bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new immune signature for survival prediction and immune checkpoint molecules in lung adenocarcinoma
Authors: Guo Dina , Wang Mian , Shen Zhihong , Zhu Jiaona 
Published: March 2020

AbstractBackgroundLung adenocarcinoma (LUAD) is the most frequent subtype of lung cancer. The prognostic signature could be reliable to stratify LUAD patients according to risk, which helps the management of the systematic treatments. In this study, a systematic and reliable immune signature was performed to estimate the prognostic stratification in LUAD.MethodsThe profiles of immune-related genes for patients with LUAD were used as one TCGA training set: n = 494, other validation set 1: n = 226 and validation set 2: n = 398. Univariate Cox survival analysis was used to identify the candidate immune-related genes from each cohort. Then, the immune signature was developed and validated in the training and validation sets.ResultsIn this study, functional analysis showed that immune-related genes involved in immune regulation and MAPK signaling pathway. A prognostic signature based on 10 immune-related genes was established in the training set and patients were divided into high-risk and low-risk groups. Our 10 immune-related gene signature was significantly related to worse survival, especially during early-stage tumors. Further stratification analyses revealed that this 10 immune-related gene signature was still an effective tool for predicting prognosis in smoking or nonsmoking patients, patients with KRAS mutation or KRAS wild-type, and patients with EGFR mutation or EGFR wild-type. Our signature was negatively correlated with B cell, CD4+ T cell, CD8+ T cell, neutrophil, dendritic cell (DC), and macrophage immune infiltration, and immune checkpoint molecules PD-1 and CTLA-4 (P < 0.05).ConclusionsThese findings suggested that our signature was a promising biomarker for prognosis prediction and can facilitate the management of immunotherapy in LUAD.
Health-related quality of life in hereditary transthyretin amyloidosis polyneuropathy: a prospective, observational study
Authors: Inês Mónica , Coelho Teresa , Conceição Isabel , Ferreira Lara , de Carvalho Mamede , Costa João 
Published: March 2020

Abstract
Background
Hereditary Transthyretin Amyloidosis Polyneuropathy is a rare life-threatening neurologic disease that imposes considerable mortality and it is associated with progressive related disabilities. In this study, we aimed to assess the effect of the disease across health-related quality of life dimensions, in both carriers of the mutation and patients, to compare health-related quality of life with general population, as well as to explore health-related quality of life prognostic factors among patients, including disease progression and treatment.

Methods
This study was a multi-institutional, longitudinal, prospective, observational study of hereditary Transthyretin Amyloidosis Polyneuropathy Portuguese adult subjects (621 asymptomatic carriers and 733 symptomatic patients) enrolled in the Transthyretin Amyloidosis Outcomes Survey. Health-related quality of life was captured with the preference-based instrument EQ-5D-3 L. For general population the dataset included all subjects enrolled in a representative national study (n = 1500). Different econometric models were specified; multivariate probit, generalized linear model and generalized estimating equations model; including demographic and clinical covariates.

Results
Hereditary Transthyretin Amyloidosis Polyneuropathy patients have their health status severely impaired in all quality of life dimensions and more anxiety/depression problems were found among asymptomatic carriers. No differences on utility were found between carriers and general population (p = 0.209). Among patients, the utility value is estimated to be 0.51 (0.021), a decrement of 0.27 as compared with general population utility. Higher disease duration, advanced disease stage and not receiving treatment are associated with impaired health-related quality of life. No differences were found between genders (p = 0.910) or between late (≥50 years) and early-onset patients (p = 0.254). The utility estimate ranged from 0.63 (0.009) in stage I to 0.01 (0.005) in stage IV.

Conclusions
Hereditary Transthyretin Amyloidosis Polyneuropathy symptoms and progressive associated disabilities substantially decrease patient’s health-related quality of life. Clinical strategies focused on health-related quality of life preservation such as close follow-up of asymptomatic carriers, prompt diagnosis and adequate, early treatment would benefit patient’s long-term outcomes, slowing the progressive decline in health-related quality of life.
Understanding acute metabolic decompensation in propionic and methylmalonic acidemias: a deep metabolic phenotyping approach
Authors: Haijes H. A. , Jans J. J. M. , van der Ham M. , van Hasselt P. M. , Verhoeven-Duif N. M. 
Published: March 2020

AbstractBackgroundPathophysiology of life-threatening acute metabolic decompensations (AMD) in propionic acidemia (PA) and isolated methylmalonic acidemia (MMA) is insufficiently understood. Here, we study the metabolomes of PA and MMA patients over time, to improve insight in which biochemical processes are at play during AMD.MethodsLongitudinal data from clinical chemistry analyses and metabolic assays over the life-course of 11 PA and 13 MMA patients were studied retrospectively. Direct-infusion high-resolution mass spectrometry was performed on 234 and 154 remnant dried blood spot and plasma samples of PA and MMA patients, respectively. In addition, a systematic literature search was performed on reported biomarkers. All results were integrated in an assessment of biochemical processes at play during AMD.ResultsWe confirmed many of the metabolite alterations reported in literature, including increases of plasma valine and isoleucine during AMD in PA patients. We revealed that plasma leucine and phenylalanine, and urinary pyruvic acid were increased during AMD in PA patients. 3-hydroxyisovaleric acid correlated positively with plasma ammonia. We found that known diagnostic biomarkers were not significantly further increased, while intermediates of the branched-chain amino acid (BCAA) degradation pathway were significantly increased during AMD.ConclusionsWe revealed that during AMD in PA and MMA, BCAA and BCAA intermediates accumulate, while known diagnostic biomarkers remain essentially unaltered. This implies that these acidic BCAA intermediates are responsible for metabolic acidosis. Based on this, we suggest to measure plasma 3-hydroxyisovaleric acid and urinary ketones or 3-hydroxybutyric acid for the biochemical follow-up of a patient’s metabolic stability.
Sex differences in blood pro-oxidant status and platelet activation in children admitted with respiratory syncytial virus bronchiolitis: a pilot study
Authors: De Jacobis Isabella Tarissi , Vona Rosa , Straface Elisabetta , Gambardella Lucrezia , Ceglie Giulia , de Gennaro Francesca , Pontini Ilenia , Vittucci Anna Chiara , Carè Alessandra , Cittadini Camilla , Villani Alberto , Pietraforte Donatella 
Published: March 2020

Abstract
Background
Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in the pediatric population worldwide and an important cause of death in developing countries. It has been demonstrated that the balance between oxidant and antioxidant systems is disrupted in children with bronchiolitis and that oxidative stress contributes to the pathogenesis of this disease. Platelets play an important role in antimicrobial host defenses and contribute to pulmonary vascular repair being either targets or source of reactive oxidizing species. The main purpose of this study was to assessing sex differences in clinical characteristics and platelets activation during RSV bronchiolitis in infancy.

Methods
In this retrospective study a total of 203 patients (112 boys and 91 girls) with bronchiolitis, aged 12 months or less, admitted to the Bambino Gesù Pediatric Hospital of Rome (Italy) in the period from January to December 2017, were enrolled. Moreover, in a select group of patients (15 boys and 12 girls) with diagnosis of moderate bronchiolitis from RSV, a pilot study on oxidative stress and platelet characteristics was carried out by electron paramagnetic resonance and flow cytometry respectively. Age-matched healthy control subjects (10 boys and 10 girls) were chosen as controls. Data were analyzed using Student’ T test, Chi Squared test and one-way ANOVA test.

Results
This study highlights the influence of sex in the clinical course of bronchiolitis. In particular we found: i) a higher incidence of bronchiolitis in boys than in girls (55% vs 45%); ii) higher C reactive protein values in girls than boys (1.11 mg/dL vs 0.92 mg/dL respectively; p < 0.05); iii) a different degree of thrombocytosis during hospitalization (mild in the girls and severe in the boys). Moreover, in selected patients we found that compared to girls with bronchiolitis, boys showed: i) higher percentage of activated platelets (8% vs 2% respectively; p < 0.05) and iii) higher number of platelets forming homotypic aggregates (2.36% vs 0.84% respectively, p < 0.05).

Conclusion
The present study affirm that the bronchiolitis is an infection in which sex seems to act as a modulating factor only in the clinical course, influencing also the choice of the therapy should be made.
Comparison of infectivity of Plasmodium vivax to wild-caught and laboratory-adapted (colonized) Anopheles arabiensis mosquitoes in Ethiopia
Authors: Chali Wakweya , Ashine Temesgen , Hailemeskel Elifaged , Gashaw Abrham , Tafesse Temesgen , Lanke Kjerstin , Esayas Endashaw , Kedir Soriya , Shumie Girma , Behaksra Sinknesh Wolde , Bradley John , Yewhalaw Delenasaw , Mamo Hassen , Petros Beyene , Drakeley Chris , Gadisa Endalamaw , Bousema Teun , Tadesse Fitsum G. 
Published: March 2020

Abstract
Background
Mosquito-feeding assays that assess transmission of Plasmodium from man-to-mosquito typically use laboratory mosquito colonies. The microbiome and genetic background of local mosquitoes may be different and influence Plasmodium transmission efficiency. In order to interpret transmission studies to the local epidemiology, it is therefore crucial to understand the relationship between infectivity in laboratory-adapted and local mosquitoes.

Methods
We assessed infectivity of Plasmodium vivax-infected patients from Adama, Ethiopia, using laboratory-adapted (colony) and wild-caught (wild) mosquitoes raised from larval collections in paired feeding experiments. Feeding assays used 4–6 day-old female Anopheles arabiensis mosquitoes after starvation for 12 h (colony) and 18 h (wild). Oocyst development was assessed microscopically 7 days post-feeding. Wild mosquitoes were identified morphologically and confirmed by genotyping. Asexual parasites and gametocytes were quantified in donor blood by microscopy.

Results
In 36 paired experiments (25 P. vivax infections and 11 co-infections with P. falciparum), feeding efficiency was higher in colony (median: 62.5%; interquartile range, IQR: 47.0–79.0%) compared to wild mosquitoes (median: 27.8%; IQR: 17.0–38.0%; Z = 5.02; P < 0.001). Plasmodium vivax from infectious individuals (51.6%, 16/31) infected a median of 55.0% (IQR: 6.7–85.7%; range: 5.5–96.7%; n = 14) of the colony and 52.7% (IQR: 20.0–80.0%; range: 3.2–95.0%; n = 14) of the wild mosquitoes. A strong association (ρ(16) = 0.819; P < 0.001) was observed between the proportion of infected wild and colony mosquitoes. A positive association was detected between microscopically detected gametocytes and the proportion of infected colony (ρ(31) = 0.452; P = 0.011) and wild (ρ(31) = 0.386; P = 0.032) mosquitoes.

Conclusions
Infectivity assessments with colony and wild mosquitoes yielded similar infection results. This finding supports the use of colony mosquitoes for assessments of the infectious reservoir for malaria in this setting whilst acknowledging the importance of mosquito factors influencing sporogonic development of Plasmodium parasites.
Genetic predisposition to smoking is associated with risk of rheumatoid arthritis: a Mendelian randomization study
Authors: Qian Yu , Zhang Lingzhi , Wu David J. H. , Xie Zhijun , Wen Chengping , Mao Yingying 
Published: March 2020

Abstract
Background
Although observational epidemiological studies have found that smoking is positively associated with risk of rheumatoid arthritis (RA), assessing the causality of this relationship has remained elusive because conventional observational studies are susceptible to bias such as confounding and reverse causation. Here, we applied the Mendelian randomization (MR) approach to examine the potential causal relationship between smoking and risk of RA.

Methods
Summary statistics data for RA were obtained from a meta-analysis of genome-wide association studies (GWAS), including 14,361 RA cases and 43,923 controls of European ancestry. The instrumental variables (IV) and the genetic association estimates for smoking initiation and lifetime smoking were obtained from a GWAS meta-analysis including 1,232,091 individuals and a GWAS of 462,690 individuals of European ancestry, respectively. MR analyses were performed using the inverse-variance weighted (IVW) method and supplemented with the weighted-median method. Potential pleiotropy was assessed using the MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test and MR-Egger regression. Sensitivity analyses were further performed to test the robustness of the association.

Results
We found that compared with never smokers, genetic predisposition to smoking initiation was positively associated with risk of RA (odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.15–1.52, P = 9.17 × 10−5 using the IVW method). Similarly, genetically predicted lifetime smoking was associated with an increased risk of RA (OR = 1.55, 95% CI = 1.13–2.14, P = 0.007). Sensitivity analyses using alternative MR methods and different sets of IVs produced similar results, suggesting the robustness of our findings.

Conclusions
These results provide support for a causal association between smoking and increased risk of RA. Further studies are warranted to explain the underlying mechanisms of smoking in the development of RA.
Thoracic ultrasound evaluation and B-type natriuretic peptide value in elective cesarean section under spinal anesthesia
Authors: Vetrugno Luigi , Dogareschi Teresa , Sassanelli Rossella , Orso Daniele , Seremet Ludmilla , Mattuzzi Lisa , Scapol Sara , Spasiano Alessandra , Cagnacci Angelo , Bove Tiziana 
Published: March 2020

Abstract
Background
Pregnancy-induced changes in cardiovascular status make women more susceptible to pulmonary edema. During cesarean section, to counterbalance the effect of hypotension caused by spinal anesthesia, anesthesiologists must choose between two fundamental approaches to maintain the hemodynamic state—intravenous fluids or vasopressors—and this choice will depend upon their particular opinions and experience. We aim to assess for any correlations between thoracic ultrasound A- and B-line artifacts, brain natriuretic peptide (BNP) levels, and the amount of intraoperative fluids administered.

Results
From December 2016 to August 2018, at the University-Hospital of Udine, we enrolled 80 consecutive pregnant women undergoing cesarean section. We observed a statistically significant difference in the volume of fluids administered in the first 24 h (p = 0.035) between the patients presenting B-lines in at least one basal area of their thoracic ultrasound and patients with no evident B-lines (AUC 66.4%; IC 0.49–0.83). Dividing the population on whether their BNP levels were higher or less than 20 pg/mL, no statistically significant difference was revealed with regard to fluids administered in the first 24 h (p = 0.537).

Conclusions
Thoracic ultrasound is a non-invasive and easy-to-use tool for detecting fluid intolerance in pregnant women undergoing cesarean section. BNP levels were slow to rise following the cesarean section and did not show any clear correlation with fluid volumes administered.
Determining spa-type of methicillin-resistant Staphylococcus aureus (MRSA) via high-resolution melting (HRM) analysis, Shiraz, Iran
Authors: Hashemizadeh Zahra , Bazargani Abdollah , Kalantar-Neyestanaki Davood , Mohebi Samane , Hadi Nahal 
Published: March 2020

Abstract
Objectives
Molecular typing methods are useful for rapid detection and control of a disease. Recently, the use of high-resolution melting (HRM) for spa typing of MRSA isolates were reported. This technique is rapid, inexpensive and simple for genotyping and mutation screening in DNA sequence. The aim of this study was to evaluate the ability of HRM-PCR to analysis spa genes amongst MRSA isolates.

Results
A total of 50 MRSA isolates were collected from two teaching hospitals in Shiraz, Iran. The isolates were confirmed as MRSA by susceptibility to cefoxitin and detection of mecA gene using PCR. We used HRM analysis and PCR-sequencing method for spa typing of MRSA isolates. In total, 15 different spa types were discriminate by HRM and sequencing method. The melting temperature of the 15 spa types, using HRM genotyping were between 82.16 and 85.66 °C. The rate of GC % content was 39.4–46.3. According to the results, spa typing of 50 clinical isolates via PCR-sequencing and HRM methods were 100% similar. Consequently, HRM method can easily identify and rapidly differentiate alleles of spa genes. This method is faster, less laborious and more suitable for high sample at lower cost and risk of contamination.
Exploratory analysis of myocardial function after extracorporeal cardiopulmonary resuscitation vs conventional cardiopulmonary resuscitation
Authors: Tonna Joseph E. , McKellar Stephen H. , Selzman Craig H. , Drakos Stavros , Koliopoulou Antigone G. , Taleb Iosif , Stoddard Gregory J. , Stehlik Josef , Welt Frederick G. P. , Fair James F. , Stoddard Kathleen , Youngquist Scott T. 
Published: March 2020

AbstractObjectiveVentricular unloading is associated with myocardial recovery. We sought to evaluate the association of extracorporeal cardiopulmonary resuscitation (ECPR) on myocardial function after cardiac arrest. We conducted a retrospective exploratory analysis, comparing ejection fraction (EF) after adult cardiac arrest, between ECPR and conventional CPR.ResultsAmong 1119 cases of cardiac arrest, 116 had an echocardiogram post-return of spontaneous circulation (ROSC) and were included. Thirty-eight patients had ≥ 2 echocardiograms. ECPR patients had differences in age, hypertension and chronic heart failure. ECPR patients had a lower EF post-ROSC (24% vs 45%;p < 0.01) and were more likely to undergo percutaneous coronary intervention (25% vs 3%; p < 0.01). In multivariate analysis, only ECPR use (β-coeff: 10.4 [95% CI 3.68–17.13];p < 0.01) independently predicted improved myocardial function. In this exploratory study, EF after cardiac arrest may be more likely to improve among ECPR patients than CCPR patients. Our methodology should be replicated to confirm or refute the validity of our findings.
Clinical application of multi-material artifact reduction (MMAR) technique in Revolution CT to reduce metallic dental artifacts
Authors: Wei Yijuan , Jia Fei , Hou Ping , Zha Kaiji , Pu Shi , Gao Jianbo 
Published: March 2020

Abstract
Background
This study aimed to explore the performance of Revolution CT virtual monoenergetic images (VMI) combined with the multi-material artifact reduction (MMAR) technique in reducing metal artifacts in oral and maxillofacial imaging.

Results
There were significant differences in image quality scores between VMI + MMAR images and VMI+MARS (multiple artifact reduction system) images at each monochromatic energy level (p = 0.000). Compared with the MARS technology, the MMAR technology further reduced metal artifacts and improved the image quality. At VMI90 keV and VMI110 keV, the SD, CNR, and AI in the Revolution CT group were significantly lower than in the Discovery CT, but no significant differences in these parameters were found between two groups at VMI50 keV, VMI70 keV, and VMI130 keV (p > 0.05). The attenuation was comparable between two groups at any energy level (p > 0.05).

Conclusions
Compared with the MARS reconstruction technique of Discovery CT, the MMAR technique of Revolution CT is better to reduce the artifacts of dental implants in oral and maxillofacial imaging, which improves the image quality and the diagnostic value of surrounding soft tissues.
Identification of the initial molecular changes in response to circulating angiogenic cells-mediated therapy in critical limb ischemia
Authors: Beltran-Camacho Lucia , Jimenez-Palomares Margarita , Rojas-Torres Marta , Sanchez-Gomar Ismael , Rosal-Vela Antonio , Eslava-Alcon Sara , Perez-Segura Mª Carmen , Serrano Ana , Antequera-González Borja , Alonso-Piñero Jose Angel , González-Rovira Almudena , Extremera-García Mª Jesús , Rodriguez-Piñero Manuel , Moreno-Luna Rafael , Larsen Martin Røssel , Durán-Ruiz Mª Carmen 
Published: March 2020

Abstract
Background
Critical limb ischemia (CLI) constitutes the most aggressive form of peripheral arterial occlusive disease, characterized by the blockade of arteries supplying blood to the lower extremities, significantly diminishing oxygen and nutrient supply. CLI patients usually undergo amputation of fingers, feet, or extremities, with a high risk of mortality due to associated comorbidities.
Circulating angiogenic cells (CACs), also known as early endothelial progenitor cells, constitute promising candidates for cell therapy in CLI due to their assigned vascular regenerative properties. Preclinical and clinical assays with CACs have shown promising results. A better understanding of how these cells participate in vascular regeneration would significantly help to potentiate their role in revascularization.
Herein, we analyzed the initial molecular mechanisms triggered by human CACs after being administered to a murine model of CLI, in order to understand how these cells promote angiogenesis within the ischemic tissues.

Methods
Balb-c nude mice (n:24) were distributed in four different groups: healthy controls (C, n:4), shams (SH, n:4), and ischemic mice (after femoral ligation) that received either 50 μl physiological serum (SC, n:8) or 5 × 105 human CACs (SE, n:8). Ischemic mice were sacrificed on days 2 and 4 (n:4/group/day), and immunohistochemistry assays and qPCR amplification of Alu-human-specific sequences were carried out for cell detection and vascular density measurements. Additionally, a label-free MS-based quantitative approach was performed to identify protein changes related.

Results
Administration of CACs induced in the ischemic tissues an increase in the number of blood vessels as well as the diameter size compared to ischemic, non-treated mice, although the number of CACs decreased within time. The initial protein changes taking place in response to ischemia and more importantly, right after administration of CACs to CLI mice, are shown.

Conclusions
Our results indicate that CACs migrate to the injured area; moreover, they trigger protein changes correlated with cell migration, cell death, angiogenesis, and arteriogenesis in the host. These changes indicate that CACs promote from the beginning an increase in the number of vessels as well as the development of an appropriate vascular network.

Graphical abstract