bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of comorbidities on health-related quality of life of people with osteoarthritis over 10 years
Authors: Zhao Ting , Winzenberg Tania , Aitken Dawn , Graaff Barbara de , Ahmad Hasnat , Jones Graeme , Palmer Andrew J 
Published: April 2021

Abstract

Objective
To investigate the impact of total number and patterns of comorbidities on health-related quality of life (HRQoL) and identify the most prevalent and influential comorbidity patterns in people with OA over 10 years.

Methods
Participants from the Tasmanian Older Adult Cohort aged 50–80 years, with self-reported OA and data on comorbidities and HRQoL were included. Participants were interviewed at baseline (n = 398), 2.5 (n = 304), 5 (n = 269) and 10 years (n = 191). Data on the self-reported presence of 10 chronic comorbidities were collected at baseline. HRQoL was assessed using the Assessment of Quality of Life-4-Dimensions. The long-term impacts of the number and of the nine most prevalent combinations of cardiovascular (CVD), non-OA musculoskeletal (Ms), metabolic and respiratory comorbidities on HRQoL over 10 years were analysed using linear mixed regressions.

Results
Compared with comorbidity-free OA participants, the health state utility (HSU) of those with 2 or ≥3 comorbidities was respectively −0.07 and −0.13 units lower over 10 years, largely driven by reduced scores for independent living, social relationships and psychological wellness. Comorbidity patterns including ‘CVD+Ms’ were most influential, and associated with up to 0.13 units lower HSU, mostly through negative impacts on independent living (up to −0.12), psychological wellness (up to −0.08) and social relationship (up to −0.06).

Conclusion
Having more comorbidities negatively impacted OA patients’ long-term HRQoL. OA patients with CVD and non-OA musculoskeletal conditions had the largest HSU impairment, and therefore optimal management and prevention of these conditions may yield improvements in OA patients’ HRQoL.
Immune Signatures of Treatment-Resistant Schizophrenia: A FondaMental Academic Centers of Expertise for Schizophrenia (FACE-SZ) Study
Authors: Leboyer Marion , Godin Ophélia , Terro Emilie , Boukouaci Wahid , Lu Ching-lieng , Andre Myrtille , Aouizerate Bruno , Berna Fabrice , Barau Caroline , Capdevielle Delphine , Clauss-Kobayashi Julie , Chereau Isabelle , D′Amato Thierry , Dubertret Caroline , Dubreucq Julien , Fond Guillaume , Laouamri Hakim , Leignier Sylvain , Lancon Christophe , Llorca Pierre-Michel , Mallet Jasmina , Le Corvoisier Philippe , Misdrahi David , Passerieux Christine , Rey Romain , Pignon Baptiste , Urbach Mathieu , Szoke Andrei , Schürhoff Franck , Tamouza Ryad ,   FACE-SZ (FondaMental Academic Centers of Expertise for Schizophrenia) Groups, Berna F , Haffen E , Leboyer M , Llorca P M , Schürhoff F , Barteau V , Bensalem S , Godin O , Laouamri H , Souryis K , Leboyer M , Offerlin-Meyer I , Pignon B , Schürhoff F , Szöke A , Aouizerate B , Deloge A , Misdrahi D , Vilà E , Blanc O , Chéreau I , Denizot H , Honciuc R M , Lacelle D , Llorca P M , Pires S , Dubertret C , Mallet J , Portalier C , Dubreucq J , Fluttaz C , Gabayet F , Roman C , Chesnoy-Servanin G , D′Amato T , Dorey J M , Rey R , Vehier A , Lançon C , Faget C , Metairie E , Peri P , Vaillant F , Berna F , Vidailhet P , Zinetti-Bertschy A , Capdevielle D , Yazbek H , Esselin S , Jarroir M , Passerieux C , Urbach M 
Published: April 2021

Abstract
Treatment-resistant schizophrenia (TRS) affects around 30% of patients with schizophrenia (SZ) resulting in poor functioning, relapses, and reduced quality of life. Convergent findings show that inflammation could contribute to resistance. We thus search for immune signatures of patients with TRS/ultra TRS (UTRS) in a sample of community-dwelling outpatients with SZ. In total, 195 stabilized SZ patients (mean age = 31.2 years, 73% male gender) were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia in France and received a thorough clinical assessment. At inclusion, psychotic symptomatology was evaluated by the Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Circulating serum/plasma levels of a large panel of markers reflecting the main inflammatory pathways were evaluated. TRS was defined by current treatment by clozapine (CLZ) and UTRS by current CLZ treatment + PANSS total score ≥ 70. The frequency of TRS and UTRS patients was, respectively, 20% and 7.7% and was defined using multivariable analysis elevated by high levels of interleukin (IL)-12/IL-23p40, IL-17A, IL-10, and beta 2 microglobulin (B2M) and IL-12/IL-23p40, IL-17A, IL-6, IL-10, IFNγ, and B2M, respectively. These observations suggest that resistance and ultra resistance to CLZ treatment are underpinned by pro-inflammatory molecules mainly belonging to the T helper 17 pathway, a finding making sense given the interplay between inflammation and antipsychotic treatment responses. If confirmed, our findings may allow us to consider IL-23/IL-17 pathway as a therapeutic target for patients with resistance to antipsychotics.
A multiplexed high-throughput neutralization assay reveals a lack of activity against multiple variants after SARS-CoV-2 infection
Authors: Fenwick Craig , Turelli Priscilla , Pellaton Céline , Farina Alex , Campos Jérémy , Raclot Charlène , Pojer Florence , Cagno Valeria , Pantaleo Giuseppe , Trono Didier 
Published: April 2021

AbstractThe detection of SARS-CoV-2-specific antibodies in the serum of an individual indicates prior infection or vaccination. However, it provides limited insight into the protective nature of this immune response. Neutralizing antibodies recognizing the viral Spike are far more revealing, yet their measurement traditionally requires virus- and cell-based systems that are costly, time-consuming, poorly flexible and potentially biohazardous. Here we present a cell-free quantitative neutralization assay based on the competitive inhibition of trimeric SARS-CoV-2 Spike protein binding to the angiotensin converting enzyme 2 (ACE2) viral receptor. This high-throughput method matches the performance of the gold standard live virus infectious assay, as verified with a panel of 206 seropositive donors with varying degrees of infection severity and virus-specific IgG titers, achieving 96.7% sensitivity and 100% specificity. Furthermore, it allows for the parallel assessment of neutralizing activities against multiple SARS-CoV-2 Spike variants of concern (VOC), which is otherwise unpredictable even in individuals displaying robust neutralizing antibody responses. Profiling serum samples from 59 hospitalized COVID-19 patients, we found that although most had high activity against the 2019-nCoV Spike and to a lesser extent the B.1.1.7 variant, only 58% could efficiently neutralize a Spike derivative containing mutations present in the B.1.351 variant. In conclusion, we have developed an assay that has proven its clinical relevance in the large-scale evaluation of effective neutralizing antibody responses to VOC after natural infection and that can be applied to the characterization of vaccine-induced antibody responses and of the potency of human monoclonal antibodies.Once sentence summaryMultiplexed cell-free neutralization assay for quantitative assessment of serum antibody responses against Spike mutations in SARS-COV-2 variants
A Systematic Review and Meta-Analysis on Mental Illness Symptoms in Spain in the COVID-19 Crisis
Authors: Chen Richard Z. , Zhang Stephen X. , Xu Wen , Yin Allen , Dong Rebecca Kechen , Chen Bryan Z. , Delios Andrew , McIntyre Roger S. , Miller Saylor , Wan Xue 
Published: April 2021

AbstractObjectiveThis paper systematically reviews and assesses the prevalence of anxiety, depression, and insomnia symptoms in the general population, frontline healthcare workers (HCWs), and adult students in Spain during the COVID-19 crisis.Data sourcesArticles in PubMed, Embase, Web of Science, PsycINFO, and medRxiv from March 2020 to February 6, 2021.ResultsThe pooled prevalence of anxiety symptoms in 23 studies comprising a total sample of 85,560 was 20% (95% CI: 15% - 25%, I2 = 99.9%), that of depression symptoms in 23 articles with a total sample comprising of 86,469 individuals was 23% (95% CI: 18% - 28%, I2 = 99.8%), and that of insomnia symptoms in 4 articles with a total sample of 915 were 52% (95% CI: 42-64%, I2 = 88.9%). The overall prevalence of mental illness symptoms in frontline HCWs, general population, and students in Spain are 42%, 19%, and 50%, respectively.DiscussionThe accumulative evidence from the meta-analysis reveals that adults in Spain suffered higher prevalence rates of mental illness symptoms during the COVID-19 crisis with a significantly higher rate relative to other countries such as China. Our synthesis reveals high heterogeneity, varying prevalence rates and a relative lack of studies in frontline and general HCWs in Spain, calling future research and interventions to pay attention to those gaps to help inform evidence-based mental health policymaking and practice in Spain during the continuing COVID-19 crisis. The high prevalence rates call for preventative and prioritization measures of the mental illness symptoms during the Covid-19 pandemic.
Plagl1is part of the mammalian retinal injury response and a critical regulator of Müller glial cell quiescence
Authors: Touahri Yacine , David Luke Ajay , Ilnytskyy Yaroslav , van Oosten Edwin , Hanna Joseph , Tachibana Nobuhiko , Adnani Lata , Zhao Jiayi , Hoffman Mary , Dixit Rajiv , Journot Laurent , Sauve Yves , Kovalchuk Igor , Aubert Isabelle , Biernaskie Jeffrey , Schuurmans Carol 
Published: April 2021

ABSTRACTRetinal damage triggers reactive gliosis in Müller glia across vertebrate species, but only in regenerative animals, such as teleost fish, do Müller glia initiate repair; proliferating and undergoing neurogenesis to replace lost cells. By mining scRNA-seq and bulk RNA-seq datasets, we found thatPlagl1, a maternally imprinted gene, is dynamically regulated in reactive Müller glia post-insult, with transcript levels transiently increasing before stably declining. To studyPlagl1retinal function, we examinedPlagl1+/-patnull mutants postnatally, revealing defects in retinal architecture, visual signal processing and a reactive gliotic phenotype.Plagl1+/-patMüller glia proliferate ectopically and give rise to inner retinal neurons and photoreceptors. Transcriptomic and ATAC-seq profiles revealed similarities betweenPlagl1+/-patretinas and neurodegenerative and injury models, including an upregulation of pro-gliogenic and pro-proliferative pathways, such as Notch, not observed in wild-type retinasPlagl1is thus an essential component of the transcriptional regulatory networks that retain mammalian Müller glia in quiescence.
Genomic patterns of transcription-replication interactions in mouse primary B cells
Authors: St Germain Commodore P. , Zhao Hongchang , Sinha Vrishti , Sanz Lionel A. , Chédin Frédéric , Barlow Jacqueline H. 
Published: April 2021

ABSTRACTConflicts between transcription and replication machinery are a potent source of replication stress and genome stability; however, no technique currently exists to identify endogenous genomic locations prone to transcription-replication interactions. Here, we report a novel method to identify genomic loci prone to transcription-replication interactions termed transcription-replication immunoprecipitation on nascent DNA sequencing, TRIPn-Seq. TRIPn-Seq employs the sequential immunoprecipitation of RNA polymerase 2 phosphorylated at serine 5 (RNAP2s5) followed by enrichment of nascent DNA previously labeled with bromodeoxyuridine. Using TRIPn-Seq, we mapped 1,009 unique transcription-replication interactions (TRIs) in mouse primary B cells characterized by a bimodal pattern of RNAP2s5, bidirectional transcription, an enrichment of RNA:DNA hybrids, and a high probability of forming G-quadruplexes. While TRIs themselves map to early replicating regions, they exhibit enhanced Replication Protein A association and replication fork termination, marks of replication stress. TRIs colocalize with double-strand DNA breaks, are enriched for deletions, and accumulate mutations in tumors. We propose that replication stress at TRIs induces mutations potentially contributing to age-related disease, as well as tumor formation and development.
Structural and mechanistic basis for protein glutamylation by the kinase fold
Authors: Osinski Adam , Black Miles H. , Pawłowski Krzysztof , Chen Zhe , Li Yang , Tagliabracci Vincent S. 
Published: April 2021

SummaryThe kinase domain transfers phosphate from ATP to substrates. However, theLegionellaeffector SidJ adopts a kinase fold yet catalyzes calmodulin (CaM)-dependent glutamylation to inactivate the SidE ubiquitin ligases. The structural and mechanistic basis in which the kinase domain catalyzes protein glutamylation is unknown. Here we present cryo-EM reconstructions of SidJ:CaM:SidE reaction intermediate complexes. We show that the kinase-like active site of SidJ adenylates an active site Glu in SidE resulting in the formation of a stable reaction intermediate complex. An insertion in the catalytic loop of the kinase domain positions the donor Glu near the acyl-adenylate for peptide bond formation. Our structural analysis led us to discover that the SidJ paralog SdjA is a glutamylase that differentially regulates the SidE-ligases duringLegionellainfection. Our results uncover the structural and mechanistic basis in which the kinase fold catalyzes non-ribosomal amino acid ligations and reveal an unappreciated level of SidE-family regulation.
Trends, wealth inequalities and the role of the private sector in caesarean section in the Middle East and North Africa: a repeat cross-sectional analysis of population-based surveys
Authors: McCall Stephen , Semaan Aline T. , Altijani Noon , Opondo Charles , Abdel-fattah Mohamed , Kabakian-Khasholian Tamar 
Published: April 2021

AbstractObjectiveTo examine trends and variations of caesarean section by economic status and type of healthcare facility in Arab countries in Middle East and North Africa (MENA).MethodsSecondary data analysis of nationally representative household surveys across nine Arab countries in MENA. The study population was women aged 15-49 years with a live birth in the two years preceding the survey. Temporal changes in the use of caesarean section in each of the nine countries were calculated using generalised linear models and presented as risk differences(RD) with 95% confidence intervals(95%CI). Caesarean section was disaggregated against household wealth index and type of healthcare facility.ResultsUse of caesarean section ranged from 57.3% (95%CI:55.6–59.1%) in Egypt to 5.7% of births (95%CI:4.9–6.6%) in Yemen. Overall, the use of caesarean section has increased across the MENA region, except in Jordan, where there was no evidence of change (RD −2.3% (95%CI:-6.0–1.4%). Within all MENA countries, caesarean section use was highest in the richest quintile compared poorest quintile, for example, 43.8% (95%CI:38.0-47.6%) vs. 22.6% (95%CI:19.6-25.9%) in Iraq, respectively. Caesarean section was higher in private sector facilities compared to public sector: 21.8% (95%CI:18.2-25.9 %) vs. 15.7% (95%CI:13.3-18.4%) in Yemen, respectively.ConclusionVariations in caesarean section exist within and between Arab countries, and it was more commonly used amongst the richest quintiles and in private healthcare facilities. The private sector has a prominent role in the trends. Urgent policies and interventions are required to address non-medically indicated intervention.
Circulating Plasma Biomarkers in Biopsy-Confirmed Kidney Disease: Results from the Boston Kidney Biopsy Cohort
Authors: Schmidt Insa M. , Mothi Suraj Sarvode , Wilson Parker C. , Palsson Ragnar , Srivastava Anand , Kibbelaar Zoe A. , Zhuo Min , Amodu Afolarin , Stillman Isaac E. , Rennke Helmut G. , Humphreys Benjamin D. , Waikar Sushrut S. 
Published: April 2021

AbstractBackgroundBiomarkers for non-invasive assessment of histopathology and prognosis are needed in patients with kidney disease.MethodsUsing a proteomics assay, we measured a multi-marker panel of 225 circulating plasma proteins in a prospective cohort study of 549 individuals with biopsy-confirmed kidney diseases and semi-quantitative assessment of histopathology. We tested the associations of each biomarker with histopathologic lesions and the risks of kidney disease progression (defined as ≥40% decline in eGFR or ESKD) and death.ResultsAfter multivariable adjustment and correction for multiple testing, 46 proteins associated with different histopathologic lesions. The top performing markers positively associated with acute tubular injury and interstitial fibrosis and tubular atrophy were kidney injury molecule-1 (KIM-1) and V-set and immunoglobulin domain-containing protein 2 (VSIG2). 30 proteins were significantly associated with kidney disease progression and 35 with death. The top performing markers for kidney disease progression were placental growth factor (PGF; HR 5.4, 95% CI 3.4 to 8.7) and BMP and Activin Membrane Bound Inhibitor (BAMBI; HR 3.0, 95% CI 2.1 to 4.2); the top performing markers for death were TRAIL-receptor-2 (TRAIL-R2; HR 2.9, 95% CI 2.0 to 4.0) and CUB Domain Containing Protein-1 (CDCP1; HR 2.4, 95% CI 1.8, 3.3).ConclusionWe identified several biomarkers associated with kidney disease histopathology and prognosis – many of which have not been reported previously and may represent important avenues for future research.
AAV-delivery of diacylglycerol kinase kappa achieves long-term rescue ofFmr1-KO mouse model deficits of fragile X syndrome
Authors: Habbas Karima , Cakil Oktay , Zambo Boglarka , Tabet Ricardos , Riet Fabrice , Dembele Doulaye , Mandel Jean-Louis , Hocquemiller Michaël , Laufer Ralph , Piguet Françoise , Moine Hervé 
Published: April 2021

AbstractFragile X syndrome (FXS) is the most frequent form of familial intellectual disability. It results from the lack of the RNA binding protein FMRP and is associated with the overactivation of signaling pathways downstream of mGluRI receptors and upstream of mRNA translation. We previously found that diacylglycerol kinase kappa (DGKk) is a main mRNA target of FMRP in cortical neurons. Here we show that diacylglycerol kinase kappa (DGKk), when modified as to become FMRP-independent and delivered into the brain of adolescent mice using adeno-associated viral vectors, corrects brain diacylglycerol and phosphatidic acid homeostasis and the main phenotypic behaviors of the Fmr1-KO mouse model of FXS. Thus, DGKk appears as a key triggering factor of FXS pathomechanism while providing a possible means of intervention for FXS gene therapy.One sentence summaryDGKkgene therapy inFmr1-KO mouse model
Genomic and transcriptomic insights into the habitat adaptation of the diazotrophic paddy‐field cyanobacteriumNostoc sphaeroides
Authors: Chen Zhen , Shang Jin‐Long , Hou Shengwei , Li Tao , Li Qi , Yang Yi‐Wen , Hess Wolfgang R. , Qiu Bao‐Sheng 
Published: April 2021

SummaryNitrogen‐fixing cyanobacteria are common in paddy fields, one of the most productive wetland ecosystems. Here, we present the complete genome ofNostoc sphaeroides,a paddy‐field diazotroph used for food and medicine for more than 1700 years and deciphered the transcriptional regulation during the developmental transition from hormogonia to vegetative filaments with heterocysts. The genome ofN. sphaeroidesconsists of one circular chromosome (6.48 Mb), one of the largest ever reported megaplasmids (2.34 Mb), and seven plasmids. Multiple gene families involved in the adaption to high solar radiation and water fluctuation conditions were found expanded, while genes involved in anoxic adaptation and phosphonate utilization are located on the megaplasmid, suggesting its indispensable role in environmental adaptation. Distinct gene expression patterns were observed during the light‐intensity‐regulated transition from hormogonia to vegetative filaments, specifically, genes encoding proteins involved in photosynthetic light reaction, carbon fixation, nitrogen metabolism and heterocyst differentiation were significantly upregulated, whereas genes related to cell motility were down‐regulated. Our results provide genomic and transcriptomic insights into the adaptation of a filamentous nitrogen‐fixing cyanobacterium to the highly dynamic paddy‐field habitat, suggestingN. sphaeroidesas an excellent system to understand the transition from aquatic to terrestrial habitats and to support sustainable rice production.
How do remittances to the Philippines affect its environmental sustainability? Evidence based on the augmented ARDL approach
Authors: Karasoy Alper 
Published: April 2021

AbstractRemittances to the Philippines constitute a prominent part of its economy. However, remittances' effects on its environment have not been researched. In this regard, this research examines the direct and indirect impacts of remittance inflows on the Philippines' environmental sustainability for the 1977–2016 period by proposing a multivariate model, and by utilising the augmented ARDL and VECM methods to estimate this model. Our findings indicate that remittance inflows threaten environmental sustainability in the long‐run both directly and indirectly through boosting income and energy (oil) consumption. The results additionally imply that income and energy consumption also increase the ecological footprint of the Philippines in the long‐run. However, economic globalisation's long‐run impact is insignificant, yet its short‐run impact is significantly negative on the country's level of environmental degradation. Additionally, the findings reveal that the feedback hypothesis is valid between income and energy consumption in the long‐run, but the neutrality hypothesis is valid in the short‐run. This research's findings reveal that remittance inflows' impact on the environment is significant, and can occur through direct and various indirect channels, therefore, these inflows should be an integral part of sustainability policies in the Philippines, as ignoring them could cause further environmental decline.
Assessment of liver fibrosis with liver and spleen stiffness measured by sound touch elastography, serum fibrosis markers in patients with chronic hepatitis B
Authors: Dong Bing Tian , Huang Shu , Lyu Guo Rong , Qin Ran , Gu Jiong Hui 
Published: April 2021

ObjectivesTo evaluate the performance of liver stiffness (LS) and spleen stiffness (SS) by using the sound touch elastography (STE) technique and compare with those of the splenic index, aspartate transaminase‐to‐platelet ratio index (APRI), fibrosis‐4 (FIB‐4) index, King's score and combined models for diagnosing and staging fibrosis in chronic hepatitis B (CHB).MethodsOne hundred patients with CHB underwent STE and serological tests. LS and SS values were measured with STE technique, and splenic index was calculated. Staging of fibrosis was determined with liver biopsy. Correlations between the individual parameters and the stage of fibrosis were evaluated with the Spearman correlation analysis. The area under the receiver operating characteristic curve (AUROC) was calculated to analyze the performance of all methods.ResultsAmong all individual parameters, LS showed the highest AUROC for diagnosing fibrosis of ≥S2, ≥S3, and S4 stages (AUROC: 0.70, 0.86, and 0.96, respectively; all P < 0.05). The AUROC of combined model 1 (LS and SS) and 2 (LS, SS, APRI, FIB‐4 index, King's score) for diagnosing ≥S2, ≥S3, and S4 fibrosis were 0.70, 0.86, 0.97, and 0.70, 0.86, 0.96, respectively, which were higher than those of APRI, FIB‐4 index and the King's score (P < 0.05). No significant differences were found between two combined models and LS for staging fibrosis (P > 0.05).ConclusionsLS measurement is reliable for diagnosing and staging fibrosis in CHB, with a better performance than SS, splenic index and serum biomarkers. It is also comparable with the performance of combined models.