bluuebunny/crossref_metadata_2025_split huggingface dataset:
Opioid Weaning Protocol Using Morphine Compared With Nonprotocolized Methadone Associated With Decreased Dose and Duration of Opioid After Norwood Procedure
Authors: Achuff Barbara-Jo , Lemming Katherine , Causey Jamie C. , Sembera Kerry A. , Checchia Paul A. , Heinle Jeffrey S. , Ghanayem Nancy S. 
Published: January 2022

OBJECTIVES:
Opioids are used to manage pain, comfort, maintain devices, and decrease oxygen consumption around Norwood palliation (NP), but in high dose and prolonged exposure, they increase risk of tolerance and iatrogenic withdrawal syndrome (IAWS). Variability in practice for IAWS prevention potentially increases opioid dose and duration. We hypothesize that protocolized weaning with morphine (MOR) versus nonprotocolized methadone (MTD) is associated with reduction in opioid exposure.

DESIGN:
A before-versus-after study of outcomes of patients weaned with protocolized MOR versus nonprotocolized MTD including subset analysis for those patients with complications postoperatively. Primary endpoints include daily, wean phase, and total morphine milligram equivalent (MMEq) dose, duration, and, secondarily, length of stay (LOS).

SETTING:
Quaternary-care pediatric cardiac ICU.

PATIENTS:
Neonates undergoing single-ventricle palliation.

INTERVENTIONS:
Introduction of IAWS prevention protocol.

MEASUREMENTS AND MAIN RESULTS:
Analysis included 54 patients who underwent the NP in 2017–2018 including the subset analysis of 34 who had a complicated postoperative course. The total and wean phase opioid doses for the MTD group were significantly higher than that for the MOR group: 258 versus 22 and 115 versus 6 MMEq/kg; p < 0.001. Duration of opioid exposure was 63 days in the MTD group and 12 days in MOR group (p < 0.001). Subanalysis of the complicated subset also identifies higher total and wean dose for MTD group (293 vs 41 and 116 vs 7 MMEq/kg; p < 0.001) with a longer duration (65 vs 22 days; p = 0.001). Within the subset, LOS was 55% longer in the MTD group than that in the MOR group (150 vs 67 d; p = 0.01) and not different in the uncomplicated group.

CONCLUSIONS:
After complex NP, a protocolized opioid weaning using MOR versus MTD is associated with 65% shorter opioid duration, 10-fold decreased dose, and shortened LOS.
Longitudinal Assessment of Acute Concussion Outcomes Through SMS Text (ConText Study)
Authors: Schoenfeld Robert , Drendel Amy , Ahamed Sheikh Iqbal , Thomas Danny 
Published: January 2022

ObjectiveMild traumatic brain injury (mTBI), or concussion, is a common health problem that has seen a recent increase in US adolescents. This study uses SMS text messaging (a mobile health [mHealth] tool) to report patient symptoms. We aim to better characterize mTBI recovery and hypothesize that this mHealth tool will have high retention rates and correlate with a conventional means of assessing symptoms, the Post-Concussion Symptom Inventory (PCSI).MethodsA prospective observational cohort pilot study. Thirty-one pediatric patients with acute mTBI were recruited to characterize their injury and report their symptoms via text messaging. Patients reported symptoms once every 3 days for the first 21 days, then once a week for 6 weeks.ResultsThere was a strong and positive correlation between the PCSI and the mHealth tool (rs = 0.875,P< 0.000, n = 22). Retention was 74% until symptom resolution and 42% until study completion. Patients with balance deficits had a significantly higher somatization score than those with normal balance (6.53 ± 3.25 vs 2.56 ± 2.30,t(22) = 3.211,P< 0.01).ConclusionsThis pilot study demonstrates that this tool is a valid and easy-to-use method of reporting pediatric mTBI symptoms—it replicates and identifies novel findings. Our results suggest that there may be a relationship between balance and the manifestation of somatic symptoms. Retention rates were lower than predicted, indicating that text messaging may not be the ideal format in this population. Text messaging may still have other applications for short-term communication/symptom measurement.
Evaluation of Related Factors of Maxillary Sinusitis After Le Fort I Osteotomy Based on Computed Tomography: A Retrospective Case-Control Study
Authors: Wang Shoupeng , Qian Yifeng , Qi Lei , Ge Weiwen , Cao Ningning , Zhang Lei , Meng Jian 
Published: January 2022

Abstract:Maxillary sinusitis is 1 of the postoperative complications of the Le Fort I osteotomy, this study investigated the related factors of maxillary sinusitis after Le Fort I osteotomy. A total of 23 cases, 92 controls, and 11 related factors were included in this case-control study with a 1:4 case-control ratio. The risk factors for maxillary sinusitis after Le Fort I were examined by least absolute shrinkage and selection operator multivariate conditional logistic regression and least absolute shrinkage and selection operator multivariate linear regression. The patency of maxillary sinus ostium at 6 months after surgery was significantly associated with maxillary sinusitis after Le Fort I osteotomy. Compared with the obstructed maxillary sinus ostium, the percentage of the volume of the healthy air cavity in the complete sinus cavity increased 70.7% when the maxillary sinus ostium was unobstructed, and 95% confidence interval was 0.610 to 0.805. Similarly, when the maxillary sinus ostium was wide, the percentage increased 6.0% compared with the narrow 1, and 95% confidence interval was 0.013 to 0.107. This study indicated that the patency of maxillary sinus ostium has an important impact on maxillary sinusitis after Le Fort I osteotomy. Close attention should be paid to maintain the maxillary sinus ostium and the drainage of maxillary sinuses unobstructed in a clinical setting.
International Human Xenotransplantation Inventory: A 10-year Follow-up
Authors: Hu Xiaowei , Geng Zhen , Gonelle-Gispert Carmen , Hawthrone Wayne J. , Deng Shaoping , Buhler Leo 
Published: January 2022

Background.
Following the recommendations by a panel of experts gathered by the World Health Organization in 2005, an inventory was established to collect practices of human xenotransplantation worldwide (www.humanxenotransplant.org). The website was activated in October 2006, in collaboration with the International Xenotransplantation Association, the University Hospital Geneva, and the World Health Organization. A first report on the collected xenotransplantation activities was published in 2010 in the journal Transplantation. In 2020, the website was redesigned, and its hosting and management were transferred to the Sichuan Provincial People’s Hospital.

Methods.
We collected information from publications in scientific journals, presentations at international congresses, the internet, and declarations of International Xenotransplantation Association members on xenotransplantation procedures in humans performed over the past 10 y.

Results.
A total of 5 new applications of human xenotransplantation were identified, with pig as source animal in all applications. The procedures involved transplantation of islets of Langerhans, skin, cornea, and choroid plexus cells. The treatments were performed in China, United States, New Zealand, and Argentina. No major complications or deaths were reported.

Conclusions.
Several clinical applications of cell or tissue xenotransplantation are ongoing around the world. Compared with the previous reported period (1995–2010, with 29 activities, mostly without governmental regulation), the recent number of clinical activities was reduced, and all were officially approved. This information should be used to inform healthcare officials, staff, and the public with the objective of encouraging good practices based on internationally harmonized guidelines driven by initiatives such as the Changsha Communiqué.
Barriers to the use of methylphenidate in paediatric neuro-oncology services
Authors: Hagan Alexander J. , Bailey Simon , Verity Sarah J. 
Published: January 2022

AbstractBackgroundThe increasing effectiveness of childhood cancer treatment has resulted in a greater number of children surviving previously incurable central nervous system tumours. This growing population of survivors report significant treatment-related difficulties, including attentional impairment associated with poor long-term intellectual development, academic attainment, and health-related quality of life. Clinical findings show benefit to attention and executive functions following methylphenidate administration. The current project explored barriers associated with use of methylphenidate in paediatric neuro-oncology services in the UK.MethodQualitative data was gathered by semi-structured questionnaire sent to clinical psychologists/neuropsychologists in 19 of the 21 NHS primary treatment oncology centres in the UK in May 2018. Thematic analytic methods were used to explore the data.Results11 responses were received from primary treatment centres. Knowledge of the evidence base for methylphenidate in paediatric brain injury was limited. This was primarily attributable to the inadequate resource of psychology into many primary treatment centres, limiting provision to service to a restricted proportion of the patient group. Psychologists reported an interest in exploring the utility of methylphenidate in their patient group. Respondents highlighted the need for provision of accessible research summaries and treatment protocols addressing the potential use of psychostimulants, stating that these would support their team to consider expanding the interventions offered.ConclusionsThe development of shared resources for clinicians will be important in supporting the application of research findings to clinical practice. We anticipate national collaboration will support the advancement of intervention for the growing clinical population of long-term survivors.
The altered entry pathway and antigenic distance of the SARS-CoV-2 Omicron variant map to separate domains of spike protein
Authors: Peacock Thomas P. , Brown Jonathan C. , Zhou Jie , Thakur Nazia , Sukhova Ksenia , Newman Joseph , Kugathasan Ruthiran , Yan Ada W.C. , Furnon Wilhelm , De Lorenzo Giuditta , Cowton Vanessa M. , Reuss Dorothee , Moshe Maya , Quantrill Jessica L. , Platt Olivia K. , Kaforou Myrsini , Patel Arvind H. , Palmarini Massimo , Bailey Dalan , Barclay Wendy S. 
Published: January 2022

AbstractThe SARS-CoV-2 Omicron/BA.1 lineage emerged in late 2021 and rapidly displaced the Delta variant before being overtaken itself globally by, the Omicron/BA.2 lineage in early 2022. Here, we describe how Omicron BA.1 and BA.2 show a lower severity phenotype in a hamster model of pathogenicity which maps specifically to the spike gene. We further show that Omicron is attenuated in a lung cell line but replicates more rapidly, albeit to lower peak titres, in human primary nasal cells. This replication phenotype also maps to the spike gene. Omicron spike (including the emerging Omicron lineage BA.4) shows attenuated fusogenicity and a preference for cell entry via the endosomal route. We map the altered Omicron spike entry route and partially map the lower fusogenicity to the S2 domain, particularly the substitution N969K. Finally, we show that pseudovirus with Omicron spike, engineered in the S2 domain to confer a more Delta-like cell entry route retains the antigenic properties of Omicron. This shows a distinct separation between the genetic determinants of these two key Omicron phenotypes, raising the concerning possibility that future variants with large antigenic distance from currently circulating and vaccine strains will not necessarily display the lower intrinsic severity seen during Omicron infection.
In vitro evaluation of therapeutic antibodies against a SARS-CoV-2 Omicron B.1.1.529 isolate
Authors: Touret Franck , Baronti Cécile , Bouzidi Hawa Sophia , de Lamballerie Xavier 
Published: January 2022

AbstractThe emergence and rapid spread of the Omicron variant of SARS-CoV-2, which has more than 30 substitutions in the spike glycoprotein, compromises the efficacy of currently available vaccines and therapeutic antibodies. Using a clinical strain of the Omicron variant, we analyzed the neutralizing power of eight currently used monoclonal antibodies compared to the ancestral B.1 BavPat1 D614G strain. We observed that six of these antibodies have lost their ability to neutralize the Omicron variant. Of the antibodies still having neutralizing activity, Sotrovimab/Vir-7831 shows the smallest reduction in activity, with a factor change of 3.1. Cilgavimab/AZD1061 alone shows a reduction in efficacy of 15.8, resulting in a significant loss of activity for the Evusheld cocktail (42.6 fold reduction) in which the other antibody, Tixagevimab, does not retain significant activity against Omicron. Our results suggest that the clinical efficacy of the initially proposed doses should be rapidly evaluated and the possible need to modify doses or propose combination therapies should be considered.
A dual-receptor mechanism between integrins and ACE2 widens SARS-CoV-2 tissue tropism
Authors: Nader Danielle , Gressett Timothy E. , Hossen Md Lokman , Chapagain Prem , Kerrigan Steven W. , Bix Gregory 
Published: January 2022

SummaryIn addition to the ACE2 receptor, SARS-CoV-2 binds to integrins to gain host cell entry and trigger pro-inflammatory integrin-mediated signalling cascades. Integrins, therefore, are likely candidates for a dual-receptor mechanism with ACE2 to explain the increased infectivity seen in SARS-CoV-2 models. As integrins are primarily expressed in vasculature and persistent vasculopathy is seen in COVID-19, examining the role of endothelial integrin involvement is crucial in uncovering the pathophysiology of SARS-CoV-2.
Druggable redox pathways against M. abscessus in cystic fibrosis patient-derived airway organoids
Authors: Leon-Icaza Stephen Adonai , Bagayoko Salimata , Vergé Romain , Iakobachvili Nino , Ferrand Chloé , Aydogan Talip , Bernard Celia , Dafun Angelique Sanchez , Murris-Espin Marlène , Mazières Julien , Bordignon Pierre Jean , Mazères Serge , Bernes-Lasserre Pascale , Ramé Victoria , Lagarde Jean-Michel , Marcoux Julien , Bousquet Marie Pierre , Chalut Christian , Guilhot Christophe , Clevers Hans , Peters Peter J. , Molle Virginie , Lugo-Villarino Geanncarlo , Cam Kaymeuang , Berry Laurence , Meunier Etienne , Cougoule Céline 
Published: January 2022

AbstractMycobacterium abscessus(Mabs) drives life-shortening mortality in cystic fibrosis (CF) patients, primarily because of its resistance to chemotherapeutic agents. To date, our knowledge on the host and bacterial determinants driving Mabs pathology in CF patient lung remains rudimentary. Here, we used human airway organoids (AOs) microinjected with smooth (S) or rough (R-)Mabs to evaluate bacteria fitness, host responses to infection, and new treatment efficacy. We show that S Mabs formed biofilm, R Mabs formed cord serpentines and displayed a higher virulence. While Mabs infection triggers enhanced oxidative stress, pharmacological activation of antioxidant pathways resulted in better control of Mabs growth. Genetic and pharmacological inhibition of the CFTR is associated with better growth and higher virulence of S and R Mabs. Finally, pharmacological activation of antioxidant pathways inhibited Mabs growth and improved efficacy in combination with cefoxitin, a first line antibiotic. In conclusion, we have established AOs as a suitable human system to decipher mechanisms of CF-driven respiratory infection by Mabs and propose antioxidants as a potential host-directed strategy to improve Mabs infection control.
Quality assessment of anatomical MRI images from Generative Adversarial Networks: human assessment and image quality metrics
Authors: Treder Matthias S. , Codrai Ryan , Tsvetanov Kamen A. 
Published: January 2022

AbstractBackgroundGenerative Adversarial Networks (GANs) can synthesize brain images from image or noise input. So far, the gold standard for assessing the quality of the generated images has been human expert ratings. However, due to limitations of human assessment in terms of cost, scalability, and the limited sensitivity of the human eye to more subtle statistical relationships, a more automated approach towards evaluating GANs is required.New methodWe investigated to what extent visual quality can be assessed using image quality metrics and we used group analysis and spatial independent components analysis to verify that the GAN reproduces multivariate statistical relationships found in real data. Reference human data was obtained by recruiting neuroimaging experts to assess real Magnetic Resonance (MR) images and images generated by a Wasserstein GAN. Image quality was manipulated by exporting images at different stages of GAN training.Results: Experts were sensitive to changes in image quality as evidenced by ratings and reaction times, and the generated images reproduced group effects (age, gender) and spatial correlations moderately well. We also surveyed a number of image quality metrics which consistently failed to fully reproduce human data. While the metrics Structural Similarity Index Measure (SSIM) and Naturalness Image Quality Evaluator (NIQE) showed good overall agreement with human assessment for lower-quality images (i.e. images from early stages of GAN training), only a Deep Quality Assessment (QA) model trained on human ratings was sensitive to the subtle differences between higher-quality images.ConclusionsWe recommend a combination of group analyses, spatial correlation analyses, and both distortion metrics (SSIM, NIQE) and perceptual models (Deep QA) for a comprehensive evaluation and comparison of brain images produced by GANs.
Demonstration of a common DPhe7 to DNal(2’)7 peptide ligand antagonist switch for the melanocortin-3 and melanocortin-4 receptors identifies systematic mischaracterization of the pharmacological properties of melanocortin peptides
Authors: Gimenez Luis E , Noblin Terry A. , Williams Savannah Y. , Bagchi Satarupa Mullick , Ji Ren-Lei , Tao Ya-Xiong , Jeppesen Claus B. , Conde-Frieboes Kilian W. , Sawyer Tomi K. , Grieco Paolo , Cone Roger D. 
Published: January 2022

ABSTRACTMelanocortin peptides containing a D-naphthylalanine residue in position 7 (DNal(2’)7), reported as melanocortin-3 receptor (MC3R) subtype-specific agonists in two separate publications, were found to lack significant MC3R agonist activity. The cell lines used at the University of Arizona for pharmacological characterization of these peptides, consisting of HEK293 cells stably transfected with human melanocortin receptor subtypes MC1R, MC3R, MC4R, or MC5R, were then obtained and characterized by quantitative PCR. While the MC1R cell line correctly expressed only the hMCR1, the three other cell lines were mischaracterized with regard to receptor subtype expression. Demonstration that a D-naphthylalanine residue in position 7, irrespective of the melanocortin peptide template, results primarily in antagonism of the MC3R and MC4R, then allowed us to search the published literature for additional errors. The erroneously characterized DNal(2’)7-containing peptides date back to 2003; thus, our analysis suggests that systematic mischaracterization of the pharmacological properties of melanocortin peptides occurred.
An integrated approach to protein discovery and detection from complex biofluids
Authors: Luu Gordon T. , Ge Chang , Tang Yisha , Li Kailiang , Cologna Stephanie M. , Burdette Joanna E. , Su Judith , Sanchez Laura M. 
Published: January 2022

AbstractOvarian cancer, a leading cause of cancer related deaths among women, has been notoriously difficult to routinely screen for and diagnose early. Researchers and clinicians continue to seek routinely usable, non-invasive, screening methods as early detection significantly improves survival. Biomarker screening is ideal; however, currently available ovarian cancer biomarkers lack desirable sensitivity and specificity. Furthermore, the most fatal forms, high grade serous cancers often originate in the fallopian tube; therefore, sampling from the vaginal environment provides more proximal sources for tumor detection. To address these shortcomings and leverage proximal sampling, we developed an untargeted mass spectrometry microprotein profiling method and identified a signature of cystatin A, validated this protein in an animal model, and sought to overcome the limits of detection inherent to mass spectrometry by demonstrating that cystatin A is present at 100 pM concentrations using a label-free microtoroid resonator. The findings highlight the potential utility for early-stage detection where cystatin A levels would be low.Significance StatementIt is now clear that high-grade serous ovarian cancer can originate in the fallopian tube epithelium. These tumors colonize the ovary and then metastasize throughout the peritoneum. This discovery has raised important, and yet unaddressed, questions how we might be able to detect and screen for this deadly disease for which there is no routine screening. We have leveraged vaginal lavages from a murine model of the disease as a complex biological fluid for untargeted discovery of microproteins using mass. We improved our limits of detection by conjugating a cystatin A antibody to the surface of a microtoroid resonator to allow us to specifically detect cystatin A from vaginal lavages at early time points across biological replicates.
Calculation of centralities in protein kinase A
Authors: Kornev Alexandr P. , Aoto Phillip C. , Taylor Susan S. 
Published: January 2022

AbstractTopological analysis of amino acid networks is a common method that can help to understand the roles of individual residues. The most popular approach for network construction is to create a connection between residues if they interact. These interactions are usually weighted by absolute values of correlation coefficients or mutual information. Here we argue that connections in such networks have to reflect levels of cohesion within the protein instead of a simple fact of interaction between residues. If this is correct, an indiscriminate combination of correlation and anti-correlation, as well as the all-inclusive nature of the mutual information metrics, should be detrimental for the analysis. To test our hypothesis, we studied amino acid networks of the protein kinase A created by Local Spatial Pattern alignment, a method that can detect conserved patterns formed by Cα-Cβ vectors. Our results showed that, in comparison with the traditional methods, this approach is more efficient in detecting functionally important residues. Out of four studied centrality metrics, Closeness centrality was the least efficient measure of residue importance. Eigenvector centrality proved to be ineffective as the spectral gap values of the networks were very low due to the bilobal structure of the kinase. We recommend using joint graphs of Betweenness centrality and Degree centrality to visualize different aspects of amino acid roles.Author SummaryProtein structures can be viewed as networks of residues with some of them being a part of highly interconnected hubs and some being connectors between the hubs. Analysis of these networks can be helpful for understanding of possible roles of single amino acids. In this paper, we challenged existing methods for the creation of such networks. A traditional way is to connect residues if they can interact. We propose that residues should be connected only if they retain their mutual positions in space during molecular dynamic simulation, that is they move cohesively. We show that this approach improves the efficiency of the analysis indicating that a significant revision of the existing views on amino acid networks is necessary.