bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of major adverse cardiac, cerebrovascular events in patients with diabetes after acute coronary syndrome
Authors: Baluja Aurora , Rodríguez-Mañero Moisés , Cordero Alberto , Kreidieh Bahij , Iglesias-Alvarez Diego , García-Acuña Jose M , Martínez-Gómez Alvaro , Agra-Bermejo Rosa , Alvarez-Rodríguez Leyre , Abou-Jokh Charigan , López-Ratón Mónica , Gude-Sampedro Francisco , Alvarez-Escudero Julián , González-Juanatey Jose R 
Published: December 2019

Background and objectives: The risk of major adverse cardiac and cerebrovascular events following acute coronary syndrome is increased in people with diabetes. Predicting out-of-hospital outcomes upon follow-up remains difficult, and no simple, well-validated tools exist for this population at present. We aim to evaluate several factors in a competing risks model for actionable evaluation of the incidence of major adverse cardiac and cerebrovascular events in diabetic outpatients following acute coronary syndrome. Methods: Retrospective analysis of consecutive patients admitted for acute coronary syndrome in two centres. A Fine–Gray competing risks model was adjusted to predict major adverse cardiac and cerebrovascular events and all-cause mortality. A point-based score is presented that is based on this model. Results: Out of the 1400 patients, there were 783 (55.9%) with at least one major adverse cardiac and cerebrovascular event (417 deaths). Of them, 143 deaths were due to non-major adverse cardiac and cerebrovascular events. Predictive Fine–Gray models show that the ‘PG-HACKER’ risk factors (gender, age, peripheral arterial disease, left ventricle function, previous congestive heart failure, Killip class and optimal medical therapy) were associated to major adverse cardiac and cerebrovascular events. Conclusion: The PG-HACKER score is a simple and effective tool that is freely available and easily accessible to physicians and patients. The PG-HACKER score can predict major adverse cardiac and cerebrovascular events following acute coronary syndrome in patients with diabetes.
A Novel Diagnostic Algorithm for Heparin-Induced Thrombocytopenia in a Retrospective Cohort of Lung Transplant Recipients
Authors: Small Bronwyn Larissa , Gomes Marcelo P. , McCurry Kenneth R. , Han Xiaozhen , Ataya Ali , Akindipe Olufemi , Lane C. Randall , Budev Marie 
Published: December 2019

Introduction: Heparin-induced thrombocytopenia (HIT) is characterized by thrombocytopenia and potential for thromboembolism. Lung transplant recipients are at risk of developing HIT due to heparin exposure peritransplant. We describe the incidence and impact of HIT in lung transplant recipient index hospital length of stay and survival. Design: A retrospective cohort was obtained from electronic medical records which were queried for all recipients treated with bivalirudin (institutional treatment of choice for HIT) between January 1, 2005, and February 16, 2017 (N = 1171). Patients who developed HIT >30 days after transplant or after their index transplant admission were excluded. A diagnostic algorithm was used retrospectively to determine clinical HIT with an intermediate or high pretest clinical suspicion (“4T” score ≥4) and either (1) positive anti-heparin–platelet-factor 4 (HPF4) assay and a positive functional platelet assay or (2) a positive HPF4 assay only, in patients who did not undergo cardiopulmonary bypass. Results: Among all lung transplant recipients, 2.1% were found to develop HIT in the peritransplant period (N = 25, mean = 88%) with a mean lung allocation score of 50.8 and an incidence of venous thromboembolism of 72%, most upper extremity in location. When matched with historical controls, patients with HIT had a longer overall index hospital length of stay of 43 days ( P = .008). There was no difference in short- or long-term survival posttransplant. Conclusion: Vigilance for the development of HIT in lung transplant recipients is necessary to prevent further morbidity from thromboembolic events. In our cohort, HIT increased hospital length of stay but did not appear to affect recipient survival.
When should cardiovascular prevention begin? The importance of antenatal, perinatal and primordial prevention
Authors: D’Ascenzi Flavio , Sciaccaluga Carlotta , Cameli Matteo , Cecere Annagrazia , Ciccone Marco M , Di Francesco Simona , Ganau Antonello , Imbalzano Egidio , Liga Riccardo , Palermo Pietro , Palmiero Pasquale , Parati Gianfranco , Pedrinelli Roberto , Scicchitano Piero , Zito Annapaola , Mattioli Anna V 
Published: December 2019

Abstract
Cardiovascular diseases represent a major health problem, being one of the leading causes of morbidity and mortality worldwide. Therefore, in this scenario, cardiovascular prevention plays an essential role although it is difficult to establish when promoting and implementing preventive strategies. However, there is growing evidence that prevention should start even before birth, during pregnancy, aiming to avoid the onset of cardiovascular risk factors, since events that occur early in life have a great impact on the cardiovascular risk profile of an adult. The two pillars of this early preventive strategy are nutrition and physical exercise, together with prevention of cardio-metabolic diseases during pregnancy. This review attempts to gather the growing evidence of the benefits of antenatal, perinatal and primordial prevention, discussing also the possibility to reverse or to mitigate the cardiovascular profile developed in the initial stages of life. This could pave the way for future research, investigating the optimal time and duration of these preventing measures, their duration and maintenance in adulthood, and the most effective interventions according to the different age and guiding in the next years, the best clinical practice and the political strategies to cope with cardiovascular disease.
Longitudinal assessment of clonal mosaicism in human hematopoiesis via mitochondrial mutation tracking
Authors: Lareau Caleb A. , Ludwig Leif S. , Sankaran Vijay G. 
Published: December 2019

Abstract
Our ability to track cellular dynamics in humans over time in vivo has been limited. Here, we demonstrate how somatic mutations in mitochondrial DNA (mtDNA) can be used to longitudinally track the dynamic output of hematopoietic stem and progenitor cells in humans. Over the course of 3 years of blood sampling in a single individual, our analyses reveal somatic mtDNA sequence variation and evolution reminiscent of models of hematopoiesis established by genetic labeling approaches. Furthermore, we observe fluctuations in mutation heteroplasmy, coinciding with specific clinical events, such as infections, and further identify lineage-specific somatic mtDNA mutations in longitudinally sampled circulating blood cell subsets in individuals with leukemia. Collectively, these observations indicate the significant potential of using tracking of somatic mtDNA sequence variation as a broadly applicable approach to systematically assess hematopoietic clonal dynamics in human health and disease.
Trends and risk factors for death and excess all-cause mortality among notified tuberculosis patients in the UK: an analysis of surveillance data
Authors: Pedrazzoli Debora , Kranzer Katharina , Thomas H. Lucy , Lalor Maeve K. 
Published: December 2019

IntroductionIn the UK, several hundred patients notified with tuberculosis (TB) die every year. The aim of this article is to describe trends in deaths among notified TB patients, explore risk factors associated with death and compare all-cause mortality in TB patients with age-specific mortality rates in the general UK population.MethodsWe used 2001–2014 data from UK national TB surveillance to explore trends and risk factors for death, and population mortality data to compare age-specific death rates among notified TB patients with annual death rates in the UK general population.ResultsThe proportion of TB patients in the UK who died each year declined steadily from 7.1% in 2002 to 5.5% in 2014. One in five patients (21.3%) was diagnosed with TB post-mortem. Where information was available, almost half of the deaths occurred within 2 months of starting treatment. Risk factors for death included demographic, disease-specific and social risk factors. Age had by far the largest effect, with patients aged ≥80 years having a 70 times increased risk of death compared with those aged <15 years. In contrast, excess mortality determined by incidence ratios comparing all-cause mortality among TB patients with that of the general population was highest among children and the working-age population (15–64 years old).ConclusionsEfforts to control TB and improve diagnosis and treatment outcomes in the UK need to be sustained. Control efforts need to focus on socially deprived and vulnerable groups. There is a need for further in-depth analysis of deaths of TB patients in the UK to identify potentially preventable factors.
Dynamic Characteristics Analysis with Multi-Directional Coupling in a TBM Mainframe
Authors: Lin Laikuang , Xia Yimin , Li Zhengguang , Wu Caizhang , Cheng Yongliang , Tan Qing 
Published: December 2019

AbstractThe cutterhead of a full-face rock tunnel boring machine (TBM) is constantly subjected to varying impact and dynamic loads during tunneling processes, resulting in relatively large vibrations that could easily lead to fatigue cracking of the entire machine and affect the tunneling performance and efficiency. To explore the dynamic characteristics of the TBM mainframe, a TBM from a water-diversion project is investigated in this research. According to the TBM vibration transmission route, an equivalent dynamic model of the TBM mainframe is established using the lumped-mass method in which the relevant dynamic parameters are solved. Additionally, the dynamic response characteristics of the TBM mainframe are analyzed. The results indicate that the vibration levels in three directions are approximately the same, the multi-directional vibration of the cutterhead is more intense than that of other components, and the vibration and external excitation exhibit identical change trends. A set of vibration field tests is performed to analyze the in situ dynamic responses of the mainframe and verify the correctness of the dynamic model. The theoretical and measured acceleration values of the TBM mainframe have the same magnitude, which proves the validity of the dynamic model and its solution. The aforementioned results provide an important theoretical value and practical significance for the design and assessment of the TBM mainframe.
Effects of the proportion of high-risk patients and control strategies on the prevalence of methicillin-resistant Staphylococcus aureus in an intensive care unit
Authors: Chamchod Farida , Palittapongarnpim Prasit 
Published: December 2019

Abstract
Background
The presence of nosocomial pathogens in many intensive care units poses a threat to patients and public health worldwide. Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen endemic in many hospital settings. Patients who are colonized with MRSA may develop an infection that can complicate their prior illness.

Methods
A mathematical model to describe transmission dynamics of MRSA among high-risk and low-risk patients in an intensive care unit (ICU) via hands of health care workers is developed. We aim to explore the effects of the proportion of high-risk patients, the admission proportions of colonized and infected patients, the probability of developing an MRSA infection, and control strategies on MRSA prevalence among patients.

Results
The increasing proportion of colonized and infected patients at admission, along with the higher proportion of high-risk patients in an ICU, may significantly increase MRSA prevalence. In addition, the prevalence becomes higher if patients in the high-risk group are more likely to develop an MRSA infection. Our results also suggest that additional infection prevention and control measures targeting high-risk patients may considerably help reduce MRSA prevalence as compared to those targeting low-risk patients.

Conclusions
The proportion of high-risk patients and the proportion of colonized and infected patients in the high-risk group at admission may play an important role on MRSA prevalence. Control strategies targeting high-risk patients may help reduce MRSA prevalence.
Mortality risk and causes of death in patients with non-cystic fibrosis bronchiectasis
Authors: Sin Sooim , Yun Seo Young , Kim Jee Min , Park Chang Min , Cho Jaeyoung , Choi Sun Mi , Lee Jinwoo , Park Young Sik , Lee Sang-Min , Yoo Chul-Gyu , Kim Young Whan , Han Sung Koo , Lee Chang-Hoon 
Published: December 2019

Abstract
Background
All-cause mortality risk and causes of death in bronchiectasis patients have not been fully investigated. The aim of this study was to compare the mortality risk and causes of death between individuals with bronchiectasis and those without bronchiectasis.

Methods
Patients with or without bronchiectasis determined based on chest computed tomography (CT) at one centre between 2005 and 2016 were enrolled. Among the patients without bronchiectasis, a control group was selected after applying additional exclusion criteria. We compared the mortality risk and causes of death between the bronchiectasis and control groups without lung disease. Subgroup analyses were also performed according to identification of Pseudomonas or non-tuberculous mycobacteria, airflow limitation, and smoking status.

Results
Of the total 217,702 patients who underwent chest CT, 18,134 bronchiectasis patients and 90,313 non-bronchiectasis patients were included. The all-cause mortality rate in the bronchiectasis group was 1608.8 per 100,000 person-years (95% confidence interval (CI), 1531.5–1690.0), which was higher than that in the control group (133.5 per 100,000 person-years; 95% CI, 124.1–143.8; P < 0.001). The bronchiectasis group had higher all-cause (adjusted hazard ratio (aHR), 1.26; 95% CI, 1.09–1.47), respiratory (aHR, 3.49; 95% CI, 2.21–5.51), and lung cancer-related (aHR, 3.48; 95% CI, 2.33–5.22) mortality risks than the control group. In subgroup analysis, patients with airflow limitation and ever smokers showed higher all-cause mortality risk among bronchiectasis patients. Therefore, we observed significant interrelation between bronchiectasis and smoking, concerning the risks of all-cause mortality (P for multiplicative interaction, 0.030, RERI, 0.432; 95% CI, 0.097–0.769) and lung cancer-related mortality (RERI, 8.68; 95% CI, 1.631–15.736).

Conclusion
Individuals with bronchiectasis had a higher risk of all-cause, respiratory, and lung cancer-related mortality compared to control group. The risk of all-cause mortality was more prominent in those with airflow limitation and in ever smokers.
The clinical impact of drug-induced hepatotoxicity on anti-tuberculosis therapy: a case control study
Authors: Song Jin Hwa , Yoon Seo-Young , Park Tae Yun , Heo Eun Young , Kim Deog Kyeom , Chung Hee Soon , Lee Jung-Kyu 
Published: December 2019

Abstract
Background
There are limited data available on whether drug-induced hepatotoxicity (DIH) affects the clinical outcomes of tuberculosis (TB) treatment. We explored the effects of DIH on the clinical course and outcomes of pulmonary TB.

Methods
In this retrospective cohort study, we included patients with culture-proven pulmonary TB treated in a tertiary hospital from 2013 to 2016. DIH was defined as proposed by the official American Thoracic Society statement. We compared the clinical outcomes of DIH and non-DIH patients.

Results
Between January 1, 2013 and December 31, 2016, a total of 168 TB patients were included, and 20 (11.9%) were diagnosed with DIH. These patients were significantly older, had a higher Charlson Comorbidity Index score, exhibited more chronic liver disease, included more chronic alcoholics, and had a lower body mass index than non-DIH patients. We found no significant differences between DIH and non-DIH patients in the 2-month sputum culture conversion rate, the time to sputum culture conversion, treatment outcomes, or total treatment duration. However, the ratio of treatment interruption time to total treatment duration and the proportion of hepatotonic users were significantly higher among DIH patients.

Conclusion
DIH development during TB treatment does not significantly affect the clinical outcomes of pulmonary TB. However, treatment interruption caused by DIH may increase the risks of future relapse and acquired resistance. Further study is needed.
Comparative analyses of long non-coding RNA profiles in vivo in cystic fibrosis lung airway and parenchyma tissues
Authors: Kumar Parameet , Sen Chaitali , Peters Kathryn , Frizzell Raymond A. , Biswas Roopa 
Published: December 2019

Abstract
Background
Recent advances in the functional analyses of endogenous non-coding RNA (ncRNA) molecules, including long non-coding RNAs (LncRNAs), have provided a new perspective on the crucial roles of RNA in gene regulation. Consequently, LncRNA deregulation is a key factor in various diseases, including pulmonary disorders like Cystic Fibrosis (CF). CF is the most common life limiting recessive disease in the U.S., and is due to mutations in the CFTR gene. CF mutations, of which the most common is F508del-CFTR, prevents correct folding, trafficking and function of the mutant CFTR protein and is further manifested by the hyper-expression of pro-inflammatory cytokines and chemokines into the airway lumen leading to bronchiectasis and culminating in lung destruction.

Methods
Here we report a distinct LncRNA signature and corresponding mRNAs that distinguishes CF lung (airway and parenchyma) tissues from matched non-CF controls (n = 4 each group), generated by microarray specific for LncRNAs which includes corresponding mRNA expressions. In silico analyses of the cellular processes that are impacted by these LncRNAs was performed using Gene Ontology (GO). A selected subset of LncRNAs were validated by quantitative real-time PCR.

Results
We have identified 636 LncRNAs differentially expressed in CF airway epithelium and 1974 in CF lung parenchyma compared to matched non-CF controls (fold change ≥2, p < 0.05), majority of which (> 50%) are intergenic. Interestingly, 15 of these differentially expressed LncRNAs and 9 coding mRNAs are common to airway and parenchyma tissues. GO analyses indicates that signaling pathways and cell membrane functions are significantly affected by the alteration in LncRNA expressions in CF lung tissues. Seven of the differentially expressed LncRNAs, exhibit similar expression trends in CFBE41o- compared to control cells.

Conclusion
Understanding the mechanisms by which these LncRNAs regulate CF disease phenotype will help develop novel therapeutic targets for CF and related pulmonary diseases, such as COPD and Asthma.
Efficient Cas9-based genome editing of Rhodobacter sphaeroides for metabolic engineering
Authors: Mougiakos Ioannis , Orsi Enrico , Ghiffary Mohammad Rifqi , Post Wilbert , de Maria Alberto , Adiego-Perez Belén , Kengen Servé W. M. , Weusthuis Ruud A. , van der Oost John 
Published: December 2019

AbstractBackgroundRhodobacter sphaeroidesis a metabolically versatile bacterium that serves as a model for analysis of photosynthesis, hydrogen production and terpene biosynthesis. The elimination of by-products formation, such as poly-β-hydroxybutyrate (PHB), has been an important metabolic engineering target forR. sphaeroides. However, the lack of efficient markerless genome editing tools forR. sphaeroidesis a bottleneck for fundamental studies and biotechnological exploitation. The Cas9 RNA-guided DNA-endonuclease from the type II CRISPR-Cas system ofStreptococcus pyogenes(SpCas9) has been extensively employed for the development of genome engineering tools for prokaryotes and eukaryotes, but not forR. sphaeroides.ResultsHere we describe the development of a highly efficient SpCas9-based genomic DNA targeting system forR. sphaeroides, which we combine with plasmid-borne homologous recombination (HR) templates developing a Cas9-based markerless and time-effective genome editing tool. We further employ the tool for knocking-out the uracil phosphoribosyltransferase (upp)genefrom the genome ofR. sphaeroides,as well as knocking it back in while altering its start codon. These proof-of-principle processes resulted in editing efficiencies of up to 100% for the knock-out yet less than 15% for the knock-in. We subsequently employed the developed genome editing tool for the consecutive deletion of the two predicted acetoacetyl-CoA reductase genesphaBandphbBin the genome ofR. sphaeroides. The culturing of the constructed knock-out strains under PHB producing conditions showed that PHB biosynthesis is supported only by PhaB, while the growth of theR. sphaeroidesΔphbBstrains under the same conditions is only slightly affected.ConclusionsIn this study, we combine the SpCas9 targeting activity with the native homologous recombination (HR) mechanism ofR. sphaeroidesfor the development of a genome editing tool. We further employ the developed tool for the elucidation of the PHB production pathway ofR. sphaeroides.We anticipate that the presented work will accelerate molecular research withR. sphaeroides.
Triple blockade of EGFR, MEK and PD-L1 has antitumor activity in colorectal cancer models with constitutive activation of MAPK signaling and PD-L1 overexpression
Authors: Napolitano S. , Matrone N. , Muddassir A. L. , Martini G. , Sorokin A. , De Falco V. , Giunta E. F. , Ciardiello D. , Martinelli E. , Belli V. , Furia M. , Kopetz S. , Morgillo F. , Ciardiello F. , Troiani T. 
Published: December 2019

Abstract
Background
Molecular mechanisms driving acquired resistance to anti-EGFR therapies in metastatic colorectal cancer (mCRC) are complex but generally involve the activation of the downstream RAS-RAF-MEK-MAPK pathway. Nevertheless, even if inhibition of EGFR and MEK could be a strategy for overcoming anti-EGFR resistance, its use is limited by the development of MEK inhibitor (MEKi) resistance.

Methods
We have generated in vitro and in vivo different CRC models in order to underline the mechanisms of MEKi resistance.

Results
The three different in vitro MEKi resistant models, two generated by human CRC cells quadruple wild type for KRAS, NRAS, BRAF, PI3KCA genes (SW48-MR and LIM1215-MR) and one by human CRC cells harboring KRAS mutation (HCT116-MR) showed features related to the gene signature of colorectal cancer CMS4 with up-regulation of immune pathway as confirmed by microarray and western blot analysis. In particular, the MEKi phenotype was associated with the loss of epithelial features and acquisition of mesenchymal markers and morphology. The change in morphology was accompanied by up-regulation of PD-L1 expression and activation of EGFR and its downstream pathway, independently to RAS mutation status. To extend these in vitro findings, we have obtained mouse colon cancer MC38- and CT26-MEKi resistant syngeneic models (MC38-MR and CT26-MR). Combined treatment with MEKi, EGFR inhibitor (EGFRi) and PD-L1 inhibitor (PD-L1i) resulted in a marked inhibition of tumor growth in both models.

Conclusions
These results suggest a strategy to potentially improve the efficacy of MEK inhibition by co-treatment with EGFR and PD-L1 inhibitors via modulation of host immune responses.