bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two-dimensional maps to predict the neurological recovery after cardiac arrest
Authors: Floyrac Aymeric , Doumergue Adrien , Legriel Stéphane , Deye Nicolas , Megarbane Bruno , Richard Alexandra , Meppiel Elodie , Masmoudi Sana , Lozeron Pierre , Vicaut Eric , Kubis Nathalie , Holcman David 
Published: November 2022

AbstractBackgroundSeverity of neuronal damage in comatose patients following anoxic brain injury is assessed through a multimodal evaluation. However, predicting the return to full consciousness of hospitalized post-anoxic comatose patients remains challenging.MethodsWe present here a method to predict the return to consciousness and good neurological outcome based on the analysis of responses to auditory periodic stimulations to auditory evoked potentials. We extracted several EEG features from the time series responses in a window of few hundreds of milliseconds from the standard and deviant auditory stimulations that we considered independently. By combining these features, we built a two-dimensional map to evaluate possible group clustering. Using Gaussian, K-neighbourhood and SVM classifiers, we could predict the neurological outcome of post-anoxic comatose patients, the validity of the method being tested by a cross-validation procedure. This method was developed using data acquired retrospectively in a cohort of 29 post-cardiac arrest comatose patients, recorded between day 3 and day 6 following admission. Data from event-related potentials (ERPs) were recorded non-invasively with four surface cranial electrodes at electro-encephalography (EEG), that we computed secondarily.ResultsAnalysis in two-dimensions of the present data revealed two separated clusters of patients with good versus bad neurological outcome. When favouring the highest specificity of our mathematical algorithms (0.91), we found a sensitivity of 0.83 and an accuracy of 0.90, maintained when calculation was performed using data from only one central electrode.To concludestatistics of standard and deviant responses considered separately provide complementary and confirmatory predictions of the outcome of anoxic comatose patients, better assessed when combining these features on a two-dimensional statistical map. The benefit of this method compared to classical EEG and ERP predictors should be tested in a large prospective cohort. If validated, this method could provide an alternative tool to intensivists, to better evaluate neurological outcome and improve patient management, without neurophysiologist assistance.
Perceived barriers to cervical cancer screening and motivators for at-home human papillomavirus self-sampling during the COVID-19 pandemic: Results from a telephone survey
Authors: Parker Susan L. , Deshmukh Ashish A. , Chen Baojiang , Lairson David R. , Daheri Maria , Vernon Sally W. , Montealegre Jane R. 
Published: November 2022

AbstractHome-based self-sample human papillomavirus (HPV) testing may be an alternative for women who do not attend clinic-based cervical cancer screening. We assessed barriers to care and motivators to use at-home HPV self-sampling kits during the COVID-19 pandemic as part of a randomized controlled trial evaluating kit effectiveness. Participants were women, aged 30-65 years and underscreened for cervical cancer in a safety-net healthcare system. We conducted telephone surveys in English/Spanish among a subgroup of trial participants, assessed differences between groups and determined statistical significance at p<0.05. Over half of 233 survey participants reported clinic-based screening (Pap) is uncomfortable (67.8%), embarrassing (52.4%), and discomfort seeing male providers (63.1%). The latter two factors were significantly more prevalent among Spanish versus English speakers (66.4% vs 30% and 69.9 vs 52.2%, respectively, p<0.01). Most women who completed the kit found Pap more embarrassing (69.3%), stressful (55.6%) and less convenient (55.6%) than the kit. The first factor was more prevalent among Spanish versus English speakers (79.6% vs 53.38%, p<0.05). The COVID-19 pandemic influenced most (59.5%) to participate in the trial due to fear of COVID, difficulty making appointments and ease of using kits. HPV self-sampling kits may reduce barriers among underscreened women in a safety-net system.
Costs and economic impacts of expanding marine protected area systems to 30%
Authors: Waldron Anthony , Heneghan Ryan , Steenbeek Jeroen , Coll Marta , Scherrer Kim J. N. 
Published: November 2022

AbstractInternational proposals for marine biodiversity seek to expand marine protected area (MPA) coverage from 8% to 30%, known as 30×30. Quadrupling MPA coverage implies considerably higher MPA system costs and governments need early knowledge of these to inform debate. Ambitious MPA expansion also implies large potential losses or “opportunity costs” for fishers, putting pressure on governments to compromise and permit some fishing inside protected areas (a mixed high/low protection system). Crafting a balanced compromise needs to be informed by model projections of future fisheries outcomes under different protection regimes, climate change scenarios and behavioural adaptations. Here, we develop the first models for management costs at national MPA-system scale. We create scenarios of 30×30 at different compromises around protection strictness. We then examine how both MPA costs and opportunity costs vary with strictness, by simultaneously applying our management cost models and two Marine Ecosystem Models. We find that a no-take (high protection) MPA system could cost just $2 billion/year for the developing world and ~$8 billion overall, but would also create opportunity costs several times larger. A compromise mix of high and medium protection would have much higher MPA costs (e.g. $4.5 billion for the developing world) but much lower opportunity costs, to the point of fisheries actually benefiting in the future. Since lower protection also compromises on biodiversity goals, our results show the trade-offs that political decisions need to consider beyond COP15. More generally, the unusually large opportunity costs show how marine contexts generate very different economic issues from terrestrial ones, by attempting to protect a common pool resource area that envisages no automatic market compensation for income lost to conservation.
The velvet family proteins mediate low resistance to isoprothiolane inMagnaporthe oryzae
Authors: Meng Fan-Zhu , Wang Zuo-Qian , Luo Mei , Wei Wen-Kai , Yin Liang-Fen , Yin Wei-Xiao , Schnabel Guido , Luo Chao-Xi 
Published: November 2022

AbstractIsoprothiolane (IPT) resistance has emerged inMagnaporthe oryzae, due to the long-term usage of IPT to control rice blast in China, yet the mechanisms of the resistance remain largely unknown. Through IPT adaptation on PDA medium, we obtained a variety of IPT-resistant mutants. Based on their EC50values to IPT, the resistant mutants were mainly divided into three distinct categories i.e., low resistance (LR, 6.5 ≤ EC50< 13.0 μg/mL), moderate resistance 1 (MR-1, 13.0 ≤ EC50< 25.0 μg/mL), and moderate resistance 2 (MR-2, 25.0 ≤ EC50< 35.0 μg/mL). Molecular analysis ofMoIRR(Magnaporthe oryzaeisoprothiolane resistance related) gene demonstrated that it was associated only with the moderate resistance in MR-2 mutants, indicating that other mechanisms were associated with resistance in LR and MR-1 mutants. In this study, we mainly focused on the characterization of low resistance to IPT inM. oryzae. Mycelial growth and conidial germination were significantly reduced, indicating fitness penalties in LR mutants. Based on the differences of whole genome sequences between parental isolate and LR mutants, we identified a conservedMoVelBgene, encoding the velvet family transcription factor, and genetic transformation of wild type isolate verified thatMoVelBgene was associated with the low resistance. Based on molecular analysis, we further demonstrated that the velvet family proteins VelB and VeA were indispensable for IPT toxicity and the deformation of the LaeA-VeA-VelB heterotrimer played a vital role for the low IPT-resistance inM. oryzae, most likely through the down-regulation of the secondary metabolism-related genes or CYP450 genes to reduce the toxicity of IPT.Author summaryIsoprothiolane (IPT) resistance has emerged inMagnaporthe oryzae, due to the long-term usage of IPT to control rice blast in China, yet the mechanisms of the resistance remain largely unknown. Here, we explored the mechanisms of low IPT resistance inM. oryzae. Combining the whole genome sequencing and genetic transformation, we identified a conservedMoVelBgene, encoding the velvet family transcription factor to be a determinant for IPT toxicity. We further demonstrated that the deformation of the LaeA-VeA-VelB heterotrimer conferred the low IPT-resistance inM. oryzae, most likely through down-regulating the secondary metabolism-related genes or CYP450 genes to reduce the toxicity of IPT. This study improved our understanding of the resistance mechanism as well as the mode of action of IPT which will be helpful for making suitable strategies to manage the emerging resistance of IPT inM. oryzae.
Modeling rod and cone photoreceptor cell survivalin vivousing optical coherence tomography
Authors: Whitmore S. Scott , DeLuca Adam P. , Andorf Jeaneen L. , Cheng Justine L. , Mansoor Mahsaw , Fortenbach Christopher R. , Critser D. Brice , Russell Jonathan F. , Stone Edwin M. , Han Ian C. 
Published: November 2022

AbstractMany retinal diseases involve the loss of light-sensing photoreceptor cells (rods and cones) over time. The severity and distribution of photoreceptor loss varies widely across diseases and affected individuals, so characterizing the degree and pattern of photoreceptor loss can clarify pathophysiology and prognosis. Currently,in vivovisualization of individual photoreceptors requires technology such as adaptive optics, which has numerous limitations and is not widely used. By contrast, optical coherence tomography (OCT) is nearly ubiquitous in daily clinical practice given its ease of image acquisition and detailed visualization of retinal structure. However, OCT cannot resolve individual photoreceptors, and no OCT-based method exists to distinguish between the loss of rods versus cones. Here, we present a computational model that quantitatively estimates rod versus cone photoreceptor loss from OCT. Using histologic data of human photoreceptor topography, we constructed an OCT-based reference model to simulate outer nuclear layer thinning caused by differential loss of rods and cones. The model was able to estimate rod and cone loss usingin vivoOCT data from patients with Stargardt disease and healthy controls. Our model provides a powerful new tool to quantify photoreceptor loss using OCT data alone, with potentially broad applications for research and clinical care.
Identification of an increased lifetime risk of major adverse cardiovascular events in UK Biobank participants with scoliosis
Authors: Santofimio Valentina Q. , Clement Adam , O’Regan Declan P. , Ware James S. , McGurk Kathryn A. 
Published: November 2022

AbstractBackgroundStructural changes caused by spinal curvature may impact the organs within the thoracic cage, including the heart. Cardiac abnormalities in idiopathic scoliosis patients are often studied post-corrective surgery or secondary to diseases. To investigate cardiac structure, function, and outcomes in participants with scoliosis, phenotype and imaging data of the UK Biobank (UKB) adult population cohort was analysed.MethodsHospital episode statistics of 502,324 adults were analysed to identify participants with scoliosis. Summary 2D cardiac phenotypes from 39,559 cardiac magnetic resonance imaging (CMR) scans were analysed alongside a 3D surface-to-surface (S2S) analysis.ResultsA total of 4,095 (0.8%, 1 in 120) UKB participants were identified to have all-cause scoliosis. These participants had increased lifetime risk of major adverse cardiac events (MACE) (HR=1.45, P<0.001), driven by heart failure (HR=1.58, P<0.001) and atrial fibrillation (HR=1.54, P<0.001). Increased radial and decreased longitudinal peak diastolic strain rates were identified in participants with scoliosis (+0.29, Padj<0.05; −0.25, Padj<0.05; respectively). Cardiac compression of the top and bottom of the heart and decompression of the sides was observed through S2S analysis. Additionally, associations between scoliosis and older age, female sex, heart failure, valve disease, hypercholesterolemia, hypertension, and decreased enrolment for CMR, were identified.ConclusionThe spinal curvature observed in participants with scoliosis alters the movement of the heart. The association with increased MACE may have clinical implications for whether to undertake surgical correction. This work identifies, in an adult population, evidence for altered cardiac function and increased lifetime risk of MACE in participants with scoliosis. Future genetic analyses would aid to assess causality.
Image Based Deep Learning in 12-Lead ECG Diagnosis
Authors: Ao Raymond , He George 
Published: November 2022

AbstractBackgroundMost studies on machine learning classification of electrocardiogram (ECG) diagnoses focus on processing raw signal data rather than ECG images. In clinical practice, it is often the case where ECGs printed on paper or only digital images are easily accessible. This study aims to evaluate the accuracy of image based deep learning algorithms on 12 lead ECG diagnosis.MethodsDeep learning models were trained on various 12-lead ECG datasets and evaluated for accuracy by testing on holdout test data as well as data from datasets not seen in training.ResultsThe results demonstrated excellent AUROC, AUPRC, sensitivity and specificity on holdout test data from datasets used in training, but poorer accuracy on unseen datasets.DiscussionThis study demonstrates feasibility of image based deep learning algorithms in ECG diagnosis, and identifies directions for future research in order to develop clinically applicable deep-learning models in ECG diagnosis.
Monogenic causes of Premature Ovarian Insufficiency are rare and mostly recessive
Authors: Shekari Saleh , Stankovic Stasa , Gardner Eugene J. , Hawkes Gareth , Kentistou Katherine A. , Beaumont Robin N. , Mörseburg Alexander , Wood Andrew R. , Mishra Gita , Day Felix , Baptista Julia , Wright Caroline F. , Weedon Michael N. , Hoffmann Eva , Ruth Katherine S. , Ong Ken , Perry John R. B. , Murray Anna 
Published: November 2022

AbstractPremature ovarian insufficiency (POI) affects 1% of women and is a leading cause of infertility. It is often considered to be a monogenic disorder, with pathogenic variants in ∼100 genes described in the literature. We sought to systematically evaluate the penetrance of variants in these genes using exome sequence data in 104,733 women from the UK Biobank, 2,231 (1.14%) of whom reported natural menopause under the age of 40. In the largest study of POI to date, we found limited evidence to support any previously reported autosomal dominant effect. For nearly all heterozygous effects on previously reported POI genes we were able to rule out even modest penetrance, with 99.9% (13,699/13,708) of all identified protein truncating variants found in reproductively healthy women. We found evidence of novel haploinsufficiency effects in several genes, includingTWNK(1.54 years earlier menopause,P=1.59*10−6) andSOHLH2(3.48 years earlier menopause,P=1.03*10−4). Collectively our results suggest that for the vast majority of women, POI is not caused by autosomal dominant variants either in genes previously reported or currently evaluated in clinical diagnostic panels. We suggest that the majority of POI cases are likely oligogenic or polygenic in nature, which has major implications for future clinical genetic studies, and genetic counselling for families affected by POI.
Predictive efficacies of vaccine dose fractionation using neutralizing antibody levels
Authors: Du Zhanwei , Liu Caifen , Bai Yuan , Wang Lin , Lim Wey Wen , Lau Eric H. Y. , Cowling Benjamin J. 
Published: November 2022

AbstractBackgroundWith the emergence of SARS-CoV-2 variants that eluded immunity from vaccines and prior infections, vaccine shortages and their effectiveness pose unprecedented challenges for governments to expand booster vaccination programs. Fractionation of vaccine doses might be an effective strategy to help society to face these challenges, which may have comparable efficacies in contrast with the standard doses.MethodsIn this study, we analyzed the relationship between in-vitro neutralization levels and the observed efficacies against asymptomatic and symptomatic infection of ten types of COVID-19 vaccines using data from 13 studies from vaccination and convalescent cohorts. We further projected efficacies for fractional doses based on 51 studies included in our systematic review.ResultsBy comparing with the convalescent level, vaccine efficacy increases from 8.8% (95% CI: 1.4%, 16.1%) to 71.8% (95% CI: 63.0%, 80.7%) against asymptomatic infection, and from 33.6% (95% CI: 23.6%, 43.6%) to 98.6% (95% CI: 97.6%, 99.7%) against symptomatic infection, respectively, along with the mean neutralization level from 0.1 to 10 folds of convalescent level. And mRNA vaccines provide the strongest protection, and decrease slowly for fractional dosing between 50% and 100% dosage.ConclusionsOur results are consistent with studies for immune protection from COVID-19 infection. Based on our study, we expect that fractional dose vaccination could provide a partial immunity for SARS-CoV-2 virus. Fractional doses of vaccines could be a viable vaccination strategy compared to full-dose vaccination and deserves further exploration.Key pointsWe analyzed the relationship between neutralization levels and efficacies against asymptomatic and symptomatic infection of ten types of COVID-19 vaccines from convalescent cohorts. Fractional doses of vaccines could be a viable strategy compared to full-dose vaccination and deserves further exploration.
Salmonella-induced SIRT1 and SIRT3 are crucial for maintaining the metabolic switch in bacteria and host for successful pathogenesis
Authors: Hajra Dipasree , Rajmani Raju S. , Chaudhary Ayushi Devendrasingh , Gupta Shashi Kumar , Chakravortty Dipshikha 
Published: November 2022

ABSTRACTSirtuins are the major players in host immuno-metabolic regulation. However, the role of sirtuins in the modulation of the immune metabolism pertaining to Salmonellosis is largely unknown. Here, our investigation focussed on the role of two important sirtuins, SIRT1 and SIRT3, shedding light on their impact on intracellularSalmonella’s metabolic switch and pathogenesis establishment. Our study indicated the ability of the liveSalmonellaTyphimurium to differentially regulate the levels of SIRT1 and SIRT3 for maintaining the high glycolytic metabolism and low fatty acid metabolism inSalmonella. Perturbing SIRT1 or SIRT3 through knockdown or inhibition, resulted in a remarkable shift in the host metabolism to low fatty acid oxidation and high glycolysis. This switch led to decreased proliferation ofSalmonellain the macrophages. Further,Salmonella-induced higher levels of SIRT1 and SIRT3 led to a skewed polarization state of the macrophages from a pro-inflammatory M1 state toward an immunosuppressive M2 making it more conducive for the intracellular life ofSalmonella. Alongside, governing immunological functions by modulating p65 NF-κB acetylation, SIRT1, and SIRT3 also skewSalmonella-induced host metabolic switch by regulating the acetylation status of HIF-1α and PDHA1. Interestingly, though knock-down of SIRT1/3 attenuatedSalmonellaproliferation in macrophages, inin vivomice-model of infection, inhibition or knockdown of SIRT1/3 led to more dissemination and higher organ burden which can be attributed to enhanced ROS and IL-6 production. Our study hence reports for the first time thatSalmonellamodulates SIRT1/3 levels to maintain its own metabolism for successful pathogenesis.
Atomistic structure of the interlocking claw-like amyloid fibril of full-length glucagon
Authors: Jeong Hyeongseop , Lin Yuxi , Kim Jin Hae , Yu Wookyung , Heo Yunseok , Won Hyung-Sik , Okumura Masaki , Lee Young-Ho 
Published: November 2022

AbstractGlucagon is a peptide hormone which posits a significant potential as a therapeutic molecule for various human diseases. One of the major challenges hampering medicinal application of glucagon, however, is its insoluble and aggregation-prone property. Although glucagon is dissolvable, it aggregates easily and forms amyloid fibrils. To date, despite many studies to understand how glucagon aggregates and fibrillizes, its detailed amyloidogenesis mechanism is still elusive, particularly due to insufficient structural information of glucagon amyloid fibrils. Here we report the novel structure of a glucagon amyloid fibril, which was determined with cryo-electron microscopy (cryo-EM) to a 3.8-Å resolution. Our model features with tight and extensive inter-monomer interactions, which efficiently stabilize the entire chain of full-length glucagon into the V-shape conformation, clamping the other monomer to construct a dimeric architecture orthogonal to the fibril axis. Notably, the current structure significantly differs from the previous solid-state NMR model, which gives direct evidence for multiple and dynamic amyloidogenesis mechanisms of glucagon. In addition, our results are expected to provide important insights to appreciate the molecular details of glucagon in its initial amyloidogenesis and fibril elongation processes.
Collagen constitutes about twelve percent in females and seventeen percent in males of the total protein in mice
Authors: Tarnutzer Katharina , Sankar Devanarayanan Siva , Dengjel Joern , Ewald Collin Y. 
Published: November 2022

AbstractCollagen has been postulated to be the most abundant protein in our body, making up one-third of the total protein content in mammals. However, to the best of our knowledge, a direct assessment of the total collagen levels of an entire mammal to confirm this estimate is missing. Here we measured hydroxyproline levels as a proxy for collagen content together with total protein levels of entire mice or of individual tissues. Collagen content normalized to the total protein is approximately 0.1% in the brain and liver, 1% in the heart and kidney, 4% in the muscle and lung, 6% in the colon, 20-40% in the skin, 25-35% in bones, and 40-50% in tendons of wild-type (CD1 and CB57BL/6) mice, consistent with previous reports. Mice consist of 37 mg of collagen and 265 mg of protein per g of body weight. To our surprise, we find that collagen is approximately 12% in females and 17% in males of the total protein content of entire wild-type (CD1 and CB57BL/6) mice. High-Performance Liquid Chromatography approaches confirmed a 10-12% collagen over total protein estimates for female mice. Collagen staining methods and extracellular matrix-enriched proteomics estimated 5-6% of collagens over the total protein extracted. Although collagen type I is the most abundant collagen, the most abundant proteins are albumin, hemoglobulin, histones, actin, serpina, and then collagen type I. Analyzing amino acid compositions of mice revealed glycine as the most abundant amino acid. Thus, we provide reference points for collagen, matrisome, protein, and amino acid composition of healthy wild-type mice that are important for tissue and biomaterial engineering and for the comparison of these factors in various disease models.