bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of COVID-19 on lifestyle and mental wellbeing in a drought-affected rural Australian population: A mixed method approach
Authors: Carlson Jack , Chan Kevin , Gray Jonah , Xue Houston , Reed Krista , Bailey Jannine K , Dutton Tegan , Osuagwu Uchechukwu Levi , Vines Robyn 
Published: September 2022

AbstractBackgroundThe Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented social and economic disruption, accompanied by the enactment of a multitude of public health measures to restrain disease transmission. These public health and social measures have had a considerable impact on lifestyle and mental wellbeing, which has been well-studied in metropolitan populations, but very little in rural populations. Additionally, the development and use of a standardised scoring system for an overall assessment of patient lifestyle management, and monitoring of changes in these, may be warranted in clinical practice.MethodsThe associations between psychological distress and changes in SNAPS health behaviours (smoking, nutrition, alcohol, physical activity, sleep) since the onset of COVID-19 in rural Australia were examined. A cross-sectional anonymous online survey was distributed among adults in the Western New South Wales Primary Health Network in August 2020. The survey included measures of psychological distress, income, disposition, lifestyle factors and behaviours during the pandemic, as well as changes in lifestyle due to COVID-19. A novel Global Lifestyle Score (GLS) was generated as a holistic assessment of lifestyle across multiple domains.ResultsThe survey was completed by 308 individuals (modal age group: 45-54 years old, 86.4% female). High distress on the K5 scale was present in over one-third of respondents (n=98, 34.3%). Negative change was reported for sleep (24.4%), nutrition (14.3%), alcohol (17.8%), physical exercise (33.8%) and smoking (26.6%) since the onset of the pandemic. Additionally, changes in sleep, nutrition, physical activity and smoking were associated with distress. Respondents with a poor lifestyle (GLS) during the pandemic were significantly more distressed. Perceived COVID-19 impact was associated with high distress, level of drought impact and loss of income.ConclusionHigh rates of distress amongst rural Australians during the COVID-19 pandemic was linked, worsening lifestyles as measured by the GLS and loss of income. Lifestyle promotion strategies should be considered by health professionals for the management of crisis-related distress. Further research may explore the impact of COVID-19 on a larger population, including a greater proportion of male respondents, and the impact of modifying lifestyle factors on the reduction of distress in the context of a stressor such as this pandemic.
Synapsin autoantibodies during pregnancy are associated with fetal abnormalities
Authors: Bünger Isabel , Kreye Jakob , Makridis Konstantin , Höltje Markus , Rasmussen Helle Foverskov , van Hoof Scott , Ullrich Tim , Sedlin Eva , Hoffmann Christian , Milovanovic Dragomir , Paul Friedemann , Meckies Jessica , Verlohren Stefan , Henrich Wolfgang , Chaoui Rabih , Kaindl Angela , Prüss Harald 
Published: September 2022

AbstractAnti-neuronal autoantibodies can be transplacentally transferred during pregnancy and may cause detrimental effects on fetal development. It is unclear whether autoantibodies against synapsin-I, one of the most abundant synaptic proteins, are associated with developmental abnormalities in humans. We prospectively recruited a cohort of 263 pregnant women and detected serum synapsin-I IgG autoantibodies in 13.3%. Seropositivity was strongly associated with abnormalities of fetal development including intrauterine growth retardation. This finding indicates that these autoantibodies may be clinically useful developmental biomarkers and/or even directly participate in the disease process, thus being amenable to antibody-targeting interventional strategies in the future.
Development of Q-LAAD, an allonamer-based antigen test for the rapid detection of SARS-CoV-2
Authors: Overgaard Elise , Li Shiwei , Covert Hunter J. , Tawara Ken , Poe Aidan M. , Shults N. Hagan , Chernish Aliona A. , Sweet Brandi , Gonzales Cara R. , Gibard Clémentine F.N. , Burden Steven J. 
Published: September 2022

ABSTRACTThe SARS-CoV-2 virus has spread globally causing coronavirus disease 2019 (COVID-19). Rapidly and accurately identifying viral infections is an ongoing necessity. We used the systematic evolution of ligands by exponential enrichment (SELEX) technique to produce a DNA allonamer with two distinct binding domains made allosteric through a linker section; one domain binds SARS-CoV-2 spike (S) protein, inducing a conformational change that allows the reporter domain to bind a fluorescent reporter molecule. We used bead-based fluorescence and immunofluorescence assays to confirm the allonamer’s affinity and specificity for S-protein and confirmed that the allonamer can bind to S-proteins with mutations corresponding to those of the alpha, beta, gamma, and delta variants. We then developed the allonamer-based Quantum-Logic Aptamer Analyte Detection (Q-LAAD) test, a rapid, high-throughput antigen test for qualitative detection of SARS-CoV-2 in clinical settings. We validated Q-LAAD against retrospective and prospective clinical anterior nasal swab samples collected from symptomatic patients suspected of having COVID-19. Q-LAAD showed 97% sensitivity and 100% specificity compared to the RT-qPCR assay. Q-LAAD has a limit of detection (LOD) of 1.88 TCID50/mL, is cost-effective and convenient, and requires only a common fluorescence plate reader. Q-LAAD may be a useful clinical diagnostic tool in the fight against SARS-CoV-2.
HIGHLIGHTSAllonamers are allosterically-regulated DNA aptamers with multiple binding pocketsQ-LAAD uses allonamers to detect SARS-CoV-2 spike protein in clinical samplesQ-LAAD has high sensitivity and specificity and a low limit of detectionQ-LAAD can detect spike proteins from multiple SARS-CoV-2 variantsQ-LAAD is a dynamic, cost-effective rapid antigen test for detection of SARS-CoV-2
Preponderant Myosin Super-Relaxed State In Skeletal Muscle From Endurance Athletes
Authors: Lewis Christopher T. A. , Tabrizian Lee , Nielsen Joachim , Laitila Jenni , Beck Thomas N. , Aagaard Per , Hokken Rune , Laugesen Simon , Ingersen Arthur , Andersen Jesper L. , Soendenbroe Casper , Helge Jørn W. , Dela Flemming , Larsen Steen , Sahl Ronni E. , Rømer Tue , Hansen Mikkel T. , Frandsen Jacob , Suetta Charlotte , Ochala Julien 
Published: September 2022

AbstractIt has recently been established that myosin, the molecular motor protein, is able to exist in two conformations in relaxed skeletal muscle. These conformations are known as super-relaxed (SRX) and disordered-relaxed (DRX) states and are finely balanced to optimize skeletal muscle metabo-lism. Indeed, SRX myosins are thought to have a 10-fold reduction in ATP turnover compared to DRX myosins. Here, we investigated whether chronic physical activity in humans would be associated with changes in the proportions of SRX and DRX skeletal myosins. For that, we isolated mus-cle fibres from various athletic and sedentary populations and ran a loaded Mant-ATP chase proto-col. We observed that, in endurance-trained athletes, the amounts of myosin molecules in the SRX state was significantly greater than in age-matched sedentary individuals or than in strength athletes. To further assess whether this change would have an impact on the potency of a SRX-inducing pharmacological compound, Mavacamten, we performed similar analyses as above with and without the drug in muscle fibres from endurance athletes. Surprisingly, we found that 0.3 μM of Mava-camten had only marginal effects. Altogether, our results indicate that chronic endurance training-status influences resting skeletal myosin conformations, and Mavacamten potency. Our findings also emphasize that environmental stimuli such as exercise can re-wire the molecular metabolism of human skeletal muscle through myosin.SummaryLewiset al., investigate how training-status influences myosin conformations involved in the resting metabolism of skeletal muscle. They find that, in endurance-trained athletes, skeletal myosin preferentially adopts an energy-saving conformation known as super-relaxed state, lowering the metabolic rate and affecting the potency of a super-relaxed state-inducing drug, Mavacamten.
Marginal Zone B Cells are Necessary for the Formation of Anti-Donor IgG After Allogeneic Sensitization
Authors: Kallarakal Melissa A. , Cohen Gregory , Ibukun Francis I. , Krummey Scott M. 
Published: September 2022

ABSTRACTThe formation of anti-MHC antibody is a significant barrier to improved outcomes in organ transplantation. Patients with pre-formed anti-HLA antibodies have limited options for suitable donors, and the formation of donor-specific anti-HLA antibodies after transplantation is a harbinger of graft rejection. Despite the recognized importance of anti-HLA antibodies, the mechanisms responsible for the differentiation of B cells after exposure to allogeneic antigen are poorly understood. In order to evaluate the differentiation of B cells in response to allogeneic antigen, we used a model of H-2bC57/Bl6 sensitization with H-2dantigen. We found that although the formation of anti-H-2dIgG was robust, few class switched B cells and germinal center B cells were formed. Sensitization induced weak expression of classical memory B cell markers, but we observed populations of CD21+and IRF4+B cells, that corresponded to an increase in the frequency of marginal zone phenotype B cells after sensitization. Depletion of marginal zone B cells prior to sensitization resulted in a significant dimunition of anti-H-2dIgG and also fewer germinal center B cells. These results demonstrate a previously unappreciated role for marginal zone B cells as a reservoir of alloreactive B cells that are activated by allogeneic antigen.
Leveraging vision to understand curiosity
Authors: Cohanpour Michael , Aly Mariam , Gottlieb Jacqueline 
Published: September 2022

AbstractHumans are immensely curious and motivated to reduce uncertainty. Inspired by studies of sensory uncertainty, we hypothesized that visual areas provide multivariate representations of uncertainty, which are read out by higher-order areas that encode confidence and, ultimately, translated into curiosity. During fMRI, participants rated their confidence in identifying distorted images of animals and objects and their curiosity to see the clear image. We found that curiosity peaked at low confidence. To link sensory certainty and curiosity, we estimated “OTC Certainty” as the product of absolute and relative evidence for animals vs. object categories in occipitotemporal cortex (OTC) while participants viewed the distorted image. OTC Certainty negatively correlated with curiosity, while univariate activity in two frontal regions – vmPFC and ACC – positively correlated with confidence. The relationship between OTC certainty and curiosity was mediated by the vmPFC but not ACC. The results reveal neural mechanisms that generate curiosity from representations of uncertainty.
Mitochondria dysregulation contributes to secondary neurodegeneration progression post-contusion injury in human 3D in vitro triculture brain tissue model
Authors: Liaudanskaya Volha , Fiore Nicholas J , Zhang Yang , Milton Yuka , Kelly Marilyn F , Coe Marly , Barreiro Ariana , Rose Victoria K , Shapiro Matthew R , Mullis Adam S , Shevzov-Zebrun Anna , Blurton-Jones Mathew , Whalen Michael J , Symes Aviva J , Georgakoudi Irene , Nieland Thomas JF , Kaplan David L 
Published: September 2022

AbstractTraumatic Brain injury-induced disturbances in mitochondrial fission-and-fusion dynamics have been linked to the onset and propagation of neuroinflammation and neurodegeneration. However, cell-type-specific contributions and crosstalk between neurons, microglia, and astrocytes in mitochondria-driven neurodegeneration after brain injury remain undefined. We developed a human three-dimensional in vitro triculture tissue model of a contusion injury, composed of neurons, microglia, and astrocytes, and examined the contributions of mitochondrial dysregulation to neuroinflammation and progression of injury-induced neurodegeneration. Pharmacological studies presented here suggest that fragmented mitochondria released by microglia are a key contributor to secondary neuronal damage progression after contusion injury, a pathway that requires astrocyte-microglia crosstalk. Controlling mitochondrial dysfunction thus offers an exciting option for the development of therapies for TBI patients.
When should healthcare workers with COVID-19 return to work? An analysis of follow-up antigen test results after a positive COVID test
Authors: Baffoe-Bonnie Anthony , Swann Mandy C. , Kim Hyun Sue 
Published: September 2022

AbstractBackgroundUnder CDC’s guidance for mitigating healthcare worker (HCW) staffing shortages, COVID-positive HCW may return to work as early as five days after their initial positive test without a negative antigen test, if symptoms are improving. Recent studies suggest a robust correlation between a positive COVID-19 antigen test and infectiousness.MethodsFrom January to June 2022, HCW employed by a large health system who tested positive for COVID on a PCR test were instructed to isolate and return for a rapid antigen test on day 5 or later if they had been fever-free for 24 hours and their symptoms were improving. We conducted chi-squared tests and a multivariate logistic regression to assess the association between demographic characteristics, vaccination status, and days from the initial positive PCR test on RTW antigen test results.ResultsCompared to day 5, HCW had a lower odds of a positive antigen result on day 7 (OR: 0.39, p<0.0001) and after at least 8 days (OR: 0.16, p<0.0001). Unexpectedly, a positive antigen result was more likely among HCW who were vaccinated (OR: 1.41, p <0.05), boosted for more than 90 days prior (OR: 2.21, p<0.0001), and boosted within 90 days (OR: 2.08, p < 0.01) compared to not being vaccinated.ConclusionsOur findings suggest that HCW returning to work before day 7 following a positive PCR test may still be infectious and future guidelines addressing contingency staffing should reflect these findings in order to minimize possible transmission in the healthcare setting. The finding that boosted individuals had over twice the odds of returning positive on the follow up antigen test compared to unvaccinated HCWs merits additional research.
FLOCK STASIS DRIVES FLYING SPEED IN PIGEONS, WHILE ARTIFICIAL MASS ADDITIONS DO NOT
Authors: Sankey Daniel W. E. , Portugal Steven J. 
Published: September 2022

AbstractAnimals are characterised, in part, by their use of voluntary movement, which is used to explore and exploit resources from their surrounding environment. Movement can therefore benefit animals, but will cost them their energetic reserves. Thus, adaptations for faster movements with negligible increases in energy expenditure will likely evolve via natural selection. Individual and social-level mechanisms have been shown to optimise this speed/energetic trade-off. Nevertheless, studies of social-level traits typically ignore individual variation, which is a cornerstone principle in evolutionary ecology. Furthermore, how individual phenotype interacts with the phenotypic composition of the group to govern the cost of transport may have been entirely overlooked. We investigate speed and the energetic consequences of individual-level phenotypic differences using body mass (both natural and artificially manipulated with additional weights) of homing pigeons (Columba livia) (N =16 birds; N = 193 useable flight trajectories). We then turn to social level phenomena, and manipulate the composition of pigeon groups by body mass (N= 12 birds in four treatments; N = 192 useable flight trajectories) and leadership rank (N = 30 birds in three groups, N = 286 useable flight trajectories) following earlier leadership identification flights (N = 33 birds, N = 306 useable flight trajectories). “Natural” body mass was predictive of flying speed in solo flights, but not in groups of greater mass by composition; “artificial” mass loading had no impact on speed in solo fliers, and was not tested in groups. Groups of leader phenotypes, showed faster speeds, and greater cohesion than follower phenotype groups, both in terms of flock spread, but also in consistency of positioning within the flock (“flock stasis”) across the flight. Flock stasis was further analysed across all other group flights. Its positive impact on speed was found to be consistent across all experimental treatments. Therefore, predicting flock stasis may be critical to understanding optimal phenotypic compositions of birds, and thus the social evolution of birds which fly together. We provide evidence that greater stasis may be driven by phenotypic compositions (i.e. groups of leaders, and homogeneous mass groups) and also discuss the implications of stasis for different flocking structures (e.g. V-formations) and human crowd control.
Impact of cross-coronavirus immunity in post-acute sequelae of COVID-19
Authors: Herman Jonathan D. , Atyeo Caroline , Zur Yonatan , Cook Claire E. , Patel Naomi J. , Vanni Kathleen M. , Kowalski Emily N. , Qian Grace , Shadick Nancy A. , Laffenburger Douglas , Wallace Zachary S. , Sparks Jeffrey A. , Alter Galit 
Published: September 2022

AbstractBeyond the unpredictable acute illness caused by SARS-CoV-2, one-fifth of infections unpredictably result in long-term persistence of symptoms despite the apparent clearance of infection. Insights into the mechanisms that underlie post-acute sequelae of COVID-19 (PASC) will be critical for the prevention and clinical management of long-term complications of COVID-19. Several hypotheses have been proposed that may account for the development of PASC, including persistence of virus or the dysregulation of immunity. Among the immunological changes noted in PASC, alterations in humoral immunity have been observed in some patient subsets. To begin to determine whether SARS-CoV-2 or other pathogen specific humoral immune responses evolve uniquely in PASC, we performed comprehensive antibody profiling against SARS-CoV-2 and a panel of endemic pathogens or routine vaccine antigens using Systems Serology in a cohort of patients with pre-existing rheumatic disease who either developed or did not develop PASC. A distinct humoral immune response was observed in individuals with PASC. Specifically, individuals with PASC harbored less inflamed and weaker Fcγ receptor binding anti-SARS-CoV-2 antibodies and a significantly expanded and more inflamed antibody response against endemic Coronavirus OC43. Individuals with PASC, further, generated more avid IgM responses and developed an expanded inflammatory OC43 S2-specific Fc-receptor binding response, linked to cross reactivity across SARS-CoV-2 and common coronaviruses. These findings implicate previous common Coronavirus imprinting as a marker for the development of PASC.One Sentence SummaryThrough high dimensional humoral immune profiling we uncovered the potential importance of previous common Coronavirus imprinting as a novel marker and potential mechanism of an endotype of PASC.
EGFR-initiated endocytosis of Wnt9a and Fzd9b is required for β-catenin signaling
Authors: Nguyen Nicole , Carpenter Kelsey A. , Thurlow Kate E. , Mu Emily , Gilliland Carla , Grainger Stephanie 
Published: September 2022

AbstractCell to cell communication through secreted ligands like those encoded by the Wnt gene family is critical for development and homeostasis during organismal life. One of the bottlenecks in the Wnt field has been identifying specific ligand/receptor pairings and decoding the mechanisms for their downstream signals. We previously discovered that the Wnt9a ligand signals through the cell surface receptors Fzd9b, LRP5/6 and EGFR to promote early proliferation of hematopoietic stem cells during development. We used this exquisitely specific ligand/receptor complex as a platform to determine if Wnt9a requires endocytosis for signaling. Using fluorescently labeled, biologically active Wnt9a and Fzd9b fusion proteins, we demonstrate here that the Wnt9a receptor complex is rapidly endocytosed within one minute of contact with Fzd9b. Following this, the Wnt9a/Fzd9b complex is trafficked through the cell to early and late endosomes, lysosomes, and the endoplasmic reticulum; it is also recycled back to the membrane. Using small molecule inhibitors, genetic and siRNA approaches, we identified that mechanistically this endocytosis requires EGFR-mediated phosphorylation of the Fzd9b tail, followed by endocytosis through a caveolin and EPS15 dependent pathway. Specific modes of endocytosis and trafficking may represent one of the ways in which Wnt/Fzd specificity is established, since other Wnt ligands do not require endocytosis for activity.
Cryopreserved cGMP-compliant human pluripotent stem cells-derived immature hepatic progenitors rescue mice from acute liver failure
Authors: Gantier Malika , Rispal Raphael , Fourrier Angélique , Menoret Séverine , Delbos Frédéric , Renault Sarah , Gary Anne-Sophie , Anegon Ignacio , Nguyen Tuan Huy 
Published: September 2022

AbstractLiver transplantation remains the only curative treatment for end-stage liver diseases. Unfortunately, there is a drastic organ donor shortage. Hepatocyte transplantation emerged as a viable alternative to liver transplantation. In light of their unique expansion capabilities and their potency to be driven towards a chosen cell fate, pluripotent stem cells (PSC) are extensively studied as an unlimited cell source of hepatocytes for cell therapy. It has been previously shown that freshly prepared hepatocyte-like cells can cure mice from acute and chronic liver failures and restore liver functions. In this study, we generated human PSC-derived immature hepatic progenitors (GStemHep) using current good manufacturing practice (cGMP) compliant conditions from PSC amplification, hepatic differentiation to cell cryopreservation. These GStemHep cells present an immature hepatic phenotype (alpha-fetoprotein positive, albumin negative), secrete hepatocyte growth factor (HGF) and do not express MHC type I or II. The therapeutic potential of GStemHep was assessed in two clinically relevant models of acute liver failure. A single dose of thawed GStemHep rescue mice from sudden death caused by acetaminophen and thioacetamide-induced acute live failure, both in immunodeficient and immunocompetent animals in absence of immunosuppression. The mode of action was studied by several analytical methods including unbiased proteomic analyses. The swiftness of the therapeutic effect suggests a paracrine mechanism of action of GStemHep leading to a rapid reduction of inflammation and a rapid cytoprotective effect. Therapeutic biological effects were observed as soon as 3 hours post-cell transplantation with reduction in serum transaminases and in liver necrosis. Mode of action of GStemHep relies on alleviation of inhibition factors of liver regeneration, increase in proliferationpromoting factors and decrease liver inflammation. In conclusion, we generated cGMP-compliant human PSC-derived immature hepatic progenitors that were highly effective in treating acute liver failure. This is also the first report highlighting that human allogeneic cells could be used as cryopreserved cells and in absence of immunosuppression for a human PSC-based regenerative medicine of acute liver injuries.