bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gold‐Mushroom Microelectrode Arrays and the Quest for Intracellular‐Like Recordings: Perspectives and Outlooks
Authors: Teixeira Henrique , Dias Catarina , Aguiar Paulo , Ventura João 
Published: December 2020

AbstractThe ongoing search to decode the brain communication system has propelled major advancements in bioelectronics research. From these, planar microelectrode arrays (MEAs) offer the possibility to record neuronal signals for extremely long periods of time and to probe fundamental principles of learning and adaptation. Unfortunately, MEAs have low neuronal coupling and are thus insensitive to sub‐threshold neuronal signals such as post‐synaptic responses. To surpass this major limitation, a novel category based on 3D high aspect ratio microstructures has emerged. In particular, gold‐mushroom microelectrode arrays (GMμEAs) have appeared as a solution. Their unique morphology, promoting cell engulfment without penetrating the neuron, prevents the occurrence of cell repairing mechanisms common in other microelectrodes. This new class of recording and/or stimulating devices have opened the door to the vast communication system of neuronal cells by enhancing the cell–microelectrode interface. This review compiles the fundamentals of these promising devices including their fabrication, work principles and focusing on how the different morphological parameters affect the recording performance. Although limitations exist, there is a growing interest to explore the new solutions that GMμEAs still offer, both as an electrophysiological tool (e.g., cell guidance) or in applications such as plasmonics.
Biointegrated Fluidic Milling
Authors: Widerker Daniel , Paratore Federico , Bercovici Moran , Kaigala Govind 
Published: December 2020

AbstractThis paper presents a device (“fluidic biomill”) and method for integrated mechanical structuring and biofunctionalization of microfluidic channels, enabling rapid prototyping of biochips. The fluidic biomill leverages hydrodynamic flow confinements (HFCs) to localize the interaction between a fluid and a substrate to a microscale region. By confining organic solvents, and scanning with the biomill over the substrate surface, microchannels as deep as 90 µm are fluidically milled. Subsequently, by switching the confined fluid from a milling solution to a patterning solution, biomolecules are immobilized on the surface of the microchannel. An in‐depth analysis of fluidic milling rates and milled microchannel properties is presented, along with a discussion on the dominant factors in controlling the dimensions of the fluidically milled channel. To demonstrate the utility of this method, a biotin functionalized biochip is fabricated in less than 5 min out of a polystyrene slide and its functionalities are validated by implementing on‐chip electrokinetic sample focusing, pressure driven flow, and a surface‐based reaction.
The effect of curvature on chondrocytes migration and bone mesenchymal stem cells differentiation
Authors: Cao Xing , Liu Xiangli , Liu Yan , Ma Rui , Sun Shichang 
Published: December 2020

AbstractNumerous cells grow in columnar tissues and organs with different curvatures and curvature gradients. Therefore, it is necessary to study the effect of curvature on cell behavior to control and promote cell development. Herein, we prepared polydimethylsiloxane (PDMS) with different micro‐nano patterns using ultraviolet soft lithography. Hydrophilic polydopamine (PDA) was modified on the PDMS surface to prepare PDMS/PDA to improve its biocompatibility. The PDMS/PDA was characterized by contact angle tester and scanning electron microscopy (SEM). The effect of curvature on bone cell migration and differentiation was studied through SEM, inverted phase contrast microscope and fluorescence microscopy. We found that different curvatures had different effects on the bone cell migration and differentiation. Chondrocytes migrated rapidly in grooves with a curvature range of 1/575–1/875 μm−1. Bone mesenchymal stem cells (BMSCs) had high efficiency of differentiation into chondrocytes in the grooves with a curvature range of 1/775–1/1375 μm−1. Furthermore, BMSCs showed high efficiency of differentiation into chondrocytes at the edges of micro‐nano patterns with different perimeter curvatures, and the differentiation efficiency was the highest at 120° convex curvature. This work shows that curvature is a principle to be considered in bone tissue regeneration engineering and provides inspiration for future biomaterials design.
Synthesis of New Tyrosol‐Based Phosphodiester Derivatives: Effect on Amyloid β Aggregation and Metal Chelation Ability
Authors: Romanucci Valeria , Giordano Maddalena , De Tommaso Gaetano , Iuliano Mauro , Bernini Roberta , Clemente Mariangela , Garcia‐Viñuales Sara , Milardi Danilo , Zarrelli Armando , Di Fabio Giovanni 
Published: December 2020

AbstractAlzheimer's disease (AD) is a multifactorial pathology that requires multifaceted agents able to address its peculiar nature. Increasing evidence has shown that aggregation of amyloid β (Aβ) and oxidative stress are strictly interconnected, and their modulation might have a positive and synergic effect in contrasting AD‐related impairments. Herein, a new and efficient fragment‐based approach towards tyrosol phosphodiester derivatives (TPDs) has been developed starting from suitable tyrosol building blocks and exploiting the well‐established phosphoramidite chemistry. The antioxidant activity of new TPDs has been tested as well as their ability to inhibit Aβ protein aggregation. In addition, their metal chelating ability has been evaluated as a possible strategy to develop new natural‐based entities for the prevention or therapy of AD. Interestingly, TPDs containing a catechol moiety have demonstrated highly promising activity in inhibiting the aggregation of Aβ40 and a strong ability to chelate biometals such as CuII and ZnII.
Widespread myofascial dysfunction and sensitisation in women with endometriosis‐associated chronic pelvic pain: A cross‐sectional study
Authors: Phan Vy T. , Stratton Pamela , Tandon Hannah K. , Sinaii Ninet , Aredo Jacqueline V. , Karp Barbara I. , Merideth Melissa A. , Shah Jay P. 
Published: December 2020

AbstractBackgroundChronic pelvic pain persists in some women with endometriosis even after lesion removal and optimized hormonal treatment.ObjectiveCharacterize the presence and distribution of pain, myofascial dysfunction and sensitisation beyond the pelvis in women with endometriosis‐associated chronic pelvic pain.MethodsCross‐sectional study of 30 women prior to participation in a clinical trial. Evaluation included pain‐focused abdominopelvic gynaecologic examination with the identification of pelvic floor muscle spasm. Neuro‐musculoskeletal examination assessed paraspinal allodynia and hyperalgesia bilaterally and myofascial trigger points in 13 paired muscles. Pressure‐pain thresholds were measured over interspinous ligaments and trigger points. Women completed the body territories element of the Body Pain Index.ResultsAll women had a pelvic floor muscle spasm that they self‐identified as a major focus of pain. Twenty of 30 women described their pelvic pain as focal. However, all demonstrated widespread myofascial dysfunction with low pressure‐pain thresholds and trigger points in over two‐thirds of 26 assessed regions. Widespread spinal segmental sensitisation was present in 17/30, thoracic in 21/30 and lumbosacral/pelvic in 18/30. Cervical sensitisation manifested as low pressure‐pain thresholds with 23/30 also reporting recurrent, severe headaches and 21/30 experiencing orofacial pain. Those reporting diffuse pelvic pain were more likely to have widespread (p = .024) and lumbosacral/pelvic (p = .036) sensitisation and report over 10 painful body areas (p = .009).ConclusionsWomen with endometriosis‐associated chronic pelvic pain often have myofascial dysfunction and sensitisation beyond the pelvic region that may be initiated or maintained by on‐going pelvic floor spasm. These myofascial and nervous system manifestations warrant consideration when managing pain in this population.Clinicaltrials.gov identifier: NCT01553201.SignificanceWomen with endometriosis often have pelvic pain persisting after surgery despite hormonal therapies and these women have regional pelvic sensitisation and myofascial dysfunction. Pelvic floor muscle spasm is a major pain focus in this population. Sensitisation and myofascial dysfunction are widespread, beyond the pelvic region. On‐going pelvic floor spasm may initiate or maintain sensitisation. Myofascial/sensitisation manifestations warrant consideration when managing pain in this population.
Dependence‐like behaviour in patients treated for medication overuse headache: A prospective open‐label randomized controlled trial
Authors: Rouw Carolien , Munksgaard Signe B. , Engelstoft Ida M.S. , Nielsen Mia , Westergaard Maria L. , Jensen Rigmor H. , Bendtsen Lars , Carlsen Louise N. 
Published: December 2020

AbstractBackgroundDependence‐like behaviour may complicate withdrawal and increase risk of relapse of medication overuse headache (MOH). The most effective treatment for reducing dependence‐like behaviour is unknown.ObjectivesTo compare patient‐reported outcomes among three treatment strategies for MOH. The primary outcome was change in Severity of Dependence Scale (SDS) score from baseline to 6 months.MethodsPatients with MOH were randomized to (1) withdrawal combined with preventive medication from start (W+P), (2) preventive medication without withdrawal (P), or (3) withdrawal with optional preventive medication 2 months after withdrawal (W). At baseline, 2, and 6 months, patients filled out SDS (used for measurements of dependence‐like behaviour and treatment feasibility), Headache Under‐Response of Treatment (HURT) and WHO Quality of Life BREF questionnaires.ResultsOut of 120 patients with MOH, 100 completed the 6‐month follow‐up and filled out questionnaires. The W+P arm was the most effective in treating MOH. After 6 months, the SDS score was reduced by 3.69 (95% CI 3.23–4.49) in the W+P arm, by 3.19 (95% CI 2.43–3.96) in the W arm, and by 1.65 (95% CI 0.96–2.33) in the P arm (p = 0.04). At baseline and after 2 months, the P arm was considered the most feasible treatment, but at 6‐month follow‐up, there was no difference in feasibility score, change in HURT score, or quality of life.ConclusionsDependence‐like behaviour was reduced most in the two withdrawal arms. Withdrawal combined with preventive medication is recommended for the treatment of MOH.SignificanceWithdrawal combined with preventive medication from start is the treatment strategy that reduces dependence‐like behaviour the most in MOH patients. Patients initially considered preventive treatment without withdrawal as the most feasible treatment. However, no difference in feasibility between the three arms was found at 6‐month follow‐up. Withdrawal combined with preventive medication is recommended for treatment of MOH.
Formation Mechanism Analysis of Shear‐Induced Microgel Filaments during Microfluidic Gelation
Authors: Fukushima Shuhei , Takayama Yuriko , Nasuno Eri , Yanagida Yasuko , Kato Norihiro 
Published: December 2020

AbstractDynamic microfluidic gelation enables the fabrication of bundle‐structured multiple parallel microgel filaments from an aqueous two‐phase system. The formation mechanism of shear‐induced filaments from an alginate (Alg)/polyvinyl alcohol (PVA) blend is studied using red‐colored PVA and a titanium alkoxide PVA crosslinker. Bundle‐structured Alg microgel filaments are formed through contact with a Ca2+ crosslinker. In this process, the PVA acts as a sacrificial polymer to maintain the Alg gel filaments because approximately 90% of the red‐colored PVA is released from the Ca2+‐crosslinked Alg gel filaments into the wash water. In addition, the fabrication of PVA gel filaments shows that the sacrificial PVA is also transformed into fibrillar domains under shear. However, the filament structure cannot be formed from a single‐phase PVA/Alg solution. These results clearly show that the bundle‐structured gel filaments are maintained by preventing the fusion of filaments during gelation based on the tendency of the non‐crosslinked filaments to cause splitting of the gelled filaments.
Adaptive Lipid Immiscibility and Membrane Remodeling Are Active Functional Determinants of Primary Ciliogenesis
Authors: Bernabé‐Rubio Miguel , Bosch‐Fortea Minerva , García Esther , Bernardino de la Serna Jorge , Alonso Miguel A. 
Published: December 2020

AbstractLipid liquid–liquid immiscibility and its consequent lateral heterogeneity have been observed under thermodynamic equilibrium in model and native membranes. However, cholesterol‐rich membrane domains, sometimes referred to as lipid rafts, are difficult to observe spatiotemporally in live cells. Despite their importance in many biological processes, robust evidence for their existence remains elusive. This is mainly due to the difficulty in simultaneously determining their chemical composition and physicochemical nature, whilst spatiotemporally resolving their nanodomain lifetime and molecular dynamics. In this study, a bespoke method based on super‐resolution stimulated emission depletion (STED) microscopy and raster imaging correlation spectroscopy (RICS) is used to overcome this issue. This methodology, laser interleaved confocal RICS and STED‐RICS (LICSR), enables simultaneous tracking of lipid lateral packing and dynamics at the nanoscale. Previous work indicated that, in polarized epithelial cells, the midbody remnant licenses primary cilium formation through an unidentified mechanism. LICSR shows that lipid immiscibility and its adaptive collective nanoscale self‐assembly are crucial for the midbody remnant to supply condensed membranes to the centrosome for the biogenesis of the ciliary membrane. Hence, this work poses a breakthrough in the field of lipid biology by providing compelling evidence of a functional role for liquid ordered‐like membranes in primary ciliogenesis.
What patients want to know, and what we actually tell them: The ABIDE project
Authors: Fruijtier Agnetha D. , Visser Leonie N.C. , Bouwman Femke H. , Lutz Rogier , Schoonenboom Niki , Kalisvaart Kees , Hempenius Liesbeth , Roks Gerwin , Boelaarts Leo , Claus Jules J. , Kleijer Mariska , de Beer Marlijn , van der Flier Wiesje M. , Smets Ellen M.A. 
Published: December 2020

AbstractBackgroundWe studied to what degree and at whose initiative 25 informational topics, formerly identified as important, are discussed in diagnostic consultations.MethodsAudio recordings of clinician–patient consultations of 71 patients and 32 clinicians, collected in eight Dutch memory clinics, were independently content‐coded by two coders. The coding scheme encompassed 25 informational topics.ResultsApproximately half (Mdn = 12) of the 25 topics were discussed per patient during the diagnostic process, with a higher frequency among individuals receiving a dementia diagnosis (Mdn = 14) compared to others (Mdn = 11). Individual topics ranged from being discussed with 2/71 (3%) to 70/71 (99%) of patients. Patients and/or care partners rarely initiated topic discussion (10%). When they did, they often enquired about one of the least frequently addressed topics.ConclusionMost patients received information on approximately half of the important informational topics. Providing the topic list to patients and care partners beforehand could allow consultation preparation and stimulate participation.
Safety and tolerability of GRF6019 in mild‐to‐moderate Alzheimer's disease dementia
Authors: Hannestad Jonas , Koborsi Katie , Klutzaritz Vicki , Chao Whitney , Ray Rebecca , Páez Antonio , Jackson Sam , Lohr Scott , Cummings Jeffrey L. , Kay Gary , Nikolich Karoly , Braithwaite Steven 
Published: December 2020

AbstractIntroductionThis phase 2 trial evaluated the safety, tolerability, and feasibility of repeated infusions of the plasma fraction GRF6019 in mild‐to‐moderate Alzheimer's disease.MethodsIn this randomized, double‐blind, dose‐comparison trial, 47 patients were randomized 1:1 to receive daily infusions of 100 mL (n = 24) or 250 mL (n = 23) of GRF6019 for 5 consecutive days over two dosing periods separated by a treatment‐free interval of 3 months.ResultsThe mean (standard deviation [SD]) age of the enrolled patients was 74.3 (6.9), and 62% were women. Most adverse events (55%) were mild, with no clinically significant differences in safety or tolerability between the two dose levels. The mean (SD) baseline Mini‐Mental State Examination score was 20.6 (3.7) in the 100 mL group and 19.6 (3.7) in the 250 mL group; at 24 weeks, the within‐patient mean change from baseline was –1.0 points (95% confidence interval [CI], –3.1 to 1.1) in the 100 mL group and +1.5 points (95% CI, –0.4 to 3.3) in the 250 mL group. The within‐patient mean change from baseline on the Alzheimer's Disease Assessment Scale‐Cognitive subscale was –0.4 points (95% CI, –2.9 to 2.2) in the 100 mL group, while in the 250 mL group it was –0.9 points (95% CI, –3.0 to 1.2). The within‐patient mean change from baseline on the Alzheimer's Disease Cooperative Study‐Activities of Daily Living was –0.7 points in the 100 mL group (95% CI, –4.3 to 3.0) and –1.3 points (95% CI, –3.4 to 0.7) in the 250 mL group. The mean change from baseline on the Category Fluency Test, Clinical Dementia Rating Scale–Sum of Boxes, Alzheimer's Disease Cooperative Study–Clinical Global Impression of Change, and Neuropsychiatric Inventory Questionnaire was similar for both treatment groups and did not show any worsening.DiscussionGRF6019 was safe and well tolerated, and patients experienced no cognitive decline and minimal functional decline. These results support further development of GRF6019.
Digital pen technology for conducting cognitive assessments: a cross-over study with older adults
Authors: Heimann-Steinert A. , Latendorf A. , Prange A. , Sonntag D. , Müller-Werdan U. 
Published: December 2020

AbstractMany digitalized cognitive assessments exist to increase reliability, standardization, and objectivity. Particularly in older adults, the performance of digitized cognitive assessments can lead to poorer test results if they are unfamiliar with the computer, mouse, keyboard, or touch screen. In a cross-over design study, 40 older adults (age M = 74.4 ± 4.1 years) conducted the Trail Making Test A and B with a digital pen (digital pen tests, DPT) and a regular pencil (pencil tests, PT) to identify differences in performance. Furthermore, the tests conducted with a digital pen were analyzed manually (manual results, MR) and electronically (electronic results, ER) by an automized system algorithm to determine the possibilities of digital pen evaluation. ICC(2,k) showed a good level of agreement for TMT A (ICC(2,k) = 0.668) and TMT B (ICC(2,k) = 0.734) between PT and DPT. When comparing MR and ER, ICC(2,k) showed an excellent level of agreement in TMT A (ICC(2,k) = 0.999) and TMT B (ICC(2,k) = 0.994). The frequency of pen lifting correlates significantly with the execution time in TMT A (r = 0.372, p = 0.030) and TMT B (r = 0.567, p < 0.001). A digital pen can be used to perform the Trail Making Test, as it has been shown that there is no difference in the results due to the type of pen used. With a digital pen, the advantages of digitized testing can be used without having to accept the disadvantages.
Determination of low environmental free cyanide concentrations in freshwaters
Authors: Knopf Burkhard , Rüdel Heinz , Hansknecht Dirk , Klawonn Thorsten , Kreuzer Knut 
Published: December 2020

AbstractCyanide compounds are naturally emitted into the environment in low levels by degradation processes or emitted from anthropogenic sources. In surface water, complex cyanide compounds as well as “free cyanide” are present. The latter term covers hydrogen cyanide and cyanide compounds which easily liberate hydrogen cyanide under slightly acidic conditions. Especially free cyanide may cause adverse effects in the environment. To exclude negative impacts on freshwater systems, in the context of the European Water Framework Directive (WFD), preventive regulatory activities for free cyanide are currently under discussion. However, established analytical methods for quantification of free cyanide only obtain limits of quantification (LOQs) in the range of 1 μg L−1. Thus, these methods are not sufficiently sensitive for a potential environmental quality standard (EQS) compliance monitoring at water concentrations below the current predicted no effect concentration (PNEC) level of free cyanide. In the present study, a standardized continuous flow analysis (CFA) method for quantification of low free cyanide concentrations was adapted by applying a special system which allows an ultra-sensitive photometric detection of a colored cyanide derivative. By this means, LOQs in a range of one magnitude below the PNEC are achievable. The method was validated according to ISO/IEC 17025 requirements. Free cyanide concentrations in tested surface water samples from a small river and a barrier lake with low anthropogenic influences were very low and clearly below the PNEC. The results prove that the adapted CFA method is suitable for the analysis of low concentration free cyanide in freshwaters and appropriate for a possible EQS compliance monitoring.
Teaching life cycle assessment in higher education
Authors: Viere Tobias , Amor Ben , Berger Nicolas , Fanous Ruba Dolfing , Arduin Rachel Horta , Keller Regula , Laurent Alexis , Loubet Philippe , Strothmann Philip , Weyand Steffi , Wright Laurie , Sonnemann Guido 
Published: December 2020

AbstractPurposeScientific Life Cycle Assessment (LCA) literature provides some examples of LCA teaching in higher education, but not a structured overview of LCA teaching contents and related competencies. Hence this paper aims at assessing and highlighting trends in LCA learning outcomes, teaching approaches and developed content used to equip graduates for their future professional practices in sustainability.MethodsBased on a literature review on teaching LCA in higher education and a collaborative consensus building approach through expert group panel discussions, an overview of LCA learning and competency levels with related teaching contents and corresponding workload is developed. The levels are built on the European Credit Transfer and Accumulation System (ECTS) and Bloom’s taxonomy of learning.Results and discussionThe paper frames five LCA learning and competency levels that differ in terms of study program integration, workload, cognitive domain categories, learning outcomes, and envisioned professional skills. It furthermore provides insights into teaching approaches and content, including software use, related to these levels.Conclusions and recommendationsThis paper encourages and supports higher educational bodies to implement a minimum of ‘life cycle literacy’ into students’ curriculum across various domains by increasing the availability, visibility and quality of their teaching on life cycle thinking and LCA.