bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical MR imaging in Parkinson’s disease: How useful is the swallow tail sign?
Authors: Prasuhn Jannik , Neumann Alexander , Strautz Robert , Dreischmeier Shalida , Lemmer Felicitas , Hanssen Henrike , Heldmann Marcus , Schramm Peter , Brüggemann Norbert 
Published: May 2021

AbstractBackgroundWith conventional MRI, no Parkinson's disease (PD)‐specific abnormalities can be detected. However, there is a critical need for accompanying neuroimaging markers to guide the diagnosis. With high‐resolution susceptibility‐weighted MRI (SWI) sequences, the imaging of nigrosome‐1 (N1) is possible. The so‐called swallow tail sign (STS) has been proposed as a suitable neuroimaging marker for the diagnosis of PD.ObjectivesTo investigate whether the absence of the STS can be applied for distinguishing PD patients from healthy controls (HCs).MethodsSWI images of 44 PD patients and 50 age‐ and gender‐matched HCs were investigated using a 3T MRI scanner. Two trained neuroradiologists blind‐rated the images and evaluated whether the STS was absent (1) on one side or (2) both sides of the participant's midbrain.ResultsOur results confirmed good interrater reliability comparable to previously published studies. However, we did not identify any group differences between PD patients and HCs. Measures of diagnostic values revealed overall poor diagnostic performance.ConclusionsEven though previously stated, our study does not confirm the potential use of the STS as a supportive neuroimaging marker for PD in a clinical setting. In conclusion, there is a critical need for improvements in N1‐targeted MRI sequences and the development of advanced segmentation algorithms.
Doing it for us: Community identification predicts willingness to receive aCOVID‐19 vaccination via perceived sense of duty to the community
Authors: Wakefield Juliet Ruth Helen , Khauser Amreen 
Published: May 2021

AbstractThe COVID‐19 pandemic has presented huge challenges for communities across the world. Vaccines offer the best hope for controlling its deleterious effects, but not everybody is willing to be vaccinated, so it is important to explore variables that might predict vaccination willingness. The present study addressed this by drawing upon the Social Identity Approach, which posits that people's membership of social groups is consequential for their thoughts and behaviour. Specifically, it was predicted that people's strength of identification with their local community (a social group that came to particular prominence during the pandemic) would positively predict their willingness to engage in community‐related prosocial normative behaviour (i.e., their perceived sense of duty, as a community member, to get vaccinated) and that this, in turn, would predict higher levels of vaccination willingness. Participants (N = 130) completed an online survey, which supported the hypothesized mediation model, even after controlling for subjective neighbourhood socio‐economic status and age (two variables that are particularly likely to impact upon vaccination willingness). To our knowledge, this is the first study to apply Social Identity Approach principles to the study of COVID‐19 vaccination willingness. The implications of the findings for governments' efforts to boost vaccine uptake are discussed. Please refer to the Supplementary Material section to find this article'sCommunity and Social Impact Statement.
Learning a deep motion interpolation network for human skeleton animations
Authors: Zhou Chi , Lai Zhangjiong , Wang Suzhen , Li Lincheng , Sun Xiaohan , Ding Yu 
Published: May 2021

AbstractMotion interpolation technology produces transition motion frames between two discrete movements. It is wildly used in video games, virtual reality and augmented reality. In the fields of computer graphics and animations, our data‐driven method generates transition motions of two arbitrary animations without additional control signals. In this work, we propose a novel carefully designed deep learning framework, named deep motion interpolation network (DMIN), to learn human movement habits from a real dataset and then to perform the interpolation function specific for human motions. It is a data‐driven approach to capture overall rhythm of two given discrete movements and generate natural in‐between motion frames. The sequence‐by‐sequence architecture allows completing all missing frames within single forward inference, which reduces computation time for interpolation. Experiments on human motion datasets show that our network achieves promising interpolation performance. The ablation study demonstrates the effectiveness of the carefully designed DMIN.1
The Impact of Computational Uncertainties on the Enantioselectivity Predictions: A Microkinetic Modeling of Ketone Transfer Hydrogenation with a Noyori‐type Mn‐diamine Catalyst
Authors: Krieger Annika M. , Pidko Evgeny A. 
Published: May 2021

AbstractSelectivity control is one of the most important functions of a catalyst. In asymmetric catalysis the enantiomeric excess (e.e.) is a property of major interest, with a lot of effort dedicated to developing the most enantioselective catalyst, understanding the origin of selectivity, and predicting stereoselectivity. Herein, we investigate the relationship between predicted selectivity and the uncertainties in the computed energetics of the catalytic reaction mechanism obtained by DFT calculations in a case study of catalytic asymmetric transfer hydrogenation (ATH) of ketones with an Mn‐diamine catalyst. Data obtained from our analysis of DFT data by microkinetic modeling is compared to results from experiment. We discuss the limitations of the conventional reductionist approach of e.e. estimation from assessing the enantiodetermining steps only. Our analysis shows that the energetics of other reaction steps in the reaction mechanism have a substantial impact on the predicted reaction selectivity. The uncertainty of DFT calculations within the commonly accepted energy ranges of chemical accuracy may reverse the predicted e.e. with the non‐enantiodetermining steps contributing to e.e. deviations of up to 25 %.
Total Synthesis and Bioactivity Mapping of Geodiamolide H
Authors: Nasufović Veselin , Küllmer Florian , Bößneck Johanna , Dahse Hans‐Martin , Görls Helmar , Bellstedt Peter , Stallforth Pierre , Arndt Hans‐Dieter 
Published: May 2021

AbstractThe first total synthesis of the actin‐stabilizing marine natural product geodiamolide H was achieved. Solid‐phase based peptide assembly paired with scalable stereoselective syntheses of polyketide building blocks and an optimized esterification set the stage for investigating the key ring‐closing metathesis. Geodiamolide H and synthetic analogues were characterized for their toxicity and for antiproliferative effects in cellulo, by characterising actin polymerization induction in vitro, and by docking on the F‐actin target and property computation in silico, for a better understanding of structure‐activity relationships (SAR). A non‐natural analogue of geodiamolide H was discovered to be most potent in the series, suggesting significant potential for tool compound design.
Construction of Stable Helical Metal‐Organic Frameworks with a Conformationally Rigid “Concave Ligand”
Authors: Zhao Kai , He Ying , Shan Chuan , Wojtas Lukasz , Ren Junyu , Yan Yu , Shi Hanzhong , Wang Haonan , Song Zhiguang , Shi Xiaodong 
Published: May 2021

AbstractA helical metal‐organic framework was prepared by using a conformationally rigid tetratopic benzoic acid ligand with binding units pointing toward each other (concave ligand). To avoid the obvious intramolecular interactions between binding units, matching spacing groups were applied to introduce atropic repulsion, thereby allowing the formation of extended frameworks for the first time. With this new ligand design, a helical‐shaped MOF with significantly improved air and moisture stability was successfully prepared, thus providing a new strategy for ligand design toward porous material constructions.
From Quinoline to Quinazoline‐Based S. aureus NorA Efflux Pump Inhibitors by Coupling a Focused Scaffold Hopping Approach and a Pharmacophore Search
Authors: Cedraro Nicholas , Cannalire Rolando , Astolfi Andrea , Mangiaterra Gianmarco , Felicetti Tommaso , Vaiasicca Salvatore , Cernicchi Giada , Massari Serena , Manfroni Giuseppe , Tabarrini Oriana , Cecchetti Violetta , Barreca Maria Letizia , Biavasco Francesca , Sabatini Stefano 
Published: May 2021

AbstractAntibiotic resistance breakers, such as efflux pump inhibitors (EPIs), represent a powerful alternative to the development of new antimicrobials. Recently, by using previously described EPIs, we developed pharmacophore models able to identify inhibitors of NorA, the most studied efflux pump of Staphylococcus aureus. Herein we report the pharmacophore‐based virtual screening of a library of new potential NorA EPIs generated by an in‐silico scaffold hopping approach of the quinoline core. After chemical synthesis and biological evaluation of the best virtual hits, we found the quinazoline core as the best performing scaffold. Accordingly, we designed and synthesized a series of functionalized 2‐arylquinazolines, which were further evaluated as NorA EPIs. Four of them exhibited a strong synergism with ciprofloxacin and a good inhibition of ethidium bromide efflux on resistant S. aureus strains coupled with low cytotoxicity against human cell lines, thus highlighting a promising safety profile.
The PhotoFlexys: A Multi‐Purpose Reactor Platform to Simplify Process Intensification and Mechanistic Studies in Photochemistry
Authors: Rößler Martin , Liauw Marcel A. 
Published: May 2021

AbstractReactor technology plays a vital role in photochemistry since process efficiency and reproducibility largely depend on the used reactor design. Considering the diverse requirements for photochemical reactions, we have developed a multi‐purpose reactor platform that aims for an equally efficient implementation of photochemical reactions under batch and continuous flow conditions. Interchangeable irradiation units and reactor functionalities reduce the necessary equipment for running photochemical reactions to a minimum. The versatility of the reactor platform has been tested on a variety of benchmark reactions under batch, multi‐batch and continuous flow conditions. Uniting the strengths of the photoreactor platform with an in‐situ monitoring approach permitted reliable kinetic and mechanistic studies.
Application of natural yellow (curcumin) dye on silk to impart multifunctional finishing and validation of dyeing process using BBD model
Authors: Palaskar Shital S. , Kale Ravindra D. , Deshmukh Rajendra R. 
Published: May 2021

AbstractDyeing of silk fabric was carried with curcumin, extracted from turmeric, which is known for its yellow colour and antioxidant properties. Design expert Box‐Behnken design (BBD) model was employed to perform dyeing experiments on silk fabric with curcumin dye. The dyed fabrics were characterized for its functional properties by colour measurement as K/S values, antioxidant activity by DPPH assay and UPF. The curcumin dyed silk samples showed upto 88% antioxidant activity and good to excellent ultraviolet protection depending on the percentage of curcumin used. The effect of pre‐mordanting using metal mordants was also studied.
Intravital Microscopy for the Study of Hepatic Glucose Uptake
Authors: Stefkovich Megan L. , Kang Sun Woo Sophie , Porat‐Shliom Natalie 
Published: May 2021

AbstractThe liver is central in maintaining glucose homeostasis. Indeed, impaired hepatic glucose uptake has been implicated in the development of hyperglycemia in type II diabetes (T2D) and non‐alcoholic fatty liver disease (NAFLD). However, current approaches to evaluate glucose mobilization rely on indirect measurements that do not provide spatial and temporal information. Here, we describe confocal‐based intravital microscopy (IVM) of the liver that allows the identification of hepatocyte spatial organization and glucose transport. Specifically, we describe a method to fluorescently label hepatic landmarks to identify different compartments within the liver. In addition, we outline an in vivo fluorescent glucose uptake assay to quantitatively measure glucose mobilization in space and time. These protocols allow direct investigation of hepatic glycemic control and can be further applied to murine models of liver disease. © Published 2021. This article is a U.S. Government work and is in the public domain in the USA.Basic Protocol 1: Mouse surgical procedure and positioning for liver intravital imagingBasic Protocol 2: Fluorescent labeling and intravital imaging of mouse hepatic compartmentsBasic Protocol 3: Mouse hepatic glucose uptake assay and intravital imaging analysis
Formation of a New Cocrystal Methyl‐4‐hydroxybenzoate:Urea and Its Structural and Thermal Properties
Authors: Vajaravel Manikandan , Karuppannan Srinivasan 
Published: May 2021

AbstractA new cocrystal comprising two pharmaceutically important molecules methyl‐4‐hydroxybenzoate (p‐MHB) (C8H8O3) and carbonyl diamide (urea) [CO(NH2)2] is crystallized together for the first time through restricted solvent evaporation method at ambient conditions. The single crystal X‐ray diffraction analysis shows that the engineered cocrystal p‐MHB:urea (1:1) (C9H12N2O4) crystallizes in monoclinic system with centrosymmetric space group C12/c1. The internal structure analysis shows that the urea molecule with its unique ability forms hydrogen bonding network throughout the cocrystal system. Different orientations of the identified synthons form the networks via supramolecular connections such as C═O⋯H─O and C═O⋯N─H. Correlation between the internal molecular configurations in the unit cell, protruding molecular groups on different growth faces, and attachment energies of different crystal planes is studied. The Hirshfeld surface analysis shows that the higher percentage of overall interactions between the carbon and oxygen atoms at the outer surfaces of the cocrystal induces further incorporation of molecular aggregation and crystal growth. The 2D finger print plots infer that about 90.9% of the overall interactions are mainly due to the H bonds. Differential scanning calorimetry analysis reveals that the grown cocrystal undergoes an observable phase transition at 105.65 °C prior to its melting endotherm that peaks at 110.29 °C.
Analysis of human chromosomes by imaging flow cytometry
Authors: Stanley Jason , Hui Henry , Erber Wendy , Clynick Britt , Fuller Kathy 
Published: May 2021

AbstractChromosomal analysis is traditionally performed by karyotyping on metaphase spreads, or by fluorescent in situ hybridization (FISH) on interphase cells or metaphase spreads. Flow cytometry was introduced as a new method to analyze chromosomes number (ploidy) and structure (telomere length) in the 1970s with data interpretation largely based on fluorescence intensity. This technology has had little uptake for human cytogenetic applications primarily due to analytical challenges. The introduction of imaging flow cytometry, with the addition of digital images to standard multi‐parametric flow cytometry quantitative tools, has added a new dimension. The ability to visualize the chromosomes and FISH signals overcomes the inherent difficulties when the data is restricted to fluorescence intensity. This field is now moving forward with methods being developed to assess chromosome number and structure in whole cells (normal and malignant) in suspension. A recent advance has been the inclusion of immunophenotyping such that antigen expression can be used to identify specific cells of interest for specific chromosomes and their abnormalities. This capability has been illustrated in blood cancers, such as chronic lymphocytic leukemia and plasma cell myeloma. The high sensitivity and specificity achievable highlights the potential imaging flow cytometry has for cytogenomic applications (i.e., diagnosis and disease monitoring). This review introduces and describes the development, current status, and applications of imaging flow cytometry for chromosomal analysis of human chromosomes.
Measurement batch differences and between‐batch conversion of Alzheimer's disease cerebrospinal fluid biomarker values
Authors: Ma Yue , Norton Derek L. , Van Hulle Carol A. , Chappell Richard J. , Lazar Karen K. , Jonaitis Erin M. , Koscik Rebecca L. , Clark Lindsay R. , Krause Rachel , Andreasson Ulf , Chin Nathaniel A. , Bendlin Barbara B. , Asthana Sanjay , Okonkwo Ozioma C. , Gleason Carey E. , Johnson Sterling C. , Zetterberg Henrik , Blennow Kaj , Carlsson Cynthia M. 
Published: May 2021

AbstractIntroductionBatch differences in cerebrospinal fluid (CSF) biomarker measurement can introduce bias into analyses for Alzheimer's disease studies. We evaluated and adjusted for batch differences using statistical methods.MethodsA total of 792 CSF samples from 528 participants were assayed in three batches for 12 biomarkers and 3 biomarker ratios. Batch differences were assessed using Bland‐Altman plot, paired t test, Pitman‐Morgan test, and linear regression. Generalized linear models were applied to convert CSF values between batches.ResultsWe found statistically significant batch differences for all biomarkers and ratios, except that neurofilament light was comparable between batches 1 and 2. The conversion models generally had high R2 except for converting P‐tau between batches 1 and 3.DiscussionBetween‐batch conversion allows harmonized CSF values to be used in the same analysis. Such method may be applied to adjust for other sources of variability in measuring CSF or other types of biomarkers.
The relationships of sex hormone‐binding globulin, total testosterone, androstenedione and free testosterone with metabolic and reproductive features of polycystic ovary syndrome
Authors: Simons Pomme I. H. G. , Valkenburg Olivier , Bons Judith A. P. , Stehouwer Coen D. A. , Brouwers Martijn C. G. J. 
Published: May 2021

AbstractObjectiveA recent Mendelian randomization study has suggested a causal role for sex hormone‐binding globulin (SHBG), total testosterone and free testosterone in the pathogenesis of polycystic ovary syndrome (PCOS). The aim of this study was to assess the relationships of SHBG, androstenedione, total and free testosterone with the individual metabolic and reproductive features of PCOS.DesignCross‐sectional data in PCOS patients (n=96) prospectively collected in a secondary/tertiary clinic for menstrual cycle disorders.MethodsMultivariable regression analyses were conducted to study the associations between SHBG, androstenedione, total and free testosterone with metabolic (BMI, waist circumference, systolic and diastolic blood pressure, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides and homeostatic model assessment for insulin resistance [HOMA2‐IR]) and reproductive features (menstrual cycle length, antral follicle count, anti‐Müllerian hormone, luteinizing hormone, follicle‐stimulating hormone and Ferriman‐Gallwey score) of PCOS.ResultsSerum SHBG and free testosterone, but not total testosterone or androstenedione, were significantly associated with BMI, waist circumference, serum triglycerides, HDL cholesterol, LDL cholesterol and HOMA2‐IR. The strength of the associations with serum lipids was reduced after adjustment for BMI, but not for HOMA2‐IR. Total testosterone was significantly associated with antral follicle count. SHBG, total testosterone and androstenedione were significantly associated with serum AMH. Only the strength of the association for SHBG was reduced after adjustment for BMI.ConclusionsSerum SHBG is associated with primarily metabolic features, whereas total testosterone and androstenedione are associated with reproductive features of PCOS. These results suggest a differential underlying pathophysiology for the metabolic and reproductive features of PCOS.
Use of diuretics and outcomes in patients with type 2 diabetes: findings from the EMPA‐REG OUTCOME trial
Authors: Pellicori Pierpaolo , Fitchett David , Kosiborod Mikhail N. , Ofstad Anne P. , Seman Leo , Zinman Bernard , Zwiener Isabella , Wanner Christoph , George Jyothis , Inzucchi Silvio E. , Testani Jeffrey M. , Cleland John G.F. 
Published: May 2021

AbstractAimsLoop diuretics (LD) relieve symptoms and signs of congestion due to heart failure (HF), but many patients prescribed LD do not have such a diagnosis. We studied the relationship between HF diagnosis, use of LD, and outcomes in patients with type 2 diabetes mellitus (T2DM) enrolled in the EMPA‐REG OUTCOME trial.Methods and resultsThe relationship between HF diagnosis, use of LD, and outcomes was evaluated in four patient subgroups with T2DM: (i) investigator‐reported HF on LD, (ii) investigator‐reported HF not on LD, (iii) no HF on LD, and (iv) no HF and not on LD, and we assessed their risk of cardiovascular events. Of 7020 participants, 706 (10%) had a diagnosis of HF at baseline, of whom 334 were prescribed LD. However, 755 (11%) patients who did not have a diagnosis of HF were prescribed LD. Compared to those with neither HF nor prescribed LD (reference group; placebo), those with both HF and receiving LD had the highest rates for all‐cause [hazard ratio (HR) (95% confidence interval) 3.19 (2.03–5.01)] and cardiovascular mortality [3.83 [(2.28–6.44)], and HF hospitalizations [9.51 (5.61–16.14)]. Patients without HF but prescribed LD had higher rates for all three outcomes [1.62 (1.10–2.39); 1.97 (1.26–3.08); 3.20 (1.90–5.39)], which were similar to patients with HF who were not receiving LD [1.42 (0.78–2.57); 1.56 (0.78–3.11); 3.00 (1.40–6.40)]. Empagliflozin had similar benefits regardless of subgroup (P for interaction >0.1 for all outcomes).ConclusionPatients with T2DM prescribed LD are at greater risk of cardiovascular events even if they are not reported to have HF; this might reflect under‐diagnosis. Empagliflozin was similarly effective in all subgroups investigated.
Inertial focusing of microparticles, bacteria, and blood in serpentine glass channels
Authors: Rodriguez‐Mateos Pablo , Ngamsom Bongkot , Dyer Charlotte E. , Iles Alexander , Pamme Nicole 
Published: May 2021

AbstractEarly detection of pathogenic microorganisms is pivotal to diagnosis and prevention of health and safety crises. Standard methods for pathogen detection often rely on lengthy culturing procedures, confirmed by biochemical assays, leading to >24 h for a diagnosis. The main challenge for pathogen detection is their low concentration within complex matrices. Detection of blood‐borne pathogens via techniques such as PCR requires an initial positive blood culture and removal of inhibitory blood components, reducing its potential as a diagnostic tool. Among different label‐free microfluidic techniques, inertial focusing on microscale channels holds great promise for automation, parallelization, and passive continuous separation of particles and cells. This work presents inertial microfluidic manipulation of small particles and cells (1–10 μm) in curved serpentine glass channels etched at different depths (deep and shallow designs) that can be exploited for (1) bacteria preconcentration from biological samples and (2) bacteria‐blood cell separation. In our shallow device, the ability to focus Escherichia coli into the channel side streams with high recovery (89% at 2.2× preconcentration factor) could be applied for bacteria preconcentration in urine for diagnosis of urinary tract infections. Relying on differential equilibrium positions of red blood cells and E. coli inside the deep device, 97% red blood cells were depleted from 1:50 diluted blood with 54% E. coli recovered at a throughput of 0.7 mL/min. Parallelization of such devices could process relevant volumes of 7 mL whole blood in 10 min, allowing faster sample preparation for downstream molecular diagnostics of bacteria present in bloodstream.