bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long term clinical impact of successful recanalization of chronic total occlusion in patients with and without type 2 diabetes mellitus
Authors: Tsai Chuan-Tsai , Huang Wei-Chieh , Teng Hsin-I , Tsai Yi-Lin , Lu Tse-Min 
Published: July 2020

Abstract
Background: Diabetes mellitus is one of the risk factors for coronary artery disease and frequently associated with multivessels disease and poor clinical outcomes. Long term outcome of successful revascularization of chronic total occlusions (CTO) in diabetes patients remains controversial.Methods and results: From January 2005 to December 2015, 739 patients who underwent revascularization for CTO in Taipei Veterans General Hospital were included in this study, of which 313 (42 %) patients were diabetes patients. Overall successful rate of revascularization was 619 (84%) patients whereas that in diabetics and non-diabetics were 265 (84%) and 354 (83%) respectively. Median follow up was 1095 days (median: 5 years, interquartile range: 1 – 10 years). During 3 years follow-up period, 59 (10%) in successful group and 18 (15%) patients in failure group died. Although successful revascularization of CTO was non-significantly associated with better outcome in total cohort (Hazard ratio (HR):0.593, 95% confidence interval (CI): 0.349–0.008, P:0.054), it might be associated with lower risk of all-cause mortality (HR: 0.307, 95% CI: 0.156 – 0.604, P: 0.001) and CV mortality (HR: 0.266, 95% CI: 0.095 – 0.748, P: 0.012) in diabetics (P: 0.512). In contrast, successful CTO revascularization didn’t improve outcomes in non-diabetics (all p>0.05). In multivariate cox regression analysis, successful CTO revascularization remained an independent predictor for 3-years survival in diabetic subgroup (HR: 0.289, 95% CI: 0.125–0.667, P: 0.004). The multivariate analysis result was similar after propensity score matching (all-cause mortality, HR: 0.348, 95% CI: 0.142 – 0.851, P: 0.021).Conclusions: Successful CTO revascularization in diabetes may be related to better long term survival benefit but not in non-diabetic population.
Implementing a Nurse-Enabled, Integrated, Shared-Care Model Involving Specialists and General Practitioners in Breast Cancer Post-Treatment Follow-Up: A Study Protocol for a Phase II Randomised Controlled Trial (The EMINENT Trial)
Authors: Chan Raymond , Emery Jon , Cuff Katharine , Teleni Laisa , Simonsen Camilla , Turner Jane , Janda Monika , Mckavanagh Daniel , Jones Lee , McKinnell Emma , Gosper Melissa , Ryan Juanita , Joseph Ria , Crowe Bethany , Harvey Jennifer , Ryan Marissa , Carrington Christine , Nund Rebecca , Crichton Megan , McPhail Steven 
Published: July 2020

Abstract
Background: Due to advances in early detection and cancer treatment, 5-year relative survival rates for early breast cancer surpass 90% in developed nations. There is increasing focus on promotion of wellness in survivorship and active approaches to reducing morbidity related to treatment; however, current models of follow-up care are heavily reliant on hospital-based specialist-led care. This study aims to test the feasibility of the EMINENT intervention for implementing an integrated, shared-care model involving both cancer center specialists and community-based general practitioners for early breast cancer post-treatment follow-up.Methods: We describe a protocol for a phase II, randomized controlled trial with two parallel arms and 1:1 allocation. A total of 60 patients with early stage breast cancer will be randomized to usual, specialist-led, follow-up care (as determined by the treating surgeons, medical oncologists, and radiation oncologists) or shared follow-up care intervention (i.e., EMINENT). EMINENT is a nurse-enabled, pre-specified shared-care pathway with follow-up responsibilities divided between cancer center specialists (i.e., surgeons and oncologists) and general practitioners. Primary outcome is health-related quality of life as measured by the Functional Assessment of Cancer Therapy-Breast Cancer. Secondary outcomes include patient experience, acceptance, and satisfaction of care; dietary, physical activity and sedentary behaviors; financial toxicity; adherence; health resource utilization; and adverse events.Discussion: The trial is designed to identify the barriers to implementing a shared-care model for breast cancer survivors following treatment. Results of this study will inform a definitive trial testing the effects of shared-care model on health-related quality of life of breast cancer survivors, as well as its ability to alleviate the growing demands on the healthcare system.Trial registration: Trial registration: Australia and New Zealand Clinical Trials Registry, ACTRN12619001594112). Registered 19 November 2019, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378690&isReview=true.
Design, Development and Deployment of a Web-Based Interoperable Registry for Inherited Retinal Dystrophies in Portugal -The Ird-Pt
Authors: Marques João Pedro , Carvalho Ana Luísa , Henriques José , Murta Joaquim Neto , Saraiva Jorge , Silva Rufino 
Published: July 2020

Abstract
BACKGROUND: The development of multicenter patient registries promotes the generation of scientific knowledge by using real-world data. A country-wide, web-based registry for inherited retinal dystrophies (IRDs) empowers patients and community organizations, while supporting formal partnerships with investigators and stakeholders in the global aim to develop high-value, high-utility research. We aim to describe the design, development and deployment of a country-wide, web-based, user-friendly and interoperable registry for IRDs – the IRD-PT.RESULTS: The IRD-PT is a clinical/genetic research registry included in the retina.pt platform (http://www.retina.com.pt), which was developed by the Portuguese Retina Study Group. The retina.pt platform collects data on individuals diagnosed with retinal diseases, from several sites across Portugal, with over 1800 participants and over 30,000 consultations to date. The IRD-PT module interacts with the retina.pt core system which provides a range of basic functions for patient data management, while the IRD-PT module allows data capture for the specific purpose of IRDs. All IRDs are coded accordingly to the International Statistical Classification of Diseases and Related Health Problems (ICD) 9, ICD 10, ICD 11, and Orphanet Rare Disease Ontology (ORPHA codes) to make the IRD-PT interoperable with other IRD registries across the world. Furthermore, the genes are coded according to the Ontology of Genes and Genomes and Online Mendelian Inheritance in Man, whereas signs and symptoms are coded according to the Human Phenotype Ontology. The IRD-PT module pre-launched at Centro Hospitalar e Universitário de Coimbra, the largest reference center for IRDs in Portugal. As of April 1st 2020, finalized data from 537 participants were available for this preliminary analysis. CONCLUSIONS: In the specific field of rare diseases, the use of registries increases research accessibility for individuals, while providing clinicians/investigators with a coherent data ecosystem necessary to boost research. Appropriate design and implementation of patient registries enables rapid decision making and ongoing data mining, ultimately leading to improved patient outcomes. We have described here the principles behind the design, development and deployment of a web-based, user-friendly and interoperable software tool aimed to generate important knowledge and collecting high-quality data on the epidemiology, genomic landscape and natural history of IRDs in Portugal.
Humic-acid-driven escape from eye parasites revealed by RNA-seq and target-specific metabarcoding
Authors: Noreikiene Kristina , Ozerov Mikhail , Ahmad Freed , Kõiv Toomas , Kahar Siim , Gross Riho , Sepp Margot , Pellizzone Antonia , Vesterinen Eero J. , Kisand Veljo , Vasemägi Anti 
Published: July 2020

Abstract
Background Next generation sequencing (NGS) technologies are extensively used to dissect the molecular mechanisms of host-parasite interactions in human pathogens. However, ecological studies have yet to fully exploit the power of NGS as a rich source for formulating and testing new hypotheses. Methods We studied Eurasian perch (Perca fluviatilis) and its eye parasite (Trematoda, Diplostomidae) communities in fourteen lakes that differed in humic content in order to explore host-parasite-environment interactions. We hypothesised that high humic content along with low pH would decrease the abundance of the intermediate hosts (gastropods), thus limiting the occurrence of diplostomid parasites in humic lakes. This hypothesis was initially invoked by whole eye RNA-seq data analysis and subsequently tested using PCR-based detection and a novel targeted metabarcoding approach.Results Whole eye transcriptome results revealed over expression of immune-related genes and the presence of eye parasite sequences in RNA-seq data obtained from perch living in clear-water lakes. Both PCR-based and targeted-metabarcoding approach showed that perch from humic lakes were completely free from diplostomid parasites, while the prevalence of eye flukes in clear-water lakes that contain low amounts of humic substances was close to 100%, with the majority of NGS reads assigned to Tylodelphys clavata. Conclusions High intraspecific diversity of T. clavata indicates that massively parallel sequencing of naturally pooled samples represents an efficient and powerful strategy for shedding light on cryptic diversity of eye parasites. Our results demonstrate that perch populations in clear-water lakes experience contrasting eye parasite pressure compared to those from humic lakes, which is reflected by prevalent differences in the expression of immune-related genes in the eye. This study highlights the utility of NGS to discover novel host-parasite-environment interactions and provide unprecedented power to characterize the molecular diversity of cryptic parasites.
Quercetin attenuates the production of pro-inflammatory cytokines in H292 human lung epithelial cells infected with Pseudomonas aeruginosa, by modulating ExoS production
Authors: Ahn Hye In , Park Ji-Won , Jang Hyun-Jae , Kwon Ok-kyoung , Kim Jung Hee , Oh Sei-Ryang , Han Sang-Bae , Ahn Kyung-Seop 
Published: July 2020

Abstract
Background: The type three secretion system (T3SS) is a major virulence system of Pseudomonas aeruginosa (P. aeruginosa). The effector protein Exotoxin S (ExoS) produced by P. aeruginosa is secreted into the host cells via the T3SS. For the purpose of screening the inhibitors with regard to ExoS secretion, we developed the sandwich-type enzyme-linked immunosorbent assay (ELISA) system. From the initial screening, quercetin was selected because it has the prominent effect of ExoS inhibition and also is known to have anti-inflammatory and antioxidant effects on mammalian cells.Results: In this study, we investigated the effects of quercetin on the expression and secretion of ExoS using the ELISA and Western blot analysis methods. The results showed that the secretion of ExoS was significantly decreased by 10, 20uM quercetin. Also, pscF and popD, which are composed of the T3SS needle, are reduced by quercetin at the mRNA level, and we confirmed the inhibitory effect of quercetin on cytokines in P. aeruginosa-infected H292 cells by real-time polymerase chain reaction (PCR). Conclusion: Collectively, quercetin inhibits the secretion of ExoS by reducing both ExoS production and the expression of the needle protein of T3SS. Furthermore, these results suggest that quercetin has the potential to be used as an anti-toxic treatment for the disease caused by P. aeruginosa infection.
Atomic Ring Invariant and Modified CANON Extended Connectivity Algorithm for Symmetry Perception in Molecular Graphs and Rigorous Canonicalization of SMILES
Authors: Krotko Dmytro G. 
Published: July 2020

Abstract
We propose new invariant (the product of the corresponding primes for the ring size of each bond of an atom) as a simple unambiguous ring invariant of an atom that allows distinguishing symmetry classes in the highly symmetrical molecular graphs using traditional local and distance atom invariants. Also, we propose modifications of Weininger’s CANON algorithm to avoid its ambiguities (swapping and leveling ranks, incorrect determination of symmetry classes in non-aromatic annulenes, arbitrary selection of atom for breaking ties). The atomic ring invariant and the Modified CANON algorithm allow us to create a rigorous procedure for the generation of canonical SMILES which can be used for accurate and fast structural searching in large chemical databases.
Learning curve of trans-sacral epiduroscopic laser decompression in herniated lumbar disc disease
Authors: Son Seong , Yoo Chan Jong , Yoo Byung Rhae , Kim Woo Seok , Jeong Tae Seok 
Published: July 2020

Abstract
Background: Trans-sacral epiduroscopic laser decompression (SELD) using slender epiduroscope and a holmium YAG laser is one of the minimally invasive surgical options for lumbar disc herniation. However, the learning curve of SELD and the effect of surgical proficiency on clinical outcome have not yet been established. We investigated patients with lumbar disc herniation undergoing SELD to report the clinical outcome and learning curve. Methods: Retrospective analysis of clinical outcome and learning curve were performed at a single center from clinical data collected from November 2015 to November 2018. A total of 82 patients who underwent single-level SELD for lumbar disc herniation with a minimum follow-up of 6.0 months were enrolled. Based on the findings that the cut-off of familiarity was 20 cases according to the cumulative study of operation time, patients were allocated to two groups: early group (n = 20) and late group (n = 62). The surgical, clinical, and radiological outcomes were retrospectively evaluated between the two groups to analyze the learning curve of SELD.Results: According to linear and log regression analyses, the operation time was obtained by the formula: operation time = 58.825 - (0.181 × [case number]) (p < 0.001). The mean operation time was significantly different between the two groups (mean 56.95 minutes; 95% confidence interval [CI], 49.12–64.78 in the early group versus mean 45.34 minutes; 95% CI, 42.45–48.22 in the late group; p = 0.008, non-parametric Mann-Whitney U test).Baseline characteristics, including demographic data, clinical factors, and findings of preoperative magnetic resonance imaging, did not differ between the two groups. Also, there was no significant difference in terms of surgical outcomes, including complication and failure rates, as well as clinical and radiological outcomes between the two groups.Conclusion: The learning curve of SELD was not as steep as that of other minimally invasive spinal surgery techniques, and the experience of surgery was not an influencing factor for outcome variation.
EvoMol: a flexible and interpretable evolutionary algorithm for unbiased de novo molecular generation
Authors: Leguy Jules , Cauchy Thomas , Glavatskikh Marta , Duval Béatrice , Mota Benoit Da 
Published: July 2020

Abstract
The objective of this work is to design a molecular generator capable of exploring known as well as unfamiliar areas of the chemical space.

Our method must be flexible to adapt to very different problems. Therefore, it has to be able to work with or without the influence of prior data and knowledge. Moreover, regardless of the success, it should be as interpretable as possible to allow for diagnosis and improvement.

We propose here a new open source generation method using an evolutionary algorithm to sequentially build molecular graphs. It is independent of starting data and can generate totally unseen compounds. To be able to search a large part of the chemical space, we define an original set of 7 generic mutations close to the atomic level.

Our method achieves excellent performances and even records on the QED, penalised logP, SAscore, CLscore as well as the set of goal-directed functions defined in GuacaMol. To demonstrate its flexibility, we tackle a very different objective issued from the organic molecular materials domain. We show that EvoMol can generate sets of optimised molecules having high energy HOMO or low energy LUMO, starting only from methane. We can also set constraints on a synthesizability score and structural features. Finally, the interpretability of EvoMol allows for the visualisation of its exploration process as a chemically relevant tree.
Proteome-wide and lysine crotonylation profiling reveals the importance of crotonylation in chrysanthemum (Dendranthema grandiforum) under low-temperature
Authors: Lin Ping , Bai Hui-ru , He Ling , Huang Qiu-xiang , Zeng Qin-han , Pan Yuan-zhi , Jiang Bei-bei , Zhang Fan , Zhang Lei , Liu Qin-lin 
Published: July 2020

Abstract
Background: Low-temperature severely affects the growth and development of chrysanthemum which is one kind of ornamental plant well-known and widely used in the world. Lysine crotonylation is a recently identified post-translational modification (PTM) with multiple cellular functions. However, lysine crotonylation under low-temperature stress has not been studied. Results: Proteome-wide and lysine crotonylation of chrysanthemum at low temperature was analyzed using TMT labeling, sensitive immuno-precipitation, and high-resolution LC-MS/MS. The results showed that 2017 crotonylation sites were identified in 1199 proteins. Treatment at 4 °C for 24 h and −4 °C for 4 h resulted in 393 upregulated proteins and 500 downregulated proteins (1.2-fold threshold and P < 0.05). Analysis of biological information showed that lysine crotonylation was involved in photosynthesis, ribosomes, and antioxidant systems. The crotonylated proteins and motifs in chrysanthemum were compared with other plants to obtain orthologous proteins and conserved motifs. To further understand how lysine crotonylation at K136 affected APX (ascorbate eroxidase), we performed a site-directed mutation at K136 in APX. Site-directed crotonylation showed that lysine decrotonylation at K136 reduced APX activity, and lysine complete crotonylation at K136 increased APX activity. Conclusion: In summary, our study comparatively analyzed proteome-wide and crotonylation in chrysanthemum under low-temperature stress and provided insights into the mechanisms of crotonylation in positively regulated APX activity to reduce the oxidative damage caused by low-temperature stress. These data provided an important basis for studying crotonylation to regulate antioxidant enzyme activity in response to low-temperature stress and a new research ideas for chilling-tolerance and freezing-tolerance chrysanthemum molecular breeding.
Comprehensive molecular profiling of Taiwanese breast cancers revealed potential therapeutic targets: prevalence of actionable mutations among 380 targeted sequencing analyses
Authors: Huang Chi-Cheng , Tsai Yi-Fang , Liu Chun-Yu , Chao Ta-Chung , Lien Pei-Ju , Lin Yen-Shu , Feng Chin-Jung , Chiu Jen-Hwey , Hsu Chih-Yi , Tseng Ling-Ming 
Published: July 2020

Abstract
IntroductionBreast cancer is one of the leading causes of cancer-related deaths in women, and the annual incidence of breast cancer has continuously increased throughout the past two decades in Taiwan. There is a demand in developing an Asian-based genetic profiling database for breast cancer in improving the treatment response and recurrence rate. This study aimed to determine molecular alternations and identify potential therapeutic targets by analyzing the genetic profiling from a cohort of Taiwanese breast cancers using a commercialized next-generation sequencing (NGS) target panel.Materials and methodsThe study population comprised a broad spectrum of breast cancer patients in Taiwan, including Group 1: planned to receive first-line surgery and followed by adjuvant therapy, or early relapse within three years, Group 2: planned to receive first-line neoadjuvant therapy and followed by surgery, and Group 3: de novo stage IV, or stage IV with recurrence beyond three years. Molecular profiles were determined using Thermo FisherTM OncomineTM Comprehensive Assay version 3 (TMO comprehensive assay) from Formalin-Fixed Paraffin-Embedded (FFPE) tissues. Level of actionability was evaluated with the ESMO Scale of clinical actionability of molecular targets (ESCAT).Results.A total of 380 TMO comprehensive assays were conducted on 372 patients, and we presented targeted sequencing analyses of Tier I: alteration-drug match associated with improved outcome in clinical trials including ERBB2 amplification, BRCA1/2 germline mutation, PIK3CA mutation, and NTRK translocation, and Tier II: antitumor activity associated with the matched alteration-drug but lack of prospective outcome data including PTEN loss, ESR1 mutation, AKT1 mutation, and ERBB2 mutation, and Tier III: matched drug-alteration that led to clinical beneﬁt in another tumor type including MDM2 amplification, and ERBB3 mutation. Among them, 249 (66%) showed at least one actionable alternation based on the ESCAT criteria. The most frequent impacted genes were PIK3CA (38%), followed by ERBB2 (23%), ESR1 (10%), AKT1 (6%), and BRCA2 (5%), and the remaining rare variants (less than 5% of assayed cohort) were BRCA1 (3%), MDM2 (2.2%), and ERBB3 (1.1%).ConclusionTargeted sequencing of actionable genes is believed to provide clinical applicability and substantial benefits for Taiwanese breast cancer patients. A valid scale of clinical actionability should be adopted for precision medicine practice under multidisciplinary molecular tumor board.