bluuebunny/crossref_metadata_2025 huggingface dataset:
Authorship diversity among systematic reviews in eyes and vision
Authors: Qureshi Riaz , Han Genie , Fapohunda Kolade , Abariga Samuel , Wilson Renee , Li Tianjing
Published: July 2020

Importance: The inclusion of authors from diverse backgrounds and with different lived experiences is critical to ensuring the questions addressed in systematic reviews (SRs), as well as the subsequent conclusions and recommendations made, are representative of the global community.Objective: To assess the gender and geographic diversity of authors among all Cochrane SRs in eyes and vision as compared with a random sample of non-Cochrane SRs of interventions in the field of eyes and vision.Design: The Cochrane Eyes and Vision United States Satellite maintains a database of SRs in the field of eyes and vision. We selected all (n = 313) eyes and vision intervention SRs published in The Cochrane Library and a random sample of 313 eyes and vision intervention SRs published elsewhere for this study. We determined gender of the first and corresponding authors (‘woman,’ ‘man,’ or ‘unknown’) using a previously developed algorithm and their location based on institution country and the World Health Organization region. Results: From the 626 reviews included in our sample, we identified 751 unique authors who comprised 887 author positions (i.e., first and/or corresponding authors). We were able to ascertain the gender of 647/751 (86%) authors: 276 women, and 371 men. Among Cochrane eyes and vision SRs, the proportions of women in first and/or corresponding author positions were consistent and approximately equal to men. Among non-Cochrane eyes and vision SRs, the representation of women was markedly lower as corresponding authors than other positions. Most authors of Cochrane eyes and vision SRs were from the United Kingdom (31%) and United States of America (26%), whereas most authors of non-Cochrane SRs were from China (34%). Conclusions and relevance: Compared with authors of non-Cochrane SRs in eyes and vision, authors of Cochrane SRs appear to have approximately equal representation of women and men among perceived important author positions and be located in European and North American countries, possibly due to the locations of the Cochrane editorial teams. Cochrane Eyes and Vision should continue to recruit authors from around the world in locations that reflect the global burden of eye disease.
Implementation and adherence to the Bedside Paediatric Early Warning System (BedsidePEWS) in a pediatric tertiary care hospital
Authors: Gawronski Orsola , Ferro Federico , Cecchetti Corrado , Atti Marta Luisa Ciofi Degli , Dall'oglio Immacolata , Tiozzo Emanuela , Raponi Massimiliano
Published: July 2020

Background Escalation of care in deteriorating children admitted to hospital wards in relation to pediatric early warning scores has been rarely reported. The aim of this study is to examine adherence to the vital signs and BedsidePEWS escalation protocol at a large tertiary care children’s hospital.Methods This is a prospective observational study. A 6-month audit on adherence to BedsidePEWS was performed on the wards in 2018. Data on the frequency and accuracy of BedsidePEWS score calculations, escalation of patient observations, monitoring and medical reviews were recorded.Two research nurses performed weekly visits to the hospital wards to collect data on BedsidePEWS scores, medical reviews, type of monitoring and vital signs recorded. Data were described through means or medians according to the distribution. Inferences were calculated either with Chi-square, Student’s t test or Wilcoxon-Mann–Whitney test, as appropriate (P <0.05 considered as significant).Results A total of 522 Vital Signs (VS) and score calculations on 177 patient clinical records were observed from 13 hospital inpatient wards. Frequency of VS and score documentation occurred <3 times per day in 33% of the observations. Adherence to the VS documentation frequency according to the hospital protocol was observed in 54% for all patients; for children with chronic health conditions (CHC) it was significantly lower than children admitted for acute medical conditions (47%, P=0.006). The BedsidePEWS score was correctly calculated and documented in 84%, systolic blood pressure was recorded in 79% and temperature in 91% of the VS recording events. Patients within a 0-2 BedsidePEWS score range were all reviewed at least once a day by a physician. Only 50% of the patients in the 5-6 score range were reviewed within 4 hours and 42% of the patients with a score ≥7 within 2 hours. Transcutaneous Oxygen Saturation continuous monitoring was applied to 60% of the children at higher risk (BedsidePEWS ≥5).Conclusions Escalation of patient observations, monitoring and medical reviews matching the BedsidePEWS is still suboptimal. Children with CHC are at higher risk of lower compliance. Impact of adherence to predefined response algorithms on patient outcomes should be further explored.
Illuminating the dark side of the human transcriptome with long read transcript sequencing
Authors: Kuo Richard , Cheng Yuanyuan , Zhang Runxuan , Brown John W.S. , Smith Jacqueline , Archibald Alan L. , Burt Dave W.
Published: July 2020

Background: The human transcriptome annotation is regarded as one of the most complete of any eukaryotic species. However, limitations in sequencing technologies have biased the annotation toward multi-exonic protein coding genes. Accurate high-throughput long read transcript sequencing can now provide stronger evidence for rare transcripts and genes such as mono-exonic and non-coding genes that were previously either undetectable or impossible to differentiate from sequencing noise. Results: We developed the Transcriptome Annotation by Modular Algorithms (TAMA) software to leverage the power of long read transcript sequencing and address the issues with current data processing pipelines. TAMA achieved high sensitivity and precision for gene and transcript model predictions in both reference guided and unguided approaches in our benchmark tests using simulated Pacific Biosciences (PacBio) and Nanopore sequencing data and real PacBio datasets. By analyzing PacBio Sequel II Iso-Seq sequencing data of the Universal Human Reference RNA (UHRR) using TAMA and other commonly used pipelines, we found that the convention of using mapping identity to measure error correction performance does not reflect actual gain in accuracy of predicted transcript models. In addition, inter-read error correction can cause major changes to read mapping, resulting in potentially over 6K erroneous gene model predictions in the Iso-Seq based human genome annotation. Using TAMA’s genome assembly based error correction and gene feature evidence, we identified 2,566 putative novel non-coding genes and 1,557 putative novel protein coding gene models.Conclusions: Long read transcript sequencing data has the power to identify novel genes within the highly annotated human genome. The use of parameter tuning and extensive output information of the TAMA software package allows for in depth exploration of eukaryotic transcriptomes. We have found long read data based evidence for thousands of unannotated genes within the human genome. More development in sequencing library preparation and data processing are required for differentiating sequencing noise from real genes in long read RNA sequencing data.
Improving the production of AHL lactonase AiiO-AIO6 from Ochrobactrum sp. M231 in intracellular protease-deficientBacillus subtilis
Authors: Xia Rui , Yang Yalin , Pan Xingliang , Gao Chenchen , Yao Yuanyuan , Liu Xuewei , Teame Tsegay , Zhang Fengli , Hu Juan , Ran Chao , Zhang Zhen , Liu-Clarke Jihong , Zhou Zhigang
Published: July 2020

Quorum quenching (QQ) blocks bacterial cell-to-cell communication (i.e., quorum sensing), and is a promising antipathogenic strategy to control bacterial infection via inhibition of virulence factor expression and biofilm formation. QQ enzyme AiiO-AIO6 from Ochrobactrum sp. M231 has several excellent properties and shows biotherapeutic potential against important bacterial pathogens of aquatic species. AiiO-AIO6 can be secretory expressed in Bacillus subtilis via a non-classical secretion pathway.To improve AiiO-AIO6 production, four intracellular protease-deletion mutants of B. subtilis1A751 were constructed by individually knocking out the intracellular protease-encoding genes (tepA, ymfH, yrrNandywpE). The AiiO-AIO6 expression plasmid pWB-AIO6BS was transformed into the B. subtilis 1A751 and its four intracellular protease-deletion derivatives. Results showed that all recombinant intracellular protease-deletion derivatives (BSΔtepA, BSΔymfH, BSΔyrrNand BSΔywpE) had a positive impact on AiiO-AIO6 production. The highest amount of AiiO-AIO6 extracellular production of BSΔywpE in shake flask reached 1416.47 U/mL/OD600, which was about 121% higher than that of the wild-type strain. Furthermore, LC-MS/MS analysis of the degrading products of 3-oxo-C8-HSL by purification of AiiO-AIO6 indicated that AiiO-AIO6 was an AHL-lactonase which hydrolyzes the lactone ring of AHLs. Phylogenetic analysis showed that AiiO-AIO6was classified as a member of the α/β hydrolase family with a conserved “nucleophile-acid-histidine” catalytic triad. In summary, this study showed that intracellular proteases were responsible for the reduced yields of heterologous proteins and provided an efficient strategy to enhance the extracellular production of AHL lactonase AiiO-AIO6.
Efficacy of Acupuncture for Sciatica: Study Protocol for A Randomized Controlled Pilot Trial.
Authors: Yu Fang-Ting , Ni Guang-Xia , Liu Zhi-Shun , Meng Xiu-Li , Li Jin-Ling , Tu Jian-Feng , Wang Li-Qiong , Yang Jing-Wen , Fu Hai-Yang , Zhang Xin-Chang , Zhang Xiao-Hui , Zhang Hao-Lin , Shi Guang-Xia , Liu Cun-Zhi
Published: July 2020

Background: Acupuncture is widely used for pain diseases while evidence of its efficacy for sciatica is insufficient. This pilot study aims to investigate the feasibility and efficacy of acupuncture for sciatica induced by lumbar disc herniation. Methods: This is a multicenter, three-arm, patient-assessor-blinded randomized controlled pilot trial. 90 patients will be assigned randomly into 3 groups including disease-affected meridians (DAM) group, non-affected meridians (NAM) group, and sham acupuncture (SA) group in a 1:1:1 ratio. The trial involves a 4-week treatment along with follow-up for 22 weeks. The primary outcome is the change of leg pain intensity measured by the Visual-Analogue Scale (VAS) from baseline to week 4 after randomization. Secondary outcomes include functional status, back pain intensity, and quality of life. Adverse events will also be recorded.Discussion: This pilot study will investigate the feasibility and efficacy of acupuncture for patients with sciatica. The results of the study will help improve a better design and establish a power calculation for a full-scale study.Trial registration: ChiCTR2000030680 (Chinese Clinical Trial Registry, http://www.chictr.org.cn, registered on 9th March 2020).
Examining the effector mechanisms of Xuebijing Injection on COVID-19 based on network pharmacology.
Authors: Zheng Wenjiang , Yan Qian , Ni Yongshi , Zhan Shaofeng , Yang Liuliu , Zhuang Hongfa , Liu Xiaohong , Jiang Yong
Published: July 2020

Objective: To examine the potential effector mechanisms of Xuebijing (XBJ) on coronavirus disease 2019 (COVID-19) based on network pharmacology.Methods: We searched Chinese and international papers to obtain the active ingredients of XBJ. Then, we compiled COVID-19 disease targets from the GeneCards gene database and via literature searches. Next, we used the SwissTargetPrediction database to predict XBJ’s effector targets and map them to the abovementioned COVID-19 disease targets in order to obtain potential therapeutic targets of XBJ. Cytoscape software version 3.7.0 was used to construct a “XBJ active-compound-potential-effector target” network and protein-protein interaction (PPI) network, and then to carry out network topology analysis of potential targets. We used the ClueGO and CluePedia plugins in Cytoscape to conduct gene ontology (GO) biological process (BP) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis of XBJ’s effector targets. Results: We obtained 144 potential COVID-19 effector targets of XBJ. Fourteen of these targets—glyceraldehyde 3-phosphate dehydrogenase (GAPDH), albumin (ALB), tumor necrosis factor (TNF), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 1 (MAPK1), Caspase-3 (CASP3), signal transducer and activator of transcription 3 (STAT3), MAPK8, prostaglandin-endoperoxide synthase 2 (PTGS2), JUN, interleukin-2 (IL-2), estrogen receptor 1 (ESR1), and MAPK14—had degree values >40 and therefore could be considered key targets. They participated in extracellular signal–regulated kinase 1 and 2 (ERK1, ERK2) cascade, the T-cell receptor signaling pathway, activation of MAPK activity, cellular response to lipopolysaccharide, and other inflammation- and immune-related BPs. XBJ exerted its therapeutic effects through the renin–angiotensin system (RAS), nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), MAPK, phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K)–protein kinase B (Akt)–vascular endothelial growth factor (VEGF), toll-like receptor (TLR), TNF, and inflammatory-mediator regulation of transient receptor potential (TRP) signaling pathways to ultimately construct a “ingredient-target-pathway” effector network. Conclusion: The active ingredients of XBJ regulated different genes, acted on different pathways, and synergistically produced anti-inflammatory and immune-regulatory effects, which fully demonstrated the synergistic effects of different components on multiple targets and pathways. Our study demonstrated that existing studies on the pharmacological mechanisms of XBJ in the treatment of sepsis and severe pneumonia, could explain the effector mechanism of XBJ in COVID-19 treatment, and those provided a preliminary examination of the potential effector mechanism in this disease.
Value of artificial ascites to assist thermal ablation of liver cancer adjacent to the gastrointestinal tract in patients with previous abdominal surgery
Authors: Huang Qiannan , Li Jianguo , Zeng Qingjing , Tan Lei , Zheng Rongqin , He Xuqi , Li Kai
Published: July 2020

Background

To evaluate the feasibility and effectiveness of artificial ascites to assist thermal ablation of liver cancer adjacent to the gastrointestinal tract in patients with previous abdominal surgery.

Methods

Thirty-nine patients with a total of 40 liver malignant tumors were enrolled between January 2016 and June 2019. All had histories of hepatectomy, splenectomy, cholecystectomy, and intestinal surgery. The distance between the tumor and the gastrointestinal tract was < 5 mm. Normal saline was used as artificial ascites to protect the gastrointestinal tract during thermal ablation. The success rate of the procedure, incidence of major complications, and the technical efficacy of ablation were recorded. Patients were followed for local tumor progression (LTP), and overall survival (OS).

Results

The use of artificial ascites was successful in 38 of the 40 procedures (95%). Major complications occurred in two of the 39 patients (5.1%) following the procedure. One was an intestinal fistula that occurred in a failed case and was associated with an infection. The other was a liver abscess that occurred in a successful case. The technical efficacy of ablation was 100% (40/40 procedures). The median follow-up was 20 months. The 1-, 2-, and 3-year LTP rates were 2.9%, 5.7% and 5.7%. The 1-, 2-, and 3-year OS rates were 97.1%, 86.8% and 69.5%.

Conclusion

In patients with previous abdominal surgery, artificial ascites is feasible and effective for assisting thermal ablation of liver cancer adjacent to the gastrointestinal tract.
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

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

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

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

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

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

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

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

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

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

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.
COVID-19 and Cancer: A Comparative Case Series
Authors: Mousavi seied Asadollah , Rostami Tahereh , kiumarsi Azadeh , Rad soroush , Rostami mohammadreza , Motamedi Fatemeh , Gandomi-Mohammadabadi Alireza , Mirhosseini Amirhossein
Published: July 2020

BackgroundCancer patients, with an incidence of more than 18 million new cases per year, may constitute a significant portion of the COVID-19 infected population. In the pandemic situation, these patients are considered highly vulnerable to infectious complications due to their immunocompromised state.Material & MethodsIn this retrospective case series, the documents of solid cancer patients infected by SARS-CoV-2, hospitalized in Shariati hospital (a tertiary care referral center designated for COVID-19 patients, affiliated by Tehran University of Medical Sciences) between 20 February and 20 April 2020, were evaluated. The diagnosis of COVID-19 was based on a positive real-time fluorescence reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 nucleic acids from nasal and/or pharyngeal specimens and/or features of chest CT scan highly suggestive for SARS-CoV-2.ResultsAmong 33 patients with solid cancer, 11 patients had a positive RT-PCR for SARS-CoV-2 and 22 patients had highly suggestive chest CT scan findings in favor of SARS-CoV-2 but negative RT-PCR . The mean age of the patients was 63.9 years, and 54.5% of the patients were males. Age and sex of the patients did not correlate with mortality. There was no difference in COVID-19 symptoms, lymphocytopenia, thrombocytopenia between survived and un-survived cancer patients. However, LDH level was significantly higher (7170±2077 vs. 932.3±324.7, P-value=0.016) and also serum albumin was significantly lower in un-survived group (3.6±0.5 vs. 2.9±0.6 p-value=0.03). Among 16 patients with stage IV cancer, thirteen patients died, which was significantly higher compared to stage I-III cancer patients (81.3% vs. 18.8% P-value= <0.001). In terms of developing complications, sepsis, invasive ventilation and mortality was significantly higher in patients who received cytotoxic chemotherapy within the last 14 days. There was no significant difference between the two groups of positive and negative SARS-CoV-2 RT-PCR regarding their sex, age, cancer type, mean Hemoglobin concentration, Platelet count, lymphocyte count, serum albumin level, ESR and CRP titer or other laboratory findings and also in terms of clinical symptoms and coexisting.ConclusionIn this study, we showed that the mortality rate among cancer patients affected by COVID-19 was higher than general population and this rate has a significant correlation with factors such as the stage of the disease, the type of cancer, the activity of cancer and finally receiving cytotoxic chemotherapy within 14 days before diagnosis of COVID-19. We also showed that the outcome of cancer patients with positive RT-PCR for COVID-19 similar to those with negative RT-PCR with highly suggestive chest CT scan findings.
Targeted imaging of esophageal adenocarcinoma with a near-infrared fluorescent peptide
Authors: Kang Xiaoyu , Li Meng , Liu Lei , Liu Shaopeng , Hu Hao , Zhang Rui , Ning Siming , Tian Zuhong , Pan Yanglin , Guo Xuegang , Wu Kaichun
Published: July 2020

Backgroud:
Targeted optical imaging offers a noninvasive and accurate method for the early detection of gastrointestinal tumors, especially for flat appearances. In our previous study, a sequence of SNFYMPL (SNF) was identified as a specific peptide to bind to esophageal carcinoma using phage-display technology. This study aimed to evaluate the tumor-targeting efficacy of Cy5.5-conjugated SNF probe for imaging of esophageal carcinoma in vitro and in vivo.
Methods
The SNF-Cy5.5 probe was synthesized and then identified using High Performance Liquid Chromatography (HPLC) and mass spectrometry (MS). Confocal fluorescence imaging and Flow cytometry analysis were performed to evaluate the binding specificity and the receptor binding affinity of SNF-Cy5.5 to OE33. In vivo imaging was performed to evaluate the targeting ability of SNF-Cy5.5 to esophageal carcinoma.
Results
The confocal imaging and flow cytometry analysis showed that SNF-Cy5.5 bound specifically to the plasma membrane of OE33 cells with a high affinity. In vivo, for non-block group, SNF-Cy5.5 probe exhibited rapid OE33 tumor targeting during 24 h p.i. and excellent tumor-to-background contrast at 2 h p.i. For the block group, SNF-Cy5.5 was not observed in the mice after 4 h p.i. Ex vivo imaging also revealed that a higher fluorescent signal intensity value of the tumors was clearly observed in the non-block group than that in the block group (2.6 ± 0.32 × 109 vs 0.8 ± 0.08 × 109, p < 0.05).
Conclusions
SNF -Cy5.5 was synthesized and characterized with a high efficiency and purity. The higher affinity, specificity, and tumor targeting efficacy of SNF-Cy5.5 were confirmed by in vitro and in vivo tests. SNF-Cy5.5 is a promising optical probe for the imaging of esophageal adenocarcinoma.
Prevalence of Orthorexia Nervosa Among Nutrition Students and Nutritionists in Jordan: Pilot Study
Authors: ABDULLAH Mai Adnan , Al-Hourani Huda Mustafa , Alkhatib Buthaina
Published: July 2020

Objective: Orthorexia Nervosa (ON) is defined as an excessive concern in choosing and preparing of meals according to strict rules. The aim of this study was evaluating the threat of orthorexia in a group of students and nutritionists and the tendency toward the presentation of ON behaviorMethods: This cross-sectional study was carried out in July and August of 2019 among 421 nutrition students from six universities, in addition to nutritionists in Jordan. Participants completed questionnaire related to individual characteristics and the ORTO-15 scale. Orthorexia Nervosa (ON) tendency was measured using ORTO-15 questionnaire, referring to different diagnostic thresholds (40/35). P<0.05 was accepted as statistically significant.Results: Orthorexia had 72.0% prevalence in our sample using the 40-point threshold; the figure was reasonably lower with the 35-point threshold (31.8%). Also, ON tendency was significantly affected by BMI categories (p=0.007) and gender (p=0.043) at 35-point threshold. Males have more tendency (39.4%) than females (28.6%) (p=0.029)Conclusion: The results of this study highlight the magnitude of ON in Jordan. Using cut-off at 35 is preferable than cut-off at 40 to identify factors influencing ON. Moreover, ON tendency is affected by gender and BMI and not affected by educational level.
Clinical and Epidemiological Characteristics and Outcome of Patients With Covid-19 in Sri Lanka; An Observational Study
Authors: Herath Meththananda , thusharika Jayasekera Madduma Mudiyanselage Priyamali , Kumari Pathirage Loku pathirage Manoji Muditha , Acharige Thushan Amila Wijesinghe Wedikkula , Gunananthan karthick , June Bernard Pingamagae Don , Hettiarachchi Nirosha Madhuwanthi , Dona Thushari Dilrukshi Kaluthantrige , Mudiyanselage Piyarathne Lasantha Roshan Samarakoon Pathirana , Senevirathne Nuwan Bhathiya , Bhishman Sivajini , Jayawardhana Asanka Gunaseela Jayawardana Kankanamage Aruna , arachchige Harsha Priya Sanjeewa Weerasinghe , Balasooriya Priyantha , Thushanthy Prasath , Senarathna Ganaka , Jayasekera Krishantha , Ponnuthurai Sutharshan , Manilgama Suranga Ravinda , Jayasinghe Inoka Kumudini , Jayalath Thilak Widana Arachchilage Ananda , Selladurai Pirasath
Published: July 2020

Background

Clinical manifestations of coronavirus disease 2019 (COVID19) can vary from asymptomatic to profusely symptomatic due to many factors. Having data on the clinical characteristics of the affected patients is important for the screening and diagnosis of COVID-19. Main objective of this study is to evaluate the clinical and epidemiological characteristics and outcomes of patients with COVID-19 admitted to six treatment centres in Sri Lanka.
Methods

For the specific epidemic situation of COVID-19, we chose to conduct a descriptive retrospective study from six treatment centres in the country between March 10, 2020 and May 30, 2020.
Results

The study included 431 laboratory confirmed patients with COVID-19. Of them, 335 (78.2%) were males and their mean age was 37 years. Most patients (373: 86.5%) had had close contact with COVID-19 positive patients. The majority were asymptomatic (243: 56.3%) and of the symptomatic patients, the most common symptom was sore throat (81, 19%), followed by cough (72, 17%), headache (72, 17%), fever (50, 12%), and nasal discharge (36, 8%). Eight patients required either high dependency care or intensive unit care two of them succumbed to the illness (0.5%). Hydroxychloroquine (HCQ) was used as a treatment in 248 patients and they had a significantly longer (17.6 days) duration of hospital stays compared those who were not treated (13.6 days) with HCQ. When the HCQ was not used as a treatment, asymptomatic individuals had significantly shorter durations of hospital (11.1 days) stays compared to symptomatic individuals (14.3 days).
Conclusions

The majority of patients remained asymptomatic during the course of illness. The most common symptom was sore throat, seen in one fifth of patients, followed by cough, and headache. Our study also indicated the possibility of reduced viral clearance and hence longer duration of hospital stays with HCQ.