bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methylome Variation Predicts Exemestane Resistance in Advanced ER+ Breast Cancer
Authors: Liu Xiao-ran , Zhang Ru-yan , Gong Hao , Rugo Hope S. , Chen Ling-bo , Fu Yuan , Che Jian-wei , Tie Jian , Shao Bin , Wan Feng-ling , Kong Wei-yao , Song Guo-hong , Jiang Han-fang , Xu Guo-bing , Li Hui-ping 
Published: March 2020

Background: More than 30% of estrogen receptor-positive breast cancers are resistant to primary hormone therapy, and about 40% that initially respond to hormone therapy eventually acquire resistance. Although the mechanisms of hormone therapy resistance remain unclear, aberrant DNA methylation has been implicated in oncogenesis and drug resistance. Purpose: We investigated the relationship between methylome variations in circulating tumor DNA and exemestane resistance, to track hormone therapy efficacy. Methods: We prospectively recruited 16 patients who were receiving first-line therapy in our center. All patients received exemestane-based hormone therapy after enrollment. We collected blood samples at baseline, first follow-up (after 2 therapeutic cycles) and at detection of disease progression. Disease that progressed within 6 months under exemestane treatment was considered exemestane resistance but was considered relatively exemestane-sensitive otherwise. We obtained circulating tumor DNA-derived methylomes using the whole-genome bisulfide sequencing method. Methylation calling was done by BISMARK software; differentially methylated regions for exemestane resistance were calculated afterward. Results: Median follow-up for the 16 patients was 19.0 months. We found 7 exemestane resistance-related differentially methylated regions, located in different chromosomes, with both significantly different methylation density and methylation ratio. Baseline methylation density and methylation ratio of chromosome 6 [32400000-32599999] were both high in exemestane resistance. High baseline methylation ratios of chromosome 3 [67800000-67999999] ( P = .013), chromosome 3 [140200000-140399999] ( P = .037), and chromosome 12 [101200000-101399999] ( P = .026) could also predict exemestane resistance. During exemestane treatment, synchronized changes in methylation density and methylation ratio in chromosome 6 [32400000-32599999] could accurately stratify patients in terms of progression-free survival ( P = .000033). Cutoff values of methylation density and methylation ratio for chromosome 6 [149600000-149799999] were 0.066 and 0.076, respectively. Conclusion: Methylation change in chromosome 6 [149600000-149799999] is an ideal predictor of exemestane resistance with great clinical potential.
Systematic Coronary Risk Evaluation estimated risk and prevalent subclinical atherosclerosis in coronary and carotid arteries: A population-based cohort analysis from the Swedish Cardiopulmonary Bioimage Study
Authors: Östgren Carl J , Söderberg Stefan , Festin Karin , Angerås Oskar , Bergström Göran , Blomberg Anders , Brandberg John , Cederlund Kerstin , Eliasson Mats , Engström Gunnar , Erlinge David , Fagman Erika , Hagström Emil , Lind Lars , Mannila Maria , Nilsson Ulf , Oldgren Jonas , Ostenfeld Ellen , Persson Anders , Persson Jonas , Persson Margaretha , Rosengren Annika , Sundström Johan , Swahn Eva , Engvall Jan E , Jernberg Tomas 
Published: March 2020

Abstract

Background
It is not clear if the European Systematic Coronary Risk Evaluation algorithm is useful for identifying prevalent subclinical atherosclerosis in a population of apparently healthy individuals. Our aim was to explore the association between the risk estimates from Systematic Coronary Risk Evaluation and prevalent subclinical atherosclerosis.

Design
The design of this study was as a cross-sectional analysis from a population-based study cohort.

Methods
From the general population, the Swedish Cardiopulmonary Bioimage Study randomly invited individuals aged 50–64 years and enrolled 13,411 participants mean age 57 (standard deviation 4.3) years; 46% males between November 2013–December 2016. Associations between Systematic Coronary Risk Evaluation risk estimates and coronary artery calcification and plaques in the carotid arteries by using imaging data from a computed tomography of the heart and ultrasonography of the carotid arteries were examined.

Results
Coronary calcification was present in 39.5% and carotid plaque in 56.0%. In men, coronary artery calcium score &gt;0 ranged from 40.7–65.9% and presence of carotid plaques from 54.5% to 72.8% in the age group 50–54 and 60–65 years, respectively. In women, the corresponding difference was from 17.1–38.9% and from 41.0–58.4%. A doubling of Systematic Coronary Risk Evaluation was associated with an increased probability to have coronary artery calcium score &gt;0 (odds ratio: 2.18 (95% confidence interval 2.07–2.30)) and to have &gt;1 carotid plaques (1.67 (1.61–1.74)).

Conclusion
Systematic Coronary Risk Evaluation estimated risk is associated with prevalent subclinical atherosclerosis in two major vascular beds in a general population sample without established cardiovascular disease or diabetes mellitus. Thus, the Systematic Coronary Risk Evaluation risk chart may be of use for estimating the risk of subclinical atherosclerosis.
Assessment of minimal residual disease using multiparametric flow cytometry in patients with AL amyloidosis
Authors: Staron Andrew , Burks Eric J. , Lee John C. , Sarosiek Shayna , Sloan J. Mark , Sanchorawala Vaishali 
Published: March 2020

Abstract
Despite achieving a hematologic complete response after treatment, many patients with AL amyloidosis do not attain recovery of organ function and/or experience hematologic relapse. A persistent plasma cell clone producing amyloidogenic light chains at levels below the detection threshold of traditional serologic methods is hypothesized to impede organ response in some patients. Assessment of minimal residual disease (MRD) may therefore have clinical importance as a more stringent treatment response tool for patients in a hematologic complete response. We used 2-tube, 10-color combination multiparametric flow cytometry to assess for MRD at a minimum sensitivity of 1 in 105 nucleated cells. Of 65 patients in hematologic complete response, 36 (55%) were found to have a residual clonal plasma cell population in the bone marrow. Comparing the MRD-negative and MRD-positive groups, renal response was observed in 88% vs 64% (P = .06), cardiac response in 75% vs 59% (P = .45), and any organ response in 90% vs 75% (P = .20) of patients. Depth of organ response as measured by the percent decrease in 24-hour proteinuria and brain natriuretic peptide was 96% vs 91% (P = .16) and 55% vs 46% (P = .66), respectively. These data suggest a possible correlation between MRD negativity and higher probability of organ response after treatment in AL amyloidosis. Future prospective studies with a larger cohort are needed to determine the clinical relevance of these improvements. This trial was registered at www.clinicaltrials.gov as #NCT00898235.
Tracing cross species transmission of Mycobacterium bovis at the wildlife/livestock interface in South Africa
Authors: Sichewo Petronillah R. , Hlokwe Tiny M. , Etter Eric M. C. , Michel Anita L. 
Published: March 2020

Abstract
Background
Bovine tuberculosis (bTB) affects cattle and wildlife in South Africa with the African buffalo (Syncerus caffer) as the principal maintenance host. The presence of a wildlife maintenance host at the wildlife/livestock interface acting as spill-over host makes it much more challenging to control and eradicate bTB in cattle. Spoligotyping and mycobacterial interspersed repetitive unit-variable number of tandem repeat (MIRU-VNTR) genotyping methods were performed to investigate the genetic diversity of Mycobacterium bovis (M. bovis) isolates from cattle and wildlife, their distribution and transmission at the wildlife/livestock interface in northern Kwa-Zulu Natal (KZN), South Africa.

Results
SB0130 was identified as the dominant spoligotype pattern at this wildlife/livestock interface, while VNTR typing revealed a total of 29 VNTR profiles (strains) in the KZN province signifying high genetic variability. The detection of 5 VNTR profiles shared between cattle and buffalo suggests M. bovis transmission between species. MIRU-VNTR confirmed co-infection in one cow with three strains of M. bovis that differed at a single locus, with 2 being shared with buffalo, implying pathogen introduction from most probably unrelated wildlife sources.

Conclusion
Our findings highlight inter and intra species transmission of bTB at the wildlife/livestock interface and the need for the implementation of adequate bTB control measures to mitigate the spread of the pathogen responsible for economic losses and a public health threat.
Fast, simple and highly specific molecular detection of Vibrio alginolyticus pathogenic strains using a visualized isothermal amplification method
Authors: Dong Yu , Zhao Panpan , Chen Li , Wu Huahua , Si Xinxin , Shen Xin , Shen Hui , Qiao Yi , Zhu Shanyuan , Chen Qiong , Jia Weiwei , Dong Jingquan , Li Juan , Gao Song 
Published: March 2020

Abstract
Background
Vibrio alginolyticus is an important pathogen that has to be closely monitored and controlled in the mariculture industry because of its strong pathogenicity, quick onset after infection and high mortality rate in aquatic animals. Fast, simple and specific methods are needed for on-site detection to effectively control outbreaks and prevent economic losses. The detection specificity towards the pathogenic strains has to be emphasized to facilitate pointed treatment and prevention. Polymerase chain reaction (PCR)-based molecular approaches have been developed, but their application is limited due to the requirement of complicated thermal cycling machines and trained personnel.

Results
A fast, simple and highly specific detection method for V. alginolyticus pathogenic strains was established based on isothermal recombinase polymerase amplification (RPA) and lateral flow dipsticks (LFD). The method targeted the virulence gene toxR, which is reported to have good coverage for V. alginolyticus pathogenic strains. To ensure the specificity of the method, the primer-probe set of the RPA system was carefully designed to recognize regions in the toxR gene that diverge in different Vibrio species but are conserved in V. alginolyticus pathogenic strains. The primer-probe set was determined after a systematic screening of amplification performance, primer-dimer formation and false positive signals. The RPA-LFD method was confirmed to have high specificity for V. alginolyticus pathogenic strains without any cross reaction with other Vibrio species or other pathogenic bacteria and was able to detect as little as 1 colony forming unit (CFU) per reaction without DNA purification, or 170 fg of genomic DNA, or 6.25 × 103 CFU/25 g in spiked shrimp without any enrichment. The method finishes detection within 30 min at temperatures between 35 °C and 45 °C, and the visual signal on the dipstick can be directly read by the naked eye. In an application simulation, randomly spiked shrimp homogenate samples were 100% accurately detected.

Conclusions
The RPA-LFD method developed in this study is fast, simple, highly specific and does not require complicated equipment. This method is applicable for on-site detection of V. alginolyticus pathogenic strains for the mariculture industry.
Compositional analysis of the associations between 24-h movement behaviours and cardio-metabolic risk factors in overweight and obese adults with pre-diabetes from the PREVIEW study: cross-sectional baseline analysis
Authors: Swindell Nils , Rees Paul , Fogelholm Mikael , Drummen Mathijs , MacDonald Ian , Martinez J. Alfredo , Navas-Carretero Santiago , Handjieva-Darlenska Teodora , Boyadjieva Nadka , Bogdanov Georgi , Poppitt Sally D. , Gant Nicholas , Silvestre Marta P. , Brand-Miller Jennie , Schlicht Wolfgang , Muirhead Roslyn , Brodie Shannon , Tikkanen Heikki , Jalo Elli , Westerterp-Plantenga Margriet , Adam Tanja , Vestentoft Pia Siig , Larsen Thomas M. , Raben Anne , Stratton Gareth 
Published: March 2020

Abstract
Background
Physical activity, sedentary time and sleep have been shown to be associated with cardio-metabolic health. However, these associations are typically studied in isolation or without accounting for the effect of all movement behaviours and the constrained nature of data that comprise a finite whole such as a 24 h day. The aim of this study was to examine the associations between the composition of daily movement behaviours (including sleep, sedentary time (ST), light intensity physical activity (LIPA) and moderate-to-vigorous activity (MVPA)) and cardio-metabolic health, in a cross-sectional analysis of adults with pre-diabetes. Further, we quantified the predicted differences following reallocation of time between behaviours.

Methods
Accelerometers were used to quantify daily movement behaviours in 1462 adults from eight countries with a body mass index (BMI) ≥25 kg·m− 2, impaired fasting glucose (IFG; 5.6–6.9 mmol·l− 1) and/or impaired glucose tolerance (IGT; 7.8–11.0 mmol•l− 1 2 h following oral glucose tolerance test, OGTT). Compositional isotemporal substitution was used to estimate the association of reallocating time between behaviours.

Results
Replacing MVPA with any other behaviour around the mean composition was associated with a poorer cardio-metabolic risk profile. Conversely, when MVPA was increased, the relationships with cardiometabolic risk markers was favourable but with smaller predicted changes than when MVPA was replaced. Further, substituting ST with LIPA predicted improvements in cardio-metabolic risk markers, most notably insulin and HOMA-IR.

Conclusions
This is the first study to use compositional analysis of the 24 h movement composition in adults with overweight/obesity and pre-diabetes. These findings build on previous literature that suggest replacing ST with LIPA may produce metabolic benefits that contribute to the prevention and management of type 2 diabetes. Furthermore, the asymmetry in the predicted change in risk markers following the reallocation of time to/from MVPA highlights the importance of maintaining existing levels of MVPA.

Trial registration
ClinicalTrials.gov (NCT01777893).
Qishen granules exerts cardioprotective effects on rats with heart failure via regulating fatty acid and glucose metabolism
Authors: Gao Kuo , Zhang Jian , Gao Pengrong , Wang Qiyan , Liu Ying , Liu Junjie , Zhang Yili , Li Yan , Chang Hong , Ren Ping , Liu Jinmin , Wang Yong , Wang Wei 
Published: March 2020

Abstract
Background
Qishen granules (QSG) has been applied to treat heart failure (HF) for decades. Our previous transcriptomics study has suggested that Qishen granules (QSG) could regulate the pathways of cardiac energy metabolism in HF, but the specific regulatory mechanism has not yet been clarified. This study was to investigate the potential mechanism of QSG in regulating myocardial fatty acid (FA) and glucose metabolism in a rat model of HF.

Methods
The model of HF was induced by left anterior descending coronary artery ligation. Cardiac structure and function were assessed by cine magnetic resonance imaging (MRI) and echocardiography. Level of glucose metabolism was non-invasively evaluated by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT). Blood lipid levels were determined by enzymatic analysis. The mitochondrial ultrastructure was observed with a transmission electron microscope. The critical proteins related to FA metabolism, glucose metabolism and mitochondrial function were measured by western blotting. The ANOVA followed by a Fisher’s LSD test was used for within-group comparisons.

Results
QSG ameliorated cardiac functions and attenuated myocardial remodeling in HF model. The levels of serum TC, TG and LDL-C were significantly reduced by QSG. The proteins mediating FA uptake, transportation into mitochondria and β-oxidation (FAT/CD36, CPT1A, ACADL, ACADM, ACAA2 and SCP2) as well as the upstreaming transcriptional regulators of FA metabolism (PPARα, RXRα, RXRβ and RXRγ) were up-regulated by QSG. As to glucose metabolism, QSG inhibited glycolytic activity by decreasing LDHA, while stimulated glucose oxidation by decreasing PDK4. Furthermore, QSG could facilitate tricarboxylic acid cycle, promote the transportation of ATP from mitochondria to cytoplasm and restore the mitochondrial function by increasing SUCLA2, CKMT2 and PGC-1α and decreasing UCP2 simultaneously.

Conclusion
QSG improved myocardial energy metabolism through increasing FA metabolism,inhibiting uncoupling of glycolysis from glucose oxidation.
Experienced complaints, activity limitations and loss of motor capacities in patients with pure hereditary spastic paraplegia: a web-based survey in the Netherlands
Authors: van Lith Bas J. H. , Kerstens Hans C. J. W. , van den Bemd Laura A. C. , der Sanden Maria W. G. Nijhuis-van , Weerdesteyn Vivian , Smeets Rob J. E. M. , Fheodoroff Klemens , van de Warrenburg Bart P. C. , Geurts Alexander C. H. 
Published: March 2020

Abstract
Background
Hereditary spastic paraplegia (HSP) is a group of inherited disorders characterized by progressive spastic paresis of the lower limbs. Treatment is often focused on reducing spasticity and its physical consequences. To better address individual patients’ needs, we investigated a broad range of experienced complaints, activity limitations, and loss of motor capacities in pure HSP. In addition, we aimed to identify patient characteristics that are associated with increased fall risk and/or reduced walking capacity.

Methods
We developed and distributed an HSP-specific online questionnaire in the Netherlands. A total of 109 out of 166 questionnaires returned by participants with pure HSP were analyzed.

Results
Participants experienced the greatest burden from muscle stiffness and limited standing and walking activities, while 72% reported leg and/or back pain. Thirty-five and 46% reported to use walking aids (e.g. crutches) indoors and outdoors, respectively; 57% reported a fall incidence of at least twice a year (‘fallers’); in 51% a fall had led to an injury at least once; and 73% reported fear of falling. Duration of spasticity and incapacity to rise from the floor were positively associated with being a ‘faller’, whereas non-neurological comorbidity and wheelchair use were negatively associated. Higher age, experienced gait problems, not being able to stand for 10 min, and incapacity to open a heavy door showed a negative association with being a ‘walker without aids’ (> 500 m).

Conclusions
Our results emphasize the large impact of spastic paraparesis on the lives of people with pure HSP and contribute to a better understanding of possible targets for rehabilitation.
Variants of uncertain significance in the era of high-throughput genome sequencing: a lesson from breast and ovary cancers
Authors: Federici Giulia , Soddu Silvia 
Published: March 2020

AbstractThe promising expectations about personalized medicine have opened the path to routine large-scale sequencing and increased the importance of genetic counseling for hereditary cancers, among which hereditary breast and ovary cancers (HBOC) have a major impact. High-throughput sequencing, or Next-Generation Sequencing (NGS), has improved cancer patient management, ameliorating diagnosis and treatment decisions. In addition to its undeniable clinical utility, NGS is also unveiling a large number of variants that we are still not able to clearly define and classify, the variants of uncertain significance (VUS), which account for about 40% of total variants. At present, VUS use in the clinical context is challenging. Medical reports may omit this kind of data and, even when included, they limit the clinical utility of genetic information. This has prompted the scientific community to seek easily applicable tests to accurately classify VUS and increase the amount of usable information from NGS data. In this review, we will focus on NGS and classification systems for VUS investigation, with particular attention on HBOC-related genes and in vitro functional tests developed for ameliorating and accelerating variant classification in cancer.
Efficacy, immunogenicity, and safety of IC43 recombinant Pseudomonas aeruginosa vaccine in mechanically ventilated intensive care patients—a randomized clinical trial
Authors: Adlbrecht Christopher , Wurm Raphael , Depuydt Pieter , Spapen Herbert , Lorente Jose A. , Staudinger Thomas , Creteur Jacques , Zauner Christian , Meier-Hellmann Andreas , Eller Philipp , Laenen Margot Vander , Molnár Zsolt , Várkonyi István , Schaaf Bernhard , Héjja Mária , Šrámek Vladimír , Schneider Hauke , Kanesa-thasan Niranjan , Eder-Lingelbach Susanne , Klingler Anton , Dubischar Katrin , Wressnigg Nina , Rello Jordi 
Published: March 2020

Abstract
Background
Pseudomonas aeruginosa infections are a serious threat in intensive care units (ICUs). The aim of this confirmatory, randomized, multicenter, placebo-controlled, double-blind, phase 2/3 study was to assess the efficacy, immunogenicity, and safety of IC43 recombinant Pseudomonas aeruginosa vaccine in non-surgical ICU patients.

Methods
Eight hundred patients aged 18 to 80 years admitted to the ICU with expected need for mechanical ventilation for ≥ 48 h were randomized 1:1 to either IC43 100 μg or saline placebo, given in two vaccinations 7 days apart. The primary efficacy endpoint was all-cause mortality in patients 28 days after the first vaccination. Immunogenicity and safety were also evaluated.

Findings
All-cause mortality rates at day 28 were 29.2% vs 27.7% in the IC43 and placebo groups, respectively (P = .67). Overall survival (Kaplan-Meier survival estimates, P = .46) and proportion of patients with ≥ one confirmed P. aeruginosa invasive infection or respiratory tract infection also did not differ significantly between both groups. The geometric mean fold increase in OprF/I titers was 1.5 after the first vaccination, 20 at day 28, after the second vaccination, and 2.9 at day 180. Significantly more patients in the placebo group (96.5%) had ≥ one adverse event (AE) versus the IC43 100 μg group (93.1%) (P = .04). The most frequently reported severe AEs in the IC43 and placebo groups were respiratory failure (6.9% vs 5.7%, respectively), septic shock (4.1% vs 6.5%), cardiac arrest (4.3% vs 5.7%), multiorgan failure (4.6% vs 5.5%), and sepsis (4.6% vs 4.2%). No related serious AEs were reported in the IC43 group.

Interpretation
The IC43 100 μg vaccine was well tolerated in this large population of medically ill, mechanically ventilated patients. The vaccine achieved high immunogenicity but provided no clinical benefit over placebo in terms of overall mortality.

Trial registration
https://clinicaltrials.gov (NCT01563263). Registration was sent to ClinicalTrials.gov on March 14, 2012, but posted by ClinicalTrials.gov on March 26, 2012. The first subject was included in the trial on March 22, 2012.