bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carotid atherosclerosis in people of European, South Asian and African Caribbean ethnicity in the Southall and Brent Revisited study (SABRE)
Authors: Anbar Rayan , Chaturvedi Nish , Eastwood Sophie V. , Tillin Therese , Hughes Alun D. 
Published: July 2022

AbstractBackgroundAtherosclerotic cardiovascular disease (CVD) risk differs by ethnicity. In comparison with Europeans (EA) South Asian (SA) people in UK experience higher risk of coronary heart disease and stroke, while African Caribbean people have a lower risk of coronary heart disease but a higher risk of stroke.AimTo compare carotid atherosclerosis in EA, SA and AC participants in the Southall and Brent Revisited (SABRE) study and establish if any differences were explained by established or novel CVD risk factors.MethodsCardiovascular risk factors were measured, and carotid ultrasound was performed in 985 individuals (438 EA, 325 SA, 228 AC). Carotid plaques, and intima-media thickness (cIMT) were measured. Associations of carotid atherosclerosis with ethnicity were investigated using regression analyses, with and without adjustment for potential confounders (age, sex) and mediators (education, diabetes, hypertension, total cholesterol, HDL-C, alcohol consumption, current smoking).ResultsPrevalence of any plaque was similar in EA and SA, and lower in AC (17%, 17%, and 6% respectively; p < 0.001 by ANOVA). Total plaque area was also similar in EA and SA but reduced in AC, but there were no major differences in the maximum height or length of plaques in people with plaques by ethnic group. These ethnic differences were unaffected by adjustment for potential confounders or mediators. After adjustment for age and sex cIMT was higher in AC but this difference was attenuated by adjustment for CVD risk factors.ConclusionsPrevalence of carotid artery atherosclerotic plaques varies by ethnicity, independent of risk factors. The similarity of plaque burden in SA and EA despite established differences in CVD risk in these ethnic groups casts some doubt on the utility of carotid ultrasound as a means of assessing risk across ethnic groups.
Influence of vitamin D supplementation on SARS-CoV-2 vaccine efficacy and immunogenicity
Authors: Jolliffe David A , Vivaldi Giulia , Chambers Emma S , Cai Weigang , Li Wenhao , Faustini Sian E , Gibbons Joseph M , Pade Corinna , Richter Alex G , McKnight Áine , Martineau Adrian R 
Published: July 2022

SUMMARYBackground & AimsVitamin D deficiency has been reported to associate with impaired development of antigen-specific responses following vaccination. We aimed to determine whether vitamin D supplements might boost immunogenicity and efficacy of SARS-CoV-2 vaccination.MethodsWe conducted three sub-studies nested within the CORONAVIT randomised controlled trial, which investigated effects of offering vitamin D supplements at a dose of 800 IU/day or 3200 IU/day vs. no offer on risk of acute respiratory infections, including COVID-19, in UK adults with circulating 25-hydroxyvitamin D concentrations <75 nmol/L. Sub-study 1 (n=2808) investigated effects of vitamin D supplementation on risk of breakthrough SARS-CoV-2 infection following two doses of SARS-CoV-2 vaccine. Sub-study 2 (n=1853) investigated effects of vitamin D supplementation on titres of combined IgG, IgA and IgM (IgGAM) anti-Spike antibodies in eluates of dried blood spots collected after SARS-CoV-2 vaccination. Sub-study 3 (n=100) investigated effects of vitamin D supplementation on neutralising antibody and cellular responses in venous blood samples collected after SARS-CoV-2 vaccination.Results1945/2808 (69.3%) sub-study 1 participants received two doses of ChAdOx1 nCoV-19 (Oxford–AstraZeneca); the remainder received two doses of BNT162b2 (Pfizer). Vitamin D supplementation did not influence risk of breakthrough SARS-CoV-2 infection (800 IU/day vs. no offer: adjusted hazard ratio 1.28, 95% CI 0.89 to 1.84; 3200 IU/day vs. no offer: 1.17, 0.81 to 1.70). Neither did it influence IgGAM anti-Spike titres, neutralising antibody titres or IFN-γ concentrations in supernatants of S peptide-stimulated whole blood.ConclusionsAmong adults with sub-optimal baseline vitamin D status, vitamin D replacement at a dose of 800 or 3200 IU/day did not influence protective efficacy or immunogenicity of SARS-CoV-2 vaccination.Clinical Trial RegistrationClinicalTrials.govNCT04579640.
Internet-based Cognitive Behaviour Therapy for the Prevention, Treatment and Relapse Prevention of Eating Disorders: A Systematic Review
Authors: Hamid Nilima 
Published: July 2022

ABSTRACTBackground and ObjectivesEating disorders (EDs) are undertreated worldwide. In the UK the lag between recognition of symptoms and treatment ranges from about 15 months to in excess of two years. Internet-based Cognitive Behaviour Therapy (ICBT) could be a viable alternative to face-to-face Cognitive Behaviour Therapy (CBT) that avoids the negative impacts of delayed interventions. Based on evidence from randomised controlled trials (RCTs) this systematic review investigated the effectiveness of minimally guided self-help ICBT, without face-to-face therapy, for the prevention, treatment and relapse prevention of all types of EDs in adults.MethodsThe electronic databases MEDLINE, PsychINFO, CENTRAL, Scopus, and Web of Science were searched between 1991 to 2021. Inclusion criteria specified RCTs with ICBT versus inactive comparison groups. The Cochrane Risk of Bias Tool was used for quality assessments. Qualitative synthesis and meta-analyses were conducted.ResultsFindings showed medium and large significant beneficial effect sizes for the prevention and treatment studies, respectively, whereas relapse prevention yielded mainly small non-significant beneficial effect sizes. Only the treatment studies reached clinical significance and cognitive symptoms improved more than behavioural symptoms.ConclusionsThis systematic review reinforces the vital need to provide evidence-based Internet interventions at times when face-to-face treatment is not an option as has been the case during the COVID-19 pandemic. Although ICBT is a promising intervention for eating disorders in adults and may be more effective than face-to-face CBT for treating cognitive symptoms further high-quality ED RCTs are required to increase the evidence-base and enable more precise meta-analyses to reach definitive conclusions.HighlightsFindings showed medium and large significant beneficial effect sizes for the prevention and treatment studies, respectively, whereas relapse prevention yielded mainly small non-significant beneficial effect sizes.For the treatment studies, 35% of effect estimates were clinically important. None of the effect estimates for either the prevention or the relapse prevention studies reached clinical significance.There were statistically significant improvements on comorbid depression and anxiety for the treatment programmes.Cognitive symptoms improved more than behavioural symptoms and it is suggested that ICBT may be more effective than face-to-face CBT for treating cognitive symptoms.
Analysis of SARS-CoV-2 amino acid mutations in New York City Metropolitan wastewater (2020-2022) reveals multiple traits with human health implications across the genome and environment-specific distinctions
Authors: Archana Anand , Long Chenghua , Chandran Kartik 
Published: July 2022

AbstractWe characterize variant diversity, amino acid mutation frequency, functionality and associations with COVID-19 infections in one of the largest datasets of SARS-CoV-2 genome sequences collected from wastewater in the New York metropolitan area. Variant diversity differed within parts of the New York City sewershed and between wastewater sludge and influent samples. P314L, D614G and T3255I occurred in >95% of wastewater samples. Enhanced infectivity, transmissibility and escape from antibody neutralization were dominant traits in the wastewater. Strikingly, over 60% of the most frequently occurring mutations were found in regions other than the spike (S) protein, and nearly 50% remain uncharacterized for functional impacts warranting further investigation. We demonstrate strong correlations between P314L, D614G, T95I, G50E, G50R, G204R, R203K, G662S, P10S, P13L and mortality rates, percent positive test results, hospitalization rates and % of population fully vaccinated. The results from our study suggest that there are relatively understudied mutations in the spike protein (H655Y, T95I) and understudied mutations occurring in non-spike proteins (N, ORF1b, ORF9b and ORF9c), that are enhancing transmissibility and infectivity among human populations, warranting further investigation.
Delineating organizational principles of the endogenous L-A virus by cryo-EM and computational analysis of native cell extracts
Authors: Schmidt Lisa , Tüting Christian , Kyrilis Fotis L. , Hamdi Farzad , Semchonok Dmitry A. , Hause Gerd , Meister Annette , Ihling Christian , Shah Pranav N. M. , Stubbs Milton T. , Sinz Andrea , Stuart David I. , Kastritis Panagiotis L. 
Published: July 2022

AbstractThe high abundance of most viruses in infected host cells benefits their structural characterization; endogenous viruses are present in low copy numbers, however, and are therefore challenging to investigate. Here, we retrieve cell extracts enriched with an endogenous virus, the yeast L-A virus. The determined cryo-EM structure discloses capsid-stabilizing cation-π stacking and an interplay of non-covalent interactions from ten distinct capsomere interfaces. The capsid-embedded mRNA decapping active site trench is supported by a constricting movement of two opposite-facing loops. tRNA-loaded polysomes and other biomacromolecules, presumably mRNA, are found in virus proximity while stacked dsRNA bundles and the sub-stoichiometric polymerase localize underneath the capsid surface. Mature viruses participate in larger viral communities resembling their rare in-cell equivalents in terms of size, composition, and inter-virus distances. Our results collectively describe a 3D-architecture of a viral milieu, opening the door to cellextract-based high-resolution structural virology.
A Multi-Tissue Comparison and Molecular Characterization of Canine Organoids
Authors: Zdyrski Christopher , Gabriel Vojtech , Ospina Oscar , Wickham Hannah , Sahoo Dipak K. , Dao Kimberly , Aguilar Meza Leeann S. , Ralston Abigail , Bedos Leila , Bastian William , Honold Sydney , Piñeyro Pablo , Douglass Eugene F. , Mochel Jonathan P. , Allenspach Karin 
Published: July 2022

ABSTRACTOrganoids are 3-dimensional (3D) stem cell-derived cell culture lines that offer a variety of technical advantages compared to traditional 2-dimensional (2D) cell cultures. Although murine models have proved useful in biomedical research, rodent models often fail to adequately mimic human physiology and disease progression, resulting in poor preclinical prediction of therapeutic drug efficacy and toxicity. With the advent of organoid technology, many of these challenges can be overcome. Previously, the use of canine organoids in drug testing and disease modeling was limited to organoids originating from the intestine, liver, kidney, lung, and urinary bladder. Here, we report the cultivation, maintenance, and molecular characterization of two novel adult-stem cell-derived canine organoid cell lines, including the endometrium and pancreas, in addition to previously reported bladder, lung, and liver organoids from two genetically related canines. Five tissues and organoid lines from each donor were characterized using bulk RNA-seq, allowing for a unique, multi-organ comparison between these two individuals and identification of specific cell types such as glandular epithelial cells in endometrial organoids.
Programming the lifestyles of engineered bacteria for cancer therapy
Authors: Fu Shengwei , Zhang Rongrong , Gao Yanmei , Xiong Jiarui , Li Ye , Pu Lu , Xia Aiguo , Jin Fan 
Published: July 2022

ABSTRACTBacteria can be genetically engineered to act as therapeutic delivery vehicles in the treatment of tumors, killing cancer cells or activating the immune system. This is known as Bacteria-Mediated Cancer Therapy (BMCT). Tumor invasion, colonization and tumor regression are major biological events, which are directly associated with antitumor effects and are uncontrollable due to the influence of tumor microenvironments during the BMCT process. Here, we developed a genetic circuit for dynamically programming bacterial lifestyles (planktonic, biofilm or lysis), to precisely manipulate the process of bacterial adhesion, colonization and drug release in BMCT process, via hierarchical modulation of the lighting power density (LPD) of near-infrared (NIR) light. The deep tissue penetration of NIR offers us a modality for spatiotemporal and noninvasive control of bacterial genetic circuits in vivo. By combining computational modeling with high throughput characterization device, we optimized the genetic circuits in engineered bacteria to program the process of bacterial lifestyle transitions by altering the illumination scheme of NIR. Our results showed that programming intratumoral bacterial lifestyle transitions allows precise control of multiple key steps throughout the BMCT process, and therapeutic efficacy can be greatly improved by controlling the localization and dosage of therapeutic agents via optimizing the illumination scheme.
Resting State Neural Networks at Complex Visual Hallucinations in Charles Bonnet Syndrome
Authors: Hanoglu Taha , Velioglu Halil Aziz , Salar Behram Ali , Yıldız Sultan , Bayraktaroglu Zübeyir , Yulug Burak , Hanoglu Lutfu 
Published: July 2022

ABSTRACTBackgroundCharles Bonnet syndrome (CBS) is a prototype phenomenon for investigating complex visual hallucination. Our research focuses on resting state neural networks features of CBS patients with a comparison of patients with equally matched visual loss and healthy subjects in order to investigate the mechanism behind complex visual hallucinations.Material and MethodsFour CBS patients CBS(+), three patients with visual loss but no visual hallucinations CBS(-) and 15 healthy individuals (HS) undergo resting state fMRI recordings and their resting state data is analyzed for Default Mode Network (DMN) changes through dual regression analysis. Cognitive functions of the participants were also evaluated through Mini Mental State Examination and University of Miami - Parkinson’s Disease Hallucination Questionnaire (um-PDHQ)ResultsAlthough we found no difference in Default Mode Networks between CBS(-) and CBS(+), and between the CBS(-) and HC groups, we detected decreased connectivity in CBS(+) compared to the HC group especially in visual heteromodal association centers (bilateral lateral occipital gyrus, bilateral lingual gyrus, occipital pole, right medial temporal cortex, right temporo-occipital cortex) when left angular gyrus was selected as ROI.Similarly, we detected decreased connectivity in CBS(+) compared to HC in right medial frontal gyrus, right posterior cingulate gyrus, left inferior temporal gyrus, right supramarginal gyrus, and right angular gyrus when selected right superior frontal gyrus as ROI. In contrast, increased connectivity was detected in CBS +compared to HC, in bilateral occipital poles, bilateral occipital fusiform gyrus, bilateral intracalcarine cortex, right lingual gyrus and precuneus regions when left medial temporal gyrus was selected as ROI.ConclusionOur findings suggest a combined mechanism in CBS related to increased internal created images caused by decreased visual external input causing visual hallucinations as well as impaired frontotemporal resource tracking system that together impair cognitive processing.
The role ofGmXTH1, a new xyloglucan endotransglycosylase/hydrolase from soybean, in regulating soybean root growth at seedling stage
Authors: Song Yang , Zhang Ye , Du Ye-yao , Fan Sujie , Qin Di , Zhang Zhuo , Wang Pi-wu 
Published: July 2022

AbstractSoybean is an important crop for both food and oil, providing high quality protein and oil for humans and animals. Drought stress has an significant effect on the yield and quality of soybean. In the early vegetative stage of soybean, the developed root system can effectively improve the tolerance of soybean plant to drought. Xyloglucan endoglycosylase/hydrolase (XTH) is a cell wall remodeling enzyme involved in cell wall expansion and degradation. However, there are few studies on XTH’s regulation of root growth and response to drought stress in soybean seedlings.The objectives of this study were to clone GmXTH1 gene and determine the effects of over and interference-expression of GmXTH1 on soybean root development at seedling stage. A 1,015 bp full-length of the GmXTH1 gene was cloned from soybean (Glycine max L. Merril) cv. RM18 with a 840 bp open reading frame (ORF) of a putative protein. The over and interference expression vectors of GmXTH1 were transformed into soybean using Agrobacterium method. Transformed strains OEA1, OEA3, IEA4, IEA5 were identified by molecular detection methods. The roots of transformed strains OEA1and OEA3 with GmXTH1 gene overexpression are clearly developed and the root phenotypic attributes, including main root length, primary root number, lateral root length, root surface area, root volume, root dry weight, root fresh weight are higher than the control. In contrast, root attributes of IEA4 and IEA5 with GmXTH1 gene interference expression were significantly lower than those of the control, suggesting that the expression of GmXTH1 gene has an important effect on the soybean root growth and development at seedling stage. Under drought stress conditions, the activities of Superoxide dismutase (SOD), Peroxidase(POD)and Catalase(CAT)in the transgenic strains with an overexpression of the GmXTH1 gene were significantly increased, and the root activity, leaf relative water content and total chlorophyll content were ranked in order of OEAs, CK, and IEAs. In conclusion, GmXHT1 plays an important role in the growth of soybean root at seedling stage. Overexpression of GmXTH1 gene can promote root development of soybean seedling. The results of activities of protective enzymes (SOD, POD, CAT), root activity, leaf relative water content and total chlorophyll content under drought stress indicated that transgenic strains OEA1 and OEA3 with overexpressing GmXTH1 gene were resistant to drought stress, suggesting that GmXTH1 may play a positive role in responding to drought stress at soybean seedling stage.
Switches to slow rhythmic neuronal activity lead to a plasticity-induced reset in synaptic weights
Authors: Jacquerie Kathleen , Minne Caroline , Ponnet Juliette , Benghalem Nora , Sacré Pierre , Drion Guillaume 
Published: July 2022

AbstractMemory formation relies on changes in synaptic connections via synaptic plasticity, which is driven by neuronal activity. Simultaneously, behavior is controlled by switches in brain states: quiet waking is characterized by large low-frequency fluctuations in cortical activity that are strongly suppressed during active waking. We use computational modeling to study how switches in brain states interact with memory formation. We show that the low-frequency rhythmic bursting activity reminiscent of quiet waking induces a reset in synaptic weights. This reset occurs regardless of the implemented synaptic plasticity rule, whether phenomenological or biophysical, and is robust to biological variability and network heterogeneity. Mathematical analysis shows that the reset is rooted in the endogenous nature of the low-frequency quiet waking rhythmic activity. This brain state-dependent reset in synaptic weights restores the ability to learn through synaptic plasticity rules between periods of active waking, which could be a key component of memory homeostasis.
Bottlenecks can constrain and channel evolutionary paths
Authors: Gamblin Jasmine , Gandon Sylvain , Blanquart François , Lambert Amaury 
Published: July 2022

AbstractPopulation bottlenecks are commonplace in experimental evolution, specifically in serial passaging experiments where microbial populations alternate between growth and dilution. Natural populations also experience such fluctuations caused by seasonality, resource limitation, or host-to-host transmission for pathogens. Yet, how unlimited growth with periodic bottlenecks influence the adaptation of populations is not fully understood. Here we study theoretically the effects of bottlenecks on the accessibility of evolutionary paths and on the rate of evolution. We model an asexual population evolving on a minimal fitness landscape consisting of two types of beneficial mutations with the empirically supported trade-off between mutation rate and fitness advantage, in the regime where multiple beneficial mutations may segregate simultaneously. In the limit of large population sizes and small mutation rates, we show the existence of a unique most likely evolutionary scenario, determined by the size of the wild-type population at the beginning and at the end of each cycle. These two key demographic parameters determine which adaptive paths may be taken by the evolving population by controlling the supply of mutants during growth and the loss of mutants at the bottleneck. We do not only show that bottlenecks act as a deterministic control of evolutionary paths but also that each possible evolutionary scenario can be forced to occur by tuning demographic parameters. This work unveils the effects of demography on adaptation of periodically bottlenecked populations and can guide the design of evolution experiments.
Liver sinusoidal endothelial cells orchestrate NK cell recruitment and activation in acute inflammatory liver injury
Authors: Papaioannou Sophia , See Jia-Xiang , Jeong Mingeum , De La Torre Carolina , Reiners-Koch Philipp-Sebastian , Sati Ankita , Mogler Carolin , Platten Michael , Cerwenka Adelheid , Stojanovic Ana 
Published: July 2022

SummaryIn both steady-state and during endotoxicosis, liver sinusoidal endothelial cells (LSECs) can rapidly clear lipopolysaccharide (LPS) from the bloodstream. They are located along blood sinusoids of the liver, and establish intimate contact with circulating and tissue-resident immune cells. However, their role in regulating immune responses during LPS-induced endotoxicosis remains poorly understood. Here, we show that LSECs play a dual role in regulating inflammatory responses, acting as modulators of NK cell pro-inflammatory output and as major producers of immune cell-attracting chemokines. We demonstrate that LSECs switch their chemokine expression pattern driven by LPS and IFN-γ, resulting in the production of the myeloid-attracting chemokine CCL2 and the lymphoid-attracting chemokine CXCL10, which accumulate in the serum of LPS-challenged animals. In livers of LPS-injected mice, monocytes and Kupffer cells expressed highest amounts of the pro-inflammatory cytokineIl12aandIl18transcripts, while NK cells expressed the highest amounts ofIfng. NK cell exposure to LSECsin vitroled to global transcriptomic changes, and primed NK cells to produce higher amounts of IFN-γ in response to IL-12 and IL-18. LSECs required exposure to IFN-γ forCxcl10expression, andCxcl10gene-deletion in endothelial cells abrogated NK cell accumulation in the liver after LPS treatment. Thus, our data indicate that LSECs occupy a unique temporal and spatial position acting as central regulators that respond to both LPS and immune-derived inflammatory signals, and fuel a positive feedback loop of immune cell attraction and activation in the inflamed liver tissue.Abstract Figure