bluuebunny/crossref_metadata_2025 huggingface dataset:
Vigorous physical activity is important in maintaining a favourable health trajectory in active children: the CHAMPS Study-DK
Authors: Sénéchal Martin , Hebert Jeffrey J. , Fairchild Timothy J. , Møller Niels Christian , Klakk Heidi , Wedderkopp Niels
Published: September 2021

Physical activity (PA) is critical to improving health factors such as weight, adiposity, and aerobic fitness. However, children who meet PA guideline recommendations demonstrate developmental differences in health-related outcomes. To investigate prospective associations between PA behaviour (overall PA and PA intensity) and trajectories of health-related factors among physically active children. This prospective study (2.5 years) included 391 children (baseline age: 8.1 ± 1.4 years; girls 36.3%) from ten public schools. All children performed 60-min or more of moderate-to-vigorous physical activity (MVPA) per day objectively measured. Trajectories of BMI, waist circumference, and aerobic fitness were constructed with a group-based multi-trajectory model. Three trajectory subgroups were identified: ‘high fitness/normal weight’ (48.4% of children), ‘moderate fitness /normal weight’ (42.5% of children), and ‘low fitness/overweight-obese’ (9.1% of children). Children performing higher overall PA, were less likely of being classified as members of the ‘Low Fitness/Overweight-Obese’ [Relative Risk Ratio (RRR and 95% CI) = 0.56 (0.37 to 0.85) compared to ‘high fitness/normal weight’ subgroup. Each additional 5% in light PA time was associated with approximately twofold [RRR 2.12 (1.24–3.61)] increased risk of being in the ‘low fitness/overweight-obese’ trajectory relative to the ‘high fitness/normal weight’ trajectory. Each additional 2% in vigorous-PA time was associated with a 42% and 85% reduced risk (relative to ‘high fitness/normal weight’) of being in the ‘moderate fitness/normal weight’ [RRR 0.58 (0.38–0.96)] and ‘low fitness/overweight-obesity’ [RRR 0.15 (0.06–0.37)] trajectory, respectively. Overall PA and additional time in vigorous-PA was associated with improved health-related outcomes, while light PA was negatively associated with health-related outcomes among children who adhere to PA guideline recommendations. Vigorous PA was the strongest predictor of the health trajectories. All PA guidelines for children should place greater emphasis on the importance of vigorous PA.
Impact of smoking, COPD and comorbidities on the mortality of COVID-19 patients
Authors: Lacedonia Donato , Scioscia Giulia , Santomasi Carla , Fuso Paolo , Carpagnano Giovanna Elisiana , Portacci Andrea , Mastroianni Franco , Larizza Giovanni , Sabato Eugenio , Profilo Emanuela , Resta Emanuela , Foschino Barbaro Maria Pia , Resta Onofrio
Published: September 2021

The prognosis of the coronavirus disease 2019 (COVID-19) patients is variable and depends on several factors. Current data about the impact of chronic obstructive pulmonary disease (COPD) and smoking on the clinical course of COVID-19 are still controversial. This study evaluated the prevalence and the prognosis of COPD patients and smokers in a cohort of 521 patients admitted to four intermediate Respiratory Intensive Care Units (Puglia, Italy) with respiratory failure due to COVID-19 pneumonia. The prevalence of COPD and current smokers was 14% and 13%, respectively. COPD patients had a higher 30-day all-cause mortality than non-COPD patients. Former smokers compared to never smokers and current smokers had higher 30-day all-cause mortality. COPD patients and former smokers had more comorbidities. This study described the prevalence and the outcomes of COPD patients and smokers in a homogenous cohort of COVID-19 patients. The study showed that the prevalence of COPD and current smokers was not high, suggesting that they were not at increased risk of getting the infection. However, when SARS-CoV-2 infection occurred, COPD patients and former smokers were those with the highest all-cause mortality, which seemed to be mainly related to the presence of comorbidities and not to COPD and smoking itself.
Repeatability, reproducibility, and agreement of three tonometers for measuring intraocular pressure in rabbits
Authors: Bertens Christian J. F. , van Mechelen Ralph J. S. , Berendschot Tos T. J. M. , Gijs Marlies , Wolters Jarno E. J. , Gorgels Theo G. M. F. , Nuijts Rudy M. M. A. , Beckers Henny J. M.
Published: September 2021

The aim of this study was to evaluate repeatability, reproducibility, and agreement of three commonly used tonometers in animal research (TonoLab, TonoVet, and TonoPEN AVIA) in a cohort of 24 rabbits. Additionally, the impact of sedation on IOP was investigated in 21 New Zealand White rabbits with the TonoVet tonometer. Repeatability was determined using the coefficient of variation (CoV) for two observers. For the TonoLab (6.55%) and TonoVet (6.38%) the CoV was lower than for the TonoPEN AVIA (10.88%). The reproducibility was highest for the TonoVet (0.2 ± 3.3 mmHg), followed by the TonoLab (0 ± 12.89 mmHg) and lowest for the TonoPEN AVIA (− 1.48 ± 10.3 mmHg). The TonoLab and TonoVet showed the highest agreement (r = 0.85, R2 = 0.73). After sedation, a significant IOP reduction (often > 25%) was observed. Our results show that among the three tonometers tested, the TonoVet tonometer is best for use in rabbits while the TonoLab should be avoided. The impact of sedation on IOP was substantial and should be taken into account during experimentation.
Delay discounting and under-valuing of recent information predict poorer adherence to social distancing measures during the COVID-19 pandemic
Authors: Lloyd Alex , McKay Ryan , Hartman Todd K. , Vincent Benjamin T. , Murphy Jamie , Gibson-Miller Jilly , Levita Liat , Bennett Kate , McBride Orla , Martinez Anton P. , Stocks Thomas V. A. , Vallières Frédérique , Hyland Philip , Karatzias Thanos , Butter Sarah , Shevlin Mark , Bentall Richard P. , Mason Liam
Published: September 2021

The COVID-19 pandemic has brought about unprecedented global changes in individual and collective behaviour. To reduce the spread of the virus, public health bodies have promoted social distancing measures while attempting to mitigate their mental health consequences. The current study aimed to identify cognitive predictors of social distancing adherence and mental health symptoms, using computational models derived from delay discounting (the preference for smaller, immediate rewards over larger, delayed rewards) and patch foraging (the ability to trade-off between exploiting a known resource and exploring an unknown one). In a representative sample of the UK population (N = 442), we find that steeper delay discounting predicted poorer adherence to social distancing measures and greater sensitivity to reward magnitude during delay discounting predicted higher levels of anxiety symptoms. Furthermore, under-valuing recently sampled information during foraging independently predicted greater violation of lockdown guidance. Our results suggest that those who show greater discounting of delayed rewards struggle to maintain social distancing. Further, those who adapt faster to new information are better equipped to change their behaviour in response to public health measures. These findings can inform interventions that seek to increase compliance with social distancing measures whilst minimising negative repercussions for mental health.
Receptor tyrosine kinase ROR1 ameliorates Aβ1–42 induced cytoskeletal instability and is regulated by the miR146a-NEAT1 nexus in Alzheimer’s disease
Authors: Chanda Kaushik , Jana Nihar Ranjan , Mukhopadhyay Debashis
Published: September 2021

Alzheimer’s disease (AD) involves severe cytoskeletal degradation and microtubule disruption. Here, we studied the altered dynamics of ROR1, a Receptor Tyrosine Kinase (RTK), and how it could counter these abnormalities. We found that in an Aβ1–42 treated cell model of AD, ROR1 was significantly decreased. Over expressed ROR1 led to the abrogation of cytoskeletal protein degradation, even in the presence of Aβ1–42, preserved the actin network, altered actin dynamics and promoted neuritogenesis. Bioinformatically predicted miRNAs hsa-miR-146a and 34a were strongly up regulated in the cell model and their over expression repressed ROR1. LncRNA NEAT1, an interactor of these miRNAs, was elevated in mice AD brain and cell model concordantly. RNA Immunoprecipitation confirmed a physical interaction between the miRNAs and NEAT1. Intuitively, a transient knock down of NEAT1 increased their levels. To our knowledge, this is the first instance which implicates ROR1 in AD and proposes its role in preserving the cytoskeleton. The signalling modalities are uniquely analyzed from the regulatory perspectives with miR-146a and miR-34a repressing ROR1 and in turn getting regulated by NEAT1.
Actin crosslinker competition and sorting drive emergent GUV size-dependent actin network architecture
Authors: Bashirzadeh Yashar , Redford Steven A. , Lorpaiboon Chatipat , Groaz Alessandro , Moghimianavval Hossein , Litschel Thomas , Schwille Petra , Hocky Glen M. , Dinner Aaron R. , Liu Allen P.
Published: September 2021

The proteins that make up the actin cytoskeleton can self-assemble into a variety of structures. In vitro experiments and coarse-grained simulations have shown that the actin crosslinking proteins α-actinin and fascin segregate into distinct domains in single actin bundles with a molecular size-dependent competition-based mechanism. Here, by encapsulating actin, α-actinin, and fascin in giant unilamellar vesicles (GUVs), we show that physical confinement can cause these proteins to form much more complex structures, including rings and asters at GUV peripheries and centers; the prevalence of different structures depends on GUV size. Strikingly, we found that α-actinin and fascin self-sort into separate domains in the aster structures with actin bundles whose apparent stiffness depends on the ratio of the relative concentrations of α-actinin and fascin. The observed boundary-imposed effect on protein sorting may be a general mechanism for creating emergent structures in biopolymer networks with multiple crosslinkers.
Regulation of the immune tolerance system determines the susceptibility to HLA-mediated abacavir-induced skin toxicity
Authors: Susukida Takeshi , Kuwahara Saki , Song Binbin , Kazaoka Akira , Aoki Shigeki , Ito Kousei
Published: September 2021

Idiosyncratic drug toxicity (IDT) associated with specific human leukocyte antigen (HLA) allotype is a rare and unpredictable life-threatening adverse drug reaction for which prospective mechanistic studies in humans are difficult. Here, we show the importance of immune tolerance for IDT onset and determine whether it is susceptible to a common IDT, HLA-B*57:01-mediated abacavir (ABC)-induced hypersensitivity (AHS), using CD4+ T cell-depleted programmed death-1 receptor (PD-1)-deficient HLA-B*57:01 transgenic mice (B*57:01-Tg/PD-1−/−). Although AHS is not observed in B*57:01-Tg mice, ABC treatment increases the proportion of cytokine- and cytolytic granule-secreting effector memory CD8+ T cells in CD4+ T cell-depleted B*57:01-Tg/PD-1−/− mice, thereby inducing skin toxicity with CD8+ T cell infiltration, mimicking AHS. Our results demonstrate that individual differences in the immune tolerance system, including PD-1highCD8+ T cells and regulatory CD4+ T cells, may affect the susceptibility of humans to HLA-mediated IDT in humans.
Submesoscale flows impact Agulhas leakage in ocean simulations
Authors: Schubert René , Gula Jonathan , Biastoch Arne
Published: September 2021

Agulhas leakage, the warm and salty inflow of Indian Ocean water into the Atlantic Ocean, is of importance for the climate-relevant Atlantic Meridional Overturning Circulation. South of Africa, the eastward turning Agulhas Current sheds Agulhas rings, cyclones and filaments of order 100 km that carry the Indian Ocean water into the Cape Basin and further into the Atlantic. Here, we show that the resolution of submesoscale flows of order 10 km in an ocean model leads to 40 % more Agulhas leakage and more realistic Cape Basin water-masses compared to a parallel non-submesoscale resolving simulation. Moreover, we show that submesoscale flows strengthen shear-edge eddies and in consequence lee cyclones at the northern edge of the Agulhas Current, as well as the leakage pathway in the region of the filaments that takes place outside of mesoscale eddies. This indicates that the increase in leakage can be attributed to stronger Agulhas filaments, when submesoscale flows are resolved.
Fabrication of a paper-based sensor from graphene quantum dots coated with a polymeric membrane for the determination of gold(iii) ions
Authors: Thanomsak Suphakan , Insombat Chanunporn , Chaiyo Phutita , Tuntulani Thawatchai , Janrungroatsakul Wanwisa
Published: September 2021

A novel paper-based sensor using graphene quantum dots (GQDs) as a colorimetric probe for Au3+ determination has been developed.
The construction of a multifunctional luminescent Eu-MOF for the sensing of Fe3+, Cr2O72− and amines in aqueous solution
Authors: Wang Cui-Li , Zheng Ya-Xin , Chen Le , Zhu Cai-Yong , Gao Wei , Li Peng , Jie-Ping Liu , Zhang Xiu-Mei
Published: September 2021

A 3D Eu(iii)-based metal–organic framework has been synthesized as a multiresponsive chemosensor for highly sensitive and selective detection of Fe3+, Cr2O72− and amines in water.
A comparative DFT study of the oxidation of Al crystals and nanoparticles
Authors: Hai Pengqi , Wu Chao
Published: September 2021

The thermodynamic and kinetic behaviors of O atoms in different Al nanoparticles (ANPs) and Al crystals have been systematically studied using first-principles calculations.
Ultrafast dynamics of fully reduced flavin in catalytic structures of thymidylate synthase ThyX
Authors: Dozova Nadia , Lacombat Fabien , Lombard Murielle , Hamdane Djemel , Plaza Pascal
Published: September 2021

Transient absorption spectroscopy reveals the impact of substrates on the ultrafast dynamics of FADH− in flavin-dependent thymidylate synthase ThyX.
The characterization of protein interactions – what, how and how much?
Authors: Walport Louise J. , Low Jason K. K. , Matthews Jacqueline M. , Mackay Joel P.
Published: September 2021

This tutorial review provides an introduction to a wide range of methods used to quantify protein interactions, outlining their strengths, weaknesses and requirements.
Density functional theory studies of transition metal carbides and nitrides as electrocatalysts
Authors: Tian Dong , Denny Steven R. , Li Kongzhai , Wang Hua , Kattel Shyam , Chen Jingguang G.
Published: September 2021

This review summarizes density functional theory (DFT) studies of TMCs and TMNs as electrocatalysts. It provides atomistic details of HER, OER, ORR, N2RR and CO2RR and also presents a future outlook in designing TMCs and TMNs based electrocatalysts.
Progress in batch preparation of single-atom catalysts and application in sustainable synthesis of fine chemicals
Authors: Hu Yifan , Li Hongxuan , Li Zesheng , Li Bolin , Wang Shaoyu , Yao Yuancheng , Yu Changlin
Published: September 2021

The batch preparation technology and the thermo-catalysis application of SACs in fine chemical industries are highlighted.
The framework of nanopesticides: a paradigm in biodiversity
Authors: Shekhar Shashank , Sharma Shreya , Kumar Amit , Taneja Anjali , Sharma Bhasha
Published: September 2021

Nanotechnology has imparted excellent substitutes in the area of agriculture for the management of insect pests without deteriorating the surrounding biota and thereby allows a more verdant environment.
Molecular dynamics investigation of the structural and energetic properties of CeO2–MOx (M = Gd, La, Ce, Zr) nanoparticles
Authors: de Mendonça João Paulo A. , Lourenço Tuanan C. , Freitas Luis Paulo M. , Santo Anderson A. E. , Feliciano Gustavo T. , Da Silva Juarez L. F.
Published: September 2021

CeO2-based materials have played a critical role in catalysis, where the substrate particles have reduced in size year by year due to experimental achievements in synthesis control.
Hybrid covalent adaptable networks from cross-reactive poly(ε-caprolactone) and poly(ethylene oxide) stars towards advanced shape-memory materials
Authors: Caprasse Jérémie , Riva Raphaël , Thomassin Jean-Michel , Jérôme Christine
Published: September 2021

The synthesis and properties of hybrid poly(ε-caprolactone) (PCL)–poly(ethylene oxide) (PEO) covalent adaptable networks have been investigated.
Potency and metabolic stability: a molecular hybrid case in the design of novel PF74-like small molecules targeting HIV-1 capsid protein
Authors: Sahani Rajkumar Lalji , Akther Thamina , Cilento Maria E. , Castaner Andres Emanuelli , Zhang Huanchun , Kirby Karen A. , Xie Jiashu , Sarafianos Stefan G. , Wang Zhengqiang
Published: September 2021

To achieve balanced potency and metabolic stability profiles, a molecular hybridization approach was used to design a novel PF74-like chemotype 4. Synthesis, SAR and molecular modeling of chemotype 4 are reported.
Tuning the interface in epoxy-based composites and laminates through epoxy grafted graphene oxide enhances mechanical properties
Authors: Katti Prajakta , Verma K. K. , Kumar S. , Bose Suryasarathi
Published: September 2021

Improved dispersion and enhanced interfacial adhesion between with reinforcement leads to superior properties in polymer nanocomposites.
Magneto-mechanical treatment of human glioblastoma cells with engineered iron oxide powder microparticles for triggering apoptosis
Authors: Thébault C. , Marmiesse M. , Naud C. , Pernet-Gallay K. , Billiet E. , Joisten H. , Dieny B. , Carrière M. , Hou Y. , Morel R.
Published: September 2021

In this work we present a new type of magnetite microparticles made by ball milling and study the influence of PEG surface functionalization on their ability to induce cell death when subjected to a low frequency magnetic field.
Optical separation and discrimination of chiral particles by vector beams with orbital angular momentum
Authors: Li Manman , Yan Shaohui , Zhang Yanan , Chen Xu , Yao Baoli
Published: September 2021

The focused vector vortex beams can selectively trap one enantiomer at inside or outside the intensity maxima depending on the sign of the OAM.
Assessing the parameters modulating optical losses of iron oxide nanoparticles under near infrared irradiation
Authors: Lozano-Pedraza Claudia , Plaza-Mayoral Elena , Espinosa Ana , Sot Begoña , Serrano Aida , Salas Gorka , Blanco-Andujar Cristina , Cotin Geoffrey , Felder-Flesch Delphine , Begin-Colin Sylvie , Teran Francisco J.
Published: September 2021

Heating mediated by iron oxide nanoparticles subjected to near infrared irradiation has recently gained lots of interest.
Activation of the methane C–H bond by Al- and Ga-doped graphenes: a DFT investigation
Authors: Mousavian Parisasadat , Esrafili Mehdi D. , Sardroodi Jaber J.
Published: September 2021

The potential of Al- and Ge-embedded graphene to activate the C–H bond of CH4 in the presence of a N2O molecule was studied using DFT calculations.
Nanospheres from coordination polymers of Ag+ with a highly hydrophilic thiol ligand formed in situ from dynamic covalent binding and a hydrophobic thiol
Authors: Xu Yan , Yan Xiao-Sheng , Zhang Si-Bo , Li Shao-Wei , Xia Ning-Shao , Jiang Tao , Li Zhao , Jiang Yun-Bao
Published: September 2021

A supramolecular nanosphere with a diameter of 8.7 nm is obtained in an aqueous alkaline solution via glucose binding to a boronic acid-based thiol (4-MPBA) as a hydrophilic ligand, together with a hydrophobic thiol ligand n-C8H17SH.
The viscoelasticity of adherent cells follows a single power-law with distinct local variations within a single cell and across cell lines
Authors: Sanchez Juan G. , Espinosa Francisco M. , Miguez Ruben , Garcia Ricardo
Published: September 2021

Nanomechanical property map of a live cell generated by AFM-based force-distance curves.
Aqueous emulsion polymerizations of methacrylates and styrene via reversible complexation mediated polymerization (RCMP)
Authors: Mao Weijia , Sarkar Jit , Peng Bo , Goto Atsushi
Published: September 2021

Aqueous emulsion polymerization via reversible complexation mediated living radical polymerization yielded low-dispersity poly(methyl methacrylate)s and polystyrenes.
Exploring the evolution process of high-performance amethyst geode-shaped hollow spherical LiFePO4
Authors: Chen Lu , Meng Yan , Wang Yujue , Wang Pengfei , Li Jianming , Lv Qinniu , Zhang Zhaokun , Zhao Qian , Xiao Dan
Published: September 2021

Ammonium polyphosphate (APP) is selected to synthesize hollow spherical LFP. The cohesion of APP results in surface tension and drives the spheroidizing process. And carbon source is a significant factor to hold the framework.
Probing the generality of spin crossover complex T½vs. ligand 15N NMR chemical shift correlations: towards predictable tuning
Authors: Bondì Luca , Rodríguez-Jiménez Santiago , Feltham Humphrey L. C. , Garden Anna L. , Brooker Sally
Published: September 2021

A study of 6 families (42 members) demonstrates that within a family the easily calculated 15N-NMR values of ligands enable predictable tuning of T1/2 in the corresponding complexes, except for 2 families with weakly influencing meta-substituents.
Electrochemical oxidative cyclization of alkenes, boronic acids, and dichalcogenides to access chalcogenated boronic esters and 1,3-diols
Authors: Huang Changfeng , Hu Jijing , Chen Guangxian , Wu Minjian , Cao Hua , Liu Xiang
Published: September 2021

A sustainable, environmentally benign electrochemical oxidative three-component cyclization of allylic alcohols, boronic acids, and dichalcogenides under metal-free and oxidant-free conditions has been developed.
The effects of green waste compost on soil N, P, K, and organic matter fractions in forestry soils: elemental analysis evaluation
Authors: Feng Xiaojie , Sun Xiangyang , Zhou Wenjie , Zhang Wei , Che Feiwei , Li Suyan
Published: September 2021

Green waste compost significantly increased soil N, P, K, and HE fractions, and the –CH/CC components of the HA structures made the biggest contribution to soil N, P, K in forestry soil.
Random laser oscillation from an organic fluorescent dye loaded inside a porous zirconia medium
Authors: Sakurayama Yukari , Onodera Tsunenobu , Araki Yasuyuki , Wada Takehiko , Oikawa Hidetoshi
Published: September 2021

Porous zirconia medium as a porous scatterer was superior to zirconia microparticles with respect to random laser oscillation.
Ion polarisation-assisted hydrogen-bonded ferroelectrics in liquid crystalline domains
Authors: Yuan Guohao , Kimura Yuko , Kobayashi Takayuki , Takeda Takashi , Hoshino Norihisa , Akutagawa Tomoyuki
Published: September 2021

An alkylamide-substituted (−NHCOC10H21) hydrogen-bonded dibenzo[18]crown-6 derivative (1) was prepared to stabilise the ionic channel structure in a discotic hexagonal columnar (Colh) liquid crystal.
The influence of modified molecular (d/l-serine) chirality on the theragnostics of PAMAM-based nanomedicine for acute kidney injury
Authors: Kong Lulu , Fan Di , Zhou Lin , Wei Shaohua
Published: September 2021

Elevated H2O2 are early events in acute kidney injury (AKI). d- and l-serine modified poly(amidoamine) ( d-SP and l-SP) were synthesized. d-SP has superior AKI kidney accumulation ability to l-SP. d-SP was used as both a H2O2 probe and an anti-inflammatory drug carrier for AKI theragnostics.
Lowest unoccupied molecular orbital managing function of CN-substituted dibenzofuran in high triplet energy hosts for blue thermally-activated delayed fluorescence organic light-emitting diodes
Authors: Byeon Sung Yong , Lee Kyung Hyung , Lee Jun Yeob
Published: September 2021

The effect of lowest unoccupied molecular orbital management of high triplet energy electron transport type hosts in organic light-emitting diodes was investigated by synthesizing three hosts derived from CN-modified dibenzofuran.
Optimization of fluxes for Yb3+:YMgB5O10 crystal growth and intense multi-wavelength emission characteristics in spectra and laser performances
Authors: Sun Shijia , Li Bingxuan , Lou Fei , Shi Xingjun , Chen Weidong , Yuan Feifei , Zhang Lizhen , Lin Zhoubin , Zhong Degao , Huang Yisheng , Teng Bing
Published: September 2021

Yb:YMB crystals were grown using the optimized Li2O–B2O3–LiF flux instead of the traditional K2O3–MoO3 flux by the TSSG method. The demonstration of dual-wavelength laser operation reveals the potential in THz generation.
All-round performance improvement of semitransparent perovskite solar cells by a pressure-assisted method
Authors: Yu Yuan , Shang Meijia , Wang Tao , Zhou Qian , Hao Yuying , Pang Zhiyong , Cui Deliang , Lian Gang , Zhang Xijian , Han Shenghao
Published: September 2021

A pressure-assisted method was used to achieve a remarkable enhancement in the crystallinity and flatness of ultra-thin MAPbI3 films. This process facilitates an all-round improvement in the photoelectric and optical properties of solar cells.
Integration of functional genomics data to uncover cell type-specific pathways affected in Parkinson's disease
Authors: Volpato Viola
Published: September 2021

Parkinson's disease (PD) is the second most prevalent late-onset neurodegenerative disorder worldwide after Alzheimer's disease for which available drugs only deliver temporary symptomatic relief. Loss of dopaminergic neurons (DaNs) in the substantia nigra and intracellular alpha-synuclein inclusions are the main hallmarks of the disease but the events that cause this degeneration remain uncertain. Despite cell types other than DaNs such as astrocytes, microglia and oligodendrocytes have been recently associated with the pathogenesis of PD, we still lack an in-depth characterisation of PD-affected brain regions at cell-type resolution that could help our understanding of the disease mechanisms. Nevertheless, publicly available large-scale brain-specific genomic, transcriptomic and epigenomic datasets can be further exploited to extract different layers of cell type-specific biological information for the reconstruction of cell type-specific transcriptional regulatory networks. By intersecting disease risk variants within the networks, it may be possible to study the functional role of these risk variants and their combined effects at cell type- and pathway levels, that, in turn, can facilitate the identification of key regulators involved in disease progression, which are often potential therapeutic targets.
Structure determination of GPCRs: cryo-EM compared with X-ray crystallography
Authors: García-Nafría Javier , Tate Christopher G.
Published: September 2021

G protein-coupled receptors (GPCRs) are the largest single family of cell surface receptors encoded by the human genome and they play pivotal roles in co-ordinating cellular systems throughout the human body, making them ideal drug targets. Structural biology has played a key role in defining how receptors are activated and signal through G proteins and β-arrestins. The application of structure-based drug design (SBDD) is now yielding novel compounds targeting GPCRs. There is thus significant interest from both academia and the pharmaceutical industry in the structural biology of GPCRs as currently only about one quarter of human non-odorant receptors have had their structure determined. Initially, all the structures were determined by X-ray crystallography, but recent advances in electron cryo-microscopy (cryo-EM) now make GPCRs tractable targets for single-particle cryo-EM with comparable resolution to X-ray crystallography. So far this year, 78% of the 99 GPCR structures deposited in the PDB (Jan–Jul 2021) were determined by cryo-EM. Cryo-EM has also opened up new possibilities in GPCR structural biology, such as determining structures of GPCRs embedded in a lipid nanodisc and multiple GPCR conformations from a single preparation. However, X-ray crystallography still has a number of advantages, particularly in the speed of determining many structures of the same receptor bound to different ligands, an essential prerequisite for effective SBDD. We will discuss the relative merits of cryo-EM and X-ray crystallography for the structure determination of GPCRs and the future potential of both techniques.
A Randomized Controlled Trial Using Automated Technology for Improving Ototoxicity Monitoring in VA Oncology Patients
Authors: Konrad-Martin Dawn , O'Connell Bennett Keri , Garinis Angela , McMillan Garnett P.
Published: September 2021

Purpose

Determine the efficacy of ototoxicity monitoring (OM) administered as automated protocols with the Oto-ID mobile audiometer (automated ototoxicity monitoring [A-OM]), compared with usual care (UC) OM in cancer patients receiving cisplatin.

Method

Participants were patients (
n
= 46, mean age 64.7 years; range: 30–78 years) receiving cisplatin-based chemotherapy at the Department of Veterans Affairs Portland Health Care System. A randomized controlled trial contrasted A-OM and UC at up to three program evaluations (PEs) conducted by the study audiologist who was blinded to arm through PE1. PE1 occurred before randomization or oncology treatment; PE2 and PE3 occurred during and/or after treatment at 35 and 365 days postrandomization. The A-OM group (
n
= 24) used Oto-ID to screen their hearing before each cisplatin dose. Oto-ID results were sent to the study audiologist for interpretation, follow-up, and care coordination. The UC group (
n
= 22) received a consult for OM services through the audiology clinic. Outcomes included hearing shift near each patient's high-frequency hearing limit, revised hearing-handicap inventory score, and survival time from the start of treatment. Adherence to OM protocols, patients' use of aural rehabilitation services, and oncologists' treatment decisions were also examined.

Results

Ototoxicity was identified at a high overall rate (46% and 76% at 35 and 365 days, respectively, postrandomization). Adherence to monitoring prior to each cisplatin dose was 83.3% for those randomized to A-OM compared with 4.5% for UC. Randomization to A-OM was not associated with reduced ototoxic hearing shifts or self-reported hearing handicap relative to UC; neither did it compromise participants' survival. Half of participants in each arm accessed aural rehabilitation services. One in each arm had a documented ototoxicity-related cisplatin dose reduction.

Conclusions

Auditory impairment was an actionable concern for the participants and their oncology providers. A dedicated surveillance program using the Oto-ID's automated protocols improved adherence to OM recommendations over a traditional UC service delivery model.

Supplemental Material

https://doi.org/10.23641/asha.16649602
Comparison of the Diagnostic Evaluation of Language Variation–Screening Test Risk Subtest to Two Other Screeners for Low-Income Prekindergartners Who Speak African American English and Live in the Urban South
Authors: Moland Christy Wynn , Oetting Janna B.
Published: September 2021

Purpose

We compared the Risk subtest of the Diagnostic Evaluation of Language Variation–Screening Test (DELV–Screening Test Risk) with two other screeners when administered to low-income prekindergartners (pre-K) who spoke African American English (AAE) in the urban South.

Method

Participants were 73 children (six with a communication disorder and 67 without) enrolled in Head Start or a publicly funded pre-K in an urban Southern city. All children completed the DELV–Screening Test Risk, the Fluharty Preschool Speech and Language Screening Test–Second Edition (FLUHARTY-2), and the Washington and Craig Language Screener (WCLS). Test order was counterbalanced across participants.

Results

DELV–Screening Test Risk error scores were higher than those reported for its standardization sample, and scores on the other screeners were lower than their respective standardization/testing samples. The 52% fail rate of the DELV–Screening Test Risk did not differ significantly from the 48% rate of the WCLS. Fail rates of the FLUHARTY-2 ranged from 34% to 75%, depending on the quotient considered and whether scoring was modified for dialect. Although items and subtests assumed to measure similar constructs were correlated to each other, the three screeners led to inconsistent pass/fail outcomes for 44% of the children.

Conclusions

Like other screeners, the DELV–Screening Test Risk subtest may lead to high fail rates for low-income pre-K children who speak AAE in the urban South. Inconsistent outcomes across screeners underscore the critical need for more study and development of screeners within the field.
Speech Rate Mediated Vowel and Stop Voicing Distinctiveness in Parkinson's Disease
Authors: Knowles Thea , Adams Scott G. , Jog Mandar
Published: September 2021

Purpose

The purpose of this study was to quantify changes in acoustic distinctiveness in two groups of talkers with Parkinson's disease as they modify across a wide range of speaking rates.

Method

People with Parkinson's disease with and without deep brain stimulation and older healthy controls read 24 carrier phrases at different speech rates. Target nonsense words in the carrier phrases were designed to elicit stop consonants and corner vowels. Participants spoke at seven self-selected speech rates from very slow to very fast, elicited via magnitude production. Speech rate was measured in absolute words per minute and as a proportion of each talker's habitual rate. Measures of segmental distinctiveness included a temporal consonant measure, namely, voice onset time, and a spectral vowel measure, namely, vowel articulation index.

Results

All talkers successfully modified their rate of speech from slow to fast. Talkers with Parkinson's disease and deep brain stimulation demonstrated greater baseline speech impairment and produced smaller proportional changes at the fast end of the continuum. Increasingly slower speaking rates were associated with increased temporal contrasts (voice onset time) but not spectral contrasts (vowel articulation). Faster speech was associated with decreased contrasts in both domains. Talkers with deep brain stimulation demonstrated more aberrant productions across all speaking rates.

Conclusions

Findings suggest that temporal and spectral segmental distinctiveness are asymmetrically affected by speaking rate modifications in Parkinson's disease. Talkers with deep brain stimulation warrant further investigation with regard to speech changes they make as they adjust their speaking rate.
A detailed understanding of the rotation-activity relationship using the 300 Myr old open cluster NGC 3532
Authors: Fritzewski D. J. , Barnes S. A. , James D. J. , Järvinen S. P. , Strassmeier K. G.
Published: September 2021

Context. The coeval stars of young open clusters provide insights into the formation of the rotation-activity relationship that elude studies of multi-age field populations.

Aims. We measure the chromospheric activity of cool stars in the 300 Myr old open cluster NGC 3532 in concert with their rotation periods to study the mass-dependent morphology of activity for this transitional coeval population.

Methods. Using multi-object spectra of the Ca II infrared triplet region obtained with the AAOmega spectrograph at the 4 m Anglo-Australian Telescope, we measure the chromospheric emission ratios RIRT′ for 454 FGKM cluster members of NGC 3532.

Results. The morphology of activity against colour appears to be a near-mirror image of the cluster’s rotational behaviour. In particular, we identify a group of ‘desaturated transitional rotators’ that branches off from the main group of unsaturated FGK slow rotators, and from which it is separated by an ‘activity gap’. The few desaturated gap stars are identical to the ones in the rotational gap. Nevertheless, the rotation-activity diagram is completely normal. In fact, the relationship is so tight that it allows us to predict rotation periods for many additional stars. We then precisely determine these periods from our photometric light curves, allowing us to construct an enhanced colour-period diagram that represents 66% of the members in our sample. Our activity measurements show that all fast rotators of near-solar mass (F-G type) have evolved to become slow rotators, demonstrating that the absence of fast rotators in a colour-period diagram is not a detection issue but an astrophysical fact. We also identify a new population of low-activity stars among the early M dwarfs, enabling us to populate the extended slow rotator sequence in the colour-period diagram.

Conclusions. The joint analysis of chromospheric activity and photometric time series data thus enables comprehensive insights into the evolution of the rotation and activity of stars during the transitional phase between the Pleiades and Hyades ages.
A minimal time optimal control for a drone landing problem
Authors: Gazzola Filippo , Marchini Elsa M.
Published: September 2021

We study a variant of the classical safe landing optimal control problem in aerospace engineering, introduced by Miele (1962), where the target was to land a spacecraft on the moon by minimizing the consumption of fuel. A more modern model consists in replacing the spacecraft by a hybrid gas-electric drone. Assuming that the drone has a failure and that the thrust (representing the control) can act in both vertical directions, the new target is to land safely by minimizing time, no matter of what the consumption is. In dependence of the initial data (height, velocity, and fuel), we prove that the optimal control can be of four different kinds, all being piecewise constant. Our analysis covers all possible situations, including the nonexistence of a safe landing strategy due to the lack of fuel or for heights/velocities for which also a total braking is insufficient to stop the drone.
Behandlungsstrategie beim radiojodrefraktären differenzierten Schilddrüsenkarzinom
Authors: Mantsopoulos Konstantinos , Mueller Sarina K. , Pavel Marianne , Kuwert Torsten , Meidenbauer Norbert , Fietkau Rainer , Sievert Matti , Iro Heinrich
Published: September 2021

Traditionell besteht das multimodale Therapiekonzept bei den differenzierten Schilddrüsenkarzinomen in der Thyreoidektomie mit Neck-Dissection (bei cN+-Halsstatus) und adjuvanten Radiojodablation mit abschließender risikoadaptierter TSH-Suppression. Das Ausmaß der Radiojodaufnahme beim metastasierten Schilddrüsenkarzinom spielt eine signifikante Rolle bei der Einschätzung der Prognose. Das fehlende Jodspeicherungsvermögen einer Läsion in Zusammenschau mit dem fehlenden Abfall des Tumormarkers Thyreoglobulin sowie radiologische Zeichen einer Tumorprogression charakterisieren den Radiojod-refraktären Patienten. Aufgrund des meistens über einen langen Zeitraum indolenten Verlaufs erscheint in den meisten Fällen ein abwartendes Verhalten in Kombination mit lokaler Metastasenbehandlung sowie Symptomlinderung primär sinnvoll zu sein. Der Nachweis einer Veränderung der Tumordynamik ist der Zeitpunkt, um eine Systemtherapie zu evaluieren. Diese beruht auf Multi-Tyrosinkinase-Inhibitoren (Sorafenib, Lenvatinib). Diese Substanzen sind größtenteils mit einem ungünstigen Nebenwirkungsprofil assoziiert (Diarrhö, Hautauschläge, arterielle Hypertonie mit hypertensiver Entgleisung, lokale Wundheilungsstörungen), welches zu einer nicht vernachlässigbaren Rate einer therapieassoziierten Morbidität sowie einer hohen Anzahl an Therapieunterbrechungen führt. Daher sind im Jahr 2020 2 selektive RET-Inhibitoren (Selpercatinib, Pralsetinib) für die differenzierten Schilddrüsenkarzinome von der FDA zugelassen worden. Eine neue Perspektive für die Zukunft wären die unterschiedlichen Redifferenzierungsstrategien, welche auf die Steigerung der Sensitivität der Tumorzellen auf Radiojod abzielen.
Patient-Reported Outcomes and Risk Factors for Decreased Improvement after Patellofemoral Arthroplasty
Authors: Dai Yike , Diao Naicheng , Lin Wei , Yang Guangmin , Kang Huijun , Wang Fei
Published: September 2021

Patellofemoral arthroplasty (PFA) is acknowledged as the method for the treatment of isolated patellofemoral osteoarthritis (PFOA). Few previous studies have assessed the patient-reported outcomes (PROs) and risk factors of less improvement of PROs in patients undergoing PFA. A retrospective analysis was performed, including all patients who had undergone PFA. Pre- and postoperative PROs included the Oxford Knee Score (OKS) and Kujala score. Univariate and multivariate statistical analyses were performed to assess influencing factors of less improvement of PROs including the demographic factors (gender, age, body mass index, smoking, opioid usage, and duration of symptoms [DOSs]), surgical factors (concomitant surgery), and imaging factors (trochlear dysplasia [TD], patellar height, the degree of PFOA). A total of 46 PFAs were analyzed with a mean follow-up of 37 ± 7 months. The mean age at surgery was 61.1 ± 7.7 years. Patients showed significant improvement in all PROs (p < 0.001). Patients with TD preoperatively have greater improvement in OKS and Kujala score postoperatively (19.2 ± 5.0 vs. 23.1 ± 3.6, p = 0.038). Longer DOSs (≥1 year) had a greater mean improvement in OKS and Kujala score (p = 0.011 and p = 0.000). According to the measurement of patella height, patients with patella alta (Caton–Deschamps index [CDI] ≥1.3) showed less improvement in both OKS and Kujala score (p = 0.000 and p = 0.002). PFA is a safe and efficient surgery with good PROs. Patella alta with a CDI ≥1.3 and duration of preoperative symptoms ≤ 1 year were risk factors for decreased OKS and Kujala score improvement, while the preoperative presence of TD was significantly predictive factors for increased OKS improvement.
Novel Predictive Markers on Computed Tomography for Predicting Early Epidural Hematoma Growth in Pediatric Patients
Authors: Kopacz Avery A. , Miears Hunter , Collins Reagan A. , Nagy Laszlo
Published: September 2021

Objective Epidural hematoma (EDH), most often caused by rupture of the middle meningeal artery secondary to head trauma with fracture of the temporal bone, is a potentially fatal condition that can lead to elevated intracranial pressure, herniation, and death within hours following the inciting traumatic incident, unless surgical evacuation is accomplished. Several markers have been found to be associated with hematoma expansion in intracerebral hemorrhage (ICH) patients, including: the CT Blend Sign, Swirl Sign, and Black Hole Sign. This study aims to examine these markers, along with intradural air close to or in the region of an EDH and/or close to a significant fracture, fractures involving the skull base, and complicated (i.e., comminuted or displaced) fractures for possible associations to EDH growth in the pediatric population. Predicting hematoma growth is a crucial part of patient management, as surgery can be a life-saving intervention.

Methods Scans from all pediatric patients with EDH from 2012 to 2019 across two separate health systems were examined and measurements were taken to determine whether these additional factors are of predictive value. Specifications such as length, transverse, and height measurements were taken from CT images.

Statistical Analysis The average percent change in the hematoma measurements was used to determine which predictive factors were associated with a “noteworthy increase,” namely, an increase of greater than 25%. Additionally, the average percent change in hematoma size was evaluated for patients whose original imaging showed either all three CT signs or intradural air in all three specified locations.

Results Most of the proposed markers were associated with EDH growth in this cohort. The established CT signs were also supported. This is notable, as most of the research on these signs has been in adult populations rather than pediatric.

Conclusions Adding these novel imaging signs could aid in the decision to operate on versus observe PEDH patients, thereby preventing unnecessary procedures or preserving brain function quickly when surgery is indicated. This study serves as a starting point for several other investigations into the validity of the proposed markers as well as a reevaluation of the current signs in the pediatric population.
Recipient Venule Selection and Anastomosis Configuration for Lymphaticovenular Anastomosis in Extremity Lymphedema: Algorithm Based on 1,000 Lymphaticovenular Anastomosis
Authors: Bianchi Alessandro , Salgarello Marzia , Hayashi Akitatsu , Yang Johnson C.-S. , Visconti Giuseppe
Published: September 2021

Background The lymphaticovenular anastomosis (LVA) has three components, lymphatics, venules, and anastomosis, and all of them influence the anastomotic pressure gradient. Although it has been demonstrated that venule flow dynamics has an independent impact on the outcomes regardless the degeneration status of lymphatic vessels, recipient venules (RV) have been mainly neglected in literature.

Methods From January 2016 to February 2020, 232 nonconsecutive patients affected by extremity lymphedema underwent LVA, for a total of 1,000 LVAs. Only patients with normal-to-ectasic lymphatic collectors were included to focus the evaluation on the RV only. The preoperative collected data included the location, diameter, and continence of the selected venules, the expected number, the anastomoses configuration, and their flow dynamics according to BSO classification.

Results The 232 patients included 117 upper limb lymphedema (ULL) and 115 lower limb lymphedema (LLL). The average size of RV was 0.81 ± 0.32 mm in end-to-end (E-E), 114 ± 0.17 mm in end-to-side (E-S), 0.39 ± 0.22 mm in side-to-end (S-E), and 0.76 ± 0.38 mm in side-to-side (S-S) anastomoses. According to the BSO classification, on a total of 732 RV, 105(14%) were backflow venules, 136 (19%) were slack, and 491 (67%) were outlet venules. Also, 824 (82%) were E-E, 107 (11%) were E-S, 51 (5%) were S-E, and 18 (2%) were S-S anastomoses.

Conclusion Based on 1,000 LVAs with similar lymphatic characteristics, we propose our algorithm that may aid the lymphatic microsurgeon in the selection of RV and the consequent anastomosis configuration, in order of obtain the best flow dynamic through the LVA. This therapeutic study reflects level of evidence IV.
Genetic Analysis of Neuroligin 4Y Gene in Autism Population of India
Authors: Hegde Rajat , Hegde Smita , Kulkarni Suyamindra S. , Pandurangi Aditya , Gai Pramod B. , Das Kusal K.
Published: September 2021

Background Autism is one of the most complex, heterogeneous neurological disorders. It is characterized mainly by abnormal communication, impaired social interaction, and restricted behaviors. Prevalence of autism is not clear in Indian population.

Aim The present study hypothesized that Y chromosome plays role in sex bias of autism in Indian autistic population. To investigate our hypothesis, we underwent genetic analysis of neuroligin 4Y [NLGN4Y] gene by sequencing 85 male autistic children after screening large population of 1,870 mentally ill children from North Karnataka region of India.

Result Detailed sequencing of the single targeted gene revealed nine variants including, one novel missense mutation and eight synonymous variants; this accounts for 88.9% of synonymous variants. A single novel missense mutation is predicted to be nonpathogenic on the functions of neuroligin4Y protein but it slightly affects the local configuration by altering the original structure of a protein by changing charge and size of amino acid.

Conclusion Probably NLGN4Y gene may not be the risk factor for autism in male children in Indian autistic population. Functional analysis was an important limitation of our study. Therefore, detailed functional analysis is necessary to determine the exact role of novel missense mutation of neuroligin 4Y [NLGN4Y] gene especially in the male predominance of autism in Indian autistic population.