bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rheological Behavior Patterns in Artificial Tears
Authors: Blasco-Martinez Alejandro , Mateo-Orobia Antonio , Blasco-Alberto Javier , Pablo-Julvez Luis 
Published: February 2022

SIGNIFICANCE
Rheological patterns were objectively calculated considering the first and last viscosity, besides the difference of viscosity with a specific shear rate. Shear thinning, shear thickening, thixotropic, and Newtonian behavior patterns were found.

PURPOSE
This study aimed to describe, in an objective way, the rheological behavior of several artificial tears.

METHODS
Seventy-eight artificial tears were included in this experimental analytical study. Its viscous behavior was measured using a cone-plate rheometer. An ascending and descending measurement range was defined for the shear rate from 1 to 1000 s−1 and vice versa. Hysteresis was calculated with the initial and final difference of viscosity. The rheological behavior pattern was calculated as the viscosity difference for the shear rate between 100 and 1000 s−1.

RESULTS
Four rheological patterns with different magnitudes were found: shear thinning, shear thickening, thixotropic, and Newtonian.

CONCLUSIONS
The viscosity of artificial tears always depends on the shear rate. It is possible to find two patterns simultaneously depending on the shear rate. These rheological patterns could serve to optimize the treatment with lubricants for different conditions of the ocular surface. In vivo studies are necessary to evaluate the clinical significance of these findings.
Clinical Report: Correlation of Serum Vitamins and Chalazion
Authors: Cheng Haixia , Lv Xuehua , Yao Jiaqi , Chen Zhijun 
Published: February 2022

SIGNIFICANCE
We demonstrate the clinical correlation between the vitamin A level with chalazion in East Chinese children. Vitamin A deficiency is likely to be a potential cause of childhood chalazion.

PURPOSE
Chalazion is the most common lid inflammatory lesion of the eyelid, which can be caused by retention of tarsal gland secretions. Studies have revealed that vitamin deficiency is an essential risk factor for children with chalazion. In this study, we measured the serum levels of vitamin A and 25-hydroxyvitamin D (25(OH)D), in patients with chalazion.

METHODS
The study included 180 subjects (90 patients with chalazion and 90 control healthy subjects) with an average age of 4.13 ± 2.01 years, and 47.8% of whom were female. Serums came from blood samples collected and used to measure the levels of vitamin A and 25(OH)D.

RESULTS
Both groups had statistically similar baseline characteristics, including age and body mass index. The average serum vitamin A levels in patients with chalazion (0.54 ± 0.15 μmol/L) were significantly lower than in their control counterparts (0.60 ± 0.15 μmol/L; P = .01). There was no significant difference in the serum 25(OH)D levels between the patients (70.15 ± 19.73 nmol/L) and control subjects (71.64 ± 24.46 nmol/L). The percentage of vitamin A deficiency in chalazion group (52.2%) was much higher than the control counterparts (28.6%; P = .001). The percentage of 25(OH)D deficiency showed no significant difference between patients with chalazion and control subjects (58.9 vs. 56.7%).

CONCLUSIONS
Low serum vitamin A was significantly associated with chalazion in children. The serum 25(OH)D level exhibited no correlation with chalazion.
Transfusion Ratios and Deficits in Injured Children With Life-Threatening Bleeding*
Authors: Spinella Philip C. , Leonard Julie C. , Marshall Callie , Luther James F. , Wisniewski Stephen R. , Josephson Cassandra D. , Leeper Christine M. ,   for the Massive Transfusion In Children (MATIC) Investigators and BloodNet
Published: February 2022

OBJECTIVES:
To assess the impact of plasma and platelet ratios and deficits in injured children with life-threatening bleeding.

DESIGN:
Secondary analysis of the MAssive Transfusion epidemiology and outcomes In Children study dataset, a prospective observational study of children with life-threatening bleeding events.

SETTING:
Twenty-four childrens hospitals in the United States, Canada, and Italy.

PATIENTS:
Injured children 0–17 years old who received greater than 40 mL/kg total blood products over 6 hours or were transfused under activation of massive transfusion protocol.

INTERVENTION/EXPOSURE:
Weight-adjusted blood product volumes received during the bleeding event were recorded. Plasma:RBC ratio (plasma/RBC weight-adjusted volume in mL/kg) and platelet:RBC ratio (platelet/RBC weight-adjusted volume in mL/kg) were analyzed. Plasma deficit was calculated as RBC mL/kg – plasma mL/kg; platelet deficit was calculated as RBC mL/kg – platelet mL/kg.

MEASUREMENTS AND MAIN RESULTS:
Of 191 patients analyzed, median (interquartile range) age was 10 years (5–15 yr), 61% were male, 61% blunt mechanism, and median (interquartile range) Injury Severity Score was 29 (24–38). After adjusting for Pediatric Risk of Mortality score, cardiac arrest, use of vasoactive medications, and blunt mechanism, a high plasma:RBC ratio (> 1:2) was associated with improved 6-hour survival compared with a low plasma:RBC ratio (odds ratio [95% CI] = 0.12 [0.03–0.52]; p = 0.004). Platelet:RBC ratio was not associated with survival. After adjusting for age, Pediatric Risk of Mortality score, cardiac arrest, and mechanism of injury, 6-hour and 24-hour mortality were increased in children with greater plasma deficits (10% and 20% increased odds of mortality for every 10 mL/kg plasma deficit at 6 hr [p = 0.04] and 24 hr [p = 0.01], respectively); 24-hour mortality was increased in children with greater platelet deficits (10% increased odds of 24-hr mortality for every 10 mL/kg platelet deficit [p = 0.02)]).

CONCLUSIONS:
In injured children, balanced resuscitation may improve early survival according to this hypothesis generating study. Multicenter clinical trials are needed to assess whether clinicians should target ratios and deficits as optimal pediatric hemostatic resuscitation practice.
Evolution and systematics of the Aculeata and kin (Hymenoptera), with emphasis on the ants (Formicoidea: †@@@idae fam. nov., Formicidae)
Authors: Boudinot Brendon E. , Khouri Ziad , Richter Adrian , Griebenow Zachary H. , van de Kamp Thomas , Perrichot Vincent , Barden Phillip 
Published: February 2022

ABSTRACTFossils provide unique opportunity to understand the tempo and mode of evolution and are essential for modeling the history of lineage diversification. Here, we interrogate the Mesozoic fossil record of the Aculeata, with emphasis on the ants (Formicidae), and conduct an extended series of ancestral state estimation exercises on distributions of tip-dated combined-evidence phylogenies. We developed and illustrated from ground-up a series of 576 morphological characters which we scored for 144 extant and 431 fossil taxa, including all families of Aculeata, Trigonaloidea, Evanioidea, and †Ephialtitoidea. We used average posterior probability support to guide composition of a target matrix of 303 taxa, for which we integrated strongly filtered ultraconserved element (UCE) data for 115 living species. We also implemented reversible jump MCMC (rjMCMC) and hidden state methods to model complex behavioral characters to test hypotheses about the pathway to obligate eusociality. In addition to revising the higher classification of all sampled groups to family or subfamily level using estimated character polarities to diagnose nodes across the phylogeny, we find that the mid-Cretaceous genera †Camelomeciaand †Camelospheciaform a clade which is robustly supported as sister to all living and fossil Formicidae. For this reason, we name this extinct clade as †@@@idaefam. nov.and provide a definition for the expanded Formicoidea. Based on our results, we recognize three major phases in the early evolution of the ants: (1) origin of Formicoidea as ground-adapted huntresses during the Late Jurassic in the “stinging aggressor” guild (Aculeata) among various lineages of “sneaking parasitoids” (non-aculeate Vespina); (2) the first formicoid radiation during the Early Cretaceous, by the end of which all major extant linages originated; and (3) turnover of the Formicoidea at the end-Cretaceous leading to the second formicoid radiation. We conclude with a concentrated series of considerations for future directions of study with this dataset and beyond.
Third dose of COVID-19 vaccine, CVnCoV, increased neutralizing activity against SARS-CoV-2 wild-type and Delta variant
Authors: Wolz Olaf-Oliver , Kays Sarah-Katharina , Junker Helga , Koch Sven D. , Mann Philipp , Quintini Gianluca , von Eisenhart-Rothe Philipp , Oostvogels Lidia 
Published: February 2022

AbstractA third dose of CVnCoV, a former candidate mRNA vaccine against SARS-CoV-2, was previously shown to boost neutralizing antibody responses against SARS-CoV-2 wild-type in adults aged 18-60 and >60 years in a phase 2a clinical study. Here we report neutralizing antibody responses to wild-type and a variant of concern, Delta, after a third dose on day (D) 57 and D180. Neutralization activity was assessed using a microneutralization assay. Comparable levels of neutralizing antibodies against wild-type and Delta were induced. These were higher than those observed after the first two doses, irrespective of age or pre-SARS-CoV-2-exposure status, indicating that the first two doses induced immune memory. Four weeks after the third dose on D180, neutralizing titers for wild-type and Delta were two-fold higher in younger participants than in older participants; seroconversion rates were 100% for wild-type and Delta in the younger group and for Delta in the older group. A third CVnCoV dose induced similar levels of neutralizing responses against wild-type virus and the Delta variant in both naïve and pre-exposed participants, aligning with current knowledge from licensed COVID-19 vaccines that a third dose is beneficial against SARS-CoV-2 variants.
A high-throughput yeast display approach to profile pathogen proteomes for MHC-II binding
Authors: Huisman Brooke D. , Dai Zheng , Gifford David K. , Birnbaum Michael E. 
Published: February 2022

AbstractT cells play a critical role in the adaptive immune response, recognizing peptide antigens presented on the cell surface by Major Histocompatibility Complex (MHC) proteins. While assessing peptides for MHC binding is an important component of probing these interactions, traditional assays for testing peptides of interest for MHC binding are limited in throughput. Here we present a yeast display-based platform for assessing the binding of tens of thousands of user-defined peptides in a high throughput manner. We apply this approach to assess a tiled library covering the SARS-CoV-2 proteome and four dengue virus serotypes for binding to human class II MHCs, including HLA-DR401, -DR402, and -DR404. This approach identifies binders missed by computational prediction, highlighting the potential for systemic computational errors given even state-of-the-art training data, and underlines design considerations for epitope identification experiments. This platform serves as a framework for examining relationships between viral conservation and MHC binding, and can be used to identify potentially high-interest peptide binders from viral proteins. These results demonstrate the utility of this approach for determining high-confidence peptide-MHC binding.
Mitoquinone mesylate targets SARS-CoV-2 infection in preclinical models
Authors: Petcherski Anton , Sharma Madhav , Satta Sandro , Daskou Maria , Vasilopoulos Hariclea , Hugo Cristelle , Ritou Eleni , Dillon Barbara Jane , Fung Eileen , Garcia Gustavo , Scafoglio Claudio , Purkayastha Arunima , Gomperts Brigitte N , Fishbein Gregory A , Arumugaswami Vaithilingaraja , Liesa Marc , Shirihai Orian S , Kelesidis Theodoros 
Published: February 2022

SummaryTo date, there is no effective oral antiviral against SARS-CoV-2 that is also anti-inflammatory. Herein, we show that the mitochondrial antioxidant mitoquinone/mitoquinol mesylate (Mito-MES), a dietary supplement, has potent antiviral activity against SARS-CoV-2 and its variants of concern in vitro and in vivo. Mito-MES had nanomolar in vitro antiviral potency against the Beta and Delta SARS-CoV-2 variants as well as the murine hepatitis virus (MHV-A59). Mito-MES given in SARS-CoV-2 infected K18-hACE2 mice through oral gavage reduced viral titer by nearly 4 log units relative to the vehicle group. We found in vitro that the antiviral effect of Mito-MES is attributable to its hydrophobic dTPP+ moiety and its combined effects scavenging reactive oxygen species (ROS), activating Nrf2 and increasing the host defense proteins TOM70 and MX1. Mito-MES was efficacious reducing increase in cleaved caspase-3 and inflammation induced by SARS-CoV2 infection both in lung epithelial cells and a transgenic mouse model of COVID-19. Mito-MES reduced production of IL-6 by SARS-CoV-2 infected epithelial cells through its antioxidant properties (Nrf2 agonist, coenzyme Q10 moiety) and the dTPP moiety. Given established safety of Mito-MES in humans, our results suggest that Mito-MES may represent a rapidly applicable therapeutic strategy that can be added in the therapeutic arsenal against COVID-19. Its potential long-term use by humans as diet supplement could help control the SARS-CoV-2 pandemic, especially in the setting of rapidly emerging SARS-CoV-2 variants that may compromise vaccine efficacy.One-Sentence SummaryMitoquinone/mitoquinol mesylate has potent antiviral and anti-inflammatory activity in preclinical models of SARS-CoV-2 infection.
Multiple bumps can enhance robustness to noise in continuous attractor networks
Authors: Wang Raymond , Kang Louis 
Published: February 2022

AbstractA central function of continuous attractor networks is encoding coordinates and accurately updating their values through path integration. To do so, these networks produce localized bumps of activity that move coherently in response to velocity inputs. In the brain, continuous attractors are believed to underlie grid cells and head direction cells, which maintain periodic representations of position and orientation, respectively. These representations can be achieved with any number of activity bumps, and the consequences of having more or fewer bumps are unclear. We address this knowledge gap by constructing 1D ring attractor networks with different bump numbers and characterizing their responses to three types of noise: fluctuating inputs, spiking noise, and deviations in connectivity away from ideal attractor configurations. Across all three types, networks with more bumps experience less noise-driven deviations in bump motion. This translates to more robust encodings of linear coordinates, like position, assuming that each neuron represents a fixed length no matter the bump number. Alternatively, we consider encoding a circular coordinate, like orientation, such that the network distance between adjacent bumps always maps onto 360 degrees. Under this mapping, bump number does not significantly affect the amount of error in the coordinate readout. Our simulation results are intuitively explained and quantitatively matched by a unified theory for path integration and noise in multi-bump networks. Thus, to suppress the effects of biologically relevant noise, continuous attractor networks can employ more bumps when encoding linear coordinates; this advantage disappears when encoding circular coordinates. Our findings provide motivation for multiple bumps in the mammalian grid network.
Frailty in individuals with depression, bipolar disorder and anxiety disorders: longitudinal analyses of all-cause mortality
Authors: Mutz Julian , Choudhury Umamah , Zhao Jinlong , Dregan Alexandru 
Published: February 2022

AbstractBackgroundFrailty is a medical syndrome that is strongly associated with mortality risk, and an emerging global health burden. Mental disorders are associated with reduced life expectancy and elevated levels of frailty. In this study, we examined the mortality risk associated with frailty in individuals with a lifetime history of mental disorders compared to non-psychiatric controls.MethodsThe UK Biobank study recruited >500,000 adults, aged 37–73, between 2006–2010. We derived the two most common albeit distinctive measures of frailty, the frailty phenotype and the frailty index. Individuals with lifetime depression, bipolar disorder or anxiety disorders were identified from multiple data sources. The primary outcome was all-cause mortality. We have also examined differences in frailty, separately by sex and age.OutcomesAnalyses included up to 297,380 middle-aged and older adults with a median follow-up of 12.19 (IQR = 1.31) years, yielding 3,516,706 person-years of follow-up. We observed higher levels of frailty in individuals with mental disorders for both frailty measures. For key comparisons, individuals with a mental disorder had greater all-cause mortality hazards than their controls. The highest hazard ratio (3.65, 95% CI 2.40-5.54) was observed among individuals with bipolar disorder and frailty, relative to the non-frail controls.InterpretationOur findings highlight elevated levels of frailty across three common mental disorders. The increased mortality risk associated with frailty and mental disorders represents a potentially modifiable target for prevention and treatment to improve life expectancy.FundingBiotechnology and Biological Sciences Research Council.
Assessing the role of vascular risk factors in dementia: Mendelian randomization meta-analysis and comparison with observational estimates
Authors: Lee L , Walker R. M. , Whiteley W. N. 
Published: February 2022

AbstractImportanceAlthough observational studies demonstrate that higher levels of vascular risk factors are associated with an increased risk of dementia, these associations might be explained by confounding or other biases. Mendelian randomization (MR) uses genetic instruments to test causal relationships in observational data.ObjectiveTo determine if genetically predicted modifiable risk factors (type 2 diabetes mellitus, low density lipoprotein cholesterol, high density lipoprotein cholesterol, total cholesterol, triglycerides, systolic blood pressure, diastolic blood pressure, body mass index, and circulating glucose) are associated with dementia by meta-analysing published MR studies. Secondary objectives were to identify heterogeneity in effect estimates across primary MR studies and to compare meta-analysis results with observational studies.Data sourcesMR studies identified by systematic search of Web of Science, OVID and Scopus.Study selectionPrimary MR studies investigating the modifiable risk factors of interest. Only one study from each cohort per risk factor was included. A quality assessment tool was developed to primarily assess the three assumptions of MR for each MR study.Data extraction and synthesisData were extracted on study characteristics, exposure and outcome, effect estimates per unit increase, and measures of variation. Effect estimates were pooled to generate an overall estimate, I2 and Cochrane Q values using fixed-effect model.Main outcomes and measuresOdds ratio (OR) of developing dementia per standardized unit increase in the risk factor of interest.ResultsWe screened 5211 studies and included 12 primary MR studies after applying inclusion and exclusion criteria. Higher genetically predicted body mass index was associated with a higher odds of dementia (OR 1.03 [1.01, 1.05] per 5 kg/m2 increase, one study, p = 0.00285). Overall estimates from MR studies showed a smaller number of associations than those from meta-analyses of observational studies.Conclusion and relevanceGenetically predicted body mass index was associated with an increase in risk of dementia.Key pointsQuestionAre genetically predicted modifiable risk factors associated with dementia?FindingsGenetically predicted higher body mass index was associated with a higher odds of dementia. No evidence was found to support an association between genetically predicted type 2 diabetes mellitus, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, total cholesterol, triglycerides, systolic blood pressure, diastolic blood pressure, plasma glucose and dementia risk.MeaningMany modifiable risk factors associated with dementia in observational studies may not play a causative role.
The interleukin-6/interleukin-23/Thelper-17-axis as a driver of neuro-immune toxicity in the major neurocognitive psychosis or deficit schizophrenia: a precision nomothetic psychiatry analysis
Authors: Al-Hakeim Hussein Kadhem , Alhusseini Ali Fattah , Al-Dujaili Arafat Hussein , Debnath Monojit , Maes Michael 
Published: February 2022

AbstractSchizophrenia and especially defcit schizophrenia (DSCZ)) are characterized by highly significantly increased activities of neuroimmunotoxic pathways and a generalized cognitive decline (G-CoDe). There are no data whether the interleukin(IL)-6/IL-23/Thelper-17 (IL6/IL23/Th17)-axis is more associated with DSCZ than with non-deficit schizophrenia (NDSCZ) and whether changes in this axis are associated with the G-CoDe and the phenome (a factor extracted from all symptom domains) of schizophrenia. This study included 45 DSCZ and 45 NDSCZ patients and 40 controls and delineated whether the IL6/IL23/Th17 axis, trace elements (copper, zinc) and ions (magnesium, calcium) are associated with DSCZ, the G-CoDe and phenome of schizophrenia. Increased plasma IL-23 and IL-6 levels were associated with Th17 upregulation, assessed as a latent vector (LV) extracted from IL-17, IL-21, IL-22, and TNF-α. The IL6/IL23/Th17-axis score, as assessed by a LV extracted from IL-23, IL-6, and the Th17 LV, was significantly higher in DSCZ than in NDSCZ and controls. We discovered that 70.7% of the variance in the phenome was explained by the IL6/IL23/Th17-axis (positively) and the G-CoDe and IL-10 (both inversely); and that 54.6% of the variance in the G-CoDe was explained by the IL6/IL23/Th17 scores (inversely) and magnesium, copper, calcium, and zinc (all positively). In conclusion, the pathogenic IL6/IL23/Th17-axis contributes to the generalized neurocognitive deficit and the phenome of schizophrenia and especially that of DSCZ due to its key role in peripheral inflammation and neuroinflammation and its consequent immunotoxic effects on neuronal circuits. These clinical impairments are more prominent in subjects with lowered IL-10, magnesium, calcium, and zinc.
Increase in SARS-CoV-2 RBD-specific IgA and IgG Antibodies in Human Milk from Lactating Women Following the COVID-19 Booster Vaccination
Authors: Henle Andrea M. 
Published: February 2022

AbstractThe CDC recommended a booster dose of the Pfizer-BioNTech Comirnaty (BNT162b2) COVID-19 mRNA vaccine in September 2021 for high-risk individuals. Pregnant and high-risk lactating women were encouraged to receive the booster to obtain potential prolonged protection for themselves and their infants. This study investigated the ability of the booster vaccine to increase IgA and IgG antibodies specific to the receptor binding domain (RBD) of the SARS-CoV-2 spike protein in human milk compared to levels pre-booster. We found a significant increase in both anti-RBD-specific IgA and IgG antibodies in human milk 1-2 weeks after the Pfizer-BioNTech booster and at the study endpoint (60 days post-booster). These results suggest the booster vaccination enhances SARS-CoV-2 specific immunity in human breast milk, which may be protective for infants.Key PointsAbs to SARS-COV-2 RBD are detected in blood ≥60 days post-Pfizer-BioNTech booster.Human milk Abs to SARS-COV-2 RBD are higher ≥60 days post-booster vs pre-booster.