bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unique characteristics of lung-resident neutrophils are maintained by PGE2/PKA/Tgm2-mediated signaling
Authors: Bae Geon Ho , Kim Ye Seon , Park Ji Ye , Lee Mingyu , Lee Sung Kyun , Kim Ji Cheol , Kim Jang Gyu , Shin Ye Ji , Lee Ho , Kim Soo-Youl , Bae Yong-Soo , Zabel Brian A. , Kim Hong Sook , Bae Yoe-Sik 
Published: June 2022

AbstractLung-resident neutrophils need to be tightly regulated to avoid degranulation- and cytokine-associated damage to fragile alveolar structures that can lead to fatal outcomes. Here we show that lung neutrophils (LNs) express distinct surface proteins and genes that distinguish LNs from bone marrow and blood neutrophils. Functionally, LNs show impaired migratory activity toward chemoattractants and produce high levels of interleukin-6 (IL-6) at steady state and low levels of tumor necrosis factor-α in response to lipopolysaccharide (LPS) challenge. Treating bone marrow neutrophils with bronchoalveolar lavage fluid or prostaglandin E2 induces LN-associated characteristics, including the expression of transglutaminase 2 (Tgm2) and reduced production of inflammatory cytokines upon LPS challenge. Neutrophils from Tgm2−/− mice release high levels of inflammatory cytokines in response to LPS. Lung damage is significantly exacerbated in Tgm2−/− mice in an LPS-induced acute respiratory distress syndrome model. Collectively, we demonstrate that prostaglandin E2 is a key factor for the generation of LNs with unique immune suppressive characteristics, acting through protein kinase A and Tgm2, and LNs play essential roles in protection of the lungs against pathogenic inflammation.
Comparative effectiveness of ZUMA-5 (axi-cel) vs SCHOLAR-5 external control in relapsed/refractory follicular lymphoma
Authors: Ghione Paola , Palomba M. Lia , Patel Anik R. , Bobillo Sabela , Deighton Kevin , Jacobson Caron A. , Nahas Myrna , Hatswell Anthony J. , Jung A. Scott , Kanters Steve , Snider Julia Thornton , Neelapu Sattva S. , Ribeiro Maria Teresa , Brookhart M. Alan , Ghesquieres Herve , Radford John , Gribben John G. 
Published: June 2022

Abstract
In the pivotal ZUMA-5 trial, axicabtagene ciloleucel (axi-cel; an autologous anti-CD19 chimeric antigen receptor T-cell therapy) demonstrated high rates of durable response in relapsed/refractory (r/r) follicular lymphoma (FL) patients. Here, outcomes from ZUMA-5 are compared with the international SCHOLAR-5 cohort, which applied key ZUMA-5 trial eligibility criteria simulating randomized controlled trial conditions. SCHOLAR-5 data were extracted from institutions in 5 countries, and from 1 historical clinical trial, for r/r FL patients who initiated a third or higher line of therapy after July 2014. Patient characteristics were balanced through propensity scoring on prespecified prognostic factors using standardized mortality ratio (SMR) weighting. Time-to-event outcomes were evaluated using weighted Kaplan-Meier analysis. Overall response rate (ORR) and complete response (CR) rate were compared using weighted odds ratios. The 143 ScHOLAR-5 patients reduced to an effective sample of 85 patients after SMR weighting vs 86 patients in ZUMA-5. Median follow-up time was 25.4 and 23.3 months for SCHOLAR-5 and ZUMA-5. Median overall survival (OS) and progression-free survival (PFS) in SCHOLAR-5 were 59.8 months and 12.7 months and not reached in ZUMA-5. Hazard ratios for OS and PFS were 0.42 (95% confidence interval [CI], 0.21-0.83) and 0.30 (95% CI, 0.18-0.49). The ORR and CR rate were 49.9% and 29.9% in SCHOLAR-5 and 94.2% and 79.1% in ZUMA-5, for odds ratios of 16.2 (95% CI, 5.6-46.9) and 8.9 (95% CI, 4.3-18.3). Compared with available therapies, axi-cel demonstrated an improvement in meaningful clinical endpoints, suggesting axi-cel addresses an important unmet need for r/r FL patients. This trial was registered at www.clinicaltrials.gov as #NCT03105336.
Comparative transcriptomic analysis reveals the molecular mechanism underlying seedling biomass heterosis in Brassica napus
Authors: Xiong Jie , Hu Kaining , Shalby Nesma , Zhuo Chenjian , Wen Jing , Yi Bin , Shen Jinxiong , Ma Chaozhi , Fu Tingdong , Tu Jinxing 
Published: June 2022

Abstract
Background
Heterosis is an important biological phenomenon in which the hybrids exceed the parents in many traits. However, the molecular mechanism underlying seedling heterosis remains unclear.

Results
In the present study, we analyzed the leaf transcriptomes of strong hybrids (AM, HM) and weak hybrids (CM, HW) and their parents (A, C, H, M, and W) at two periods. Phenotypically, hybrids had obvious biomass heterosis at the seedling stage, with statistically significant differences between the strong and weak hybrids. The transcriptomic analysis demonstrated that the number of differentially expressed genes (DEGs) between parents was the highest. Further analysis showed that most DEGs were biased toward parental expression. The biological processes of the two periods were significantly enriched in the plant hormone signal transduction and photosynthetic pathways. In the plant hormone signaling pathway, DEG expression was high in hybrids, with expression differences between strong and weak hybrids. In addition, DEGs related to cell size were identified. Similar changes were observed during photosynthesis. The enhanced leaf area of hybrids generated an increase in photosynthetic products, which was consistent with the phenotype of the biomass. Weighted gene co-expression network analysis of different hybrids and parents revealed that hub genes in vigorous hybrid were mainly enriched in the plant hormone signal transduction and regulation of plant hormones.

Conclusion
Plant hormone signaling and photosynthesis pathways, as well as differential expression of plant cell size-related genes, jointly regulate the dynamic changes between strong and weak hybrids and the generation of seedling-stage heterosis. This study may elucidate the molecular mechanism underlying early biomass heterosis and help enhance canola yield.
Arterial catheterization and in-hospital mortality in sepsis: a propensity score-matched study
Authors: Ou Qitian , Cai Gengxin , Zhou Yuan , Zha Wanjie , Huang Linqiang , Zeng Hongke , Jiang Wenqiang , Chen Shenglong , Wen Miaoyun 
Published: June 2022

Abstract
Background
Despite the extensive use of arterial catheterization (AC), clinical effectiveness of AC to alter the outcomes among patients with sepsis and septic shock has not been evaluated. The purpose of this study is to examine the association between the use of AC and in-hospital mortality in septic patients.

Methods
Adult patients with sepsis from Medical Information Mart for Intensive Care database were screened to conduct this retrospective observational study. Propensity score matching (PSM) was employed to estimate the relationship between arterial catheterization (AC) and in-hospital mortality. Multivariable logistic regression and inverse probability of treatment weighing (IPTW) were used to validate our findings.

Results
A total of 14,509 septic patients without shock and 4,078 septic shock patients were identified. 3,489 pairs in sepsis patients without shock and 589 pairs in septic shock patients were yielded respectively after PSM. For patients in the sepsis without shock group, AC placement was associated with increased in-hospital mortality (OR, 1.34; 95% CI, 1.17–1.54; p < 0.001). In the septic shock group, there was no significant difference in hospital mortality between AC group and non-AC group. The results of logistic regression and propensity score IPTW model support our findings.

Conclusions
In hemodynamically stable septic patients, AC is independently associated with higher in-hospital mortality, while in patients with septic shock, AC was not associated with improvements in hospital mortality.
Major cardiovascular events after bone marrow mononuclear cell transplantation following acute myocardial infarction: an updated post-BAMI meta-analysis of randomized controlled trials
Authors: Attar Armin , Hosseinpour Alireza , Hosseinpour Hamidreza , Kazemi Asma 
Published: June 2022

Abstract
Background
The effect of bone marrow-derived mononuclear cells (BM-MNCs) after acute myocardial infarction (AMI) on myocardial function indices such as left ventricular ejection fraction has been widely studied. However, the effect of this intervention on major adverse cardiovascular events (MACE) was not the principal purpose of most investigations and its role is unclear. The aim of this study was to investigate the possible long-term clinical efficacy of BM-MNCs on MACE after AMI.

Methods
A comprehensive search was conducted through electronic databases for potentially eligible randomized trials investigating the impact of BM-MNC therapy following acute MI on clinical outcomes. Risk of bias of the eligible studies was assessed using the Cochrane Collaboration’s tool. The effect of treatment was displayed by risk ratio (RR) and its 95% confidence interval (CI) using random-effects model.

Results
Initial database searching found 1540 records and 23 clinical trials with a total of 2286 participants eligible for meta-analysis. Injection of BM-MNCs was associated with lower risk of composite end points of hospitalization for congestive heart failure (CHF), re-infarction, and cardiac-related mortality (91/1191 vs. 111/812, RR = 0.643, 95% CI = 0.489 to 0.845, p = 0.002). This effect was derived from both reduction of CHF (47/1220 vs. 62/841, RR = 0.568, 95% CI = 0.382 to 0.844, p = 0.005) and re-infarction rate (23/1159 vs. 30/775, RR = 0.583, 95% CI = 0.343 to 0.991, p = 0.046), but not cardiac-related mortality (28/1290 vs. 31/871, RR = 0.722, 95% CI = 0.436 to 1.197, p = 0.207).

Conclusion
This is the first meta-analysis focused on the cardiovascular outcomes of stem cell therapy after AMI and it revealed that transplantation of BM-MNCs may reduce composite endpoint of hospitalization for CHF, re-infarction, and cardiac related mortality driven mainly by reducing reinfarction and hospitalization for heart failure rates but not cardiovascular mortality.
An investigation of penalization and data augmentation to improve convergence of generalized estimating equations for clustered binary outcomes
Authors: Geroldinger Angelika , Blagus Rok , Ogden Helen , Heinze Georg 
Published: June 2022

AbstractBackgroundIn binary logistic regression data are ‘separable’ if there exists a linear combination of explanatory variables which perfectly predicts the observed outcome, leading to non-existence of some of the maximum likelihood coefficient estimates. A popular solution to obtain finite estimates even with separable data is Firth’s logistic regression (FL), which was originally proposed to reduce the bias in coefficient estimates. The question of convergence becomes more involved when analyzing clustered data as frequently encountered in clinical research, e.g. data collected in several study centers or when individuals contribute multiple observations, using marginal logistic regression models fitted by generalized estimating equations (GEE). From our experience we suspect that separable data are a sufficient, but not a necessary condition for non-convergence of GEE. Thus, we expect that generalizations of approaches that can handle separable uncorrelated data may reduce but not fully remove the non-convergence issues of GEE.MethodsWe investigate one recently proposed and two new extensions of FL to GEE. With ‘penalized GEE’ the GEE are treated as score equations, i.e. as derivatives of a log-likelihood set to zero, which are then modified as in FL. We introduce two approaches motivated by the equivalence of FL and maximum likelihood estimation with iteratively augmented data. Specifically, we consider fully iterated and single-step versions of this ‘augmented GEE’ approach. We compare the three approaches with respect to convergence behavior, practical applicability and performance using simulated data and a real data example.ResultsOur simulations indicate that all three extensions of FL to GEE substantially improve convergence compared to ordinary GEE, while showing a similar or even better performance in terms of accuracy of coefficient estimates and predictions. Penalized GEE often slightly outperforms the augmented GEE approaches, but this comes at the cost of a higher burden of implementation.ConclusionsWhen fitting marginal logistic regression models using GEE on sparse data we recommend to apply penalized GEE if one has access to a suitable software implementation and single-step augmented GEE otherwise.
Prevalence of chronic kidney diseases and its determinants among Iranian adults: results of the first phase of Shahedieh cohort study
Authors: Dehghani Ali , Alishavandi Sadegh , Nourimajalan Nader , Fallahzadeh Hossein , Rahmanian Vahid 
Published: June 2022

Abstract
Background
Chronic kidney disease (CKD) is one of the major global causes of mortality, described as the most neglected chronic disease. This study aimed to determine the prevalence and determinants of CKD in the setting of the Shahedieh cohort study in Yazd, Iran.

Methods
This cross-sectional study was conducted on adults in the baseline phase of the Shahedieh cohort study in Yazd, Iran. In this study, 9781 participants aged 30–73-year-old were investigated. The data used in this study included demographic and clinical variables and blood samples. Adjusted odds ratios were employed using multivariate logistic regression; meanwhile, population attributable risks for CKD were calculated and reported.

Results
CKD prevalence was 27.5% (95%CI: 26.57–28.34) in all participants, 24% in male, and 30.3% in female. The results of multivariate logistic regression analysis identified age (OR = 1.89, 95%CI:1.082–1.96), women (OR = 1.62, 95%CI: 1.45–1.79), BMI ≥ 30 (OR = 1.40,95%CI: 1.20–1.62), diabetes (OR = 1.38, 95%CI: 1.22–1.57), hypertriglyceridemia(OR = 1.20, 95%CI: 1.01–1.43), history of cardiovascular disease (OR = 1.20, 95%CI: 1.01–1.43), hypertension (OR = 1.18, 95%CI: 1.04–1.33), smoking (OR = 1.17, 95% CI: 1.02–1.33), LDL ≥ 130 (OR = 1.15, 95%CI: 1.01–1.31), history of kidney stone (OR = 1.14, 95%CI: 1.01–1.32) and hypercholesterolemia (OR = 1.14, 95%CI: 1.01–1.32) as risk factors for CKD. Among individual factors, obesity (11.25%), Hypertriglyceridemia (9.21%), LDL ≥ 130 (7.12%) had the greatest Population-Attributable Fraction, followed by Hypercholesterolemia (5.2%), diabetes (5.05%), smoking (3.73%) and high blood pressure (2.82%).

Conclusion
The results showed that the main determinants of CKD are potentially modifiable risk factors. Therefore, implementing early detection and screening programs in people at risk as well as preventive measures such as lifestyle modification programs and risk factors controlling can prevent the disease.
Surrogate biomarkers of outcome for wake-up ischemic stroke
Authors: Hervella Pablo , Alonso-Alonso María Luz , Pérez-Mato María , Rodríguez-Yáñez Manuel , Arias-Rivas Susana , López-Dequidt Iria , Pumar José M. , Sobrino Tomás , Campos Francisco , Castillo José , Iglesias-Rey Ramón 
Published: June 2022

Abstract
Background
Wake-up ischemic stroke (IS) has been usually excluded from acute stroke therapy options for being outside of the safe treatment window. We identified risk factors, and clinical or molecular biomarkers that could be therapeutic targets for wake-up stroke prevention, thus hopefully leading to a decrease in its mortality and disability in medium to long-term outcome.

Methods
4251 ischemic stroke (IS) patients from a prospectively registered database were recruited; 3838 (90.3%) had known onset-symptom time, and 413 (9.7%) were wake-up strokes. The main endpoint was to analyze the association between different serum biomarkers with wake-up IS episodes and their progression. Leukocytes count, serum levels of C-reactive protein, fibrinogen, interleukin 6 (IL-6), and vitamin D were analyzed as inflammation biomarkers; N-terminal pro-B-type Natriuretic-Peptide and microalbuminuria, used as atrial/endothelial dysfunction biomarkers; finally, glutamate levels as excitotoxicity biomarker. In addition, demographic, clinical and neuroimaging variables associated with the time-evolution of wake-up IS patients and functional outcome at 3 months were evaluated. Good and poor functional outcome were defined as mRS ≤2 and mRS > 2 at 3 months, respectively.

Results
Wake-up IS showed a poorer outcome at 3-months than in patients with known on-set-symptom time (59.1% vs. 48.1%; p < 0.0001). Patients with wake-up IS had higher levels of inflammation biomarkers; IL-6 levels at admission (51.5 ± 15.1 vs. 27.8 ± 18.6 pg/ml; p < 0.0001), and low vitamin D levels at 24 h (5.6 ± 5.8 vs. 19.2 ± 9.4 ng/ml; p < 0.0001) are worthy of attention. In a logistic regression model adjusted for vitamin D, OR was 15.1; CI 95%: 8.6–26.3, p < 0.0001. However, we found no difference in vitamin D levels between patients with or without clinical-DWI mismatch (no: 18.95 ± 9.66; yes: 17.84 ± 11.77 ng/mL, p = 0.394). No difference in DWI volume at admission was found (49.3 ± 96.9 ml in wake-up IS patients vs. 51.7 ± 98.2 ml in awake IS patients; p = 0.895).

Conclusions
Inflammatory biomarkers are the main factors that are strongly associated with wake-up IS episodes. Wake-up IS is associated with lower vitamin D levels. These data indicate that vitamin D deficiency could become a therapeutic target to reduce wake-up IS events.
Meta-analysis of diagnostic cell-free circulating microRNAs for breast cancer detection
Authors: Sehovic Emir , Urru Sara , Chiorino Giovanna , Doebler Philipp 
Published: June 2022

Abstract
Background
Breast cancer (BC) is the most frequently diagnosed cancer among women. Numerous studies explored cell-free circulating microRNAs as diagnostic biomarkers of BC. As inconsistent and rarely intersecting microRNA panels have been reported thus far, we aim to evaluate the overall diagnostic performance as well as the sources of heterogeneity between studies.

Methods
Based on the search of three online search engines performed up to March 21st 2022, 56 eligible publications that investigated diagnostic circulating microRNAs by utilizing Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) were obtained. Primary studies’ potential for bias was evaluated with the revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2). A bivariate generalized linear mixed-effects model was applied to obtain pooled sensitivity and specificity. A novel methodology was utilized in which the sample and study models’ characteristics were analysed to determine the potential preference of studies for sensitivity or specificity.

Results
Pooled sensitivity and specificity of 0.85 [0.81—0.88] and 0.83 [0.79—0.87] were obtained, respectively. Subgroup analysis showed a significantly better performance of multiple (sensitivity: 0.90 [0.86—0.93]; specificity: 0.86 [0.80—0.90]) vs single (sensitivity: 0.82 [0.77—0.86], specificity: 0.83 [0.78—0.87]) microRNA panels and a comparable pooled diagnostic performance between studies using serum (sensitivity: 0.87 [0.81—0.91]; specificity: 0.83 [0.78—0.87]) and plasma (sensitivity: 0.83 [0.77—0.87]; specificity: 0.85 [0.78—0.91]) as specimen type. In addition, based on bivariate and univariate analyses, miRNA(s) based on endogenous normalizers tend to have a higher diagnostic performance than miRNA(s) based on exogenous ones. Moreover, a slight tendency of studies to prefer specificity over sensitivity was observed.

Conclusions
In this study the diagnostic ability of circulating microRNAs to diagnose BC was reaffirmed. Nonetheless, some subgroup analyses showed between-study heterogeneity. Finally, lack of standardization and of result reproducibility remain the biggest issues regarding the diagnostic application of circulating cell-free microRNAs.
Post-recurrence survival analysis in patients with oligo-recurrence after curative esophagectomy
Authors: Tsai Ping-Chung , Chien Hung-Che , Hsu Po-Kuei , Hung Jung-Jyh , Huang Chien-Sheng , Hsu Wen-Hu , Hsu Han-Shui 
Published: June 2022

Abstract
Background
Recurrent esophageal cancer is associated with dismal prognosis. There is no consensus about the role of surgical treatments in patients with limited recurrences. This study aimed to evaluate the role of surgical resection in patients with resectable recurrences after curative esophagectomy and to identify their prognostic factors.

Methods
We retrospectively reviewed patients with recurrent esophageal cancer after curative esophagectomy between 2004 and 2017 and included those with oligo-recurrence that was amenable for surgical intent. The prognostic factors of overall survival (OS) and post-recurrence survival (PRS), as well as the survival impact of surgical resection, were analyzed.

Results
Among 654 patients after curative esophagectomies reviewed, 284 (43.4%) had disease recurrences. The recurrences were found resectable in 63 (9.6%) patients, and 30 (4.6%) patients received surgery. The significant prognostic factors of PRS with poor outcome included mediastinum lymph node (LN) recurrence and pathologic T3 stage. In patients with and without surgical resection for recurrence cancer, the 3-year OS rates were 65.6 and 47.6% (p = 0.108), while the 3-year PRS rates were 42.9 and 23.5% (p = 0.100). In the subgroup analysis, surgery for resectable recurrence, compared with non-surgery, could achieve better PRS for patients without any comorbidities (hazard ratio 0.36, 95% CI: 0.14 to 0.94, p = 0.038).

Conclusions
Mediastinum LN recurrence or pathologic T3 was associated with worse OS and PRS in patients with oligo-recurrences after curative esophagectomies. No definite survival benefit was noted in patients undergoing surgery for resectable recurrence, except in those without comorbidities.
Analysis of the completeness of self-harm and suicide records in Pernambuco, Brazil, 2014–2016
Authors: da Fonsêca Jéssica Ramalho , de Oliveira Conceição Maria , de Castro Cláudia Cristina Lima , da Costa Heitor Victor Veiga , Galvão Pauliana Valéria Machado , da Costa Ceballos Albanita Gomes , do Bonfim Cristine Vieira 
Published: June 2022

Abstract
Introduction
Suicides and suicide attempts are major public health problems, and coping strategies are hampered by insufficient or inadequate notifications. Data accuracy influences the formulation of public and mental health policies and suicide prevention strategies. The objective of this study was to analyze the completeness of self-harm and suicide records in the state of Pernambuco, Brazil, 2014–2016.

Methods
This is an evaluative study with a descriptive design. The data were collected from suicide attempt records from the Notifiable Diseases Information System and suicide records from the Mortality Information System. Probabilistic linkage was used to relate these databases, and the degree of completeness of the variables was calculated. Completeness was classified into the following categories: good (≥ 75.1%), regular (50.1%–75.0%), low (25.1%–50.0%), and very low (≤ 25.0%).

Results
In the analyzed period, 1,404 notifications of self-harm were studied, with an overall mean completeness of 86.2%. In addition, 1,050 suicide records were analyzed, with an overall mean completeness of 95.8%. Most variables referring to suicide attempts had good completeness, with the exception of the variables “occupation” and “education.” The completeness of all suicide-related variables was rated as good. After linkage, a significant improvement was observed in the degree of completeness of the variable “occupation”.

Conclusion
The results of this study showed that the completeness of self-harm and suicide variables improved from the first to the last year. The integration of data from different information systems provides an opportunity to improve suicide prevention programs and the quality of available information. Continuous efforts to increase the completeness and reliability of suicide surveillance systems are fundamental to describe the epidemiological profile and, consequently, plan preventive actions, in addition to contributing to the development and reformulation of strategies aimed at reducing morbidity and mortality related to suicidal behavior.