bluuebunny/crossref_metadata_2025 huggingface dataset:
The fast and the furious: rapid long-range signaling in plants
Authors: Johns Sarah , Hagihara Takuma , Toyota Masatsugu , Gilroy Simon
Published: January 2021

Plants possess a systemic signaling system whereby local stimuli can lead to rapid, plant-wide responses. In addition to the redistribution of chemical messengers that range from RNAs and peptides to hormones and metabolites, a communication system acting through the transmission of electrical, Ca2+, reactive oxygen species and potentially even hydraulic signals has also been discovered. This latter system can propagate signals across many cells each second and researchers are now beginning to uncover the molecular machineries behind this rapid communications network. Thus, elements such as the reactive oxygen species producing NAPDH oxidases and ion channels of the two pore channel, glutamate receptor-like and cyclic nucleotide gated families are all required for the rapid propagation of these signals. Upon arrival at their distant targets, these changes trigger responses ranging from the production of hormones, to changes in the levels of primary metabolites and shifts in patterns of gene expression. These systemic responses occur within seconds to minutes of perception of the initial, local signal, allowing for the rapid deployment of plant-wide responses. For example, an insect starting to chew on just a single leaf triggers preemptive antiherbivore defenses throughout the plant well before it has a chance to move on to the next leaf on its menu.
Attracted to membranes: lipid-binding domains in plants
Authors: de Jong Femke , Munnik Teun
Published: January 2021

Membranes are essential for cells and organelles to function. As membranes are impermeable to most polar and charged molecules, they provide electrochemical energy to transport molecules across and create compartmentalized microenvironments for specific enzymatic and cellular processes. Membranes are also responsible for guided transport of cargoes between organelles and during endo- and exocytosis. In addition, membranes play key roles in cell signaling by hosting receptors and signal transducers and as substrates and products of lipid second messengers. Anionic lipids and their specific interaction with target proteins play an essential role in these processes, which are facilitated by specific lipid-binding domains. Protein crystallography, lipid-binding studies, subcellular localization analyses, and computer modeling have greatly advanced our knowledge over the years of how these domains achieve precision binding and what their function is in signaling and membrane trafficking, as well as in plant development and stress acclimation.
ThePhyscomitrella patenschromatin adaptor PpMRG1 interacts with H3K36me3 and regulates light-responsive alternative splicing
Authors: Wang Chien-Chang , Hsieh Hsin-Yu , Hsieh Hsu-Liang , Tu Shih-Long
Published: January 2021

Plants perceive dynamic light conditions and optimize their growth and development accordingly by regulating gene expression at multiple levels. Alternative splicing (AS), a widespread mechanism in eukaryotes that post-transcriptionally generates two or more messenger RNAs (mRNAs) from the same pre-mRNA, is rapidly controlled by light. However, a detailed mechanism of light-regulated AS is still not clear. In this study, we demonstrate that histone 3 lysine 36 trimethylation (H3K36me3) rapidly and differentially responds to light at specific gene loci with light-regulated intron retention (IR) of their transcripts in the moss Physcomitrella patens. However, the level of H3K36me3 following exposure to light is inversely related to that of IR events. Physcomitrella patens MORF-related gene 1 (PpMRG1), a chromatin adaptor, bound with higher affinity to H3K36me3 in light conditions than in darkness and was differentially targeted to gene loci showing light-responsive IR. Transcriptome analysis indicated that PpMRG1 functions in the regulation of light-mediated AS. Furthermore, PpMRG1 was also involved in red light-mediated phototropic responses. Our results suggest that light regulates histone methylation, which leads to alterations of AS patterns. The chromatin adaptor PpMRG1 potentially participates in light-mediated AS, revealing that chromatin-coupled regulation of pre-mRNA splicing is an important aspect of the plant’s response to environmental changes.
WARPP—web application for the research of parasitic plants
Authors: Kösters Lara M , Wiechers Sarah , Lyko Peter , Müller Kai F , Wicke Susann
Published: January 2021

The lifestyle of parasitic plants is associated with peculiar morphological, genetic, and physiological adaptations that existing online plant-specific resources fail to adequately represent. Here, we introduce the Web Application for the Research of Parasitic Plants (WARPP) as an online resource dedicated to advancing research and development of parasitic plant biology. WARPP is a framework to facilitate international efforts by providing a central hub of curated evolutionary, ecological, and genetic data. The first version of WARPP provides a community hub for researchers to test this web application, for which curated data revolving around the economically important Broomrape family (Orobanchaceae) is readily accessible. The initial set of WARPP online tools includes a genome browser that centralizes genomic information for sequenced parasitic plant genomes, an orthogroup summary detailing the presence and absence of orthologous genes in parasites compared with nonparasitic plants, and an ancestral trait explorer showing the evolution of life-history preferences along phylogenies. WARPP represents a project under active development and relies on the scientific community to populate the web app’s database and further the development of new analysis tools. The first version of WARPP can be securely accessed at https://parasiticplants.app. The source code is licensed under GNU GPLv2 and is available at https://github.com/wickeLab/WARPP.
Biotin attachment domain-containing proteins mediate hydroxy fatty acid-dependent inhibition of acetyl CoA carboxylase
Authors: Yu Xiao-Hong , Cai Yuanheng , Keereetaweep Jantana , Wei Kenneth , Chai Jin , Deng Elen , Liu Hui , Shanklin John
Published: January 2021

Hundreds of naturally occurring specialized fatty acids (FAs) have potential as desirable chemical feedstocks if they could be produced at large scale by crop plants; however, transgenic expression of their biosynthetic genes has generally been accompanied by dramatic reductions in oil yield. For example, expression of castor (Ricinus communis) FA hydroxylase (FAH) in the Arabidopsis thaliana FA elongation mutant fae1 resulted in a 50% reduction of FA synthesis rate that was attributed to inhibition of acetyl-CoA carboxylase (ACCase) by an undefined mechanism. Here, we tested the hypothesis that the ricinoleic acid-dependent decrease in ACCase activity is mediated by biotin attachment domain-containing (BADC) proteins. BADCs are inactive homologs of biotin carboxy carrier protein that lack a biotin cofactor and can inhibit ACCase. Arabidopsis contains three BADC genes. To reduce expression levels of BADC1 and BADC3 in fae1/FAH plants, a homozygous badc1,3/fae1/FAH line was created. The rate of FA synthesis in badc1,3/fae1/FAH seeds doubled relative to fae1/FAH, restoring it to fae1 levels, increasing both native FA and HFA accumulation. Total FA per seed, seed oil content, and seed yield per plant all increased in badc1,3/fae1/FAH, to 5.8 µg, 37%, and 162 mg, respectively, relative to 4.9 µg, 33%, and 126 mg, respectively, for fae1/FAH. Transcript levels of FA synthesis-related genes, including those encoding ACCase subunits, did not significantly differ between badc1,3/fae1/FAH and fae1/FAH. These results demonstrate that BADC1 and BADC3 mediate ricinoleic acid-dependent inhibition of FA synthesis. We propose that BADC-mediated FAS inhibition as a general mechanism that limits FA accumulation in specialized FA-accumulating seeds.
Characterization of the Bubblegum acyl-CoA synthetase of Microchloropsis gaditana
Authors: Billey Elodie , Magneschi Leonardo , Leterme Sébastien , Bedhomme Mariette , Andres-Robin Amélie , Poulet Laurent , Michaud Morgane , Finazzi Giovanni , Dumas Renaud , Crouzy Serge , Laueffer Frédéric , Fourage Laurent , Rébeillé Fabrice , Amato Alberto , Collin Séverine , Jouhet Juliette , Maréchal Eric
Published: January 2021

The metabolic pathways of glycerolipids are well described in cells containing chloroplasts limited by a two-membrane envelope but not in cells containing plastids limited by four membranes, including heterokonts. Fatty acids (FAs) produced in the plastid, palmitic and palmitoleic acids (16:0 and 16:1), are used in the cytosol for the synthesis of glycerolipids via various routes, requiring multiple acyl-Coenzyme A (CoA) synthetases (ACS). Here, we characterized an ACS of the Bubblegum subfamily in the photosynthetic eukaryote Microchloropsis gaditana, an oleaginous heterokont used for the production of lipids for multiple applications. Genome engineering with TALE-N allowed the generation of MgACSBG point mutations, but no knockout was obtained. Point mutations triggered an overall decrease of 16:1 in lipids, a specific increase of unsaturated 18-carbon acyls in phosphatidylcholine and decrease of 20-carbon acyls in the betaine lipid diacylglyceryl–trimethyl–homoserine. The profile of acyl-CoAs highlighted a decrease in 16:1-CoA and 18:3-CoA. Structural modeling supported that mutations affect accessibility of FA to the MgACSBG reaction site. Expression in yeast defective in acyl-CoA biosynthesis further confirmed that point mutations affect ACSBG activity. Altogether, this study supports a critical role of heterokont MgACSBG in the production of 16:1-CoA and 18:3-CoA. In M. gaditana mutants, the excess saturated and monounsaturated FAs were diverted to triacylglycerol, thus suggesting strategies to improve the oil content in this microalga.
Identification and characterization of sorgomol synthase in sorghum strigolactone biosynthesis
Authors: Wakabayashi Takatoshi , Ishiwa Shunsuke , Shida Kasumi , Motonami Noriko , Suzuki Hideyuki , Takikawa Hirosato , Mizutani Masaharu , Sugimoto Yukihiro
Published: January 2021

Strigolactones (SLs), first identified as germination stimulants for root parasitic weeds, act as endogenous phytohormones regulating shoot branching and as root-derived signal molecules mediating symbiotic communications in the rhizosphere. Canonical SLs typically have an ABCD ring system and can be classified into orobanchol- and strigol-type based on the C-ring stereochemistry. Their simplest structures are 4-deoxyorobanchol (4DO) and 5-deoxystrigol (5DS), respectively. Diverse canonical SLs are chemically modified with one or more hydroxy or acetoxy groups introduced into the A- and/or B-ring of these simplest structures, but the biochemical mechanisms behind this structural diversity remain largely unexplored. Sorgomol in sorghum (Sorghum bicolor [L.] Moench) is a strigol-type SL with a hydroxy group at C-9 of 5DS. In this study, we characterized sorgomol synthase. Microsomal fractions prepared from a high-sorgomol-producing cultivar of sorghum, Sudax, were shown to convert 5DS to sorgomol. A comparative transcriptome analysis identified SbCYP728B subfamily as candidate genes encoding sorgomol synthase. Recombinant SbCYP728B35 catalyzed the conversion of 5DS to sorgomol in vitro. Substrate specificity revealed that the C-8bS configuration in the C-ring of 5DS stereoisomers was essential for this reaction. The overexpression of SbCYP728B35 in Lotus japonicus hairy roots, which produce 5DS as an endogenous SL, also resulted in the conversion of 5DS to sorgomol. Furthermore, SbCYP728B35 expression was not detected in nonsorgomol-producing cultivar, Abu70, suggesting that this gene is responsible for sorgomol production in sorghum. Identification of the mechanism modifying parental 5DS of strigol-type SLs provides insights on how plants biosynthesize diverse SLs.
The gibberellin signaling negative regulator RGA-LIKE3 promotes seed storage protein accumulation
Authors: Hu Yilong , Zhou Limeng , Yang Yuhua , Zhang Wenbin , Chen Zhonghui , Li Xiaoming , Qian Qian , Kong Fanjiang , Li Yuge , Liu Xu , Hou Xingliang
Published: January 2021

Seed storage protein (SSP) acts as one of the main components of seed storage reserves, of which accumulation is tightly mediated by a sophisticated regulatory network. However, whether and how gibberellin (GA) signaling is involved in this important biological event is not fully understood. Here, we show that SSP content in Arabidopsis (Arabidopsis thaliana) is significantly reduced by GA and increased in the GA biosynthesis triple mutant ga3ox1/3/4. Further investigation shows that the DELLA protein RGA-LIKE3 (RGL3), a negative regulator of GA signaling, is important for SSP accumulation. In rgl3 and 35S:RGL3-HA, the expression of SSP genes is down- and upregulated, respectively, compared with that in the wild-type. RGL3 interacts with ABSCISIC ACID INSENSITIVE3 (ABI3), a critical transcription factor for seed developmental processes governing SSP accumulation, both in vivo and in vitro, thus greatly promoting the transcriptional activating ability of ABI3 on SSP genes. In addition, genetic evidence shows that RGL3 and ABI3 regulate SSP accumulation in an interdependent manner. Therefore, we reveal a function of RGL3, a little studied DELLA member, as a coactivator of ABI3 to promote SSP biosynthesis during seed maturation stage. This finding advances the understanding of mechanisms in GA-mediated seed storage reserve accumulation.
Phosphorus deprivation affects composition and spatial distribution of membrane lipids in legume nodules
Authors: Dokwal Dhiraj , Romsdahl Trevor B , Kunz Daniel A , Alonso Ana Paula , Dickstein Rebecca
Published: January 2021

In legumes, symbiotic nitrogen (N) fixation (SNF) occurs in specialized organs called nodules after successful interactions between legume hosts and rhizobia. In a nodule, N-fixing rhizobia are surrounded by symbiosome membranes, through which the exchange of nutrients and ammonium occurs between bacteria and the host legume. Phosphorus (P) is an essential macronutrient, and N2-fixing legumes have a higher requirement for P than legumes grown on mineral N. As in the previous studies, in P deficiency, barrel medic (Medicago truncatula) plants had impaired SNF activity, reduced growth, and accumulated less phosphate in leaves, roots, and nodules compared with the plants grown in P sufficient conditions. Membrane lipids in M. truncatula tissues were assessed using electrospray ionization–mass spectrometry. Galactolipids were found to increase in P deficiency, with declines in phospholipids (PL), especially in leaves. Lower PL losses were found in roots and nodules. Subsequently, matrix-assisted laser desorption/ionization–mass spectrometry imaging was used to spatially map the distribution of the positively charged phosphatidylcholine (PC) species in nodules in both P-replete and P-deficient conditions. Our results reveal heterogeneous distribution of several PC species in nodules, with homogeneous distribution of other PC classes. In P poor conditions, some PC species distributions were observed to change. The results suggest that specific PC species may be differentially important in diverse nodule zones and cell types, and that membrane lipid remodeling during P stress is not uniform across the nodule.
Stromal NADH supplied by PHOSPHOGLYCERATE DEHYDROGENASE3 is crucial for photosynthetic performance
Authors: Höhner Ricarda , Day Philip M , Zimmermann Sandra E , Lopez Laura S , Krämer Moritz , Giavalisco Patrick , Correa Galvis Viviana , Armbruster Ute , Schöttler Mark Aurel , Jahns Peter , Krueger Stephan , Kunz Hans-Henning
Published: January 2021

During photosynthesis, electrons travel from light-excited chlorophyll molecules along the electron transport chain to the final electron acceptor nicotinamide adenine dinucleotide phosphate (NADP) to form NADPH, which fuels the Calvin–Benson–Bassham cycle (CBBC). To allow photosynthetic reactions to occur flawlessly, a constant resupply of the acceptor NADP is mandatory. Several known stromal mechanisms aid in balancing the redox poise, but none of them utilizes the structurally highly similar coenzyme NAD(H). Using Arabidopsis (Arabidopsis thaliana) as a C3-model, we describe a pathway that employs the stromal enzyme PHOSPHOGLYCERATE DEHYDROGENASE 3 (PGDH3). We showed that PGDH3 exerts high NAD(H)-specificity and is active in photosynthesizing chloroplasts. PGDH3 withdrew its substrate 3-PGA directly from the CBBC. As a result, electrons become diverted from NADPH via the CBBC into the separate NADH redox pool. pgdh3 loss-of-function mutants revealed an overreduced NADP(H) redox pool but a more oxidized plastid NAD(H) pool compared to wild-type plants. As a result, photosystem I acceptor side limitation increased in pgdh3. Furthermore, pgdh3 plants displayed delayed CBBC activation, changes in nonphotochemical quenching, and altered proton motive force partitioning. Our fluctuating light-stress phenotyping data showed progressing photosystem II damage in pgdh3 mutants, emphasizing the significance of PGDH3 for plant performance under natural light environments. In summary, this study reveals an NAD(H)-specific mechanism in the stroma that aids in balancing the chloroplast redox poise. Consequently, the stromal NAD(H) pool may provide a promising target to manipulate plant photosynthesis.
Autophagy is required for lipid homeostasis during dark-induced senescence
Authors: Barros Jessica A S , Magen Sahar , Lapidot-Cohen Taly , Rosental Leah , Brotman Yariv , Araújo Wagner L , Avin-Wittenberg Tamar
Published: January 2021

Autophagy is an evolutionarily conserved mechanism that mediates the degradation of cytoplasmic components in eukaryotic cells. In plants, autophagy has been extensively associated with the recycling of proteins during carbon-starvation conditions. Even though lipids constitute a significant energy reserve, our understanding of the function of autophagy in the management of cell lipid reserves and components remains fragmented. To further investigate the significance of autophagy in lipid metabolism, we performed an extensive lipidomic characterization of Arabidopsis (Arabidopsis thaliana) autophagy mutants (atg) subjected to dark-induced senescence conditions. Our results revealed an altered lipid profile in atg mutants, suggesting that autophagy affects the homeostasis of multiple lipid components under dark-induced senescence. The acute degradation of chloroplast lipids coupled with the differential accumulation of triacylglycerols (TAGs) and plastoglobuli indicates an alternative metabolic reprogramming toward lipid storage in atg mutants. The imbalance of lipid metabolism compromises the production of cytosolic lipid droplets and the regulation of peroxisomal lipid oxidation pathways in atg mutants.
Designing Ghosts, Queer Readership, and the Phantom Public in E. M. Forster’s ‘Dr Woolacott’
Authors: Christie Stuart
Published: January 2021

In an undated manuscript from the 1920s, E. M. Forster sketched out notes towards a theory he called ‘writing to the body with the body’, a ‘melting’ of sentiment into disinterested aesthetics, he identified as pornographic. The ‘On Pornography and Sentiment’ fragment not only reframes our understanding of Forster’s emerging stance during this period as a champion of free speech but also highlights his less well-known status as the nodal figure for a younger generation of gay writers with whom he shared drafts of his erotic short stories. My close readings of selections from Forster’s unfinished notes, his roughly contemporary work of criticism, Aspects of the Novel (1927), as well as his posthumously published short story, ‘Dr Woolacott’, suggest that Forster’s theory of sentimentalized aesthetics made the beginnings of a capable critique. By circulating his short stories, Forster sought to check mainstream censoriousness concerning ‘obscene’ texts; moreover, his ‘refunctioning’ of illicit desires to an ethical purpose enlivened the ‘phantom’ potential of the modernist public sphere (Robbins) and actively facilitated the formation of an inter-generational intimate public (Berlant).
Abnormal Brain Bioenergetics in First-Episode Psychosis
Authors: Yuksel Cagri , Chen Xi , Chouinard Virginie-Anne , Nickerson Lisa D , Gardner Margaret , Cohen Talia , Öngür Dost , Du Fei
Published: January 2021

Background

Converging evidence indicates impaired brain energy metabolism in schizophrenia and other psychotic disorders. Creatine kinase (CK) is pivotal in providing adenosine triphosphate in the cell and maintaining its levels when energy demand is increased. However, the activity of CK has not been investigated in patients with first-episode schizophrenia spectrum disorders.

Methods

Using in vivo phosphorus magnetization transfer spectroscopy, we measured CK first-order forward rate constant (kf) in the frontal lobe, in patients with first-episode psychosis (FEP; n = 16) and healthy controls (n = 34), at rest.

Results

CK kf was significantly reduced in FEP compared to healthy controls. There were no differences in other energy metabolism-related measures, including phosphocreatine (PCr) or ATP, between groups. We also found increase in glycerol-3-phosphorylcholine, a putative membrane breakdown product, in patients.

Conclusions

The results of this study indicate that brain bioenergetic abnormalities are already present early in the course of schizophrenia spectrum disorders. Future research is needed to identify the relationship of reduced CK kf with psychotic symptoms and to test treatment alternatives targeting this pathway. Increased glycerol-3-phosphorylcholine is consistent with earlier studies in medication-naïve patients and later studies in first-episode schizophrenia, and suggest enhanced synaptic pruning.
Using ecological variables to predict Ross River virus disease incidence in South Australia
Authors: Liu Jingwen , Hansen Alana , Cameron Scott , Williams Craig , Fricker Stephen , Bi Peng
Published: January 2021

Background

Ross River virus (RRV) disease is Australia's most widespread vector-borne disease causing significant public health concern. The aim of this study was to identify the ecological covariates of RRV risk and to develop epidemic forecasting models in a disease hotspot region of South Australia.

Methods

Seasonal autoregressive integrated moving average models were used to predict the incidence of RRV disease in the Riverland region of South Australia, an area known to have a high incidence of the disease. The model was developed using data from January 2000 to December 2012 then validated using disease notification data on reported cases for the following year.

Results

Monthly numbers of the mosquito Culex annulirostris (β=0.033, p<0.001) and total rainfall (β=0.263, p=0.002) were significant predictors of RRV transmission in the study region. The forecasted RRV incidence in the predictive model was generally consistent with the actual number of cases in the study area.

Conclusions

A predictive model has been shown to be useful in forecasting the occurrence of RRV disease, with increased vector populations and rainfall being important factors associated with transmission. This approach may be useful in a public health context by providing early warning of vector-borne diseases in other settings.
What's in an “ASAM-based Assessment?” Variations in Assessment and Level of Care Determination in Systems Required to Use ASAM Patient Placement Criteria
Authors: Padwa Howard , Mark Tami L. , Wondimu Betselot
Published: January 2021

Objectives:

When clients begin substance use disorder (SUD) treatment, it is critical to ensure that they receive treatment that matches their needs and preferences. A growing number of payors are requiring the use of multidimensional assessments such as assessments based on the American Society of Addiction Medicine (ASAM) criteria, which describe 6 dimensions that should be used to inform decisions about patient placement. However, ASAM guidance does not list specific questions to ask or instruments to use to elicit this information. This paper evaluates differences among the assessment tools being used by SUD service systems that are required to use ASAM-based assessments to make patient placement decisions.

Methods:

We analyzed 29 different ASAM-based assessments being used by California counties to make patient placement decisions using conventional and summative content analysis techniques.

Results:

All assessments were organized by the 6 ASAM dimensions. However, some of them only ask 1 or 2 questions per dimension, while others ask over 20, and some ask over 100 depending on patient responses. There is significant heterogeneity in the information the assessments collect and how it is used to generate patient placement decisions. Among the 29 assessments examined, there are 8 different algorithms or instructions on how to translate information from assessments into level of care recommendations.

Conclusions:

The differences among the ASAM-based assessments examined in this paper suggest a need to implement fidelity standards, enhance training, and create resources to help systems create and utilize assessment and patient placement tools that are consistent across the SUD treatment field.
Geriatric Conditions Among Middle-aged and Older Adults on Methadone Maintenance Treatment: A Pilot Study
Authors: Han Benjamin H. , Cotton Brandi Parker , Polydorou Soteri , Sherman Scott E. , Ferris Rosie , Arcila-Mesa Mauricio , Qian Yingzhi , McNeely Jennifer
Published: January 2021

Objectives:

The number of older adults on methadone maintenance treatment (MMT) for opioid use disorder is increasing, but little is known about the characteristics and healthcare needs of this aging treatment population. This population may experience accelerated aging due to comorbidities and health behaviors. The aim of this study was to compare the prevalence of geriatric conditions among adults age ≥50 on MMT to a nationally representative sample of community-dwelling older adults.

Methods:

We performed a geriatric assessment on 47 adults age ≥50 currently on MMT enrolled in 2 opioid treatment programs, in New York City and in East Providence, Rhode Island. We collected data on self-reported geriatric conditions, healthcare utilization, chronic medical conditions, physical function, and substance use. The results were compared to 470 age, sex, and race/ethnicity-matched adults in the national Health and Retirement Study.

Results:

The mean age of the study sample was 58.8 years and 23.4% were female. The most common chronic diseases were hypertension (59.6%) and arthritis (55.3%) with 66% reporting ≥2 diseases. For geriatric conditions, adults on MMT had a significantly higher prevalence of mobility, hearing, and visual impairments as well as falls, urinary incontinence, chronic pain, and insomnia than the Health and Retirement Study sample.

Conclusions:

Older adults on MMT in 2 large opioid treatment programs have a high prevalence of geriatric conditions. An interdisciplinary, geriatric-based approach to care that focuses on function and addresses geriatric conditions is needed to improve the health of this growing population.
Global research collaboration in a pandemic-challenges and opportunities: the COVID-19 Global Rheumatology Alliance
Authors: Robinson Philip C. , Yazdany Jinoos , Machado Pedro M.
Published: January 2021

Purpose of review

This review discusses the coronavirus disease-2019 (COVID-19) Global Rheumatology Alliance (GRA), the reason for its formation, the challenges with running the registry, and future opportunities for global collaborative research in rheumatology.

Recent findings

The GRA has been successful in collecting and publishing a large volume of case data on patients with rheumatic disease with COVID-19. In addition, the GRA has published reviews, opinion pieces, and patient-directed summaries of research to further assist in disseminating timely and accurate information about COVID-19 in rheumatic diseases. There have been numerous challenges in the journey but they have been addressed through a collaborative problem-solving approach.

The initial objectives of the GRA to describe the outcomes in patients with rheumatic disease who developed COVID-19 have been achieved. There has been extensive use of the data in the clinic and also to try and understand the mechanisms of disease and opportunities for drug repurposing. There remain numerous important areas for research which the GRA will continue to pursue as the pandemic evolves.
Post-traumatic cubitus varus: long-term follow-up of corrective osteotomy using the Ilizarov method of compression distraction osteogenesis
Authors: Agrawal Rajat , Agrawal Ram Avtar , Kaul Rajiv , Akhoon Neha , Bollabathini Raju
Published: January 2021

The term cubitus varus describes the inward inclination of the supinated forearm on the extended elbow. The deformity manifests clinically as a decreased carrying angle, decreased range of motion (ROM) along with a cosmetically unsightly appearance. The aim of the present study was to evaluate the technique of compression-distraction osteogenesis using the Ilizarov apparatus in the management of patients with post-traumatic cubitus varus deformity. The objectives were to study the impact of this method on the ROM, the Humerus Elbow Wrist (HEW) angle as well as the Lateral Prominence Index. A total of 32 patients who presented with a cubitus varus deformity of ≥10° at the elbow were retrospectively analyzed using data retrieved from a computerized hospital database. All patients had undergone a mini-incision subperiosteal osteotomy followed by application of an Ilizarov frame. Cinico-radiological follow-up was carried out at regular intervals until union was achieved and yearly thereafter. The mean time to union was 11 weeks. The mean follow-up period ranged from 2 to 12 years (mean 4.0 years). Results were graded as excellent in 25 cases (78.1%), good in 2 (6.3%) and poor in 5 case (15.6%) using the grading system of Oppenheim. The mean HEW angle at final follow-up improved from 20° of varus to 6° of valgus. The mean flexion/extension improved from 121°/−3° preoperatively to 125°/−4° at final follow-up. The Mayo Elbow Performance scores at final follow-up were excellent in 23 cases, good in 7 and fair in 2. Complications encountered included superficial pintract infections in three cases, lateral condylar prominence in one case, loss of terminal flexion in three cases and valgus over-correction in one case.
Reconstructive hip surgery in children with cerebral palsy: factors influencing risk of femoral head avascular necrosis
Authors: Minaie Arya , Smythe Margaret , Gordon Joe Eric , Schoenecker Perry , Hosseinzadeh Pooya
Published: January 2021

Femoral head avascular necrosis (AVN) is a complication of hip reconstruction in children with cerebral palsy (CP) with uncertain incidence. The purpose of this study was to establish the rate of AVN in children undergoing hip reconstruction and to identify the factors associated with AVN. Medical records and radiographs of patients aged 1-18 with a diagnosis of CP who have undergone hip reconstruction over a 9-year period (2010–2018) with at least 1-year follow-up were reviewed. Age at time of surgery, sex, Gross Motor Function Classification System (GMFCS), procedure(s), preoperative migration percentage (MP), and signs of AVN on anterioposterior pelvis radiographs at routine follow-up visits (3 months, 6 months, and years 1–9, annually) according to the Bucholz–Ogden (BO) and Kalamchi–MacEwen (KM) classification systems were recorded. Univariate analysis was used to test for significance. Three hundred forty-nine hips in 209 patients met our inclusion criteria. Eleven hips (rate; 3%), in 11 patients, developed AVN. Classification of AVN was found to consist of: class I-4 (36%), class II-1 (9%), class III-[BO: 4 (36%)] [KM: 3 (27%)], and Class IV-[BO: 2 (18%)] [KM: 3 (27%)]. Average follow-up was of 3.5 years. The AVN cohort displayed older age (11.0 ± 2.8 vs. 8.1 ± 3.4; P = 0.005). Open reduction was associated with increased AVN, occurring in 9% of the hips (P = 0.004). No significant association was found between preoperative MP, GMFCS, or acetabular osteotomy. The method of open reduction (anterior vs. medial) was not significantly associated with AVN (P = 0.4471). In this large series, the observed rate of AVN was 3%, associated with open reductions at time of hip reconstruction. If possible, closed reduction would be preferred at time of hip reconstruction in children with CP to lower the risk of AVN. Level of evidence: III.
Diagnosis and treatment of flexible flatfoot: results of 2019 flexible flatfoot survey from the European Paediatric Orthopedic Society
Authors: Pavone Vito , Testa Gianluca , Vescio Andrea , Wirth Thomas , Andreacchio Antonio , Accadbled Franck , Canavese Federico
Published: January 2021

The aim of the study was to evaluate flexible flatfoot (FFF) diagnostic and current therapeutic modalities, as well as treatment expectations, among members of the European Paediatric Orthopaedic Society (EPOS). A 59-questions survey on FFF diagnosis and treatment preferences was distributed to EPOS members. The survey consisted of six sections (1) general clinical parameters; (2) foot aspects; (3) X-ray angles (or lines); (4) expectations; (5) standard clinical assessment; and (6) management options. Descriptive statistics were performed. A total of 93 responses were analysed. In general, clinical parameters, age (91.4% of cases), laxity (81.7%), diffuse pain (84.9%), and pain at the ankle joint (81.7%) were rated as ‘average’ and ‘crucial importance’ by the vast majority of respondents. Meary’s angle (47.3% of cases), talonavicular coverage (35.5%), and lateral talocalcaneal angle (35.5%) were assessed as main radiological tools in the FFF evaluation. Among respondents, 61.3% rated ‘improved ability to walk longer without symptoms’ as of ‘crucial importance’. Eighty-two percent of the respondents felt less than 10% of patients with FFF are candidates for corrective surgery. Arthroereisis (29.3%) was the most common surgical procedure (16.4% for subtalar and 12.9% for extra-articular arthroereisis, respectively), followed by lateral column lengthening (17.9%) and medializing calcaneal osteotomy (12.3%). There is great variation among respondents in diagnostic and treatment preferences in the management of children with FFF. The results of the EPOS 2019 FFF survey clearly show that large-scale, multicentric, international studies are necessary to elucidate which diagnostic and treatment practices lead to the best outcomes.
Evaluating paediatric orthopaedic teleradiology services at a tertiary care centre
Authors: Habib Eva , Krishnaswamy Wendy , Wu Judy K. , Schaeffer Emily K. , Mulpuri Kishore
Published: January 2021

Telehealth services are innovative healthcare strategies that utilize communication technologies to improve healthcare access for patients. Teleradiology is a form of telehealth service that involves the transmission of radiological images, such as x-rays, CTs and MRIs, from one location to another to share patient information with other physicians. The purpose of this study was to assess teleradiology consultations for orthopaedic patients at a paediatric tertiary care centre. A retrospective review was conducted of patients who received teleradiology consultations with a single orthopaedic surgeon from 2015 to 2018 through the paediatric orthopaedic hip clinic at our institution. Teleradiology consultations involved follow-up radiographic imaging at a local community facility for patients who initially received healthcare services at our institution, followed by a telephone consultation to review imaging results and communicate next steps in care. Data collected included patient demographics, imaging type, facility location and distance from our institution. Eighty patients (F = 66, M = 14) who received teleradiology services were reviewed. Mean age was 3.5 years [95% confidence interval (CI): 2.5–4.4] at time of imaging. The average distance from community facilities to our institution was 1167 km (95% confidence interval: 920–1414), a measure of the total distance saved in travel for each patient in a single direction. The travel distance saved was substantial. Paediatric orthopaedic teleradiology services provide families specialized consultations and care continuity without costly travel. With increased implementation of teleradiology services, more patients and families can remain in their home communities while receiving the same quality of care.
Dual-energy X-ray Absorptiometry Does Not Represent Bone Structure in Patients with Osteoporosis
Authors: Pumberger Matthias , Palmowski Yannick , Strube Patrick , Schwemmer Christin , Roll Stephanie , Zippelius Timo , Putzier Michael
Published: January 2021

Study Design

Prospective cross-sectional exploratory study.

Objective

To evaluate the correlation between in vivo lumbar dual-energy x-ray absorptiometry (DXA) and parameters of bone architecture in micro–computed tomography (micro-CT) in patients with osteoporosis.

Summary of Background Data

DXA is the current diagnostic standard for evaluating osteoporosis. However, there are various concerns regarding its validity, especially in the spine. No study has so far investigated whether in vivo DXA correlates with the actual lumbar bone architecture.

Methods

Lumbar DXA scans were compared with micro-CT analysis of vertebral biopsies in patients with osteoporotic vertebral fractures (fracture group) and those without (control group). Preoperatively, all patients underwent a DXA scan (L1-L4). Intraoperative biopsies from nonfractured vertebrae (preferably L3) were analyzed by micro-CT regarding bone quantity and quality. The groups were compared regarding differences in DXA and micro-CT results. In each group, a correlation analysis was performed between DXA and micro-CT.

Results

The study included 66 patients (33 per group). Preoperative DXA results were worse in the fracture group than the control group (areal bone mineral density [aBMD] 0.95 vs. 1.31, T-score −1.97 vs. 0.92, each P < 0.001). Micro-CT analysis confirmed differences regarding quantitative parameters (bone/total volume: 0.09 vs. 0.12, P < 0.001) and qualitative parameters (connectivity index: 15.73 vs. 26.67, P < 0.001; structure model index: 2.66 vs. 2.27, P < 0.001; trabecular number: 2.11 vs. 2.28, P = 0.014) of bone architecture between both groups. The DXA results did not correlate with micro-CT parameters in the fracture group. In the control group, correlations were found for some parameters (bone/total volume vs. aBMD: r = 0.51, P = 0.005; trabecular number vs. aBMD: r = 0.56, P = 0.001).

Conclusion

These data constitute the first comparison of DXA measurements with microstructural analysis of vertebral biopsies in patients with osteoporosis. Our results indicate that lumbar DXA neither qualitatively nor quantitatively represents microstructural bone architecture and is therefore not a reliable tool for the evaluation of bone quality in the spine.

Level of Evidence: 3
Residual Motion and Graft Type Do Not Influence Patient-reported Outcomes Following One- or Two-level Anterior Cervical Discectomy and Fusion
Authors: Couch Brandon K. , Wawrose Richard A. , LeVasseur Clarissa M. , Pitcairn Samuel W. , Shaw Jeremy D. , Donaldson William F. , Lee Joon Y. , Anderst William J.
Published: January 2021

Study Design.

Prospective cohort.

Objective.

The aim of this study was to determine the effect of graft type on residual motion and the relationship among residual motion, smoking, and patient-reported outcome (PRO) scores following anterior cervical discectomy and fusion (ACDF).

Summary of Background Data.

Although most patients develop solid fusion based on static imaging following ACDF, dynamic imaging has revealed that many patients continue to have residual motion at the arthrodesis.

Methods.

Forty-eight participants performed dynamic neck flexion/extension and axial rotation within a biplane radiography system 1 year following ACDF (21 one-level, 27 two-level). PRO scores included the Short Form-36, Neck Disability Index, and Cervical Spine Outcomes Questionnaire. An automated model-based tracking process matched subject-specific bone models to the biplane radiographs with sub-millimeter accuracy. Residual motion was measured across the entire arthrodesis site for both one- and two-level fusions in patients who received either allograft or autograft. Patients were divided into “pseudarthrosis” (>3° of flexion/extension residual motion) and “solid fusion” groups. Residual motion and PROs were compared between groups using Student t tests.

Results.

Patients who received allograft showed more total flexion/extension residual motion (4.1° vs. 2.8°, P = 0.12), although this failed to reach significance. No differences were noted in PROs based on graft type (all P > 0.08) or the presence of pseudarthrosis (all P > 0.13). No differences were noted in residual motion between smokers and nonsmokers (all P > 0.15); however, smokers who received allograft reported worse outcomes than nonsmokers who received allograft and smokers who received autograft.

Conclusion.

Allograft may result in slightly more residual motion at the arthrodesis site 1 year after ACDF. However, there is minimal evidence that PROs are adversely affected by slightly increased residual motion, suggesting that the current definition of pseudarthrosis correlates poorly with clinically significant findings. Additionally, autograft appears to result in superior outcomes in patients who smoke.

Level of Evidence: 2
Utilization Trends of Recombinant Human Bone Morphogenetic Protein in the United States
Authors: Kerezoudis Panagiotis , Alvi Mohammed Ali , Freedman Brett A , Nassr Ahmad , Bydon Mohamad
Published: January 2021

Study Design

Retrospective.

Objective

The aim of this study was to explore the utilization trends of recombinant human bone morphogenetic protein (rh-BMP) in the United States using the largest inpatient administrative database.

Summary of Background Data

Since 2002, the rh-BMP has been widely used by the surgical spine community in fusion surgery. In light of the rising evidence regarding the safety and efficacy of this novel and expensive bone biological technology, a comprehensive examination of its utilization in the American population is warranted.

Methods

We queried the 2002-Q3 2015 National Inpatient Sample for patients that underwent spinal fusion with rh-BMP. We calculated population-level estimates of rh-BMP utilization trends per 100,000 spinal fusions. Trends were estimated for the overall use as well as broken down by primary versus revision fusion, fusion type, number of levels, age category, US region, and hospital type.

Results

A total of 5,563,282 fusions were performed, of which 19.9% (n = 1,108,984) utilized rh-BMP. We detected an increase in rh-BMP use in spinal fusion surgery from 0.7% in 2002 to a peak of 29.5% in 2010, followed by a gradual decline till Q3 2015, where it represented 14.7% of all fusion surgeries. These trends paralleled all fusion types. It was most commonly used in fusions spanning two to three levels. The South remained the most common region, whereas West has recently surpassed the Midwest. Its use is becoming more pervasive among older patients, particularly in the 65- to 74 years’ age group.

Conclusion

Further studies are needed to provide insights into the correlation of these trends with the technology's safety and efficacy profile in contemporary series.

Level of Evidence: 3
Responsiveness of Outcome Measures in Nonsurgical Patients with Lumbar Spinal Stenosis
Authors: Carlesso Cristiane , Piva Sara R. , Smith Clair , Ammendolia Carlo , Schneider Michael J.
Published: January 2021

Study Design.

Secondary analysis from a randomized controlled trial on nonsurgical interventions for patients with lumbar spinal stenosis (LSS).

Objective.

The aim of this study was to assess the responsiveness of the Self-Paced Walking Test (SPWT), Swiss Spinal Stenosis Questionnaire (SSS), and Oswestry Disability Index (ODI) and determine their minimal clinically important differences (MCID) in nonsurgical LSS patients.

Summary of Background Data.

Limited information is available about the responsiveness of these tests in nonsurgical LSS population.

Methods.

A total of 180 participants completed the SPWT, SSS, and ODI at baseline, 2, and 6 months. Responsiveness was assessed by distribution-based method, including effect size and standardized response mean, and anchor-based method, using the patient global index of change (PGIC) as the external anchor to distinguish responders and non-responders. Areas under the curve (AUC) were calculated along with MCIDs for “minimal” and “moderate improvement” subgroups.

Results.

The following values represent 2- and 6-month analyses of each outcome measure, respectively. Standard effect sizes: 0.48 and 0.50 for SPWT, −0.42 and −0.36 for SSS, and −0.29 and −0.25 for ODI. Spearman correlation coefficients between PGIC and outcomes were: 0.44 and 0.39 for SPWT, −0.53 and −0.55 for SSS, and −0.46 and −0.54 for ODI. MCIDs for the “minimal improvement” subgroup were: 375.9 and 319.3 ms for SPWT, −5.3 and −5.8 points for SSS, and −9.3 and −10.8 points for ODI. AUCs was 0.68 to 0.76. MCIDs for the “moderate improvement” subgroup were: 344.2 and 538.2 m for SPWT, −5.5 and −7.5 points for SSS, and −9.1 and −13.6 points for ODI. AUCs ranged from 0.68 to 0.76.

Conclusion.

The SPWT, SSS, and ODI are responsive outcome measures to assess nonsurgical patients with LSS. This finding, along with the reported MCIDs, can help clinicians to monitor changes in their patients’ walking and physical function over time and make clinical decisions. They also provide researchers with reference for future studies in LSS.

Level of Evidence: 2