bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic Fatigue and Postexertional Malaise in People Living With Long COVID: An Observational Study
Authors: Twomey Rosie , DeMars Jessica , Franklin Kelli , Culos-Reed S Nicole , Weatherald Jason , Wrightson James G 
Published: January 2022

Abstract

Objective
People living with long COVID describe a high symptom burden, and a more detailed assessment is needed to inform rehabilitation recommendations. The objectives were to use validated questionnaires to measure the severity of fatigue and compare this with normative data and thresholds for clinical relevance in other diseases; measure and describe the impact of postexertional malaise (PEM); and assess symptoms of dysfunctional breathing, self-reported physical activity, and health-related quality of life.

Methods
This was an observational study with a cross-sectional survey design (data collection from February 2021 to April 2021). Eligible participants were adults experiencing persistent symptoms due to COVID-19 that did not predate the confirmed or suspected infection. Questionnaires included the Functional Assessment of Chronic Illness Therapy–Fatigue Scale and the DePaul Symptom Questionnaire–Post-Exertional Malaise.

Results
After data cleaning, 213 participants were included in the analysis. The total Functional Assessment of Chronic Illness Therapy–Fatigue Scale score was 18 (SD = 10) (where the score can range from 0 to 52, and a lower score indicates more severe fatigue), and 71.4% were experiencing chronic fatigue. Postexertional symptom exacerbation affected most participants, and 58.7% met the PEM scoring thresholds used in people living with myalgic encephalomyelitis/chronic fatigue syndrome.

Conclusion
Long COVID is characterized by chronic fatigue that is clinically relevant and at least as severe as fatigue in several other clinical conditions. PEM is a significant challenge for this patient group. Because of the potential for setbacks and deteriorated function following overexertion, fatigue and postexertional symptom exacerbation must be monitored and reported in clinical practice and in studies involving interventions for people with long COVID.

Impact
Physical therapists working with people with long COVID should measure and validate the patient’s experience. Postexertional symptom exacerbation must be considered, and rehabilitation needs to be carefully designed based on individual presentation. Beneficial interventions might first ensure symptom stabilization via pacing, a self-management strategy for the activity that helps minimize postexertional malaise.
Evaluation of sensitivity and specificity of diagnostic criteria for Behçet’s disease in the absence of a gold standard
Authors: Zhong Zhenyu , Liao Weiting , Gao Yu , Su Guannan , Feng Xiaojie , Yang Peizeng 
Published: January 2022

Abstract

Objective
The performance of existing diagnostic criteria for Behçet’s disease (BD) is usually evaluated by comparison with expert opinions, which may be limited by misclassification and disagreement among experts. We aim to evaluate these criteria in the absence of a gold standard.

Methods
We obtained two datasets involving possible BD and other mimickers from a uveitis registry using case–cohort and nested case–control analyses, respectively. With a Bayesian inference approach, the sensitivity and specificity of International Study Group (ISG) and International Criteria for Behçet’s Disease (ICBD) criteria were simultaneously estimated when true BD state was unknown.

Results
A total of 2440 and 2224 participants were included in case–cohort and nested case–control analyses, respectively. In case–cohort analysis, with scores of ≥4 for BD diagnosis, ICBD criteria showed higher sensitivity (median 97.6%; 95% credible interval 96.9, 98.2) than ISG criteria (median 90.0%; 95% credible interval 88.8, 91.2) but had lower specificity (median 90.8%; 95% credible interval 89.4, 92.1) than ISG criteria (median 98.8%; 95% credible interval 98.3, 99.3). With scores of ≥5 for diagnosis, ICBD criteria demonstrated higher sensitivity (median 97.5%; 95% credible interval 96.8, 98.1) and specificity (median 99.6%; 95% credible interval 99.3, 99.8) than the sensitivity (median 92.3%; 95% credible interval 91.2, 93.3) and specificity (median 98.8%; 95% credible interval 98.2, 99.2) for ISG criteria. The highest diagnostic consistency was observed between ISG criteria and ICBD criteria with scores of ≥5 for diagnosis (Kappa = 0.999; P &lt; 0.001). Nested case–control analysis showed similar results.

Conclusion
ICBD criteria showed optimum discriminatory properties in sensitivity and specificity with scores of ≥5 for BD diagnosis in uveitis. The diagnostic threshold of ICBD criteria could be considered adjustable according to medical specialty, disease prevalence and local practice characteristics.
Wildlife in Cameroon harbor diverse coronaviruses, including many closely related to human coronavirus 229E
Authors: Ntumvi Nkom F , Ndze Valantine Ngum , Gillis Amethyst , Le Doux Diffo Joseph , Tamoufe Ubald , Takuo Jean-Michel , Mouiche Moctar M M , Nwobegahay Julius , LeBreton Matthew , Rimoin Anne W , Schneider Bradley S , Monagin Corina , McIver David J , Roy Sanjit , Ayukekbong James A , Saylors Karen E , Joly Damien O , Wolfe Nathan D , Rubin Edward M , Lange Christian E 
Published: January 2022

Abstract
Zoonotic spillover of animal viruses into human populations is a continuous and increasing public health risk. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the global impact of emergence. Considering the history and diversity of coronaviruses (CoVs), especially in bats, SARS-CoV-2 will likely not be the last to spillover from animals into human populations. We sampled and tested wildlife in the Central African country Cameroon to determine which CoVs are circulating and how they relate to previously detected human and animal CoVs. We collected animal and ecological data at sampling locations and used family-level consensus PCR combined with amplicon sequencing for virus detection. Between 2003 and 2018, samples were collected from 6,580 animals of several different orders. CoV RNA was detected in 175 bats, a civet, and a shrew. The CoV RNAs detected in the bats represented 17 different genetic clusters, coinciding with alpha (n = 8) and beta (n = 9) CoVs. Sequences resembling human CoV-229E (HCoV-229E) were found in 40 Hipposideridae bats. Phylogenetic analyses place the human-derived HCoV-229E isolates closest to those from camels in terms of the S and N genes but closest to isolates from bats for the envelope, membrane, and RNA-dependent RNA polymerase genes. The CoV RNA positivity rate in bats varied significantly (P &lt; 0.001) between the wet (8.2 per cent) and dry seasons (4.5 per cent). Most sampled species accordingly had a wet season high and dry season low, while for some the opposite was found. Eight of the suspected CoV species of which we detected RNA appear to be entirely novel CoV species, which suggests that CoV diversity in African wildlife is still rather poorly understood. The detection of multiple different variants of HCoV-229E-like viruses supports the bat reservoir hypothesis for this virus, with the phylogenetic results casting some doubt on camels as an intermediate host. The findings also support the previously proposed influence of ecological factors on CoV circulation, indicating a high level of underlying complexity to the viral ecology. These results indicate the importance of investing in surveillance activities among wild animals to detect all potential threats as well as sentinel surveillance among exposed humans to determine emerging threats.
Sleep and circadian indices for planning post-pandemic university timetables
Authors: Montagnese Sara , Zarantonello Lisa , Formentin Chiara , Giusti Gianluca , Mangini Chiara , Isherwood Cheryl M. , Ferrari Paolo , Paoli Antonio , Mapelli Daniela , Rizzuto Rosario , Toppo Stefano , Skene Debra J. , Vettor Roberto , Costa Rodolfo 
Published: January 2022

AbstractThe aims of the present study were to obtain sleep quality and sleep timing information in a group of university students, and to evaluate the effects of a circadian hygiene education initiative. All students of the University of Padova (approximately 64,000) were contacted by e-mail (major campaigns in October 2019 and October 2020) and directed to anad hocwebsite for collection of demographics and sleep quality/timing information. Participants (n=5740) received one of two sets of circadian hygiene advice (“A regular life”or“Bright days and dark nights”). Every month, they were then asked how easy it had been to comply, and provided with the advice again. At any even month from joining, they completed the sleep quality/timing questionnaires again. Information on academic performance was obtainedpost hoc, together with representative samples of lecture (n=5972) and exam (n=1800) timings, plus lecture attendances (n=25,302). 52% of students had poor sleep quality and 82% showed signs of sleep deprivation. Those who joined in October 2020, after several months of lockdown and distance learning, had better sleep quality, less sleep deprivation and later sleep habits. The“Bright days and dark nights”advice resulted in earlier get-up time/midsleep compared to the“A regular life”advice. Significant changes in most sleep quality and sleep timing variables were observed in both advice groups over time, also in relation to pandemic-related events characterising 2020. Early-chronotype students had better academic performances compared to their later chronotype counterparts. In a multivariate model, sleep quality, chronotype and study subject were independent predictors of academic performance. Taken together, these results underlie the importance of designing circadian-friendly university timetables.
Persistence of immunity and impact of a third (booster) dose of an inactivated SARS-CoV-2 vaccine, BBV152; a phase 2, double-blind, randomised controlled trial
Authors: Vadrevu Krishna Mohan , Ganneru Brunda , Reddy Siddharth , Jogdand Harsh , Raju Dugyala , Praturi Usha , Sapkal Gajanan , Yadav Pragya , Reddy Prabhakar , Verma Savita , Singh Chandramani , Redkar Sagar Vivek , Gillurkar Chandra Sekhar , Kushwaha Jitendra Singh , Mohapatra Satyajit , Bhate Amit , Rai Sanjay , Ella Raches , Abraham Priya , Prasad Sai , Ella Krishna 
Published: January 2022

AbstractBackgroundNeutralising antibody responses to SARS-CoV-2 vaccines have been reported to decline within 6 months of vaccination, particularly against Variants of Concern (VOC). We assessed the immunogenicity and safety of a booster dose of BBV152 administered 6 months after the second of a two-dose primary vaccination series.MethodsIn an ongoing phase 2 trial (ClinicalTrials.gov: NCT04471519) the protocol was amended after six months to re-consent and randomise 184 previously vaccinated participants to receive a third dose of vaccine or placebo on Day 215. The primary outcome was to measure neutralising antibody titres by plaque-reduction neutralisation test (PRNT50) four weeks after the booster; safety as serious adverse events (SAE) was the key secondary outcome.FindingsFour weeks after a second BBV152 vaccination geometric mean titres (GMTs) of neutralising antibodies were 197·0 PRNT50 (95% CI: 155·6–249·4); this level declined to 23·9 PRNT50 (14·0–40·6) six months later, with a seroconversion rate of 75·4% (95% CI: 68·4–81·6). Four weeks after booster vaccination the GMT increased on Day 243 to 746·6 PRNT50 (514·9–1081) compared with 100·7 PRNT50 (43·6–232·6) in the placebo group. Corresponding seroconversion rates were 98·7% (92·8–99·9) and 79·8% (69·6–87·8). Increased titres in the placebo group were attributed to natural infection as the study was conducted during the second wave of COVID-19 in India. PRNT50 titres against the SARS-CoV-2 variants increased—Alpha (32·6-fold), Beta (161·0-fold), Delta (264·7-fold), and Delta plus (174·2-fold)—after the booster vaccination. We found that vaccine induces both memory B and T cells with a distinct AIM+ specific CD4+T central and effector memory phenotype, including CD8+ TEMRA phenotype. Reactogenicity after vaccine and placebo was minimal and comparable, and no SAEs were reported.InterpretationSix months after a two-dose BBV152 vaccination series cell mediated immunity and neutralising antibodies to both homologous (D614G) and heterologous strains (Alpha, Beta, Delta and Delta plus) persisted above baseline, although the magnitude of the responses had declined. Neutralising antibodies against homologous and heterologous SARS-CoV-2 variants increased 19- to 97-fold after a third vaccination. Booster BBV152 vaccination is safe and may be necessary to ensure persistent immunity to prevent breakthrough infections.FundingThis work was supported and funded by Bharat Biotech International Limited.
Duckweed roots are dispensable and are on a trajectory toward vestigiality
Authors: Ware Alex , Jones Dylan H , Flis Paulina , Smith Kellie , Kümpers Britta , Yant Levi , Atkinson Jonathan A , Wells Darren M , Bishopp Anthony 
Published: January 2022

AbstractDuckweeds are morphologically simplified, free floating aquatic monocots comprising both rooted and rootless genera. This has led to the idea that roots in these species may be vestigial, but empirical evidence supporting this is lacking. Here we show that duckweed roots are no longer required for their ancestral role of nutrient uptake. Comparative analyses of nearly all rooted duckweed species revealed a highly reduced anatomy, with greater simplification in the more recently diverged genus Lemna. A series of root excision experiments demonstrated that roots are dispensable for normal growth in Spirodela polyrhiza and Lemna minor. Furthermore, ionomic analyses of fronds in these two species showed little difference in the elemental composition of plants in rooted versus root-excised samples. In comparison, another free-floating member of the Araceae, Pistia stratiotes, which colonized the aquatic environment independently of duckweeds, has retained a more complex root anatomy. Whilst Pistia roots were not absolutely required for growth, their removal inhibited plant growth and resulted in a broad change in the mineral profile of aerial tissues. Collectively, these observations suggest that duckweeds and Pistia may be different stages along a trajectory towards root vestigialization Given this, along with the striking diversity of root phenotypes, culminating in total loss in the most derived species, we propose that duckweed roots are a powerful system with which to understand organ loss and vestigiality.One sentence summaryThrough their adaption to the aquatic environment, duckweed roots have progressively become structurally reduced making them an ideal plant model with which to study vestigiality.
The diversity and functional capacity of microbes associated with coastal phototrophs
Authors: Miranda Khashiff , Weigel Brooke L. , Fogarty Emily C. , Veseli Iva A. , Giblin Anne E. , Eren A. Murat , Pfister Catherine A. 
Published: January 2022

AbstractCoastal marine phototrophs exhibit some of the highest rates of primary productivity in the world. They have been found to host a diverse set of microbes, many of which may impact the biology of their phototroph hosts through metabolisms that are unique to microbial taxa. Here we characterized the metabolic functions of phototroph-associated microbial communities using metagenomes collected from 2 species of kelp (Laminaria setchelliiandNereocystis luetkeana) and 3 marine angiosperms (Phyllospadix scouleri, P. serrulatusandZostera marina), including the rhizomes of two surfgrass species (Phyllospadixspp.) and the seagrassZostera marina, and the sediments surroundingP. scouleriandZ. marina. Using metagenomic sequencing, we describe 72 metagenome assembled genomes (MAGs) that potentially benefit from being associated with macrophytes and may contribute to macrophyte fitness through their metabolic gene content. All host-associated metagenomes contained genes for the use of dissolved organic matter from hosts and vitamin (B1, B2, B7, B12) biosynthesis. Additionally, we found a range of nitrogen metabolism genes that transform dissolved inorganic nitrogen into forms that may be more available to the host. The rhizosphere of surfgrass and seagrass contained genes for anaerobic microbial metabolisms, includingnifHgenes associated with nitrogen fixation, despite residing in a well-mixed and oxygenated environment. The range of oxygen environments engineered by macrophytes likely explains the diversity of both oxidizing and reducing microbial metabolisms, and contributes to the functional capabilities of microbes and their influence on carbon and nitrogen cycling in nearshore ecosystems.ImportanceKelps, seagrasses and surfgrasses are ecosystem engineers on rocky shorelines where they show remarkably high levels of primary production. Through analysis of their associated microbial communities, we found a variety of microbial metabolisms that may benefit the host, including nitrogen metabolisms and the production of B vitamins. In turn, these microbes have the genetic capability to assimilate the dissolved organic compounds released by their phototroph hosts. We describe a range of oxygen environments associated with surfgrass, including low-oxygen microhabitats in their rhizomes that host genes for nitrogen fixation. The tremendous productivity of coastal phototrophs is likely due in part to the activities of associated microbes and an increased understanding of these associations is needed.
Characterization of ultrapotent chemogenetic ligands for research applications in non-human primates
Authors: Raper Jessica , Eldridge Mark A. G. , Sternson Scott. M. , Shim Jalene Y. , Fomani Grace P. , Richmond Barry J. , Wichmann Thomas , Galvan Adriana 
Published: January 2022

ABSTRACTChemogenetics is a technique for obtaining selective pharmacological control over a cell population by expressing an engineered receptor that is selectively activated by an exogenously administered ligand. A promising approach for neuronal modulation involves the use of “Pharmacologically Selective Actuator Modules” (PSAMs); these chemogenetic receptors are selectively activated by ultrapotent “Pharmacologically Selective Effector Molecules” (uPSEMs). To extend the use of PSAM/PSEMs to studies in nonhuman primates it is necessary to thoroughly characterize the efficacy and safety of these tools. We describe the time course and brain penetrance in rhesus monkeys of two compounds with promising binding specificity and efficacy profiles in in vitro studies, uPSEM792 and uPSEM817, after systemic administration. Rhesus macaques received subcutaneous (s.c.) or intravenous (i.v.) administration of uPSEM817(0.064 mg/kg) or uPSEM792 (0.87 mg/kg) and plasma and CSF samples were collected over the course of 48 hours. Both compounds exhibited good brain penetrance, relatively slow washout and negligible conversion to potential metabolites - varenicline or hydroxyvarenicline. In addition, we found that neither of these uPSEMs significantly altered heart rate or sleep. Our results indicate that both compounds are suitable candidates for neuroscience studies using PSAMs in nonhuman primates.
Translational buffering by ribosome stalling in upstream open reading frames
Authors: Bottorff Ty , Geballe Adam P. , Subramaniam Arvind Rasi 
Published: January 2022

AbstractUpstream open reading frames (uORFs) are present in over half of all human mRNAs. uORFs can potently regulate the translation of downstream open reading frames by several mechanisms: siphoning away scanning ribo-somes, regulating re-initiation, and allowing interactions between scanning and elongating ribosomes. However, the consequences of these different mechanisms for the regulation of protein expression remain incompletely understood. Here, we performed systematic measurements on the uORF-containing 5’ UTR of the cytomegaloviral UL4 mRNA to test alternative models of uORF-mediated regulation in human cells. We find that a terminal diproline-dependent elongating ribosome stall in the UL4 uORF prevents decreases in main ORF translation when ribosome loading onto the mRNA is reduced. This uORF-mediated buffering is insensitive to the location of the ribosome stall along the uORF. Computational kinetic modeling based on our measurements suggests that scanning ribosomes dissociate rather than queue when they collide with stalled elongating ribosomes within the UL4 uORF. We identify several human uORFs that repress main ORF translation via a similar terminal diproline motif. We propose that ribosome stalls in uORFs provide a general mechanism for buffering against reductions in main ORF translation during stress and developmental transitions.
Sulfane sulfur post-translationally modifies the global regulator AdpA to influence actinorhodin production and morphological differentiation of Streptomyces coelicolor
Authors: Lu Ting , Wu Xiaohua , Cao Qun , Xia Yongzhen , Xun Luying , Liu Huaiwei 
Published: January 2022

ABSTRACTThe transcription factor AdpA is a key regulator controlling both secondary metabolism and morphological differentiation in Streptomyces. Due to its critical functions, its expression undergoes multi-level regulations at transcriptional, post-transcriptional, and translational levels, yet no post-translational regulation has been reported. Sulfane sulfur, such as organic polysulfide (RSnH, n≥2), is common inside microorganisms, but its physiological functions are largely unknown. Herein, we discovered that sulfane sulfur post-translationally modifies AdpA in S. coelicolor via specifically reacting with Cys62 of AdpA to form a persulfide (Cys62-SSH). This modification decreases the affinity of AdpA to its self-promoter PadpA, allowing increased expression of adpA, further promoting the expression of its target genes actII-4 and wblA. ActII-4 activates actinorhodin biosynthesis and WblA regulates morphological development. Bioinformatics analyses indicated that AdpA-Cys62 is highly conserved in Streptomyces, suggesting the prevalence of such modification in this genus. Thus, our study unveils a new type of regulation on the AdpA activity and sheds a light on how sulfane sulfur stimulates the production of antibiotics in Streptomyces.IMPORTANCEStreptomyces produce myriad of polyketide compounds having (potential) clinical applications. While the database of polyketide gene clusters are quickly expanding, the regulation mechanisms of them are rarely known. Sulfane sulfur species are commonly present in microorganisms with unclear functions. Herein, we discovered that sulfane sulfur increases actinorhodin (ACT) production in S. coelicolor. The underlying mechanism is sulfane sulfur specifically reacts with AdpA, a global transcription factor controlling both ACT gene cluster and morphological differentiation related genes, to form sulfhydrated AdpA. This modification changes dynamics of AdpA-controlled gene network and leads to high expression of ACT biosynthetic genes. Given the wide prevalence of AdpA and sulfane sulfur in Streptomyces, this mechanism may represent a common regulating pattern of polyketide gene clusters. Thus, this finding provides a new strategy for mining and activating valuable polyketide gene clusters.