Miracle-dz/UniFAR-FTUs huggingface dataset:
Preclinical Evaluation of Gilteritinib on NPM1-ALK–Driven Anaplastic Large Cell Lymphoma Cells

Anaplastic large cell lymphoma (ALCL) is an aggressive type of non-Hodgkin lymphoma. More than three-fourths of anaplastic lymphoma kinase (ALK)-positive ALCL cases express the nucleophosmin 1 (NPM1)-ALK fusion gene as a result of t(2;5) chromosomal translocation. The homodimerization of NPM1-ALK fusion protein mediates constitutive activation of the chimeric tyrosine kinase activity and downstream signaling pathways responsible for lymphoma cell proliferation and survival. Gilteritinib is a tyrosine kinase inhibitor recently approved by the FDA for the treatment of FMS-like tyrosine kinase mutation–positive acute myeloid leukemia. In this study, we demonstrate for the first time gilteritinib-mediated growth inhibitory effects on NPM1-ALK–driven ALCL cells. We utilized a total of five ALCL model cell lines, including both human and murine. Gilteritinib treatment inhibits NPM1-ALK fusion kinase phosphorylation and downstream signaling, resulting in induced apoptosis. Gilteritinib-mediated apoptosis was associated with caspase 3/9, PARP cleavage, the increased expression of proapoptotic protein BAD, and decreased expression of antiapoptotic proteins, survivin and MCL-1. We also found downregulation of fusion kinase activity resulted in decreased c-Myc protein levels. Furthermore, cell-cycle analysis indicated gilteritinib induced G0–G1-phase cell-cycle arrest and reduced CD30 expression. In summary, our preclinical studies explored the novel therapeutic potential of gilteritinib in the treatment of ALCL cells expressing NPM1-ALK and potentially in other ALK or ALK fusion–driven hematologic or solid malignancies. Implications: Our preclinical results explore the use of gilteritinib for the treatment of NPM1-ALK–driven ALCL cells and pave a path for developing future clinical trials. Visual Overview: http://mcr.aacrjournals. org/content/molcanres/19/5/913/F1.large. jpg. Visual Overview
Influence of single nucleotide polymorphisms among cigarette smoking and non-smoking patients with coronary artery disease, urinary bladder cancer and lung cancer

Introduction Cigarette smoke is suggested to be a risk factor for coronary artery disease (CAD), urinary bladder cancer (UBCa) or lung cancer (LCa). However, not all heavy smokers develop these diseases and elevated cancer risk among first-degree relatives suggests an important role of genetic factor. Methods Three hundred and ten healthy blood donors (controls), 98 CAD, 74 UBCa and 38 LCa patients were included in this pilot study. The influence of 92 single nucleotide polymorphisms (SNPs) and impact of cigarette smoking were analysed. Results Out of 92 SNPs tested, differences in distribution of 14 SNPs were detected between controls and patient groups. Only CTLA4 rs3087243 showed difference in both CAD and UBCa patient group compared to control group. Stratified by smoking status, the impact of smoking was associated to frequencies of 8, 3 and 4 SNPs in CAD, UBCa, LCa patients, respectively. None of these 92 SNPs showed a statistically significant difference to more than one type of disease among smoking patients. In non-smoking patients, 7, 3 and 6 SNPs were associated to CAD, UBCa, LCa, respectively. Out of these 92 SNPs, CTLA4 rs3087243 was associated to both non-smoking CAD and UBCa. The XRCC1 rs25487 was associated to both non-smoking UBCa and LCa. Conclusion SNPs might be important risk factors for CAD, UBCa and LCa. Distribution of the SNPs was specific for each patient group, not a random event. Impact of cigarette smoking on the disease was associated to the specific SNP sequences. Thus, smoking individuals with SNPs associated to risk of these serious diseases is an important target group for smoking cessation programs.
New twists in actin–microtubule interactions

Actin filaments and microtubules are cytoskeletal polymers that participate in many vital cell functions including division, morphogenesis, phagocytosis, and motility. Despite the persistent dogma that actin filament and microtubule networks are distinct in localization, structure, and function, a growing body of evidence shows that these elements are choreographed through intricate mechanisms sensitive to either polymer. Many proteins and cellular signals that mediate actin–microtubule interactions have already been identified. However, the impact of these regulators is typically assessed with actin filament or microtubule polymers alone, independent of the other system. Further, unconventional modes and regulators coordinating actin–microtubule interactions are still being discovered. Here we examine several methods of actin–microtubule crosstalk with an emphasis on the molecular links between both polymer systems and their higher-order interactions.
Structural relationships in intermetallic compounds of the Al-Li-(Cu, Mg, Zn) system

Abstract Intermetallic compounds with compositions in the vicinity of Al0·6 (Cu, Zn), (Li, Mg)0·3, namely the so-called R, Z, C and τ phases, have been selected for structural studies because of their presumed relation with the Al-Cu-Li quasicrystal. Neutron diffraction data strongly suggest unicity for short- and medium-range arrangements in these phases. Transmission electron microscopy confirms the point and allows detailed modelling, based on connections of atomic clusters having icosahedral symmetries and taken from the crystallographic structure of the b.c.c. R-phase.
Association of Dilated Perivascular Spaces With Cognitive Decline and Incident Dementia

Objective To determine whether severe perivascular space (PVS) dilation is associated with longitudinal cognitive decline and incident dementia over 4 and 8 years, respectively, we analyzed data from a prospective cohort study. Methods A total of 414 community-dwelling older adults aged 72–92 years were assessed at baseline and biennially for up to 8 years, with cognitive assessments, consensus dementia diagnoses, and 3T MRI. The numbers of PVS in 2 representative slices in the basal ganglia (BG) and centrum semiovale (CSO) were counted and severe PVS pathology defined as the top quartile. The effects of severe PVS pathology in either region or both regions and those with severe BG PVS and severe CSO PVS were examined. White matter hyperintensity volume, cerebral microbleed number, and lacune number were calculated. Results Participants with severe PVS pathology in both regions or in the CSO alone had greater decline in global cognition over 4 years, even after adjustment for the presence of other small vessel disease neuroimaging markers. The presence of severe PVS pathology in both regions was an independent predictor of dementia across 8 years (odds ratio 2.91, 95% confidence interval 1.43–5.95, p = 0.003). The presence of severe PVS pathology in all groups examined was associated with greater dementia risk at either year 4 or 6. Conclusions Severe PVS pathology is a marker for increased risk of cognitive decline and dementia, independent of other small vessel disease markers. The differential cognitive associations for BG and CSO PVS may represent differences in their underlying pathology.
Combined Ozonation Using Alumino-Silica Materials for the Removal of 2,4-Dimethylphenol from Water

This study deals with an advanced oxidation process combining adsorption and ozonation for treating petrochemical effluents. The compound 2,4-dimethylphenol (DMP) was the paradigm molecule and faujasite-Y, mordenite, ZSM-5 and γ-alumina were tested. Single ozonation showed rapid DMP degradation but limited by gas to liquid ozone transfer. No catalytic effect occurred during ozonation combined with any of the adsorbents: DMP removal was not accelerated. However, a good synergistic effect was observed for TOC removal with γ-alumina, yet the various zeolites are less efficient. Some specific oxidation by-products produced during ozonation are eliminated by adsorption in the presence of γ-alumina, although they persist in the other cases.
Retrieval of Bard Simon Nitinol inferior vena cava filters: Approaches, technical successes, complications, and clinical outcomes

Objective The Simon Nitinol filter is a bi-level filtration device designed for permanent implantation that is no longer commercially available, but may result in similar complications to current commercially available long term indwelling temporary or permanent filters. Complications related to indwelling inferior vena cava filters include inferior vena cava thrombosis, inferior vena cava penetration, filter migration, and filter fracture. There is a paucity of reports describing the technical aspects related to retrieval of Simon Nitinol filters. Materials and methods This study consisted of five patients with Simon Nitinol filters and describes the indication for retrieval, the retrieval techniques used to remove the filters, technical success, complications, and clinical course. Results The indications for retrieval included: abdominal pain (n = 2; 40%), iliocaval thrombosis (n = 1; 20%), identification of an intracardiac filter fragment (n = 1; 20%), and recurrent venous thromboembolic events (n = 1; 20%). Retrieval techniques included: biopsy forceps (n = 3; 60%), excimer laser extraction sheaths (n = 3; 60%), hangman modified loop snares (n = 3; 60%), rigid endobronchial forceps (n = 2; 40%), and balloon deflection (n = 2; 40%). All filters were successfully retrieved. One patient developed a post-procedural intramuscular hematoma near the site of right internal jugular sheath placement. Conclusions Simon Nitinol filters may be retrieved safely and effectively using advanced inferior vena cava filter retrieval techniques.
Estimating ammonia volatilization losses from urea fertilizers using a simplified micrometeorological sampler

The large amount of unincorporated, urea-containing fertilizer that is used on no-till corn (Zea mays L.) makes it imperative that we know the magnitude of NH 3 volatilization loss from these fertilizers. Although there have been numerous studies to estimate these losses, in almost none of them were the losses measured under undisturbed field conditions. A simplified, micrometeorological method with NH 3 samplers placed at the center of three replicates of 25-m-radius circular plots was used to estimate NH 3 volatilization losses from 134 kg N ha -1 of surface-applied, unincorporated urea, sprayed urea-ammonium nitrate (UAN) solution, and dribbled UAN. The average NH 3 volatilization losses during the first 10 to 20 d after application for a 3-yr period were 40, 22, and 17 kg N ha -1 from urea, sprayed UAN, and dribbled UAN, respectively. The losses from sprayed and dribbled UAN were not significantly different from each other and were, on average, significantly less than from urea. The rainfall in the first 6 d after application was <5 mm for all 3 yr of the experiment. Corn yields and N uptake generally reflected the measured NH 3 volatilization losses, but were considered to be much less precise indicators of NH 3 volatilization loss. One drawback of the simplified micrometeorological method is that large areas are needed to accommodate the 50-m-diam. plots and 100-m buffers between plots.
The antimicrobial efficacy of shielded ultraviolet germicidal irradiation in CT rooms with intense human circulation.

PURPOSE Computed tomography (CT) premises are one of the strategic points in the spread of hospital-acquired infections. Ultraviolet germicidal irradiation (UVGI) is an effective method that could potentially be used to purify the ambient air in them. However, it cannot be directly used in the presence of humans and, therefore, it is not operationally suitable in such units with continuous human circulation. Newer devices have been developed to purify air with more efficient and shielded UV-C sources. This study aims to assess the microbial air contamination in CT scanning rooms and investigates the efficacy and technical considerations of shielded UV-C arrays. METHODS Two shielded UVGI systems, each equipped with 15 Watt UV-C LED arrays, were tested in a very busy CT unit. Initially, a pilot study was performed to determine ambient microorganisms under routine conditions before UVGI installation, followed by three basic scenarios of UVGI use under normal and abnormal conditions: A, UVGI, with both air-conditioning (AC) and ventilation on; B, UVGI, with AC on and ventilation off; C, UVGI, with both AC and ventilation off. Ambient air was sampled in various time points before and after the initialization of UV irradiation and analyzed for colony formation. RESULTS The mean total colony count in the pilot study was 1360±450 CFU/m3. Pre-UVGI colony count was 3510 CFU/m3 for Scenario A, ~10000 CFU/m3 for Scenario B and 990 CFU/m3 for Scenario C. Thirty minutes after UVGI, total colony counts in all three scenarios dropped to 30 to 70 CFU/m3. Under normal operating conditions and UVGI, the mean colony count was found as 21.4±13.5 CFU/m3 and the average efficacy of the UVGI was found as 99.39%. CONCLUSION This study identified substantial microbial air contamination in CT scanning rooms during normal and abnormal operating conditions. UV-C LED arrays effectively eliminate these microbiological contaminants. This effect is also observed under abnormal operating conditions where no other means of ventilation or air conditioning exists.
Pulp Vitality Testing with a Developed Universal Pulse Oximeter Probe Holder

Background and Objectives An accurate determination of the pulp status is relevant for a proper endodontic diagnosis. Objectives: The aim was to develop a universal pulse oximeter probe holder for measuring the oxygen saturation and to evaluate the use of pulse oximetry as a test for pulp vitality, by comparing the levels of oxygen saturation in the index finger and in the healthy dental pulp. Materials and Methods The universal holder was designed with software and printed with a 3D printer. The study was carried out on 128 healthy teeth. They were divided into eight groups according to tooth type. Ten root canal treated teeth served as a negative control group. For each patient, a pulse oximeter was first applied on the tooth followed by the index finger. The significance level (α) was set at 0.05. Results: The developed and manufactured universal pulse oximeter probe holder was suitable to measure the pulp vitality of all types of teeth. The handle allowed for holding the pulse oximeter on the tooth in parallel, firmly and securely. Significantly higher oxygen saturation was observed in the index finger (97.22%) compared to the dental pulp (93.17%) (p < 0.001). No correlation was observed between the maxillary teeth and index finger oxygen saturation values (r = 0.05, p = 0.72), whereas, between the mandibular teeth and index finger, a positive correlation was detected (r = 0.29, p = 0.02). There were no significant differences in the pulp oxygen saturation values between different teeth groups. Conclusion: The newly developed universal pulse oximeter probe holder is an effective device for pulp vitality testing.
A Mitochondrial Polymorphism Alters Immune Cell Metabolism and Protects Mice from Skin Inflammation

Several genetic variants in the mitochondrial genome (mtDNA), including ancient polymorphisms, are associated with chronic inflammatory conditions, but investigating the functional consequences of such mtDNA polymorphisms in humans is challenging due to the influence of many other polymorphisms in both mtDNA and the nuclear genome (nDNA). Here, using the conplastic mouse strain B6-mtFVB, we show that in mice, a maternally inherited natural mutation (m.7778G > T) in the mitochondrially encoded gene ATP synthase 8 (mt-Atp8) of complex V impacts on the cellular metabolic profile and effector functions of CD4+ T cells and induces mild changes in oxidative phosphorylation (OXPHOS) complex activities. These changes culminated in significantly lower disease susceptibility in two models of inflammatory skin disease. Our findings provide experimental evidence that a natural variation in mtDNA influences chronic inflammatory conditions through alterations in cellular metabolism and the systemic metabolic profile without causing major dysfunction in the OXPHOS system.
ADAM10-Mediated Cleavage of ICAM-1 Is Involved in Neutrophil Transendothelial Migration

To efficiently cross the endothelial barrier during inflammation, neutrophils first firmly adhere to the endothelial surface using the endothelial adhesion molecule ICAM-1. Upon actual transmigration, the release from ICAM-1 is required. While Integrin LFA1/Mac1 de-activation is one described mechanism that leads to this, direct cleavage of ICAM-1 from the endothelium represents a second option. We found that a disintegrin and metalloprotease 10 (ADAM10) cleaves the extracellular domain of ICAM-1 from the endothelial surface. Silencing or inhibiting endothelial ADAM10 impaired the efficiency of neutrophils to cross the endothelium, suggesting that neutrophils use endothelial ADAM10 to dissociate from ICAM-1. Indeed, when measuring transmigration kinetics, neutrophils took almost twice as much time to finish the diapedesis step when ADAM10 was silenced. Importantly, we found increased levels of ICAM-1 on the transmigrating neutrophils when crossing an endothelial monolayer where such increased levels were not detected when neutrophils crossed bare filters. Using ICAM-1-GFP-expressing endothelial cells, we show that ICAM-1 presence on the neutrophils can also occur by membrane transfer from the endothelium to the neutrophil. Based on these findings, we conclude that endothelial ADAM10 contributes in part to neutrophil transendothelial migration by cleaving ICAM-1, thereby supporting the release of neutrophils from the endothelium during the final diapedesis step.
Volume analysis of second molar pulp chamber using cone beam computed tomography for age estimation in Egyptian adults.

AIM The present work aimed to evaluate age-related variations in the dental pulp chamber volume of second molars using cone beam computed tomography (CBCT) imaging, in order to establish a specific mathematical model for second molars and measure its accuracy, especially in the case of Egyptian adults. SUBJECTS AND METHODS From 187 subjects between 21-50 years of age, CBCT images of 257 maxillary and 248 mandibular second molars were included. A mathematical model for human age estimation was established. An independent additional set of CBCT images was obtained to test the model's accuracy. RESULTS For maxillary and mandibular teeth, R2 for the pooled sexes were 0.51 and 0.52, and SEE were 5.92 and 5.71, respectively. A model for each sex was established, due to the significant difference between them, where R2 was equal to 0.668 and 0.650 in males and 0.46 and 0.48 in females, concerning maxillary and mandibular teeth, respectively. When testing the validation samples, the mean absolute error (MAE) between the actual and estimated ages from the pooled sex model were 4.89 and 4.61 for maxillary and mandibular teeth, respectively. CONCLUSION The pulp chamber volume of second molars is a relatively accurate indicator for age estimation in Egyptian adults.
Effect of Size and Shape on Electrochemical Performance of Nano-Silicon-Based Lithium Battery

Silicon is a promising material for high-energy anode materials for the next generation of lithium-ion batteries. The gain in specific capacity depends highly on the quality of the Si dispersion and on the size and shape of the nano-silicon. The aim of this study is to investigate the impact of the size/shape of Si on the electrochemical performance of conventional Li-ion batteries. The scalable synthesis processes of both nanoparticles and nanowires in the 10–100 nm size range are discussed. In cycling lithium batteries, the initial specific capacity is significantly higher for nanoparticles than for nanowires. We demonstrate a linear correlation of the first Coulombic efficiency with the specific area of the Si materials. In long-term cycling tests, the electrochemical performance of the nanoparticles fades faster due to an increased internal resistance, whereas the smallest nanowires show an impressive cycling stability. Finally, the reversibility of the electrochemical processes is found to be highly dependent on the size/shape of the Si particles and its impact on lithiation depth, formation of crystalline Li15Si4 in cycling, and Li transport pathways.
Use of Botulinum Neurotoxin in Parkinson’s Disease: A Critical Appraisal

For well over 30 years, the botulinum neurotoxin (BoNT) has been used for a large number of indications, some of which however have not been licensed. Admittedly, approval varies in many countries and this permits a large spectrum for evaluation. Thus, BoNT is used for patients with Parkinson’s disease (PD) and other Parkinson’s syndromes (PS) in varying degrees of frequency. We have to distinguish between (1) indications that are either approved or (2) those not approved, (3) indications that might be a result of PS and (4) finally those which appear independent of PS. The most important indication for BoNT in PS patients is probably sialorrhea, for which approval has been granted in the majority of countries. Cervical dystonia is a frequent symptom in PS, with anterocollis as a specific entity. A further indication is blepharospasm in the different forms, especially the inhibition of eyelid opening in atypical PS. The use of BoNT in cases of camptocormia, the Pisa syndrome and neck rigidity is still a matter of debate. In dystonia of the extremities BoNT can be recommended, especially in dystonia of the feet. One well-known indication, for which however sufficient data are still lacking, involves treating tremor with BoNT. As to autonomic symptoms: Focal hyperhidrosis and detrusor hyperactivity can be mentioned, in this last case BoNT has already been approved. A number of further but rare indications such as freezing-of-gait, dyskinesia, and dysphagia will be discussed and evaluated.
Cytogenetics of Four Species of the Green Clade Aplastodiscus Lutz, 1950 (Anura: Cophomantinae): New Insights into the Chromosomal Evolution of the Genus

The tree frog Aplastodiscus is a Neotropical taxon that encompasses 15 species in the Atlantic forest biome, with one isolated species in the Central Brazilian Cerrado. To date, only 8 species have been karyotyped, showing high levels of diploid number variation, which allowed clustering species in chromosome number groups: 2n = 24 (Aplastodiscus perviridis group), 2n = 22 (Aplastodiscus albofrenatus group), 2n = 20, and 2n = 18 (both within Aplastodiscus albosignatus group). This study aims to report karyotypic information on 4 species from the last 2 groups using classical and molecular cytogenetic techniques and hypothesize chromosomal evolutionary trends within the species groups. Aplastodiscus weygoldti showed 2n = 22; Ag-NOR and FISH 18S rDNA signals were located in the interstitial region of the short arms of chromosome pair 6. Aplastodiscus cavicola, Aplastodiscus sp. 4, and Aplastodiscus sp. 6 showed 2n = 18; Ag-NOR and FISH 18S rDNA bands were located in the terminal region of the long arm of chromosome pair 9. Our results support multiple and independent chromosome fusion events within Aplastodiscus, including a new chromosome fission event. Ag-NOR and FISH 18S rDNA patterns were restricted to the small chromosome pairs, similar to the other species within this genus, and confirm overall chromosome morphology conservation among the genera of Cophomantinae.