bluuebunny/crossref_metadata_2025 huggingface dataset:
Preoperative Magnetic Resonance Imaging Signal Intensity Classification Is Associated With Clinical Presentation and Surgical Outcomes in Myelopathy Caused by Thoracic Ossification of Ligamentum Flavum: A Multicenter Study
Authors: Zhang Chao , Yang Shengdong , Wang Lin , Wang Nan , Ke Zhenyong , Liu Peng , Zhang Chengmin , Xiong Chuang , Zhao Runhan , Liang Hao , Luo Xiaoji
Published: December 2021

Study Design

Retrospective Cohort Study

Objectives

To explore whether classification of the increased signal intensity (ISI) on magnetic resonance imaging (MRI) correlates with clinical presentations and outcomes in symptomatic thoracic ossification of ligamentum flavum (T-OLF) patients.

Methods

All patients with symptomatic T-OLF who underwent laminectomy at four institutions were reviewed. The ISI on preoperative T2-weighted MRI was divided into 3 groups, Grade 0, none; Grade 1, light (obscure); and Grade 2, intense (bright). Neurological function before surgery and at follow-up was evaluated by the revised Japanese Orthopedic Association (JOA) score. Patients’ demographics, clinical manifestations, and surgical outcomes were compared.

Results

A total of 94 patients were involved. Preoperative MRI showed 32 patients in Grade 0, 39 patients in Grade 1, and 23 patients in Grade 2. Low extremities numbness, weakness, and clinical signs were less frequent in Grade 0 patients. The grade of ISI was correlated with the duration of symptoms and cord compression. Grade 0 patients had a better preoperative JOA score than those with ISI changes, while Grade 2 patients showed worse neurological recovery, longer duration of operation, more intraoperative blood loss, and a higher incidence of perioperative complications.

Conclusion

The classification of ISI is an effective parameter for preoperatively assessing cord compression, clinical severity, and surgical outcomes in T-OLF patients. Grade 0 patients have relatively mild neurological impairment but are more likely to be misdiagnosed. Grade 2 indicates the worst clinical impairment and neurological recovery, and implies a risky and challenging surgery.
The impact of social capital on entrepreneurial intention and its antecedents: Differences between social capital online and offline
Authors: Pérez Fernández Héctor , Rodríguez Escudero Ana Isabel , Martín Cruz Natalia , Delgado García Juan Bautista
Published: December 2021

Entrepreneurial intention is a key research question in entrepreneurship. Previous studies have proven the theory of planned behavior (TPB) to explain entrepreneurial intention. Scholars have thus focused on analyzing factors to develop the three antecedents of TPB, one of which is social capital. However, research has barely considered social capital online. We extend research by exploring the effect of social capital on these antecedents and on entrepreneurial intention, and by analyzing the differences in these influences between social capital online and offline. Using partial least squares and commonality analysis for 587 individuals in Spain, we find that social capital influences these antecedents and entrepreneurial intention. Furthermore, social capital online has a greater effect in attitude toward entrepreneurship, a similar effect on perceived behavioral control, and a lesser effect on social norms than social capital offline. Finally, social capital online has a greater influence on entrepreneurial intention than social capital offline.

JEL CLASSIFICATION: M1 Business Administration, M13 New Firms • Startups
Gender Role Attitudes Cannot Explain How British Couples Responded to Increased Housework Demands during the COVID-19 Pandemic
Authors: Hudde Ansgar , Hank Karsten , Jacob Marita
Published: December 2021

Previous research has shown that gender role attitudes can predict changes in couples’ housework division over critical life events, but these studies might have suffered from endogeneity because such life events are anticipated and may be affected by gender role attitudes. In contrast, the coronavirus disease 2019 (COVID-19) pandemic was a truly exogenous shock that hit couples unexpectedly. Estimating fixed-effects regression models, the authors examine the role of gender ideologies in how couples adjusted their division of housework during the COVID-19 pandemic in 2020 compared with a prepandemic baseline observation. The data cover 3,219 couples from the UK Household Longitudinal Study. Both partners spent substantially more time on housework throughout the COVID-19 crisis than before, especially in the early stages. However, we found no evidence that individuals’ or couples’ precrisis gender role attitudes affected changes in men’s and women’s absolute or relative contributions to housework at any time during the lockdown.
Methodological foundation of a numerical taxonomy of urban form
Authors: Fleischmann Martin , Feliciotti Alessandra , Romice Ombretta , Porta Sergio
Published: December 2021

Cities are complex products of human culture, characterised by a startling diversity of visible traits. Their form is constantly evolving, reflecting changing human needs and local contingencies, manifested in space by many urban patterns. Urban morphology laid the foundation for understanding many such patterns, largely relying on qualitative research methods to extract distinct spatial identities of urban areas. However, the manual, labour-intensive and subjective nature of such approaches represents an impediment to the development of a scalable, replicable and data-driven urban form characterisation. Recently, advances in geographic data science and the availability of digital mapping products open the opportunity to overcome such limitations. And yet, our current capacity to systematically capture the heterogeneity of spatial patterns remains limited in terms of spatial parameters included in the analysis and hardly scalable due to the highly labour-intensive nature of the task. In this paper, we present a method for numerical taxonomy of urban form derived from biological systematics, which allows the rigorous detection and classification of urban types. Initially, we produce a rich numerical characterisation of urban space from minimal data input, minimising limitations due to inconsistent data quality and availability. These are street network, building footprint and morphological tessellation, a spatial unit derivative of Voronoi tessellation, obtained from building footprints. Hence, we derive homogeneous urban tissue types and, by determining overall morphological similarity between them, generate a hierarchical classification of urban form. After framing and presenting the method, we test it on two cities – Prague and Amsterdam – and discuss potential applications and further developments. The proposed classification method represents a step towards the development of an extensive, scalable numerical taxonomy of urban form and opens the way to more rigorous comparative morphological studies and explorations into the relationship between urban space and phenomena as diverse as environmental performance, health and place attractiveness.
Augmentative and Alternative Communication and Remote Learning
Authors: Lohmann Marla J. , Kappel Alexandria , Taylor Matthew S.
Published: December 2021

For rural locations, the use of remote learning may provide schools the opportunity to meet student needs without requiring students to travel long distances to access services. It is critical that teachers of students with disabilities understand how to support learning and know how to use the accommodations, modifications, and assistive technologies listed in student Individualized Education Programs (IEPs) in online classrooms. Students with language disabilities sometimes require augmentative and alternative communication (AAC) systems to effectively communicate. This article provides teachers with practical tips of teaching students to use AAC online and supporting its continued use in the virtual classroom.
Evaluation of a novel CFTR potentiator in COPD ferrets with acquired CFTR dysfunction
Authors: Kaza Niroop , Lin Vivian Y. , Stanford Denise , Hussain Shah S. , Falk Libby Emily , Kim Harrison , Borgonovi Monica , Conrath Katja , Mutyam Venkateshwar , Byzek Stephen A. , Tang Li Ping , Trombley John E. , Rasmussen Lawrence , Schoeb Trenton , Leung Hui Min , Tearney Guillermo J. , Raju S. Vamsee , Rowe Steven M.
Published: December 2021

Rationale

The majority of chronic obstructive pulmonary disease (COPD) patients have chronic bronchitis, for which specific therapies are unavailable. Acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction is observed in chronic bronchitis, but has not been proven in a controlled animal model with airway disease. Furthermore, the potential of CFTR as a therapeutic target has not been testedin vivo,given limitations to rodent models of COPD. Ferrets exhibit cystic fibrosis-related lung pathology when CFTR is absent and COPD with bronchitis following cigarette smoke exposure.

Objectives

To evaluate CFTR dysfunction induced by smoking and test its pharmacological reversal by a novel CFTR potentiator, GLPG2196, in a ferret model of COPD with chronic bronchitis.

Methods

Ferrets were exposed for 6 months to cigarette smoke to induce COPD and chronic bronchitis and then treated with enteral GLPG2196 once daily for 1 month. Electrophysiological measurements of ion transport and CFTR function, assessment of mucociliary function by one-micron optical coherence tomography imaging and particle-tracking microrheology, microcomputed tomography imaging, histopathological analysis and quantification of CFTR protein and mRNA expression were used to evaluate mechanistic and pathophysiological changes.

Measurements and main results

Following cigarette smoke exposure, ferrets exhibited CFTR dysfunction, increased mucus viscosity, delayed mucociliary clearance, airway wall thickening and airway epithelial hypertrophy. In COPD ferrets, GLPG2196 treatment reversed CFTR dysfunction, increased mucus transport by decreasing mucus viscosity, and reduced bronchial wall thickening and airway epithelial hypertrophy.

Conclusions

The pharmacologic reversal of acquired CFTR dysfunction is beneficial against pathological features of chronic bronchitis in a COPD ferret model.
Phenotype and severity of asthma determines bronchial epithelial immune responses to a viral mimic
Authors: Porsbjerg Celeste , Nieto-Fontarigo Juan Jose , Cerps Samuel , Ramu Sangheeta , Menzel Mandy , Hvidtfeldt Morten , Silberbrandt Alexander , Frøssing Laurits , Klein Ditte , Sverrild Asger , Uller Lena
Published: December 2021

Background

Asthma is characterised by an aggravated immune response to respiratory viral infections. This phenomenon is a clinically well-recognised driver of acute exacerbations, but how different phenotypes of asthma respond immunologically to viruses is unclear.

Objectives

To describe the association between different phenotypes and severity of asthma and bronchial epithelial immune responses to viral stimulation.

Methods

In the Immunoreact study, healthy subjects (n=10) and 50 patients with asthma were included; 30 (60%) were atopic, and 34 (68%) were eosinophilic; 14 (28%) had severe asthma. All participants underwent bronchoscopy with collection of bronchial brushings. Bronchial epithelial cells (BECs) were expanded and stimulated with the viral replication mimic poly (I:C) (Toll-like receptor (TLR)3 agonist)in vitro. The expression of TLR3-induced pro-inflammatory and antiviral responses of BECs were analysed using reverse transcriptase quantitative PCR and multiplex ELISA and compared across asthma phenotypes and severity of disease.

Results

Patients with atopic asthma had increased induction of interleukin (IL)-4, interferon (IFN)-β, IL-6, tumour necrosis factor-α, and IL-1β after poly (I:C) stimulation compared to non-atopic patients, whereas in patients with eosinophilic asthma only IL-6 and IL-8 induction was higher than in non-eosinophilic asthma. Patients with severe asthma displayed a decreased antiviral IFN-β, and increased expression of IL-8, most pronounced in atopic and eosinophilic asthmatics. Furthermore, induction of IL-33 in response to poly (I:C) was increased in severe atopic and in severe eosinophilic asthma, but thymic stromal lymphopoietin only in severe eosinophilic asthma.

Conclusions

The bronchial epithelial immune response to a viral mimic stimulation differs between asthma phenotypes and severities, which may be important to consider when targeting novel asthma treatments.
Cloud Control System Architectures, Technologies and Applications on Intelligent and Connected Vehicles: a Review
Authors: Chu Wenbo , Wuniri Qiqige , Du Xiaoping , Xiong Qiuchi , Huang Tai , Li Keqiang
Published: December 2021

The electrification of vehicle helps to improve its operation efficiency and safety. Due to fast development of network, sensors, as well as computing technology, it becomes realizable to have vehicles driving autonomously. To achieve autonomous driving, several steps, including environment perception, path-planning, and dynamic control, need to be done. However, vehicles equipped with on-board sensors still have limitations in acquiring necessary environmental data for optimal driving decisions. Intelligent and connected vehicles (ICV) cloud control system (CCS) has been introduced as a new concept as it is a potentially synthetic solution for high level automated driving to improve safety and optimize traffic flow in intelligent transportation. This paper systematically investigated the concept of cloud control system from cloud related applications on ICVs, and cloud control system architecture design, as well as its core technologies development. Based on the analysis, the challenges and suggestions on cloud control system development have been addressed.
In vitro activities of cellulase and ceftazidime, alone and in combination against Pseudomonas aeruginosa biofilms
Authors: Kamali Esmat , Jamali Ailar , Izanloo Ahdieh , Ardebili Abdollah
Published: December 2021

Background

Biofilms are a main pathogenicity feature of Pseudomonas aeruginosa and has a significant role in antibiotic resistance and persistent infections in humans. We investigated the in vitro activities of antibiotic ceftazidime and enzyme cellulase, either alone or in combination against biofilms of P. aeruginosa.

Results

Both ceftazidime and cellulase significantly decreased biofilm formation in all strains in a dose-dependent manner. Combination of enzyme at concentrations of 1.25, 2.5, 5, and 10 U/mL tested with 1/16× MIC of antibiotic led to a significant reduction in biofilm biomass. Cellulase showed a significant detachment effect on biofilms at three concentrations of 10 U/mL, 5 U/mL, and 2.5 U/mL. The MIC, MBC, and MBEC values of ceftazidime were 2 to 4 µg/mL, 4 to 8 µg/mL, and 2048 to 8192 µg/mL. When combined with cellulase, the MBECs of antibiotic showed a significant decrease from 32- to 128-fold.

Conclusions

Combination of the ceftazidime and the cellulase had significant anti-biofilm effects, including inhibition of biofilm formation and biofilm eradication in P. aeruginosa. These data suggest that glycoside hydrolase therapy as a novel strategy has the potential to enhance the efficacy of antibiotics and helps to resolve biofilm-associated wound infections caused by this pathogen.
The effect of patient education based on health belief model on hospital readmission preventive behaviors and readmission rate in patients with a primary diagnosis of acute coronary syndrome: a quasi-experimental study
Authors: Habibzadeh Hossein , Bagherzadi Aynaz , Didarloo Alireza , Khalkhali Hamidreza
Published: December 2021

Background

The health belief model is one of the applicable methods of training health preventive behaviors, especially in patients with cardiovascular diseases. Therefore, this study aimed to determine the effect of patient education based on the health belief model on readmission preventive behaviors and readmission rate in patients with a primary diagnosis of acute coronary syndrome.

Methods

The present quasi-experimental study was conducted in 2020 on patients with a primary diagnosis of acute coronary syndrome who were discharging from Seyed Al-Shohada Hospital, Urmia, Iran. In this study, a total of 70 samples were recruited using convenience sampling and then randomly assigned to two groups of intervention and control (n = 35 in each group). A total of 7 face-to-face group training sessions were held with the participation of the patients and one of their family members during 14 days after hospital discharge. These sessions were conducted along with concentration on the structures of the health belief model. Data were collected at three time points of immediately before, one month, and three months after the intervention using a demographic questionnaire, a researcher-made questionnaire of readmission preventive behaviors in cardiovascular diseases, and a checklist of hospital readmission. Data were analyzed using SPSS Statistics for Windows, version 17.0 (SPSS Inc., Chicago, Ill., USA).

Results

The results showed that there was a statistically significant difference in the mean score of preventive behaviors between the two groups at time points of one month and three months after the intervention (p < .05). However, there was no statistically significant difference in the readmission rate between the two groups after the intervention (p > .05).

Conclusion

Health belief model-based education was shown to be effective on readmission preventive behaviors in patients with acute coronary syndrome, although this model had no effect on the readmission rate in these patients. Other factors affecting the readmission rate are recommended to be investigated.
An unusual cause of ascites: Castleman disease
Authors: Zhu XiuLi , Chen Si , Fang Fang , Jia Yong , Zhang KaiGuang
Published: December 2021

Background

Castleman disease (CD) is a group of rare lymphoproliferative diseases with common lymph node histological features that can easily be misdiagnosed as infections, multiple autoimmune diseases, and malignant tumors.

Case presentation

Here we report a rare case of a Chinese male with refractory ascites for two years and was eventually diagnosed as CD.

Conclusions

The challenges in diagnosis of CD arise from the large differential, clinical heterogeneity and our limited understanding of pathology. In case of rare ascites, CD needs to be considered.
Immature granulocyte percentage for prediction of sepsis in severe burn patients: a machine leaning-based approach
Authors: Jeon Kibum , Lee Nuri , Jeong Seri , Park Min-Jeong , Song Wonkeun
Published: December 2021

Background

Of the existing sepsis markers, immature granulocytes (IG) most frequently reflect the presence of an infection. The importance of IG as an early predictor of sepsis and bacteremia is evaluated differently for each study. This study aimed to evaluate the effectiveness of the Sysmex XN series’ IG% as an independent prognostic indicator of sepsis using machine learning.

Methods

A total of 2465 IG% results from 117 severe burn patients in the intensive care unit of one institution were retrospectively analyzed. We evaluated the IG% for sepsis using the receiver operating characteristic, logistic regression, and partial dependence plot analyses. Clinical characteristics and other laboratory markers associated with sepsis, including WBC, procalcitonin, and C-reactive protein, were compared with the IG% values.

Results

Twenty-six of the 117 patients were diagnosed with sepsis. The median IG% value was 2.6% (95% CI: 1.4–3.1). The area under the receiver operating characteristic curve was 0.77 (95% CI: 0.78–0.84) and the optimal cut-off value was 3%, with a sensitivity of 76.9% and specificity of 68.1%. The partial dependence plot of IG% on predicting sepsis showed that an IG% < 4% had low predictability, but increased thereafter. The interaction plot of IG% and C-reactive protein showed an increase in sepsis probability at an IG% of 6% and C-reactive protein of 160 mg/L.

Conclusions

IG% is moderately useful for predicting sepsis. However, since it can be determined from routine laboratory test results and requires no additional intervention or cost, it could be particularly useful as an auxiliary marker.
Difficulties accessing health care services during the COVID-19 pandemic in Canada: examining the intersectionality between immigrant status and visible minority status
Authors: Etowa Josephine , Sano Yujiro , Hyman Ilene , Dabone Charles , Mbagwu Ikenna , Ghose Bishwajit , Osman Muna , Mohamoud Hindia
Published: December 2021

Background

Difficulties accessing health care services can result in delaying in seeking and obtaining treatment. Although these difficulties are disproportionately experienced among vulnerable groups, we know very little about how the intersectionality of realities experienced by immigrants and visible minorities can impact their access to health care services since the pandemic.

Methods

Using Statistics Canada’s Crowdsourcing Data: Impacts of COVID-19 on Canadians—Experiences of Discrimination, we combine two variables (i.e., immigrant status and visible minority status) to create a new variable called visible minority immigrant status. This multiplicative approach is commonly used in intersectionality research, which allows us to explore disadvantages experienced by minorities with multiplicative identities.

Results

Main results show that, compared to white native-born, visible minority immigrants are less likely to report difficulties accessing non-emergency surgical care (OR = 0.55, p < 0.001), non-emergency diagnostic test (OR = 0.74, p < 0.01), dental care (OR = 0.71, p < 0.001), mental health care (OR = 0.77, p < 0.05), and making an appointment for rehabilitative care (OR = 0.56, p < 0.001) but more likely to report difficulties accessing emergency services/urgent care (OR = 1.46, p < 0.05).

Conclusion

We conclude that there is a dynamic interplay of factors operating at multiple levels to shape the impact of COVID-19 related needs to be addressed through changes in social policies, which can tackle unique struggles faced by visible minority immigrants.
A descriptive study on multisystem inflammatory syndrome in children in a single center in West Michigan
Authors: Shabab Jonathan , Dubisky Allysen , Singh Ambaris , Crippen Megan , Abulaban Khalid , Aldrich Aileen
Published: December 2021

Background

Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare hyperinflammatory condition that occurs following SARS-CoV-2 infection. There is a paucity of research describing risk factors, optimal management, and outcomes of this life-threatening condition.

Methods

This is a case series of 26 patients diagnosed with MIS-C in a West Michigan pediatric tertiary care center from April 2020 to February 2021. We describe the clinical, imaging, and laboratory characteristics of these patients and detail their treatments and outcomes with comparisons between Pediatric Intensive Care Unit (PICU) and non-PICU patients. Categorical testing utilized Chi-square and Fisher’s Exact tests. Comparison between groups used T-tests or Kruskal-Wallis.

Results

Fifteen patients (57%) required intensive care. There was no statistically significant difference in demographics between PICU and non-PICU patients, however all Black patients required intensive care. Gastrointestinal symptoms were present in 22 patients (84%). Seventeen patients (65%) had Kawasaki-like features and 12 (46%) developed coronary artery dilation. Patients requiring intensive care were less likely to have a reported history of COVID-19 disease or exposure (p = 0.0362). Statistically significant differences were also noted in peak ferritin (p = 0.0075), procalcitonin, and BNP in those who required intensive care.

Conclusions

Although overlap exists with other hyperinflammatory conditions, our study provides further evidence that MIS-C is a distinct, albeit heterogenous, disorder with various degrees of cardiac involvement. Anakinra, in conjunction with steroid use, appears to be effective and safe in the treatment of MIS-C. This report identifies procalcitonin, peak ferritin, and BNP as potentially useful biomarkers for severity of disease.
Positive end-expiratory pressure in COVID-19 acute respiratory distress syndrome: the heterogeneous effects
Authors: Chiumello Davide , Bonifazi Matteo , Pozzi Tommaso , Formenti Paolo , Papa Giuseppe Francesco Sferrazza , Zuanetti Gabriele , Coppola Silvia
Published: December 2021

Background

We hypothesized that as CARDS may present different pathophysiological features than classic ARDS, the application of high levels of end-expiratory pressure is questionable. Our first aim was to investigate the effects of 5–15 cmH2O of PEEP on partitioned respiratory mechanics, gas exchange and dead space; secondly, we investigated whether respiratory system compliance and severity of hypoxemia could affect the response to PEEP on partitioned respiratory mechanics, gas exchange and dead space, dividing the population according to the median value of respiratory system compliance and oxygenation. Thirdly, we explored the effects of an additional PEEP selected according to the Empirical PEEP-FiO2 table of the EPVent-2 study on partitioned respiratory mechanics and gas exchange in a subgroup of patients.

Methods

Sixty-one paralyzed mechanically ventilated patients with a confirmed diagnosis of SARS-CoV-2 were enrolled (age 60 [54–67] years, PaO2/FiO2 113 [79–158] mmHg and PEEP 10 [10–10] cmH2O). Keeping constant tidal volume, respiratory rate and oxygen fraction, two PEEP levels (5 and 15 cmH2O) were selected. In a subgroup of patients an additional PEEP level was applied according to an Empirical PEEP-FiO2 table (empirical PEEP). At each PEEP level gas exchange, partitioned lung mechanics and hemodynamic were collected.

Results

At 15 cmH2O of PEEP the lung elastance, lung stress and mechanical power were higher compared to 5 cmH2O. The PaO2/FiO2, arterial carbon dioxide and ventilatory ratio increased at 15 cmH2O of PEEP. The arterial–venous oxygen difference and central venous saturation were higher at 15 cmH2O of PEEP. Both the mechanics and gas exchange variables significantly increased although with high heterogeneity. By increasing the PEEP from 5 to 15 cmH2O, the changes in partitioned respiratory mechanics and mechanical power were not related to hypoxemia or respiratory compliance. The empirical PEEP was 18 ± 1 cmH2O. The empirical PEEP significantly increased the PaO2/FiO2 but also driving pressure, lung elastance, lung stress and mechanical power compared to 15 cmH2O of PEEP.

Conclusions

In COVID-19 ARDS during the early phase the effects of raising PEEP are highly variable and cannot easily be predicted by respiratory system characteristics, because of the heterogeneity of the disease.
Real-world corticosteroid use in severe pneumonia: a propensity-score-matched study
Authors: Ceccato A. , Russo A. , Barbeta E. , Oscanoa P. , Tiseo G. , Gabarrus A. , Di Giannatale P. , Nogas S. , Cilloniz C. , Menichetti F. , Ferrer M. , Niederman M. , Falcone M. , Torres A.
Published: December 2021

Background

Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide despite correct antibiotic use. Corticosteroids have long been evaluated as a treatment option, but heterogeneous effects on survival have precluded their widespread implementation. We aimed to evaluate whether corticosteroids might improve clinical outcomes in patients with severe CAP and high inflammatory responses.

Study design and methods

We analyzed two prospective observational cohorts of patients with CAP in Barcelona and Rome who were admitted to intensive care with a high inflammatory response. Propensity score (PS) matching was used to obtain balance among the baseline variables in both groups, and we excluded patients with viral pneumonia or who received hydrocortisone.

Results

Of the 610 patients admitted with severe CAP, 198 (32%) received corticosteroids and 387 had major criteria for severe CAP. All patients had a baseline serum C-reactive protein above 15 mg/dL. Patients who received corticosteroids were more commonly male, had more comorbidities (e.g., cancer or chronic obstructive pulmonary disease), and presented with significantly higher sequential organ failure assessment scores. Eighty-nine patients met major severity criteria (invasive mechanical ventilation and/or septic shock) and were matched per group. Twenty-eight-day mortality was lower among patients receiving corticosteroids (16 patients, 18%) than among those not receiving them (28 patients, 31%; p = 0.037). After PS matching, corticosteroid therapy reduced the 28-day mortality risk in patients who met major severity criteria (hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.29–0.98) (p = 0.043). In patients who did not meet major severity criteria, no benefits were observed with corticosteroid use (HR 0.88 (95%CI 0.32–2.36).

Conclusions

Corticosteroid treatment may be of benefit for patients with CAP who have septic shock and/or a high inflammatory response and requirement for invasive mechanical ventilation. Corticosteroids appear to have no impact on mortality when these features are not present.
Beyondcell: targeting cancer therapeutic heterogeneity in single-cell RNA-seq data
Authors: Fustero-Torre Coral , Jiménez-Santos María José , García-Martín Santiago , Carretero-Puche Carlos , García-Jimeno Luis , Ivanchuk Vadym , Di Domenico Tomás , Gómez-López Gonzalo , Al-Shahrour Fátima
Published: December 2021

We present Beyondcell, a computational methodology for identifying tumour cell subpopulations with distinct drug responses in single-cell RNA-seq data and proposing cancer-specific treatments. Our method calculates an enrichment score in a collection of drug signatures, delineating therapeutic clusters (TCs) within cellular populations. Additionally, Beyondcell determines the therapeutic differences among cell populations and generates a prioritised sensitivity-based ranking in order to guide drug selection. We performed Beyondcell analysis in five single-cell datasets and demonstrated that TCs can be exploited to target malignant cells both in cancer cell lines and tumour patients. Beyondcell is available at: https://gitlab.com/bu_cnio/beyondcell.
Methylation-derived inflammatory measures and lung cancer risk and survival
Authors: Zhao Naisi , Ruan Mengyuan , Koestler Devin C. , Lu Jiayun , Salas Lucas A. , Kelsey Karl T. , Platz Elizabeth A. , Michaud Dominique S.
Published: December 2021

Background

Examining immunity-related DNA methylation alterations in blood could help elucidate the role of the immune response in lung cancer etiology and aid in discovering factors that are key to lung cancer development and progression. In a nested, matched case–control study, we estimated methylation-derived NLR (mdNLR) and quantified DNA methylation levels at loci previously linked with circulating concentrations of C-reactive protein (CRP). We examined associations between these measures and lung cancer risk and survival.

Results

Using conditional logistic regression and further adjusting for BMI, batch effects, and a smoking-based methylation score, we observed a 47% increased risk of non-small cell lung cancer (NSCLC) for one standard deviation (SD) increase in mdNLR (n = 150 pairs; OR: 1.47, 95% CI 1.08, 2.02). Using a similar model, the estimated CRP Scores were inversely associated with risk of NSCLC (e.g., Score 1 OR: 0.57, 95% CI: 0.40, 0.81). Using Cox proportional hazards models adjusting for age, sex, smoking status, methylation-predicted pack-years, BMI, batch effect, and stage, we observed a 28% increased risk of dying from lung cancer (n = 145 deaths in 205 cases; HR: 1.28, 95% CI: 1.09, 1.50) for one SD increase in mdNLR.

Conclusions

Our study demonstrates that immunity status measured with DNA methylation markers is associated with lung cancer a decade or more prior to cancer diagnosis. A better understanding of immunity-associated methylation-based biomarkers in lung cancer development could provide insight into critical pathways.
From nasal to basal: single-cell sequencing of the bursa of Fabricius highlights the IBDV infection mechanism in chickens
Authors: Shah Abid Ullah , Li Yuchen , Ouyang Wei , Wang Zhisheng , Zuo Jinjiao , Shi Song , Yu Qinghua , Lin Jian , Yang Qian
Published: December 2021

Background

Chickens, important food animals and model organisms, are susceptible to many RNA viruses that invade via the nasal cavity. To determine the nasal entry site of the virus and clarify why avians are susceptible to RNA viruses, infectious bursal disease virus (IBDV) was selected because it is a typical avian RNA virus that infects chickens mainly via the nasal route.

Results

First, we found that IBDV infected the posterior part of the nasal cavity in chickens, which is rich in lymphoid tissue and allows the virus to be easily transferred to the blood. Via the blood circulation, IBDV infected peripheral blood mononuclear cells (PBMCs) and was transferred to the bursa of Fabricius to damage the IgM + B lymphocyte population. Subsequently, the single-cell RNA sequencing (scRNA-seq) results suggested the more detailed response of different bursal cell populations (B cells, epithelial cells, dendritic cells, and fibroblasts) to IBDV. Regarding B cells, IBDV infection greatly decreased the IgM + B cell population but increased the IgA + B cell population in the bursal follicles. In contrast to B cells, bursal epithelial cells, especially basal cells, accumulated a large number of IBDV particles. Furthermore, we found that both innate RNA sensors and interferon-stimulated genes (ISGs) were highly expressed in the IBDV-infected groups, while dicer and ago2 expression was largely blocked by IBDV infection. This result suggests that dicer-related RNA interference (RNAi) might be an effective antiviral strategy for IBDV infection in avian.

Conclusion

Our study not only comprehensively elaborates on the transmission of airborne IBDV via the intranasal route and establishes the main target cell types for productive IBDV infection but also provides sufficient evidence to explain the cellular antiviral mechanism against IBDV infection.

Graphical Abstract
The effect of the volemic and cardiac status on brain oxygenation in patients with subarachnoid hemorrhage: a bi-center cohort study
Authors: Rass Verena , Bogossian Elisa Gouvea , Ianosi Bogdan-Andrei , Peluso Lorenzo , Kofler Mario , Lindner Anna , Schiefecker Alois J. , Putnina Lauma , Gaasch Max , Hackl Werner O. , Beer Ronny , Pfausler Bettina , Taccone Fabio Silvio , Helbok Raimund
Published: December 2021

Background

Fluid management in patients after subarachnoid hemorrhage (SAH) aims at the optimization of cerebral blood flow and brain oxygenation. In this study, we investigated the effects of hemodynamic management on brain oxygenation by integrating advanced hemodynamic and invasive neuromonitoring.

Methods

This observational cohort bi-center study included data of consecutive poor-grade SAH patients who underwent pulse contour cardiac output (PiCCO) monitoring and invasive neuromonitoring. Fluid management was guided by the transpulmonary thermodilution system and aimed at euvolemia (cardiac index, CI ≥ 3.0 L/min/m2; global end-diastolic index, GEDI 680–800 mL/m2; stroke volume variation, SVV < 10%). Patients were managed using a brain tissue oxygenation (PbtO2) targeted protocol to prevent brain tissue hypoxia (BTH, PbtO2 < 20 mmHg). To assess the association between CI and PbtO2 and the effect of fluid challenges on CI and PbtO2, we used generalized estimating equations to account for repeated measurements.

Results

Among a total of 60 included patients (median age 56 [IQRs 47–65] years), BTH occurred in 23% of  the monitoring time during the first 10 days since admission. Overall, mean CI was within normal ranges (ranging from 3.1 ± 1.3 on day 0 to 4.1 ± 1.1 L/min/m2 on day 4). Higher CI levels were associated with higher PbtO2 levels (Wald = 14.2; p < 0.001). Neither daily fluid input nor fluid balance was associated with absolute PbtO2 levels (p = 0.94 and p = 0.85, respectively) or the occurrence of BTH (p = 0.68 and p = 0.71, respectively). PbtO2 levels were not significantly different in preload dependent patients compared to episodes of euvolemia. PbtO2 increased as a response to fluid boluses only if BTH was present at baseline (from 13 ± 6 to 16 ± 11 mmHg, OR = 13.3 [95% CI 2.6–67.4], p = 0.002), but not when all boluses were considered (p = 0.154).

Conclusions

In this study a moderate association between increased cardiac output and brain oxygenation was observed. Fluid challenges may improve PbtO2 only in the presence of baseline BTH. Individualized hemodynamic management requires advanced cardiac and brain monitoring in critically ill SAH patients.
Effectiveness and experiences of the Extension for Community Healthcare Outcomes (ECHO) Model in developing competencies among healthcare professionals: a mixed methods systematic review protocol
Authors: Chicoine Gabrielle , Côté José , Pepin Jacinthe , Fontaine Guillaume , Maheu-Cadotte Marc-André , Hong Quan Nha , Rouleau Geneviève , Ziegler Daniela , Jutras-Aswad Didier
Published: December 2021

Background

The Extension for Community Healthcare Outcomes (ECHO) Model of continuing tele-education is an innovative guided-practice model aiming at amplifying healthcare professionals’ competencies in the management of chronic and complex health conditions. While data on the impact of the ECHO model is increasingly available in the literature, what influences the model effectiveness remains unclear. Therefore, the overarching aim of this systematic review is to identify, appraise, and synthesize the available quantitative (QUAN) and qualitative (QUAL) evidence regarding the ECHO Model effectiveness and the experiences/views of ECHO’s participants about what influences the development of competencies in healthcare professionals.

Methods

The proposed systematic review was inspired by the Joanna Briggs Institute (JBI) methodology for Mixed Methods Systematic Reviews (MMSR) and will follow a convergent segregated approach. A systematic search will be undertaken using QUAN, QUAL and mixed methods (MM) studies of ECHO-affiliated programs identified in six databases. A publication date filter will be applied to find the articles published from 2003 onwards. Sources of unpublished studies and gray literature will be searched as well. Retrieved citations will independently be screened by two reviewers. Disagreements will be resolved through discussion until a consensus is reached or by including a third reviewer. Studies meeting the predefined inclusion criteria will be assessed on methodological quality and the data will be extracted using standardized data extraction forms. Separate QUAN and QUAL synthesis will be performed, and findings will be integrated using a matrix approach for the purpose of comparison and complementarity.

Discussion

This MMSR will fulfill important gaps in the current literature on the ECHO Model as the first to provide estimates on its effectiveness and consider simultaneously the experiences/views of ECHO’s participants. As each replication of the ECHO Model greatly varies depending on the context, topic, and targeted professionals, a better understanding of what influences the model effectiveness in developing healthcare professionals’ competencies is crucial to inform future implementation.

Systematic review registration

PROSPEROCRD42020197579
Utilization of agro-industrial by-products in Monascus fermentation: a review
Authors: Srianta Ignatius , Kusdiyantini Endang , Zubaidah Elok , Ristiarini Susana , Nugerahani Ira , Alvin Andreas , Iswanto Nathania , Zhang Bo-Bo
Published: December 2021

The Monascus fermentation industry has gained global attention. Its key products, i.e., pigments, functional food ingredients, food supplements, and medicinal use, are growing in the world’s market. Efforts to find the cost-effective substrate for Monascus fermentation have remained the target. This paper aimed to appraise the utilization of agro-industrial by-products (cereal, starchy tuber and root, legume, fruit, and coffee processing) as a cost-effective substrate for Monascus fermentation. The specific objective was to review the by-products pre-treatment, the fermentation process, product yield, and the bioactivity of the fermented products. Among all the by-products that could be used as the fermentation substrate, cereal brans do not need pre-treatment, but others need a suitable pre-treatment step, e.g., cassava peel, okara, and jackfruit seed to list a few, that need to be powdered beforehand. Other substrates, such as corn cob and durian seed, need soaking and size reduction through the pre-treatment step. During fermentation, Monascus produce many pigments, monacolin K, associated with rise in phenolic and flavonoid contents. These products possess antioxidant, antihypercholesterol, antidiabetes, and antiatherosclerosis activities which underpin their health significance. In conclusion, we report in this review the agro-industrial by-products which have potential prospects for pigments, functional food ingredients, food supplements, and therapeutic usages produced from Monascus fermentation.
Zymomonas mobilis as an emerging biotechnological chassis for the production of industrially relevant compounds
Authors: Braga Adelaide , Gomes Daniela , Rainha João , Amorim Cláudia , Cardoso Beatriz B. , Gudiña Eduardo J. , Silvério Sara C. , Rodrigues Joana L. , Rodrigues Lígia R.
Published: December 2021

Zymomonas mobilis is a well-recognized ethanologenic bacterium with outstanding characteristics which make it a promising platform for the biotechnological production of relevant building blocks and fine chemicals compounds. In the last years, research has been focused on the physiological, genetic, and metabolic engineering strategies aiming at expanding Z. mobilis ability to metabolize lignocellulosic substrates toward biofuel production. With the expansion of the Z. mobilis molecular and computational modeling toolbox, the potential of this bacterium as a cell factory has been thoroughly explored. The number of genomic, transcriptomic, proteomic, and fluxomic data that is becoming available for this bacterium has increased. For this reason, in the forthcoming years, systems biology is expected to continue driving the improvement of Z. mobilis for current and emergent biotechnological applications. While the existing molecular toolbox allowed the creation of stable Z. mobilis strains with improved traits for pinpointed biotechnological applications, the development of new and more flexible tools is crucial to boost the engineering capabilities of this bacterium. Novel genetic toolkits based on the CRISPR-Cas9 system and recombineering have been recently used for the metabolic engineering of Z. mobilis. However, they are mostly at the proof-of-concept stage and need to be further improved.

Graphical Abstract
Duodenal stenosis associated with an ectopic opening of the common bile duct into the duodenal bulb: a case report
Authors: Kobayashi Kazuki , Murayama Michinori , Sugasawa Hidekazu , Nishikawa Makoto , Nishiyama Kiyoshi , Takeo Hiroaki
Published: December 2021

Background

Ectopic opening of the common bile duct is a rare congenital biliary anomaly. Herein, we present a case of duodenal stenosis with ectopic opening of the common bile duct into the duodenal bulb.

Case presentation

A 54-year-old man was referred with fever, nausea, and vomiting. He had experienced epigastric pain several times over the past 30 years. Endoscopy showed a post-bulbar ulcer, a submucosal tumor of the duodenum, and a small opening with bile secretion. Contrast duodenography revealed duodenal stenosis and bile reflux with a common bile duct deformity. Pancreatoduodenectomy was performed because of the clinical suspicion of a biliary neoplasm or groove pancreatitis. The resected specimen showed an ectopic opening of the common bile duct into the duodenal bulb and no tumor.

Conclusions

Ectopic opening of the common bile duct into the duodenal bulb is complicated by a duodenal ulcer, deformity, and stenosis mimicking groove pancreatitis or pancreatic tumors. Although rare, we should be aware of this anomaly for an accurate diagnosis.
Seismic-while-drilling by drill-bit source and large-aperture ocean-bottom array
Authors: Poletto Flavio , Goertz Alex , Bellezza Cinzia , Vange Bergfjord Endre , Corubolo Piero , Lindgård John Even , Moskvil Lars Martin
Published: December 2021

Seismic-while-drilling (SWD) by drill-bit source has been successfully used in the past few decades and is proven using variable configurations in onshore applications. The method creates a reverse vertical seismic profile (RVSP) data set from surface sensors deployed as arrays in the proximity of the monitored wells. The typical application makes use of rig-pilot reference (pilot) sensors at the top of the drill string and also downhole. This approach provides while-drilling checkshots as well as multioffset RVSP for 2D and 3D imaging around the well and prediction ahead of the bit. For logistical (sensor deployment) and cost (rig time related to technical installation) reasons, the conventional drill-bit SWD application is typically much easier onshore than offshore. We have developed a novel approach that uses a network of passive-monitoring sea-bottom nodes predeployed for microseismic monitoring to simultaneously and effectively record offshore SWD data. We study the results of a pilot test in which we passively monitored the drilling of an appraisal well at the Wisting discovery in the Barents Sea with an ocean-bottom cable deployed temporarily around the drilling rig. The continuous passive recording of vibration signals emitted during the drilling of the well provides the SWD data set, which is treated as an RVSP. The study is performed without rig-pilot signal. The results are compared with legacy data and demonstrate the effectiveness of the approach and point to future applications for real-time monitoring of the drilling progress, in terms of geosteering the drill bit and predicting formation properties ahead of the bit by reflection imaging.
Deblending based on the frequency-structure weighted threshold: The case of the slope-constrainedf-ktransform
Authors: Chen Siyuan , Cao Siyuan , Sun Yaoguang
Published: December 2021

In the process of separating blended data, conventional methods based on sparse inversion assume that the primary source is coherent and the secondary source is randomized. The L1-norm, the commonly used regularization term, uses a global threshold (GT) to process the sparse spectrum in the transform domain; however, when the threshold is relatively high, more high-frequency information from the primary source will be lost. For this reason, we have analyzed the generation principle of blended data based on the convolution theory and then conclude that the blended data are only randomly distributed in the spatial domain. Taking the slope-constrained frequency-wavenumber ( f- k) transform as an example, we adopt a frequency-dependent threshold, which reduces the high-frequency loss during the deblending process. Then, we use a structure-weighted threshold (SWT) in which the energy from the primary source is concentrated along the wavenumber direction. The combination of frequency and SWTs effectively improves the deblending performance. Model and field data find that our frequency-structure weighted threshold has better frequency preservation than the GT. The weighted threshold can better retain the high-frequency information of the primary source, and the similarity between other frequency-band data and the unblended data has been improved.