by octopamine. Moreover, octopamine-dependent memory formation requires signalling through dopamine neurons. Part of the octopamine signal requires the ?-adrenergic-like OAMB receptor in an identified subset of mushroom-body-targeted dopamine neurons. Octopamine triggers an increase in intracellular calcium in these dopamine neurons, and their direct activation can substitute for sugar to form appetitive memory, even in flies lacking octopamine. Analysis of the ?-adrenergic-like OCT?2R receptor reveals that octopamine-dependent reinforcement also requires an interaction with dopamine neurons that control appetitive motivation. These data indicate that sweet taste engages a distributed octopamine signal that reinforces memory through discrete subsets of mushroom-body-targeted dopamine neurons. In addition, they reconcile previous findings with octopamine and dopamine and suggest that reinforcement systems in flies are more similar to mammals than previously thought. [ABSTRACT FROM AUTHOR]

Left Ventricular Outflow Tract (LVOT) obstruction occurs in approximately 70% of Hypertrophic Cardiomyopathy (HCM) patients and currently requires imaging or invasive testing for diagnosis, sometimes in conjunction with provocative physiological or pharmaceutical stimuli. To identify potential biomarkers of LVOT obstruction, we performed proteomics profiling of 1305 plasma proteins in 12 HCM patients with documented LVOT obstruction, referred for surgical myectomy. Plasma was collected at the surgical preoperative visit, approximately one month prior to surgery and then at the post-surgical visit, approximately 3 months later. Proteomic profiles were generated using the aptamer-based SOMAscan assay. Principal Component Analysis using the highest statistically significant proteins separated all preoperative samples from all postoperative samples. Further analysis revealed a set of 25 proteins that distinguished the preoperative and postoperative states with a paired t-test p-value of <0.01. Ingenuity Pathway analysis facilitated the generation of protein interaction networks and the elucidation of key upstream regulators of differentially expressed proteins, such as interferon-γ, TGF-β1, and TNF. Biological pathways affected by surgery included organ inflammation, migration, and motility of leukocytes, fibrosis, vasculogenesis, angiogenesis, acute coronary events, endothelial proliferation, eicosanoid metabolism, calcium flux, apoptosis, and morphology of the cardiovascular system. Our results indicate that surgical relief of dynamic outflow tract obstruction in HCM patients is associated with unique alterations in plasma proteomic profiles that likely reflect improvement in organ inflammation and physiological function. [ABSTRACT FROM AUTHOR]