bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health-Related Quality of Life and psychological distress of adolescents during the COVID-19 pandemic in Geneva
Authors: Dumont Roxane , Richard Viviane , Baysson Hélène , Lorthe Elsa , Piumatti Giovanni , Schrempft Stephanie , Wisniak Ania , Barbe Rémy P. , Posfay-Barbe Klara M. , Guessous Idris , Stringhini Silvia 
Published: September 2021

AbstractPurposeOur objective was to assess adolescent’s Health-Related Quality of Life (HRQoL) and psychological distress, from their own and their parents’ perspective, and to examine associated risk factors during the COVID-19 pandemic in Geneva, Switzerland.MethodsA random sample of adolescents, aged 14-17 years, and their families was invited to a serosurvey in November and December 2020. Adolescents’ HRQoL was evaluated using the validated adolescent-reported KIDSCREEN-10 and parent-reported KINDL®scales. Psychological distress was assessed with self-reported sadness and loneliness, and using the KINDL®emotional well-being scale. Risk factors for adolescents’ low HRQoL and psychological distress were identified using generalized estimating equations and both adolescents’ and their parents’ perceptions were compared.ResultsAmong 240 adolescents, 11% had a low HRQoL, 35% reported sadness and 23% reported loneliness. Based on parents’ perception, 12% of the adolescents had a low HRQoL and 16% a low emotional well-being. Being a girl (aOR=3.29; 95%CI: 1.64-6.57), increased time on social media (aOR=2.05; 95%CI: 1.08-3.88), parents’average to poormood (aOR=2.81; 95%CI: 1.21-6.56) andaverage to poorhousehold financial situation (aOR=2.30; 95%CI: 1.00-5.29) were associated with an increased risk of sadness. Mismatches between adolescents’ and their parents’ perception of HRQoL were more likely for girls (aOR=2.88; 95%CI: 1.54-5.41) and in households with lower family well-being (aOR=0.91; 95%CI: 0.86-0.96).ConclusionA meaningful proportion of adolescents experienced low well-being during the second wave of COVID-19. Adolescents living in underprivileged or distressed families seemed particularly affected. Monitoring is necessary to evaluate the long-term effects of the pandemic on adolescents.Implications and ContributionThis study describes the psychological well-being of a population-based sample of adolescents in Geneva, Switzerland amid the COVID-19 pandemic, and identifies adolescents at risk of distress. This study provides further insight by comparing adolescents’ well-being as reported by themselves and their parents.
HUMORAL AND CELLULAR IMMUNOGENICITY and SAFETY UP TO 4 MONTHS AFTER VACCINATION WITH BNT162B2 mRNA COVID-19 VACCINE IN HEART AND LUNG TRANSPLANTED YOUNG ADULTS
Authors: Cotugno Nicola , Pighi Chiara , Morrocchi Elena , Ruggiero Alessandra , Amodio Donato , Medri Chiara , Colagrossi Luna , Russo Cristina , Cesare Silvia Di , Santilli Veronica , Manno Emma Concetta , Zangari Paola , Giancotta Carmela , Bernardi Stefania , Nicolosi Luciana , Degli Atti Marta Ciofi , Raponi Massimiliano , Zaffina Salvatore , Alfieri Sara , Kirk Richard , Perno Carlo Federico , Rossi Paolo ,   CONVERS study Team, Amodeo Antonino , Palma Paolo 
Published: September 2021

ABSTRACTBackgroundImmunizations among vulnerable population, including solid organ transplant recipients (SOT), present suboptimal responses at vaccination and over time. We investigated safety and immunogenicity of the BNT162B2 mRNA COVID-19 vaccine in 34 SOT young adults as compared to 36 healthy controls (HC).Methodsimmunogenicity was measured through the analysis of anti SARS-CoV2 IgG Antibodies and antigen specific CD4 T cells (CD40L+), detected by flow cytometry before vaccination, 21 days after priming (T21), 7 days after booster dose (T28) and 2-4 months after priming (T120). Baseline T and B cell immune phenotype was deeply investigated. The safety profile was investigated by close monitoring and self-reported diary.ResultsAnti-S and anti-Trimeric Ab responses were significantly lower in SOT vs HC at T21 (p<0.0001) and at T28 (p<0.0001). Ten out of 34 SOT (29%) at T28 and 3 out of 33 (9%) at T120 had undetectable SARS-CoV-2 IgG. The analysis of SARS-CoV-2 specific CD4 T cells showed lower CD40L expression after in vitro stimulation in SOT compared to HC. Lower frequencies of memory B cells were found in patients not responding to vaccination. Lack of seroconversion was higher in patients treated with mycophenolate (p=0.0005). The vaccination was safe and well tolerated. Only short-term adverse events, were reported and no hospitalization or graft rejection were observed after vaccinations.ConclusionsThese data show that SOT have a suboptimal immune response following mRNA vaccinations as compared to HC. Alternative strategies should be investigated to improve the immunization against SARS-CoV-2 in these patients.
Childhood Asthma and COVID-19: A Nested Case-Control Study
Authors: Gaietto Kristina , Freeman Megan Culler , DiCicco Leigh Anne , Rauenswinter Sherry , Squire Joseph R , Aldewereld Zachary , Iagnemma Jennifer , Campfield Brian T , Wolfson David , Kazmerski Traci M , Forno Erick 
Published: September 2021

ABSTRACTBackgroundMost pediatric studies of asthma and COVID-19 to date have been ecological, which offer limited insight. We evaluated the association between asthma and COVID-19 at an individual level.MethodsUsing data from prospective clinical registries, we conducted a nested case-control study comparing three groups: children with COVID-19 and underlying asthma (“A+C” cases); children with COVID-19 without underlying disease (“C+” controls); and children with asthma without COVID-19 (“A+” controls).ResultsThe cohort included 142 A+C cases, 1110 C+ controls, and 140 A+ controls. A+C cases were more likely than C+ controls to present with dyspnea and wheezing, to receive pharmacologic treatment including systemic steroids (all p<0.01), and to be hospitalized (4.9% vs 1.7%, p=0.01). In the adjusted analysis, A+C cases were nearly 4 times more likely to be hospitalized than C+ controls (adjusted OR=3.95 [95%CI=1.4-10.9]); however, length of stay and respiratory support level did not differ between groups. Among A+C cases, 8.5% presented with an asthma exacerbation and another 6.3% developed acute exacerbation symptoms shortly after testing positive for SARS-CoV-2. Compared to historic A+ controls, A+C cases had less severe asthma, were less likely to be on controller medications, and had better asthma symptom control (all p<0.01).ConclusionsIn our cohort, asthma was a risk factor for hospitalization in children with COVID-19, but not for worse COVID-19 outcomes. SARS-CoV-2 does not seem to be a strong trigger for pediatric asthma exacerbations. Asthma severity was not associated with higher risk of COVID-19.Key messagesIn this pediatric cohort, asthma was a risk factor for hospitalization in children with COVID-19, but not for worse COVID-19 outcomes. Baseline asthma severity was not associated with higher risk of COVID-19, and SARS-CoV-2 did not seem to be a strong trigger for pediatric asthma exacerbations.
The impact of health literacy-sensitive design and heart age in a cardiovascular disease prevention decision aid: randomised controlled trial and end user testing
Authors: Bonner Carissa , Batcup Carys , Ayre Julie , Cvejic Erin , Trevena Lyndal , McCaffery Kirsten , Doust Jenny 
Published: September 2021

ABSTRACTIntroductionShared decision making is as an essential principle for cardiovascular disease (CVD) prevention, where asymptomatic people are considering lifelong medication and lifestyle changes. This project aimed to develop and evaluate the first literacy-sensitive CVD prevention decision aid (DA) developed for people with low health literacy, and investigate the impact of literacy-sensitive design and heart age.MethodsWe developed the standard DA based on international standards. The literacy-sensitive version included simple language, supporting images, white space and a lifestyle action plan. A randomised trial included 859 people aged 45-74 using a 3 (DA: standard, literacy-sensitive, control) x 2 (heart age: heart age + percentage risk, percentage risk only) factorial design, with outcomes including prevention intentions/behaviours, gist/verbatim knowledge of risk, credibility, emotional response and decisional conflict. We iteratively improved the literacy-sensitive version based on end user testing interviews with 20 people with varying health literacy levels.ResultsImmediately post-intervention (n=859), there were no differences between the DA groups on any outcome. The heart age group was less likely to have a positive emotional response, perceived the message as less credible, and had higher gist/verbatim knowledge of heart age risk but not percentage risk. After 4 weeks (n=596), the DA groups had better gist knowledge of percentage risk than control. The literacy-sensitive decision aid group had higher fruit consumption, and the standard decision aid group had better verbatim knowledge of percentage risk. Verbatim knowledge was higher for heart age than percentage risk amongst those who received both.DiscussionThe literacy-sensitive DA resulted in increased knowledge and lifestyle change for participants with varying health literacy levels and CVD risk results. Adding heart age did not increase lifestyle change intentions or behaviour but did affect psychological outcomes, consistent with previous findings.MeSH TermsHealth Literacy, Cardiovascular Diseases, Decision Making (Shared), Life Style, Decision Support Techniques
Proton export drives the Warburg Effect
Authors: Russell Shonagh , Xu Liping , Kam Yoonseok , Abrahams Dominique , Verduzco Daniel , Johnson Joseph , Epstein Tamir , Ruiz Epifanio , Lloyd Mark C. , Wojtkowiak Jonathan , Lopez Alex S. , Bui Marilyn M. , Gillies Robert J. , Swietach Pawel , Ordway Bryce 
Published: September 2021

AbstractAggressive cancers commonly ferment glucose to lactic acid at high rates, even in the presence of oxygen. This is known as aerobic glycolysis, or the “Warburg Effect”. It is widely assumed that this is a consequence of the upregulation of glycolytic enzymes. Oncogenic drivers can increase the expression of most proteins in the glycolytic pathway, including the terminal step of exporting H+ equivalents from the cytoplasm. Proton exporters maintain an alkaline cytoplasmic pH, which can enhance all glycolytic enzyme activities, even in the absence of oncogene-related expression changes. Based on this observation, we hypothesized that increased uptake and fermentative metabolism of glucose could be driven by the expulsion of H+ equivalents from the cell. To test this hypothesis, we stably transfected lowly-glycolytic MCF-7, U2-OS, and glycolytic HEK293 cells to express proton exporting systems: either PMA1 (yeast H+-ATPase) or CAIX (carbonic anhydrase 9). The expression of either exporter in vitro enhanced aerobic glycolysis as measured by glucose consumption, lactate production, and extracellular acidification rate. This resulted in an increased intracellular pH, and metabolomic analyses indicated that this was associated with an increased flux of all glycolytic enzymes upstream of pyruvate kinase. These cells also demonstrated increased migratory and invasive phenotypes in vitro, and these were recapitulated in vivo by more aggressive behavior, whereby the acid-producing cells formed higher grade tumors with higher rates of metastases. Neutralizing tumor acidity with oral buffers reduced the metastatic burden. Therefore, cancer cells with increased H+ export increase intracellular alkalization, even without oncogenic driver mutations, and this is sufficient to alter cancer metabolism towards a Warburg phenotype.
Calculating the force-dependent unbinding rate of biological macromolecular bonds from the force-ramp optical trapping assays
Authors: Paul Apurba , Alper Joshua 
Published: September 2021

AbstractThe non-covalent biological bonds that constitute protein-protein or protein-ligand interactions play crucial roles in many cellular functions, including mitosis, motility, and cell-cell adhesion. The effect of external force (F) on the unbinding rate (koff(F)) of macromolecular interactions is a crucial parameter to understanding the mechanisms behind these functions. Optical tweezer-based single-molecule force spectroscopy is frequently used to obtain quantitative force-dependent dissociation data on slip, catch, and ideal bonds. However, analyses of this data using dissociation time or dissociation force histograms often quantitatively compare bonds without fully characterizing their underlying biophysical properties. Additionally, the results of histogram-based analyses can depend on the rate at which force was applied during the experiment and the experiment’s sensitivity. Here, we present an analytically derived cumulative distribution function-like approach to analyzing force-dependent dissociation force spectroscopy data. We demonstrate the benefits and limitations of the technique using stochastic simulations of various bond types. We show that it can be used to obtain the detachment rate and force sensitivity of biological macromolecular bonds from force spectroscopy experiments by explicitly accounting for loading rate and noisy data. We also discuss the implications of our results on using optical tweezers to collect force-dependent dissociation data.
Identification of topoisomerase as a precision-medicine target in chromatin reader SP140-driven Crohn’s disease
Authors: Amatullah Hajera , Digumarthi Sreehaas , Fraschilla Isabella , Adiliaghdam Fatemeh , Bonilla Gracia , Wong Lai Ping , Sadreyev Ruslan I. , Jeffrey Kate L. 
Published: September 2021

SummaryHow mis-regulated chromatin directly impacts human immunological disease is poorly understood. Speckled Protein 140 (SP140) is an immune-restricted PHD and bromodomain-containing chromatin ‘reader’ whose loss-of-function associates with Crohn’s disease (CD), multiple sclerosis (MS) and chronic lymphocytic leukemia (CLL). However, mechanisms underlying SP140-driven pathogenicity and therapeutic approaches that rescue SP140 remain unexplored. Using a global proteomic strategy, we identified SP140 as a repressor of topoisomerases (TOP) that maintains heterochromatin and immune cell fate. In humans and mice, SP140 loss resulted in unleashed TOP activity, genome instability, severely compromised lineage-defining and microbe-inducible innate transcriptional programs and defective bacterial killing. Pharmacological inhibition of TOP1 or TOP2 rescued these defects. Furthermore, exacerbated colitis was restored with TOP1 or TOP2 inhibitors in Sp140−/− mice, but not wild-type mice, in vivo. Collectively, we identify SP140 as a repressor of topoisomerases and reveal repurposing of TOP inhibition as a precision strategy for reversing SP140-driven immune disease.
Symmetry reduction in a hyperpolarization-activated homotetrameric ion channel
Authors: Dickinson Miles Sasha , Gupta Meghna , Pourmal Sergei , Bi Maxine , Stroud Robert M. 
Published: September 2021

AbstractPlants obtain nutrients from the soil via transmembrane transporters and channels in their root hairs, from which ions radially transport in towards the xylem for distribution across the plant body. We determined structures of the hyperpolarization-activated channel AKT1 from Arabidopsis thaliana, which mediates K+ uptake from the soil into plant roots. These structures of AtAKT1 embedded in lipid nanodiscs show that the channel undergoes a reduction of C4 to C2 symmetry, possibly to regulate its electrical activation.
Did the COVID-19 pandemic result in more family physicians stopping practice? Results from Ontario, Canada
Authors: Kiran Tara , Green Michael E. , Wu Fangyun C. , Kopp Alexander , Latifovic Lidija , Frymire Eliot , Glazier Richard H. 
Published: September 2021

AbstractPurposeTo understand changes in family physician practice patterns and whether more family physicians stopped working during the COVID-19 pandemic compared to previous years.MethodsWe analyzed administrative data from Ontario, Canada two ways: cross-sectional and longitudinal. First, we identified the percentage and characteristics of all family physicians who had a minimum of 50 billing days in 2019 but no billings during the first six months of the pandemic. Second, for each year from 2010 to 2020, we calculated the percentage of physicians who billed for services in the first quarter of the calendar year but submitted no bills between April and September of the given year.ResultsWe found 3.1% of physicians working in 2019 (N=385/12,247) reported no billings in the first six months of the pandemic. Compared with other family physicians, a higher portion were age 75 or older (13.0% vs. 3.4%, p<0.001), had fee-for-service reimbursement (38% vs 25%, p<0.001), and had a panel size under 500 patients (40% vs 25%, p<0.001). Between 2010 and 2019, an average of 1.6% of physicians who practiced in the first quarter had no billings in each of the second and third quarters of the calendar year compared to 3.0% in 2020 (p<0.001).ConclusionsApproximately twice as many family physicians stopped work in Ontario, Canada during COVID-19 compared to previous years, but the absolute number was small and those who did had smaller patient panels. More research is needed to understand the impact on primary care attachment and access to care.
Crowding within synaptic junctions influence the degradation of adenoside nucleotides by CD39 and CD73 ectonucleotidases
Authors: Rahmaninejad Hadi , Pace Tom , Kekenes-Huskey Peter 
Published: September 2021

1AbstractSynapsed cells can communicate using exocytosed nucleotides like adenosine triphosphate (ATP). Ectonucleotidases localized to a synaptic junction degrade such nucleotides into metabolites like adenosine monophosphate (AMP) or adenosine, oftentimes in a sequential manner. CD39 and CD73 are a representative set of coupled ectonucleotidases, where CD39 first converts ATP and adenosine diphosphate (ADP) into AMP, after which the AMP product is dephosphorylated into adenosine by CD73. Hence, CD39/CD73 help shape cellular responses to extracellular ATP. In a previous study [1] we demonstrated that the rates of coupled CD39/CD73 activity within synapse-like junctions are strongly controlled by the enzymes’ co-localization, their surface charge densities, and the electrostatic potential of the surrounding cell membranes. In this study, we demonstrate that crowders within a synaptic junction, which can include globular proteins like cytokines and membrane-bound proteins, impact coupled CD39/CD73 electronucleotidase activity and in turn, the availability of intrasynapse ATP. Specifically, we simulated a spatially-explicit, reaction-diffusion model for the coupled conversion of ATP→AMP and AMP→adenosine in a model synaptic junction with crowders via the finite element method. Our modeling results suggest that the association rate for ATP to CD39 is strongly influenced by the density of intrasynaptic protein crowders, as increasing crowder density suppressed ATP association kinetics. Much of this suppression can be rationalized based on a loss of configurational entropy. The surface charges of crowders can further influence the association rate, with the surprising result that favorable crowder/nucleotide electrostatic interactions can yield CD39 association rates that are faster than crowder-free configurations. However, attractive crowder/nucleotide interactions decrease the rate and efficiency of adenosine production, which in turn increases the availability of ATP and AMP within the synapse relative to crowder-free configurations. These findings highlight how CD39/CD73 ectonucleotidase activity, electrostatics and crowding within synapses influence the availability of nucleotides for intercellular communication.
The Incubascope : a simple, compact and large field of view microscope for long-term imaging inside an incubator
Authors: Badon Amaury , Andrique Laetitia , Mombereau Amaël , Rivet Louis , Boyreau Adeline , Nassoy Pierre , Recher Gaëlle 
Published: September 2021

Optical imaging has rapidly evolved in the last decades. Sophisticated microscopes allowing optical sectioning for 3D imaging or sub-diffraction resolution are available. Due to price and maintenance issues, these microscopes are often shared between users in facilities. Consequently, long term access is often prohibited and does not allow to monitor slowly evolving biological systems or to validate new models like organoids. Preliminary coarse long-term data that do not require acquisition of terabytes of high-resolution images are important as a first step. By contrast with expansive all-in-one commercialized stations, standard microscopes equipped with incubator stages offer a more cost-effective solution despite imperfect long run atmosphere and temperature control.Here, we present the Incubascope, a custom-made compact microscope that fits into a table-top incubator. It is cheap and simple to implement, user-friendly and yet provides high imaging performances. The system has a field of view of 5.5 × 8 mm2, a 3 μm resolution, a 10 frames/second acquisition rate, and is controlled with a Python-based graphical interface. We exemplify the capabilities of the Incubascope on biological applications such as the hatching of Artemia salina eggs, the growth of the slime mold Physarum polycephalum and of encapsulated spheroids of mammalian cells.
Role of Disulfide Bonds in Membrane Partitioning of a Viral Peptide
Authors: Sikdar Samapan , Banerjee Manidipa , Vemparala Satyavani 
Published: September 2021

AbstractThe importance of disulfide bond in mediating viral peptide entry into host cells is well known. In the present work, we elucidate the role of disulfide (SS) bond in partitioning mechanism of membrane active Hepatitis A Virus-2B (HAV-2B) peptide, which harbours three cysteine residues promoting formation of multiple SS-bonded states. The inclusion of SS-bond not only results in a compact conformation but also induces distorted α-helical hairpin geometry in comparison to SS-free state, resulting in reduced hydrophobic exposure. Owing to this, the partitioning of HAV-2B peptide is completely or partly abolished. In a way, the disulfide bond regulates the partitioning of HAV-2B peptide, such that the membrane remodelling effects of this viral peptide are significantly reduced. The current findings may have potential implications in drug designing, targeting the HAV-2B protein by promoting disulfide bond formation within its membrane active region.