bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemotherapy-induced CDA expression renders resistant non-small cell lung cancer cells sensitive to 5′-deoxy-5-fluorocytidine (5′-DFCR)
Authors: Gao Yanyun , Zens Philipp , Su Min , Gemperli Camila Anna , Yang Haitang , Deng Haibin , Yang Zhang , Xu Duo , Hall Sean R. R. , Berezowska Sabina , Dorn Patrick , Peng Ren-Wang , Schmid Ralph Alexander , Wang Wenxiang , Marti Thomas Michael 
Published: April 2021

Abstract
Background
Pemetrexed (MTA) plus cisplatin combination therapy is considered the standard of care for patients with advanced non-small-cell lung cancer (NSCLC). However, in advanced NSCLC, the 5-year survival rate is below 10%, mainly due to resistance to therapy. We have previously shown that the fraction of mesenchymal-like, chemotherapy-resistant paraclone cells increased after MTA and cisplatin combination therapy in the NSCLC cell line A549.
Cytidine deaminase (CDA) and thymidine phosphorylase (TYMP) are key enzymes of the pyrimidine salvage pathway. 5′-deoxy-5-fluorocytidine (5′-DFCR) is a cytidine analogue (metabolite of capecitabine), which is converted by CDA and subsequently by TYMP into 5-fluorouracil, a chemotherapeutic agent frequently used to treat solid tumors. The aim of this study was to identify and exploit chemotherapy-induced metabolic adaptations to target resistant cancer cells.

Methods
Cell viability and colony formation assays were used to quantify the efficacy of MTA and cisplatin treatment in combination with schedule-dependent addition of 5′-DFCR on growth and survival of A549 paraclone cells and NSCLC cell lines. CDA and TYMP protein expression were monitored by Western blot. Finally, flow cytometry was used to analyze the EMT phenotype, DNA damage response activation and cell cycle distribution over time after treatment. CDA expression was measured by immunohistochemistry in tumor tissues of patients before and after neoadjuvant chemotherapy.

Results
We performed a small-scale screen of mitochondrial metabolism inhibitors, which revealed that 5′-DFCR selectively targets chemotherapy-resistant A549 paraclone cells characterized by high CDA and TYMP expression. In the cell line A549, CDA and TYMP expression was further increased by chemotherapy in a time-dependent manner, which was also observed in the KRAS-addicted NSCLC cell lines H358 and H411. The addition of 5′-DFCR on the second day after MTA and cisplatin combination therapy was the most efficient treatment to eradicate chemotherapy-resistant NSCLC cells. Moreover, recovery from treatment-induced DNA damage was delayed and accompanied by senescence induction and acquisition of a hybrid-EMT phenotype. In a subset of patient tumors, CDA expression was also increased after treatment with neoadjuvant chemotherapy.

Conclusions
Chemotherapy increases CDA and TYMP expression thereby rendering resistant lung cancer cells susceptible to subsequent 5′-DFCR treatment.
Ovarian sex cord stromal tumours: analysis of the clinical and sonographic characteristics of different histopathologic subtypes
Authors: Jiang Mei-jiao , Le Qian , Yang Bo-wen , Yuan Fei , Chen Hui 
Published: April 2021

Abstract
Background
Ovarian sex cord stromal tumours (OSCSTs) are rare ovarian tumours and include different histopathologic subtypes. This study aimed to analyse the clinical and sonographic characteristics of different histopathologic OSCST subtypes.

Methods
A total of 63 patients with surgically proven OSCSTs were enrolled in this retrospective study to analyse their clinical and sonographic features. Ultrasound examinations and predictive models were performed before surgery. The clinical and sonographic findings were compared according to the type of OSCST based on the histopathological diagnosis.

Results
The mean age of 63 patients was 52.17 years (range: 17–78 years). Eighteen patients experienced irregular vaginal bleeding (28.57% 18/63), 7 patients exhibited abnormal body hair (11.11%). 2 patients (3.17%) showed an increased level of CA125, and 25 patients (39.68%, 25/63) showed an increased level of testosterone. Forty-two patients had ovarian thecoma-fibroma groups (OTFGs). Six patients had Sertoli-Leydig cell tumours (S-LCTs), 4 patients had Leydig cell tumours (LCTs), 8 patients had ovarian granulosa cell tumours (OGCTs), 2 patients had ovarian steroid cell tumours, not otherwise specified (OSCTs-NOS), and one patient had sclerosing stromal tumours (SSTs). The mean diameter of the tumour was 47.9 mm (range: 10–258 mm). Forty-seven masses were hypoechoic (74.60%). Twenty-eight masses had posterior echo attenuation, 22 masses exhibited abundant Doppler flow signals (34.92%), and one patient had ascites (1.59%). The diagnostic accuracy of the Simple Rules (SR) and the Assessment of Different NEoplasias in the adneXa (ADNEX) model in distinguishing benign and malignant OSCSTs was 44% (30/63) and 84% (53/63), respectively. The diagnostic accuracy of the SR for OTFGs, S-LCTs & LCTs & OSCTs-NOS, OGCTs, and SSTs was 47.6% (20/42), 16.67% (2/12), 100% (8/8), and 0% (0/1), respectively. The diagnostic accuracy of the ADNEX model for OTFGs, S-LCTs & LCTs & OSCTs-NOS, OGCTs, and SSTs was 93% (31/42), 58.33% (7/12), 75% (6/8), and 100% (1/1), respectively.

Conclusions
OSCSTs generally appear as a solid mass on ultrasound. Posterior echo attenuation indicates an OTFG. A solid mass with abundant Doppler flow signals indicates an S-LCT, LCT, OSCT-NOS or OGCT. Current predictive models are not very effective, but symptoms, sonographic features and serum hormones are helpful for diagnosis.
Broadly sampled orthologous groups of eukaryotic proteins for the phylogenetic study of plastid-bearing lineages
Authors: Van Vlierberghe Mick , Philippe Hervé , Baurain Denis 
Published: April 2021

Abstract
Objectives
Identifying orthology relationships among sequences is essential to understand evolution, diversity of life and ancestry among organisms. To build alignments of orthologous sequences, phylogenomic pipelines often start with all-vs-all similarity searches, followed by a clustering step. For the protein clusters (orthogroups) to be as accurate as possible, proteomes of good quality are needed. Here, our objective is to assemble a data set especially suited for the phylogenomic study of algae and formerly photosynthetic eukaryotes, which implies the proper integration of organellar data, to enable distinguishing between several copies of one gene (paralogs), taking into account their cellular compartment, if necessary.

Data description
We submitted 73 top-quality and taxonomically diverse proteomes to OrthoFinder. We obtained 47,266 orthogroups and identified 11,775 orthogroups with at least two algae. Whenever possible, sequences were functionally annotated with eggNOG and tagged after their genomic and target compartment(s). Then we aligned and computed phylogenetic trees for the orthogroups with IQ-TREE. Finally, these trees were further processed by identifying and pruning the subtrees exclusively composed of plastid-bearing organisms to yield a set of 31,784 clans suitable for studying photosynthetic organism genome evolution.
Adjunct therapy with probiotics for chronic urticaria in children: randomised placebo-controlled trial
Authors: Bi Xiao-Dong , Lu Bao-Zhen , Pan Xin-Xin , Liu Sha , Wang Jiu-Yao 
Published: April 2021

Abstract
Backgrounds
Chronic urticaria is a common disorder of the skin, characterised by recurrent skin wheals and angioedema. Recent reports have shown that altered diversity and composition of the gut microbiota may lead to imbalances in immune regulation, a causal factor in the occurrence of chronic urticaria.

Objective
This study aimed to evaluate the efficacy of the Yimingjia® probiotic formula in the adjuvant treatment of chronic urticaria in children.

Methods
We enrolled 206 children with confirmed diagnoses of chronic urticaria and randomly assigned them to the treatment (n = 104) or placebo group (n = 102). The children in each group were treated with desloratadine dry suspension, and those in the treatment group also received Yimingjia®. Clinical efficacy was evaluated at 1, 2 and 4 weeks.

Results
Clinical symptom scores did not differ significantly at weeks 1 and 2 (p > 0.05), but at 4 weeks, wheal size and attack frequency were significantly reduced in the treatment group (p = 0.049 and 0.03, respectively). The overall response rate (significant improvement + complete response) significantly differed between the treatment (80.8%) and placebo groups (62.5%) (χ2 = 4.20, p = 0.04).

Conclusion
Adjunct therapy with Yimingjia® was safe and effective at 4 weeks in the treatment of chronic urticaria in children. The study was registered under trial number NCT03328897.
Flame: an open source framework for model development, hosting, and usage in production environments
Authors: Pastor Manuel , Gómez-Tamayo José Carlos , Sanz Ferran 
Published: April 2021

AbstractThis article describes Flame, an open source software for building predictive models and supporting their use in production environments. Flame is a web application with a web-based graphic interface, which can be used as a desktop application or installed in a server receiving requests from multiple users. Models can be built starting from any collection of biologically annotated chemical structures since the software supports structural normalization, molecular descriptor calculation, and machine learning model generation using predefined workflows. The model building workflow can be customized from the graphic interface, selecting the type of normalization, molecular descriptors, and machine learning algorithm to be used from a panel of state-of-the-art methods implemented natively. Moreover, Flame implements a mechanism allowing to extend its source code, adding unlimited model customization. Models generated with Flame can be easily exported, facilitating collaborative model development. All models are stored in a model repository supporting model versioning. Models are identified by unique model IDs and include detailed documentation formatted using widely accepted standards. The current version is the result of nearly 3 years of development in collaboration with users from the pharmaceutical industry within the IMI eTRANSAFE project, which aims, among other objectives, to develop high-quality predictive models based on shared legacy data for assessing the safety of drug candidates.
Preferences of patients with asthma or COPD for treatments in pulmonary rehabilitation
Authors: Damm Kathrin , Lingner Heidrun , Schmidt Katharina , Aumann-Suslin Ines , Buhr-Schinner Heike , van der Meyden Jochen , Schultz Konrad 
Published: April 2021

AbstractIntroductionPulmonary rehabilitation (PR) aims to improve disease control in patients with chronic obstructive pulmonary disease (COPD) and asthma. However, the success of PR-programs depends on the patients’ participation and willingness to cooperate. Taking the patients’ preferences into consideration might improve both of these factors. Accordingly, our study aims to analyze patients’ preferences regarding current rehabilitation approaches in order to deduce and discuss possibilities to further optimize pulmonary rehabilitation.Methods and analysisAt the end of a 3 weeks in-house PR, patients’ preferences concerning the proposed therapies were assessed during two different time slots (summer 2015 and winter 2015/2016) in three clinics using a choice-based conjoint analysis (CA). Relevant therapy attributes and their levels were identified through literature search and expert interviews. Inclusion criteria were as follows: PR-inpatient with asthma and/or COPD, confirmed diagnosis, age over 18 years, capability to write and read German, written informed consent obtained. The CA analyses comprised a generalized linear mixed-effects model and a latent class mixed logit model.ResultsA total of 542 persons participated in the survey. The most important attribute was sport and exercise therapy. Rehabilitation preferences hardly differed between asthma and COPD patients. Health-related quality of life (HRQoL) as well as time since diagnosis were found to have a significant influence on patients’ rehabilitation preferences.ConclusionsPatients in pulmonary rehabilitation have preferences regarding specific program components. To increase the adherence to, and thus, the effectiveness of rehabilitation programs, these results must be considered when developing or optimizing PR-programs.
Dietary fiber in poultry nutrition and their effects on nutrient utilization, performance, gut health, and on the environment: a review
Authors: Jha Rajesh , Mishra Pravin 
Published: April 2021

AbstractDietary fiber (DF) was considered an antinutritional factor due to its adverse effects on feed intake and nutrient digestibility. However, with increasing evidence, scientists have found that DF has enormous impacts on the gastrointestinal tract (GIT) development, digestive physiology, including nutrient digestion, fermentation, and absorption processes of poultry. It may help maintain the small and large intestine’s integrity by strengthening mucosal structure and functions and increasing the population and diversity of commensal bacteria in the GIT. Increasing DF content benefits digestive physiology by stimulating GIT development and enzyme production. And the inclusion of fiber at a moderate level in diets also alters poultry growth performance. It improves gut health by modulating beneficial microbiota in the large intestine and enhancing immune functions. However, determining the source, type, form, and level of DF inclusion is of utmost importance to achieve the above-noted benefits. This paper critically reviews the available information on dietary fibers used in poultry and their effects on nutrient utilization, GIT development, gut health, and poultry performance. Understanding these functions will help develop nutrition programs using proper DF at an appropriate inclusion level that will ultimately lead to enhanced DF utilization, overall health, and improved poultry growth performance. Thus, this review will help researchers and industry identify the sources, type, form, and amount of DF to be used in poultry nutrition for healthy, cost-effective, and eco-friendly poultry production.
Critical incidents in anorexia nervosa: perspectives of those with a lived experience
Authors: Leppanen Jenni , Tosunlar Lara , Blackburn Rachael , Williams Steven , Tchanturia Kate , Sedgewick Felicity 
Published: April 2021

AbstractBackgroundAlthough social-emotional difficulties are believed play a key role in anorexia nervosa (AN), there is uncertainty regarding what these difficulties might look like. Previous research has largely focused on a “disease model” of social-emotional processing in AN with little attention paid to positive emotions and experiences. Therefore, the aim of the present study was to obtain a fuller picture of critical life events as identified by those with lived AN experience.MethodsThirty-four participants aged 16–48 with current or past AN completed an online survey describing self-defined positive and difficult critical events. Thematic analysis was used to assess patterns in participants narrative responses.ResultsTwo major themes were identified in the descriptions of positive critical events:Moments of celebrationandUnexpected positive outcomes. These major themes revealed increased external focus and some corrective experiences that challenged the participants pre-existing expectations leading to new positive outcomes. Difficult events clustered into life events that were identified asEating disorder (ED) relatedandNon-ED relatedand included the dimensions of relational conflict and feeling unsupported.DiscussionThe findings suggest that although negative emotionality was identified in the accounts of those with lived experience of AN capacity for “big-picture” thinking with and explicit focus on others was also identified. Moreover, an openness to corrective experiences that worked to challenge negative expectations was evident for some participants. Together these findings have scope as targets for further clinical research and treatment interventions.
A review on the multi-criteria seismic hazard analysis of Ethiopia: with implications of infrastructural development
Authors: Ayele Alemayehu , Woldearegay Kifle , Meten Matebie 
Published: April 2021

AbstractEarthquake is a sudden release of energy due to faults. Natural calamities like earthquakes can neither be predicted nor prevented. However, the severity of the damages can be minimized by development of proper infrastructure which includes microzonation studies, appropriate construction procedures and earthquake resistant designs. The earthquake damaging effect depends on the source, path and site conditions. The earthquake ground motion is affected by topography (slope, hill, valley, canyon, ridge and basin effects), groundwater and surface hydrology. The seismic hazard damages are ground shaking, structural damage, retaining structure failures and lifeline hazards. The medium to large earthquake magnitude (< 6) reported in Ethiopia are controlled by the main Ethiopian rift System. The spatial and temporal variation of earthquake ground motion should be addressed using the following systematic methodology. The general approaches used to analyze damage of earthquake ground motions are probabilistic seismic hazard assessment (PSHA), deterministic seismic hazard assessment (DSHA) and dynamic site response analysis. PSHA considers all the scenarios of magnitude, distance and site conditions to estimate the intensity of ground motion distribution. Conversely, DSHA taken into account the worst case scenarios or maximum credible earthquake to estimate the intensity of seismic ground motion distribution. Furthermore, to design critical infrastructures, DSHA is more valuable than PSHA. The DSHA and PSHA ground motion distributions are estimated as a function of earthquake magnitude and distance using ground motion prediction equations (GMPEs) at top of the bedrock. Site response analysis performed to estimate the ground motion distributions at ground surface using dynamic properties of the soils such as shear wave velocity, density, modulus reduction, and material damping curves. Seismic hazard evaluation of Ethiopia shown that (i) amplification is occurred in the main Ethiopian Rift due to thick soil, (ii) the probability of earthquake recurrence due to active fault sources. The situation of active fault is oriented in the N-S direction. Ethiopia is involved in huge infrastructural development (including roads, industrial parks and railways), increasing population and agricultural activity in the main Ethiopian Rift system. In this activity, socio-economic development, earthquake and earthquake-generated ground failures need to be given attention in order to reduce losses from seismic hazards and create safe geo-environment.
Adult onset Still’s disease in the elderly: a case-based literature review
Authors: Mollaeian Arash , Chen Jingjing , Chan Nina N. , Nizialek Gregory A. , Haas Christopher J. 
Published: April 2021

Abstract
Background
Adult onset Still’s disease (AOSD) is a rare inflammatory disorder that classically presents with high spiking fevers, evanescent rash, and arthritis. The diagnosis is one of exclusion and can be further complicated by atypical presentations, particularly in elderly patients in whom AOSD is very rare.

Case presentation
A case of AOSD in a 73-year-old woman with a non-classic presentation, leading to delayed diagnosis and management, is presented along with a review of the English literature for AOSD cases in elderly people over 70 years of age. Thirty nine case reports and series were identified and the current case was added, totaling 42 individual cases. Significant findings included a four-times higher prevalence in females, a higher prevalence of macrophage activation syndrome despite lower mortality, the presence of pruritic rash in almost one fifth of the cases, and high prevalence of delayed diagnosis.

Conclusions
AOSD in the elderly may vary from the classic criteria described in the medical literature and may lead to delayed diagnosis and management. Further evaluation and better characterization of AOSD in the elderly remains an area of interest.
Conditioning and PPP processing of smartphone GNSS measurements in realistic environments
Authors: Shinghal Ganga , Bisnath Sunil 
Published: April 2021

AbstractSmartphones typically compute position using duty-cycled Global Navigation Satellite System (GNSS) L1 code measurements and Single Point Positioning (SPP) processing with the aid of cellular and other measurements. This internal positioning solution has an accuracy of several tens to hundreds of meters in realistic environments (handheld, vehicle dashboard, suburban, urban forested, etc.). With the advent of multi-constellation, dual-frequency GNSS chips in smartphones, along with the ability to extract raw code and carrier-phase measurements, it is possible to use Precise Point Positioning (PPP) to improve positioning without any additional equipment. This research analyses GNSS measurement quality parameters from a Xiaomi MI 8 dual-frequency smartphone in varied, realistic environments. In such environments, the system suffers from frequent phase loss-of-lock leading to data gaps. The smartphone measurements have low and irregular carrier-to-noise (C/N0) density ratio and high multipath, which leads to poor or no positioning solution. These problems are addressed by implementing a prediction technique for data gaps and a C/N0-based stochastic model for assigning realistic a priori weights to the observables in the PPP processing engine. Using these conditioning techniques, there is a 64% decrease in the horizontal positioning Root Mean Square (RMS) error and 100% positioning solution availability in sub-urban environments tested. The horizontal and 3D RMS were 20 cm and 30 cm respectively in a static open-sky environment and the horizontal RMS for the realistic kinematic scenario was 7 m with the phone on the dashboard of the car, using the SwiftNav Piksi Real-Time Kinematic (RTK) solution as reference. The PPP solution, computed using the YorkU PPP engine, also had a 5–10% percentage point more availability than the RTK solution, computed using RTKLIB software, since missing measurements in the logged file cause epoch rejection and a non-continuous solution, a problem which is solved by prediction for the PPP solution. The internal unaided positioning solution of the phone obtained from the logged NMEA (The National Marine Electronics Association) file was computed using point positioning with the aid of measurements from internal sensors. The PPP solution was 80% more accurate than the internal solution which had periodic drifts due to non-continuous computation of solution.
Research progress in optical neural networks: theory, applications and developments
Authors: Liu Jia , Wu Qiuhao , Sui Xiubao , Chen Qian , Gu Guohua , Wang Liping , Li Shengcai 
Published: April 2021

AbstractWith the advent of the era of big data, artificial intelligence has attracted continuous attention from all walks of life, and has been widely used in medical image analysis, molecular and material science, language recognition and other fields. As the basis of artificial intelligence, the research results of neural network are remarkable. However, due to the inherent defect that electrical signal is easily interfered and the processing speed is proportional to the energy loss, researchers have turned their attention to light, trying to build neural networks in the field of optics, making full use of the parallel processing ability of light to solve the problems of electronic neural networks. After continuous research and development, optical neural network has become the forefront of the world. Here, we mainly introduce the development of this field, summarize and compare some classical researches and algorithm theories, and look forward to the future of optical neural network.