bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ground truth labels challenge the validity of sepsis consensus definitions in critical illness
Authors: Lindner Holger A. , Schamoni Shigehiko , Kirschning Thomas , Worm Corinna , Hahn Bianka , Centner Franz-Simon , Schoettler Jochen J. , Hagmann Michael , Krebs Jörg , Mangold Dennis , Nitsch Stephanie , Riezler Stefan , Thiel Manfred , Schneider-Lindner Verena 
Published: January 2022

Abstract
Background
Sepsis is the leading cause of death in the intensive care unit (ICU). Expediting its diagnosis, largely determined by clinical assessment, improves survival. Predictive and explanatory modelling of sepsis in the critically ill commonly bases both outcome definition and predictions on clinical criteria for consensus definitions of sepsis, leading to circularity. As a remedy, we collected ground truth labels for sepsis.

Methods
In the Ground Truth for Sepsis Questionnaire (GTSQ), senior attending physicians in the ICU documented daily their opinion on each patient’s condition regarding sepsis as a five-category working diagnosis and nine related items. Working diagnosis groups were described and compared and their SOFA-scores analyzed with a generalized linear mixed model. Agreement and discriminatory performance measures for clinical criteria of sepsis and GTSQ labels as reference class were derived.

Results
We analyzed 7291 questionnaires and 761 complete encounters from the first survey year. Editing rates for all items were > 90%, and responses were consistent with current understanding of critical illness pathophysiology, including sepsis pathogenesis. Interrater agreement for presence and absence of sepsis was almost perfect but only slight for suspected infection. ICU mortality was 19.5% in encounters with SIRS as the “worst” working diagnosis compared to 5.9% with sepsis and 5.9% with severe sepsis without differences in admission and maximum SOFA. Compared to sepsis, proportions of GTSQs with SIRS plus acute organ dysfunction were equal and macrocirculatory abnormalities higher (p < 0.0001). SIRS proportionally ranked above sepsis in daily assessment of illness severity (p < 0.0001). Separate analyses of neurosurgical referrals revealed similar differences. Discriminatory performance of Sepsis-1/2 and Sepsis-3 compared to GTSQ labels was similar with sensitivities around 70% and specificities 92%. Essentially no difference between the prevalence of SIRS and SOFA ≥ 2 yielded sensitivities and specificities for detecting sepsis onset close to 55% and 83%, respectively.

Conclusions
GTSQ labels are a valid measure of sepsis in the ICU. They reveal suspicion of infection as an unclear clinical concept and refute an illness severity hierarchy in the SIRS-sepsis-severe sepsis spectrum. Ground truth challenges the accuracy of Sepsis-1/2 and Sepsis-3 in detecting sepsis onset. It is an indispensable intermediate step towards advancing diagnosis and therapy in the ICU and, potentially, other health care settings.
GDF11 alleviates neointimal hyperplasia in a rat model of artery injury by regulating endothelial NLRP3 inflammasome activation and rapid re-endothelialization
Authors: Li Lei , Gao Yan , Liu Zhenchuan , Dong Chenglai , Wang Wenli , Wu Kaiqin , Gu Shaorui , Zhou Yongxin 
Published: January 2022

AbstractBackgroundNeointimal hyperplasia induced by interventional surgery can lead to progressive obliteration of the vascular lumen, which has become a major factor affecting prognosis. The rate of re-endothelialization is known to be inversely related to neointima formation. Growth differentiation factor 11 (GDF11) is a secreted protein with anti-inflammatory, antioxidant, and antiaging properties. Recent reports have indicated that GDF11 can improve vascular remodeling by maintaining the differentiated phenotypes of vascular smooth muscle cells. However, it is not known whether and how GDF11 promotes re-endothelialization in vascular injury. The present study was performed to clarify the influence of GDF11 on re-endothelialization after vascular injury.MethodsAn adult Sprague–Dawley rat model of common carotid artery balloon dilatation injury was surgically established. A recombinant adenovirus carrying GDF11 was delivered into the common carotid artery to overexpress GDF11. Vascular re-endothelialization and neointima formation were assessed in harvested carotid arteries through histomolecular analysis. CCK-8 analysis, LDH release and Western blotting were performed to investigate the effects of GDF11 on endothelial NLRP3 inflammasome activation and relevant signaling pathways in vitro.ResultsGDF11 significantly enhanced re-endothelialization and reduced neointima formation in rats with balloon-dilatation injury by suppressing the activation of the NLRP3 inflammasome. Administration of an endoplasmic reticulum stress (ER stress) inhibitor, 4PBA, attenuated endothelial NLRP3 inflammasome activation induced by lysophosphatidylcholine. In addition, upregulation of LOX-1 expression involved elevated ER stress and could result in endothelial NLRP3 inflammasome activation. Moreover, GDF11 significantly inhibited NLRP3 inflammasome-mediated endothelial cell pyroptosis by negatively regulating LOX-1-dependent ER stress.ConclusionsWe conclude that GDF11 improves re-endothelialization and can attenuate vascular remodeling by reducing endothelial NLRP3 inflammasome activation. These findings shed light on new treatment strategies to promote re-endothelialization based on GDF11 as a future target.
Evaluation of exosomal non-coding RNAs in cancer using high-throughput sequencing
Authors: Hosseini Kamran , Ranjbar Maryam , Pirpour Tazehkand Abbas , Asgharian Parina , Montazersaheb Soheila , Tarhriz Vahideh , Ghasemnejad Tohid 
Published: January 2022

AbstractClinical oncologists need more reliable and non-invasive diagnostic and prognostic biomarkers to follow-up cancer patients. However, the existing biomarkers are often invasive and costly, emphasizing the need for the development of biomarkers to provide convenient and precise detection. Extracellular vesicles especially exosomes have recently been the focus of translational research to develop non-invasive and reliable biomarkers for several diseases such as cancers, suggesting as a valuable source of tumor markers. Exosomes are nano-sized extracellular vesicles secreted by various living cells that can be found in all body fluids including serum, urine, saliva, cerebrospinal fluid, and ascites. Different molecular and genetic contents of their origin such as nucleic acids, proteins, lipids, and glycans in a stable form make exosomes a promising approach for various cancers’ diagnoses, prediction, and follow-up in a minimally invasive manner. Since exosomes are used by cancer cells for intercellular communication, they play a critical role in the disease process, highlighting the importance of their use as clinically relevant biomarkers. However, regardless of the advantages that exosome-based diagnostics have, they suffer from problems regarding their isolation, detection, and characterization of their contents. This study reviews the history and biogenesis of exosomes and discusses non-coding RNAs (ncRNAs) and their potential as tumor markers in different types of cancer, with a focus on next generation sequencing (NGS) as a detection method. Moreover, the advantages and challenges associated with exosome-based diagnostics are also presented.
Pediococcus pentosaceus CECT 8330 protects DSS-induced colitis and regulates the intestinal microbiota and immune responses in mice
Authors: Dong Fang , Xiao Fangfei , Li Xiaolu , Li Youran , Wang Xufei , Yu Guangjun , Zhang Ting , Wang Yizhong 
Published: January 2022

Abstract
Background
Compelling evidences demonstrated that gut microbiota dysbiosis plays a critical role in the pathogenesis of inflammatory bowel diseases (IBD). Therapies for targeting the microbiota may provide alternative options for the treatment of IBD, such as probiotics. Here, we aimed to investigate the protective effect of a probiotic strain, Pediococcus pentosaceus (P. pentosaceus) CECT 8330, on dextran sulfate sodium (DSS)-induced colitis in mice.

Methods
C57BL/6 mice were administered phosphate-buffered saline (PBS) or P. pentosaceus CECT 8330 (5 × 108 CFU/day) once daily by gavage for 5 days prior to or 2 days after colitis induction by DSS. Weight, fecal conditions, colon length and histopathological changes were examined. ELISA and flow cytometry were applied to determine the cytokines and regulatory T cells (Treg) ratio. Western blot was used to examine the tight junction proteins (TJP) in colonic tissues. Fecal short-chain fatty acids (SCFAs) levels and microbiota composition were analyzed by targeted metabolomics and 16S rRNA gene sequencing, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Cluster of orthologous groups of proteins (COG) pathway analysis were used to predict the microbial functional profiles.

Results
P. pentosaceus CECT 8330 treatment protected DSS-induced colitis in mice as evidenced by reducing the weight loss, disease activity index (DAI) score, histological damage, and colon length shortening. P. pentosaceus CECT 8330 decreased the serum levels of proinflammatory cytokines (TNF-α, IL-1β, and IL-6), and increased level of IL-10 in DSS treated mice. P. pentosaceus CECT 8330 upregulated the expression of ZO-1, Occludin and the ratio of Treg cells in colon tissue. P. pentosaceus CECT 8330 increased the fecal SCFAs level and relative abundances of several protective bacteria genera, including norank_f_Muribaculaceae, Lactobacillus, Bifidobacterium, and Dubosiella. Furthermore, the increased abundances of bacteria genera were positively correlated with IL-10 and SCFAs levels, and negatively associated with IL-6, IL-1β, and TNF-α, respectively. The KEGG and COG pathway analysis revealed that P. pentosaceus CECT 8330 could partially recover the metabolic pathways altered by DSS.

Conclusions
P. pentosaceus CECT 8330 administration protects the DSS-induced colitis and modulates the gut microbial composition and function, immunological profiles, and the gut barrier function. Therefore, P. pentosaceus CECT 8330 may serve as a promising probiotic to ameliorate intestinal inflammation.
Proteomics based markers of clinical pain severity in juvenile idiopathic arthritis
Authors: Van Der Heijden Hanne , Fatou Benoit , Sibai Diana , Hoyt Kacie , Taylor Maria , Cheung Kin , Lemme Jordan , Cay Mariesa , Goodlett Benjamin , Lo Jeffery , Hazen Melissa M. , Halyabar Olha , Meidan Esra , Schreiber Rudy , Jaimes Camilo , Ecklund Kirsten , Henderson Lauren A. , Chang Margaret H. , Nigrovic Peter A. , Sundel Robert P. , Steen Hanno , Upadhyay Jaymin 
Published: January 2022

Abstract
Introduction
Juvenile idiopathic arthritis (JIA) is a cluster of autoimmune rheumatic diseases occurring in children 16 years of age or less. While it is well-known that pain may be experienced during inflammatory and non-inflammatory states, much remains ambiguous regarding the molecular mechanisms that may drive JIA pain. Thus, in this pilot study, we explored the variability of the serum proteomes in relation to pain severity in a cohort of JIA patients.

Methods
Serum samples from 15 JIA patients (male and female, 12.7 ± 2.8 years of age) were assessed using liquid chromatography/mass spectrometry (LC/MS). Correlation analyses were performed to determine the relationships among protein levels and self-reported clinical pain severity. Additionally, how the expression of pain-associated proteins related to markers of inflammation (Erythrocyte Sedimentation Rate (ESR)) or morphological properties of the central nervous system (subcortical volume and cortical thickness) implicated in JIA were also evaluated.

Results
306 proteins were identified in the JIA cohort of which 14 were significantly (p < 0.05) associated with clinical pain severity. Functional properties of the identified pain-associated proteins included but were not limited to humoral immunity (IGLV3.9), inflammatory response (PRG4) and angiogenesis (ANG). Associations among pain-associated proteins and ESR (IGHV3.9, PRG4, CST3, VWF, ALB), as well as caudate nucleus volume (BTD, AGT, IGHV3.74) and insular cortex thickness (BTD, LGALS3BP) were also observed.

Conclusions
The current proteomic findings suggest both inflammatory- and non-inflammatory mediated mechanisms as potential factors associated with JIA pain. Validation of these preliminary observations using larger patient cohorts and a longitudinal study design may further point to novel serologic markers of pain in JIA.
Reduced and highly diverse peripheral HIV-1 reservoir in virally suppressed patients infected with non-B HIV-1 strains in Uganda
Authors: Joussef-Piña Samira , Nankya Immaculate , Nalukwago Sophie , Baseke Joy , Rwambuya Sandra , Winner Dane , Kyeyune Fred , Chervenak Keith , Thiel Bonnie , Asaad Robert , Dobrowolski Curtis , Luttge Benjamin , Lawley Blair , Kityo Cissy M. , Boom W. Henry , Karn Jonathan , Quiñones-Mateu Miguel E. 
Published: January 2022

AbstractBackgroundOur understanding of the peripheral human immunodeficiency virus type 1 (HIV-1) reservoir is strongly biased towards subtype B HIV-1 strains, with only limited information available from patients infected with non-B HIV-1 subtypes, which are the predominant viruses seen in low- and middle-income countries (LMIC) in Africa and Asia.ResultsIn this study, blood samples were obtained from well-suppressed ART-experienced HIV-1 patients monitored in Uganda (n = 62) or the U.S. (n = 50), with plasma HIV-1 loads < 50 copies/ml and CD4+T-cell counts > 300 cells/ml. The peripheral HIV-1 reservoir, i.e., cell-associated HIV-1 RNA and proviral DNA, was characterized using our novel deep sequencing-based EDITS assay. Ugandan patients were slightly younger (median age 43 vs 49 years) and had slightly lower CD4+counts (508 vs 772 cells/ml) than U.S. individuals. All Ugandan patients were infected with non-B HIV-1 subtypes (31% A1, 64% D, or 5% C), while all U.S. individuals were infected with subtype B viruses. Unexpectedly, we observed a significantly larger peripheral inducible HIV-1 reservoir in U.S. patients compared to Ugandan individuals (48 vs. 11 cell equivalents/million cells,p < 0.0001). This divergence in reservoir size was verified measuring proviral DNA (206 vs. 88 cell equivalents/million cells,p < 0.0001). However, the peripheral HIV-1 reservoir was more diverse in Ugandan than in U.S. individuals (8.6 vs. 4.7 p-distance,p < 0.0001).ConclusionsThe smaller, but more diverse, peripheral HIV-1 reservoir in Ugandan patients might be associated with viral (e.g., non-B subtype with higher cytopathicity) and/or host (e.g., higher incidence of co-infections or co-morbidities leading to less clonal expansion) factors. This highlights the need to understand reservoir dynamics in diverse populations as part of ongoing efforts to find a functional cure for HIV-1 infection in LMICs.
Sexual and reproductive health education and its association with ever use of contraception: a cross-sectional study among women in urban slums, Accra
Authors: Seidu Abdul-Aziz , Ameyaw Edward Kwabena , Ahinkorah Bright Opoku , Baatiema Leonard , Dery Samuel , Ankomah Augustine , Ganle John Kuumuori 
Published: January 2022

Abstract
Background
Sexual and reproductive health education among girls and women has several reproductive health benefits, including improved contraceptive knowledge, contraception use at first intercourse, increased chance of contraceptive use in a lifetime, and effective usage of contraceptives. It is however not clear whether women/girls in urban slums who have had sexual and reproductive health education would likely utilize contraception. This study sets out to test the hypothesis that Accra slum women who have had sex education have higher chances of ever using contraception.

Methods
A cross-sectional survey was conducted among reproductive aged women in two slums (i.e. Agbogbloshie and Old Fadama) in Accra, Ghana. A sample size of 691, made up of respondents who provided responses to the question on ever used contraception, sex education as well as those with complete information on all the other variables of interest was considered in this study. Binary logistic regression models were fitted to examine association between sexual and reproductive health education and ever use of contraception. Crude odds ratios (cOR) and adjusted odds ratios (aOR) at p-value less than 0.05 were used to assess the strength of the association between the outcome and independent variables.

Results
More than half (56.73%) of the women have never received sexual and reproductive health education. Most of the respondents (77.28%) had ever used contraceptives. Women who had no form of sexual and reproductive health education had lower odds of ever using contraception (OR = 0.641, 95% CI 0.443, 0.928) and this persisted after controlling for the effect of demographic factors (AOR = 0.652, 95% CI 0.436, 0.975] compared to those who have ever received any form of sex education. Non-married women as well as women who were exposed to media (newspapers/radio/television) were also more likely to use contraceptives in slums in Accra, Ghana.

Conclusion
The study revealed a relatively low prevalence of sex education among women in urban slums in Accra. However, sex education was found to increase the odds of ever use of contraception. These findings call for intensified sexual and reproductive health education among reproductive aged girls and women in urban slums in Accra using existing informal social networks and local media platforms.
Teenage childbearing and school dropout in a sample of 18,791 single mothers in Cameroon
Authors: Sobngwi-Tambekou Joëlle L. , Tsague-Agnoux Marthe , Fezeu Léopold K. , Ndonko Flavien 
Published: January 2022

Abstract
Background
Adolescent childbearing increases the risk of adverse health and social consequences including school dropout (SDO). However, it remains unclear why some teenage mothers drop out of school and others do not, especially in sub-Saharan Africa settings. We aimed to investigate the background and behavioral characteristics of single mothers, associated with school dropout in a sample of 18,791 Cameroonian girls, who had their first child during adolescence.

Methods
We used data from a national registry of single mothers, collected during the years 2005–2008 and 2010–2011. Both bivariate analysis and logistic binary regression models were used to explore the relationship between adolescence motherhood and SDO controlling for a range of socio-economic, family, sexual and health seeking behavior characteristics.

Results
Among the 18,791 single mothers, 41.6% had dropped out of school because of pregnancy. The multivariable regression model showed that SDO was more common in those who were evicted from their parental home (aOR: 1.85; 95% CI: 1.69–2.04), those who declared having other single mothers in their family (aOR: 1.16; 95% CI 1.08–1.25) and in mothers who had their first child before 15. Using modern contraceptive methods, having declared no sexual partner during the last year and having less than 2 children were associated with a reduced likelihood of school dropout.

Conclusions
Strong social support is essential to ensure school continuity in this vulnerable population. Dropping out of school may put the teenage mother more at risk of unsafe health behaviour and new pregnancies.
Clinical characteristics, risk factors and antiviral treatments of influenza in immunosuppressed inpatients in Beijing during the 2015–2020 influenza seasons
Authors: Liu Yafen , Wang Yue , Mai Huan , Chen YuanYuan , Liu Baiyi , Liu YiSi , Ji Ying , Cong Xu , Gao Yan 
Published: January 2022

AbstractBackgroundCompared with immunocompetent patients, immunosuppressed patients have higher morbidity and mortality, a longer duration of viral shedding, more frequent complications, and more antiviral resistance during influenza infections. However, few data on this population in China have been reported. We analysed the clinical characteristics, effects of antiviral therapy, and risk factors for admission to the intensive care unit (ICU) and death in this population after influenza infections and explored the influenza vaccination situation for this population.MethodsWe analysed 111 immunosuppressed inpatients who were infected with influenza virus during the 2015–2020 influenza seasons. Medical data were collected through the electronic medical record system and analysed. Univariate analysis and multivariate logistics analysis were used to identify risk factors.ResultsThe most common cause of immunosuppression was malignancies being treated with chemotherapy (64.0%, 71/111), followed by haematopoietic stem cell transplantation (HSCT) (23.4%, 26/111). The most common presenting symptoms were fever and cough. Dyspnoea, gastrointestinal symptoms and altered mental status were more common in HSCT patients than in patients with immunosuppression due to other causes. Approximately 14.4% (16/111) of patients were admitted to the ICU, and 9.9% (11/111) of patients died. Combined and double doses of neuraminidase inhibitors did not significantly reduce the risk of admission to the ICU or death. Risk factors for admission to the ICU were dyspnoea, coinfection with other pathogens and no antiviral treatment within 48 h. The presence of dyspnoea and altered mental status were independently associated with death. Only 2.7% (3/111) of patients less than 12 months old had received a seasonal influenza vaccine.ConclusionFever and other classic symptoms of influenza may be absent in immunosuppressed recipients, especially in HSCT patients. Conducting influenza virus detection at the first presentation seems to be a good choice for early diagnosis. Clinicians should pay extra attention to immunosuppressed patients with dyspnoea, altered mental status, coinfection with other pathogens and no antiviral treatment within 48 h because these patients have a high risk of severe illness. Inactivated influenza vaccines are recommended for immunosuppressed patients.