bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute kidney injury following on-pump or off-pump coronary artery bypass grafting in elderly patients: a retrospective propensity score matching analysis
Authors: Wang Rui , Wang Xian , Zhu Yifan , Chen Wen , Li Liangpeng , Chen Xin 
Published: July 2020

Abstract
Objectives
This single-centre, retrospective propensity score matching (PSM) study designed to study the impact of cardiopulmonary bypass (CPB) on postoperative acute kidney injury (AKI) and the relationship between AKI and long-term outcomes in elderly patients undergoing coronary artery bypass grafting (CABG).

Methods
After PSM, 466 pairs of patients (A group, on-pump; B group, off-pump) who were aged≥70 years undergoing first isolated CABG surgery from January 2012 to December 2016 entered the study. AKI was defined and classified according to the Acute Kidney Injury Network (AKIN) criteria. The incidence and severity of in-hospital AKI were compared. The impacts of AKI on the long-term outcomes including new onset of dialysis and mortality were analyzed.

Results
The two PSM groups had similar baseline and procedure except whether the CPB was used or not. In hospital and 30-day mortality was of no difference(χ2 = 0.051, p = 0.821). AKI of any severity occurred in 40.3% of all patients, with stage 1 accounting for most cases. No difference regarding the incidence and severity of AKI could be found: AKIN stage 1: 139 (29.8%) vs 131 (28.1%); AKIN stage 2: 40 (8.6%) vs 35 (7.5%); AKIN stage 3: 18 (3.9%) vs 13 (2.8%), (u = 0.543, p = 0.532). No difference was observed in the in-hospital new onset of dialysis (χ2 = 0.312, P = 0.576). The use of CPB was not found to influence long-term new onset of dialysis (χ2 = 0.14, p = 0.708) and mortality (χ2 = 0.099, p = 0.753). Comparing with non-AKI patients, AKI patients were associated with an increased rates of new onset of dialysis (χ2 = 8.153, p = 0.004) and mortality (χ2 = 6.277, p = 0.012) during the follow-up. Multivariable logistic regression manifested that the HR for long-term new onset of dialysis and mortality in AKI patients vs. non-AKI patients was 1.83 and 1.31 respectively (95%CI 1.12–2.86, p = 0.007; 95%CI 1.17–2.58, p = 0.015). The HR for long-term new onset of dialysis and mortality in on-pump group vs. off-pump group was 1.07 and 1.11 respectively (95%CI 1.03–1.23, p = 0.661; 95%CI 1.09–1.64, p = 0.702).

Conclusions
For elderly CABG patients, AKI was common, but deterioration of dialysis was a seldom incidence. Comparing with on-pump, off-pump did not decrease the rates or severity of AKI, long-term new onset of dialysis or mortality. AKI was associated with an increased long-term new onset of dialysis and decreased long-term survival.
Microbial involvement in Alzheimer disease development and progression
Authors: Bulgart Hannah R. , Neczypor Evan W. , Wold Loren E. , Mackos Amy R. 
Published: July 2020

AbstractAlzheimer disease (AD) is the most prominent form of dementia and the 5th leading cause of death in individuals over 65. AD is a complex disease stemming from genetic, environmental, and lifestyle factors. It is known that AD patients have increased levels of senile plaques, neurofibrillary tangles, and neuroinflammation; however, the mechanism(s) by which the plaques, tangles, and neuroinflammation manifest remain elusive. A recent hypothesis has emerged that resident bacterial populations contribute to the development and progression of AD by contributing to neuroinflammation, senile plaque formation, and potentially neurofibrillary tangle accumulation (Fig. 1). This review will highlight recent studies involved in elucidating microbial involvement in AD development and progression.
Pediatric obesity: prevention is better than care
Authors: Romanelli Roberta , Cecchi Nicola , Carbone Maria Grazia , Dinardo Michele , Gaudino Giuseppina , Miraglia del Giudice Emanuele , Umano Giuseppina Rosaria 
Published: July 2020

AbstractPediatric obesity is one of the most relevant health issues of the last century. Obesity-related short and long-term consequences are responsible of a large amount of economic cost. In addition, the different therapeutic strategies, such as lifestyle correction, drug, and bariatric surgery have displayed low effectiveness. Considering this evidence, prevention appears to be more promising than treatment in contrasting obesity epidemic. In this review, we summarize obesity pathogenesis with the aim of highlight the main obesity risk factors that can be addressed as target of preventive interventions. Moreover, we report the evidence about effectiveness of different interventions targeting family, school, and community. A multiple-component intervention, addressing different targets and settings, might be desirable, however more studies are needed to confirm long-term efficacy and to direct policy interventions.
Rationale and design of individualized quality improvement based on the Computer Analysing system to improve Stroke management quality Evaluation (CASE): a multicenter historically controlled study
Authors: Chen Yi , Zhong Wansi , Gong Xiaoxian , Hu Haitao , Yan Shenqiang , Zhang Xuting , Chen Zhicai , Zhou Ying , Lou Min 
Published: July 2020

Abstract
Background
Guideline-based medical care has been identified to improve outcomes in stroke. However, data acquisition and medical quality management during hospital stay still need to be improved in China. We have developed a computer-based medical data collecting system, together with automated calculation of key performance indicators (KPIs) and regular individualized education, and thus aim to explore whether it can improve the medical care quality of acute ischemic stroke (AIS) during hospital stay in stroke centers.

Methods
The individualized quality improvement based on the Computer Analysing system to improve Stroke management quality Evaluation (CASE) trial is a prospective, multicenter, historical control study among 30 stroke centers in China. In this trial, the data is directly extracted from the saved original medical record of each AIS patient during hospital stay, regardless of different Electronic Medical Record System (EMRS) in each center. Then, the automated calculation of KPIs and the regular education via teleconference per month allow the clinicians to examine the causes of non-compliance of guideline-based care and develop programs to decrease their frequency.

Discussion
We compare KPIs between pre-intervention stage and post-intervention stage (without or with education) among stroke centers. If proved effective, this approach might be generalized around China and even worldwide, where a unified EMRS is difficult to be applied and in-patient care needs to be improved.

Trial registration
ClinicalTrials.gov NCT03684629. Registered on 9 December 2018. Retrospectively registered.
Interpretation of vintage 2D seismic reflection data along the Austrian-Hungarian border: Subsurface expression of the Rechnitz metamorphic core complex
Authors: Tari Gabor C. , Gjerazi Ingrid , Grasemann Bernhard 
Published: July 2020

In the border zone between Austria and Hungary, the Miocene extension of the Pannonian Basin was characterized by extreme, large-magnitude upper crustal extension accommodated along low-angle detachment faults. Although some of these prominent normal faults have already been described using 2D seismic data sets and well data on the Hungarian side, we offer the first systematic interpretation using the Austrian and Hungarian vintage seismic data sets acquired in the 1970s and 1980s. The refinement of the previously proposed metamorphic core complex (MCC) style, east-northeast–west-southwest-trending very high-strain extension provides a modern understanding of back-arc extension in this part of the Pannonian Basin system as the result of the collapse of the Alpine orogen. Although previous interpretations could not achieve the subsurface correlation of major structural elements across the border, we did systematically map these for the first time. Numerous exploration wells, drilled on both sides of the border, were integrated with reflection seismic data to differentiate between the lower versus upper plates of the major low-angle detachment faults, including the largest one responsible for the formation of the Rechnitz MCC. Based on our new interpretation, the regionally mapped Rechnitz detachment fault has an unexpectedly large subsurface extent, on the order of 1000 km2. Moreover, the unusually large number of industry 2D seismic profiles (approximately 50) used to map this and other prominent faults, in the Austrian and Hungarian sides, makes the Rechnitz MCC possibly the best constrained one in the world in terms of subsurface definition by reflection seismic data.
Reduced Morbidity and Mortality in Survivors of Childhood Acute Lymphoblastic Leukemia: A Report From the Childhood Cancer Survivor Study
Authors: Dixon Stephanie B. , Chen Yan , Yasui Yutaka , Pui Ching-Hon , Hunger Stephen P. , Silverman Lewis B. , Ness Kirsten K. , Green Daniel M. , Howell Rebecca M. , Leisenring Wendy M. , Kadan-Lottick Nina S. , Krull Kevin R. , Oeffinger Kevin C. , Neglia Joseph P. , Mertens Ann C. , Hudson Melissa M. , Robison Leslie L. , Armstrong Gregory T. , Nathan Paul C. 
Published: July 2020

PURPOSE Risk-stratified therapy, which modifies treatment on the basis of clinical and biologic features, has improved 5-year overall survival of childhood acute lymphoblastic leukemia (ALL) to 90%, but its impact on long-term toxicity remains unknown. METHODS We assessed all-cause and health-related late mortality (including late effects of cancer therapy), subsequent malignant neoplasms (SMNs), chronic health conditions, and neurocognitive outcomes among 6,148 survivors of childhood ALL (median age, 27.9 years; range, 5.9-61.9 years) diagnosed between 1970 and 1999. Therapy combinations and treatment intensity defined 6 groups: 1970s-like (70s), standard- or high-risk 1980s-like (80sSR, 80sHR) and 1990s-like (90sSR, 90sHR), and relapse/transplantation (R/BMT). Cumulative incidence, standardized mortality ratios, and standardized incidence ratios were compared between treatment groups and with the US population. RESULTS Overall, 20-year all-cause late mortality was 6.6% (95% CI, 6.0 to 7.1). Compared with 70s, 90sSR and 90sHR experienced lower health-related late mortality (rate ratio [95% CI]: 90sSR, 0.2 [0.1 to 0.4]; 90sHR, 0.3 [0.1 to 0.7]), comparable to the US population (standardized mortality ratio [95% CI]: 90sSR, 1.3 [0.8 to 2.0]; 90sHR, 1.7 [0.7 to 3.5]). Compared with 70s, 90sSR had a lower rate of SMN (rate ratio [95% CI], 0.3 [0.1 to 0.6]) that was not different from that of the US population (standardized incidence ratio [95% CI], 1.0 [0.6 to 1.6]). The 90sSR group had fewer severe chronic health conditions than the 70s (20-year cumulative incidence [95% CI], 11.0% [9.7% to 12.3%] v 22.5% [19.4% to 25.5%]) and a lower prevalence of impaired memory (prevalence ratio [95% CI], 0.7 [0.6 to 0.9]) and task efficiency (0.5 [0.4 to 0.7]). CONCLUSION Risk-stratified therapy has reduced late morbidity and mortality among contemporary survivors of standard-risk ALL, represented by 90sSR. Health-related late mortality and SMN risks among 5-year survivors of contemporary, standard-risk childhood ALL are comparable to the general population.
Randomized Phase III Trial of Pegvorhyaluronidase Alfa With Nab-Paclitaxel Plus Gemcitabine for Patients With Hyaluronan-High Metastatic Pancreatic Adenocarcinoma
Authors: Van Cutsem Eric , Tempero Margaret A. , Sigal Darren , Oh Do-Youn , Fazio Nicola , Macarulla Teresa , Hitre Erika , Hammel Pascal , Hendifar Andrew E. , Bates Susan E. , Li Chung-Pin , Hingorani Sunil R. , de la Fouchardiere Christelle , Kasi Anup , Heinemann Volker , Maraveyas Anthony , Bahary Nathan , Layos Laura , Sahai Vaibhav , Zheng Lei , Lacy Jill , Park Joon Oh , Portales Fabienne , Oberstein Paul , Wu Wilson , Chondros Dimitrios , Bullock Andrea J. ,   on behalf of the HALO 109-301 Investigators
Published: July 2020

PURPOSE To evaluate the efficacy and safety of pegvorhyaluronidase alfa (PEGPH20) plus nab-paclitaxel/gemcitabine (AG) in patients with hyaluronan-high metastatic pancreatic ductal adenocarcinoma (PDA). PATIENTS AND METHODS HALO 109-301 was a phase III, randomized, double-blind, placebo-controlled study. Patients ≥ 18 years of age with untreated, metastatic, hyaluronan-high PDA were randomly assigned 2:1 to PEGPH20 plus AG or placebo plus AG. Treatment was administered intravenously in 4-week cycles (3 weeks on, 1 week off) until progression or intolerable adverse events: PEGPH20 3.0 µg/kg twice per week for cycle 1 and once per week thereafter; nab-paclitaxel 125 mg/m2 once per week; and gemcitabine 1,000 mg/m2 once per week. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety. Response was independently assessed per RECIST v1.1. RESULTS At data cutoff, 494 patients were randomly assigned, with 492 (327 for PEGPH20 and 165 for placebo) included in intention-to-treat analyses. Baseline characteristics were balanced for PEGPH20 plus AG versus placebo plus AG. There were 330 deaths, with a median OS of 11.2 months for PEGPH20 plus AG versus 11.5 months for placebo plus AG (hazard ratio [HR], 1.00; 95% CI, 0.80 to 1.27; P = .97); median PFS was 7.1 months versus 7.1 months (HR, 0.97 [95% CI, 0.75 to 1.26]); ORR was 47% versus 36% (ORR ratio, 1.29 [95% CI, 1.03 to 1.63]). Grade ≥ 3 adverse events with a ≥ 2% higher rate with PEGPH20 plus AG than with placebo plus AG included fatigue (16.0% v 9.6%), muscle spasms (6.5% v 0.6%), and hyponatremia (8.0% v 3.8%). CONCLUSION The addition of PEGPH20 to AG increased the ORR but did not improve OS or PFS. The safety profile of PEGPH20 plus AG was consistent with that found in previous studies. These results do not support additional development of PEGPH20 in metastatic PDA.
Frequent Molecular Subtype Switching and Gene Expression Alterations in Lung and Pleural Metastasis From Luminal A–Type Breast Cancer
Authors: Klebe Max , Fremd Carlo , Kriegsmann Mark , Kriegsmann Katharina , Albrecht Thomas , Thewes Verena , Kirchner Martina , Charoentong Pornpimol , Volk Nadine , Haag Johannes , Wirtz Ralph , Oskarsson Thordur , Schulz Alexandra , Heil Jörg , Schneeweiss Andreas , Winter Hauke , Sinn Peter 
Published: July 2020

PURPOSE Conversion of tumor subtype frequently occurs in the course of metastatic breast cancer but is a poorly understood phenomenon. This study aims to compare molecular subtypes with subsequent lung or pleural metastasis. PATIENTS AND METHODS In a cohort of 57 patients with breast cancer and lung or pleural metastasis (BCLPM), we investigated paired primary and metastatic tissues for differential gene expression of 269 breast cancer genes. The PAM50 classifier was applied to identify intrinsic subtypes, and differential gene expression and cluster analysis were used to further characterize subtypes and tumors with subtype conversion. RESULTS In primary breast cancer, the most frequent molecular subtype was luminal A (lumA; 49.1%); it was luminal B (lumB) in BCLPM (38.6%). Subtype conversion occurred predominantly in lumA breast cancers compared with other molecular subtypes (57.1% v 27.6%). In lumA cancers, 62 genes were identified with differential expression in metastatic versus primary disease, compared with only 10 differentially expressed genes in lumB, human epidermal growth factor receptor 2 (HER2)–enriched, and basal subtypes combined. Gene expression changes in lumA cancers affected not only the repression of the estrogen receptor pathway and cell cycle–related genes but also the WNT pathway, proteinases ( MME, MMP11), and motility-associated cytoskeletal proteins (CK5, CK14, CK17). Subtype-switched lumA cancers were further characterized by cell proliferation and cell cycle checkpoint gene upregulation and dysregulation of the p53 pathway. This involved 83 notable gene expression changes. CONCLUSION Our results indicate that gene expression changes and subsequent subtype conversion occur on a large scale in metastatic luminal A–type breast cancer compared with other molecular subtypes. This underlines the significance of molecular changes in metastatic disease, especially in tumors of initially low aggressive potential.
Distinct DNA Methylation Signatures in Neuroendocrine Tumors Specific for Primary Site and Inherited Predisposition
Authors: Tirosh Amit , Killian Jonathan Keith , Petersen David , Zhu Yuelin Jack , Walker Robert L , Blau Jenny E , Nilubol Naris , Patel Dhaval , Agarwal Sunita K , Weinstein Lee Scott , Meltzer Paul , Kebebew Electron 
Published: July 2020

Abstract

Purpose
To compare the deoxyribonucleic acid (DNA) methylation signature of neuroendocrine tumors (NETs) by primary tumor site and inherited predisposition syndromes von Hippel–Lindau disease (VHL) and multiple endocrine neoplasia type 1 (MEN1).

Methods
Genome-wide DNA methylation (835 424 CpGs) of 96 NET samples. Principal components analysis (PCA) and unsupervised hierarchical clustering analyses were used to determine DNA methylome signatures.

Results
Hypomethylated CpGs were significantly more common in VHL-related versus sporadic and MEN1-related NETs (P &lt; .001 for both comparisons). Small-intestinal NETs (SINETs) had the most differentially methylated CpGs, either hyper- or hypomethylated, followed by duodenal NETs (DNETs) and pancreatic NETs (PNETs, P &lt; .001 for all comparisons). There was complete separation of SINETs on PCA, and 3 NETs of unknown origin clustered with the SINET samples. Sporadic, VHL-related, and MEN1-related PNETs formed distinct groups on PCA, and VHL clustered separately, showing pronounced DNA hypomethylation, while sporadic and MEN1-related NETs clustered together. MEN1-related PNETs, DNETs, and gastric NETs each had a distinct DNA methylome signature, with complete separation by PCA and unsupervised clustering. Finally, we identified 12 hypermethylated CpGs in the 1A promoter of the APC (adenomatous polyposis coli) gene, with higher methylation levels in MEN1-related NETs versus VHL-related and sporadic NETs (P &lt; .001 for both comparisons).

Conclusions
DNA CpG methylation profiles are unique in different primary NET types even when occurring in MEN1-related NETs. This tumor DNA methylome signature may be utilized for noninvasive molecular characterization of NETs, through DNA methylation profiling of biopsy samples or even circulating tumor DNA in the near future.
FGF2 modulates simultaneously the mode, the rate of division and the growth fraction in cultures of radial glia
Authors: Ledesma-Terrón Mario , Peralta-Cañadas Nuria , Míguez David G. 
Published: July 2020

ABSTRACT
Radial glial progenitors in the mammalian developing neocortex have been shown to follow a deterministic differentiation program restricted to an asymmetric-only mode of division. This feature seems incompatible with their well-known ability to increase in number when cultured in vitro, driven by fibroblast growth factor 2 and other mitogenic signals. The changes in their differentiation dynamics that allow this transition from in vivo asymmetric-only division mode to an in vitro self-renewing culture have not been fully characterized. Here, we combine experiments of radial glia cultures with numerical models and a branching process theoretical formalism to show that fibroblast growth factor 2 has a triple effect by simultaneously increasing the growth fraction, promoting symmetric divisions and shortening the length of the cell cycle. These combined effects partner to establish and sustain a pool of rapidly proliferating radial glial progenitors in vitro. We also show that, in conditions of variable proliferation dynamics, the branching process tool outperforms other commonly used methods based on thymidine analogs, such as BrdU and EdU, in terms of accuracy and reliability.
MRI of placenta accreta: diagnostic accuracy and impact of interventional radiology on foetal–maternal delivery outcomes in high-risk women
Authors: Fiocchi Federica , Monelli Filippo , Besutti Giulia , Casari Federico , Petrella Elisabetta , Pecchi Annarita , Caporali Cristian , Bertucci Emma , Busani Stefano , Botticelli Laura , Facchinetti Fabio , Torricelli Pietro 
Published: July 2020

Objective:
To assess accuracy and reproducibility of MRI diagnosis of invasive placentation (IP) in high-risk patients and to evaluate reliability of MRI features. Secondary aim was to evaluate impact of interventional radiology (IR) on delivery outcomes in patients with IP at MRI.

Methods:
26 patients (mean age 36.24 y/o,SD 6.16) with clinical risk-factors and echographic suspicion of IP underwent 1.5 T-MRI. Two readers reviewed images. Gold-standard was histology in hysterectomised patients and obstetric evaluation at delivery for patients with preserved uterus. Accuracy and reproducibility of MRI findings were calculated.

Results:
Incidence of IP was 50% (13/26) and of PP was 11.54% (3/26). MRI showed 100% sensitivity (95% CI = 75.3–100%) and 92.3% specificity (95% CI = 64.0–100%) in the diagnosis of IP. Gold-standard was histology in 10 cases and obstetric evaluation in 16. MRI findings with higher sensitivity were placental heterogeneity, uterine bulging and black intraplacental bands. Uterine scarring, placental heterogeneity, myometrial interruption and tenting of the bladder showed better specificity. MRI inter-rater agreement with Cohen’s K was 1. 11 patients among 14 with MRI diagnosis of IP received IR assistance with positive impact on delivery outcomes in terms of blood loss, red cells count, intense care unit length of stay, days of hospitalisation and risk of being transfused.

Conclusion:
MRI is an accurate and reproducible technique in prenatal diagnosis of IP. MRI helps planning a safe and appropriate delivery eventually assisted by IR, which positively affects foetal and maternal outcomes.

Advances in knowledge:
The adoption of MRI evaluation in patients with high risk of invasive placentation allows a more accurate diagnosis in terms of both presence of the disease and its extension to or through or even beyond the myometrium. This led to a better dedicated delivery management with eventual adoption of interventional radiology with a global positive effect on foetal and maternal outcomes.
Comparison of gross tumor volumes of pulmonary metastasis defined by CT and MRI in 0.345 T MRI-guided radiotherapy
Authors: Hama Yukihiro , Tate Etsuko 
Published: July 2020

Objective: To assess the difference in gross tumor volumes (GTVs) defined by CT (GTV-CT) and by low magnetic field strength (0.345 T) MRI (GTV-MRI) in patients simulated for MRI-guided radiotherapy forlung metastasis. Methods: 28 patients (148 lesions) who underwent CT and MRI simulation with the tri-60Co MRI-guided radiotherapy system (MRIdian, ViewRay) were included in this study. GTV-CT and GTV-MRI were compared using the paired t-test. The equivalence of variance between GTV-CT and GTV-MRI of small lesions (GTV-CT <1 ml) and large ones (GTV-CT >= 1 ml) was evaluated using F-test. The correlation between GTV-CT and GTV-MRI was evaluated by the correlation coefficient. Results: GTV-MRI was 120% larger than GTV-CT (p < 0.001) for small lesions, whereas GTV-MRI was 40% larger than GTV-CT (p < 0.001) for large lesions. In small lesions, the variation in GTV-MRI was significantly larger than that of GTV-CT (p < 0.001). There was no significant difference in the variation of GTV-MRI and GTV-CT in large lesions (p = 0.121). The correlation coefficient for small lesions was 0.93, whereas that for large lesions was 0.99, with large lesions having better correlation. Conclusions: GTV-MRI was larger than GTV-CT and the correlation between GTV-MRI and GTV-CT was better in large lesions. If the tumor volume is 1 ml or larger, the lesion can be accurately monitored even with a low magnetic field strength MRI. Advances in knowledge: This study is the first clinical report to evaluate the tolerability of MRI images in 0.345 T MRI-guided radiotherapy for lung metastasis. GTV contoured by MRI was larger than GTV by CT, and this tendency was more pronounced in small tumors of less than 1 ml.