bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractWe 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

Abstract
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

Abstract
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

Abstract
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

AbstractBackgroundThe 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.MethodsThe 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.DiscussionThis 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 registrationPROSPEROCRD42020197579
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

AbstractThe 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.