bluuebunny/crossref_metadata_2025 huggingface dataset:
TIMEx: tumor-immune microenvironment deconvolution web-portal for bulk transcriptomics using pan-cancer scRNA-seq signatures
Authors: Xie Mengyu , Lee Kyubum , Lockhart John H , Cukras Scott D , Carvajal Rodrigo , Beg Amer A , Flores Elsa R , Teng Mingxiang , Chung Christine H , Tan Aik Choon
Published: April 2021

The heterogeneous cell types of the tumor-immune microenvironment (TIME) play key roles in determining cancer progression, metastasis and response to treatment. We report the development of TIMEx, a novel TIME deconvolution method emphasizing on estimating infiltrating immune cells for bulk transcriptomics using pan-cancer single-cell RNA-seq signatures. We also implemented a comprehensive, user-friendly web-portal for users to evaluate TIMEx and other deconvolution methods with bulk transcriptomic profiles.

Availability and implementation

TIMEx web-portal is freely accessible at http://timex.moffitt.org.

Supplementary information

Supplementary data are available at Bioinformatics online.
Application of Tandem Dispersive Liquid–Liquid Microextraction as an Efficient Method for Preconcentration of Two Antidepressant Drugs in Real Samples Combined with High Performance Liquid Chromatography
Authors: Arabkhani Bahare , Goudarzi Nasser , Bagherian Ghadamali , Chamjangali Mansour Arab
Published: April 2021

In the present work, tandem dispersive liquid–liquid microextraction (TDLLME) coupled with liquid chromatography was used for the determination of the two antidepressant drugs citalopram (CIT) and sertraline (SER) in complicated matrices. Indeed, the present approach was used to improve the suitability and appropriateness of the dispersive liquid–liquid microextraction (DLLME) method in complicated matrices. Firstly, 10 mL of the sample solution containing the two understudied drugs was extracted into an organic solvent (200 μL of 1,2-dichloromethane) using the DLLME method. Then the extracted analytes were back-extracted into 100 μL of an aqueous acceptor phase. The total extraction time of this method is about 6 min. To achieve the best efficiency for this method, efficient parameters like the kind and volume of the organic solvent and the effect of the ionic strength on the effectiveness of extraction were reviewed and improved. Under the optimized experimental conditions, TDLLME showed good linearity in the range of 100.0–7000.0 ng mL−1. The limits of detection were found to be 10.0 ng mL−1 for CIT and 2.0 ng mL−1 for SER. The relative standard deviation (RSD) is obtained in the range of 0.7–4.1%.
Association between new-onset right bundle branch block and primary or secondary ventricular fibrillation in ST-segment elevation myocardial infarction
Authors: Galcerá-Jornet Emilio , Consuegra-Sánchez Luciano , Galcerá-Tomás José , Melgarejo-Moreno Antonio , Gimeno-Blanes Juan Ramón , Jaulent-Huertas Leticia , Wasniewski Samantha , de Gea-García José , Vicente-Gilabert Marta , Padilla-Serrano Antonio
Published: April 2021

Aims

New-onset right bundle branch block (RBBB) in myocardial infarction (MI) is often associated with ventricular fibrillation (VF) but the nature of this relationship has not been determined.

Methods and results

Between 1998 and 2014, among other data, incidence and duration of RBBB and VF occurrence were prospectively collected in 5301 patients with ST-segment elevation MI (STEMI) admitted to two University Hospitals in Murcia (Spain). Multinomial adjusted logistic regression analyses were used to examine the association between RBBB, attending to its duration, and VF according to its primary VF (PVF) or secondary VF (SVF) character. Among 284 (5.4%) patients with new-onset RBBB, 158 were transient and 126 permanent. VF occurred in 339 (6.4%) patients, 201 PVF and 138 SVF, documented within the first 2 h of symptoms-onset in 78% and 60%, respectively. New-onset RBBB was more frequent in PVF (11.4%) and SVF (20.3%), than in non-VF (4.7%). Transient RBBB incidence was higher in PVF (9.0%) and SVF (9.4) than in non-VF (2.6%), whereas permanent RBBB was higher in SVF (10.9%) than PVF (2.5%) and non-VF (2.1%). New-onset RBBB 1.83 [95% confidence interval (CI): 1.07–3.11] and new-onset transient RBBB 2.39 (95% CI: 1.32–4.32) were independently associated with PVF. New-onset 3.03 (95% CI: 1.83–5.02), transient 2.40 (95% CI: 1.27–4.55), and permanent 2.99 (95% CI: 1.52–5.86) RBBB were independently associated with SVF.

Conclusion

New-onset RBBB and VF in STEMI are independently associated and show particularities based on the duration of the conduction disturbance and/or the primary or secondary character of the arrhythmia.
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

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

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.
Levodopa responsiveness in Parkinson’s disease patients and white matter alterations in diffusion tensor imaging: a cross-sectional tract-based spatial statistics study
Authors: Zhou Wen , Jiang Jin , Peng Wuxue , Zhou Xuan , Du Juncong , Mo Lijuan , Tan Changhong , Liu Xi , Chen Lifen
Published: April 2021

This study aimed to investigate the relationship between levodopa responsiveness and white matter alterations in Parkinson’s disease patients using diffusion tensor imaging (DTI). Twenty-six recruited Parkinson’s disease patients were evaluated using the Mini-Mental State Examination, Hoehn and Yahr scale (H&Y) and Unified Parkinson’s Disease Rating Scale (UPDRS). Each patient underwent a DTI scan and an acute levodopa challenge test. The improvement rate of UPDRS-III was calculated, Parkinson’s disease patients were grouped into a responsive group (improvement rate ≥30%) and a nonresponsive group (improvement rate <30%). The differences in fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity between the two groups were measured using tract-based spatial statistics. There was no difference in demographic features or baseline evaluations between groups. The UPDRS-III score after the challenge was higher in the nonresponsive group than that in the responsive group. Compared to the responsive group, patients in the nonresponsive group exhibited decreased fractional anisotropy in the corpus callosum; cingulum; left corona radiata; left internal capsule; left middle frontal gyrus; left superior longitudinal fasciculus and right somatosensory cortex. Mean diffusivity and radial diffusivity were increased in wide-ranging areas in the nonresponsive group. No difference was observed in axial diffusivity. White matter alterations in the abovementioned areas may affect the function of the dopaminergic network and thus may be associated with the levodopa response in Parkinson’s disease patients. Further studies are needed to analyze the specific mechanism and pathological changes underlying these effects.
Studying the quenching resulted from the formation of an association complex between olsalazine or sulfasalazine with acriflavine
Authors: Tolba Manar , Elmansi Heba
Published: April 2021

We report the detection and quantification of important ulcerative colitis drugs olsalazine (OLS) and sulfasalazine (SUL) by the spectrofluorometric method. The proposed method was optimized and validated by using the quenching effect on the acriflavine fluorescence. The method was applied on the detection and quantification of OLS and SUL under optimized conditions showing the calibration curves were linear (range: 1.0–10.0 µg ml
−1
), with correlation coefficients
R
2
of 0.9999 for both drugs. The limits of detection (LOD) and quantification (LOQ) were 53 and 104 ng ml
−1
for the OLS and 160 and 315 ng ml
−1
for the SUL. This method permitted the analysis of OLS and SUL in their pure and pharmaceutical forms. The proposed spectrofluorimetric method was also evaluated against ‘green’ criteria and all the experimental results make it an eco-friendly and safe method for the detection of OLS and SUL.
Learning to stop: a unifying principle for legged locomotion in varying environments
Authors: George Thuruthel Thomas , Picardi G. , Iida F. , Laschi C. , Calisti M.
Published: April 2021

Evolutionary studies have unequivocally proven the transition of living organisms from water to land. Consequently, it can be deduced that locomotion strategies must have evolved from one environment to the other. However, the mechanism by which this transition happened and its implications on bio-mechanical studies and robotics research have not been explored in detail. This paper presents a unifying control strategy for locomotion in varying environments based on the principle of ‘learning to stop’. Using a common reinforcement learning framework, deep deterministic policy gradient, we show that our proposed learning strategy facilitates a fast and safe methodology for transferring learned controllers from the facile water environment to the harsh land environment. Our results not only propose a plausible mechanism for safe and quick transition of locomotion strategies from a water to land environment but also provide a novel alternative for safer and faster training of robots.
Long-term noise pollution affects seedling recruitment and community composition, with negative effects persisting after removal
Authors: Phillips Jennifer N. , Termondt Sarah E. , Francis Clinton D.
Published: April 2021

Noise pollution can affect species' behaviours and distributions and may hold significant consequences for natural communities. While several studies have researched short-term effects of noise, no long-term research has examined whether observed patterns persist or if community recovery can occur. We used a long-term study system in New Mexico to examine the effects of continuous natural gas well noise exposure on seedling recruitment of foundational tree species (Pinus edulis,Juniperus osteosperma) and vegetation diversity. First, we examined seedling recruitment and vegetation diversity at plots where current noise levels have persisted for greater than 15 years. We then examined recruitment and diversity on plots where noise sources were recently removed or added. We found support for long-term negative effects of noise on tree seedling recruitment, evenness of woody plants and increasingly dissimilar vegetation communities with differences in noise levels. Furthermore, seedling recruitment and plant community composition did not recover following noise removal, possibly due in part to a lag in recovery among animals that disperse and pollinate plants. Our results add to the limited evidence that noise has cascading ecological effects. Moreover, these effects may be long lasting and noise removal may not lead to immediate recovery.
Quantifying pyrodiversity and its drivers
Authors: Steel Zachary L. , Collins Brandon M. , Sapsis David B. , Stephens Scott L.
Published: April 2021

Pyrodiversity or variation in spatio-temporal fire patterns is increasingly recognized as an important determinant of ecological pattern and process, yet no consensus surrounds how best to quantify the phenomenon and its drivers remain largely untested. We present a generalizable functional diversity approach for measuring pyrodiversity, which incorporates multiple fire regime traits and can be applied across scales. Further, we tested the socioecological drivers of pyrodiversity among forests of the western United States. Largely mediated by burn activity, pyrodiversity was positively associated with actual evapotranspiration, climate water deficit, wilderness designation, elevation and topographic roughness but negatively with human population density. These results indicate pyrodiversity is highest in productive areas with pronounced annual dry periods and minimal fire suppression. This work can facilitate future pyrodiversity studies including whether and how it begets biodiversity among taxa, regions and fire regimes.
Nothing as it seems: behavioural plasticity appears correlated with morphology and colour, but is not in a Neotropical tadpole
Authors: Reuben Phoebe L. , Touchon Justin C.
Published: April 2021

In response to environmental stressors, organisms often demonstrate flexible responses in morphology, life history or behaviour. However, it is currently unclear if such plastic responses are coordinated or operate independently of one another. In vertebrates, this may partly result from studies examining population- or species-level mean responses, as opposed to finer grained analyses of individuals or families. We measured predator-specific morphological and coloration plasticity in 42 families of tadpoles of the treefrog
Dendropsophus ebraccatus
and behavioural plasticity from 18 of these families, allowing us to examine the correlation between three predator-induced plastic responses. For all three plastic responses, tadpoles showed strong opposing responses to each of two predators, providing the appearance of covariation in plasticity. However, the examination of individual families revealed a strong correlation between morphological and coloration plasticity, but no correlations between either morphology or colour and behavioural plasticity. Thus, our analysis shows that some aspects of the plastic phenotype develop together while others function independently. This highlights the importance of examining individual- and family-level variation for understanding the adaptive significance of developmental plasticity, which is crucial for a holistic appreciation of phenotypic plasticity and its importance in ecology and evolution.
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

The 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 summary

Multiplexed 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

Objective

This 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 sources

Articles in PubMed, Embase, Web of Science, PsycINFO, and medRxiv from March 2020 to February 6, 2021.

Results

The 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.

Discussion

The 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

Retinal 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

Conflicts 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

The 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

Objective

To 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).

Methods

Secondary 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.

Results

Use 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.

Conclusion

Variations 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

Background

Biomarkers for non-invasive assessment of histopathology and prognosis are needed in patients with kidney disease.

Methods

Using 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.

Results

After 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).

Conclusion

We 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

Fragile 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 summary

DGKkgene 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

Nitrogen‐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

Remittances 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

Objectives

To 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).

Methods

One 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.

Results

Among 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).

Conclusions

LS 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.
Quality of life preferences in colorectal cancer patients aged 80 and over
Authors: McCombie Andrew M. , Frampton Chris M. , Frizelle Frank A.
Published: April 2021

Background

Management of patients with colorectal cancer (CRC) is about not only survival, but also quality of life (QoL). What patients want is important but is not well researched or understood for elderly patients where it is very relevant. This study aimed to measure and compare what patients with CRC aged 80 and over and surgeons consider important in terms of survivorship after surgery for CRC.

Methods

Patients aged 80 and over who were having surgery for CRC were recruited and interviewed using closed and open questions about their expectations of surgery and various QoL dimensions. These were assessed preoperatively and 3 months post‐operatively. Surgeons ranked the same QoL dimensions of patients by questionnaire.

Results

Nineteen patients (median age 87.5, range 80–95, eight males and 11 females) were recruited. Patients rated items relating to health, mobility and independence (n = 23) as top three items most often followed by people outside self (n = 13). Surgeons underestimated importance in 17 domains with the biggest discrepancy being in ‘avoiding a stoma’ (4.11 versus 2.3, P < 0.01).

Conclusion

With patients over 80 years having surgery for CRC, there is a lack of concordance between what surgeons think is important and what patients think is important. Despite this, CRC patients aged 80 and older are almost always satisfied with the outcome of surgery. Surgeons should ensure that they understand patients' expectations and that they are aligned with likely outcomes of surgery.
Rectovaginal fistula: Risk factors for failure after graciloplasty—A bicentric retrospective European study of 61 patients
Authors: Frontali Alice , Rottoli Matteo , Chierici Andrea , Poggioli Gilberto , Panis Yves
Published: April 2021

Aim

Graciloplasty (GP) is indicated in the case of recurrent rectovaginal fistula (RVF) after failure of previous local treatments. The aim of this study was to assess risk factors for GP failure performed for RVF.

Methods

This is a retrospective study based on a prospective database on GP, coming from two expert centres.

Results

Sixty‐one patients undergoing a first GP for RVF (n = 51) or ileal‐vaginal fistula after ileal pouch anal anastomosis (n = 10), with a mean age of 42 years (range 24–72), were analysed. After a mean follow‐up of 56 ± 48 months (range 1–183), failure of GP (considered as persistent stoma and/or clinical RVF) was noted in 24/61 patients (39%). The failure rate was 43% (13/30) in the case of Crohn's disease, 38% (3/8) in the case of ileal‐vaginal fistula after ileal pouch anal anastomosis for ulcerative colitis, 30% (3/10) in the case of obstetrical RVF, 33% (1/3) in the case of post radiotherapy RVF and 40% (4/10) for other causes (not significant). Two risk factors for failure of GP were found on univariate analysis: (1) absence of postoperative antibiotic prophylaxis—only 3/24 (13%) patients with failure of GP received postoperative antibiotic prophylaxis versus 18/37 (49%) patients with success of GP (P = 0.0053); (2) postoperative perineal infection—11/23 (48%) with failure of GP developed postoperative perineal infection versus only 4/37 (10%) patients with success of GP (P = 0.0021).

Conclusions

Failure of GP for RVF is observed in approximately 40% of the patients whatever the aetiology of the fistula. A reduced failure rate was associated with systematic postoperative antibiotic prophylaxis.
The role of laparoscopic surgery in repeat ileocolic resection for Crohn’s disease
Authors: Carmichael Heather , Peyser Daniel , Baratta Vanessa M. , Bhasin Deepika , Dean Adrienne , Khaitov Sergey , Greenstein Alexander J. , Sylla Patricia
Published: April 2021

Aim

Laparoscopic surgery is the preferred approach for primary uncomplicated ileocolic resection (ICR); however, its role for repeat resections is unclear. This study assessed the outcomes of primary and repeated ICRs for Crohn's disease to examine rates of laparoscopy and patient morbidity.

Methods

A retrospective review of a prospectively maintained database was conducted at a tertiary centre between 2013 and 2019. All patients undergoing ICRs for Crohn's disease were included. The cohort was divided into three groups based on number of resections—primary (1R), secondary (2R) and tertiary or more (>2R) groups. The primary outcome was 30‐day postoperative morbidity.

Results

Over a 6‐year period, 474 patients underwent ICR for Crohn's disease, including 369 primary (1R, 77.8%) and 105 repeat (≥2R, 22.2%) resections. A laparoscopic approach was less common in the ≥2R versus 1R groups (79.0% vs. 93.8%, P < 0.001), but rates of conversion to an open procedure were comparable. Morbidity was higher amongst repeat resections although this was not significant (20.0% vs. 14.1%, P = 0.18). Amongst cases approached laparoscopically (n = 429), rates of conversion and postoperative morbidity did not differ by stage of resection, although operative time was longer for repeat operations. Even in the group undergoing laparoscopy for tertiary or greater resections (>2R, n = 29), the rates of conversion (10%) and morbidity (14%) were relatively low.

Conclusion

In this contemporary series of primary and reoperative ICR for ileal CD, a laparoscopic approach is feasible and safe for the majority of repeat ICRs when performed at a high volume centre.
Atelectasis in primary graft dysfunction survivors after lung transplantation
Authors: Li David , Abele Jonathan , Weinkauf Justin , Kapasi Ali , Hirji Alim , Varughese Rhea , Nagendran Jayan , Lien Dale , Doucette Karen , Halloran Kieran
Published: April 2021

Background

Primary graft dysfunction (PGD) is an important contributor to early mortality in lung transplant recipients and is associated with impaired lung function. The radiographic sequelae of PGD on computed tomography (CT) have not been characterized.

Methods

We studied adult double lung transplant recipients from 2010 to 2016 for whom protocol 3‐month post‐transplant CT scans were available. We assessed CTs for changes including pleural effusions, ground glass opacification, atelectasis, centrilobular nodularity, consolidation, interlobular septal thickening, air trapping and fibrosis, and their relationship to prior post‐transplant PGD, future lung function, post‐transplant baseline lung allograft dysfunction (BLAD), and chronic lung allograft dysfunction (CLAD).

Results

Of 237 patients studied, 50 (21%) developed grade 3 PGD (PGD3) at 48 or 72 h. PGD3 was associated with increased interlobular septal thickening (p = .0389) and atelectasis (p = .0001) at 3 months, but only atelectasis remained associated after correction for multiple testing. Atelectasis severity was associated with lower peak forced expiratory volume in 1 s (FEV1) and increased risk of BLAD (p = .0014) but not with future CLAD onset (p = .7789).

Conclusions

Severe PGD was associated with atelectasis on 3‐month post‐transplant CT in our cohort. Atelectasis on routine CT may be an intermediary identifiable stage between PGD and future poor lung function.
Predictors for and outcomes after bone marrow biopsy in Scandinavian patients with chronic immune thrombocytopenia
Authors: Gotschalck Madeleine Andersson , Nørgaard Mette , Risbo Nickolaj , Christiansen Christian Fynbo , Bahmanyar Shahram , Ghanima Waleed , Alam Naufil , Frederiksen Henrik , Nielson Carrie M. , Sørensen Henrik Toft
Published: April 2021

Objectives

To examine predictors for bone marrow biopsy (BMB) and the outcome following BMB in patients with chronic immune thrombocytopenia (cITP).

Methods

We identified patients diagnosed with cITP during 2009‐2017 and obtained information on BMB, cITP treatment and subsequent thrombotic events, hospitalized bleeding, hematological cancer, and death using data from population‐based healthcare databases and medical records in Denmark, Norway, and Sweden.

Results

Among 4471 adults (≥18 years) with cITP, 1683 (37.6%) underwent BMB before cITP diagnosis, while cumulative BMB incidence after cITP diagnosis date was 3.1% at 1 year and 7.5% at 5 years. Predictors of having a BMB after cITP diagnosis included older age, male sex, low baseline platelet count, splenectomy, and number of cITP treatments. Compared with patients without BMB, patients with BMB had higher rates of thrombotic events (1 year adjusted hazard ratio [HR] 1.53 [95% CI, 0.92‐2.54]), hospitalized bleeding episodes (1 year adjusted HR 1.72 [95% CI, 1.15‐2.58]), hematological cancer (1 year adjusted HR 35.26 [95% CI 17.67‐70.34]), and all‐cause mortality (1 year adjusted HR 1.97 [95% CI, 1.44‐2.68]).

Conclusion

Patients who undergo BMB after cITP diagnosis represent a subset of patients with more severe disease and increased rates of complications as well as hematological malignancies.
A narrative review of caudal epidural anaesthesia and analgesia in horses. Part 2: Clinical indications and techniques
Authors: Rønnow Kjærulff L. N. , Lindegaard C.
Published: April 2021

This is the second of a two‐part review of caudal epidural anaesthesia and analgesia in horses (CEAA). In Part 1, we provided a detailed review of the efficacy and safety of epidurally administered drugs showing that the epidural administration of many different drugs can provide effective regional anaesthesia or analgesia with only minimal side effects. In Part 2, the clinical indications and benefits of CEAA are reviewed and a detailed practical guide on how to perform an epidural injection and insert an epidural catheter is provided.
Deformation and ductile fracture of nanocrystalline gold ultrathin nanoribbon: Width effect
Authors: Liu Jialin , Fan Xiaofeng , Shi Yunfeng , Singh David J. , Zheng Weitao
Published: April 2021

Molecular dynamics simulations are used to investigate the mechanical properties of finite‐width nanocrystalline gold nanoribbons with a thickness of one grain size under tensile strain. We find strong variations in the Young's modulus and flow stress especially for the sample with narrow width. With statistical analysis, Young's modulus has a trend of increase with the decrease of width. Flow stress does not follow this trend. Ductile fracture is observed at large strain in these nanocrystalline nanoribbons, but the fracture strain and mechanism are different from those of thick films as observed in existing experiments. For small widths below 80 nm, fracture is a necking effect, while for larger widths, shear bands and formation of nanovoids due to stress concentration are the main mechanism. Voids are mainly distributed in special GBs that are parallel to the direction of the maximum principal stress of the plastic deformation tensor. We find there is a width regime (about 80–130 nm) for the ultrathin nanoribbon gold, which have good ductility and large fracture strain.