bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of long-term effects in individuals diagnosed with COVID-19: an updated living systematic review
Authors: Domingo Francesca Reyes , Waddell Lisa A , Cheung Angela M. , Cooper Curtis L. , Belcourt Veronica J. , Zuckermann Alexandra M. E. , Corrin Tricia , Ahmad Rukshanda , Boland Laura , Laprise Claudie , Idzerda Leanne , Khan Anam , Morissette Kate , Garcia Alejandra Jaramillo 
Published: June 2021

AbstractObjectivePost COVID-19 condition refers to persisting or recurring symptoms weeks after acute COVID-19 illness which can significantly impact quality of life and health systems. It is important to understand the manifestation and magnitude of this condition. The objective of this living systematic review is to summarize the prevalence of symptoms and sequelae reported by people ≥4 weeks after COVID-19 diagnosis.DesignSystematic review, meta-analysis and narrative synthesis.Data sourcesEmbase, Medline, PsychInfo, Cochrane Central and select grey literature up to April 14, 2021.MethodsWe adapted a previous search strategy used by the U.K. National Institute for Health and Care Excellence and updated it to search for new literature. Two reviewers screened references independently; one extracted data and assessed risk of bias and certainty of the evidence while another verified them. Prevalence data from laboratory-confirmed populations were meta-analyzed using a random effects model and synthesized separately in the short-term (4-12 weeks) and long-term (>12 weeks) periods after diagnosis. Data from clinically-diagnosed populations were synthesized narratively.ResultsOf the 4444 unique citations, 84 observational studies met our inclusion criteria. Over 100 post COVID-19 symptoms and sequelae were reported. Sixty-one percent (95% CI: 44-76%,low certainty) and 53% (95% CI: 41-65%,low certainty) of laboratory-confirmed individuals reported persistence or presence of one or more symptoms in the short- and long-term periods, respectively. The most prevalent symptoms in both periods included: fatigue, general pain or discomfort, shortness of breath, cognitive impairment and mental health symptoms.ConclusionsA substantial proportion of individuals reported a variety of symptoms ≥4 weeks after COVID-19 diagnosis. Due to gaps in the research base, and the low certainty of the evidence currently available, further research is needed to determine the true burden of post COVID-19 condition in the general population and in specific subgroups.PROSPERO registration numberCRD42021231476.
Non-Coding Genetic Analysis Implicates Interleukin 18 Receptor Accessory Protein 3′UTR in Amyotrophic Lateral Sclerosis
Authors: Eitan Chen , Siany Aviad , Barkan Elad , Olender Tsviya , van Eijk Kristel R. , Moisse Matthieu , Farhan Sali M. K. , Danino Yehuda M. , Yanowski Eran , Marmor-Kollet Hagai , Rivkin Natalia , Yacovzada Nancy , Hung Shu-Ting , Cooper-Knock Johnathan , Yu Chien-Hsiung , Louis Cynthia , Masters Seth L. , Kenna Kevin P. , van der Spek Rick A. A. , Sproviero William , Al Khleifat Ahmad , Iacoangeli Alfredo , Shatunov Aleksey , Jones Ashley R. , Elbaz-Alon Yael , Cohen Yahel , Chapnik Elik , Rothschild Daphna , Weissbrod Omer , Beck Gilad , Ainbinder Elena , Ben-Dor Shifra , Werneburg Sebastian , Schafer Dorothy P. , Brown Robert H. , Shaw Pamela J. , Van Damme Philip , van den Berg Leonard H. , Phatnani Hemali P. , Segal Eran , Ichida Justin K. , Al-Chalabi Ammar , Veldink Jan H. ,   Project MinE ALS Sequencing Consortium,   NYGC ALS Consortium, Hornstein Eran 
Published: June 2021

AbstractThe non-coding genome is substantially larger than the protein-coding genome but is largely unexplored by genetic association studies. Here, we performed region-based burden analysis of >25,000 variants in untranslated regions of 6,139 amyotrophic lateral sclerosis (ALS) whole-genomes and 70,403 non-ALS controls. We identified Interleukin-18 Receptor Accessory Protein (IL18RAP) 3′UTR variants significantly enriched in non-ALS genomes, replicated in an independent cohort, and associated with a five-fold reduced risk of developing ALS. Variant IL18RAP 3′UTR reduces mRNA stability and the binding of RNA-binding proteins. Variant IL18RAP 3′UTR further dampens neurotoxicity of human iPSC-derived C9orf72-ALS microglia that depends on NF-κB signaling. Therefore, the variant IL18RAP 3′UTR provides survival advantage for motor neurons co-cultured with C9-ALS microglia. The study reveals direct genetic evidence and therapeutic targets for neuro-inflammation, and emphasizes the importance of non-coding genetic association studies.One Sentence SummaryNon-coding genetic variants in IL-18 receptor 3’UTR decrease ALS risk by modifying IL-18-NF-κB signaling in microglia.
Depletion of TAX1BP1 amplifies innate immune responses during respiratory syncytial virus infection
Authors: Descamps Delphyne , de Oliveira Andressa Peres , Gonnin Lorène , Madrières Sarah , Fix Jenna , Drajac Carole , Marquant Quentin , Bouguyon Edwige , Pietralunga Vincent , Iha Hidekatsu , Ventura Armando Morais , Tangy Frédéric , Vidalain Pierre-Olivier , Eléouët Jean-François , Galloux Marie 
Published: June 2021

ABSTRACTRespiratory syncytial virus (RSV) is the main cause of acute respiratory infections in young children, and also has a major impact in the elderly and immunocompromised people. In the absence of vaccine or efficient treatment, a better understanding of RSV interactions with the host antiviral response during infection is needed. Previous studies revealed that cytoplasmic inclusion bodies (IBs) where viral replication and transcription occur could play a major role in the control of innate immunity during infection by recruiting cellular proteins involved in the host antiviral response. We recently showed that the morphogenesis of IBs relies on a liquid-liquid phase separation mechanism depending on the interaction between viral nucleoprotein (N) and phosphoprotein (P). These scaffold proteins are expected to play a central role in the recruitment of cellular proteins to IBs. Here, we performed a yeast two-hybrid screen using RSV N protein as a bait, and identified the cellular protein TAX1BP1 as a potential partner of N. This interaction was validated by pulldown and immunoprecipitation assays. We showed that TAX1BP1 suppression has only a limited impact on RSV infection in cell cultures. On the contrary, in vivo experiments showed that RSV replication is decreased in TAX1BP1KO mice, whereas the production of inflammatory and antiviral cytokines is enhanced. In vitro infection of either wild-type or TAX1BP1KO alveolar macrophages confirmed that the innate immune response to RSV infection is enhanced in the absence of TAX1BP1. Altogether, our results suggest that RSV could hijack TAX1BP1 to restrain the host immune response during infection.ImportanceRespiratory syncytial virus (RSV), which is the leading cause of lower respiratory tract illness in infants, still remains a medical problem in the absence of vaccine or efficient treatment. This virus is also recognized as a main pathogen in the elderly and immunocompromised people, and the occurrence of co-infections (with other respiratory viruses and bacteria) amplifies the risks of developing respiratory distress. In this context, a better understanding of the pathogenesis associated to viral respiratory infections, which depends on both viral replication and the host immune response, is needed. The present study reveals that the cellular protein TAX1BP1, which interacts with the RSV nucleoprotein N, participates in the control of the innate immune response during RSV infection, suggesting that N-TAX1BP1 interaction represents a new target for the development of antivirals.
Screening of Botanical Drugs against SARS-CoV-2 Entry
Authors: Cao Junyuan , Liu Yang , Zhou Minmin , Dong Siqi , Jia Xiaoying , Lan Xiaohao , Zhang Yueli , Guo Jiao , Xiao Gengfu , Wang Wei 
Published: June 2021

ABSTRACTAn escalating pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is impacting global health. Specific treatment options for diseases caused by SARS-CoV-2 are largely lacking. Herein, we used a pseudotype virus (pv) bearing the SARS-CoV-2 S glycoprotein to screen a botanical drug library to identify an agent against SARS-CoV-2 entry. All the four hits, including angeloylgomisin O, schisandrin B, procyanidin, and oleanonic acid, were identified for effective inhibition of SARS-CoV-2 S pv entry in the micromolar range. A mechanistic study revealed that these four agents inhibit SARS-CoV-2 S pv entry by blocking S-mediated membrane fusion. Furthermore, angeloylgomisin O, schisandrin B, and oleanonic acid inhibited authentic SARS-CoV-2 with a high selective index (SI). We also showed that all the four hits could also inhibit the entry of pv of Middle East respiratory syndrome coronavirus (MERS-CoV) and newly emerged SARS-CoV-2 variants (D614G, K417N/E484K/N501Y/D614G). In drug combination studies performed in cellular antiviral assays, angeloylgomisin O and schisandrin B displayed synergistic effects in combination with remdesivir. These results indicated that angeloylgomisin O, schisandrin B, procyanidin, and oleanonic acid can inhibit SARS-CoV-2 and that they are potential therapeutic agents for COVID-19.
Costs and predictors of early readmissions in patients with Infective Endocarditis. Utilizing the Nationwide Readmission Database
Authors: Zaman Jesan , Amritphale Amod , Malozzi Christopher , Amritphale Nupur , Sehgal Mukul , Bassam Omar 
Published: June 2021

ABSTRACTBACKGROUNDThere have been previous studies detailing the variables involved in readmissions in patients with a primary admission diagnosis of infective endocarditis – however those studies were done prior to the 2015 change in AHA guidelines and introduction to ICD-10 codes.OBJECTIVESThe aim of this study was to describe the frequency, causes, factors, and costs associated with infective endocarditis encounters.METHODSUtilizing the 2017 national readmission database (NRD), we identified all patients that were admitted with infective endocarditis. These patients were evaluated for the rates, predictors, and costs of unplanned 30 days readmissions. Weighted analysis was performed to obtain nationally representative data.RESULTS56,357 patients were identified to have been admitted with a diagnosis of infective endocarditis of whom 13,004 patients (23%) were readmitted within 30 days of the index discharge. The most common causes of readmission were septicemia (15.1%), endocarditis and endocardial disease (10.5%), heart failure (9.5%), and complication of cardiovascular device, implant or graft, initial encounter (5.6%). Data showed that there were certain comorbidities that resulted in a higher risk of being readmitted, these include chronic kidney disease, COPD, tobacco use, and hepatic failure. Cost of readmissions per patient was approximately $22,059 (IQR $11,630 - $49,964).CONCLUSIONSThirty-day unplanned readmissions remain a significant issue affecting nearly 1 in 6 patients with infective endocarditis. This is associated with significant mortality and financial burden. Multi-disciplinary approach may help decrease readmissions, reduce complications, and improve overall outcomes as well as the overall quality of life of our patients.
Factors influencing plasma galectin-3 concentrations in catheter-bearing hospitalized patients
Authors: Iftimie Simona , Hernández-Aguilera Anna , López-Azcona Ana F. , Castañé Helena , Rodríguez-Tomàs Elisabet , Baiges-Gaya Gerard , Castro Antoni , Camps Jordi , Joven Jorge 
Published: June 2021

ABSTRACTIntroductionCatheters are an integral part of modern medicine although their use is not without complications. Catheter-related infection triggers a strong inflammatory reaction and has been associated with high morbidity, mortality, and healthcare costs. The clinical diagnosis of catheter-related infection is made difficult by non-specific symptoms. Investigating the alterations in biochemical parameters related to infectious and inflammatory processes in these patients constitute an active line of research. The aim of this study was to investigate factors influencing the plasma concentration of galectin-3 in catheter-bearing patients and to explore its potential usefulness as an index for catheter-related infections.MethodsCirculating concentrations of galectin-3, chemokine (C-C) motif ligand 2, procalcitonin and C-reactive protein were measured in 110 patients with a central venous catheter, 165 patients with a urinary catheter, and 72 control subjects.ResultsCatheter-bearing patients had significantly higher concentrations of galectin-3 and the other markers than the control group. We identified chronic kidney disease as an independent determinant of plasma galectin-3 concentrations in patients with a central catheter, and serum creatinine concentration, cardiovascular disease and the number of days the catheter was indwelling as determinants in urinary catheter patients. We also found that measuring galectin-3 in urinary catheter patients with a catheter-related infection was more accurate for diagnosis than the other parameters. At galectin-3 = 15 ng/mL, sensitivity was 90%.ConclusionWe conclude that measurement of galectin-3 concentration may be useful for assessing the inflammatory status of catheter-bearing patients and may contribute to the diagnosis of catheter-related infection in those with a urinary catheter.
SARS-CoV-2 variants of concern dominate in Lahore, Pakistan in April 2021
Authors: Sarwar Muhammad Bilal , Yasir Muhammad , Alikhan Nabil-Fareed , Afzal Nadeem , de Oliveira Martins Leonardo , Viet Thanh Le , Trotter Alexander J , Prosolek Sophie J , Kay Gemma L , Foster-Nyarko Ebenezer , Rudder Steven , Baker David J , Sidra-tul-muntaha  , Roman Muhammad , Webber Mark A , Shafiq Almina , Shabir Balqees , Akram Javed , Page Andrew J , Jahan Shah 
Published: June 2021

AbstractBackgroundThe SARS-CoV-2 pandemic continues to expand globally, with case numbers rising in many areas of the world, including the Indian sub-continent. Pakistan has one of the world ‘s largest population, of over 200 million people and is experiencing a severe third wave of infections caused by SARS-CoV-2 that begun in March 2021.In Pakistan, during third wave until now only 12 SARS-CoV-2 genomes have been collected and among these 9 are from Islamabad. This highlights the need for more genome sequencing to allow surveillance of variants in circulation. In fact more genomes are available among travellers with a travel history from Pakistan, than from within the country itself.MethodsFor a better understanding of the circulating variants in Lahore and surrounding areas with a combined population of 11.1 million, within a week of April 2021, 102 samples were sequenced. The samples were randomly collected from 2 hospitals with a diagnostic polymerase chain reaction (PCR) cutoff value of less than 25 cycles.ResultsAnalysis of the lineages shows that B.1.1.7 (first identified in the UK, Alpha variant) dominates, accounting for 97.9% (97/99) of cases, with B.1.351 (first identified in South Africa, Beta variant) accounting for 2.0% (2/99) of cases. No other lineages were observed.DiscussionIn depth analysis of the B.1.1.7 lineages indicates multiple separate introductions and subsequent establishment within the region. Eight samples were identical to genomes observed in Europe (7 UK, 1 Switzerland), indicating recent transmission. Genomes of other samples show evidence that these have evolved, indicating sustained transmission over a period of time either within Pakistan or other countries with low density genome sequencing. Vaccines remain effective against B.1.1.7, however the low level of B.1.351 against which some vaccines are less effective demonstrates the requirement for continued prospective genomic surveillance.
Law, Criminalisation and HIV in the World: Have countries that criminalise achieved more or less successful AIDS pandemic response?
Authors: Kavanagh Matthew M. , Agbla Schadrac C. , Pillinger Mara , Joy Marissa , Case Alaina , Erondu Ngozi , Aneja Kashish , Erkkola Taavi , Graeden Ellie 
Published: June 2021

AbstractHow does the use of criminal law affect disease-fighting efforts, particularly in a pandemic? This longstanding question for governments around the world is felt acutely in the context of the COVID-19 and HIV pandemics. Many countries have laws and policies that criminalise behaviours, making same-sex relationships, illicit drug use, and sex work illegal. Meanwhile, some countries have enshrined gender- and rights-protective institutions in law. Under the global AIDS strategy of the last five years, national AIDS response efforts in countries have focused on reaching people living with HIV with testing and antiretroviral treatment to suppress the HIV virus, preventing mortality and HIV transmission. At the end of this 5-year push, this article provides an ecological analysis of whether those countries with criminalising legal environments achieved more or less success. In countries where same-sex relationships were fully criminalised, the portion of people living with HIV who knew their status was 11% lower and viral suppression rates were 8% lower. Under sex-work criminalization, the rate of people living with HIV who knew their status was 10% lower and viral suppression 6% lower. Drug use criminalisation was associated with 14% lower knowledge of status and viral. On the other hand in countries with laws advancing non-discrimination, human rights institutions, and gender-based violence response, HIV services indicators were significantly better. This ecological evidence on the relationships between the legal environment and successful HIV response provides support for a strategy that includes a focus on law reform to achieve goals missed in 2020.Summary BoxCountries around the world, across economic and geographic boundaries, have taken different approaches to the application of criminal law to same-sex sex, sex work, and drug use—with most taking a partially or fully criminalising legal approach in one or more of these areas.In tackling the AIDS pandemic, globally agreed goals for 2020 focused on ensuring most people living with HIV were aware of their HIV status and had suppressed the HIV virus through effective antiretroviral treatment.The AIDS response in countries that criminalised was less successful than those that did not—achieving significantly lower levels of HIV status knowledge and HIV viral suppression.Countries with clear laws advancing non-discrimination, human rights institutions, and gender-based violence response had better knowledge of HIV status and viral suppression rates.This analysis suggests a new global AIDS strategy that includes a focus on law reform may hold promise in achieving goals that were missed in 2020.
Genetic expression of 4E-BP1 in juvenile mice alleviates mTOR-induced neuronal dysfunction and epilepsy
Authors: Nguyen Lena H. , Xu Youfen , Mahadeo Travorn , Zhang Longbo , Lin Tiffany V. , Born Heather A. , Anderson Anne E. , Bordey Angélique 
Published: June 2021

SUMMARYHyperactivation of mTOR signaling during fetal neurodevelopment alters neuron structure and function, leading to focal malformation of cortical development (FMCD) and intractable epilepsy. Recent evidence suggests increased cap-dependent translation downstream of mTOR contributes to FMCD formation and seizures. However, whether reducing overactive translation once the developmental pathologies are established reverses neuronal abnormalities and seizures is unknown. Here, we found that the translational repressor 4E-BP1, which is inactivated by mTOR-mediated phosphorylation, is hyperphosphorylated in patient FMCD tissue and in a mouse model of FMCD. Expressing constitutive active 4E-BP1 to repress aberrant translation in juvenile mice with FMCD reduced neuronal cytomegaly and corrected several electrophysiological alterations, including depolarized resting membrane potential, irregular firing pattern, and aberrant HCN4 channel expression. This was accompanied by improved cortical spectral activity and decreased seizures. Although mTOR controls multiple pathways, our study shows that targeting 4E-BP1-mediated translation alone is sufficient to alleviate neuronal dysfunction and ongoing epilepsy.
Multi-omics approach reveals new insights into the gut microbiome of Galleria mellonella (Lepidoptera:Pyralidae) exposed to polyethylene diet
Authors: Latour Samuel , Noël Grégoire , Serteyn Laurent , Sare Abdoul Razack , Massart Sébastien , Delvigne Frank , Francis Frédéric 
Published: June 2021

AbstractThe current plastic pollution throughout the world implies a crucial optimization of its (bio)degradation processes. In order to identify plastic degrading bacteria and associated enzymes, the gut microbiota of insects has raised interest. Some entomological models such as Tenebrio molitor (L. 1758), Plodia interpunctella (Hübner 1813) or Galleria mellonella (L. 1758) have the ability to ingest and degrade polyethylene. Then, it is promising to identify the composition and the role of the gut microbiota in this process. This study takes part in this issue by investigating G. mellonella as a biological model feeding with a polyethylene diet. Gut microbiome samples were processed by high throughput 16S rRNA sequencing, and Enterococcaceae and Oxalobacteraceae were found to be the major bacterial families. At low polyethylene dose, we detect no bacterial community change and no amplicon sequence variant associated with the polyethylene diet suggesting microbiome resilience. The functional analysis of insects gut content was promising for the identification of plastic degrading enzymes such as the phenylacetaldehyde dehydrogenase which participate in styrene degradation. This study allows a better characterization of the gut microbiota of G. mellonella and provides a basis for the further biodegradation study of polyethylene based on the microorganism valorization from insect guts.
Toll-like receptor 2 orchestrates a potent anti-tumor response in non-small cell lung cancer
Authors: Millar Fraser R. , Pennycuick Adam , Muir Morwenna , Quintanella Andrea , Hari Priya , Freyer Elisabeth , Gautier Philippe , Meynert Alison , Teixeira Vitor H. , Connelly John , Wallace William AH , Sims Andrew H , Frame Margaret C. , Boulter Luke , Janes Sam M. , Wilkinson Simon , Acosta Juan Carlos 
Published: June 2021

AbstractTargeting early-stage lung cancer is vital to improve overall survival. We previously identified Toll-like receptor 2 (TLR2) as a regulator of oncogene-induced senescence (OIS) and the senescence-associated secretory phenotype (SASP), both key for tumor suppression. Here, we demonstrate that TLR2 is widely expressed in human lung tumor epithelium where it correlates with improved survival and clinical regression. Using genetically engineered mouse models of lung cancer we have shown that Tlr2 is a tumor suppressor in lung cancer initiation via regulation of proliferation and the SASP. The SASP is integral in the regulation of immune surveillance of premalignant cells, and we observe impaired myeloid derived immune surveillance following Tlr2 loss. Lastly, we show that administration of a synthetic Tlr2 agonist significantly reduces preinvasive lung tumor growth. Our data highlight an unexpected tumor surveillance pathway in early-stage lung cancer with therapeutic potential.Statement of significanceLung cancer is a major cancer of unmet need. This study identifies a novel tumor suppressor mechanism in lung cancer. Not only does this highlight a potential therapeutic target for early-stage disease but also multiple secreted candidate biomarkers that could be exploited to augment lung cancer screening approaches.