bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased prevalence of attention-deficit hyperactivity disorder symptomatology in patients with familial Mediterranean fever
Authors: Lavi Eran , Maree Aus , Eisenstein Eli M , Wexler Isaiah , Berger Itai , Berkun Yackov
Published: October 2021

Objectives

Previous studies suggest that exposure to inflammation in infancy may increase the risk for attention-deficit and hyperactivity disorder (ADHD). We studied the ADHD manifestations among 124 familial Mediterranean fever (FMF) patients and examined the relationship between FMF patient characteristics and ADHD.

Methods

Clinical, demographic, and genetic data were abstracted from patients’ medical records and supplemented by information obtained during clinic visits. ADHD manifestations were assessed using the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) questionnaire.

Results

ADHD was diagnosed in 42 (32.8%) FMF patients, a rate significantly higher than in unselected populations (∼8%). A majority (n = 27, 64.3%) had combined inattentive, hyperactive-impulsive manifestations. Eight (19%) had predominantly hyperactive-impulsive, and seven (16.6%) had predominantly inattentive symptoms. FMF patients with severe manifestations reported more ADHD symptoms. FMF patients with ADHD symptoms were less adherent to their treatment regimen, with only 61.9% of the patients with ADHD symptoms adhering to colchicine therapy compared to 92.7% of the patients without ADHD symptoms.

Conclusion

The high prevalence of ADHD characteristics in children with FMF may support the neuroimmune hypothesis that chronic inflammation increases the risk for ADHD. Children with FMF should be screened for ADHD as its presence may adversely affect adherence to treatment.
The European Genome-phenome Archive in 2021
Authors: Freeberg Mallory Ann , Fromont Lauren A , D’Altri Teresa , Romero Anna Foix , Ciges Jorge Izquierdo , Jene Aina , Kerry Giselle , Moldes Mauricio , Ariosa Roberto , Bahena Silvia , Barrowdale Daniel , Barbero Marcos Casado , Fernandez-Orth Dietmar , Garcia-Linares Carles , Garcia-Rios Emilio , Haziza Frédéric , Juhasz Bela , Llobet Oscar Martinez , Milla Gemma , Mohan Anand , Rueda Manuel , Sankar Aravind , Shaju Dona , Shimpi Ashutosh , Singh Babita , Thomas Coline , de la Torre Sabela , Uyan Umuthan , Vasallo Claudia , Flicek Paul , Guigo Roderic , Navarro Arcadi , Parkinson Helen , Keane Thomas , Rambla Jordi
Published: October 2021

The European Genome-phenome Archive (EGA - https://ega-archive.org/) is a resource for long term secure archiving of all types of potentially identifiable genetic, phenotypic, and clinical data resulting from biomedical research projects. Its mission is to foster hosted data reuse, enable reproducibility, and accelerate biomedical and translational research in line with the FAIR principles. Launched in 2008, the EGA has grown quickly, currently archiving over 4,500 studies from nearly one thousand institutions. The EGA operates a distributed data access model in which requests are made to the data controller, not to the EGA, therefore, the submitter keeps control on who has access to the data and under which conditions. Given the size and value of data hosted, the EGA is constantly improving its value chain, that is, how the EGA can contribute to enhancing the value of human health data by facilitating its submission, discovery, access, and distribution, as well as leading the design and implementation of standards and methods necessary to deliver the value chain. The EGA has become a key GA4GH Driver Project, leading multiple development efforts and implementing new standards and tools, and has been appointed as an ELIXIR Core Data Resource.
iProX in 2021: connecting proteomics data sharing with big data
Authors: Chen Tao , Ma Jie , Liu Yi , Chen Zhiguang , Xiao Nong , Lu Yutong , Fu Yinjin , Yang Chunyuan , Li Mansheng , Wu Songfeng , Wang Xue , Li Dongsheng , He Fuchu , Hermjakob Henning , Zhu Yunping
Published: October 2021

The rapid development of proteomics studies has resulted in large volumes of experimental data. The emergence of big data platform provides the opportunity to handle these large amounts of data. The integrated proteome resource, iProX (https://www.iprox.cn), which was initiated in 2017, has been greatly improved with an up-to-date big data platform implemented in 2021. Here, we describe the main iProX developments since its first publication in Nucleic Acids Research in 2019. First, a hyper-converged architecture with high scalability supports the submission process. A hadoop cluster can store large amounts of proteomics datasets, and a distributed, RESTful-styled Elastic Search engine can query millions of records within one second. Also, several new features, including the Universal Spectrum Identifier (USI) mechanism proposed by ProteomeXchange, RESTful Web Service API, and a high-efficiency reanalysis pipeline, have been added to iProX for better open data sharing. By the end of August 2021, 1526 datasets had been submitted to iProX, reaching a total data volume of 92.42TB. With the implementation of the big data platform, iProX can support PB-level data storage, hundreds of billions of spectra records, and second-level latency service capabilities that meet the requirements of the fast growing field of proteomics.
G-quadruplex RNA motifs influence gene expression in the malaria parasite Plasmodium falciparum
Authors: Dumetz Franck , Chow Eugene Yui-Ching , Harris Lynne M , Liew Shiau Wei , Jensen Anders , Umar Mubarak I , Chung Betty , Chan Ting Fung , Merrick Catherine J , Kwok Chun Kit
Published: October 2021

G-quadruplexes are non-helical secondary structures that can fold in vivo in both DNA and RNA. In human cells, they can influence replication, transcription and telomere maintenance in DNA, or translation, transcript processing and stability of RNA. We have previously showed that G-quadruplexes are detectable in the DNA of the malaria parasite Plasmodium falciparum, despite a very highly A/T-biased genome with unusually few guanine-rich sequences. Here, we show that RNA G-quadruplexes can also form in P. falciparum RNA, using rG4-seq for transcriptome-wide structure-specific RNA probing. Many of the motifs, detected here via the rG4seeker pipeline, have non-canonical forms and would not be predicted by standard in silico algorithms. However, in vitro biophysical assays verified formation of non-canonical motifs. The G-quadruplexes in the P. falciparum transcriptome are frequently clustered in certain genes and associated with regions encoding low-complexity peptide repeats. They are overrepresented in particular classes of genes, notably those that encode PfEMP1 virulence factors, stress response genes and DNA binding proteins. In vitro translation experiments and in vivo measures of translation efficiency showed that G-quadruplexes can influence the translation of P. falciparum mRNAs. Thus, the G-quadruplex is a novel player in post-transcriptional regulation of gene expression in this major human pathogen.
PLSDB: advancing a comprehensive database of bacterial plasmids
Authors: Schmartz Georges P , Hartung Anna , Hirsch Pascal , Kern Fabian , Fehlmann Tobias , Müller Rolf , Keller Andreas
Published: October 2021

Plasmids are known to contain genes encoding for virulence factors and antibiotic resistance mechanisms. Their relevance in metagenomic data processing is steadily growing. However, with the increasing popularity and scale of metagenomics experiments, the number of reported plasmids is rapidly growing as well, amassing a considerable number of false positives due to undetected misassembles. Here, our previously published database PLSDB provides a reliable resource for researchers to quickly compare their sequences against selected and annotated previous findings. Within two years, the size of this resource has more than doubled from the initial 13,789 to now 34,513 entries over the course of eight regular data updates. For this update, we aggregated community feedback for major changes to the database featuring new analysis functionality as well as performance, quality, and accessibility improvements. New filtering steps, annotations, and preprocessing of existing records improve the quality of the provided data. Additionally, new features implemented in the web-server ease user interaction and allow for a deeper understanding of custom uploaded sequences, by visualizing similarity information. Lastly, an application programming interface was implemented along with a python library, to allow remote database queries in automated workflows. The latest release of PLSDB is freely accessible under https://www.ccb.uni-saarland.de/plsdb.
A randomized phase II trial of efficacy and safety of the immunotherapy ALECSAT as an adjunct to radiotherapy and temozolomide for newly diagnosed glioblastoma
Authors: Werlenius Katja , Stragliotto Giuseppe , Strandeus Michael , Blomstrand Malin , Carén Helena , Jakola Asgeir S , Rydenhag Bertil , Dyregaard Dorte , Dzhandzhugazyan Karine N , Kirkin Alexei F , Raida Martin K , Smits Anja , Kinhult Sara
Published: October 2021

Background

There is an urgent need for effective treatments against glioblastoma (GBM). In this trial, we investigated the efficacy and safety of an adoptive cell-based immunotherapy.

Methods

Patients with newly diagnosed GBM were recruited at 4 study sites in Sweden. The patients were randomized 1:2 to receive either radiotherapy (RT), 60 Gy/30 fractions, with concomitant and adjuvant temozolomide (TMZ) only, or RT and TMZ with the addition of Autologous Lymphoid Effector Cells Specific Against Tumor (ALECSAT) in an open-label phase II trial. The primary endpoint was investigator-assessed progression-free survival (PFS). The secondary endpoints were survival and safety of ALECSAT.

Results

Sixty-two patients were randomized to either standard of care (SOC) with RT and TMZ alone (n = 22) or SOC with ALECSAT (n = 40). Median age was 57 years (range 38–69), 95% of the patients were in good performance status (WHO 0–1). There was no significant difference between the study arms (SOC vs ALECSAT + SOC) in PFS (7.9 vs 7.8 months; hazard ratio [HR] 1.28; 95% confidence interval [CI] 0.70–2.36; P = .42) or in median overall survival (OS) (18.3 vs 19.2 months; HR 1.16, 95% CI 0.58–2.31; P = .67). The treatment groups were balanced in terms of serious adverse events (52.4% vs 52.5%), but adverse events ≥grade 3 were more common in the experimental arm (81.0% vs 92.5%).

Conclusion

Addition of ALECSAT immunotherapy to standard treatment with radiochemotherapy was well tolerated but did not improve PFS or OS for patients with newly diagnosed GBM.
A review of West African monsoon penetration during Green Sahara periods; implications for human evolution and dispersals over the last three million years
Authors: Larrasoaña Juan Cruz
Published: October 2021

Green Sahara periods (GSPs) represent episodes during which the present-day Sahara was transformed into a savannah in response to intensification of the West African monsoon (WAM). Although GSPs might have dramatically altered the size, structure, and connectivity of human populations in Africa and nearby regions of Asia, their significance for human evolution remains unknown due to the problems involved in gauging the penetration of the WAM over the Sahara at evolutionary timescales. Here I reanalyse monsoon run-off and dust records back to 3 million years ago from Eastern Mediterranean ODP Site 967, and assimilate them with North African palaeoenvironmental data to substantiate penetration of the WAM front during GSPs to latitudes beyond 28°N. These results, coupled with demographic and ecological data for modern hunter-gatherers, point to a significant expansion of human populations during GSPs compared with background desert conditions. Given the clustering of GSPs around long-term maxima in the eccentricity of the Earth’s orbit, I propose that recurrent periods of human population expansion driven by GSPs led to an increased number of favourable mutations. Along with environmental factors favourable for triggering epigenetic changes, this might have led to the rise in enhanced phenotypic plasticity that underpins the speciation of hominin lineages at times of high climate variability envisaged by the variability selection hypothesis. Clustering of GSPs around the Pliocene/Pleistocene boundary, simultaneously with a protracted period of wetter conditions in East Africa and the Sinai Peninsula, further suggests that the initial colonization of Eurasia by hominins occurred circa 2.6 Ma, much earlier than typically considered.
Abnormal paraoxonase-1 (PON1) enzyme activity in idiopathic inflammatory myopathies
Authors: Bae Sangmee Sharon , Shahbazian Ani , Wang Jennifer , Golub Ilana , Oganesian Buzand , Dowd Tyler , Vayngortin Beata , Wang Ryan , Elashoff David , Reddy Srinivasa T , Charles-Schoeman Christina
Published: October 2021

Objectives

Patients with idiopathic inflammatory myopathies (IIM) have severe vascular involvement, which contributes to disease morbidity and mortality. Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL) associated protein that protects the vascular endothelium from oxidative injury and damage. The current work assessed the functional and genetic determinants of PON1 activity in IIM patients.

Methods

A total of 184 IIM patients and 112 healthy controls (HC) were included. PON1 enzyme activity was assessed by paraoxonase, arylesterase and lactonase assays, and the Q192R PON1 single nucleotide polymorphism (SNP) was analysed. Multivariate regression models examined associations of PON1 activity with IIM diagnosis and myositis disease outcomes.

Results

The arylesterase and lactonase activities of PON1 were significantly lower in IIM patients compared with HC. Higher myositis disease activity, the presence of severe IIM-associated interstitial lung disease (ILD), and the presence of MDA5 or anti-synthetase antibodies were significantly associated with lower PON1 activity. The PON1 Q192R polymorphism was strongly linked to the paraoxonase activity of PON1 in IIM, and patients with the PON1 QQ genotype had better IIM disease outcomes compared with patients with the QR or RR genotypes.

Conclusions

The arylesterase and lactonase activities of PON1 are significantly impaired in IIM patients compared with HC, and inversely associate with IIM disease activity and the presence of severe ILD. The PON1 QQ genotype associates with more favourable disease outcomes in IIM patients. Large prospective studies are needed to further evaluate the role of PON1 and PON1 genetic polymorphisms in the development and propagation of IIM and IIM-ILD.
Accountability in Humanitarian Action
Authors: Hilhorst Dorothea , Melis Samantha , Mena Rodrigo , van Voorst Roanne
Published: October 2021

Although a growing number of NGOs are combining humanitarian and development activities, it was long the case that humanitarian action was isolated from discussions and practices in the world of development. The work of saving lives was deemed to be guided solely by the humanitarian principles, and discussions on accountability were rare. In the 1990s, humanitarian standards initiatives arose in recognition that humanitarian organisations were not accountable to affected populations. This article aims to take stock of accountability initiatives and practices in the sector. It builds on accountability theory in distinguishing upward, sideways, and downward accountability, and incorporates formal and informal forms of accountability. It is based on empirical research in Myanmar, Afghanistan, and Sierra Leone. The first part of the article outlines the history of accountability in the humanitarian sector, including an accountability timeline, and discusses current trends in performances around accountability towards displaced people, minorities, and other recipients of aid. It then presents the findings from the three countries. The article concludes by calling attention to the everyday politics of accountability, the widening accountability arena, the differential accountability demands on international and national aid providers, and the crucial importance of sideways accountability to bring accountability to a next level.
The Globalization of an Interaction Ritual Chain: “Clapping for Carers” During the Conflict Against COVID-19
Authors: Rigal Alexandre , Joseph-Goteiner David
Published: October 2021

Sociologists have long been interested in the theoretical possibility of a universal ritual. Despite a growing number of indicators of world society and globalization, there have not been attempts to observe and analyze the international reach of particular rituals. We propose an extension of the “interaction ritual chain” by theorizing how an interaction ritual might be created and diffused internationally. We look at the case of the COVID-19 pandemic, which created shared conditions of social distancing and emotional distress. We analyze a discontinuous chain of urban and national interaction rituals that focused attention on the efforts of healthcare workers fighting the virus. We count clapping and noise-making in 101 countries and 26 global cities. While we find similar ritual forms and international symbols of solidarity, there was also substantial evidence of conflict and particularism.
Chronic Benzene Exposure Aggravates Pressure Overload-Induced Cardiac Dysfunction
Authors: Zelko Igor N , Dassanayaka Sujith , Malovichko Marina V , Howard Caitlin M , Garrett Lauren F , Uchida Shizuka , Brittian Kenneth R , Conklin Daniel J , Jones Steven P , Srivastava Sanjay
Published: October 2021

Benzene is a ubiquitous environmental pollutant abundant in household products, petrochemicals, and cigarette smoke. Benzene is a well-known carcinogen in humans and experimental animals; however, little is known about the cardiovascular toxicity of benzene. Recent population-based studies indicate that benzene exposure is associated with an increased risk for heart failure. Nonetheless, it is unclear whether benzene exposure is sufficient to induce and/or exacerbate heart failure. We examined the effects of benzene (50 ppm, 6 h/day, 5 days/week, and 6 weeks) or high-efficiency particulate absorbing-filtered air exposure on transverse aortic constriction (TAC)-induced pressure overload in male C57BL/6J mice. Our data show that benzene exposure had no effect on cardiac function in the Sham group; however, it significantly compromised cardiac function as depicted by a significant decrease in fractional shortening and ejection fraction, as compared with TAC/Air-exposed mice. RNA-seq analysis of the cardiac tissue from the TAC/benzene-exposed mice showed a significant increase in several genes associated with adhesion molecules, cell-cell adhesion, inflammation, and stress response. In particular, neutrophils were implicated in our unbiased analyses. Indeed, immunofluorescence studies showed that TAC/benzene exposure promotes infiltration of CD11b+/S100A8+/myeloperoxidase+-positive neutrophils in the hearts by 3-fold. In vitro, the benzene metabolites, hydroquinone, and catechol, induced the expression of P-selectin in cardiac microvascular endothelial cells by 5-fold and increased the adhesion of neutrophils to these endothelial cells by 1.5- to 2.0-fold. Benzene metabolite-induced adhesion of neutrophils to the endothelial cells was attenuated by anti-P-selectin antibody. Together, these data suggest that benzene exacerbates heart failure by promoting endothelial activation and neutrophil recruitment.
Advances in Assessing Hazard and Risk to Emerging Threats and Emergency Response: Comparing and Contrasting Efforts of 3 Federal Agencies
Authors: Mumtaz Moiz M , Nickle Rich A , Lambert Jason C , Johnson Mark S
Published: October 2021

Federal statutes authorize several agencies to protect human populations from chemical emergencies and provide guidance to evacuate, clean, and reoccupy affected areas. Each of the authorized federal agencies has developed programs to provide managers, public health officials, and regulators, with a rapid assessment of potential hazards and risks associated with chemical emergencies. Emergency responses vary based on exposure scenarios, routes, temporal considerations, and the substance(s) present. Traditional chemical assessments and derivation of toxicity values are time-intensive, typically requiring large amounts of human epidemiological and experimental animal data. When a rapid assessment of health effects is needed, an integrated computational approach of augmenting extant toxicity data with in vitro (new alternative toxicity testing methods) data can provide a quick, evidence-based solution. In so doing, multiple streams of data can be used, including literature searches, hazard, dose-response, physicochemical, environmental fate, transport property data, in vitro cell bioactivity testing, and toxicogenomics. The field of toxicology is moving, towards increased use of this approach as it transforms from observational to predictive science. The challenge is to objectively and transparently derive toxicity values using this approach to protect human health and the environment. Presented here are examples and efforts toward rapid risk assessment that demonstrate unified, parallel, and complementary work to provide timely protection in times of chemical emergency.
Detection of Mycobacterium leprae infection in family clusters from six leprosy-endemic regions in Colombia
Authors: Serrano-Coll Héctor , Osorio-Leal Yuliana , Escobar-Builes María Victoria , Cardona-Castro Nora
Published: October 2021

Background

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which continues to be endemic in tropical countries, making it necessary to implement strategies for its elimination. The objective of the current article was to detect M. leprae infection and associated factors through serological and epidemiological evaluation in family clusters of leprosy patients.

Methods

Mycobacterium leprae infection was determined in 50 family clusters of leprosy patients from the departments of Bolívar, Atlántico, Santander, Boyacá, Chocó and Antioquia through the detection of antibodies (protein A, IgM, IgG) against anti-natural octyl disacharide-leprosy IDRI diagnostic (NDO-LID).

Results

Higher seroconversion and elevated titers of these antibodies against NDO-LID were observed in the population of Chocó and Atlántico (p<0.05). Additionally, a higher frequency of infection was observed in large family groups that consumed armadillo meat and belonged to a low socioeconomic stratum (p<0.05). Multivariate analysis established that the main associated factors for a family cluster experiencing this infection were belonging to a vulnerable economic stratum and a large family group.

Conclusions

This study found that the set of social and demographic variables (i.e. armadillo consumption, geographic area, low socioeconomic status and belonging to a large family cluster) are related to the promotion of seropositivity in family clusters.
Clinical Outcome of Nerve Decompression Surgery for Migraine Improves with Nerve Wrap
Authors: Alizadeh Kaveh , Kreinces Jason B. , Smiley Abbas , Gachabayov Mahir
Published: October 2021

Background:

Chronic migraine headaches affect nearly 30 million Americans every year and are responsible for roughly 1.2 million emergency department visits annually. Many of the standard therapies commonly used to treat migraines are often unsuccessful and may furthermore introduce unwanted side effects. The purpose of this study was to identify independent predictors of clinical improvement in patients undergoing surgical nerve decompression for migraine.

Methods:

A retrospective chart review between 2010 and 2020 was conducted. The primary endpoint was clinical improvement at 1-year follow-up, defined as an independence from prescription medications. Patients were stratified into two groups: clinical improvement and treatment failure. Backward multivariable logistic regression was used to examine the associations between migraine improvement and different patient characteristics.

Results:

A total of 153 patients were included. In total, 129 (84.3%) patients improved and 24 (15.7%) did not. Significant associations with clinical improvement at multivariable logistic regression were found with acellular dermal matrix nerve wrap (OR = 10.80, 95%CI: 6.18–16.27), and operation of trigger sites four (OR = 37.96, 95%CI: 2.16–73.10) and five (OR = 159, 95%CI: 10–299).

Conclusion:

The use of acellular dermal matrix nerve wraps in surgery was significantly associated with clinical migraine improvement, as was operation at trigger sites four and five.
The Impact of COVID-19 on Patient Interest in Facial Plastic Surgery
Authors: Sharma Giriraj K. , Asaria Jamil
Published: October 2021

Background:

The coronavirus disease 2019 (COVID-19) pandemic has led to an unforeseen surge in demand for facial plastic surgery (FPS). The objective of this study was to survey patients who pursued cosmetic FPS during COVID-19 to better understand how changes in lifestyle, digital media usage, and their facial self-image influenced their decision to pursue surgery.

Methods:

A web-based survey was sent to 150 patients who had undergone FPS at an outpatient clinic between May 1 and July 30, 2020. Questions included changes in patients’ lifestyle habits, use of video conferencing and social media, Likert scale ratings of motivational factors to pursue FPS, and changes in perception of their own facial aesthetics during COVID-19.

Results:

The survey response rate was 41%. Overall increases in video conferencing for social (79% of respondents) and occupational (73%) purposes, and social media usage (82%) were noted. The most commonly cited motivating factors to pursue FPS during COVID-19 were having ample privacy from family, friends, and co-workers (77%) and not requiring extended leave of absence from work (69%) during the postoperative recovery period. Patients were more aware of their nose than any other facial feature during COVID-19 compared to prior.

Conclusions:

The popularity of FPS during COVID-19 can be partially attributed to increased usage of video conferencing and social media, digital applications which often accentuate personal and idealized facial aesthetics. As surgeons adjust to increased demand for FPS, a better understanding of patient perspectives and motivations can help optimize doctor–patient relations and the delivery of care.
Rejection-associated Phenotype of De Novo Thrombotic Microangiopathy Represents a Risk for Premature Graft Loss
Authors: Petr Vojtech , Hruba Petra , Kollar Marek , Krejci Karel , Safranek Roman , Stepankova Sona , Dedochova Jarmila , Machova Jana , Zieg Jakub , Slatinska Janka , Pokorna Eva , Viklicky Ondrej
Published: October 2021

Background.

Thrombotic microangiopathy (TMA) significantly affects kidney graft survival, but its pathophysiology remains poorly understood.

Methods.

In this multicenter, retrospective, case–control paired study designed to control for donor-associated risks, we assessed the recipients’ risk factors for de novo TMA development and its effects on graft survival. The study group consists of patients with TMA found in case biopsies from 2000 to 2019 (n = 93), and the control group consists of recipients of paired kidney grafts (n = 93). Graft follow-up was initiated at the time of TMA diagnosis and at the same time in the corresponding paired kidney graft.

Results.

The TMA group displayed higher peak panel-reactive antibodies, more frequent retransplantation status, and longer cold ischemia time in univariable analysis. In the multivariable regression model, longer cold ischemia times (odds ratio, 1.18; 95% confidence interval [CI], 1.01-1.39; P = 0.043) and higher peak pretransplant panel-reactive antibodies (odds ratio, 1.03; 95% CI, 1.01-1.06; P = 0.005) were found to be associated with increased risk of de novo TMA. The risk of graft failure was higher in the TMA group at 5 y (hazard ratio [HR], 3.99; 95% CI, 2.04-7.84; P < 0.0001). Concomitant rejection significantly affected graft prognosis at 5 y (HR, 6.36; 95% CI, 2.92-13.87; P < 0.001). De novo TMA associated with the active antibody-mediated rejection was associated with higher risk of graft failure at 5 y (HR, 3.43; 95% CI, 1.69-6.98; P < 0.001) compared with other TMA.

Conclusions.

Longer cold ischemia and allosensitization play a role in de novo TMA development, whereas TMA as a part of active antibody-mediated rejection was associated with the highest risk for premature graft loss.
Symptoms compatible with long-COVID in healthcare workers with and without SARS-CoV-2 infection – results of a prospective multicenter cohort
Authors: Strahm Carol , Seneghini Marco , Güsewell Sabine , Egger Thomas , Leal Onicio , Brucher Angela , Lemmenmeier Eva , Kleeb Dorette Meier , Möller J. Carsten , Rieder Philip , Ruetti Markus , Rutz Remus , Schmid Hans-Ruedi , Stocker Reto , Vuichard-Gysin Danielle , Wiggli Benedikt , Besold Ulrike , Kuster Stefan P. , McGeer Allison , Risch Lorenz , Friedl Andrée , Schlegel Matthias , Schmid Dagmar , Vernazza Pietro , Kahlert Christian R. , Kohler Philipp
Published: October 2021

Background

The burden of long-term symptoms (i.e. long-COVID) in patients after mild COVID-19 is debated. Within a cohort of healthcare workers (HCW), frequency and risk factors for symptoms compatible with long-COVID are assessed.

Methods

Participants answered baseline (August/September 2020) and weekly questionnaires on SARS-CoV-2 nasopharyngeal swab (NPS) results and acute disease symptoms. In January 2021, SARS-CoV-2 serology was performed; in March, symptoms compatible with long-COVID (including psychometric scores) were asked and compared between HCW with positive NPS, seropositive HCW without positive NPS (presumable a-/pauci-symptomatic infections), and negative controls. Also, the effect of time since diagnosis and quantitative anti-S was evaluated. Poisson regression was used to identify risk factors for symptom occurrence.

Results

Of 3’334 HCW (median 41 years; 80% female), 556 (17%) had a positive NPS and 228 (7%) were only seropositive. HCW with positive NPS more frequently reported ≥1 symptom compared to controls (73%vs.52%, p<0.001); seropositive HCW without positive NPS did not score higher than controls (58%vs.52%, p=0.13), although impaired taste/olfaction (16%vs.6%, p<0.001) and hair loss (17%vs.10%, p=0.004) were more common. Exhaustion/burnout was reported by 24% of negative controls. Many symptoms remained elevated in those diagnosed >6 months ago; anti-S titers correlated with high symptom scores. Acute viral symptoms in weekly questionnaires best predicted long-COVID symptoms. Physical activity at baseline was negatively associated with neurocognitive impairment and fatigue scores.

Conclusions

Seropositive HCW without positive NPS are only mildly affected by long-COVID. Exhaustion/burnout is common, even in non-infected HCW. Physical activity might be protective against neurocognitive impairment/fatigue symptoms after COVID-19.

summary

In this prospective healthcare worker cohort, participants with SARS-CoV-2-positive nasopharyngeal swab were most likely to report long-COVID symptoms, whereas seropositive participants without positive swab were only mildly affected. Physical activity at baseline was negatively associated with neurocognitive impairment and fatigue.
General Practitioner perspectives and wellbeing during the COVID-19 Pandemic: a mixed method social media analysis
Authors: Golder Su , Jefferson Laura , McHugh Elizabeth , Essex Holly , Heathcote Claire , Avila Ana Castro , Dale Veronica , Feltz-Cornelis Christina Van Der , Bloor Karen
Published: October 2021

Background

General practitioners (GPs) adapted their work practices rapidly in response to the COVID-19 pandemic. Limited research has explored their perspectives over this time, and factors that may affect their wellbeing.

Method

We conducted a social media analysis of NHS GPs practising in the UK during the COVID-19 pandemic to identify issues which may affect their wellbeing. To identify trends, we assessed 91,034 tweets from 185 GPs on Twitter who posted before and during the pandemic, (January 2019 to February 2021). To identify themes related to wellbeing, we analysed qualitatively 7145 tweets posted during the pandemic from 200 GPs.

Results

We identified inter-connecting themes that affect GP wellbeing, predominately around resources and support. Lack of personal protective equipment (PPE) and testing led to discussion of safety and risk, as well as increased workload resulting from staff isolating. Expressions of low morale and feeling undervalued were widespread, resulting from the perceived lack of support from the government, media and the general public at a time of staff shortages and high workload.

Trends in themes were apparent, with emphasis on PPE, testing and safety March to May 2020 and morale, abuse, ‘closed’ GP surgeries, testing, flu vaccines and overworked September to October 2020. From December 2020 the COVID-19 vaccine dominated posts.

Conclusion

GPs’ experiences and perceptions as reflected in their social media posts during the pandemic have changed over time; perceived lack of support and resources, and negative public perceptions have exacerbated their concerns about existing underlying pressures.
Influence of the hospital upon the outcomes of gastrointestinal fistulas: results of a multi-continent, multi-national, multi-center cohort
Authors: Márquez Humberto Arenas , Correia María Isabel Turcios , García Juan Francisco , Prado Roberto Anaya , Vergara Arturo , Garnica Jorge Luis , Cacho Alejandra , Guerra Daniel , Navarrete Miguel Mendoza , Porbén Sergio Santana
Published: October 2021

Rationale

Prognosis and outcomes of gastrointestinal fistulas (GIF) might depend upon the operational characteristics of the hospital containing and caring for the patients.

Objective

To assess how selected operational characteristics of the hospital participating in the exercises of the “Fistula Day” Project (FDP) influence upon prognosis and outcomes of GIF.

Study design

Cohort-type study. Enrolled patients were followed for 60 days. Three cross-sectional examinations were made during the completion of the exercises of the FDP, namely, upon admission of the patient in the study, and 30 and 60 days after admission.

Study serie

Seventy-six hospitals of Latin America (13 countries) and Europe (4).

Methods

Associations between survival of the patient, prolongation of hospital stay, and (likely) spontaneous closure of the fistula, on one hand; and selected operational characteristics of the participating hospital, on the other; were assessed.

Results

Specialties hospitals prevailed. Most of the hospitals assisted between 1 – 2 GIF patients a month. Participating hospitals distributed evenly regarding the number of beds. Most of the hospitals had an intensive care unit. Similarly, three-quarters of the hospitals had a multidisciplinary unit dedicated to clinical and hospital nutrition. However, a unit dedicated to the management of intestinal failure and/or postoperative fistulas was present only in a fifth of them. Experience of the physician attending GIF was rated between “Expert” and “High” in one third of the hospitals. Number of hospitals beds associated with increased survival of GIF patients (χ2 = 5.997; p = 0.092), prolonged hospital stay (χ2 = 7.885; p < 0.05), and higher rate of spontaneous closure of the fistula (χ2 = 11.947; p < 0.05). In addition, rate of spontaneous closure of the fistula was (marginally) higher among patients assisted by a hospital unit specialized on intestinal failure (χ2 = 3.610; p = 0.0574). On the other hand, survival of the patient was dependent (also marginally) upon the number of patients assisted in a month (χ2 = 5.934; p = 0.0514).

Conclusions

It is likely number of hospital beds to determine prognosis and outcomes of GIF. Other operational characteristics of the hospital might exert a marginal influence upon survival of the patient and the likely spontaneous closure of the fistula.
The Carotid Body Detects Circulating Tumor Necrosis Factor-Alpha to Activate a Sympathetic Anti-Inflammatory Reflex
Authors: Katayama Pedro L. , Leirão Isabela P. , Kanashiro Alexandre , Luiz João Paulo M. , Cunha Fernando Q. , Navegantes Luiz C. C. , Menani Jose V. , Zoccal Daniel B. , Colombari Débora S. A. , Colombari Eduardo
Published: October 2021

Recent evidence has suggested that the carotid bodies might act as immunological sensors, detecting pro-inflammatory mediators and signalling to the central nervous system, which, in turn, orchestrates autonomic responses. Here, we demonstrated that the TNF-α receptor type I is expressed in the carotid bodies of rats. The systemic administration of TNF-α increased carotid body afferent discharge and activated glutamatergic neurons in the nucleus tractus solitarius (NTS) that project to the rostral ventrolateral medulla (RVLM), where the majority of pre-sympathetic neurons reside. The activation of these neurons was accompanied by generalized activation of the sympathetic nervous system. Carotid body ablation blunted the TNF-α-induced activation of RVLM-projecting NTS neurons and the increase in splanchnic sympathetic nerve activity. Finally, plasma and spleen levels of cytokines after TNF-α administration were higher in rats subjected to either carotid body ablation or splanchnic sympathetic denervation. Collectively, our findings indicate that the carotid body detects circulating TNF-α to activate a counteracting sympathetic anti-inflammatory mechanism.
BglC of Streptomyces scabiei is a scopolin-hydrolyzing β-glucosidase interfering with the host defense mechanism
Authors: Deflandre Benoit , Rigali Sébastien
Published: October 2021

The beta-glucosidase BglC fulfills multiple functions in both primary metabolism and induction of pathogenicity of Streptomyces scabiei, the causative agent of the common scab disease of root and tuber crops. Indeed, this enzyme hydrolyzes cellobiose and cellotriose to directly feed glycolysis with glucose, but also modifies the intracellular concentration of these cello-oligosaccharides which are the virulence elicitors. The inactivation of bglC also led to unexpected phenotypes such as the constitutive overproduction of thaxtomin A, the main virulence determinant of S. scabiei. In this work we revealed a new target substrate of BglC, the phytoalexin scopolin. Removal of the glucose moiety of scopolin generates scopoletin, a potent inhibitor of thaxtomin A production. The hydrolysis of scopolin by BglC presents substrate inhibition kinetics which contrasts with the typical Michaelis–Menten saturation curve previously observed for the degradation of its natural substrate cellobiose. Our work therefore reveals that BglC targets both cello-oligosaccharide elicitors emanating from the hosts of S. scabiei, and the scopolin phytoalexin generated by the host defense mechanisms, thereby occupying a key position to fine-tune the production of the main virulence determinant thaxtomin A.
TAL effectors with avirulence activity in African strains of Xanthomonas oryzae pv. oryzae
Authors: Lachaux Marlène , Thomas Emilie , Bogdanove Adam J. , Szurek Boris , Hutin Mathilde
Published: October 2021

Background

Xanthomonas oryzae pv. oryzae causes bacterial leaf blight, a devastating disease of rice. Among the type-3 effectors secreted by Xanthomonas oryzae pv. oryzae to support pathogen virulence, the Transcription Activator-Like Effector (TALE) family plays a critical role. Some TALEs are major virulence factors that activate susceptibility (S) genes, overexpression of which contributes to disease development. Host incompatibility can result from TALE-induced expression of so-called executor (E) genes leading to a strong and rapid resistance response that blocks disease development. In that context, the TALE functions as an avirulence (Avr) factor. To date no such avirulence factors have been identified in African strains of Xanthomonas oryzae pv. oryzae.

Results

With respect to the importance of TALEs in the Rice-Xoo pathosystem, we aimed at identifying those that may act as Avr factor within African Xoo. We screened 86 rice accessions, and identified 12 that were resistant to two African strains while being susceptible to a well-studied Asian strain. In a gain of function approach based on the introduction of each of the nine tal genes of the avirulent African strain MAI1 into the virulent Asian strain PXO99A, four were found to trigger resistance on specific rice accessions. Loss-of-function mutational analysis further demonstrated the avr activity of two of them, talD and talI, on the rice varieties IR64 and CT13432 respectively. Further analysis of TalI demonstrated the requirement of its activation domain for triggering resistance in CT13432. Resistance in 9 of the 12 rice accessions that were resistant against African Xoo specifically, including CT13432, could be suppressed or largely suppressed by trans-expression of the truncTALE tal2h, similarly to resistance conferred by the Xa1 gene which recognizes TALEs generally independently of their activation domain.

Conclusion

We identified and characterized TalD and TalI as two African Xoo TALEs with avirulence activity on IR64 and CT13432 respectively. Resistance of CT13432 against African Xoo results from the combination of two mechanisms, one relying on the TalI-mediated induction of an unknown executor gene and the other on an Xa1-like gene or allele.
High-resolution spatiotemporal transcriptomic maps of developing Drosophila embryos and larvae
Authors: Wang Mingyue , Hu Qinan , Lv Tianhang , Wang Yuhang , Lan Qing , Tu Zhencheng , Xiang Rong , Wei Yanrong , Han Kai , An Yanru , Cheng Mengnan , Xu Jiangshan , Esteban Miguel A. , Lu Haorong , Li Wangsheng , Zhang Shaofang , Chen Ao , Chen Wei , Li Yuxiang , Wang Xiaoshan , Xu Xun , Hu Yuhui , Liu Longqi
Published: October 2021

Drosophila has long been a successful model organism in multiple fields such as genetics and developmental biology. Drosophila genome is relatively smaller and less redundant, yet largely conserved with mammals, making it a productive model in studies of embryogenesis, cell signaling, disease mechanisms, etc. Spatial gene expression pattern is critical for understanding of complex signaling pathways and cell-cell interactions, whereas temporal gene expression changes need to be tracked during highly dynamic activities such as tissue development and disease progression. Systematic studies in Drosophila as a whole are still impeded by lack of these spatiotemporal transcriptomic information. Drosophila embryos and tissues are of relatively small size, limiting the application of current technologies to comprehensively resolve their spatiotemporal gene expression patterns. Here, utilizing SpaTial Enhanced REsolution Omics-sequencing (Stereo-seq), we dissected the spatiotemporal transcriptomic changes of developing Drosophila with high resolution and sensitivity. Our data recapitulated the spatial transcriptomes of embryonic and larval development in Drosophila. With these data, we identified known and previously undetected subregions in several tissues during development, and revealed known and potential gene regulatory networks of transcription factors within their topographic background. We further demonstrated that Stereo-seq data can be used for 3D reconstruction of Drosophila embryo spatial transcriptomes. Our data provides Drosophila research community with useful resources of spatiotemporally resolved transcriptomic information across developmental stages.
High-frequency hearing is required for generating a topographic map of auditory space in the mouse superior colliculus
Authors: Si Yufei , Ito Shinya , Litke Alan M. , Feldheim David A.
Published: October 2021

A topographic map of auditory space is a feature found in the superior colliculus (SC) of many species, including CBA/CaJ mice. In this genetic background, high-frequency monaural spectral cues and interaural level differences are used to generate spatial receptive fields (RFs) that form a topographic map along the azimuth. Unfortunately, C57BL/6 mice, a strain widely used for transgenic manipulation, display age-related hearing loss (AHL) due to an inbred mutation in the Cadherin 23 gene (Cdh23)that affects hair cell mechanotransduction. To overcome this problem, researchers have used young C57BL/6 mice in their studies, as they have been shown to have normal hearing thresholds. However, important details of the auditory response characteristics of the SC such as spectral responses and spatial localization, have not been characterized in young C57BL/6 mice.

Here we show that 2-4-month C57BL/6 mice lack neurons with frontal auditory RFs and therefore lack a topographic representation of auditory space in the SC. Analysis of the spectrotemporal receptive fields (STRFs) of the SC auditory neurons shows that C57BL/6 mouse SC neurons lack the ability to detect the high-frequency (>40kHz) spectral cues that are needed to compute frontal RFs. We also show that crossing C57BL/6 mice with CBA/CaJ mice or introducing one copy of the wild-typeCdh23to C57BL/6 mice rescues the high-frequency hearing deficit and improves the topographic map of auditory space. Taken together, these results demonstrate the importance of high-frequency hearing in computing a topographic map of auditory space.

Significance Statement

Despite the strain’s age-dependent hearing loss, C57BL/6 mice are widely used in auditory studies because of the development of transgenic reporter and Cre lines in this genetic background. Here we examined the topographic map of auditory space and spectrotemporal properties of neurons in the SC of C57BL/6 mice. We found an early-onset high-frequency hearing deficit that results in the loss of SC neurons with frontal RFs and, consequently, an absence of a topographic map of auditory space. These findings stress the importance of high-frequency hearing in generating spatially restricted receptive fields and serve as a caution to researchers that doing auditory-related research using the C57BL/6 genetic background may not be representative of true wild-type mice.
Hot corrosion behaviour of CNT-reinforced ZrO2-Y2O3 composite coatings on boiler tube steel at 900°C
Authors: Kumar Sandeep , Bhatia Rakesh , Singh Hazoor
Published: October 2021

Purpose

In Indian thermal power plants, the main cause of boiler tube failure is the presence of molten sulphates and vanadates, which deteriorate the tube material at high temperatures. To combat the hot corrosion failure of metals, thermal spray technology is adopted. This study aims to investigate and study the effect of hot corrosion behaviour of carbon nanotube (CNT)-reinforced ZrO2-Y2O3 composite coatings on T-91 boiler tube steel in a molten salt environment at 900 °C for 50 cycles.

Design/methodology/approach

A plasma spray technique was used for development of the coatings. The samples were exposed to hot corrosion in a silicon tube furnace at 900 °C for 50 cycles. After testing, the test coupons were analysed by X-ray diffraction, scanning electron microscopy/energy dispersive spectroscopy and cross-sectional analysis techniques to aid understanding the kinetics of the corrosion reaction.

Findings

CNT-based reinforced coatings showed lower weight gain along with the formation of protective oxide scales during the experimentation. Improvement in protection against hot corrosion was observed with increase in CNT content in the coating matrix.

Originality/value

It is pertinent to mention here that the high temperature behaviour of CNT-reinforced ZrO2-Y2O3 composite on T-91 steel at 900°C temperature in molten salt environment has never been studied. Thus, the present research was conducted to provide useful results for the application of CNT-reinforced composite coatings at elevated temperature.