bluuebunny/crossref_metadata_2025 huggingface dataset:
Drought acclimation of Quercus ilex leaves improves tolerance to moderate drought but not resistance to severe water stress
Authors: Limousin Jean‐Marc , Roussel Amélie , Rodríguez‐Calcerrada Jesús , Torres‐Ruiz José M. , Moreno Myriam , Garcia de Jalon Laura , Ourcival Jean‐Marc , Simioni Guillaume , Cochard Hervé , Martin‐StPaul Nicolas
Published: April 2022

Increasing temperature and drought can result in leaf dehydration and defoliation even in drought‐adapted tree species such as the Mediterranean evergreen Quercus ilex L. The stomatal regulation of leaf water potential plays a central role in avoiding this phenomenon and is constrained by a suite of leaf traits including hydraulic conductance and vulnerability, hydraulic capacitance, minimum conductance to water vapour, osmotic potential and cell wall elasticity. We investigated whether the plasticity in these traits may improve leaf tolerance to drought in two long‐term rainfall exclusion experiments in Mediterranean forests. Osmotic adjustment was observed to lower the water potential at turgor loss in the rainfall‐exclusion treatments, thus suggesting a stomatal closure at more negative water potentials and a more anisohydric behaviour in drier conditions. Conversely, leaf hydraulic conductance and vulnerability did not exhibit any plasticity between treatments so the hydraulic safety margins were narrower in the rainfall‐exclusion treatments. The sequence of leaf responses to seasonal drought and dehydration was conserved among treatments and sites but trees were more likely to suffer losses of turgor and hydraulic functioning in the rainfall‐exclusion treatments. We conclude that leaf plasticity might help the trees to tolerate moderate drought but not to resist severe water stress.
Catastrophic hydraulic failure and tipping points in plants
Authors: Johnson Daniel M. , Katul Gabriel , Domec Jean‐Christophe
Published: April 2022

Water inside plants forms a continuous chain from water in soils to the water evaporating from leaf surfaces. Failures in this chain result in reduced transpiration and photosynthesis and are caused by soil drying and/or cavitation‐induced xylem embolism. Xylem embolism and plant hydraulic failure share several analogies to ‘catastrophe theory’ in dynamical systems. These catastrophes are often represented in the physiological and ecological literature as tipping points when control variables exogenous (e.g., soil water potential) or endogenous (e.g., leaf water potential) to the plant are allowed to vary on time scales much longer than time scales associated with cavitation events. Here, plant hydraulics viewed from the perspective of catastrophes at multiple spatial scales is considered with attention to bubble expansion within a xylem conduit, organ‐scale vulnerability to embolism, and whole‐plant biomass as a proxy for transpiration and hydraulic function. The hydraulic safety‐efficiency tradeoff, hydraulic segmentation and maximum plant transpiration are examined using this framework. Underlying mechanisms for hydraulic failure at fine scales such as pit membranes and cell‐wall mechanics, intermediate scales such as xylem network properties and at larger scales such as soil–tree hydraulic pathways are discussed. Understudied areas in plant hydraulics are also flagged where progress is urgently needed.
Transcriptome dissection of candidate genes associated with lentil seed quality traits
Authors: Song J. , Mavraganis I. , Shen W. , Yang H. , Cram D. , Xiang D. , Patterson N. , Zou J.
Published: April 2022

Lentils provide a rich plant‐based protein source and staple food in many parts of the world. Despite numerous nutritional benefits, lentil seeds also possess undesirable elements, such as anti‐nutritional factors. Understanding the genetic networks of seed metabolism is of great importance for improving the seed nutritional profile.

We applied RNA sequencing analysis to survey the transcriptome of developing lentil seeds and compared this with that of the pod shells and leaves. In total, we identified 2622 genes differentially expressed among the tissues examined. Genes preferentially expressed in seeds were enriched in the Gene Ontology (GO) terms associated with development, nitrogen and carbon (N/C) metabolism and lipid synthesis.

We further categorized seed preferentially expressed genes based on their involvement in storage protein production, starch accumulation, lipid and suberin metabolism, phytate, saponin and phenylpropanoid biosynthesis.

The availability of transcript profile datasets on lentil seed metabolism and a roadmap of candidate genes presented here will be of great value for breeding strategies towards further improvement of lentil seed quality traits.
OsHUB2 inhibits function of OsTrx1 in heading date in rice
Authors: Xu Zuntao , Li Enze , Xue Gan , Zhang Cheng , Yang Yachun , Ding Yong
Published: April 2022

Heading date is one of the most pivotal agronomic traits for rice (Oryza sativa) yield and adaptation. Little is known about the crosstalk between histone ubiquitination and histone methylation in rice heading date regulation. Here, we reported HISTONE MONOUBIQUITINATION 1 (OsHUB1) and OsHUB2 are involved in heading date regulation via the Hd1 and Ehd1 pathway. Loss of OsHUB1 and OsHUB2 function resulted in early heading under long‐day and short‐day photoperiods. The expression of Hd3a, RFT1, and Ehd1 was induced and the transcript levels of Hd1, Ghd7, OsCCA1, OsGI, OsFKF1, and OsTOC1 were reduced under long‐day conditions, whereas RFT1 and Ehd1 expression was induced in oshub2 mutants under short‐day conditions. OsHUB2 interacted with OsTrx1 and repressed the gene expression of OsTrx1. OsHUB2 directly bound to Ehd1 to ubiquitinate H2B at Ehd1, and H2B ubiquitination levels were reduced in oshub2‐2 and oshub2‐3 mutants. OsTrx1 were highly enriched at Ehd1, and H3K4me3 levels of Ehd1 were upregulated in oshub2‐2. Mutations of OsTrx1 in the oshub2‐2 background rescued the early‐heading phenotype of oshub2‐2. The increases in Ehd1 H3K4me3 levels and transcript levels in oshub2‐2 mutants were attenuated in oshub2‐2 ostrx1‐2 double mutants. Together, our results (i) reveal that OsHUB2 represses the function of OsTrx1 and H3K4me3 levels at Ehd1 and (ii) suggest that OsHUB2‐mediated H2B ubiquitination plays critical roles together with H3K4me3 in rice heading date regulation.
Evaluation of Heat Transfer Enhancement on Rotational Gas Turbine Blade Internal Cooling Channel With Dimpled Surface
Authors: Nourin Farah Nazifa , Blum Brinn Leighton , Amano Ryoichi S.
Published: April 2022

The present investigation represents the rotational effect on gas turbine blade internal cooling with a uniform heat flux of 2000 W/m2 at the bottom wall. The experiment was conducted with three different rpms, such as 300 rpm, 600 rpm, and 900 rpm, with Reynolds number (Re) ranging from 6000 to 50,000 with a two-pass cooling channel. The numerical investigation was conducted with the large eddy simulation (LES) technique to understand the rotational flow behavior of the cooling channel. Four distinct arrangements of dimpled cooling channel surfaces were considered with two different dimple shapes, i.e., partial spherical and leaf. It is found that the rotation effect, dimple arrangement, and design have significant influences on heat transfer. Results indicated that the partial spherical 1-row dimpled surface experienced the highest heat transfer coefficient and pressure drop. In contrast, the leaf-shaped dimpled cooling channel experienced the highest thermal efficiency.
Real-Time Multi-Modal Human–Robot Collaboration Using Gestures and Speech
Authors: Chen Haodong , Leu Ming C. , Yin Zhaozheng
Published: April 2022

As artificial intelligence and industrial automation are developing, human–robot collaboration (HRC) with advanced interaction capabilities has become an increasingly significant area of research. In this paper, we design and develop a real-time, multi-model HRC system using speech and gestures. A set of 16 dynamic gestures is designed for communication from a human to an industrial robot. A data set of dynamic gestures is designed and constructed, and it will be shared with the community. A convolutional neural network is developed to recognize the dynamic gestures in real time using the motion history image and deep learning methods. An improved open-source speech recognizer is used for real-time speech recognition of the human worker. An integration strategy is proposed to integrate the gesture and speech recognition results, and a software interface is designed for system visualization. A multi-threading architecture is constructed for simultaneously operating multiple tasks, including gesture and speech data collection and recognition, data integration, robot control, and software interface operation. The various methods and algorithms are integrated to develop the HRC system, with a platform constructed to demonstrate the system performance. The experimental results validate the feasibility and effectiveness of the proposed algorithms and the HRC system.
Active acoustic scene monitoring through spectro-temporal modulation filtering for intruder detection
Authors: Cheong Kah-Meng , Shen Yih-Liang , Chi Tai-Shih
Published: April 2022

An indoor acoustic scene monitoring system using a periodic impulse signal was previously developed. Compared with the impulse signal, the chirp signal is more robust against environmental noise due to its specific spectro-temporal structure. Such specific structure makes the chirp sound easily detected using a spectro-temporal modulation filtering mechanism. In this paper, we demonstrated a system that employs a two-dimensional spectro-temporal filtering mechanism on a Fourier spectrogram to measure the total energy of the reverberations of the chirp signal as the representation of the acoustic scene. The system compares the reverberation energy difference between consecutive chirps with a predefined threshold to automatically detect the change in the acoustic scene. Simulations were conducted in real living rooms with various types of background noise. Test results demonstrated that the proposed system is much more effective than previously developed systems for detecting the acoustic scene changes due to the intruder silently walking in the rooms. In the biggest test room (18 × 9.8 × 2.5 m3) with heavy background noise, the proposed system can still yield a correct identification rate higher than 80% to the intruder walking at 7 m from the microphone without producing any false alarms.
Auralization of aircraft flyovers with turbulence-induced coherence loss in ground effect
Authors: Pieren Reto , Lincke Dorothea
Published: April 2022

Residents around airports are impacted by noise produced by civil aircraft operations. With the aim of reducing the negative effects of noise, new low-noise aircraft concepts and flight procedures are being developed. The design processes and the assessments of design variants can be supported by auralization of virtual flyovers. The plausibility of auralized aircraft is increased by considering the effects of atmospheric turbulence on sound propagation. This paper presents a simple approach to include turbulence-induced coherence loss in ground effect. Compared to earlier approaches, the proposed model is closer to the physical mechanisms. It is based on the von Kármán turbulence spectrum and a time-variant partial decorrelation filter. The application of the model to jet aircraft flyovers revealed audible improvements by reducing unnatural flanging. The proposed model increases the accuracy and plausibility of aircraft flyover auralizations. It will thus be applied in the perception-based evaluation of future aircraft concepts.
Awakening to Elsewheres: Collectively Restorying Embodied Experiences of (Be)longing
Authors: McGuire-Adams Tricia , Joseph Janelle , Peers Danielle , Eales Lindsay , Bridel William , Chen Chen , Hamdon Evelyn , Kingsley Bethan
Published: April 2022

“Mainstream” spaces of movement cultures within settler colonial states invite bodies that are White, cis, able, thin, and heterosexual, just as “mainstream” academic space validates knowledge about the world produced by these very subjects. Such mainstream assemblages are embedded within the broader structure of settler colonialism, mutually buttressed by White supremacy, heteropatriarchy, and (neo)imperialism. In this article, a Collective of scholars who represent voices from the margins writes back to settler colonialism, ableism, anti-Black racism, and other exclusions and harms. We do this to both elucidate relationships between systems of oppression and craft spaces of embodied freedom and to show/demonstrate belonging within decolonial enactments of “elsewheres.” in the field of sociology of sport.
LATS1 is a central signal transmitter for achieving full type-I interferon activity
Authors: Zuo Yibo , He Jiuyi , Liu Siying , Xu Ying , Liu Jin , Qiao Caixia , Zang Lichao , Sun Wenhuan , Yuan Yukang , Zhang Hongguang , Chen Xiangjie , Jin Lincong , Miao Ying , Huang Fan , Ren Tengfei , Wang Jun , Qian Feng , Zhu Chuanwu , Zhang Wei , Liu Yaobo , Xu Guoqiang , Ma Feng , Zheng Hui
Published: April 2022

Interferons (IFNs) have broad-spectrum antiviral activity to resist virus epidemic. However, IFN antiviral efficacy needs to be greatly improved. Here, we reveal that LATS1 is a vital signal transmitter governing full type-I IFN (IFN-I) signaling activity. LATS1 constitutively binds with the IFN-I receptor IFNAR2 and is rapidly tyro-phosphorylated by Tyk2 upon IFN-I engagement. Tyro-phosphorylation of LATS1 promotes LATS1 activation and YAP degradation, thereby promoting IFN-mediated antiproliferation activity. Moreover, activated LATS1 translocates into the nucleus and induces CDK8-Ser62 phosphorylation, which in turn phosphorylates STAT1 at Ser
727
and induces full IFN-I antiviral activity. LATS1 deficiency restricts in vivo IFN-I signaling and attenuates host antiviral immune response. Our study identifies IFN-I as a previously unidentified extracellular diffusible ligand signal for activation of the Hippo core LATS1 pathway and reveals Tyk2-LATS1-CDK8 as a complete signaling cascade controlling full IFN-I activity.
Early SRC activation skews cell fate from apoptosis to senescence
Authors: Anerillas Carlos , Herman Allison B. , Rossi Martina , Munk Rachel , Lehrmann Elin , Martindale Jennifer L. , Cui Chang-Yi , Abdelmohsen Kotb , De Supriyo , Gorospe Myriam
Published: April 2022

Cells responding to DNA damage implement complex adaptive programs that often culminate in one of two distinct outcomes: apoptosis or senescence. To systematically identify factors driving each response, we analyzed human IMR-90 fibroblasts exposed to increasing doses of the genotoxin etoposide and identified SRC as a key kinase contributing early to this dichotomous decision. SRC was activated by low but not high levels of etoposide. With low DNA damage, SRC-mediated activation of p38 critically promoted expression of cell survival and senescence proteins, while SRC-mediated repression of p53 prevented a rise in proapoptotic proteins. With high DNA damage, failure to activate SRC led to elevation of p53, inhibition of p38, and apoptosis. In mice exposed to DNA damage, pharmacologic inhibition of SRC prevented the accumulation of senescent cells in tissues. We propose that inhibiting SRC could be exploited to favor apoptosis over senescence in tissues to improve health outcomes.
Z-α
1
-antitrypsin polymers impose molecular filtration in the endoplasmic reticulum after undergoing phase transition to a solid state
Authors: Chambers Joseph E. , Zubkov Nikita , Kubánková Markéta , Nixon-Abell Jonathon , Mela Ioanna , Abreu Susana , Schwiening Max , Lavarda Giulia , López-Duarte Ismael , Dickens Jennifer A. , Torres Tomás , Kaminski Clemens F. , Holt Liam J. , Avezov Edward , Huntington James A. , George-Hyslop Peter St , Kuimova Marina K. , Marciniak Stefan J.
Published: April 2022

Misfolding of secretory proteins in the endoplasmic reticulum (ER) features in many human diseases. In α
1
-antitrypsin deficiency, the pathogenic Z variant aberrantly assembles into polymers in the hepatocyte ER, leading to cirrhosis. We show that α
1
-antitrypsin polymers undergo a liquid:solid phase transition, forming a protein matrix that retards mobility of ER proteins by size-dependent molecular filtration. The Z-α
1
-antitrypsin phase transition is promoted during ER stress by an ATF6-mediated unfolded protein response. Furthermore, the ER chaperone calreticulin promotes Z-α
1
-antitrypsin solidification and increases protein matrix stiffness. Single-particle tracking reveals that solidification initiates in cells with normal ER morphology, previously assumed to represent a healthy pool. We show that Z-α
1
-antitrypsin–induced hypersensitivity to ER stress can be explained by immobilization of ER chaperones within the polymer matrix. This previously unidentified mechanism of ER dysfunction provides a template for understanding a diverse group of related proteinopathies and identifies ER chaperones as potential therapeutic targets.
River network rearrangements promote speciation in lowland Amazonian birds
Authors: Musher Lukas J. , Giakoumis Melina , Albert James , Del-Rio Glaucia , Rego Marco , Thom Gregory , Aleixo Alexandre , Ribas Camila C. , Brumfield Robb T. , Smith Brian Tilston , Cracraft Joel
Published: April 2022

Large Amazonian rivers impede dispersal for many species, but lowland river networks frequently rearrange, thereby altering the location and effectiveness of river barriers through time. These rearrangements may promote biotic diversification by facilitating episodic allopatry and secondary contact among populations. We sequenced genome-wide markers to evaluate the histories of divergence and introgression in six Amazonian avian species complexes. We first tested the assumption that rivers are barriers for these taxa and found that even relatively small rivers facilitate divergence. We then tested whether species diverged with gene flow and recovered reticulate histories for all species, including one potential case of hybrid speciation. Our results support the hypothesis that river rearrangements promote speciation and reveal that many rainforest taxa are micro-endemic, unrecognized, and thus threatened with imminent extinction. We propose that Amazonian hyper-diversity originates partly from fine-scale barrier displacement processes—including river dynamics—which allow small populations to differentiate and disperse into secondary contact.
Cryo-EM structures of the human surfactant lipid transporter ABCA3
Authors: Xie Tian , Zhang Zike , Yue Jian , Fang Qi , Gong Xin
Published: April 2022

The adenosine 5′-triphosphate (ATP)–binding cassette (ABC) transporter ABCA3 plays a critical role in pulmonary surfactant biogenesis. Mutations in human ABCA3 have been recognized as the most frequent causes of inherited surfactant dysfunction disorders. Despite two decades of research, in vitro biochemical and structural studies of ABCA3 are still lacking. Here, we report the cryo-EM structures of human ABCA3 in two distinct conformations, both at resolution of 3.3 Å. In the absence of ATP, ABCA3 adopts a “lateral-opening” conformation with the lateral surfaces of transmembrane domains (TMDs) exposed to the membrane and features two positively charged cavities within the TMDs as potential substrate binding sites. ATP binding induces pronounced conformational changes, resulting in the collapse of the potential substrate binding cavities. Our results help to rationalize the disease-causing mutations in human ABCA3 and suggest a conserved “lateral access and extrusion” mechanism for both lipid export and import mediated by ABCA transporters.
ILC killer: Qu’est-ce que c’est?
Authors: Withers David R. , Hepworth Matthew R.
Published: April 2022

A new study published in this issue by Nixon
et al
. demonstrates a cytotoxic transcriptional program, characterized by granzyme C expression, that distinguishes group 1 innate lymphoid cells from classical natural killer cells across multiple tissues in mice.
Mechanisms of strain localization and nucleation of earthquake faulting by grain-scale processes at the middle crustal level
Authors: Hou Chunru , Liu Junlai , Zheng Yuanyuan , Sun Yanqi , Zhang Tieying , Zhou Baojun , Fan Wenkui
Published: April 2022

The mechanism of strain localization is the key to our understanding of the transition from steady-state to unstable flow, and therefore of earthquake faulting in the middle crust. In this study, biotite grains in mylonitic gneisses along the Jinzhou detachment fault zone, Liaodong peninsula, northeast China, acted as a preexisting weak phase that had important influences on deformation of mid-crustal rocks. High phase strength contrasts between biotite and other mineral phases resulted in stress concentrations at the tips of biotite grains and induced semi-brittle deformation of neighboring quartz and feldspar grains. As a consequence, the biotite grains became interconnected to form zones of weakness, while basal plane slip and grain boundary sliding operated in biotite grains and fine-grained biotite-feldspar-quartz aggregates, respectively. The zones filled with biotite grains and fine-grained quartz-feldspar aggregates continued to propagate and coalesce during the deformation. These processes led to transition from load-bearing (i.e., coarse plagioclase grains) framework to interconnected weak phase (i.e., biotite grains and finegrained feldspar aggregates) domination, that further led to the formation of initial strain localization zones (SLZs). With the propagation and linkage of the SLZs, high stress concentrations at the tips of the SLZs led to nucleation of rupture along the SLZs. As a consequence, there occurred an abrupt increase in strain rates that resulted in transition from stable to unstable slip within the SLZs. The processes were accompanied by occurrence of mid-crustal earthquake faulting and formation of pseudotachylites along the SLZs.
Analysis of Content of 2-Oxoacids in Rat Brain Extracts Using High-Performance Liquid Chromatography
Authors: Tashlitsky Vadim N. , Artiukhov Artem V. , Fedorova Natalia V. , Sukonnikov Maxim A. , Ksenofontov Alexander L. , Bunik Victoria I. , Baratova Ludmila A.
Published: April 2022

2-Oxoacids are involved in a number of important metabolic processes and can be used as biomarkers in some human diseases. A new optimized method for quantification of 2,4-dinitrophenylhydrazine derivatives of 2-oxoacids using high-performance liquid chromatography was developed based on available techniques for quantification of 2-oxoacids in mammalian brain. The use of the 2,4-dinitrophenylhydrazine derivatives of 2-oxoacids was shown to be more advantageous in comparison with the previously used phenylhydrazine derivatives, due to a high chemical stability of the former. Here, we determined the concentrations of pyruvate, glyoxylate, 2-oxoglutarate, 2-oxomalonate, and 4-methylthio-2-oxobutyrate in the methanol/acetic acid extracts of the rat brain using the developed method, as well discussed the procedures for the sample preparation in analysis of mammalian brain extracts. The validation parameters of the method demonstrated that the quantification limits for each of the analyzed of 2-oxoacids was 2 nmol/mg tissue. The developed method facilitates identification of subtle changes in the tissue and cellular content of 2-oxoacids as (patho)physiological biomarkers of metabolism in mammalian tissues.
SIDS is associated with prenatal drug use: a meta-analysis and systematic review of 4 238 685 infants
Authors: Makarious Louise , Teng Arthur , Oei Ju Lee
Published: April 2022

Objective

To conduct a meta-analysis to determine the association between prenatal drug exposure and risk of sudden infant death syndrome (SIDS).

Design

Studies were searched using PubMed, Medline and Embase and restricted to English, with no publication date limit. Selected studies included published cohort, population or case studies comparing the incidence of SIDS among drug-exposed with drug-free controls. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology guidelines. Data were pooled using a random-effects model to evaluate risk ratios (RR).

Setting

High-income countries.

Patients

Children with a history of prenatal drug exposure.

Interventions

None.

Main outcome measures

RR of SIDS between drug-exposed and control infants.

Results

Sixteen studies (36 730 infants with any prenatal drug exposure, 21 661 exposed to opioids, 21 571 exposed to cocaine, 5031 exposed to methadone compared with 4 201 955 with no exposure). Any prenatal drug exposure was associated with an increased crude risk of SIDS (RR 7.84, 95% CI 5.21 to 11.81). Prenatal opioid exposure had the highest associative crude risk of SIDS (RR 9.76, 95% CI 5.28 to 18.05), followed by methadone (RR 9.52, 95% CI 4.60 to 19.70) and cocaine (RR 4.40, 95% CI 2.52 to 7.67). Increased crude risk persisted after adjusting for socioeconomic factors (RR 4.24, 95% CI 1.39 to 12.88). The incidence of SIDS for this cohort decreased between 1972 and 2020 but remained significantly higher than controls.

Conclusion

Exposure to any drug of dependency during pregnancy is associated with an increased risk of SIDS after controlling for socioeconomic factors. Further study to evaluate mechanisms and contribution of other confounders (eg, smoking) is warranted.
Early changes in photopic negative response in eyes with glaucoma with and without choroidal detachment after filtration surgery
Authors: Igawa Yuro , Shoji Takuhei , Weinreb Robert , Miyake Yozo , Yoshikawa Yuji , Takano Shunichiro , Shinoda Kei
Published: April 2022

Background/aims

To evaluate the electroretinographic (ERG) changes in the early postoperative period following glaucoma filtration surgery, and its relationship with choroidal detachment (CD).

Methods

This retrospective observational single-centre study included 57 consecutive patients with primary open-angle glaucoma who underwent unilateral glaucoma filtration surgery. The patients were divided into two groups according to the presence or absence of CD. ERG components, including the photopic negative response (PhNR), a-wave and b-wave were compared before and after surgery using skin electrodes.

Results

There were 46 patients in the non-CD group and 11 in the CD group. ERG was recorded within 5.1 (2.1 to 8.1) (mean (95% CI)) days after surgery. In the non-CD group, the PhNR amplitude, PhNR/b-wave amplitude ratio and PhNR implicit time improved significantly after surgery (p=0.008, 0.002 and 0.039, respectively). In the CD group, the amplitude of the PhNR, a-wave and b-wave were significantly deteriorated after surgery (p=0.002, 0.001 and 0.001, respectively). Postoperative intraocular pressure (IOP) (p=0.031) and postoperative CD (p<0.001) were significantly associated with change in the PhNR amplitude in the univariate models. In the multivariate analysis, severe CD (stage 3) cases tended to be deteriorated more.

Conclusion

Even in the early postoperative period within several days, the PhNR amplitude increased with IOP lowering following filtration surgery in the absence of CD. The presence of CD may arrest the improvement of the retinal ganglion cell function. The present results enhance understanding the structural and functional recovery after glaucoma surgery and the role of postoperative CD.
Outcome measures in the management of gluteal tendinopathy: a systematic review of their measurement properties
Authors: Nasser Anthony M , Fearon Angela M , Grimaldi Alison , Vicenzino Bill , Mellor Rebecca , Spencer Trevor , Semciw Adam Ivan
Published: April 2022

Objective

Evaluate properties of outcome measures for gluteal tendinopathy.

Design

Multistage scoping/systematic review.

Data sources

Cochrane, PubMed, Embase, Scopus, Web of Science, PEDro, CINAHL, SPORTDISCUS were searched (December 2021) to identify measures used to evaluate gluteal tendinopathy. Measures were mapped to the core health domains for tendinopathy. Medline, CINAHL, Embase and PubMed were searched (December 2021) for studies evaluating measurement properties of gluteal tendinopathy outcome measures captured in the initial search. Both reviews included studies that evaluated a treatment in participants with gluteal tendinopathy, diagnosed by a professional. Consensus-based-Standards for the Selection of Health Instruments methodology were followed—including bias assessment and synthesis of findings.

Results

Six studies reported on the Victorian Institute of Sport Assessment—Gluteal Tendinopathy (VISA-G). One study reported on the Hip Outcome Score (HOS)—activities of daily living (ADL) and Sport.

The VISA-G had moderate-quality evidence of sufficient construct validity (known group) and responsiveness (pre–post intervention), low-quality evidence of sufficient reliability, measurement error, comprehensibility and insufficient construct validity (convergent), and very low-quality evidence of sufficient comprehensiveness, relevance and responsiveness (comparison with other outcome measures).

Both the HOS(ADL) and HOS(Sport) had very low-quality evidence of sufficient reliability, relevance and insufficient construct validity and comprehensiveness. The HOS(ADL) had very low-quality evidence of sufficient comprehensibility and insufficient measurement error. The HOS(Sport) had very low quality evidence of inconsistent comprehensibility and sufficient measurement error.

Conclusion

Rigorously validated outcome measures for gluteal tendinopathy are lacking. The VISA-G is the preferred available option to capture the disability associated with gluteal tendinopathy.
Differences in career longevity before and after implementation of the Women’s Tennis Association Tour Age Eligibility Rule and Player Development Programmes: a 25-year study
Authors: Otis Carol L , Hainline Brian , Harwood Christopher , Jayanthi Neeru A , Jensen Rick , Keber Ashley , Kroshus Emily , Livengood Thomas , Stroia Kathleen , Quinn Ann , Vitkova Sarka , Kliethermes Stephanie A
Published: April 2022

Objectives

To assess differences in career longevity, as a potential marker of athlete well-being, before and after the 1995 implementation of the Women’s Tennis Association (WTA) Age Eligibility Rule (AER) and Player Development Programmes (PDP), which focused on organisational, physical and psychosocial education, skill building and support for adolescent athletes (≤17 years).

Methods

Career longevity data were collected through 2019 on adolescent players who began professional tournament play between 1970 and 2014 and reached a WTA singles ranking of 1–150 for a minimum of 1 week during their careers. Players were separated into pre-AER/PDP and post-AER/PDP groups, consisting of those who played their first professional events (FPE) before or after 1 January 1995. Measures of career longevity included career duration and premature retirement.

Results

Eight-hundred and eleven players were included in this study (51% pre-AER/PDP). The median career duration was 14.2 years for the post-AER/PDP group compared with 12.1 years for the pre-AER/PDP group (p<0.001). Moreover, post-AER/PDP players had higher probabilities of 10-year and 15-year careers compared with pre-AER/PDP players. After adjusting for age at FPE, athletes in the pre-AER/PDP group had an increased risk of shorter career duration (HR 1.55; 95% CI 1.31 to 1.83) and increased odds of premature retirement (OR 5.39; 95% CI 2.28 to 12.75) than athletes in the post-AER/PDP group.

Conclusions

Adolescent athletes participating on the WTA after the combined AER/PDP initiative had longer career durations, higher probabilities of 10-year and 15-year careers, and decreased risk of premature retirement compared with those participating prior to AER/PDP. Organisational practices that encompass both education and competition regulation can positively affect career longevity related to improving athlete well-being.
Greater proportion of patients report an acceptable symptom state after ACL reconstruction compared with non-surgical treatment: a 10-year follow-up from the Swedish National Knee Ligament Registry
Authors: Persson Kajsa , Bergerson Emma , Svantesson Eleonor , Horvath Alexandra , Karlsson Jon , Musahl Volker , Samuelsson Kristian , Hamrin Senorski Eric
Published: April 2022

Objectives

To compare the proportion of patients with anterior cruciate ligament (ACL) injury reporting an acceptable symptom state, between non-surgical and surgical treatment during a 10-year follow-up.

Methods

Data were extracted from the Swedish National Knee Ligament Registry. Exceeding the Patient Acceptable Symptom State (PASS) for the Knee injury and Osteoarthritis Outcome Score (KOOS) was the primary outcome. The PASS and KOOS4(aggregated KOOS without the activities of daily living (ADL) subscale) were compared cross-sectionally at baseline and 1, 2, 5 and 10 years after ACL injury, where patients treated non-surgically were matched with the maximum number of patients with ACL reconstruction for age, sex and activity at injury.

Results

The non-surgical group consisted of 982 patients, who were each matched against 9 patients treated with ACL reconstruction (n=8,838). A greater proportion of patients treated with ACL reconstruction exceeded the PASS in KOOS pain, ADL, sports and recreation, and quality of life compared with patients treated non-surgically at all follow-ups. With respect to quality of life, significantly more patients undergoing ACL reconstruction achieved a PASS compared with patients receiving non-surgical treatment at all follow-ups except at baseline, with differences ranging between 11% and 25%; 1 year −25.4 (−29.1; −21.7), 2 years −16.9 (−21.2; −12.5), 5 years −11.0 (−16.9; −5.1) and 10 years −24.8 (−36.0; −13.6). The ACL-reconstructed group also reported statistically greater KOOS4at all follow-ups.

Conclusion

A greater proportion of patients treated with ACL reconstruction report acceptable knee function, including higher quality of life than patients treated non-surgically at cross-sectional follow-ups up to 10 years after the treatment of an ACL injury.
Safety and immunogenicity of an inactivated virus particle vaccine for SARS-CoV-2, BIV1-CovIran: findings from double-blind, randomised, placebo-controlled, phase I and II clinical trials among healthy adults
Authors: Mohraz Minoo , Salehi Mohammadreza , Tabarsi Payam , Abbasi-Kangevari Mohsen , Ghamari Seyyed-Hadi , Ghasemi Erfan , Amini Pouya Maryam , Rezaei Negar , Ahmadi Naser , Heidari Kazem , Malekpour Mohammad-Reza , Nasiri Mojtaba , Amirzargar Ali Akbar , Saeedi Moghaddam Sahar , Larijani Bagher , Hosseini Hamed
Published: April 2022

Objective

Assessing safety and immunogenicity of an inactivated whole virus particle vaccine.

Design

Single-centre, double-blind, randomised, placebo-controlled, phase I (stage I: 18–50, stage II: 51–75 years), phase II (18–75 years) clinical trials.

Setting

29 December 2020 to 22 April 2021.

Participants

Stage I-phase I: 56 participants; stage II-phase I: 32; phase II: 280.

Intervention

During stage I, participants randomly (3:3:1) received 3 µg, 5 µg vaccine or placebo in a 14-day interval. Participants in stage II received two shots of 5 µg vaccine or placebo (3:1). In phase II, participants received 5 µg vaccine or placebo (4:1) in a 28-day interval.

Primary and secondary outcome measures

Safety assessment and immunogenicity assessment via antibody response and conventional virus neutralisation test (cVNT).

Results

All adverse events (AEs) were mild or moderate and transient in both phase I and phase II, and no AEs of special interest were reported. The seroconversion-rate of neutralising, antireceptor binding-domain (RBD) and anti-spike-glycoprotein (anti-S) antibodies 14-days after second dose of 5 µg vaccine in stage I was 70.8% (95% CI 48.9% to 87.4%), 87.5% (95% CI 67.6% to 97.3%), 91.7% (95% CI 73.0% to 99.0%). The antibody titres increased more among 5 µg than 3 µg. The corresponding rates for 3 µg vaccine were 45.8% (95% CI 25.6% to 67.2%), 54.2% (95% CI 32.8% to 74.5%) and 70.8% (95% CI 48.9% to 87.4%), respectively. In stage II, 100% (95% CI 84.6% to 100%), 86.4% (95% CI 65.1% to 97.1%) and 86.4% (95% CI 65.1% to 97.1%) of participants seroconverted for neutralising, anti-RBD and anti-S antibodies. In phase II, the seroconversion rate of neutralising-antibody was 82.8% (95% CI 77.0% to 87.6%), anti-RBD 77.0% (95% CI 70.7% to 82.6%) and anti-S 79.9% (95% CI 73.8% to 85.1%) on day 42. In the cVNT, the sera at 1/64 times dilution would neutralise SARS-CoV-2 among 91.7%, 77.3% and 82.5% of vaccinated participants in phase I-stage I, phase I-stage II and phase II clinical trials, respectively.

Conclusions

These results support further evaluation of this inactivated whole virus particle vaccine.

Trial registration numbers

IRCT20201202049567N1 and IRCT20201202049567N2 for phase I and IRCT20201202049567N3 for phase II.
Adaptation of the PERCEPT myeloma prehabilitation trial to virtual delivery: changes in response to the COVID-19 pandemic
Authors: McCourt Orla , Fisher Abigail , Ramdharry Gita , Roberts Anna L , Land Joanne , Rabin Neil , Rowe Katie , Yong Kwee
Published: April 2022

Introduction and objective

Research activity was impacted by the novel COVID-19 pandemic, the PERCEPT myeloma trial was no exception. This pilot randomised trial delivered a face-to-face exercise intervention prior to and during autologous stem cell transplantation (ASCT) in myeloma patients, as a consequence of COVID-19 it required significant adaptions to continue. This brief communication describes how the previously published study protocol was adapted for virtual delivery. In addition, we highlight the challenge of continuing the study which was embedded within a clinical pathway also impacted by the pandemic.

The original trial protocol was amended and continued to recruit and deliver an exercise prehabilitation intervention virtually. Continued delivery of the intervention was deemed important to participants already enrolled within the trial and the adapted virtual version of the trial was acceptable to the research ethics committee as well as participants. Development of effective, remotely delivered rehabilitation and physical activity programmes are likely to benefit people living with myeloma. The COVID-19 pandemic provided an opportunity to explore the feasibility of a virtual programme for ASCT recipients, however, continued changes to the clinical pathway within which the study was embedded posed the greatest challenge and ultimately led to early termination of recruitment.

Trial registration number

ISRCTN15875290; pre-results
Overexpression of integrin alpha 2 (ITGA2) correlates with poor survival in patients with pancreatic ductal adenocarcinoma
Authors: Deichmann Steffen , Schindel Leif , Braun Rüdiger , Bolm Louisa , Taylor Martin , Deshpande Vikram , Schilling Oliver , Bronsert Peter , Keck Tobias , Ferrone Cristina , Wellner Ulrich , Honselmann Kim
Published: April 2022

Aims

Due to the known malignant potential and the poor overall prognosis of pancreatic ductal adenocarcinoma (PDAC), the identification of new biomarkers is of utmost importance. It has been reported that integrin alpha 2 (ITGA2), plakophilin 3 (PKP3) and adenylate kinase 4 (AK4) are associated with poor survival and more aggressive malignant behaviour in multiple cancers; however, their role in PDAC is still unknown. Therefore, the aim of this study was to investigate the correlation of ITGA2, PKP3 and AK4 expression with PDAC tumour characteristics and patient survival.

Methods

Of 105 patients undergoing oncological pancreatic resection between 2012 and 2018, tissue microarrays were prepared from formalin-fixed, paraffin-embedded PDAC tissues and immunohistochemically stained with PKP3, AK4 and ITGA2. Clinical and pathological patient data were retrieved from the electronic patient charts and correlated with biomarker staining scores.

Results

ITGA2 expression was high in 43% of patients with PDAC, whereas AK4 and PKP3 expressions were high in 28% and 57%, respectively. Overall survival was negatively associated with high ITGA2 expression in comparison with low expression (13 months (95% CI 10 to 18 months) vs 25 months (95% CI 20 to 30 months), p<0.001). Expression of AK4 and PKP3 did not correlate with overall survival. Multivariate Cox regression identified ITGA2 as an independent predictor of shorter overall survival in PDAC of different lymph node status and high tumour grade (G3/G4).

Conclusions

ITGA2 is an independent prognostic parameter for survival in patients with resected PDAC. PKP3 and AK4 do not appear to have prognostic value for survival in PDAC.
GLRA2gene mutations cause high myopia in humans and mice
Authors: Tian Qi , Tong Ping , Chen Gong , Deng Meichun , Cai Tian'e , Tian Runyi , Zhang Zimin , Xia Kun , Hu Zhengmao
Published: April 2022

Background

High myopia (HM) is a leading cause of blindness that has a strong genetic predisposition. However, its genetic and pathogenic mechanisms remain largely unknown. Thus, this study aims to determine the genetic profile of individuals from two large Chinese families with HM and 200 patients with familial/sporadic HM. We also explored the pathogenic mechanism of HM using HEK293 cells and a mouse model.

Methods

The participants underwent genome-wide linkage analysis and exome sequencing. Visual acuity, electroretinogram response, refractive error, optical parameters and retinal rod cell genesis were measured in knockout mice. Immunofluorescent staining, biotin-labelled membrane protein isolation and electrophysiological characterisation were conducted in cells transfected with overexpression plasmids.

Results

A novel HM locus on Xp22.2-p11.4 was identified. Variant c.539C>T (p.Pro180Leu) inGLRA2gene was co-segregated with HM in the two families. Another variant, c.458G>A (p.Arg153Gln), was identified in a sporadic sample. TheGlra2knockout mice showed myopia-related phenotypes, decreased electroretinogram responses and impaired retinal rod cell genesis. Variants c.458G>A and c.539C>T altered the localisation of GlyRα2 on the cell membrane and decreased agonist sensitivity.

Conclusion

GLRA2was identified as a novel HM-causing gene. Its variants would cause HM through altered visual experience by impairing photoperception and visual transmission.
Aetiology, secondary prevention strategies and outcomes of ischaemic stroke despite oral anticoagulant therapy in patients with atrial fibrillation
Authors: Polymeris Alexandros A , Meinel Thomas R , Oehler Hannah , Hölscher Kyra , Zietz Annaelle , Scheitz Jan F , Nolte Christian H , Stretz Christoph , Yaghi Shadi , Stoll Svenja , Wang Ruihao , Häusler Karl Georg , Hellwig Simon , Klammer Markus G , Litmeier Simon , Leon Guerrero Christopher R , Moeini-Naghani Iman , Michel Patrik , Strambo Davide , Salerno Alexander , Bianco Giovanni , Cereda Carlo , Uphaus Timo , Gröschel Klaus , Katan Mira , Wegener Susanne , Peters Nils , Engelter Stefan T , Lyrer Philippe A , Bonati Leo H , Grunder Lorenz , Ringleb Peter Arthur , Fischer Urs , Kallmünzer Bernd , Purrucker Jan C , Seiffge David J
Published: April 2022

Objective

To investigate the aetiology, subsequent preventive strategies and outcomes of stroke despite anticoagulation in patients with atrial fibrillation (AF).

Methods

We analysed consecutive patients with AF with an index imaging-proven ischaemic stroke despite vitamin K-antagonist (VKA) or direct oral anticoagulant (DOAC) treatment across 11 stroke centres. We classified stroke aetiology as: (i) competing stroke mechanism other than AF-related cardioembolism; (ii) insufficient anticoagulation (non-adherence or low anticoagulant activity measured with drug-specific assays); or, (iii) AF-related cardioembolism despite sufficient anticoagulation. We investigated subsequent preventive strategies with regard to the primary (composite of recurrent ischaemic stroke, intracranial haemorrhage, death) and secondary endpoint (recurrent ischaemic stroke) within 3 months after index stroke.

Results

Among 2946 patients (median age 81 years; 48% women; 43% VKA, 57% DOAC), stroke aetiology was competing mechanism in 713 patients (24%), insufficient anticoagulation in 934 (32%) and cardioembolism despite sufficient anticoagulation in 1299 (44%). We found high rates of the primary (27% of patients; completeness 91.6%) and secondary endpoint (4.6%; completeness 88.5%). Only DOAC (vs VKA) treatment after index stroke showed lower odds for both endpoints (primary: adjusted OR (aOR) (95% CI) 0.49 (0.32 to 0.73); secondary: 0.44 (0.24 to 0.80)), but not switching between different DOAC types. Adding antiplatelets showed higher odds for both endpoints (primary: aOR (95% CI) 1.99 (1.25 to 3.15); secondary: 2.66 (1.40 to 5.04)). Only few patients (1%) received left atrial appendage occlusion as additional preventive strategy.

Conclusions

Stroke despite anticoagulation comprises heterogeneous aetiologies and cardioembolism despite sufficient anticoagulation is most common. While DOAC were associated with better outcomes than VKA, adding antiplatelets was linked to worse outcomes in these high-risk patients. Our findings indicate that individualised and novel preventive strategies beyond the currently available anticoagulants are needed.

Trial registration number

ISRCTN48292829.
Results of the COMPARE trial of Constraint-induced or Multimodality Aphasia Therapy compared with usual care in chronic post-stroke aphasia
Authors: Rose Miranda L , Nickels Lyndsey , Copland David , Togher Leanne , Godecke Erin , Meinzer Marcus , Rai Tapan , Cadilhac Dominique A , Kim Joosup , Hurley Melanie , Foster Abby , Carragher Marcella , Wilcox Cassie , Pierce John E , Steel Gillian
Published: April 2022

Background

While meta-analyses confirm treatment for chronic post-stroke aphasia is effective, a lack of comparative evidence for different interventions limits prescription accuracy. We investigated whether Constraint-Induced Aphasia Therapy Plus (CIAT-plus) and/or Multimodality Aphasia Therapy (M-MAT) provided greater therapeutic benefit compared with usual community care and were differentially effective according to baseline aphasia severity.

Methods

We conducted a three-arm, multicentre, parallel group, open-label, blinded endpoint, phase III, randomised-controlled trial. We stratified eligible participants by baseline aphasia on the Western Aphasia Battery-Revised Aphasia Quotient (WAB-R-AQ). Groups of three participants were randomly assigned (1:1:1) to 30 hours of CIAT-Plus or M-MAT or to usual care (UC). Primary outcome was change in aphasia severity (WAB-R-AQ) from baseline to therapy completion analysed in the intention-to-treat population. Secondary outcomes included word retrieval, connected speech, functional communication, multimodal communication, quality of life and costs.

Results

We analysed 201 participants (70 in CIAT-Plus, 70 in M-MAT and 61 in UC). Aphasia severity was not significantly different between groups at postintervention: 1.05 points (95% CI −0.78 to 2.88; p=0.36) UC group vs CIAT-Plus; 1.06 points (95% CI −0.78 to 2.89; p=0.36) UC group vs M-MAT; 0.004 points (95% CI −1.76 to 1.77; p=1.00) CIAT-Plus vs M-MAT. Word retrieval, functional communication and communication-related quality of life were significantly improved following CIAT-Plus and M-MAT. Word retrieval benefits were maintained at 12-week follow-up.

Conclusions

CIAT-Plus and M-MAT were effective for word retrieval, functional communication, and quality of life, while UC was not. Future studies should explore predictive characteristics of responders and impacts of maintenance doses.

Trial registration number

ACTRN 2615000618550.