bluuebunny/crossref_metadata_2025_split huggingface dataset:
Agarose Micro‐Well Platform for Rapid Generation of Homogenous 3D Tumor Spheroids
Authors: Krishnan Mena Asha , Yadav Kratika , Chelvam Venkatesh 
Published: July 2021

AbstractIn recent years, 3D culture of tumor spheroids has managed to revolutionize cancer research and drug discovery. 2D monolayer cells grown in cell culture flasks undergo radical changes in cell behavior, structure, and function owing to varying environmental cues and are unable to provide predictive data for preclinical evaluation. 3D tumor spheroids can better recapitulate tumor architecture, cell‒cell and cell‒matrix connectivity, and the tissue complexity of tumors grown in animal models. However, many of the existing techniques to culture 3D spheroids are time‐consuming and ineffective and produce irregular‐shaped spheroids that cannot be easily incorporated in biological assays. The set of protocols described herein makes use of a commercial hair brush as a template to create concave micro‐well impressions in agarose. This technique is easy, inexpensive, and adaptable and also has the ability to produce uniform, homogenous cancer spheroids, with large diameter (∼1000 μm) and thickness (∼250 μm), within 24 to 48 hr after cell seeding. The 3D spheroids produced using the agarose micro‐well platform function as an excellent 3D in vitro model for understanding the extent of penetration, uptake, and distribution of targeted cargos such as a diagnostic or therapeutic agents for identification and treatment of cancer. © 2021 Wiley Periodicals LLC.Basic Protocol 1: Fabrication of agarose micro‐well scaffold for growing tumor spheroids using a commercial hair brushBasic Protocol 2: Formation of homogenous tumor spheroids in agarose micro‐well platformBasic Protocol 3: Assessing viability of 3D tumor spheroids grown in agarose micro‐wells using confocal microscopyBasic Protocol 4: Analyzing uptake and penetration of targeted fluorescent bioconjugate in 3D tumor spheroids using two‐photon imaging
Photocrosslinking O‐GlcNAcylated Proteins to Neighboring Biomolecules
Authors: Capota Emanuela , Wu Han , Kohler Jennifer J. 
Published: July 2021

AbstractThis protocol enables identification of the interaction partners of O‐GlcNAcylated proteins. The method involves the introduction of the diazirine photocrosslinker onto the O‐GlcNAc modification within living cells. The photocrosslinker is activated by UV light to yield covalent crosslinking between O‐GlcNAcylated proteins and neighboring molecules. The binding partners can be further characterized by immunoblot or proteomics mass spectrometry methods. The benefits of using the photocrosslinker include the capacity to trap low‐affinity binding interactions and the ability to selectively target the interaction partners of the O‐GlcNAcylated form of the protein of interest. © 2021 Wiley Periodicals LLC.Basic Protocol 1: In‐cell production and crosslinking of O‐GlcNDAzylated proteinsBasic Protocol 2: Immunoblot analysis to assess O‐GlcNDAz crosslinkingSupport Protocol: Detection of UDP‐GlcNDAz from cell lysates
Graphene with Covalently Grafted Amino Acid as a Route Toward Eco‐Friendly and Sustainable Supercapacitors
Authors: Vermisoglou Eleni C. , Jakubec Petr , Bakandritsos Aristides , Kupka Vojtěch , Pykal Martin , Šedajová Veronika , Vlček Jakub , Tomanec Ondřej , Scheibe Magdalena , Zbořil Radek , Otyepka Michal 
Published: July 2021

AbstractEco‐friendly, electrochemically active electrode materials based on covalent graphene derivatives offer enormous potential for energy storage applications. However, covalent grafting of functional groups onto the graphene surface is challenging due to its low reactivity. Here, fluorographene chemistry was employed to graft an arginine moiety via its guanidine group homogeneously on both sides of graphene. By tuning the reaction conditions and adding a non‐toxic pore‐forming agent, an optimum degree of functionalization and hierarchical porosity was achieved in the material. This tripled the specific surface area and yielded a high capacitance value of approximately 390 F g−1 at a current density of 0.25 A g−1. The applicability of the electrode material was investigated under typical operating conditions by testing an assembled supercapacitor device for up to 30000 charging/discharging cycles, revealing capacitance retention of 82.3 %. This work enables the preparation of graphene derivatives with covalently grafted amino acids for technologically important applications, such as supercapacitor‐based energy storage.
Valorization of Small Alkanes by Biocatalytic Oxyfunctionalization
Authors: Mahor Durga , Cong Zhiqi , Weissenborn Martin J. , Hollmann Frank , Zhang Wuyuan 
Published: July 2021

AbstractThe oxidation of alkanes into valuable chemical products is a vital reaction in organic synthesis. This reaction, however, is challenging, owing to the inertness of C−H bonds. Transition metal catalysts for C−H functionalization are frequently explored. Despite chemical alternatives, nature has also evolved powerful oxidative enzymes (e. g., methane monooxygenases, cytochrome P450 oxygenases, peroxygenases) that are capable of transforming C−H bonds under very mild conditions, with only the use of molecular oxygen or hydrogen peroxide as electron acceptors. Although progress in alkane oxidation has been reviewed extensively, little attention has been paid to small alkane oxidation. The latter holds great potential for the manufacture of chemicals. This Minireview provides a concise overview of the most relevant enzyme classes capable of small alkanes (C<6) oxyfunctionalization, describes the essentials of the catalytic mechanisms, and critically outlines the current state‐of‐the‐art in preparative applications.
Current advances in digital cognitive assessment for preclinical Alzheimer's disease
Authors: Öhman Fredrik , Hassenstab Jason , Berron David , Schöll Michael , Papp Kathryn V. 
Published: July 2021

AbstractThere is a pressing need to capture and track subtle cognitive change at the preclinical stage of Alzheimer's disease (AD) rapidly, cost‐effectively, and with high sensitivity. Concurrently, the landscape of digital cognitive assessment is rapidly evolving as technology advances, older adult tech‐adoption increases, and external events (i.e., COVID‐19) necessitate remote digital assessment. Here, we provide a snapshot review of the current state of digital cognitive assessment for preclinical AD including different device platforms/assessment approaches, levels of validation, and implementation challenges. We focus on articles, grants, and recent conference proceedings specifically querying the relationship between digital cognitive assessments and established biomarkers for preclinical AD (e.g., amyloid beta and tau) in clinically normal (CN) individuals. Several digital assessments were identified across platforms (e.g., digital pens, smartphones). Digital assessments varied by intended setting (e.g., remote vs. in‐clinic), level of supervision (e.g., self vs. supervised), and device origin (personal vs. study‐provided). At least 11 publications characterize digital cognitive assessment against AD biomarkers among CN. First available data demonstrate promising validity of this approach against both conventional assessment methods (moderate to large effect sizes) and relevant biomarkers (predominantly weak to moderate effect sizes). We discuss levels of validation and issues relating to usability, data quality, data protection, and attrition. While still in its infancy, digital cognitive assessment, especially when administered remotely, will undoubtedly play a major future role in screening for and tracking preclinical AD.
The effects of lower body compression on left ventricular rotational mechanics in lymphoedema (from the MAGYAR‐Path Study)
Authors: Nemes Attila , Kormányos Árpád , Domsik Péter , Kalapos Anita , Kemény Lajos , Szolnoky Győző 
Published: July 2021

AbstractAimsLower body half compression of bilateral secondary leg lymphoedema (LE) without relevant cardiac insufficiency gives rise to whether external leg compression may influence left ventricular (LV) function. Patients with LE were subjected to baseline two‐dimensional transthoracic echocardiography (2DTTE) for general assessment then three‐dimensional speckle‐tracking echocardiography (3DSTE) before and 1 h after lower body half external compression for LV torsion analysis.Methods and resultsBaseline 2DTTE was performed in the cohort of 25 LE patients, and the results were compared with those of age‐ and gender‐matched 52 healthy controls (mean age: 47.8 ± 12.8 vs. 40.7 ± 14.0 years, 24 women/1 man vs. 49 women/3 men, respectively). 3DSTE was conducted for the assessment of LV rotational mechanics where apical (AR), and basal rotations (BR) were measured before and 1 h after the use of compression class 2 (ccl 2) flat‐knitted medical compression pantyhoses (pressure range: 23–32 mmHg). 2DTTE showed significantly larger LV end‐diastolic volume and ejection fraction among LE patients compared with control subjects (108.3 ± 20.1 vs. 98.5 ± 21.7 mL, 69.8 ± 4.8 vs. 65.5 ± 4.3%, respectively) and notably smaller LV end‐systolic diameter and posterior wall thickness (28.9 ± 3.5 vs. 31.2 ± 3.4 mm, 8.1 ± 1.0 vs. 9.0 ± 1.7 mm, respectively). The results of 20 patients with LE were considered in 3DSTE examinations due to the drop‐out of five probands with technical failures. The data of four LE patients showing significant LV rotational abnormalities were managed separately, and the rotational parameters of the remaining sixteen patients did not differ significantly from those of matched controls except significant reduction of LV BR following the application of medical compression stockings (MCS) (−2.70 ± 1.26 degrees after 1 h use of pantyhose in patient group vs. −4.28 ± 2.18 degrees of the control group; P < 0.05).ConclusionsThe application of compression pantyhoses moderately but significantly decreased LV BR without a remarkable impact on twisting mechanism in LE patients in the absence of LV rotational abnormalities.
Alkali Metallosilicates: Synthesis, Structure and Evaluation in the ROP of ϵ‐Caprolactone
Authors: Pérez‐Pérez Jovana , Hernández‐Balderas Uvaldo , Martínez‐Otero Diego , Moya‐Cabrera Mónica , Jancik Vojtech 
Published: July 2021

AbstractA series of metallosilicate complexes (tBuO)2(RO)SiOM (R=tBu, iPr, Et, Me; M=Li, Na, K) were prepared from tailor‐made silanols. The complexes show different degree of association and feature heterocubane, double‐heterocubane or hexagonal prism framework in solid state while ESI‐MS shows fragmentation of the oligomers. The steric hindrance around the silicon atom has a direct influence over the association of the alkali derivatives, and the size of the alkali metal influences the shape of the MxOx core. These compounds were studied as initiators in the ROP of ϵ‐caprolactone, varying temperature, reaction‐time, monomer/initiator ratio, metal center variation and association degree. The best results were achieved with [{(tBuO)3SiO}4Li4] (1) producing an almost quantitive yield of polycaprolactone (97 %, Mn=35 kg mol−1, Mw/Mn=1.72).
Hydrogen‐Bonding Interactions of Methylated Adenine Derivatives
Authors: Osifová Zuzana , Socha Ondřej , Mužíková Čechová Lucie , Šála Michal , Janeba Zlatko , Dračínský Martin 
Published: July 2021

AbstractHydrogen bonding between nucleobases is a crucial noncovalent interaction for the life on Earth. Apart from Watson‐Crick binding, Hoogsteen pairing has been found in many structures of nucleic acids. Methylation of nucleic acids (NAs) is a post‐replication or post‐transcription mechanism that can modulate the structure and function of a NA without changing its sequence. Methylation of adenine at the N6 position to form m6A is one of the most important and common epigenetic markers. This paper describes an investigation of intermolecular H‐bonding interactions of methylated derivatives of adenine with its complementary partner, thymine. Adenine derivatives with (di)methylamino groups in positions 2 or 6 have been prepared and their interactions with a thymine derivative have been studied by NMR spectroscopy and DFT calculations. It has been found that Hoogsteen pairing is preferred for adenine derivatives, which offer two hydrogen‐bond sites on both Watson‐Crick and Hoogsteen sides of the molecule. Methylation of the N6 position leads to further stabilization of the Hoogsteen pair.
Modulatory role of the orexin system in stress‐induced analgesia: Involvement of the ventral tegmental area
Authors: Askari Kobra , Oryan Shahrbanoo , Eidi Akram , Zaringhalam Jalal , Haghparast Abbas 
Published: July 2021

AbstractBackgroundExposure to stressful experiences is often accompanied by suppressing pain perception, referred to as stress‐induced analgesia. The neuropeptides orexins are essential in regulating the mechanism that responds to stressful and painful stimuli. Meanwhile, the ventral tegmental area (VTA), as a part of descending pain inhibitory system, responds to noxious stimuli. This study aimed to investigate the role of intra‐VTA administration of orexin receptor antagonists on stress‐induced antinociceptive responses in the animal model of acute pain.MethodNinety‐three adult Wistar rats weighing 230–250 g were unilaterally implanted by a cannulae above the VTA. Animals were pretreated with different doses (1, 3, 10 and 30 nM/0.3 μl) of SB334867 as the orexin‐1 receptor antagonist and TCS OX2 29 as the orexin‐2 receptor antagonist into the VTA, just 5 min before 6 min exposure to forced swim stress (FSS). Nociceptive threshold was measured using the tail‐flick test as a model of acute pain.ResultsThe results showed that exposure to FSS could significantly increase analgesic responses. Moreover, intra‐VTA administration of SB334768 and TCS OX2 29 blocked the antinociceptive effect of FSS in the tail‐flick test.ConclusionThe findings suggest that OX1 and OX2 receptors in the VTA might modulate the antinociceptive behaviours induced by FSS in part.SignificanceAcute exposure to physical stress suppresses pain‐related behaviors in the animal model of acute pain. Blockade of the OX1 and OX2 receptors in the VTA attenuates antinociceptive responses induced by FSS. The contribution of the OX2 receptors in the VTA is more predominant than OX1 receptors in stress‐induced analgesia.
Phantom limb pain after unilateral arm amputation is associated with decreased heat pain thresholds in the face
Authors: Fuchs Xaver , Diers Martin , Trojan Jörg , Kirsch Pinar , Milde Christopher , Bekrater‐Bodmann Robin , Rance Mariela , Foell Jens , Andoh Jamila , Becker Susanne , Flor Herta 
Published: July 2021

AbstractBackgroundThe mechanisms underlying chronic phantom limb pain (PLP) are complex and insufficiently understood. Altered sensory thresholds are often associated with chronic pain but quantitative sensory testing (QST) in PLP has so far been inconclusive due to large methodological variation between studies and small sample sizes.MethodsIn this study, we applied QST in 37 unilateral upper‐limb amputees (23 with and 14 without PLP) and 19 healthy controls. We assessed heat pain (HPT), pressure pain, warmth detection and two‐point discrimination thresholds at the residual limb, a homologous point and the thenar of the intact limb as well as both corners of the mouth.ResultsWe did not find significant differences in any of the thresholds between the groups. However, PLP intensity was negatively associated with HPT at all measured body sites except for the residual limb, indicating lower pain thresholds with higher PLP levels. Correlations between HPT and PLP were strongest in the contralateral face (r = −0.65,p < 0.001). Facial HPT were specifically associated with PLP, independent of residual limb pain (RLP) and various other covariates. HPT at the residual limb, however, were significantly associated with RLP, but not with PLP.ConclusionWe conclude that the association between PLP and, especially facial, HPT could be related to central mechanisms.SignificancePhantom limb pain (PLP) is still poorly understood. We show that PLP intensity is associated with lower heat pain thresholds, especially in the face. This finding could be related to central nervous changes in PLP.
Direct and Delayed Mortality of Ceriodaphnia dubia and Rainbow Trout Following Time-Varying Acute Exposures to Zinc
Authors: Mebane Christopher A. , Ivey Christopher D. , Wang Ning , Steevens Jeffery A. , Cleveland Danielle , Elias Michael C. , Justice James R. , Gallagher Kathryn , Brent Robert N. 
Published: July 2021

Abstract
The potential for delayed mortality following short-term episodic pollution events was evaluated by exposing cladocerans (Ceriodaphnia dubia) and rainbow trout (Oncorhynchus mykiss) to zinc (Zn) in various 1- to 48-h and 1- to 96-h exposures, respectively, followed by transferring the exposed organisms to clean water for up to 47 h for C. dubia and up to 95 h for trout for additional observation. For C. dubia, 1-h exposures of up to 3790 µg Zn/L never resulted in mortality during the actual Zn exposures, but by 48 h, a 1-h exposure to 114 µg/L, a concentration similar to the present US national water quality acute criterion for the test water conditions, ultimately killed 70% of C. dubia. With C. dubia, the speed of action of Zn toxicity was faster for intermediate concentrations than for the highest concentrations tested. For rainbow trout, pronounced delayed mortalities by 96 h only occurred following ≥8-h exposures. For both species, ultimate mortalities from Zn exposures ≤8 h mostly presented as delayed mortalities, whereas for exposures ≥24 h, almost all ultimate mortalities presented during the actual exposure periods. With Zn, risks of delayed mortality following exposures to all concentrations tested were much greater for the more sensitive, small-bodied invertebrate (C. dubia) than for the less sensitive, larger-bodied fish (rainbow trout). These results, along with previous studies, show that delayed mortality is an important consideration in evaluating risks to aquatic organisms from brief, episodic exposures to some substances. Environ Toxicol Chem 2021;40:2484–2498. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.
Abstract
Rainbow trout could withstand extreme Zn pulses of 1 to 3 h, with few subsequent deaths. Few Ceriodaphnia dubia died during 1- to 3-h Zn pulses, but after 48 h, most were dead. Time to effects decreased as expected as rainbow trout were exposed to increasing Zn concentrations. Not so with C. dubia: time to effects was fastest in intermediate Zn exposures, with longer survivals in higher Zn exposures.
The Impact of Disturbed Soil Structure on the Degradation of 2 Fungicides Under Constant and Variable Moisture
Authors: Hand Laurence H. , Marshall Samantha J. , Dougan Christine , Nichols Carol , Kende Aniko , Ritz Karl , Oliver Robin G. 
Published: July 2021

Abstract
Degradation of agrochemicals in soil is frequently faster under field conditions than in laboratory studies. Field studies are carried out on relatively undisturbed soil, whereas laboratory studies typically use sieved soil, which can have a significant impact on the physical and microbial nature of the soil and may contribute to differences in degradation between laboratory and field studies. A laboratory study was therefore conducted to determine the importance of soil structure and variable soil moisture on the degradation of 2 fungicides (azoxystrobin and paclobutrazol) that show significant differences between laboratory and field degradation rates in regulatory studies. Degradation rates were measured in undisturbed cores of a sandy clay loam soil (under constant or variable moisture contents) and in sieved soil. For azoxystrobin, degradation rates under all conditions were similar (median degradation time [DegT50] 34–37 d). However, for paclobutrazol, degradation was significantly faster in undisturbed cores (DegT50 255 d in sieved soil and 63 d in undisturbed cores). Varying the moisture content did not further enhance degradation of either fungicide. Further examination into the impact of soil structure on paclobutrazol degradation, comparing undisturbed and sieved/repacked cores, revealed that the impact of sieving could not be mitigated by repacking the soil to a realistic bulk density. Examination of fungal and bacterial community structure using automated ribosomal spacer analysis showed significant initial differences between sieved/repacked and intact soil cores, although such differences were reduced at the end of the study (70 d). The present study demonstrates that disruption of soil structure significantly impacts microbial community structure, and for some compounds this may explain the differences between laboratory and field degradation rates. Environ Toxicol Chem 2021;40:2715–2725. © 2021 SETAC
Abstract
Investigation of the impact of retention of soil structure on the degradation rates of azoxystrobin and paclobutrazol.
Sublethal Effect Concentrations for Nonpolar Narcosis in the Zebrafish Embryo
Authors: Massei Riccardo , Knapen Dries , Covaci Adrian , Blust Ronny , Mayer Philipp , Vergauwen Lucia 
Published: July 2021

Abstract
Nonpolar narcosis, also known as baseline toxicity, has been described as the minimal toxicity that an organic chemical may elicit based on its lipophilicity. Although lethal effects of narcosis-inducing chemicals (NICs) have been thoroughly investigated, knowledge of sublethal effects is still very limited. We investigated the effects of 3 well-known NICs (phenanthrene, 1,3,5-trichlorobenzene, and pentachlorobenzene) on a variety of organismal endpoints (malformations, swim bladder inflation, respiration, heart rate, swimming activity, and turning angles), which can be plausibly linked to narcosis in zebrafish embryos. Baseline toxicity recorded as mortality is typically observed in similar exposure ranges in a wide variety of species including fish, corresponding to a chemical activity range between 0.01 and 0.1. In the present study, we found that sublethal effects occurred at concentrations approximately 5 times below lethal concentrations. Altered swimming activity and impaired swim bladder inflation were the most sensitive endpoints occurring at exposure levels below the generally accepted threshold for baseline toxicity for 2 out of 3 compounds. Overall, most effective exposure levels across the sublethal endpoints and compounds did fall within the range typically associated with baseline toxicity, and deviations were generally limited to a factor 10. Although there could be benefit in adding sublethal endpoints to toxicity tests, such as the fish embryo acute toxicity (FET) test, based on the present sublethal endpoints and available evidence from our and other studies, the underestimation of toxicity as a result of the sole assessment of mortality as an endpoint in an FET test may be limited for narcosis. Environ Toxicol Chem 2021;40:2802–2812. © 2021 SETAC