bluuebunny/crossref_metadata_2025_split huggingface dataset:
Taking Stock and Looking Ahead
Authors: Popov Vitaliy , Ruis Andrew R. , Cooke James M. 
Published: January 2022

Introduction
Since 2005, the American College of Surgeons Accredited Educational Institutes has provided accreditation of surgically focused simulation centers with the added benefit of identifying best practices defined as areas far exceeding the accreditation standards or novel methods of advancing high-quality, impactful education. This study aimed to examine the evolution of the best practices observed by accreditors during site visits over the 8-year period.

Methods
Accreditation included the completion of an application form followed by a site visit by a simulation expert and review of all materials by an accreditation committee to identify areas out of compliance along with areas far exceeding accreditation standards. These are termed “best practices.” To evaluate the evolution of accreditation feedback and embedded associations, the compiled list of 337 best practices identified from all 247 site visits over an 8-year period was analyzed and visualized using epistemic network analysis, a quantitative ethnographic technique for modeling the structure of connections in qualitative data.

Results
The overall association network of the data indicates that the strongest associations were between assessment, curriculum development, faculty development, research, and teaching methods, demonstrating a highly interconnected model of accreditation feedback. Best practices evolved from an early focus on teaching methods, faculty, and curriculum development to more advanced educational topics including assessment, research, resources, and overall center governance. Distribution of associations also increased over the 8-year period with more nuanced and interconnected statements demonstrating higher-level feedback including explanations, contributing factors, impact on other areas, and, in some cases, recommendations to share best practices outside the organization.

Conclusions
The epistemic network analysis of this 8-year database of simulation center feedback provides a novel perspective on an organization and the evolving field of simulation from an optional to essential modality in healthcare professions education.
Improved Survival With Higher-risk Donor Grafts in Liver Transplant With Acute-on-chronic Liver Failure
Authors: Kitajima Toshihiro , Kuno Yasutaka , Ivanics Tommy , Lu Mei , Moonka Dilip , Shimada Shingo , Shamaa Tayseer , Abouljoud Marwan S. , Nagai Shunji 
Published: January 2022

Background.
Use of higher-risk grafts in liver transplantation for patients with acute-on-chronic liver failure (ACLF) has been associated with poor outcomes. This study analyzes trends in liver transplantation outcomes for ACLF over time based on the donor risk index (DRI).

Methods.
Using the Organ Procurement and Transplantation Network and the United Network for Organ Sharing registry, 17 300 ACLF patients who underwent liver transplantation between 2002 and 2019 were evaluated. Based on DRI, adjusted hazard ratios for 1-y patient death were analyzed in 3 eras: Era 1 (2002–2007, n = 4032), Era 2 (2008–2013, n = 6130), and Era 3 (2014–2019, n = 7138). DRI groups were defined by DRI <1.2, 1.2–1.6, 1.6–2.0, and >2.0.

Results.
ACLF patients had significantly lower risks of patient death within 1 y in Era 2 (adjusted hazard ratio, 0.69; 95% confidence interval, 0.61-0.78; P < 0.001) and Era 3 (adjusted hazard ratio, 0.48; 95% confidence interval, 0.42-0.55; P < 0.001) than in Era 1. All DRI groups showed lower hazards in Era 3 than in Era 1. Improvement of posttransplant outcomes were found both in ACLF-1/2 and ACLF-3 patients. In ACLF-1/2, DRI 1.2 to 1.6 and >2.0 had lower adjusted risk in Era 3 than in Era 1. In ACLF-3, DRI 1.2 to 2.0 had lower risk in Era 3. In the overall ACLF cohort, the 2 categories with DRI >1.6 had significantly higher adjusted risks of 1-y patient death than DRI <1.2. When analyzing hazards in each era, DRI > 2.0 carried significantly higher adjusted risks in Eras 1 and 3‚ whereas DRI 1.2 to 2.0 had similar adjusted risks throughout eras. Similar tendency was found in ACLF-1/2. In the non-ACLF cohort, steady improvement of posttransplant outcomes was obtained in all DRI categories. Similar results were obtained when only hepatitis C virus-uninfected ACLF patients were evaluated.

Conclusions.
In ACLF patients, posttransplant outcomes have significantly improved, and outcomes with higher-risk organs have improved in all ACLF grades. These results might encourage the use of higher-risk donors in ACLF patients and provide improved access to transplant.
Association between urbanization and Internet addiction
Authors: Ko Chih-Hung , Yen Ju-Yu , Lin Pai-Cheng 
Published: January 2022

Purpose of review
Understanding the association between urbanization and Internet addiction is essential to the design and implementation of Internet addiction prevention measures in urban areas. This epidemiological review explores the urbanization-Internet addiction association and its potential underlying factors.

Recent findings
Nine studies have reported that Internet addiction prevalence is higher in urban areas, but three studies have noted the opposite. Psychiatric disorders and stress are the most commonly mentioned factors underlying the association. The effects of urbanization on Internet availability, Internet cafes, online gaming, outdoor or interactive activities, and family regulation and monitoring have been suggested to lead to higher Internet addiction risk. The ongoing COVID-19 pandemic, obesity, sleep problems, and the migration of parents to urban areas in search of work have strengthened the effect of urbanization on Internet addiction.

Summary
Early assessment and treatment provided by mental health services are crucial for mitigating the effect of urbanization on Internet addiction risk. Cities should be designed to provide adequate space for physical and interactive activities. To promote outdoor activities, air pollution, traffic congestion, and crime should be controlled. Prospective face-to-face studies involving analysis of data on pollution, traffic, and Internet addiction could provide evidence to elucidate the urbanization- Internet addiction association.
The McGill Approach to Core Stabilization in the Treatment of Chronic Low Back Pain: A Review
Authors: Laurin Erica , Minerbi Amir , Besemann LCol Markus , Courchesne Captain Isabel , Gupta Gaurav 
Published: January 2022

AbstractIntroductionLow back pain (LBP) is a major cause of disability and is progressively becoming worse on a global scale. [1,2] The prevention and rehabilitation of LBP lacks clarity in part due to the heterogeneity of the exercise programs prescribed to treat low back pain. Some authors have proposed stabilizing exercises for lower back pain which exert minimal loads on the spine. [3,4,5] Despite a multitude of existing exercise therapies, McGill has introduced three exercises for rehabilitating lower back pain, termed the McGill Big Three (MGB3). [6,7,8,9,10] These include the curl-up, side plank and bird-dog. The purpose of this review is to investigate the clinical outcomes from prescribing the MGB3 to individuals with chronic LBP.MethodsInclusion criteria were randomized control trials that involved an intervention with MGB3 core stabilization exercises for patients with chronic low back pain. The research included articles published during any period in full English text. Studies were critically reviewed by two authors EL and GG independently and collaboratively.ResultsIn total, four randomized control trials were included in this review. Multiple cohorts, with varying age, demographics and occupation were studied. Outcomes studied included various pain scores, patient reported functional and performance measures.DiscussionControlled clinical trials employing this method in low back pain treatment showed low quality data with mixed statistical significance, and little to no clinical significance irrespective of the measure used or even when compared to baseline. Limitations of these trials are detailed herein.ConclusionCurrently there is limited data supporting the clinical benefit of the McGill approach for the treatment of low back pain based on the available randomized clinical trials. More study is required prior to widespread adoption into clinical practice.
COVID-19 vaccination recruits and matures cross-reactive antibodies to conserved epitopes in endemic coronavirus Spike proteins
Authors: Elko Evan A , Nelson Georgia A , Mead Heather L , Kelley Erin J , Verche Virginia Le , Cardoso Angelo A , Ely Jennifer L , Boyle Annalee S , Piña Alejandra , Henson Sierra N , Rahee Fatima , Keim Paul S , Celona Kimberly R , Yi Jinhee , Settles Erik W , Yu George C , Morris Sheldon R , Zaia John A , Ladner Jason T , Altin John A 
Published: January 2022

AbstractThe COVID-19 pandemic has triggered the first widespread vaccination campaign against a coronavirus. Most vaccinated subjects are naïve to SARS-CoV-2, however almost all have previously encountered other coronaviruses (CoVs) and the role of this immunity in shaping the vaccine response remains uncharacterized. Here we use longitudinal samples and highly-multiplexed serology to identify mRNA-1273 vaccine-induced antibody responses against a range of CoV Spike epitopes and in both phylogenetically conserved and non-conserved regions. Whereas reactivity to SARS-CoV-2 epitopes showed a delayed but progressive increase following vaccination, we observed distinct kinetics for the endemic CoV homologs at two conserved sites in Spike S2: these became detectable sooner, and decayed at later timepoints. Using homolog-specific depletion and alanine-substitution experiments, we show that these distinctly-evolving specificities result from cross-reactive antibodies as they mature against rare, polymorphic residues within these epitopes. Our results reveal mechanisms for the formation of antibodies with broad reactivity against CoVs.
Projection of Healthcare Demand in Germany and Switzerland Urged by Omicron Wave (January-March 2022)
Authors: Gorji Hossein , Stauffer Noé , Lunati Ivan , Caduff Alexa , Bühler Martin , Engel Doortje , Chung Ho Ryun , Loukas Orestis , Feig Sabine , Renz Harald 
Published: January 2022

AbstractAfter the implementation of broad vaccination programs, there is an urgent need to understand how the population immunity affects the dynamics of the COVID-19 pandemic in presence of the protection waning and of the emergence of new vari-ants of concern. In the current Omicron wave that is propagating across Europe, assessing the risk of saturation of the healthcare systems is crucial for pandemic management, as it allows us to support the transition towards the endemic course of SARS-CoV-2 and implement more refined mitigation strategies that shield the most vulnerable groups and protect the healthcare systems. We investigated the current pandemic dynamics by means of compartmental models that describe the age-stratified social-mixing, and consider vaccination status, vaccine types, and their waning efficacy. Our goal is to provide insight into the plausible scenarios that are likely to be seen in Switzerland and Germany in the coming weeks and help take informed decisions. Despite the huge numbers of new positive cases, our results suggest that the current wave is unlikely to create an overwhelming health-care demand: owing to the lower hospitalization rate of the novel variant and the effectiveness of the vaccines. Our findings are robust with respect to the plausible variability of the main parameters that govern the severity and the progression of the Omicron infection. In a broader context, our framework can be applied also to future endemic scenarios, offering quantitative support for refined public health interventions in response to recurring COVID-19 waves.
Gasdermin-D activation by SARS-CoV-2 trigger NET and mediate COVID-19 immunopathology
Authors: Silva Camila Meirelles , Wanderley Carlos Wagner S , Veras Flavio Protasio , Gonçalves Augusto Veloso , Lima Mikhael Haruo Fernandes , Toller Kawahisa Juliana E. , Gomes Giovanni Freitas , Nascimento Daniele Carvalho , Silva Monteiro Valter V. , Paiva Isadora Marques , Almeida Cícero José Luíz Ramos , Caetité Diego Brito , Silva Juliana da Costa , Lopes Maria Isabel Fernandes , Bonjorno Letícia Pastorelli , Giannini Marcela Cavichioli , Amaral Natalia Brasil , Benatti Maíra Nilson , Damasceno Luis Eduardo Alves , Silva Bruna Manuella Souza , Schneider Ayda Henriques , Castro Icaro Maia Santos , Silva Juan Carlo Santos , Vasconcelos Amanda Pereira , Gonçalves Tiago Tomazini , Batah Sabrina Setembre , Rodrigues Tamara Silva , Costa Victor Ferreira , Pontelli Marjorie Cornejo , Martins Ronaldo B , Martins Timna Varela , Espósito Danillo Lucas Alves , Cebinelli Guilherme Cesar Martelossi , da Fonseca Benedito Antônio Lopes , Leiria Luiz Osório Silveira , Cunha Larissa Dias , Arruda Eurico , Nakaia Helder I , Fabro Alexandre Todorovic , Oliveira Renê D , Zamboni Dario S , Junior Paulo Louzada , Cunha Thiago Mattar , Alves Filho José Carlos Farias , Cunha Fernando de Queiroz 
Published: January 2022

AbstractThe release of neutrophil extracellular traps (NETs) is associated with inflammation, coagulopathy, and organ damage found in severe cases of COVID-19. However, the molecular mechanisms underlying the release of NETs in COVID-19 remain unclear. Using a single-cell transcriptome analysis we observed that the expression of GSDMD and inflammasome-related genes were increased in neutrophils from COVID-19 patients. Furthermore, high expression of GSDMD was found associated with NETs structures in the lung tissue of COVID-19 patients. The activation of GSDMD in neutrophils requires live SARS-CoV-2 and occurs after neutrophil infection via ACE2 receptors and serine protease TMPRSS2. In a mouse model of SARS-CoV-2 infection, the treatment with GSDMD inhibitor (disulfiram) reduced NETs release and organ damage. These results demonstrated that GSDMD-dependent NETosis plays a critical role in COVID-19 immunopathology, and suggests that GSDMD inhibitors, can be useful to COVID-19 treatment.In BriefHere, we showed that the activation of the Gasdermin-D (GSDMD) pathway in neutrophils controls NET release during COVID-19. The inhibition of GSDMD with disulfiram, abrogated NET formation reducing lung inflammation and tissue damage. These findings suggest GSDMD as a target for improving the COVID-19 therapy.
Who Develops Pandemic Fatigue?
Authors: Taylor Steven , Rachor Geoffrey S. , Asmundson Gordon J. G. 
Published: January 2022

AbstractAccording to the World Health Organization, pandemic fatigue poses a serious threat for managing COVID-19. The cardinal feature of pandemic fatigue is a progressive decline in adherence to social distancing (SDIS) guidelines, which is associated with pandemic-related emotional burnout. Little is known about the nature of pandemic fatigue; for example, it is unclear who is most likely to develop pandemic fatigue. We sought to evaluate this issue based on data from 5,812 American and Canadian adults recruited during the second year of the COVID-19 pandemic. Past-year decline in adherence to SDIS had a categorical latent structure according to Latent Class Analysis, consisting of an SDIS adherent group (Class 1: 92% of the sample) and a group reporting a progressive decline in adherence to SDIS (i.e., pandemic fatigue; Class 2: 8% of the sample). Class 2, compared to Class 1, was associated with greater pandemic-related burnout, pessimism, and apathy about the COVID-19 pandemic. They also tended to be younger, perceived themselves to be more affluent, tended to have greater levels of narcissism, entitlement, and gregariousness, and were more likely to report having been previously infected with SARSCOV2, which they regarded as an exaggerated threat. People in Class 2 also self-reported higher levels of pandemic-related stress, anxiety, and depression, and described making active efforts at coping with SDIS restrictions that they perceived as unnecessary and stressful. People in Class 1 generally reported that they engaged in SDIS for the benefit of themselves and their community, although 35% of this class also feared they would be publicly shamed if they did not comply with SDIS guidelines. The findings suggest that pandemic fatigue affects a substantial minority of people and even many SDIS-adherent people experience emotionally adverse effects (i.e., fear of being shamed). Implications for the future of SDIS are discussed.
Human NLRP1 is activated by ZAKɑ-driven ribotoxic stress response
Authors: Robinson Kim S. , Toh Gee Ann , Rozario Pritisha , Bayat Shima , Sun Zijin , Bauernfried Stefan , Nadkarni Rhea , Harapas Cassandra R. , Lim Chrissie K. , Chu Werncui , Tan Kiat Yi , Bonnard Carine , Sobota Radoslaw , Connolly John E. , Masters Seth L. , Chen Kaiwen W. , Ho Lena , Hornung Veit , Zhong Franklin L. 
Published: January 2022

ABSTRACTHuman NLRP1 is a multifunctional inflammasome sensor predominantly expressed in skin and airway epithelium; however its function in skin-specific immunity and its mechanisms of activation are not fully understood. Here we report that human NLRP1 is specifically activated by the ZAKɑ- driven ribotoxic stress response pathway (RSR) induced by ultraviolet B (UVB) irradiation or select microbial ribotoxins. Biochemically, RSR-triggered NLRP1 activation requires ZAKɑ- dependent hyperphosphorylation of a human-specific linker region of NLRP1 (NLRP1DR), leading to the ‘functional degradation’ of the auto-inhibitory NLRP1 N-terminal fragment. Additionally, we show that fusing NLRP1DRto the signaling domains of CARD8, which in itself is insensitive to RSR, creates a minimal inflammasome sensor for UVB and ribotoxins. In summary, these discoveries resolve the mechanisms of UVB sensing by human NLRP1, identify ZAKɑ-activating toxins as novel human NLRP1 activators, and establish NLRP1 inflammasome-dependent pyroptosis as an integral component of the ribotoxic stress response in primary human cells.UVB-induced NLRP1 activation in human keratinocytes involves a nuclear DNA-independent stress response involving photodamaged RNAZAKɑ kinase is required for UVB-triggered, but not VbP- or dsRNA-induced human NLRP1 activationZAKɑ-activating microbial ribotoxins specifically activate the NLRP1 inflammasome in multiple primary human cell typesHyperphosphorylation of a linker region (NLRP1DR) is required for RSR-dependent human NLRP1 activation
Transcriptional, post-transcriptional, and post-translational mechanisms rewrite the tubulin code during cardiac hypertrophy and failure
Authors: Phyo Sai Aung , Uchida Keita , Chen Christina Yingxian , Caporizzo Matthew A. , Bedi Kenneth , Griffin Joanna , Margulies Kenneth , Prosser Benjamin L. 
Published: January 2022

AbstractA proliferated and post-translationally modified microtubule network underlies cellular growth in cardiac hypertrophy and contributes to contractile dysfunction in heart failure. Yet how the heart achieves this modified network is poorly understood. Determining how the “tubulin code” – the permutations of tubulin isoforms and post-translational modifications - is rewritten upon cardiac stress may provide new targets to modulate cardiac remodeling. Further, while tubulin can autoregulate its own expression, it is unknown if autoregulation is operant in the heart or tuned in response to stress. Here we use heart failure patient samples and murine models of cardiac remodeling to interrogate transcriptional, autoregulatory, and post-translational mechanisms that contribute to microtubule network remodeling at different stages of heart disease. We find that autoregulation is operant across tubulin isoforms in the heart and leads to an apparent disconnect in tubulin mRNA and protein levels in heart failure. We also find that within 4 hours of a hypertrophic stimulus and prior to cardiac growth, microtubule detyrosination is rapidly induced to help stabilize the network. This occurs concomitant with rapid transcriptional and autoregulatory activation of specific tubulin isoforms and microtubule motors. Upon continued hypertrophic stimulation, there is an increase in post-translationally modified microtubule tracks and anterograde motors to support cardiac growth, while total tubulin content increases through progressive transcriptional and autoregulatory induction of tubulin isoforms. Our work provides a new model for how the tubulin code is rapidly rewritten to establish a proliferated, stable microtubule network that drives cardiac remodeling, and provides the first evidence of tunable tubulin autoregulation during pathological progression.
The Existence of At Least Three Genomic Signature Patterns and At Least Seven Subtypes of COVID-19 and the End of the Disease
Authors: Zhang Zhengjun 
Published: January 2022

AbstractHoping to find genomic clues linked to COVID-19 and end the pandemic has driven scientists’ tremendous efforts to try all kinds of research. Signs of progress have been achieved but are still limited. This paper intends to prove the existence of at least three genomic signature patterns and at least seven subtypes of COVID-19 driven by five critical genes (the smallest subset of genes). These signatures and subtypes provide crucial genomic information in COVID-19 diagnosis (including ICU patients), research focuses, and treatment methods. Unlike existing approaches focused on gene fold-changes and pathways, gene-gene nonlinear and competing interactions are the driving forces in finding the signature patterns and subtypes. Furthermore, the method leads to 100% accuracy, which shows biological and mathematical equivalences between COVID-19 status and the signature patterns and a methodological advantage over other existing methods that cannot lead to 100% accuracy. As a result, as new biomarkers, the new findings can be much more informative than other findings for interpreting biological mechanisms, developing the second (third) generation of vaccines, antiviral drugs, and treatment methods, and eventually bringing new hopes to an end of the pandemic.
Binding of Human ACE2 and RBD of Omicron Enhanced by Unique Interaction Patterns Among SARS-CoV-2 Variants of Concern
Authors: Kim Seonghan , Liu Yi , Ziarnik Matthew , Cao Yiwei , Zhang X. Frank , Im Wonpil 
Published: January 2022

ABSTRACTThe 2019 coronavirus disease (COVID-19) pandemic has had devastating impacts on our global health. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing COVID-19, has continued to mutate and spread worldwide despite global vaccination efforts. In particular, the Omicron variant, first identified in South Africa in late November 2021, has now overtaken the Delta variant and become the dominant strain worldwide. Compared to the original strain identified in Wuhan, Omicron features 50 genetic mutations, with 15 mutations in the receptor-binding domain (RBD) of the spike protein, which binds to the human angiotensin-converting enzyme 2 (ACE2) receptor for viral entry. However, it is not completely understood how these mutations alter the interaction and binding strength between the Omicron RBD and ACE2. In this study, we used a combined steered molecular dynamics (SMD) simulation and experimental microscale thermophoresis (MST) approach to quantify the interaction between Omicron RBD and ACE2. We report that the Omicron brings an enhanced RBD-ACE2 interface through N501Y, Q493K/R, and T478K mutations; the changes further lead to unique interaction patterns, reminiscing the features of previously dominated variants, Alpha (N501Y) and Delta (L452R and T478K). Our MST data confirmed that the Omicron mutations in RBD are associated with a five-fold higher binding affinity to ACE2 compared to the RBD of the original strain. In conclusion, our result could help explain the Omicron variant’s prevalence in human populations, as higher interaction forces or affinity for ACE2 likely promote greater viral binding and internalization, leading to increased infectivity.TOC GRAPHIC