bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of hybrid immunity, school reopening, and the Omicron variant on trajectory of COVID-19 epidemic in India: A modelling study
Authors: Mozaffer Farhina , Cherian Philip , Krishna Sandeep , Wahl Brian , Menon Gautam I 
Published: June 2022

SUMMARYBackgroundThe course of the COVID-19 pandemic has been driven by several dynamic behavioral, immunological, and viral factors. We used mathematical modeling to explore how the concurrent reopening of schools, increasing levels of hybrid immunity, and the emergence of the Omicron variant have affected the trajectory of the pandemic in India, using the model Indian state of Andhra Pradesh (pop: 53 million).MethodsWe constructed an age- and contact-structured compartmental model that allows for individuals to proceed through various states depending on whether they have received zero, one, or two doses of the COVID-19 vaccine. Our model is calibrated using results from other models as well as available serosurvey data. The introduction of the Omicron variant is modelled alongside protection gained from hybrid immunity. We predict disease dynamics in the background of hybrid immunity coming from infections and well as an ongoing vaccination program, given prior levels of seropositivity from earlier waves of infection. We describe the consequences of school reopening on cases across different age-bands, as well as the impact of the Omicron (BA.2) variant.ResultsWe show the existence of an epidemic peak that is strongly related to the value of background seroprevalence. As expected, because children were not vaccinated in India, re-opening schools increases the number of cases in children more than in adults, although most such cases are asymptomatic or mild. The height of this peak reduced as the background infection-induced seropositivity was increased from 20% to 40%. At reported values of seropositivity of 64%, no discernable peak was seen. We also explore counterfactual scenarios regarding the effect of vaccination on hybrid immunity. We find that in the absence of vaccination, even at such high levels of seroprevalence, the emergence of the Omicron variant would have resulted in a large rise in cases across all age bands. We conclude that the presence of high levels of hybrid immunity thus resulted in relatively fewer cases in the Omicron wave than in the Delta wave.InterpretationIn India, the decreasing prevalence of immunologically naïve individuals of all ages helped reduce the number of cases reported once schools were reopened. In addition, hybrid immunity, together with the lower intrinsic severity of disease associated with the Omicron variant, contributed to low reported COVID-19 hospitalizations and deaths.FundingWorld Health Organization, Mphasis
The mental wellbeing of prison staff in England during the COVID-19 pandemic: a cross-sectional study
Authors: Johnson Luke , Czachorowski Maciej , Gutridge Kerry , McGrath Nuala , Parkes Julie , Plugge Emma 
Published: June 2022

AbstractObjectivesTo examine the mental wellbeing of prison staff in England within the pandemic, and determine factors associated with wellbeing.DesignCross-sectional study, with self-completed hardcopy and online surveys.Setting26 prisons across England, chosen to be representative of the wider closed prison estate in EnglandParticipantsAll staff within the 26 prisons from 20th July 2020 and 2nd October 2020 were eligible.Primary outcome measureWellbeing, measured using the Short-version of Warwick-Edinburgh Wellbeing Scale (SWEMWBS). Staff wellbeing was compared to that of the English population using indirectly standardised data from the Health Survey for England 2010-13 and a one-sample t-test. Multivariate linear regression modelling explored associations with mental wellbeing score.Results2534 individuals were included (response rate 22.2%). The mean age was 44 years, 53% were female, and 93% were white. The sample mean SWEMWBS score was 23.84 and the standardised population mean score was 23.57. The difference in means was statistically significant (95% CI 0.09 to 0.46), but not of at a clinically meaningful level. The multivariate linear regression model was adjusted for age category, sex, ethnicity, smoking status, presence of comorbidities, occupation, and HMPPS region. Higher wellbeing was significantly associated with older age, male sex, Black/Black British ethnicity, never having smoked, working within the health staff team, and working in certain prison regions. The overall model had a low predictive value (adjusted R2 = 0.0345).ConclusionsUnexpectedly, prison staff wellbeing as measured by SWEMWBS was similar to that of the general population. Reasons for this are unclear but could include the reduction in violence within prisons since the start of the pandemic. Qualitative research across a diverse sample of prison settings would enrich understanding of staff wellbeing within the pandemic.Strengths and limitations of this studyThis is the largest study to date to explore the mental wellbeing of prison staff in the UK (n=2534) and the first peer-reviewed study examining this during the COVID-19 pandemic.The sampling frame used (all staff at 26 prisons in England) is more likely to be representative of the prison staff population than other studies which have measured prison staff wellbeing and recruited through trade union channelsWellbeing was measured using SWEMWBS, which has been validated within the UK populationResponse rate was low (22.2%) and a number of variables adjusted for in the regression model were self-reported which could lead to a degree of bias
Health facility assessments of cervical cancer prevention, screening, and treatment services in Gulu, Uganda
Authors: Chongsuwat Tana , Ibrahim Aaliyah O , Evensen Ann , Conway James H , Zwick Margaret , Oloya William 
Published: June 2022

AbstractBackgroundCervical cancer is ranked globally in the top 3 cancers for women younger than 45 years, with the average age of death at 59 years of age. The highest burden of disease is in low- and low-to-middle income countries (LLMICs), responsible for 90% of the 311,000 cervical cancer deaths in 2018. This growing health disparity is due to the lack of quality screening and treatment programs, low human papillomavirus (HPV) vaccination rates, and high human immunodeficiency virus (HIV) co-infection rates. To address these gaps in care, we need to develop a clear understanding of the resources and capability of LLMIC’s health care facilities to provide prevention, screening, and treatment for cervical cancer.ObjectivesThis project aimed to (1) develop a health facility assessment (HFA) to assess available cervical cancer prevention, screening, and treatment resources and (2) implement the HFA to determine the cervical cancer resources available in Gulu, Uganda.MethodsWe adapted the World Health Organization’s Harmonized Health Facility Assessment for our own HFA and grading scale, deploying it in October 2021 to analyze 21 health centers in Gulu.ResultsGrading of Health Center IIIs (n=16) concluded that 37% had “excellent” or “good” resources available, and 63% of facilities had “poor” or “fair” resources available. Grading of Health Center IVs and above (n=5) concluded that 60% of facilities had “excellent” or “good” resources, and 40% had “fair” resources available.DiscussionThe analysis of health facilities in Gulu demonstrated subpar resources available for cervical cancer prevention, screening, and treatment. Focused efforts are needed to expand health centers’ resources and capability to address rising cervical cancer rates and related health disparities in LLMICs. The development process for the study HFA can be applied to global cervical cancer programming to determine gaps in resources and indicate areas to target improved health equity.
Comparing P300 flashing paradigms in online typing with language models
Authors: Chandravadia Nand , Pendekanti Shrita , Roberts Dustin , Tran Robert , Panchavati Saarang , Arnold Corey , Pouratian Nader , Speier William 
Published: June 2022

AbstractThe P300 Speller is a brain-computer interface system that allows victims of motor neuron diseases to regain the ability to communicate by typing characters into a computer by thought. Since the system has a relatively slow typing speed, different stimulus presentation paradigms have been proposed designed to allow users to input information faster by reducing the number of required stimuli or increase signal fidelity. This study compares the typing speeds of the Row-Column, Checkerboard, and Combinatorial Paradigms to examine how their performance compares in online and offline settings. When the different flashing patterns were tested in conjunction with other established optimization techniques such as language models and dynamic stopping, they did not make a significant impact on P300 speller performance. This result could indicate that further performance improvements on the system lie beyond optimizing flashing patterns.
Ectoparasitism in Polystomatidae (Neodermata, Monogenea): phylogenetic position and mitogenome of Sphyranura euryceae, a parasite of the Oklahoma salamander
Authors: Leeming Samuel J. , Hahn Christoph , Koblmüller Stephan , McAllister Chris T. , Vanhove Maarten P. M. , Kmentová Nikol 
Published: June 2022

AbstractBackgroundPolystomatidae represents a monogenean group whose representatives infect mainly (semi)-aquatic tetrapods. Sphyranuridae with its single genus (Sphyranura) exhibits ectoparasitism on salamander hosts and was traditionally considered a sister-group to Polystomatidae based on the presence of a well-developed opisthaptor yet was distinguished due to the presence of a single pair of haptoral suckers, as opposed to the three pairs present in polystomatids. However, more recent molecular work supported its inclusion within Polystomatidae, at an early diverging, yet unresolved, position in the clade of polystomatids that otherwise exhibit endoparasitism of batrachians. Resolving the position of Sphyranura in relation to Polystomatidae is a prerequisite for understanding the factors driving evolution and the shifts between ecto- and endoparasitism in Polystomatidae.MethodsVarious staining methods were used to morphologically characterise collected specimens of Sphyranura. The mitochondrial genome was assembled from WGS data. Based on a combination of nuclear (18S, 28S rRNA) and mitochondrial markers (cox1, 12S) we inferred the phylogeny of Polystomatidae using Bayesian inference and maximum likelihood methods.ResultsBased on morphological examination and comparison with type material, specimens of Sphyranura infecting Oklahoma salamander (Eurycea tynerensis) at Greathouse Spring, Arkansas (USA), were identified as S. euryceae, a new distributional record for the species. Along with an amended diagnosis of Sphyranura we provide the first molecular data for S. euryceae. Mitochondrial level comparison reveals instances of tRNA gene rearrangements in polystomatids. Our phylogeny identifies two clades within polystomatids infecting tetrapods, one infecting exclusively batrachians, the other mainly known from chelonians. Although not fully supported, Sphyranura appears as the earliest branching lineage within the former.ConclusionsWith Sphyranura nested within Polystomatidae, we consider Sphyranuridae invalid. Sphyranura’s apparent early branching position indicates ectoparasitism is an ancestral trait with endoparasitism having evolved later in the ‘Polbatrach’ clade. However, the reduced number of haptoral suckers in representatives of Sphyranura is a derived characteristic potentially resulting from paedomorphic evolution. Whilst there is an indication towards phylogenetic congruence of polystomatids and their batrachian hosts, the same was not true for polystomatid parasites of chelonians with evidence of multiple host switches. Furthermore, geographic distribution of hosts was not found to drive polystomatid phylogeny.
Equilibrium dynamics of a biomolecular complex analyzed at single-amino acid resolution by cryo-electron microscopy
Authors: Luque Daniel , Ortega-Esteban Alvaro , Valbuena Alejandro , Vilas Jose Luis , Rodríguez-Huete Alicia , Mateu Mauricio G. , Castón José R. 
Published: June 2022

AbstractThe biological function of macromolecular complexes depends not only on large-scale transitions between conformations, but also on small-scale conformational fluctuations at equilibrium. This study shows that detailed information on the equilibrium dynamics of a biocomplex obtained from local resolution (LR) data in cryo-electron microscopy (cryo-EM) density maps matches the information obtained in solution by hydrogen-deuterium exchange mass-spectrometry. The structure of the minute virus of mice (MVM) capsid as a model system was determined by cryo-EM, and LR values were found to correlate with both crystallographic B-factors and hydrogen-deuterium exchange values. Once validated, the cryo-EM LR-based approach was used to compare the equilibrium dynamics of wild-type and two mutant MVM capsids. The results revealed a linkage between mechanical stiffening and impaired equilibrium dynamics in a biocomplex. Cryo-EM is emerging as a powerful approach for simultaneously acquiring information on the atomic structure and local equilibrium dynamics of biomolecular complexes.
Opioid Suppression of an Excitatory Pontomedullary Respiratory Circuit by Convergent Mechanisms
Authors: Bateman Jordan T. , Levitt Erica S. 
Published: June 2022

ABSTRACTOpioids depress breathing by inhibition of inter-connected respiratory nuclei in the pons and medulla. Mu opioid receptor (MOR) agonists directly hyperpolarize a population of neurons in the dorsolateral pons, particularly the Kölliker-Fuse (KF) nucleus, that are key mediators of opioid-induced respiratory depression. However, the projection target and synaptic connections of MOR-expressing KF neurons is unknown. Here, we used retrograde labeling and brain slice electrophysiology to determine that MOR-expressing KF neurons project to respiratory nuclei in the ventrolateral medulla, including the pre-Bötzinger complex (preBötC) and rostral ventral respiratory group (rVRG). These medullary projecting, MOR-expressing dorsolateral pontine neurons express FoxP2 and are distinct from calcitonin gene-related peptide-expressing lateral parabrachial neurons. Furthermore, dorsolateral pontine neurons release glutamate onto excitatory preBötC and rVRG neurons via monosynaptic projections, which is inhibited by presynaptic opioid receptors. The excitatory preBötC and rVRG neurons receiving MOR-sensitive glutamatergic synaptic input from the dorsolateral pons are themselves hyperpolarized by opioids. Thus, opioids can synergistically inhibit this excitatory pontomedullary respiratory circuit by three distinct mechanisms—somatodendritic MORs on dorsolateral pontine and ventrolateral medullary neurons and presynaptic MORs on dorsolateral pontine neuron terminals in the ventrolateral medulla—all of which could contribute to opioid-induced respiratory depression.
Replicative aging impedes stress-induced assembly of a key human protein disaggregase
Authors: Mathangasinghe Yasith , Alberts Niels , Rosado Carlos J. , Cox Dezerae , Payne Natalie L. , Ormsby Angelique R. , Alp Keziban Merve , Sakson Roman , Uthishtran Sanjeev , Ruppert Thomas , Arumugam Senthil , Hatters Danny M. , Kampinga Harm H. , Nillegoda Nadinath B. 
Published: June 2022

AbstractThe collapse of protein homeostasis manifests itself in a toxic protein aggregation cascade, which is associated with degenerative diseases and aging. To solubilize aggregates, dedicated protein disaggregases exist in unicellular organisms, but these have no nuclear/cytosolic orthologs in metazoa. Alternative metazoan disaggregation machines have been described, but how these are operated and regulatedin vivoremained unknown. We show that protein disaggregases are functionally diversified in human cells to efficiently target different types of stress-induced aggregates in sequential and temporally distinct phases. In particular, we show the selective assembly of an Hsp70-DNAJA1-DNAJB1 trimeric disaggregase that forms during late phase of stress recovery.,i.e., after VCP-dependent solubilization of non-native proteins that accumulate in cellular condensates such as nucleoli or stress granules. When activated, the trimeric disaggregase provides resistance to stress toxicity and contributes to amyloid disposal. Strikingly, this disaggregase collapses early in cells undergoing replicative aging with important underlining pathophysiological consequences.
Generation of functional posterior spinal motor neurons from hPSCs-derived human spinal cord neural progenitor cells
Authors: Xu Jax H. , Yao Yao , Yao Fenyong , Chen Jiehui , Li Meishi , Yang Xianfa , Li Sheng , Lu Fangru , Hu Ping , He Shuijin , Peng Guangdun , Jing Naihe 
Published: June 2022

SUMMARYSpinal motor neurons deficiency results in a series of devastating disorders such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA) and spinal cord injury (SCI). These disorders are currently incurable, while human pluripotent stem cells (hPSCs)-derived spinal motor neurons are promising but suffered from low-efficiency, functional immaturity and lacks of posterior cellular identity. In this study, we have established human spinal cord neural progenitor cells (hSCNPCs) via hPSCs differentiated neuromesodermal progenitors (NMPs) and demonstrated the hSCNPCs can be continuously expanded up to 40 passages. hSCNPCs can be rapidly differentiated into posterior spinal motor neurons with high efficiency. The functional maturity has been examined in detail. Moreover, a co-culture scheme which is compatible for both neural and muscular differentiation is developed to mimic the neuromuscular junction (NMJ) formation in vitro. Together, these studies highlight the potential avenues for generating clinically relevant spinal motor neurons and modeling neuromuscular diseases through our defined hSCNPCs.
sRNA-controlled iron sparing response in Staphylococci
Authors: Coronel-Tellez Rodrigo H. , Pospiech Mateusz , Barrault Maxime , Liu Wenfeng , Bordeau Valérie , Vasnier Christelle , Felden Brice , Sargueil Bruno , Bouloc Philippe 
Published: June 2022

ABSTRACTStaphylococcus aureus, a human opportunist pathogen, adjusts its metabolism to cope with iron deprivation within the host. We investigated the potential role of small non-coding RNAs (sRNAs) in dictating this process. A single sRNA, named here IsrR, emerged from a competition assay with tagged-mutant libraries as being required during iron starvation. IsrR is iron-repressed and predicted to target mRNAs expressing iron-containing enzymes. Among them, we demonstrated that IsrR down-regulates the translation of mRNAs of enzymes that catalyze anaerobic nitrate respiration. The IsrR sequence reveals three single-stranded C-rich regions (CRRs). Mutational and structural analysis indicated a differential contribution of these CRRs according to targets. We also report that IsrR is required for full lethality of S. aureus in a mouse septicemia model, underscoring its role as a major contributor to the iron-sparing response for bacterial survival during infection. IsrR is conserved among staphylococci, but it is not ortholog to the proteobacterial sRNA RyhB, nor to other characterized sRNAs down-regulating mRNAs of iron-containing enzymes. Remarkably, these distinct sRNAs regulate common targets, illustrating that RNA-based regulation provides optimal evolutionary solutions to improve bacterial fitness when iron is scarce.
A forskolin-mediated increase in cAMP promotes T helper cell differentiation into the Th1 and Th2 subsets rather than into the Th17 subset
Authors: Daďová Petra , Mikulová Antónia , Jaroušek Radim , Uldrijan Stjepan , Kubala Lukáš 
Published: June 2022

AbstractThe cyclic adenosine monophosphate (cAMP) signaling pathway is involved in various physiological and pathophysiological processes. Forskolin (FSK), a labdane diterpene well known as an activator of cAMP production, is suggested to possess significant immunomodulatory potential. However, the specific effects of elevated cAMP levels caused by the FSK-mediated activation of adenylate cyclase (AC) on T helper (Th) cell differentiation and functions are still unclear. We speculated that the increased levels of cAMP in Th cells affect the differentiation program of distinct Th populations differently, in particular the development of Th1, Th2, and Th17 subsets. Only minor changes in the expressions of isoforms of ACs and phosphodiesterases (PDE), enzymes responsible for the degradation of cAMP, were observed in differentiating human Th cells with prevailingADCY1, ADCY3, ADCY7, andADCY9andPDE3B,PDE4A/B/D,PDE7A/B, andPDE8Aisoforms. FSK mediated elevation in Th1-specific markers reinforcing the Th1 cell phenotype. The differentiation of Th2 was not altered by FSK, though cell metabolism was affected. In contrast, the Th17 immunophenotype was severely suppressed leading to the highly specific upregulation of the level of CXCL13. The causality between FSK-elicited cAMP production and the observed modulation of Th2 differentiation was proven by using cAMP inhibitor 2’,5’-dideoxyadenosine that reverted the FSK effects. Overall, an FSK-mediated cAMP increase has an effect on Th1, Th2 and Th17 differentiation and can contribute to the identification of novel therapeutic targets for the treatment of Th cell-related pathological processes.
An ERK-dependent molecular switch antagonizes fibrosis and promotes regeneration in spiny mice (Acomys)
Authors: Tomasso Antonio , Bartscherer Kerstin , Seifert Ashley W. 
Published: June 2022

AbstractAlthough most mammals heal wounds with scar tissue, spiny mice (Acomys cahirinus) naturally regenerate skin and complex musculoskeletal tissues. The core signaling pathways driving mammalian tissue regeneration are poorly characterized. Here, we show that MAPK/ERK signaling acts as a major hub directing cellular injury responses towards regeneration. While immediate ERK activation was a shared feature of scarring (Mus musculus) and regenerating (Acomys) wounds, ERK activity was only sustained during regeneration. Upon ERK inhibition, theAcomyswound microenvironment exhibited key hallmarks of fibrosis, including a pro-scarring matrisome, epidermal differentiation and reduced proliferation. These findings indicate that ERK inhibition shifts tissue regeneration towards fibrosis. Conversely, the ectopic release of ERK activators (FGF/Neuregulin) in fibrotic scars, stimulated a pro-regenerative matrisome, cell proliferation and hair follicle neogenesis, thus promoting skin regeneration. Our data provide new insights into why some mammals regenerate better than others and open avenues to reverse fibrosis in favor of regeneration.TeaserFGF2 and NRG1 stimulate skin and hair follicle regeneration through ERK-mediated control of cell behavior in adult mammals.