bluuebunny/crossref_metadata_2025_split huggingface dataset:
FKBPL-based peptide, ALM201, targets angiogenesis and cancer stem cells in ovarian cancer
Authors: Annett Stephanie , Moore Gillian , Short Amy , Marshall Andrea , McCrudden Cian , Yakkundi Anita , Das Sudipto , McCluggage W. Glenn , Nelson Laura , Harley Ian , Moustafa Nermeen , Kennedy Catherine J. , deFazio Anna , Brand Alison , Sharma Raghwa , Brennan Donal , O’Toole Sharon , O’Leary John , Bates Mark , O’Riain Ciarán , O’Connor Darran , Furlong Fiona , McCarthy Helen , Kissenpfennig Adrien , McClements Lana , Robson Tracy 
Published: November 2019

Abstract
Background
ALM201 is a therapeutic peptide derived from FKBPL that has previously undergone preclinical and clinical development for oncology indications and has completed a Phase 1a clinical trial in ovarian cancer patients and other advanced solid tumours.

Methods
In vitro, cancer stem cell (CSC) assays in a range of HGSOC cell lines and patient samples, and in vivo tumour initiation, growth delay and limiting dilution assays, were utilised. Mechanisms were determined by using immunohistochemistry, ELISA, qRT-PCR, RNAseq and western blotting. Endogenous FKBPL protein levels were evaluated using tissue microarrays (TMA).

Results
ALM201 reduced CSCs in cell lines and primary samples by inducing differentiation. ALM201 treatment of highly vascularised Kuramochi xenografts resulted in tumour growth delay by disruption of angiogenesis and a ten-fold decrease in the CSC population. In contrast, ALM201 failed to elicit a strong antitumour response in non-vascularised OVCAR3 xenografts, due to high levels of IL-6 and vasculogenic mimicry. High endogenous tumour expression of FKBPL was associated with an increased progression-free interval, supporting the protective role of FKBPL in HGSOC.

Conclusion
FKBPL-based therapy can (i) dually target angiogenesis and CSCs, (ii) target the CD44/STAT3 pathway in tumours and (iii) is effective in highly vascularised HGSOC tumours with low levels of IL-6.
Recent population genomic insights into the genetic basis of arsenic tolerance in humans: the difficulties of identifying positively selected loci in strongly bottlenecked populations
Authors: Apata Mario , Pfeifer Susanne P. 
Published: November 2019

AbstractRecent advances in genomics have enabled researchers to shed light on the evolutionary processes driving human adaptation, by revealing the genetic architectures underlying traits ranging from lactase persistence, to skin pigmentation, to hypoxic response, to arsenic tolerance. Complicating the identification of targets of positive selection in modern human populations is their complex demographic history, characterized by population bottlenecks and expansions, population structure, migration, and admixture. In particular, founder effects and recent strong population size reductions, such as those experienced by the indigenous peoples of the Americas, have severe impacts on genetic variation that can lead to the accumulation of large allele frequency differences between populations due to genetic drift rather than natural selection. While distinguishing the effects of demographic history from selection remains challenging, neglecting neutral processes can lead to the incorrect identification of candidate loci. We here review the recent population genomic insights into the genetic basis of arsenic tolerance in Andean populations, and utilize this example to highlight both the difficulties pertaining to the identification of local adaptations in strongly bottlenecked populations, as well as the importance of controlling for demographic history in selection scans.
A revised model for promoter competition based on multi-way chromatin interactions at the α-globin locus
Authors: Oudelaar A. Marieke , Harrold Caroline L. , Hanssen Lars L. P. , Telenius Jelena M. , Higgs Douglas R. , Hughes Jim R. 
Published: November 2019

AbstractSpecific communication between gene promoters and enhancers is critical for accurate regulation of gene expression. However, it remains unclear how specific interactions between multiple regulatory elements contained within a single chromatin domain are coordinated. Recent technological advances which can detect multi-way chromatin interactions at single alleles can provide insights into how multiple regulatory elements cooperate or compete for transcriptional activation. Here, we use such an approach to investigate how interactions of the α-globin enhancers are distributed between multiple promoters in a mouse model in which the α-globin domain is extended to include several additional genes. Our data show that gene promoters do not form mutually exclusive interactions with enhancers, but all interact simultaneously in a single complex. These findings suggest that promoters do not structurally compete for interactions with enhancers, but form a regulatory hub structure, which is consistent with recent models of transcriptional activation occurring in non-membrane bound nuclear compartments.
A rotary plasmonic nanoclock
Authors: Xin Ling , Zhou Chao , Duan Xiaoyang , Liu Na 
Published: November 2019

AbstractOne of the fundamental challenges in nanophotonics is to gain full control over nanoscale optical elements. The precise spatiotemporal arrangement determines their interactions and collective behavior. To this end, DNA nanotechnology is employed as an unprecedented tool to create nanophotonic devices with excellent spatial addressability and temporal programmability. However, most of the current DNA-assembled nanophotonic devices can only reconfigure among random or very few defined states. Here, we demonstrate a DNA-assembled rotary plasmonic nanoclock. In this system, a rotor gold nanorod can carry out directional and reversible 360° rotation with respect to a stator gold nanorod, transitioning among 16 well-defined configurations powered by DNA fuels. The full-turn rotation process is monitored by optical spectroscopy in real time. We further demonstrate autonomous rotation of the plasmonic nanoclock powered by DNAzyme-RNA interactions. Such assembly approaches pave a viable route towards advanced nanophotonic systems entirely from the bottom-up.
A clinical trial to evaluate the effect of the Mediterranean diet on smokers lung function
Authors: Martín-Luján Francisco , Catalin Roxana-Elena , Salamanca-González Patricia , Sorlí-Aguilar Mar , Santigosa-Ayala Antoni , Valls-Zamora Rosa Maria , Martín-Vergara Núria , Canela-Armengol Teresa , Arija-Val Victoria , Solà-Alberich Rosa 
Published: November 2019

AbstractData on the association between lung function and some dietary patterns have been published. However, it is not yet well known if whether the Mediterranean Diet (MD) pattern can preserve or improve lung function. Our purpose is to evaluate the effect of increased MD adherence on lung function in smokers. A multicenter, parallel, cluster-randomized, controlled clinical trial is proposed. A total of 566 active smokers (>10 packs-year), aged 25–75 years will be included, without previous respiratory disease and who sign an informed consent to participate. Twenty Primary Care Centres in Tarragona (Spain) will be randomly assigned to a control or an intervention group (1:1). All participants will receive advice to quit smoking, and the intervention group, a nutritional intervention (2 years) designed to increase MD adherence by: (1) annual visit to deliver personalized nutritional education, (2) annual telephone contact to reinforce the intervention, and (3) access to an online dietary blog. We will evaluate (annually for 2 years): pulmonary function by forced spirometry and MD adherence by a 14-item questionnaire and medical tests (oxidation, inflammation and consumption biomarkers). In a statistical analysis by intention-to-treat basis, with the individual smoker as unit of analysis, pulmonary function and MD adherence in both groups will be compared; logistic regression models will be applied to analyze their associations. We hope to observe an increased MD adherence that may prevent the deterioration of lung function in smokers without previous respiratory disease. This population may benefit from a dietary intervention, together with the recommendation of smoking cessation.
Development of ISSR-derived SCAR Marker and SYBR Green I Real-time PCR Method for Detection of Teliospores of Tilletia laevis Kühn
Authors: Yao Zhaoqun , Qin Dandan , Chen Delai , Liu Changzhong , Chen Wanquan , Liu Taiguo , Liu Bo , Gao Li 
Published: November 2019

AbstractCommon bunt, caused by Tilletia laevis Kühn [syn. T. foetida (Wallr) Liro] and Tilletia tritici (Bjerk.) Wint. [syn. T. caries (DC) Tul.], is an important wheat disease worldwide. To quickly differentiate the closely related fungi T. laevis, T. tritici and Tilletia controversa (a pathogen that causes dwarf bunt of wheat and has been requested as a quarantined pathogen in many countries), a rapid diagnostic and detection method for an ISSR molecular marker was developed for the first time in this study. Based on the T. laevis-specific band (1300 bp) amplified by the primer ISSR860, a pair of SCAR primers (L60F/L60R) was designed to amplify a specific 660-bp DNA fragment from the isolates of T. laevis but not other related pathogens. The detection limit of the SCAR marker was 0.4 ng/μl of DNA from T. laevis; moreover, a SYBR Green I real-time PCR method was also successfully developed based on the SCAR marker with the detection limit of 10 fg/μl T. laevis DNA. This is the first report of a rapid, specific and highly sensitive SCAR marker and SYBR Green I real-time PCR method for detection of the teliospores of T. laevis based on ISSR technology. This method allows highly efficient, rapid and accurate differentiation of the pathogen from related pathogens, especially from the very similar pathogens T. tritici and T. controversa.
Prevalence and characterization of breakthrough pain in patients with cancer in Spain: the CARPE-DIO study
Authors: Pérez-Hernández Concepción , Blasco Ana , Gándara Álvaro , Mañas Ana , Rodríguez-López Manuel Jesús , Martínez Vicente , Fernandez-Nistal Alonso , Montoto Carmen 
Published: November 2019

AbstractWe aimed to evaluate the prevalence, characteristics and impact of breakthrough pain (BTP) in patients with cancer attending the main specialties involved in the diagnosis and management of BTP in Spain using a multicenter, observational, cross-sectional, multidisciplinary study. Investigators had to record all patients seen at the clinic during 1 month, determine whether the patients had cancer pain, and apply the Davies algorithm to ascertain whether the patients were suffering from BTP. Of the 3,765 patients with cancer, 1,117 (30%) had cancer-related pain, and of these patients, 539 had BTP (48%, 95%CI:45–51). The highest prevalence was found in patients from palliative care (61%, 95%CI:54–68), and the lowest was found in those from hematology (25%, 95%CI:20–31). Prevalence varied also according to sex and type of tumor. According to the Alberta Breakthrough Pain Assessment Tool duration, timing, frequency, location, severity, quality, causes, and predictability of the BTP varied greatly among these patients. BTP was moderate (Brief Pain Inventory [BPI]-severity median score = 5.3), and pain interference was moderate (BPI-interference median score = 6.1) with a greater interference with normal work, general activity, and enjoyment of life. Patients with BTP showed a mean ± standard deviation score of 28.5 ± 8.0 and 36.9 ± 9.5 in the physical and mental component, respectively, of the SF-12 questionnaire. In conclusion, prevalence of BTP among patients exhibiting cancer-related pain is high. Clinical presentation is heterogeneous, and therefore, BTP cannot be considered as a single entity. However, uniformly BTP has an important impact on a patient’s functionality, which supports the need for early detection and treatment.
Tumor suppressor properties of the small C-terminal domain phosphatases in non-small cell lung cancer
Authors: Krasnov George S. , Puzanov Grigory A. , Afanasyeva Marina A. , Dashinimaev Erdem B. , Vishnyakova Khava S. , Beniaminov Artemy D. , Adzhubei Alexei A. , Kondratieva Tatiana T. , Yegorov Yegor E. , Senchenko Vera N. 
Published: November 2019

AbstractNon-Small Cell Lung Cancer (NSCLC) is responsible for the majority of deaths caused by cancer. Small C-terminal domain (CTD) phosphatases (SCP), CTDSP1, CTDSP2 and CTDSPL (CTDSPs) belong to SCP/CTDSP subfamily and are involved in many vital cellular processes and tumorigenesis. High similarity of their structures suggests similar functions. However their role in NSCLC remains insufficiently understood. For the first time we revealed the suppressor function of CTDSPs leading to a significant growth slowdown and senescence of A549 lung adenocarcinoma (ADC) cells in vitro. Their tumor-suppressive activity can be realized through increasing the proportion of the active form of Rb protein dephosphorylated at Ser807/811, Ser780, and Ser795 (P&lt;0.05) thereby negatively regulating cancer cell proliferation. Moreover, we observed that a frequent (84%, 39/46) and highly concordant (Spearman’s rank correlation coefficient (rs) = 0.53–0.62, P≤0.01) down-regulation of CTDSPs and RB1 is characteristic of primary NSCLC samples (n=46). A clear difference in their mRNA levels was found between lung ADCs with and without lymph node metastases, but not in squamous cell carcinomas (SCCs) (P≤0.05). Based on The Cancer Genome Atlas (TCGA) data and the results obtained using the CrossHub tool, we suggest that the well-known oncogenic cluster miR-96/182/183 could be a common expression regulator of CTDSPs. Indeed, according to our qPCR, the expression of CTDSPs negatively correlates with these miRs, but positively correlates with their intronic miR-26a/b. Our results reflect functional association of CTDSP1, CTDSP2, and CTDSPL, expand knowledge about their suppressor properties through Rb dephosphorylation and provide new insights into the regulation of NSCLC growth.
Association of vitamin E on the risk of ovarian cancer: a meta-analysis
Authors: Leng Youxu , Zhou Hairong , Meng Fanjing , Tian Tian , Xu Jianying , Yan Fengjuan 
Published: November 2019

AbstractMany researches were conducted to assess the association of vitamin E intake on the risk of ovarian cancer, with conflict results. The current meta-analysis of published observational studies aimed to investigate the effect of vitamin E intake on ovarian cancer risk. The summary relative risks (RRs) with corresponding 95% confidence intervals (CIs) were calculated to measure the effectiveness of vitamin E intake on ovarian cancer risk using a random-effects model. As a result, 14 studies including 4597 patients were identified. Eleven studies reported about total vitamin E intake, eight studies about vitamin E intake from food only and five studies about vitamin E intake from supplement only on the risk of ovarian cancer. Overall, the summary RRs on ovarian cancer risk was 0.95 (95%CIs = 0.78–1.16) in total vitamin E intake, 0.99 (95%CIs = 0.77–1.27) in vitamin E intake from food only and 0.82 (95%CIs = 0.54–1.25) in vitamin E intake from supplement only. Results in subgroup analyses by study design and geographic location were consistent with overall result. In conclusions, the findings of this meta-analysis suggested that high intake of vitamin E from food or vitamin E supplement had no significant effect on the risk of ovarian cancer.
Security‐constrained transmission expansion planning using linear sensitivity factors
Authors: Mehrtash Mahdi , Kargarian Amin , Rahmani Mohsen 
Published: November 2019

Formulating power flow equations with linear sensitivity factors (LSFs) reduces the number of variables and constraints, and consequently, the computational burden of power systems’ optimisation problems. This study proposes a transformative, computationally efficient model for transmission expansion planning (TEP). While the existing TEP models use bus voltage angles, the proposed TEP takes advantages of LSFs to formulate an optimisation. LSFs allow to omit voltage angles from the formulation and replace all nodal power balance constraints by one equivalent constraint. Thus, the proposed model includes less number of variables and constraints compared with the classical angle‐based model. These features significantly reduce computational costs of TEP and enhance its scalability, especially for large‐scale systems. Load and generation uncertainties are modelled using a data‐driven approach, and N − 1 security criteria are taken into account to ensure system security. All equations under normal and N − 1 conditions are considered using data of the complete network graph. Simulation results show that the proposed model provides the same results as the conventional angle‐based model while being much faster (more than 58% based on the authors’ case studies) and computationally more efficient.
Verhandeln: mit Gefühl und Verstand
Authors: Schön Wolfram 
Published: November 2019

Verhandlungen sind alltäglicher Bestandteil des Arbeitslebens. Viele Verhandlungen scheitern jedoch, bevor sie richtig begonnen haben. Gründe dafür sind häufig das Nichtbeachten der psychischen Grundbedürfnisse und das Beharren auf eigenen inhaltlichen Positionen. Nachfolgend möchte ich, nach einem kurzen Swing in das Thema psychische Grundbedürfnisse, die 4 Grundprinzipien (nach Shapiro und Fisher) erfolgreicher Verhandlungen darstellen.
Training of Residents in Cardiac Surgery—Does It Have Impact on the Outcome?
Authors: Szczechowicz Marcin Piotr , Easo Jerry , Zhigalov Konstantin , Mashhour Ahmed , Mkalaluh Sabreen , Weymann Alexander 
Published: November 2019

Abstract
Objectives In many centers, training in cardiac surgery is considered to increase perioperative risk. This study aims to test whether a resident working as the main operator is a genuine risk factor.
Methods We analyzed patients who underwent elective isolated aortic valve replacement, elective isolated coronary artery bypass grafting, or both, in our institution, from 2008 to 2016. Redo- and off-pump surgery, ejection fraction < 30%, and other concomitant procedures were the exclusion criteria. After this selection, we included 3,077 patients in our study. Within this group, 357 (11.6%) had been operated by residents and 2,720 (88.4%) by senior surgeons. We performed propensity score matching using the nearest neighbor method with a ratio of 1:2, considering the most important preoperative conditions. In this way, the 357 patients operated by residents were matched with the 714 patients who were operated by senior surgeons. The standardized mean differences were highly reduced after matching, so both groups had similar risk profiles. We compared surgical data, postoperative adverse events, and the 30-day mortality between the two groups.
Results The times of surgery, cardiopulmonary bypass, and cross-clamp were longer if residents operated (p < 0.001). There were no differences regarding postoperative adverse events, time of mechanical ventilation, and the intensive care unit length of stay. The 30-day mortality rates of the two groups were very similar (p = 0.75, power = 0.8).
Conclusion Training in cardiac surgery is safe, and carefully selected patients can be operated by residents without increased risk of perioperative mortality and complications.
Acute Kidney Injury and Bronchopulmonary Dysplasia in Premature Neonates Born Less than 32 Weeks' Gestation
Authors: Starr Michelle C. , Boohaker Louis , Eldredge Laurie C. , Menon Shina , Griffin Russell , Mayock Dennis E. , Li Linzi , Askenazi David , Hingorani Sangeeta ,   on behalf of the Neonatal Kidney Collaborative
Published: November 2019

Abstract
Objective This study aimed to evaluate the association between acute kidney injury (AKI) and bronchopulmonary dysplasia (BPD) in infants born <32 weeks of gestational age (GA).
Study Design Present study is a secondary analysis of premature infants born at <32 weeks of GA in the Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) retrospective cohort (n = 546). We stratified by gestational age and used logistic regression to determine association between AKI and moderate or severe BPD/mortality.
Results Moderate or severe BPD occurred in 214 of 546 (39%) infants, while death occurred in 32 of 546 (6%); the composite of moderate or severe BPD/death occurred in 246 of 546 (45%). For infants born ≤29 weeks of gestation, the adjusted odds ratio (OR) of AKI and the primary outcome was 1.15 (95% confidence interval [CI] = 0.47–2.86; p = 0.76). Infants born between 29 and 32 weeks of gestation with AKI had four-fold higher odds of moderate or severe BPD/death that remained after controlling for multiple factors (adjusted OR = 4.21, 95% CI: 2.07–8.61; p < 0.001).
Conclusion Neonates born between 29 and 32 weeks who develop AKI had a higher likelihood of moderate or severe BPD/death than those without AKI. Further studies are needed to validate our findings and evaluate mechanisms of multiorgan injury.
Levosimendan Reduces Mortality and Low Cardiac Output Syndrome in Cardiac Surgery
Authors: Deppe Antje Christin , Wahlers Thorsten C. W. , Weber Carolyn , Esser Matthias , Eghbalzadeh Kaveh , Sabashnikov Anton , Djordjevic Ilija , Maier Johanna , Merkle Julia , Choi Yeong-Hoon , Madershahian Navid , Liakopoulos Oliver 
Published: November 2019

Abstract
Background There has been conflicting evidence concerning the effect of levosimendan on clinical outcomes in patients undergoing cardiac surgery. Therefore, we performed a systematic review and conducted this meta-analysis to provide evidence for/against the administration of levosimendan in cardiac surgery patients.
Methods We performed a meta-analysis from literature search in PubMed, EMBASE, and Cochrane Library. Only randomized controlled trials comparing the administration of levosimendan in cardiac surgery patients with a control group (other inotrope, standard therapy/placebo, or an intra-aortic balloon pump) were included. In addition, at least one clinical outcome had to be mentioned: mortality, myocardial infarction, low cardiac output syndrome (LCOS), acute kidney injury, renal replacement therapy, atrial fibrillation, prolonged inotropic support, length of intensive care unit, and hospital stay. The pooled treatment effects (odds ratio [OR], 95% confidence intervals [CI]) were assessed using a fixed or random effects model.
Results The literature search retrieved 27 randomized, controlled trials involving a total of 3,198 patients. Levosimendan led to a significant reduction in mortality (OR: 0.67; 95% CI: 0.49–0.91; p = 0.0087). Furthermore, the incidence of LCOS (OR: 0.56, 95% CI: 0.42–0.75; p < 0.0001), acute kidney injury (OR: 0.63; 95% CI: 0.46–0.86; p = 0.0039), and renal replacement therapy (OR: 0.70; 95% CI: 0.50–0.98; p = 0.0332) was significantly decreased in the levosimendan group.
Conclusion Our meta-analysis suggests beneficial effects for the prophylactic use of levosimendan in patients with severely impaired left ventricular function undergoing cardiac surgery. The administration of levosimendan was associated with a reduced mortality, less LCOS, and restored adequate organ perfusion reflected in less acute kidney injury.