bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic nanostructures and nanotoxicity
Authors: Sarma Anupam , Bania Ratnali , Devi Juti Rani , Deka Satyendra 
Published: February 2021

AbstractNanotechnology, with its continuous advancement, leads to the development of nanoscale‐level therapeutics to mitigate many complex diseases. This results in the emergence of numerous novel nanomaterials and its composite products into the market such as liposome, polymeric nanoparticles, dendrimers, and nanostructured lipid carrier. However, their application is always determined by a high benefit to risk ratio. Very few research have been done on the toxicity assessment of nanoparticles in the biological system; therefore, the limited knowledge regarding the toxicity profile of nanotherapeutics is available leading to the ignorance of its side effects. Nanoparticles can distribute in the whole body through translocating in the bloodstream by crossing membrane barriers efficiently and shows effect in organs and tissues at cellular and molecular levels. The interaction of nanoparticle with cell may consequences into nanotoxicity. The narrow size distribution, large surface area to mass ratio and surface properties of nanoparticle are significantly associated with nanotoxicity. Nanoparticles can enter into the tissue and cell by invading the membranes and cause cellular injury as well as toxicity. Therefore, the exploration of mechanisms of nanotoxicity has prime importance now a day. The toxicity assessment should be an integral part of the development of nanotherapeutics using various toxicity evaluation models. This review has focused on the exploration of different nanostructures for therapeutic delivery system along with its physicochemical characteristics responsible for adverse effects on human biology, various toxicity evaluation models, and environmental and regulatory hurdles.
Renal Outcomes After Simultaneous Liver‐Kidney Transplantation: Results from the US Multicenter Simultaneous Liver‐Kidney Transplantation Consortium
Authors: Sharma Pratima , Sui Zhiyu , Zhang Min , Magee John C. , Barman Pranab , Patel Yuval , Schluger Aaron , Walter Kara , Biggins Scott W. , Cullaro Giuseppe , Wong Randi , Lai Jennifer C. , Jo Jennifer , Sinha Jasmine , VanWagner Lisa , Verna Elizabeth C. 
Published: February 2021

Simultaneous liver‐kidney transplantation (SLKT) is increasingly common in the United States. However, little is known about the renal‐related outcomes following SLKT, which are essential to maximize the health of these allografts. We examined the factors impacting renal function following SLKT. This is an observational multicenter cohort study from the US Multicenter SLKT Consortium consisting of recipients of SLKT aged ≥18 years of transplantations performed between February 2002 and June 2017 at 6 large US centers in 6 different United Network for Organ Sharing regions. The primary outcome was incident post‐SLKT stage 4‐5 chronic kidney disease (CKD) defined as <30 mL/minute/1.73 m2 or listing for kidney transplant. The median age of the recipients (n = 570) was 58 years (interquartile range, 51‐64 years), and 37% were women, 76% were White, 33% had hepatitis C virus infection, 20% had nonalcoholic steatohepatitis (NASH), and 23% had alcohol‐related liver disease; 68% developed ≥ stage 3 CKD at the end of follow‐up. The 1‐year, 3‐year, and 5‐year incidence rates of post‐SLKT stage 4‐5 CKD were 10%, 12%, and 16%, respectively. Pre‐SLKT diabetes mellitus (hazard ratio [HR], 1.45; 95% CI, 1.00‐2.15), NASH (HR, 1.58; 95% CI, 1.01‐2.45), and delayed kidney graft function (HR, 1.72; 95% CI, 1.10‐2.71) were the recipient factors independently associated with high risk, whereas the use of tacrolimus (HR, 0.44; 95% CI, 0.22‐0.89) reduced the risk. Women (β = −6.22 ± 2.16 mL/minute/1.73 m2; P = 0.004), NASH (β = −7.27 ± 3.27 mL/minute/1.73 m2; P = 0.027), and delayed kidney graft function (β = −7.25 ± 2.26 mL/minute/1.73 m2; P = 0.007) were independently associated with low estimated glomerular filtration rate at last follow‐up. Stage 4‐5 CKD is common after SLKT. There remains an unmet need for personalized renal protective strategies, specifically stratified by sex, diabetes mellitus, and liver disease, to preserve renal function among SLKT recipients.
Nutritive Manganese and Zinc Overdosing in Aging C. elegans Result in a Metallothionein‐Mediated Alteration in Metal Homeostasis
Authors: Baesler Jessica , Michaelis Vivien , Stiboller Michael , Haase Hajo , Aschner Michael , Schwerdtle Tanja , Sturzenbaum Stephen R. , Bornhorst Julia 
Published: February 2021

ScopeManganese (Mn) and zinc (Zn) are not only essential trace elements, but also potential exogenous risk factors for various diseases. Since the disturbed homeostasis of single metals can result in detrimental health effects, concerns have emerged regarding the consequences of excessive exposures to multiple metals, either via nutritional supplementation or parenteral nutrition. This study focuses on Mn‐Zn‐interactions in the nematode Caenorhabditis elegans (C. elegans) model, taking into account aspects related to aging and age‐dependent neurodegeneration.Methods and ResultsChronic co‐exposure of C. elegans to Mn and Zn increases metal uptake, exceeding levels of single metal exposures. Supplementation with Mn and/or Zn also leads to an age‐dependent increase in metal content, a decline in overall mRNA expression, and metal co‐supplementation induced expression of target genes involved in Mn and Zn homeostasis, in particular metallothionein 1 (mtl‐1). Studies in transgenic worms reveal that mtl‐1 played a prominent role in mediating age‐ and diet‐dependent alterations in metal homeostasis. Metal dyshomeostasis is further induced in parkin‐deficient nematodes (Parkinson's disease (PD) model), but this did not accelerate the age‐dependent dopaminergic neurodegeneration.ConclusionsA nutritive overdose of Mn and Zn can alter interactions between essential metals in an aging organism, and metallothionein 1 acts as a potential protective modulator in regulating homeostasis.
Membrane‐dependent amyloid aggregation of human BAX α9 (173–192)
Authors: Price David A. , Hill Tayler D. , Hutson Kaitlyn A. , Rightnowar Blaze W. , Moran Sean D. 
Published: February 2021

AbstractMitochondrial outer membrane permeabilization, which is a critical step in apoptosis, is initiated upon transmembrane insertion of the C‐terminal α‐helix (α9) of the proapoptotic Bcl‐2 family protein BAX. The isolated α9 fragment (residues 173–192) is also competent to disrupt model membranes, and the structures of its membrane‐associated oligomers are of interest in understanding the potential roles of this sequence in apoptosis. Here, we used ultrafast two‐dimensional infrared (2D IR) spectroscopy, thioflavin T binding, and transmission electron microscopy to show that the synthetic BAX α9 peptide (α9p) forms amyloid aggregates in aqueous environments and on the surfaces of anionic small unilamellar vesicles. Its inherent amyloidogenicity was predicted by sequence analysis, and 2D IR spectra reveal that vesicles modulate the β‐sheet structures of insoluble aggregates, motivating further examination of the formation or suppression of BAX amyloids in apoptosis.
Cardiolipin interacts with beta‐2‐glycoprotein I and forms an open conformation–Mechanisms analyzed using hydrogen/deuterium exchange
Authors: Tang Kuo‐Tung , Wu Ting‐Yuan , Chen Hsin‐Hua , Lin Chi‐Chien , Hsu Yuan‐Hao Howard 
Published: February 2021

AbstractBeta‐2‐glycoprotein I (β2GPI) is the major antigen for the antiphospholipid antibodies in the antiphospholipid syndrome. The exposed epitope in domain I of β2GPI can be recognized by the anti‐β2GPI antibody. Here, we prepared the anionic di‐oleoyl‐phosphatidylserine (DOPS) and cardiolipin (CL) liposomes to interact with the β2GPI. The conformational changes of β2GPI upon binding with the liposomes were analyzed using hydrogen/deuterium exchange mass spectrometry. The exchange level of sequences 21–27 significantly increased after β2GPI had interacted with DOPS. This change indicated a reduced interaction between domain I and domain V, inferring to a protrusion of the sequences 21–27 from the ring conformation. After β2GPI had interacted with CL for 30 min, the exchange levels in 4 of the 5 domains increased significantly. The deuteration levels of sequences 1–20, 21–27, 196–205, 273–279 and 297–306 increased, suggesting that these regions had become more exposed, and the domain I was no longer in contact with domain V. The increasing deuteration levels in sequences 70–86, 153–162, 191–198, 196–205 and 273–279 indicated β2GPI undergoing conformational changes to expose these inner regions, suggesting a structural transition. Overall, DOPS and CL induced minor conformational changes of β2GPI at sequences 21–27 and forms an intermediate conformation after 10 min of interaction. After a complete protein–lipid interaction, high negatively charged CL membrane induced a major conformation transition of β2GPI.
Studies of transmembrane peptides by pulse dipolar spectroscopy with semi-rigid TOPP spin labels
Authors: Tkach Igor , Diederichsen Ulf , Bennati Marina 
Published: February 2021

AbstractElectron paramagnetic resonance (EPR)-based pulsed dipolar spectroscopy measures the dipolar interaction between paramagnetic centers that are separated by distances in the range of about 1.5–10 nm. Its application to transmembrane (TM) peptides in combination with modern spin labelling techniques provides a valuable tool to study peptide-to-lipid interactions at a molecular level, which permits access to key parameters characterizing the structural adaptation of model peptides incorporated in natural membranes. In this mini-review, we summarize our approach for distance and orientation measurements in lipid environment using novel semi-rigid TOPP [4-(3,3,5,5-tetramethyl-2,6-dioxo-4-oxylpiperazin-1-yl)-L-phenylglycine] labels specifically designed for incorporation in TM peptides. TOPP labels can report single peak distance distributions with sub-angstrom resolution, thus offering new capabilities for a variety of TM peptide investigations, such as monitoring of various helix conformations or measuring of tilt angles in membranes.
Graphical Abstract
Laser-impact-induced splashing: an analysis of the splash crown evolution after Nd:YAG ns-pulse laser impact on a liquid tin pool
Authors: Hermens J. , Gelderblom H. , Liu B. , Duffhues J. , Rindt P. , Versolato O. O. 
Published: February 2021

AbstractThe splash created by intense laser pulse impact onto a liquid tin layer is studied experimentally using time-delayed stroboscopic shadowgraphy. An 8-ns infrared (1064 nm) laser pulse is focused onto a deep liquid tin pool. Various laser spot sizes (70, 120, and 130 $$\upmu$$
μ
m in diameter) and various laser pulse energies (ranging 2.5–30 mJ) are used, resulting in laser fluences of $$\sim$$
∼
10–1000 J/cm$$^2$$

2

inducing pronounced splashing. Specifically, we study the time evolution of the splash crown-width. The crown width expansion velocity is found to be linearly dependent on the laser energy, and independent of the focal spot size. A collapse of all crown width evolution data onto a single master curve confirms that the hydrodynamic evolution of our laser-impact-induced splash is equivalent to droplet-impact-induced splashing. Laser-impact splashing is particularly relevant, e.g. for high-brightness laser-assisted discharge-produced plasma and laser-produced plasma sources of extreme ultraviolet light for nanolithography.
Efficacy and Safety of Intravenous rtPA in Ischemic Strokes Due to Small-Vessel Occlusion: Systematic Review and Meta-Analysis
Authors: Karaszewski Bartosz , Wyszomirski Adam , Jabłoński Bartosz , Werring David J. , Tomaka Dominika 
Published: February 2021

AbstractIntravenous recombinant tissue plasminogen activator (iv-rtPA) has been routinely used to treat ischemic stroke for 25 years, following large clinical trials. However, there are few prospective studies on the efficacy and safety of this therapy in strokes attributed to cerebral small vessel disease (SVD). We evaluated functional outcome (modified Rankin scale, mRS) and symptomatic intracerebral hemorrhage (sICH) using all available data on the effects of iv-rtPA in SVD-related ischemic stroke (defined either using neuroimaging, clinical features, or both). Using fixed-effect and random-effects models, we calculated the pooled effect estimates with regard to excellent and favorable outcomes (mRS=0–1 and 0–2 respectively, at 3 months), and the rate of sICH. Twenty-three studies fulfilled the eligibility criteria, 11 of which were comparative, and there were only 3 randomized clinical trials. In adjusted analyses, there was an increased odds of excellent outcome (adjusted OR=1.53, 95% CI: 1.29–1.82, I2: 0%) or favorable outcome (adjusted OR=1.68, 95% CI: 1.31–2.15,I2: 0%) in patients who received iv-rtPA compared with placebo. Across the six studies which reported it, the incidence of sICH was higher in the treatment group (M-H RR = 8.83, 95% CI: 2.76–28.27). The pooled rate of sICH in patients with SVD administered iv-rtPA was only 0.72% (95% CI: 0.12%–1.64%). We conclude that when ischemic stroke attributed to SVD is considered separately, available data on the effects of iv-rtPA therapy are insufficient for the highest level of recommendation, but it seems to be safe. Although further therapeutic trials in SVD-related ischemic stroke appear to be justified, our findings should not prevent its continued use for this group of patients in clinical practice.
Bench-scale assessment of three copper-based algaecide products for cyanobacteria management in source water
Authors: Crafton Elizabeth , Glowczewski Jessica , Cutright Teresa , Ott Don 
Published: February 2021

AbstractThree copper-based algaecide products were investigated for use in a drinking water source to address cyanobacteria growth. Bench-scale experiments were used to determine the optimal dose of each product given Lake Rockwell’s indigenous population and reservoir-specific characteristics. The optimal dose of Cutrine Ultra was determined to be a quarter dose (corresponding to 0.125 mg/L Cu) as it decreased 55% of the cyanobacteria population with limited release of microcystin and minimal rebound in the cyanobacteria population. The optimal dose for EarthTec was determined to be a half dose (i.e., 0.5 mg/L). The full dose was optimal for SeClear (1 mg/L Cu). The optimal doses had extracellular microcystin levels of 0.99 ± 0.09 µg/L (quarter dose Cutrine Ultra), 3.69 ± 0.43 µg/L (half dose EarthTec) and 0.92 ± 0.26 µg/L (full dose SeClear) by day 2. EarthTec and Cutrine Ultra facilitated a similar overall response, and the cyanobacteria population was predominately suppressed in the initial 2 days following treatment and then increased between 7 and 14 days after treatment (i.e., rebound). Both the suppression within the first 2 days and the rebound between 7 and 14 days after treatment were a function of dose (e.g., lower dose, larger increase in rebound). Although SeClear suppressed the cyanobacteria population during the initial 2 days after treatment (42,000 ± 3240 cells/mL at the baseline to 4822 ± 841), the cyanobacteria population rebounded significantly (p < 0.05) between 2 and 7 days after treatment.
TRIM41 is required to innate antiviral response by polyubiquitinating BCL10 and recruiting NEMO
Authors: Yu Zhou , Li Xuelian , Yang Mingjin , Huang Jiaying , Fang Qian , Jia Jianjun , Li Zheng , Gu Yan , Chen Taoyong , Cao Xuetao 
Published: February 2021

AbstractSensing of pathogenic nucleic acids by pattern recognition receptors (PRR) not only initiates anti-microbe defense but causes inflammatory and autoimmune diseases. E3 ubiquitin ligase(s) critical in innate response need to be further identified. Here we report that the tripartite motif-containing E3 ubiquitin ligase TRIM41 is required to innate antiviral response through facilitating pathogenic nucleic acids-triggered signaling pathway. TRIM41 deficiency impairs the production of inflammatory cytokines and type I interferons in macrophages after transfection with nucleic acid-mimics and infection with both DNA and RNA viruses. In vivo, TRIM41 deficiency leads to impaired innate response against viruses. Mechanistically, TRIM41 directly interacts with BCL10 (B cell lymphoma 10), a core component of CARD proteins−BCL10 − MALT1 (CBM) complex, and modifies the Lys63-linked polyubiquitylation of BCL10, which, in turn, hubs NEMO for activation of NF-κB and TANK-binding kinase 1 (TBK1) − interferon regulatory factor 3 (IRF3) pathways. Our study suggests that TRIM41 is the potential universal E3 ubiquitin ligase responsible for Lys63 linkage of BCL10 during innate antiviral response, adding new insight into the molecular mechanism for the control of innate antiviral response.
Surgical Treatment of Middle Cerebral Artery Aneurysms: Hints and Precautions for Young Cerebrovascular Surgeons
Authors: Sturiale Carmelo Lucio , Rapisarda Alessandro , Marchese Enrico , Puca Alfredo , Olivi Alessandro , Albanese Alessio 
Published: February 2021

Abstract
Background and Objective Clipping is still considered the treatment of choice for middle cerebral artery (MCA) aneurysms due to their angioarchitectural characteristics as they are often bifurcation dysplasias, needing a complex reconstruction rather than a simple exclusion. Thus, maintaining this surgical expertise is of paramount importance to train of young cerebrovascular surgeons. To balance for the increasingly limited experience due the worldwide general inclination toward the endovascular approaches, it is important to provide to the young neurosurgeons rules and operative nuances to guide this complex surgery. We describe the technical algorithm we use to teach our residents to approach ruptured and unruptured MCA aneurysms, which may help to develop a procedural memory useful to perform an effective and safe surgery.
Materials and Methods We reviewed our last 10 years' institutional experience of about 400 cases of ruptured and unruptured MCA aneurysms clipping, analyzing our technical refinements and the difficulties in residents and young neurosurgeons teaching, to establish fundamental key-points and design a didactic algorithm that includes operative instructions and safety rules.
Results We recognized seven pragmatic technical key points regarding craniotomy, sylvian fissure opening, basal cisternostomy, proximal vessel control, lenticulostriate arteries preservation, aneurysm neck microdissection, and clipping to use as a didactic algorithm for teaching residents, and as operative instructions for inexperienced neurosurgeons.
Conclusion In the setting of clipping MCA aneurysms, respect for surgical rules is of paramount importance to perform an effective and safe procedure, ensure the best aneurysm exclusion, and preserve the flow in collaterals and perforators.
Novel Use of Intraoperative Fluoroscopy in an Era of ICG for Complex Laparoscopic Cholecystectomy
Authors: Gandhi Jignesh A. , Shinde Pravin H. , Chaudhari Sadashiv N. , Banker Amay M. 
Published: February 2021

Abstract
Background Laparoscopic cholecystectomy (LC) is increasingly being used as a first-line treatment for acute cholecystitis. Bile duct injury (BDI) remains the most feared complication of the minimally invasive approach specially in cases with an inflamed calots triangle. While use of indocyanine dye (ICG) to delineate biliary anatomy serves to reduce BDI, the high cost of the technology prohibits its use in the developing world. We propose a novel use of common bile duct (CBD) stenting preoperatively in cases of cholecystitis secondary to choledocholithiasis as a means of identification and safeguarding the CBD.
Methods A retrospective review was conducted on 22 patients of Grade 2 or Grade 3 cholecystitis who underwent an early LC at our institution. All patients were stented preoperatively and the stent was used for a much-needed tactile feedback during dissection. A c-arm with intraoperative fluoroscopy was used to identify the CBD prior to clipping of the cystic duct.
Results The gall bladder was gangrenous in all the cases while two cases had evidence of end organ damage. This innovative use of CBD stenting allowed us to correctly delineate biliary anatomy in all of the cases and we report no instances of BDI despite a severely inflamed local environment.
Conclusion This technique can become a standard of care in all teaching institutions in developing countries further enhancing the safety of cholecystectomy in gangrenous cholecystitis with a distorted biliary anatomy.
High-temperature resistant polypropylene films enhanced by atomic layer deposition
Authors: Wu Xudong , Tang Shaokai , Song Guanghui , Zhang Zihan , Tan Daniel Q 
Published: February 2021

Abstract
Last two decades has witnessed various technical programs towards the development of new dielectric films for high temperature and high energy density capacitor technology. Yet, the organic polypropylene film still holds its top position for film capacitors required for electric and electronic power applications such as power grid, hybrid electric vehicles, oil and gas exploration, and aviation. However, its low temperature stability determined by its structural nature limits its further adoption for more rising markets. This work thus developed a creative method (ultrathin coating of inorganic compound using atomic layer deposition) to increase the high temperature stability and the dielectric strength of such a strategically important polymer film from below 105 °C to above 140 °C. Several techniques also confirmed the effective minimization of the dimensional change and crystallinity loss at higher temperatures, i.e., Thermomechanical analysis, Dynamic mechanical analysis, Dynamic Scanning calorimetry, x-ray diffraction and electron microscopy techniques. This breakthrough discovery adds a huge value to the commercial PP films and relevant capacitor industry and will extend the operation of high-performance PP film capacitors to various high standard applications.
A survey on computational models for predicting protein–protein interactions
Authors: Hu Lun , Wang Xiaojuan , Huang Yu-An , Hu Pengwei , You Zhu-Hong 
Published: February 2021

AbstractProteins interact with each other to play critical roles in many biological processes in cells. Although promising, laboratory experiments usually suffer from the disadvantages of being time-consuming and labor-intensive. The results obtained are often not robust and considerably uncertain. Due recently to advances in high-throughput technologies, a large amount of proteomics data has been collected and this presents a significant opportunity and also a challenge to develop computational models to predict protein–protein interactions (PPIs) based on these data. In this paper, we present a comprehensive survey of the recent efforts that have been made towards the development of effective computational models for PPI prediction. The survey introduces the algorithms that can be used to learn computational models for predicting PPIs, and it classifies these models into different categories. To understand their relative merits, the paper discusses different validation schemes and metrics to evaluate the prediction performance. Biological databases that are commonly used in different experiments for performance comparison are also described and their use in a series of extensive experiments to compare different prediction models are discussed. Finally, we present some open issues in PPI prediction for future work. We explain how the performance of PPI prediction can be improved if these issues are effectively tackled.