bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of Perioperative Blood Pressure on Hematoma Development After Panniculectomy
Authors: Rudolph Megan , Galazra Laura , Greer Madison , Hemal Kshipra , Runyan Christopher 
Published: June 2021

Purpose
Hematoma affects 10% to 13% of patients undergoing panniculectomy. Although elevated perioperative blood pressure has been associated with hematoma after rhytidectomy, this has not been established for panniculectomy. We sought to determine the impact of perioperative blood pressure on hematoma development in patients undergoing panniculectomy.

Methods
A retrospective review was performed on patients undergoing isolated panniculectomy procedures. Blood pressure parameters recorded included systolic blood pressures (SBPs), diastolic blood pressures (DBPs), and mean arterial pressure. The mean, peak, and trough blood pressure values were recorded. Preoperative, intraoperative, and postoperative blood pressures were recorded, and differences between phases were calculated. Univariate and multivariate logistic regressions were performed.

Results
One hundred forty-three patients were identified, which included 84% (n = 120) women and 17% (n = 23) men. A history of hypertension was present in 55% (n = 79) of patients, of which 91% (n = 72) were medically controlled. Preoperative antiplatelet or anticoagulation was used in 21% (n = 31) of patients. Seven patients (5%) developed a hematoma, of which 5 required operative drainage. Development of hematoma was not associated with patient, surgical, or postoperative pain variables. There was an association between hematoma and elevated postoperative blood pressures on univariate and multivariate analyses. The mean peak SBP in the hematoma group was 160 mm Hg in comparison to 141 mm Hg in the nonhematoma group. For each 10-mm Hg increase in postoperative peak SBP, the odds of a hematoma increased by 2.8 times. When comparing phases of care, hematoma patients had similar intraoperative and postoperative peak SBP, but their postoperative SBP was 19 mm Hg higher than preoperative baseline. Conversely, nonhematoma patients had a postoperative blood pressure that was similar to their preoperative baseline and 20 mm Hg lower than their intraoperative values.

Conclusions
Hematoma is associated with elevated postoperative blood pressures. A postoperative mean peak SBP of 160 mm Hg was associated with hematoma, and for each 10 mm Hg, the risk of hematomsa increased by 2.8 times. The risk of hematoma may be reduced by strict postoperative blood pressure control. We recommend a postoperative peak SBP goal of 140 mm Hg or less, with a value equal to or less than their preoperative baseline and 20 mm Hg lower than their intraoperative pressure.
Disrupted Ca2+ homeostasis and immunodeficiency in patients with functional Inositol 1,4,5-trisphosphate receptor subtype 3 defects
Authors: Neumann Julika , Van Nieuwenhove Erika , Terry Lara E , Staels Frederik , Knebel Taylor R , Welkenhuyzen Kirsten , Baker Mariah R , Gerbaux Margaux , Willemsen Mathijs , Barber John S. , Serysheva Irina I , De Waele Liesbeth , Vermeulen François , Meyts Isabelle , Yule David I , Bultynck Geert , Schrijvers Rik , Humblet-Baron Stephanie , Liston Adrian 
Published: June 2021

AbstractCalcium signaling is essential for lymphocyte activation, with genetic disruptions resulting in severe immunodeficiency. The inositol 1,4,5-trisphosphate receptor (IP3R), formed from homo- or hetero-tetramers of the IP3R isoforms 1-3, amplifies lymphocyte signaling by releasing Ca2+ from ER stores into the cytosol following antigen-stimulation. While knockout of all 3 IP3R isoforms results in immunodeficiency in mice, the seeming redundancy of subunits was thought to explain the absence of IP3R mutation as a cause of human immunodeficiency. Here, we identify compound heterozygous variants in ITPR3 in two unrelated Caucasian patients presenting with combined immunodeficiency, in one case requiring hematopoietic stem cell transplantation. We observed disrupted Calcium homeostasis in patient-derived fibroblasts and immune cells, with abnormal proliferation and activation responses following B and T cell receptor stimulation. Reconstitution of IP3R knockout cell lines identified the variants as functional hypomorphs with reduced discrimination between homeostatic and induced states, validating a link between genotype and phenotype. These results demonstrate a functional linkage between defective ER Ca2+ channels and immunodeficiency, and identify IP3Rs as diagnostic targets for patients with specific inborn errors of immunity.
Knowledge, attitude and practice towards antibiotic use and resistance among the veterinarians in Bangladesh
Authors: Sarker Md Samun , Ahmed Iftekhar , Siddiky Nure Alam , Islam Shariful , Begum Ruhena , Ahmed Ayesha , Mahua Fatema Akter , Kabir Md Ehsanul , Samad Mohammed A. 
Published: June 2021

AbstractBackgroundThe emergence of antimicrobial resistance is growing human and animal health concern around the world. When a number of studies have emphasized the Knowledge, Attitude and Practice (KAP) regarding antibiotic use and resistance in humans, little attention has been paid to the veterinary sector. The aim of this study was to understand the KAP towards antibiotic use and resistance among the veterinarians in Bangladesh.MethodsA cross-sectional online based questionnaire survey was conducted from August to September 2020 among the registered veterinary practitioners. A self-administered Google form questionnaire consists of 45 questions on knowledge, attitude and practice regarding antibiotic use and resistance were used.ResultsA total of 208 registered veterinarians participated in this study. 85.1% of the participants were male and 54.8% of the participants had a Masters degree. Around 52% of the veterinarians were poultry practitioners. All respondents were familiar with antimicrobials. The participants (91.4%) knew that antibiotics can not cure viral infections while 97.6% believed that frequent antibiotic prescription rendered them less effective. Participants claimed that only they are eligible to prescribe drugs for the treatment of animals and around 80% disagreed with adding antibiotics with feed/water as a growth promoter in livestock. Of the total participants, 87% believed that a local antimicrobial guideline would be more effective than an international one. However, gaps in practices were highlighted in our study, suggesting training deficiencies.ConclusionThe present study for the first time conducted in Bangladesh dictates the future interventions like academic courses, workshops, and seminars on antibiotic usage and resistance are needed to ameliorate the knowledge, behavior and practice of veterinarians with regards to the rational use of antibiotics.
B.1.1.7 and B.1.351 variants are highly virulent in K18-ACE2 transgenic mice and show different pathogenic patterns from early SARS-CoV-2 strains
Authors: Radvak Peter , Kwon Hyung Joon , Kosikova Martina , Ortega-Rodriguez Uriel , Xiang Ruoxuan , Phue Je-Nie , Shen Rong-Fong , Rozzelle James , Kapoor Neeraj , Rabara Taylor , Fairman Jeff , Xie Hang 
Published: June 2021

AbstractSARS-CoV-2 continues to circulate globally resulting in emergence of several variants of concern (VOC), including B.1.1.7 and B.1.351 that show increased transmissibility and enhanced resistance to antibody neutralization. In a K18-hACE2 transgenic mouse model, we demonstrate that Both B.1.1.7 and B.1.351 are 100 times more lethal than the original SARS-CoV-2 bearing 614D. Mice infected with B.1.1.7 and B.1.351 exhibited more severe lesions in internal organs than those infected with early SARS-CoV-2 strains bearing 614D or 614G. Infection of B.1.1.7 and B.1.351 also results in distinct tissue-specific cytokine signatures, significant D-dimer depositions in vital organs and less pulmonary hypoxia signaling before death as compared to the mice infected with early SARS-CoV-2 strains. However, K18-hACE2 mice with the pre-existing immunity from prior infection or immunization were resistant to the lethal reinfection of B.1.1.7 or B.1.351, despite having reduced neutralization titers against these VOC. Our study reveals distinguishing pathogenic patterns of B.1.1.7 and B.1.351 variants from those early SARS-CoV-2 strains in K18-hACE2 mice, which will help to inform potential medical interventions for combatting COVID-19.
Raman spectroscopy on blood serum samples of patients with end-stage liver disease
Authors: René Staritzbichler , Pascal Hunold , Irina Estrela-Lopis , Hildebrand Peter W. , Berend Isermann , Thorsten Kaiser 
Published: June 2021

AbstractRaman spectroscopy has shown to be a promising method for the examination of biomedical samples. However, until now, its efficacy has not been established in clinical diagnostics. In this study, Raman spectroscopy’s potential application in medical laboratories is evaluated for a large variety (38) of biomarkers. Given 234 serum samples from a cohort of patients with different stages of liver disease, we performed Raman spectroscopy at 780nm excitation wavelength. The Raman spectra were analyzed in combination with the results of routine diagnostics using specifically developed complex mathematical algorithms, including fluorescence filtering, frequency subset selection and several overfitting circumventing strategies, such as independent validation. With the results of this cohort, which were validated in 328 independent samples, a significant proof-of-concept study was completed. This study highlights the need to prevent overfitting and to use independent data for validation. The results reveal that Raman spectroscopy has high potential for use in medical laboratory diagnostics to simultaneously quantify multiple biomarkers.
Multifunctionality of belowground food webs: resource, size and spatial energy channels
Authors: Potapov Anton 
Published: June 2021

AbstractThe belowground compartment of terrestrial ecosystems drives nutrient cycling, the decomposition and stabilisation of organic matter, and supports aboveground life. Belowground consumers create complex food webs that regulate functioning, ensure stability and support biodiversity both below and above ground. However, existing soil food-web reconstructions do not match recently accumulated empirical evidence and there is no comprehensive reproducible approach that accounts for the complex resource, size and spatial structure of food webs in soil. Here I build on generic food-web organization principles and use multifunctional classification of soil protists, invertebrates and vertebrates, to reconstruct ‘multichannel’ food-web across size classes of soil-associated consumers. This reconstruction is based on overlying feeding preference, prey protection, size spectrum and spatial distribution matrices combined with biomasses of trophic guilds to infer weighted trophic interactions. I then use food-web reconstruction, together with assimilation efficiencies, to calculate energy fluxes assuming a steady-state energetic system. Based on energy fluxes, I describe a number of indicators, related to stability, biodiversity and multiple ecosystem-level functions such as herbivory, top-down control, translocation and transformation of organic matter. I illustrate the approach with an empirical example, comparing it with traditional resource-focused soil food-web reconstruction. The multichannel reconstruction can be used to assess trophic multifunctionality (analogous to ecosystem multifunctionality), i.e. simultaneous support of multiple trophic functions by the food-web, and compare it across communities and ecosystems spanning beyond the soil. With further validation and parametrization, my multichannel reconstruction approach provides an effective tool for understanding and analysing soil food webs. I believe that having this tool will inspire more people to comprehensively describe soil communities and belowground-aboveground interactions. Such studies will provide informative indicators for including consumers as active agents in biogeochemical models, not only locally but also on regional and global scales.
AGNOSTOS-DB: a resource to unlock the uncharted regions of the coding sequence space
Authors: Vanni Chiara , Schechter Matthew S. , Delmont Tom O. , Eren A. Murat , Steinegger Martin , Glöckner Frank Oliver , Fernandez-Guerra Antonio 
Published: June 2021

AbstractGenomes and metagenomes contain a considerable percentage of genes of unknown function, which are often excluded from downstream analyses limiting our understanding of the studied biological systems. To address this challenge, we developed AGNOSTOS, a combined database-computational workflow resource that unifies the known and unknown coding sequence space of genomes and metagenomes. Here, we present AGNOSTOS-DB, an extensive database of high-quality gene clusters enriched with functional, ecological and phylogenetic information. Moreover, AGNOSTOS allows integrating new data into existing AGNOSTOS-DBs, maximizing the information retrievable for the genes of unknown function. As a proof of concept, we provide a seed database that integrates the predicted genes from marine and human metagenomes, as well as from Bacteria, Archaea, Eukarya and giant viruses environmental and cultivar genomes. The seed database comprises 6,572,081 gene clusters connecting 342 million genes and represents a comprehensive and scalable resource for the inclusion and exploration of the unknown fraction of genomes and metagenomes.
E156G and Arg158, Phe-157/del mutation in NTD of spike protein in B.1.617.2 lineage of SARS-CoV-2 leads to immune evasion through antibody escape
Authors: Chaudhari Armi M , Kumar Dinesh , Joshi Madhvi , Patel Amrutlal , Joshi Chaitanya 
Published: June 2021

AbstractEmerging variants of SARS-CoV-2 with better immune escape mechanisms and higher transmissibility remains a persistent threat across the globe. B.1.617.2 (Delta) variant was first emerged from Maharashtra, India in December, 2020. This variant is classified to be a major cause and concern of the second wave of COVID-19 in India. In the present study, we explored the genomic and structural basis of this variant through computational analysis, protein modelling and molecular dynamics (MD) simulations approach. B.1.617.2 variant carried E156G and Arg158, Phe-157/del mutations in NTD of spike protein. These mutations in N-terminal domain (NTD) of spike protein of B.1.617.2 variant revealed more rigidity and reduced flexibility compared to spike protein of Wuhan isolate. Further, docking and MD simulation study with 4A8 monoclonal antibody which was reported to bind NTD of spike protein suggested reduced binding of B.1.617.2 spike protein compared to that of spike protein of Wuhan isolate. The results of the present study demonstrate the possible case of immune escape and thereby fitness advantage of the new variant and further warrants demonstration through experimental evidence. Our study identified the probable mechanism through which B.1.617.2 variant is more pathogenically evolved with higher transmissibility as compared to the wild-type.Abstract Figure
Generation of star-shaped human induced astrocytes with a mature inflammatory phenotype for CNS disease modeling
Authors: Voulgaris Dimitrios , Nikolakolpoulou Polyxeni , Herland Anna 
Published: June 2021

SummaryGenerating astrocytes from induced pluripotent stem cells has been hampered by either prolonged differentiation -spanning over two months -or by shorter protocols that generate immature astrocytes, devoid of salient inflammation-associated astrocytic traits pivotal for CNS neuropathological modeling. We directed human neural stem cells derived from induced pluripotent stem cells to astrocytic commitment and maturity by orchestrating an astrocytic-tuned culturing environment. In under 28 days, the generated cells express canonical and mature astrocytic markers, denoted by the expression of AQP4 and, remarkably, the expression and functionality of glutamate transporter EAAT2. We also show that this protocol generates astrocytes that encompass traits critical in CNS disease modeling, such as glutathione synthesis and secretion, upregulation of ICAM-1 and a cytokine secretion profile which is on par with primary astrocytes. This protocol generates a multifaceted astrocytic model suitable for CNS in vitro disease modeling and personalized medicine through brain-on-chip technologies.
Mitochondria decode firing frequency and coincidences of postsynaptic APs and EPSPs
Authors: Stoler Ohad , Stavsky Alexandra , Khrapunsky Yana , Melamed Israel , Stutzmann Grace , Gitler Daniel , Sekler Israel , Fleidervish Ilya 
Published: June 2021

SummaryMitochondrial metabolism is critical for brain function. However, the mechanisms linking mitochondrial energy production to neuronal activity are elusive. Using whole-cell electrical recordings from Layer 5 pyramidal neurons in cortical slices and fluorescence imaging of cytosolic, mitochondrial Ca2+ indicators and endogenous NAD(P)H, we revealed ultra-fast, spike-evoked mitochondrial Ca2+ transients temporally similar to cytosolic Ca2+ elevations. We demonstrate that, whereas single or few spikes elicit the mitochondrial Ca2+ transients throughout the cell, their amplitude is differentially regulated in distinct neuronal compartments. Thus, these signals were prominent in the soma and apical dendrites and ∼3 times smaller in basal dendrites and axons. The spike firing frequency had a subtle effect on the amplitude of the cytosolic Ca2+ elevations but dramatically affected mitochondrial Ca2+ transients and NAD(P)H oxidation and recovery rates. Moreover, while subthreshold EPSPs alone caused no detectable Ca2+ elevation in dendritic mitochondria, the Hebbian coincidence of unitary EPSP and postsynaptic spike produced a localized, single mitochondrial Ca2+ elevation. These findings suggest that neuronal mitochondria are uniquely capable of decoding firing frequency and EPSP-to-spike time intervals for tuning the metabolic rate and triggering changes in synaptic efficacy.
Characterization of a recombinant plastid translocon co-chaperone
Authors: Nurmohamed Salima Sarah , Ko Kenton 
Published: June 2021

AbstractThe transport of proteins into plastids is dependent on how the different translocon components work together. One translocon component, Tic40, possesses functional features found in other proteins such as co-chaperones and may thus work similarly in this capacity. To enhance the understanding of Tic40’s mode of operation, a more basic characterization of the protein itself is required. This study was designed largely to examine the properties of recombinant Tic40 without the predicted transmembrane region. The properties of Tic40 revealed in this report are: 1) In plants, overall Tic40 levels can adjust to temperature; 2) Recombinant Tic40 proteins appear to display some level of functionality in the soluble form; and 3) Outside of a membranous context, the formation of complexes involving recombinant Tic40 can be influenced by temperature. The potential significance of these basic properties is discussed.
Toxicity of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NKK) in early development: a wide-scope metabolomics assay in zebrafish embryos
Authors: Merino Carla , Casado Marta , Piña Benjamí , Vinaixa Maria , Ramírez Noelia 
Published: June 2021

AbstractThe tobacco-specific nitrosamine 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a carcinogenic and ubiquitous environmental pollutant which carcinogenic and cytotoxic activity has been thoroughly investigated in murine models and human tissues. However, its potential deleterious effects on vertebrate early development are yet poorly understood. In this work, we characterized the impact of NNK exposure during early developmental stages of zebrafish embryos, a known alternative model for mammalian toxicity studies. Embryos exposed to different NNK concentrations were monitored for lethality and for the appearance of malformations during the first five days after fertilization. LC/MS-based untargeted metabolomics was subsequently performed for a wide-scope assay of NNK-related metabolic alterations. Our results revealed the presence of not only the parental compound, but also of two NKK known metabolites, 4-Hydroxy-4-(3-pyridyl)-butyric acid (HPBA) and 4-(Methylnitrosamino)-1-(3-pyridyl-N-oxide)-1-butanol (NNAL-N-oxide) in exposed embryos likely resulting from active CYP450-mediated α-hydroxylation and NNK detoxification pathways, respectively. This was paralleled by a disruption in purine and pyrimidine metabolisms and the activation of the base excision repair pathway. Our results confirm NNK as a harmful embryonic agent and demonstrate zebrafish embryos to be a suitable early development model to monitor NNK toxicity.
A biochemically-realisable relational model of the self-manufacturing cell
Authors: Hofmeyr Jan-Hendrik S. 
Published: June 2021

ABSTRACTAs shown by Hofmeyr, the processes in the living cell can be divided into three classes of efficient causes that produce each other, so making the cell closed to efficient causation, the hallmark of an organism. They are the enzyme catalysts of covalent metabolic chemistry, the intracellular milieu that drives the supramolecular processes of chaperone-assisted folding and self-assembly of polypeptides and nucleic acids into functional catalysts and transporters, and the membrane transporters that maintain the intracellular milieu, in particular its electrolyte composition. Each class of efficient cause can be modelled as a relational diagram in the form of a mapping in graph-theoretic form, and a minimal model of a self-manufacturing system that is closed to efficient causation can be constructed from these three mappings using the formalism of relational biology. This Fabrication-Assembly or (F,A)-system serves as an alternative to Robert Rosen’s replicative Metabolism-Repair or (M,R)-system, which has been notoriously problematic to realise in terms of real biochemical processes. A key feature of the model is the explicit incorporation of formal cause, which arrests the infinite regress that plagues all relational models of the cell. The (F,A)-system is extended into a detailed relational model of the self-manufacturing cell that has a clear biochemical realisation. This (F,A) cell model allows the interpretation and visualisation of concepts such as the metabolism and repair components of Rosen’s (M,R)-system, John von Neumann’s universal constructor, Howard Pattee’s symbol-function split via the symbol-folding transformation, Marcello Barbieri’s genotype-ribotype-phenotype ontology, and Tibor Gánti’s chemoton.