bluuebunny/crossref_metadata_2025_split huggingface dataset:
PF4-Dependent Immunoassays in Patients with Vaccine-Induced Immune Thrombotic Thrombocytopenia: Results of an Interlaboratory Comparison
Authors: Tiede Andreas , Althaus Karina , Sachs Ulrich J. , Cooper Nina , Czwalinna Andreas , Müller Jens , Pötzsch Bernd 
Published: June 2021

Abstract
Background Coronavirus disease 2019 vaccine ChAdOx1 nCov-19 may rarely lead to vaccine-induced thrombotic thrombocytopenia (VITT). Antibody-mediated, platelet factor 4 (PF4)-dependent platelet activation appears to resemble a key mechanism in VITT, partially comparable to heparin-induced thrombocytopenia. The use of PF4/heparin immunoassays has been proposed as part of a diagnostic approach, but their sensitivity has not been established.
Methods Sera from 12 well-defined VITT patients were first studied by two different laboratories in functional assays. Sera where then used for an interlaboratory comparison, in which five different PF4/heparin immunoassays were used by four laboratories.
Results Results for functional testing were highly concordant. VITT antibodies were also reliably detected by PF4/heparin enzyme-linked immunosorbent assays (ELISAs) (92–100%). In contrast, only 25% of VITT antibodies were reactive in a particle gel immunoassay (PaGIA), and 8% in a lateral flow assay (LFA). An automated chemiluminescence immunoassay (CLIA) was negative for all sera tested (0%).
Conclusion It seems feasible to establish functional antibody testing for the confirmation of VITT. For the initial screening of suspected VITT cases, PaGIA, LFA, and CLIA are useless when applied as single tests. Only ELISA-based PF4/heparin immunoassays are sensitive enough to be incorporated in the diagnostic workup. However, a combination of a positive ELISA and a negative CLIA may be useful to identify VITT antibodies in the absence of confirmatory functional assays.
Admission Anion Gap Metabolic Acidosis and Its Impact on Patients in Medical Intensive Care Unit
Authors: Dafal Akshay , Kumar Sunil , Agrawal Sachin , Acharya Sourya , Nirmal Apoorva 
Published: June 2021

Abstract
Introduction Anion gap (AG) metabolic acidosis is common in critically ill patients. The relationship between initial AG at the time of admission to the medical intensive care unit (MICU) and mortality or length of stay is unclear. This study was undertaken to evaluate this relationship.
Materials and Method We prospectively examined the acid–base status of 500 consecutive patients at the time of MICU admission and outcome was measured in terms of mortality, length of ICU stay, need of ventilator, and laboratory parameters. The patients were divided into four stages based on the severity of AG. Outcome based on the severity of AG was measured, and comparisons that adjusted for baseline characteristics were performed.
Results This study showed that increased AG was associated with the higher mortality. Patients with the highest AG also had the longest length of stay in the MICU, and patients with normal acid–base status had the shortest ICU length of stays (p < 0.05).
Conclusion A high AG at the time of admission to the MICU was associated with higher mortality and length of stays. Initial risk stratification based on AG and metabolic acidosis may help guide appropriate patient disposition (especially in patients without other definitive criteria for MICU admission) and assist with prognosis.
Characteristics, Treatment, and Prognosis of Cracked Teeth: A Comparison with Data from 10 Years Ago
Authors: Lee Tae Yeon , Yang Sung Eun , Kim Hye Min , Kye Min Joo 
Published: June 2021

Abstract
Objectives The purpose of this study was to analyze and to compare retrospectively the characteristics, the treatment process, and the prognosis of cracked teeth by comparing recent data with data from 10 years ago.
Materials and Methods Sixty-eight cracked teeth from March 2009 to June 2010 (2009 data) and 185 cracked teeth from March 2019 to June 2020 (2019 data) were analyzed. The characteristics of cracked teeth and the treatment method depending on probing depth, caries, and symptoms, and prognosis depending on pocket depth and apical lesions were analyzed using R version 3.3.3 (R Foundation for Statistical Computing, Vienna, Austria) and T&F version 3.0 (YooJin BioSoft, Korea). To compare proportions, the two-sample proportion test was performed. The distribution of proportions within the samples from 2009 and 2019 data was analyzed using the Chi-square test or binomial test. A p-value <0.05 was considered to indicate statistical significance.
Results Significantly fewer cracked teeth received root canal treatment before crown in 2019 than in 2009 (p = 0.032). In both 2009 and 2019, symptomatic cracked teeth and those with deep periodontal pockets (>6 mm) were significantly more likely to receive root canal treatment. In both years, cracked teeth with a probing depth less than 6 mm or without an apical lesion were significantly more likely to be asymptomatic at 3-month and 6-month follow-ups (p < 0.001).
Conclusion Cracked teeth with a deep periodontal pocket or symptoms had a higher likelihood of endodontic treatment, and the presence of a deep periodontal pocket or apical lesion was associated with a higher risk of persistent symptoms. Therefore, clinicians should consider these factors when planning treatment and predicting patients’ prognosis.
The Impact of the COVID-19 Pandemic on Head and Neck Surgery Training: A Brazilian National Survey
Authors: Leite Ana Kober , Matos Leandro Luongo , Cernea Claudio R. , Kowalski Luiz Paulo 
Published: June 2021

Abstract
Introduction The COVID-19 pandemic has had a high impact on surgical training around the world due to required measures regarding the suspension of elective procedures and the dismissal of nonessential personnel.
Objectives To understand the impact the pandemic had on head and neck surgery training in Brazil.
Methods We conducted a 29-question online survey with head and neck surgery residents in Brazil, assessing the impact the pandemic had on their training.
Results Forty-six residents responded to the survey, and 91.3% of them reported that their residency was affected by the pandemic, but most residents were not assigned to work directly with patients infected with the new coronavirus (71.4%). All residents reported decrease in clinic visits and in surgical procedures, mostly an important reduction of ∼ 75%. A total of 56.5% of the residents described that the pandemic has had a negative impact on their mental, health and only 4 (8.7%) do not have any symptoms of burnout. The majority (78.3%) of the residents reported that educational activities were successfully adapted to online platforms, and 37% were personally infected with the virus.
Conclusion Most surgical residencies were greatly affected by the pandemic, and residents had an important decrease in surgical training. Educational activities were successfully adapted to online modalities, but the residency programs should search for ways of trying to compensate for the loss of practical activities.
Rapid Release of Interleukin-1β from Human Platelets Is Independent of NLRP3 and Caspase
Authors: Pennings Gabrielle J. , Reddel Caroline J. , Traini Mathew , Lam Magdalena , Kockx Maaike , Chen Vivien M. , Kritharides Leonard 
Published: June 2021

AbstractObjective Platelets are critical in mediating both rapid responses to injury and the development and progression of coronary disease. Several studies have shown that, after prolonged exposure to agonists, they produce and release inflammatory mediators including interleukin-1β (IL-1β), via the classical pathway (NLRP3 inflammasome and caspase-1 cleavage to release active IL-1β) as described for leukocytes. This study aimed to determine whether there is rapid release of IL-1β in response to soluble platelet agonists and whether such rapid release is NLRP3- and caspase-1-dependent.Methods and Results Using flow cytometry to detect platelet activation (and release of α and dense granule contents) and the combination of Western blotting, enzyme-linked-immunosorbent assay, and immunogold labeling transmission electron and immunofluorescence microscopy, we identified that resting human platelets contain mature IL-1β. Platelets release IL-1β within minutes in response to adenosine diphosphate (ADP), collagen, and thrombin receptor agonists, but not in response to conventional NLRP3 inflammasome agonists—lipopolysaccharide and adenosine triphosphate. The rapid release of IL-1β in response to ADP and thrombin receptor agonists was independent of caspases (including caspase-1) and NLRP3. Immature and mature IL-1β were identified as low-abundance proteins on transmission electron microscopy of human platelets, and were localized to the platelet cytosol, open canalicular system, and the periphery of α granules.Conclusion Unlike monocytes and neutrophils, human platelets are capable of rapid agonist- and time-dependent release of IL-1β by a mechanism which is independent of caspase-1 and NLRP3.
Systematic improvement of molecular excited state calculations by inclusion of nuclear quantum motion: A mode-resolved picture and the effect of molecular size
Authors: Hele Timothy J. H. , Monserrat Bartomeu , Alvertis Antonios M. 
Published: June 2021

The energies of molecular excited states arise as solutions to the electronic Schrödinger equation and are often compared to experiment. At the same time, nuclear quantum motion is known to be important and to induce a redshift of excited state energies. However, it is thus far unclear whether incorporating nuclear quantum motion in molecular excited state calculations leads to a systematic improvement of their predictive accuracy, making further investigation necessary. Here, we present such an investigation by employing two first-principles methods for capturing the effect of quantum fluctuations on excited state energies, which we apply to the Thiel set of organic molecules. We show that accounting for zero-point motion leads to much improved agreement with experiment, compared to “static” calculations that only account for electronic effects, and the magnitude of the redshift can become as large as 1.36 eV. Moreover, we show that the effect of nuclear quantum motion on excited state energies largely depends on the molecular size, with smaller molecules exhibiting larger redshifts. Our methodology also makes it possible to analyze the contribution of individual vibrational normal modes to the redshift of excited state energies, and in several molecules, we identify a limited number of modes dominating this effect. Overall, our study provides a foundation for systematically quantifying the shift of excited state energies due to nuclear quantum motion and for understanding this effect at a microscopic level.
Structural differences in the FAD-binding pockets and lid loops of mammalian CRY1 and CRY2 for isoform-selective regulation
Authors: Miller Simon , Srivastava Ashutosh , Nagai Yoshiko , Aikawa Yoshiki , Tama Florence , Hirota Tsuyoshi 
Published: June 2021

Significance
CRY1 and CRY2 regulate circadian rhythms, and their dysfunction has been associated with many diseases. Since they have not only similar but also independent functions, understanding of intrinsic differences between these highly similar proteins is required. Here, we determined CRY1 and CRY2 static and dynamic structures that exhibited conformational isomerism in their ligand-binding FAD pockets and neighboring lid loops, allowing mechanistic insight into structural features specific to each isoform. Structure-guided mutations supported important roles of interactions between a key “gatekeeper” tryptophan residue in the FAD pocket and lid loop residues in determining the effects of isoform-selective compounds. Our results provide insight into how near-identical ligand-binding pockets can intrinsically regulate compound selectivity through unique interactions with neighboring structural elements.
All loop structures in supergravity amplitudes on AdS5 × S5 from CFT
Authors: Bissi Agnese , Fardelli Giulia , Georgoudis Alessandro 
Published: June 2021

Abstract
We compute a set of structures which appear in the four-point function of protected operators of dimension two in

N
=
4

super Yang Mills with SU(N) gauge group, at any order in a large N expansion. They are determined only by leading order CFT data. By focusing on a specific limit, we make connection with the dual supergravity amplitude in flat space, where such structures correspond to iterated s-cuts. We make several checks and we conjecture that the same interpretation holds for supergravity amplitudes on AdS5 × S5.
Free vibration analysis of composite conical shells using Walsh series method
Authors: Guo Shibai , Hu Ping , Li Sheng 
Published: June 2021

Abstract
As a typical structure of underwater vehicles, the vibration characteristics of the conical shell are of great significance to the selection of structural design parameters. This paper aims at the free vibration of composite conical shells with general boundary conditions by presenting a simple yet efficient solution based on the Walsh series (WS). The theoretical model is formulated on the basis of the first-order shear deformation shell theory. Elastic boundary conditions are equivalent by introducing weight parameters at boundary positions. The governing differential equation and boundary equation are obtained directly by the Hamilton principle, and decomposed by separating variables. Then Walsh series (WS) is applied for the axial direction and the Fourier series is assumed with respect to the circumferential direction. The unknown constants generated during integration can be determined by boundary conditions, and thus the partial differential equations are transformed into algebraic equations. By solving these algebraic equations, then natural frequencies and mode shapes of the composite conical shells are obtained. Compared with the existing solutions, the accuracy and reliability of the proposed method are verified. The effects of geometric and material parameters on the natural frequencies of composite conical shells are studied.
Effects of Sn addition on dynamic grain growth in a binary Mg-1Ca alloy
Authors: Rashed H M M A , Mesbah M B 
Published: June 2021

Abstract
The possibility of dynamic grain growth of a binary Mg-1Ca alloy with minor tin contents was investigated at various conditions of temperature and strain rate. Mg-1Ca, Mg-1Ca-1Sn and Mg-1Ca-2Sn alloys were cast and homogenized at 410 °C followed by hot-rolling at 400 °C with equal strains. Calcium contributed to refining of grains, with an additional support from tin. In the as-cast alloys, tin was found to promote dendrite formation. Though presence of Ca2Sn phase was predicted by thermodynamic modelling, microstructurally a ternary phase MgCaSn was predominantly found. This ternary phase was also comparatively coarser in size. Uniaxial tensile test of rolled samples was carried out at temperatures 300, 350, 400 and 450 °C, and at two different strain rates 5 × 10−4 s−1 and 1 ×

10

−
4

s

−
1

.

Variation of grain distribution was also measured at the grip and gauge regions at different locations. Samples were taken from six different locations of the deformed samples. Even at faster deformation, the grains were not elongated. At slower strain rate condition, extent of dynamic grain growth was higher compared to that of the higher strain rate condition. Mg2Ca particles were not effective in restricting movement of grain boundaries. Mg2Sn particles were dissolved in the matrix at the elevated temperatures, and the grain growth limiting was profoundly dominated by the presence of MgCaSn phase.
Enduring images
Authors: Slack Paul 
Published: June 2021

Abstract
‘Enduring images’ describes the various images which have been attached to plague. These include graphic metaphors, like the arrows of Apollo and the swords of biblical angels, which symbolize its causes; and literary conventions, such as those of Thucydides and Boccaccio about the disruption of families and societies, which summarize its consequences. Over time, new icons have been added to them, such as plague-saints and plague-doctors, and metaphors were borrowed from other contexts, like the Dance of Death and visions of the Apocalypse. Taken together, they determined how plague was imagined in the past. Ultimately, images of plague have a continuous history, invented and then elaborated over the centuries.
Productive Social Engagement as a Vehicle to Promote Activity and Neuro-Cognitive Health in Later Adulthood
Authors: Carlson Michelle C 
Published: June 2021

Abstract

Objective
We have witnessed two key findings that shift our understanding of human brain aging in new directions. First, we learned that the adult brain remains plastic beyond childhood development, generating new neurons in response to activity and new experiences, particularly in regions that integrate memories in social contexts. The second emerging finding is the importance of physical activity and social engagement to cognitive aging. I integrate these and other empirical findings with our understanding of brain development over the life span and the later-life developmental need to give back to younger generations to posit the importance of maintaining our “social” brain through retirement and into later life when activity remains beneficial to brain health.

Conclusions
Opportunities for improved cognitive and brain health that can be brought to scale need to capitalize on aging adults’ need to remain socially relevant and on community infrastructures so that those with lower neighborhood access to activity can safely engage. Evidence is summarized here from one such community-based model of social engagement through school-based, volunteer service, entitled Experience Corps®. This program seeks to increase daily physical, cognitive, and social activity to promote cognitive and mental health.
Systematic evaluation of transcriptomics-based deconvolution methods and references using thousands of clinical samples
Authors: Nadel Brian B , Oliva Meritxell , Shou Benjamin L , Mitchell Keith , Ma Feiyang , Montoya Dennis J , Mouton Alice , Kim-Hellmuth Sarah , Stranger Barbara E , Pellegrini Matteo , Mangul Serghei 
Published: June 2021

Abstract
Estimating cell type composition of blood and tissue samples is a biological challenge relevant in both laboratory studies and clinical care. In recent years, a number of computational tools have been developed to estimate cell type abundance using gene expression data. Although these tools use a variety of approaches, they all leverage expression profiles from purified cell types to evaluate the cell type composition within samples. In this study, we compare 12 cell type quantification tools and evaluate their performance while using each of 10 separate reference profiles. Specifically, we have run each tool on over 4000 samples with known cell type proportions, spanning both immune and stromal cell types. A total of 12 of these represent in vitro synthetic mixtures and 300 represent in silico synthetic mixtures prepared using single-cell data. A final 3728 clinical samples have been collected from the Framingham cohort, for which cell populations have been quantified using electrical impedance cell counting. When tools are applied to the Framingham dataset, the tool Estimating the Proportions of Immune and Cancer cells (EPIC) produces the highest correlation, whereas Gene Expression Deconvolution Interactive Tool (GEDIT) produces the lowest error. The best tool for other datasets is varied, but CIBERSORT and GEDIT most consistently produce accurate results. We find that optimal reference depends on the tool used, and report suggested references to be used with each tool. Most tools return results within minutes, but on large datasets runtimes for CIBERSORT can exceed hours or even days. We conclude that deconvolution methods are capable of returning high-quality results, but that proper reference selection is critical.
TimeCycle: topology inspired method for the detection of cycling transcripts in circadian time-series data
Authors: Ness-Cohn Elan , Braun Rosemary 
Published: June 2021

Abstract

Motivation
The circadian rhythm drives the oscillatory expression of thousands of genes across all tissues. The recent revolution in high-throughput transcriptomics, coupled with the significant implications of the circadian clock for human health, has sparked an interest in circadian profiling studies to discover genes under circadian control.

Result
We present TimeCycle: a topology-based rhythm detection method designed to identify cycling transcripts. For a given time-series, the method reconstructs the state space using time-delay embedding, a data transformation technique from dynamical systems theory. In the embedded space, Takens’ theorem proves that the dynamics of a rhythmic signal will exhibit circular patterns. The degree of circularity of the embedding is calculated as a persistence score using persistent homology, an algebraic method for discerning the topological features of data. By comparing the persistence scores to a bootstrapped null distribution, cycling genes are identified. Results in both synthetic and biological data highlight TimeCycle’s ability to identify cycling genes across a range of sampling schemes, number of replicates and missing data. Comparison to competing methods highlights their relative strengths, providing guidance as to the optimal choice of cycling detection method.

Availabilityand implementation
A fully documented open-source R package implementing TimeCycle is available at: https://nesscoder.github.io/TimeCycle/.

Supplementary information
Supplementary data are available at Bioinformatics online.
Placebo effect in pharmacological management of fibromyalgia: a meta-analysis
Authors: Migliorini Filippo , Maffulli Nicola , Eschweiler Jörg , Betsch Marcel , Tingart Markus , Colarossi Giorgia 
Published: June 2021

Abstract

Introduction
The management of fibromyalgia involves a combination of pharmacological and non-pharmacological treatments.

Source of data
Recently published literature in PubMed, Google Scholar and Embase databases.

Areas of agreement
Several pharmacological and non-pharmacological strategies have been proposed for the management of fibromyalgia. However, the management of fibromyalgia remains controversial. The administration of placebo has proved to be more effective than no treatment in many clinical settings and evidence supports the ‘therapeutic’ effects of placebo on a wide range of symptoms.

Areas of controversy
The placebo effect is believed to impact the clinical outcomes, but its actual magnitude is controversial.

Growing points
A meta-analysis comparing pharmacological management versus placebo administration for fibromyalgia was conducted.

Areas timely for developing research
Drug treatment resulted to be more effective than placebo administration for the management of fibromyalgia. Nevertheless, placebo showed a beneficial effect in patients with fibromyalgia. Treatment-related adverse events occurred more frequently in the drug treatment.

Level of evidence
I, Bayesian network meta-analysis of double-blind randomized clinical trials.