Miracle-dz/UniFAR-FTUs huggingface dataset:
Scaling agile in large organizations: Practices, challenges, and success factors

Context: Agile software development has nowadays reached wide adoption. However, moving agile to large‐scale contexts is a complex task with many challenges involved. Objective: In this paper, we review practices, challenges, and success factors for scaling agile both from literature and within a large software company, identifying the most critical factors. Method: We conduct a focused literature review to map the importance of scaling practices, challenges, and success factors. The outcome of this focused literature review is used to guide action research within a software company with a view to scaling agile processes. Results: Company culture, prior agile and lean experience, management support, and value unification were found to be key success factors during the action research process. Resistance to change, an overly aggressive roll‐out time frame, quality assurance concerns, and integration into preexisting nonagile business processes were found to be the critical challenges in the scaling process. Conclusion: The action research process allowed to cross‐fertilize ideas from literature to the company's context. Scaling agile within an organization does not need to follow a specific scheme, rather the process can be tailored to the needs while keeping the core values and principles of agile methodologies.
Kinetic Modeling of pH-Dependent Oxidation of Dopamine by Iron and Its Relevance to Parkinson's Disease

Parkinson's disease is the second most common neurodegenerative disease. While age is the most significant risk factor, the exact cause of this disease and the most effective approaches to mitigation remain unclear. It has long been proposed that dopamine may play a role in the pathology of Parkinson's disease in view of its ability to generate both protein-modifying quinones such as aminochrome and reactive oxygen species, especially in the presence of pathological iron accumulation in the primary site of neuron loss. Given the clinically measured acidosis of post-mortem Parkinson's disease brain tissue, the interaction between dopamine and iron was investigated over a pH range of 7.4 to 6.5 with emphasis on the accumulation of toxic quinones and generation of reactive oxygen species. Our results show that the presence of iron accelerates the formation of aminochrome with ferrous iron (Fe[II]) being more efficient in this regard than ferric iron (Fe[III]). Our results further suggest that a reduced aminochrome rearrangement rate coupled with an enhanced turnover rate of Fe[II] as a result of brain tissue acidosis could result in aminochrome accumulation within cells. Additionally, under these conditions, the enhanced redox cycling of iron in the presence of dopamine aggravates oxidative stress as a result of the production of damaging reactive species, including hydroxyl radicals.
Pineal parenchymal tumour of intermediate differentiation: a rare differential diagnosis of pineal region tumours

Pineal parenchymal tumours of intermediate differentiation are a rare type of pineal parenchymal tumours. As indicated by their name, these tumours fall between pineoblastoma (a malignant pineal parenchymal tumour) and pineocytoma (a benign pineal parenchymal tumour). In this article, we present a case of pineal parenchymal tumour of intermediate differentiation that was successfully treated by resection via the supracerebellar approach. We also discuss the differential consideration based on epidemiological, pathological and radiological findings.
An Overview of Internet of Energy (IoE) Based Building Energy Management System

Buildings are important contributors to energy consumption accounting for around one-third of the total primary energy in the world. A building energy management system (BEMs) is an efficient method used for monitoring and controlling a building’s energy needs. To solve these existing issues of the current building energy management system such as the large amounts of BEMs energy data, energy data loss and energy overload problems, a BEMs based on Internet of Energy (IoE) has been proposed. In this paper, we will give the potential of IoE-based BEMs for enhancing the performance of building energy utilization in the future. Within the scope of this paper, the future trends of IoE in various fields will be discussed.
Determining k-Value with Regard to Freeze-Thaw Resistance of Concretes Containing GGBS

The European concrete standard EN 206 introduces the k-value concept as one of the three methods allowing the use of granulated blast furnace slag in the design of the freeze-thaw-resistant concrete mix. It is assumed that the freeze-thaw durability of the concrete, whose composition (w/c ratio) has been corrected by adopting a certain k-value, is the same as the freeze-thaw resistance of the reference concrete made with the cement containing no addition (CEM I). This article presents the results of freeze-thaw resistance analysis (modified with the ASTM C666A standard Class XF3) of 24 series of concretes made with a binder containing varied amounts of slag, with a w/b ratio ranging from 0.25 to 0.55. The aim of the study was to estimate the k-value as a parameter defined by the w/b ratio and the slag content in the binder. In this approach, the k-value is determined by trial and error in such a way that the deformation of the concrete specimens containing the slag corresponds to the deformation of the reference concrete. As shown by the analysis, the k-value decreases with increasing slag content in the binder.
Auxin Controlled by Ethylene Steers Root Development

Roots are important plant ground organs, which absorb water and nutrients to control plant growth and development. Phytohormones have been known to play a crucial role in the regulation of root growth, such as auxin and ethylene, which are central regulators of this process. Recent findings have revealed that root development and elongation regulated by ethylene are auxin dependent through alterations of auxin biosynthesis, transport and signaling. In this review, we focus on the recent advances in the study of auxin and auxin–ethylene crosstalk in plant root development, demonstrating that auxin and ethylene act synergistically to control primary root and root hair growth, but function antagonistically in lateral root formation. Moreover, ethylene modulates auxin biosynthesis, transport and signaling to fine-tune root growth and development. Thus, this review steps up the understanding of the regulation of auxin and ethylene in root growth.
Training Multi-task Adversarial Network for Extracting Noise-robust Speaker Embedding

Under noisy environments, to achieve the robust performance of speaker recognition is still a challenging task. Motivated by the promising performance of multi-task training in a variety of image processing tasks, we explore the potential of multitask adversarial training for learning a noise-robust speaker embedding. In this paper, we present a novel framework that consists of three components: an encoder that extracts the noise-robust speaker embeddings; a classifier that classifies the speakers; a discriminator that discriminates the noise type of the speaker embeddings. Additionally , we propose a training strategy using the training accuracy as an indicator to stabilize the multi-class adversarial optimization process. We conduct our experiments on the English and Mandarin corpuses and the experimental results demonstrate that our proposed multi-task adversarial training method could greatly outperform the other methods without adversarial training in noisy environments. Furthermore, the experiments indicate that our method is also able to improve the speaker verification performance under the clean condition.
Neuroprotective Activity of Some Marine Fungal Metabolites in the 6-Hydroxydopamin- and Paraquat-Induced Parkinson’s Disease Models

A new melatonin analogue 6-hydroxy-N-acetyl-β-oxotryptamine (1) was isolated from the marine-derived fungus Penicillium sp. KMM 4672. It is the second case of melatonin-related compounds isolation from microfilamentous fungi. The neuroprotective activities of this metabolite, as well as 3-methylorsellinic acid (2) and 8-methoxy-3,5-dimethylisochroman-6-ol (3) from Penicillium sp. KMM 4672, candidusin A (4) and 4″-dehydroxycandidusin A (5) from Aspergillus sp. KMM 4676, and diketopiperazine mactanamide (6) from Aspergillus flocculosus, were investigated in the 6-hydroxydopamine (6-OHDA)- and paraquat (PQ)-induced Parkinson’s disease (PD) cell models. All of them protected Neuro2a cells against the damaging influence of 6-OHDA to varying degrees. This effect may be realized via a reactive oxygen species (ROS) scavenging pathway. The new melatonin analogue more effectively protected Neuro2A cells against the 6-OHDA-induced neuronal death, in comparison with melatonin, as well as against the PQ-induced neurotoxicity. Dehydroxylation at C-3″ and C-4″ significantly increased free radical scavenging and neuroprotective activity of candidusin-related p-terphenyl polyketides in both the 6-OHDA- and PQ-induced PD models.
Guidelines for the diagnosis and management of primary central nervous system diffuse large B‐cell lymphoma

Clinical Haematology, Nottingham University Hospitals NHS Trust, Nottingham, Department of Haematology, University College Hospital, London, Department of Haematology, Division of Cancer Sciences, School of Medical Sciences, Aintree Hospital NHS Trust, Liverpool, University of Manchester, Manchester, Velindre Cancer Centre, Cardiff, Department of Haematology, Barking, Havering and Redbridge University Hospitals, Essex, Division of Clinical Neuroscience, Radiological Sciences, University of Nottingham, Nottingham, Department of Neuropsychology, Barking, Havering and Redbridge University Hospitals, Essex, Department of Medical Oncology, Southampton General Hospital, Southampton, and Department of Haematology, Beatson West of Scotland Cancer Centre, Glasgow, UK
Investigating the Role of MicroRNA and Transcription Factor Co-regulatory Networks in Multiple Sclerosis Pathogenesis

MicroRNAs (miRNAs) and transcription factors (TFs) play key roles in complex multifactorial diseases like multiple sclerosis (MS). Starting from the miRNomic profile previously associated with a cohort of pediatric MS (PedMS) patients, we applied a combined molecular and computational approach in order to verify published data in patients with adult-onset MS (AOMS). Six out of the 13 selected miRNAs (miR-320a, miR-125a-5p, miR-652-3p, miR-185-5p, miR-942-5p, miR-25-3p) were significantly upregulated in PedMS and AOMS patients, suggesting that they may be considered circulating biomarkers distinctive of the disease independently from age. A computational and unbiased miRNA-based screening of target genes not necessarily associated to MS was then performed in order to provide an extensive view of the genetic mechanisms underlying the disease. A comprehensive MS-specific miRNA-TF co-regulatory network was hypothesized; among others, SP1, RELA, NF-κB, TP53, AR, MYC, HDAC1, and STAT3 regulated the transcription of 61 targets. Interestingly, NF-κB and STAT3 cooperatively regulate the expression of immune response genes and control the cross-talk between inflammatory and immune cells. Further functional analysis will be performed on the identified critical hubs. Above all, in our view, this approach supports the need of multidisciplinary strategies for shedding light into the pathogenesis of MS.
Individual dynamic predictions using landmarking and joint modelling: Validation of estimators and robustness assessment

After the diagnosis of a disease, one major objective is to predict cumulative probabilities of events such as clinical relapse or death from the individual information collected up to a prediction time, usually including biomarker repeated measurements. Several competing estimators have been proposed, mainly from two approaches: joint modelling and landmarking. These approaches differ by the information used, the model assumptions and the complexity of the computational procedures. This paper aims to review the two approaches, precisely define the derived estimators of dynamic predictions and compare their performances notably in case of misspecification. The ultimate goal is to provide key elements for the use of individual dynamic predictions in clinical practice. Prediction of two competing causes of prostate cancer progression from the history of prostate-specific antigen is used as a motivated example. We formally define the quantity to estimate and its estimators, propose techniques to assess the uncertainty around predictions and validate them. We then conduct an in-depth simulation study compare the estimators in terms of prediction error, discriminatory power, efficiency and robustness to model assumptions. We show that prediction tools should be handled with care, in particular by properly specifying models and estimators.
Efficacy of sequential sorafenib plus hepatic arterial infusion chemotherapy in patients with Barcelona Clinic Liver Cancer stage B and C hepatocellular carcinoma: a retrospective single-institution study

Aim of the study To evaluate the efficacy of sequential combination therapy using sorafenib and hepatic arterial infusion chemotherapy (HAIC) in patients with Barcelona Clinic Liver Cancer stage B/C hepatocellular carcinoma (HCC). Material and methods We recruited 98 BCLC stage B/C HCC patients at our institute, who received either sorafenib monotherapy or planned sequential sorafenib-HAIC combination therapy. A total of 26 patients (combination group) received sorafenib for one or two months, followed by HAIC with a single dose of cisplatin-lipiodol suspension and a continuous infusion of 5-fluorouracil. Sorafenib-HAIC cycles were repeated every 2–3 months. The remaining 72 patients (control group) were treated with sorafenib alone. Clinical characteristics and treatment outcomes were compared between the groups. Inverse probability weighting (IPW) using propensity scores was applied to adjust for the between-group differences in baseline characteristics. Results The combination group had a significantly lower frequency of extrahepatic metastasis and BCLC stage C disease compared with the control group but had more intrahepatic lesions. The crude median overall survival (OS) was 17.1 months in the combination group compared with 9.7 months in the control group (p = 0.01). The objective response rate was 23.1% in the combination group vs. 6.9% in the control group (p = 0.06). Multivariate analysis identified receipt of sorafenib-HAIC combination (HR: 0.521, 95% CI: 0.297–0.915, p = 0.02) and α-fetoprotein (≥ 400 ng/ml) at baseline as independent factors associated with OS. After adjustment with IPW the combination group still had significantly better OS than the control group (p = 0.04). Conclusions The sequential sorafenib-HAIC combination can be an effective and promising treatment option for selected patients with BCLC stage B/C HCC.
Critical Success Factors for Information Systems Development: A Case Study in e-Government

Information Systems (IS) development for government is prone to failure, which also happened to the development of Administration and Credit Information Systems (Sistem Informasi Pengadministrasian dan Angka Kredit or SIPARKIT) by the ICT unit at Finance Education and Training Agency (BPPK), Ministry of Finance, Republic of Indonesia. This study investigates the Critical Success Factors (CSF) of the SIPARKIT to determine the priority of each CSF. These factors were identified from the literature and interviewed with SIPARKIT development team and experts in IS project management. The CSFs were then ranked using pair wise comparison questionnaire by the IS development team and high rank ICT officers. The data collected from the questionnaires were analyzed using the Analytic Hierarchy Process (AHP). The results show that business process re-engineering and system integration are the most important factor for the success of IS development. Other CSFs are project plan and schedule, team skills, competencies, and composition, top management support, and politics within the organization, communication, leadership, performance assessment, and knowledge management. Interviews with top management were also conducted to support the analysis results.
Discovery of Non-Peptidic Compounds against Chagas Disease Applying Pharmacophore Guided Molecular Modelling Approaches

Chagas disease is one of the primary causes of heart diseases accounting to 50,000 lives annually and is listed as the neglected tropical disease. Because the currently available therapies have greater toxic effects with higher resistance, there is a dire need to develop new drugs to combat the disease. In this pursuit, the 3D QSAR ligand-pharmacophore (pharm 1) and receptor-based pharmacophore (pharm 2) search was initiated to retrieve the candidate compounds from universal natural compounds database. The validated models were allowed to map the universal natural compounds database. The obtained lead candidates were subjected to molecular docking against cysteine protease (PDB code: 1ME3) employing -Cdocker available on the discovery studio. Subsequently, two Hits have satisfied the selection criteria and were escalated to molecular dynamics simulation and binding free energy calculations. These Hits have demonstrated higher dock scores, displayed interactions with the key residues portraying an ideal binding mode complemented by mapping to all the features of pharm 1 and pharm 2. Additionally, they have rendered stable root mean square deviation (RMSD) and potential energy profiles illuminating their potentiality as the prospective antichagastic agents. The study further demonstrates the mechanism of inhibition by tetrad residues compromising of Gly23 and Asn70 holding the ligand at each ends and the residues Gly65 and Gly160 clamping the Hits at the center. The notable feature is that the Hits lie in close proximity with the residues Glu66 and Leu67, accommodating within the S1, S2 and S3 subsites. Considering these findings, the study suggests that the Hits may be regarded as effective therapeutics against Chagas disease.
Single‐molecule real‐time sequencing reveals diverse allelic variations in carotenoid biosynthetic genes in pepper (Capsicum spp.)

Summary The diverse colours of mature pepper (Capsicum spp.) fruit result from the accumulation of different carotenoids. The carotenoid biosynthetic pathway has been well elucidated in Solanaceous plants, and analysis of candidate genes involved in this process has revealed variations in carotenoid biosynthetic genes in Capsicum spp. However, the allelic variations revealed by previous studies could not fully explain the variation in fruit colour in Capsicum spp. due to technical difficulties in detecting allelic variation in multiple candidate genes in numerous samples. In this study, we uncovered allelic variations in six carotenoid biosynthetic genes, including phytoene synthase (PSY1,PSY2), lycopene β‐cyclase, β‐carotene hydroxylase, zeaxanthin epoxidase and capsanthin‐capsorubin synthase (CCS) genes, in 94 pepper accessions by single‐molecule real‐time (SMRT) sequencing. To investigate the relationship between allelic variations in the candidate genes and differences in fruit colour, we performed ultra‐performance liquid chromatography analysis using 43 accessions representing each allelic variation. Different combinations of dysfunctional mutations in PSY1 and CCS could explain variation in the compositions and levels of carotenoids in the accessions examined in this study. Our results demonstrate that SMRT sequencing technology can be used to rapidly identify allelic variation in target genes in various germplasms. The newly identified allelic variants will be useful for pepper breeding and for further analysis of carotenoid biosynthesis pathways.
Macular ganglion cell asymmetry for detecting paracentral scotoma in early glaucoma

Purpose We evaluated macular ganglion cell asymmetry as a tool for diagnosing paracentral scotoma (PCS) in early glaucoma. Patients and methods This prospective study compared 58 patients with early glaucoma and PCS to 58 age-matched control individuals. All glaucomatous eyes had scotoma within the central 12 degrees of fixation and confined to one hemifield. We measured circumpapillary retinal nerve fiber layer (cpRNFL) thickness, macular ganglion cell-inner plexiform layer (GCIPL) thickness, and optic nerve head (ONH) parameters with Cirrus spectral domain optical coherence tomography. Macular ganglion cell asymmetry was expressed as the absolute differences and the ratios between the inferior and superior hemispheres, inferotemporal (IT) and superotemporal (ST) areas, IT and superonasal (SN) areas, IT and inferonasal (IN) areas, and ST and IN areas. The asymmetry index was the absolute log10 of the ratio. The area under the receiver operating characteristics curve (AUROC) and partial AUROC (pAUROC, specificities ≥90%) were analyzed for each parameter. Results All GCIPL parameters and most cpRNFL parameters were significantly lower in early glaucoma than in controls. The best discriminating parameters were inferior RNFL thickness, average RNFL thickness, and minimum GCIPL thickness. The macular ganglion cell asymmetry parameters with the largest AUROCs were the log IT/ST index, the absolute difference in IT−ST GCIPL thicknesses, and the log IT/SN index. Performance was comparable between the log IT/ST index and the cpRNFL (inferior RNFL thickness, P=0.129), GCIPL (minimum GCIPL thickness, P=0.358), and ONH parameters (vertical cup-to-disc ratio, P=0.475). Conclusion The IT/ST asymmetry index may be useful as a new parameter for detecting structural changes in glaucoma patients with PCS.
Comprehensive Profiling and Inheritance Patterns of Metabolites in Foxtail Millet

Metabolomics aims at determining a sample's metabolites profile and hence provides a straight functional statement of an organism's physiological condition. Here, we investigated comprehensive profiling, natural variation and species-specific accumulation of both primary and secondary metabolites in foxtail millet using LC-MS, and inheritance patterns of metabolome in millet hybrids. The application of a broad target metabolomics method facilitated the simultaneous identification and quantification of more than 300 metabolites. The metabolic analysis of these compounds, such as flavonoids, phenolamides, hydrocinnamoyl derivatives, vitamins and LPCs, revealed their developmentally controlled accumulation, and natural variation in different tissues/varieties. Species-specific accumulation of secondary metabolites was observed based on a comparative metabolic analysis between millet and rice, such as flavonoid O-rutinosides/neohesperidosides and malonylated flavonoid O-glycosides. In analyzing the metabolic variations between hybrid progenies and their parental lines, including a photothermo-sensitive genic male sterility line and five Zhangzagu varieties, metabolic overdominant, and dominant patterns of inheritance could be observed. For example, hydrocinnamoyl derivatives and feruloylated flavonoids were identified as over-parent heterosis (overdominant) metabolites in milet hybrids. Our work paves the way for developing predictors of hybrid performance and the future analysis of the biosynthesis and regulation of relevant metabolic pathways in millet.