bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diversity Oriented Deep Reinforcement Learning for Targeted Molecule Generation
Authors: Pereira Tiago , Abbasi Maryam , Ribeiro Bernardete , Arrais Joel P. 
Published: November 2020

Abstract
In this work, we explore the potential of deep learning to streamline the process of identifying new potential drugs through the computational generation of molecules with interesting biological properties. Two deep neural networks compose our targeted generation framework: the Generator, which is trained to learn the building rules of valid molecules employing SMILES strings notation, and the Predictor which evaluates the newly generated compounds by predicting their aﬃnity for the desired target. Then, the Generator is optimized through Reinforcement Learning to produce molecules with bespoken properties. The innovation of this approach is the exploratory strategy applied during the reinforcement training process that seeks to add novelty to the generated compounds. This training strategy employs two Generators interchangeably to sample new SMILES: the initially trained model that will remain ﬁxed and a copy of the previous one that will be updated during the training to uncover the most promising molecules. The evolution of the reward assigned by the Predictor determines how often each one is employed to select the next token of the molecule. This strategy establishes a compromise between the need to acquire more information about the chemical space and the need to sample new molecules, with the experience gained so far. To demonstrate the eﬀectiveness of the method, the Generator is trained to design molecules with high inhibitory power for the adenosine A2A and κ opioid receptors. The results reveal that the model can eﬀectively modify the biological aﬃnity of the newly generated molecules towards the craved direction. More importantly, it was possible to ﬁnd auspicious sets of unique and diverse molecules, which was the main purpose of the newly implemented strategy.
Regression Based Prediction of Minimental State Examination Score Using the Tablet Based Trail Making Test
Authors: Kubo Kouki , Hama Seiji , Furui Akira , Mizuguchi Tomohiko , Yanagawa Akiko , Kandori Akihiko , Sakai Hiroto , Morisako Yutaro , Orino Yuki , Hamai Maho , Fujita Kasumi , Yamawaki Shigeto , Tsuji Toshio 
Published: November 2020

Abstract
Trail making test (TMT) is one of the most extensively used neuropsychological tests. In this study, we examined the equivalence between the iPad version of TMT part A (iTMT-A) and the paper version of TMT part A (pTMT-A), and predicted the cognitive function with various data extracted from repeated TMT-A. Forty-two patients who performed five repeated TMT-A (1st–3rd: iTMT-A, 4th: pTMT-A, 5th: inverse version of iTMT-A) and Mini-Mental State Examination (MMSE) were included. The Kruskal–Wallis one-way analysis of variance revealed no statistical differences between the completion times of iTMT-A and pTMT-A. Factors contributing to the MMSE prediction were selected by stepwise multiple regression analysis and Bland–Altman plots. Then, the prediction abilities of the three models—multiple linear, partial least squares (PLS), and neural network regression—were compared. When using the completion time, the linear regression model with the 1st–5th results exhibited the highest prediction ability. However, when the move time and dwell time were used, the multiple linear and PLS regression models using the 1st and 2nd iTMT-A data exhibited the highest prediction ability. Compared with pTMT-A, iTMT-A extracted a large amount of data with fewer repetitions, and the prediction accuracy of cognitive function was improved.
Reliability of Urinary Charged Metabolite Concentrations in a Large-Scale Cohort Study Using Capillary Electrophoresis-Mass Spectrometry
Authors: Ishibashi Yoshiki , Harada Sei , Takeuchi Ayano , Iida Miho , Kurihara Ayako , Kato Suzuka , Kuwabara Kazuyo , Hirata Aya , Shibuki Takuma , Okamura Tomonori , Sugiyama Daisuke , Sato Asako , Amano Kaori , Hirayama Akiyoshi , Sugimoto Masahiro , Soga Tomoyoshi , Tomita Masaru , Takebayashi Toru 
Published: November 2020

Abstract
Currently, large-scale cohort studies for metabolome analysis have been launched globally. However, only a few studies have evaluated the reliability of urinary metabolome analysis. This study aimed to establish the reliability of urinary metabolomic profiling in cohort studies.In the Tsuruoka Metabolomics Cohort Study, 123 charged metabolites were identified and routinely quantified using capillary electrophoresis-mass spectrometry (CE-MS). We evaluated approximately 750 quality control (QC) samples and 6,720 participants’ spot urine samples. We calculated inter- and intra-batch coefficients of variation in the QC and participant samples and technical intraclass correlation coefficients (ICC). A correlation of metabolite concentrations between spot and 24-hour urine samples obtained from 32 sub-cohort participants was also evaluated. The coefficient of variation (CV) was less than 20% for 87 metabolites (70.7%) and 20–30% for 19 metabolites (15.4%) in the QC samples. There was less than 20% inter-batch CV for 106 metabolites (86.2%). The 96 metabolites (78.0%) was above 0.75 for the estimated ICC. Among individuals, the Pearson correlation coefficient of 24-hours and spot urine was more than 70% for 59 of the 99 metabolites. These results show that the profiling of charged metabolites using CE-MS in morning spot human urine is suitable for epidemiological studies.
Postoperative Pain After Cesarean Section at University of Gondar Comprehensive Specialized Hospital, Gondar, Northwest Ethiopia, 2019; a Cross-sectional Follow-Up Study
Authors: Woldegerima Yophtahe , Demelash Geta , Hailekiros Amare , Birlie Wubie 
Published: November 2020

Abstract
BackgroundCesarean section is one of the most common obstetric procedures worldwide. Following this, parturients experience moderate to severe pain in the acute postoperative period. Therefore, in resource-limited settings, for full utilization of basic analgesic modalities and to take appropriates interventions, it is vital to know about the magnitude of the problem and its factors.ObjectiveTo assess the prevalence and factors associated with postoperative pain after cesarean section at the University of Gondar Comprehensive Specialized Hospital (UoGCSH), Northwest Ethiopia, 2019.MethodsA hospital-based prospective follow-up study was conducted among parturients who undergo cesarean section in the University of Gondar Comprehensive Specialized Hospital, from mid-February to April 20, 2019, after approval of the ethical review committee. Consecutively, a total of 290 parturients were included with a response rate of 97%. To measure pain severity numerical rating scale was used. Data was entered into Epi-data version 4.2 and analyzed by SPSS version 20 (IBM Corporate). The association between independent factors and the outcome variable was determined at 95% CI with the chi-squared test, bivariate, and multivariate logistic regression. Hosmer-Lemeshow test was used to assess the goodness of fit. Variables with a p-value of < 0.05 were considered significant.ResultsIn this study, the incidence of moderate to severe post-operative pain after cesarean section was 85.5% (95% CI: 81.4%, 89.0%) within the first 24 postoperative hours. On the multi-variable analysis, preoperative anxiety (AOR: 2.3, 95% CI: 1.1, 4.9), history of previous cesarean section (AOR: 2.3, 95% CI: 1.1, 5.0), Pfannenstiel incision (AOR: 3.2, 95% CI: 1.3, 8.0) and absence of regional analgesia (AOR: 3.7, 95% CI: 1.7, 7.9) were significantly associated with moderate to severe postoperative pain after cesarean section.ConclusionsIn this study, a large proportion of parturients had experienced moderate to severe post-cesarean pain in the first 24 postoperative hours. Preoperative anxiety, history of previous cesarean section, Pfannenstiel incision, and parturients with no regional analgesia were significantly associated with post-cesarean pain. Pain severity needs to be assessed and documented by using pain-rating scales and there should be an interdisciplinary approach to provide adequate pain management in our hospital.
Influence of Weekday of Admission and Level of Distress on Length of Hospital Stay in Patients With Low Back Pain: A Retrospective Cohort Study
Authors: Brunner Emanuel , Meichtry André , Vancampfort Davy , Imoberdorf Reinhard , Gisi David , Dankaerts Wim , Graf Anita , Rebsamen Stefanie , Suter Daniela , Wildi Lukas , Buechi Stefan , Sieber Cornel 
Published: November 2020

Abstract
BackgroundLow back pain (LBP) is often a complex problem requiring interdisciplinary management to address patients’ multidimensional needs. The inpatient care for patients with LBP in primary care hospitals is a challenge. In this setting, interdisciplinary LBP management is often unavailable during the weekend. Delays in therapeutic procedures may result in prolonged length of hospital stay (LoS). The impact of delays on LoS might be strongest in patients reporting high levels of psychological distress. Therefore, this study investigates which influence the weekday of admission and distress have on LoS of inpatients with LBP.MethodsRetrospective cohort study conducted between 1 February 2019 and 31 January 2020. ANOVA was used to test the hypothesized difference in mean effects of the weekday of admission on LoS. Further, a linear model was fitted for LoS with distress, categorical weekday of admission (Friday/Saturday vs. Sunday-Thursday), and their interactions.ResultsWe identified 173 patients with LBP. Mean LoS was 7.8 days (SD=5.59). Patients admitted on Friday (mean LoS=10.3) and Saturday (LoS=10.6) had longer stays but not those admitted on Sunday (LoS=7.1). Analysis of the weekday effect (Friday/Saturday vs. Sunday-Thursday) showed that admission on Friday or Saturday was associated with significant increase in LoS compared to admission on other weekdays (t=3.43, p=<0.001). 101 patients (58%) returned questionnaires, and complete data on distress was available from 86 patients (49%). According to a linear model for LoS, the effect of distress on LoS was significantly modified (t=2.51, p=0.014) by dichotomic weekdays of admission (Friday/Saturday vs. Sunday-Thursday).ConclusionsPatients with LBP are hospitalized significantly longer if they have to wait more than two days for interdisciplinary LBP management. This particularly affects patients reporting high distress. Our study provides a platform to further explore whether interdisciplinary LBP management addressing patients’ multidimensional needs reduces LoS in primary care hospitals.
Improving Soybean Production Under Light Supplementation at Field - A Case Study
Authors: Lemes Ernane , Azevedo Breno , Domiciano Matheus , Andrade Samuel 
Published: November 2020

Abstract
In modern agriculture, there is a growing need for cropping efficiency e low environmental impacts. Diverse technologies are becoming available in a recent wave of modernization and integration of knowledge. The use of high-efficiency light supplementation to plant development is scarce to high-productive crops at field conditions (outdoor). The objectives of this study were to evaluate soybean plant and yield responses in an open commercial area (field scale) cultivated with artificial light supplementation. A commercial irrigated (pivot) area received an illumination system for light supplementation (LS) in the inner pivot spans. The light applied was a composition of blue, green and red bands. The outer pivot spans did not receive light supplementation (nLS). About 40 hours of LS were applied to the plants during the soybean crop cycle. Internode number, plant height, pods per plant were weekly evaluated to compose the area under the progress curve (AUPC). The grain yield was also evaluated at harvest. Analysis of variance and test of averages were used to evaluate the data. The AUPC of the internode number, plant height and pods per plant were 15.6, 23.3 and 25.3% higher than for the LS treatment. The regular soybean cycle (nLS) was about 17 weeks; however, the harvest of the LS treatment happened three weeks later. The grain productivity of the nLS was about 4,500 kg ha-1 (75 bags), and of the LS treatment was about 7,080 kg ha-1 (118 bags) - 57.3% superior. Light supplementation at field scale is a challenge; however, affordable and field resistant technologies are now accessible. The present study is the first report of light supplementation used to improve soybean crop production at field scale. The possibility of using light regulation as an additional technique for increasing yields and sustainable production are also discussed.
Development of a Clinical Tool for Rating the Body Function Categories of the ICF Generic-30/Rehabilitation Set in Japanese Rehabilitation Practice, and Examination of its Interrater Reliability
Authors: Senju Yuki , Mukaino Masahiko , Prodinger Birgit , Selb Melissa , Okouchi Yuki , Mizutani Kouji , Suzuki Megumi , Yamada Shin , Izumi Shin-Ichi , Sonoda Shigeru , Otaka Yohei , Saitoh Eiichi , Stucki Gerold 
Published: November 2020

Abstract
BackgroundThe International Classification of Functioning, Disability, and Health (ICF) Generic-30 (Rehabilitation) Set is a tool for assessing the functioning of a clinical population in rehabilitation. The ICF Generic-30 consists of 9 ICF categories from the component “body functions” and 21 from the component “activities and participation”. This study aimed to develop a rating reference guide for the 9 body function categories of the ICF Generic-30 Set using a predefined, structured process and to examine the interrater reliability of the ratings using the rating reference guide.MethodsThe development of the first version of the rating reference guide involved the following steps: (1) A trial of rating patients by several raters; (2) cognitive interviews with each rater to analyze the thought process involved in each rating; (3) the drafting of the rating reference guide by a multidisciplinary panel; and (4) a review by ICF specialists to confirm consistency with the ICF. Subsequently, we conducted a first field test to gain insight on the use of the guide in practice. The reference guide was modified based on the raters’ feedback in the field test, and an interrater reliability test was conducted thereafter. Interrater agreement was evaluated using weighted kappa statistics with linear weights.ResultsThe first version of the rating reference guide was successfully developed and field tested. The weighted kappa coefficient in the field testing ranged from 0.25 to 0.92. The interrater reliability testing of the rating reference guide modified based on the field test results yielded an improved weighted kappa coefficient ranging from 0.54 to 0.85. ConclusionsIn this study, we developed and modified a rating reference guide for the body function categories of the ICF Generic-30 Set. The interrater reliability test using the final version of the rating reference guide showed moderate to excellent interrater agreement, which encourages the use of the ICF in rehabilitation practice.Trial registrationNot applicable.
Multi-Dimensional Optimization of In0.53Ga0.47As Thermophotovoltaic Cell using Real Coded Genetic Algorithm
Authors: Gamel Mansur , Ker Pin Jern , Lee Hui Jing , Rashid Wan Emilin Suliza Wan Abdul , Hannan M.A. , David John , Jamaludin Md Zaini 
Published: November 2020

Abstract
The optimization of thermophotovoltaic (TPV) cell efficiency is essential since it leads to a significant increase in the output power. Typically, the optimization of In0.53Ga0.47As TPV cell has been limited to single variable such as the emitter thickness, while the effects of the variation in other design variables are assumed to be negligible. The reported efficiencies of In0.53Ga0.47As TPV cell mostly remain < 15%. Therefore, this work develops a multi-variable or multi-dimensional optimization of In0.53Ga0.47As TPV cell using the real coded genetic algorithm (RCGA) under various radiation temperatures. RCGA was developed using Visual Basic and it was hybridized with Silvaco TCAD for the electrical characteristics simulation. Under radiation temperatures from 800 K to 2000 K, the optimized In0.53Ga0.47As TPV cell efficiency increases by an average percentage of 11.86% (from 8.5% to 20.35%) as compared to the non-optimized structure. It was found that the incorporation of a thicker base layer with the back-barrier layers enhances the separation of charge carriers and increases the collection of photo-generated carriers near the band-edge, producing an optimum output power of 0.55 W/cm2 (cell efficiency of 22.06%, without antireflection coating) at 1400 K radiation spectrum. The results of this work demonstrate the great potential to generate electricity sustainably from industrial waste heat and the multi-dimensional optimization methodology can be adopted to optimize semiconductor devices, such as solar cell, TPV cell and photodetectors.
Early detection of drug-resistant Streptococcus pneumoniae and Haemophilus influenzae by quantitative flow cytometry
Authors: Sawada Takahiro , Katayama Masayuki , Takatani Shogo , Ohiro Yoshiyuki 
Published: November 2020

Abstract
Early detection of drug resistance contributes to combating drug-resistant bacteria and improving patient outcomes. Microbial testing in the laboratory is essential for treating infectious diseases because it can provide critical information related to identifying pathogenic bacteria and their resistance profiles. Despite these clinical requirements, conventional phenotypic testing is time-consuming. In addition, recent rapid drug resistance tests are not compatible with fastidious bacteria such as Streptococcus and Haemophilus species.In this study, we validated the feasibility of direct bacteria counting using highly sensitive quantitative flow cytometry. Furthermore, by combining flow cytometry and a nucleic acid intercalator, we constructed a highly sensitive method for counting viable fastidious bacteria. These are inherently difficult to measure due to interfering substances from nutrients contained in the medium. Based on the conventional broth microdilution method, our method acquired a few microliter samples in a time series from the same microplate well to exclude the growth curve inconsistency between the samples. Fluorescent staining and FCM measurements were completed within 10 minutes. Therefore, this approach enabled us to determine antimicrobial resistance for these bacteria within a few hours. Highly sensitive quantitative flow cytometry presents a novel avenue for conducting rapid antimicrobial susceptibility tests.
Microstructured Collagen Films for 3D Corneal Stroma Modelling
Authors: Prittinen Juha , Zhou Xin , Backman Ludvig , Danielson Patrik 
Published: November 2020

Abstract
Corneal injury is a major cause for impaired vision around the globe. The fine structure of the corneal stroma plays a pivotal role in the phenotype and behaviour of the embedded cells during homeostasis and healing after trauma or infection. In order to study healing processes in the cornea, it is important to create culture systems that functionally mimic the natural environment as well as possible. In this study, we aimed to create a microstructured collagen film-based culture system that guides keratocytes (stromal cells) to their native, layerwise perpendicular orientation in 3D. By casting a micropattern (1,000 grooves/mm) on collagen vitrigels, we were able to make thin and transparent films that align cells along the grooves. The films provide an easily reproducible stroma model that maintains high cell viability and improves the preservation of the keratocyte phenotype in keratocytes that were subjected to fibroblast differentiation.
LEDGF/p75 is Required for an Efficient DNA Damage Response
Authors: Liedtke Victoria , Schröder Christian , Roggenbuck Dirk , Weiss Romano , Stohwasser Ralf , Schierack Peter , Rödiger Stefan , Schenk Lysann 
Published: November 2020

Abstract

BackgroundLens epithelium derived growth factor splice variant of 75 kDa (LEDGF/p75), is overexpressed in different solid cancers and cancer cell lines and various autoinflammatory diseases. Due to its ability to bind chromatin, it acts as a transcriptional co-activator and promotes anti-apoptotic signalling pathways that lead to increased tumour aggressiveness and resistance to chemotherapy. The role of LEDGF/p75 in DNA-damage repair (DDR) is still not completely elucidated particularly regarding the ubiquitin-dependent regulation and degradation of DDR signalling molecules.MethodsDifferent LEDGF model cell lines were generated, a complete knock-out of LEDGF (KO) as well as the re-expression of LEDGF/p75 or LEDGF/p52 using CRISPR/Cas9 technology. Then, various assays were performed to determine their proliferation and migration capacity as well as their chemosensitivity. Moreover, DDR signalling pathways were investigated by western blot and immunofluorescence.ResultsLEDGF-deficient cells exhibited a decreased proliferation (dt (WT) = 21 h, dt (KO) = 26 h) , 60 % decreased migration, as well as an 30-50 % increased sensitivity towards the topoisomerase II inhibitor etoposide. Moreover, LEDGF depleted cells showed a significant reduction by 65 % in the recruitment of downstream DDR-related proteins like replication protein A 32 kDa subunit (RPA32) after exposure to etoposide. Re-expression of LEDGF/p75 rescued all knock-out effects, while re-expression of LEDGF/p52 had no effect.Surprisingly, untreated LEDGF KO cells showed an increased amount of DNA fragmentation combined with an increased formation of γH2AX and Breast cancer type 1 susceptibility protein (BRCA1). In contrast, the protein levels of ubiquitin-conjugating enzyme UBC13 and nuclear proteasome activator PA28γ were substantially reduced upon LEDGF KO. ConclusionsThis study provides evidence that LEDGF is not only an important player in the DDR after chemotherapeutic treatments but is also involved in the maintenance of the general genome integrity. Moreover, this study provides for the first time an insight into the possible role of LEDGF in the ubiquitin-dependent regulation of DDR signalling molecules and highlights the involvement of LEDGF/p75 in homology-directed DNA repair.