Miracle-dz/UniFAR-FTUs huggingface dataset:
An Evolutionary Variable Neighborhood Search for Selecting Combinational Gene Signatures in Predicting Chemo-Response of Osteosarcoma

In genomic studies of cancers, identification of genetic biomarkers from analyzing microarray chip that interrogate thousands of genes is important for diagnosis and therapeutics. However, the commonly used statistical significance analysis can only provide information of each single gene, thus neglecting the intrinsic interactions among genes. Therefore, methods aiming at combinational gene signatures are highly valuable. Supervised classification is an effective way to assess the function of a gene combination in differentiating various groups of samples. In this paper, an evolutionary variable neighborhood search (EVNS) that integrated the approaches of evolutionary algorithm and variable neighborhood search (VNS) is introduced. It consists of a population of solutions that evolution is performed by a variable neighborhood search operator, instead of the more usual reproduction operators, crossover and mutation used in evolutionary algorithms. It is an efficient search algorithm especially suitable for tremendous solution space. The proposed EVNS can simultaneously optimize the feature subset and the classifier through a common solution coding mechanism. This method was applied in searching the combinational gene signatures for predicting histologic response of chemotherapy on osteosarcoma patients, which is the most common malignant bone tumor in children. Cross-validation results show that EVNS outperforms the other existing approaches in classifying initial biopsy samples.
Dynamics and conformational propensities of staphylococcal CntA

Abstract Enzymes use transition metals as co-factors for catalytic roles in biological processes. Notably, manganese, iron, cobalt, nickel, copper and zinc are abundantly used. Staphylococcus aureus, a commensal bacterium asymptomatically, lies on the human body causing variety of infections. S. aureus is equipped by advanced virulence-regulatory circuits of metal acquisition like Cnt that acquires metals at infection sites by utilizing a nicotianamine-like metallophore staphylopine. Despite significant growth in structural studies, how CntA of Cnt system transmits conformational signal upon staphylopine recognition remains elusive. Here, we analyzed the structural changes adopted by CntA during close-to-open transition by computational approaches. CntA uses a bi-domain architectural form of domain II which performed 37° rigid body rotation and 1.1 Å translation assisted by inter-domain hinge cluster residues. Important clustered communities were found regulating the conformational changes in CntA where communities 4 and 5 are found crucial. Besides open and close states, the fluctuating regions sampled two additional intermediate states which were considered close or open previously. CntA prefers fluctuating the non-conserved regions rather than conserved where domain II turned out to be rigid and maintains a stable fold. Overall, the CntA system is a potential target for structural biologist to hamper such conformational behaviors at family level. Communicated by Ramaswamy H. Sarma
Critiques of PVA Ask the Wrong Questions: Throwing the Heuristic Baby Out with the Numerical Bath Water

*Key Centre for Tropical Wildlife Management, Northern Territory University, Darwin, Northern Territory 0909, Australia†School of Botany, University of Melbourne, Parkville, Victoria 3052, Australia‡Applied Biomathematics, 100 North Country Road, Setauket, NY 11733, U.S.A. §Key Centre for Biodiversity and Bioresources, Macquarie University, New South Wales 2109, Australia
Runx2 Regulates Mouse Tooth Root Development Via Activation of WNT Inhibitor NOTUM

Progenitor cells are crucial in controlling organ morphogenesis. Tooth development is a well‐established model for investigating the molecular and cellular mechanisms that regulate organogenesis. Despite advances in our understanding of how tooth crown formation is regulated, we have limited understanding of tooth root development. Runt‐related transcription factor 2 (RUNX2) is a well‐known transcription factor in osteogenic differentiation and early tooth development. However, the function of RUNX2 during tooth root formation remains unknown. We revealed in this study that RUNX2 is expressed in a subpopulation of GLI1+ root progenitor cells, and that loss of Runx2 in these GLI1+ progenitor cells and their progeny results in root developmental defects. Our results provide in vivo evidence that Runx2 plays a crucial role in tooth root development and in regulating the differentiation of root progenitor cells. Furthermore, we identified that Gli1, Pcp4, NOTUM, and Sfrp2 are downstream targets of Runx2 by integrating bulk and single‐cell RNA sequencing analyses. Specifically, ablation of Runx2 results in downregulation of WNT inhibitor NOTUM and upregulation of canonical WNT signaling in the odontoblastic site, which disturbs normal odontoblastic differentiation. Significantly, exogenous NOTUM partially rescues the impaired root development in Runx2 mutant molars. Collectively, our studies elucidate how Runx2 achieves functional specificity in regulating the development of diverse organs and yields new insights into the network that regulates tooth root development. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Robustness of Alpine Pollination Networks: Effects of Network Structure and Consequences for Endemic Plants

Abstract Global threats to plant-pollinator interactions are potentially serious in alpine ecosystems, which combine great diversity with particular fragility. We utilized tools from complex network theory to assess the robustness to species extinction of two Spanish alpine pollination networks. A comparison with ten additional alpine and subalpine pollination (ASP) networks allowed us to give our assessment a broader scope and provide a general view of ASP network robustness. We found a broad range of robustness among ASP networks. The two Spanish pollination networks ranked intermediate to high in robustness. This could be due to two of their structural features, connectance (proportion of potential interactions actually observed) and asymmetry (normalized difference between pollinator and plant richness), which showed a positive relationship with network robustness. A finer-scale focus on the two Spanish networks did not reveal differences between endemic and nonendemic plants in their functional role within the network but indicated that they differed in their robustness to pollinator extinction. Contrasting patterns across networks suggested that endemic robustness depends on community particularities. To improve the utility of robustness assessment as a conservation tool, we should increase our understanding on (1) the order in which network species will get extinct, (2) how species rewire once they have lost their partners, and (3) how much species depend on their mutualistic interaction.
Field resistance to fire blight in a diverse apple (Malus sp.) germplasm collection

Incidence and severity of fire blight (Erwinia amylovora (Burr.) Winslow, Broadhurst, Buchanan, Krumwiede, Rogers, and Smith) following field infection were recorded using families resulting primarily from open-pollination of Malus sylvestris (L.) Mill. var.domestica (Borkh.) Mansf. cultivars and a few other Malus Mill. sp. The families were structured as three sublines, planted in three successive years (1992 to 1994), of a diverse population of apple germplasm established at HortResearch, Hawkes Bay, New Zealand. The incidence of fire blight varied among the sublines with the oldest planting exhibiting more fire blight. Flowering trees were more likely to be infected than nonflowering trees, in terms of both incidence and severity. Furthermore, the level of fire blight was related to flowering date, with later flowering trees having higher levels. Thus, family means and narrow-sense heritability estimates were computed after first adjusting the fire blight score for flowering date by fitting a linear model. Provenance of origin of the maternal parent explained little variation except that M. sieversii Lebed. families were more resistant than M. sylvestris var. domestica families in one subline. Family means computed using all trees, and those from only flowering trees were highly correlated. Families from open-pollination of M. honanensis Rehder and M. xhartwiggii Koehne females were among the more susceptible. Those from several European M. sylvestris var. domestica cultivars as well as from M. baccata (L.) Borkh. and M. toringoides (Rehder) Hughes females were among the more resistant families. Narrow-sense heritability estimates ranged from 0.05 to 0.85 depending on the subline, with most estimates between 0.12 and 0.36. They were higher in the two older sublines that consisted primarily of open-pollinated families from M. sylvestris var. domestica, and lower in the younger subline that consisted primarily of M. sieversii, due to lower incidence and severity in the latter subline. Breeders who consider potential complications of juvenility, tree size, and flowering date in relation to infection periods should be able to exploit field epidemics to perform effective selection.
Differences in host range and reproductive compatibility among populations of Panonychus mori Yokoyama (Acari : Tetranychidae)

Abstract Developmental success and oviposition of five different populations of Panonychus mori Yokoyama on 46 species of plants were studied. The populations were collected from five species of trees: muku (Aphanantha aspera (Thunb.) ), peach (Prunus persica (L.) ), Japanese pear (Pyrus pyrifolia var. culta (Makino)), moonseed (Cocculus trilobus (Thunb.)) and mulberry (Morus bombycis Koidz.). The host range of the mulberry population was considerably different from those of the other four populations: the mulberry population of spider mites was able to use only 2 species as host plants, whereas the others could use 9 species. The muku, peach, pear and moonseed populations were reproductively compatible with one another, while the mulberry population was bidirectionally incompatible with other populations and produced a small number of F1 adult females. Thus, the mulberry population was determined to differ in host range and reproductive traits from the other populations.
MRI findings, including diffusion-weighted imaging, in seven cats with nasal lymphoma and two cats with nasal adenocarcinoma

Objectives Primary nasal tumours in cats are rare, with lymphoma being the most common feline nasal tumour, followed by adenocarcinoma. Although CT can reliably detect feline nasal tumours, there are no specific CT features that identify each tumour type. To our knowledge, there have been no reports describing MRI findings, including diffusion-weighted imaging (DWI), for nasal lymphomas and adenocarcinomas in cats. Therefore, this retrospective study aimed to evaluate the MRI findings of nasal lymphoma and adenocarcinoma, including qualitative and quantitative analysis of DWI. Methods MRI examination was performed on seven cats with histologically confirmed lymphoma and on two with adenocarcinoma. The MRI protocol included T2-weighted imaging (T2WI), T1-weighted imaging (T1WI) and DWI. Apparent diffusion coefficient (ADC) values were measured using DWI. Contrast agent was not used in one cat with lymphoma. Results Of the cats with lymphoma, three (43%) were iso- and hyperintense on T2WI, seven (100%) were isointense on T1WI, five (83%) exhibited mild heterogeneous enhancement, including a prominent region of non-enhancement on post-contrast T1WI, and seven (100%) cats exhibited hyperintensity on DWI. The median ADC values were 0.45 × 10−3 mm2/s (range 0.37–0.53 × 10−3 mm2/s). For adenocarcinoma, two (100%) were iso- and hyperintense on T2WI, two (100%) were isointense on T1WI, two (100%) exhibited marked heterogeneous enhancement on post-contrast T1WI and two (100%) were isointense on DWI. The median ADC values were 1.08 × 10−3 mm2/s (range 0.88–1.27 × 10−3 mm2/s). The median ADC values of lymphoma tended to be lower than adenocarcinoma (P = 0.056). Conclusions and relevance Determining ADC value and tumours with a large area of non-enhancement may be helpful in differentiating nasal lymphoma from nasal adenocarcinoma.
Dissecting the phenotypic components and genetic architecture of maize stem vascular bundles using high‐throughput phenotypic analysis

Summary High‐throughput phenotyping is increasingly becoming an important tool for rapid advancement of genetic gain in breeding programmes. Manual phenotyping of vascular bundles is tedious and time‐consuming, which lags behind the rapid development of functional genomics in maize. More robust and automated techniques of phenotyping vascular bundles traits at high‐throughput are urgently needed for large crop populations. In this study, we developed a standard process for stem micro‐CT data acquisition and an automatic CT image process pipeline to obtain vascular bundle traits of stems including geometry‐related, morphology‐related and distribution‐related traits. Next, we analysed the phenotypic variation of stem vascular bundles between natural population subgroup (480 inbred lines) based on 48 comprehensively phenotypic information. Also, the first database for stem micro‐phenotypes, MaizeSPD, was established, storing 554 pieces of basic information of maize inbred lines, 523 pieces of experimental information, 1008 pieces of CT scanning images and processed images, and 24 192 pieces of phenotypic data. Combined with genome‐wide association studies (GWASs), a total of 1562 significant single nucleotide polymorphism (SNPs) were identified for 30 stem micro‐phenotypic traits, and 84 unique genes of 20 traits such as VBNum, VBAvArea and PZVBDensity were detected. Candidate genes identified by GWAS mainly encode enzymes involved in cell wall metabolism, transcription factors, protein kinase and protein related to plant signal transduction and stress response. The results presented here will advance our knowledge about phenotypic trait components of stem vascular bundles and provide useful information for understanding the genetic controls of vascular bundle formation and development.
Neurochemical metabolite alterations of the occipital lobe in migraine without aura by proton magnetic resonance spectroscopy

Background Migraine without aura is the most common type of migraine headache, accounting for about 80% of all migraines. The aim of the present investigation was to determine the neurochemical metabolite alterations in the occipital lobe of patients suffering from migraine without aura using proton magnetic resonance spectroscopy (1H-MRS). Methods Fifteen patients suffering from migraine without aura with an occipital plaque and 16 healthy controls were included in this study. Changes in the neurochemical metabolites in the occipital lobe were assessed using 1H-MRS. The ratios of N-acetylaspartate (NAA) to creatine (Cr), choline (Cho) to Cr and myo-inositol (MI) to NAA were measured by voxel volume at 8 cm3. Results The mean NAA/Cr ratio decreased significantly in patients compared to controls. Cho/Cr and MI/NAA ratios increased significantly in patients. In addition, the duration of the disease and the frequency of headache attacks were significantly associated with a decrease in the NAA/Cr ratio and an increase in the Cho/Cr ratio. Conclusions Migraine without aura shows a significant association with changes in neurochemical metabolites detectable by 1H-MRS in the occipital lobe of patients. In addition, changes in metabolic ratios showed a significant relationship with the duration of the disease and the frequency of headache attacks.
Rapid and sustained improvements in patient-reported signs and symptoms with ixekizumab in biologic-naive and TNF-inadequate responder patients with psoriatic arthritis.

OBJECTIVES To analyse the onset and sustainability of patient-reported improvements in symptoms of psoriatic arthritis (PsA) following treatment with ixekizumab (IXE) up to Week 108. METHODS In patients with active PsA, either naive to biological DMARDs (SPIRIT-P1) or having inadequate response or intolerance to 1 or 2 prior TNF-inhibitors (TNFi‑experienced; SPIRIT-P2), we analysed the change from baseline in joint pain visual analogue scale (VAS; 0-100 scale), patient global assessment (PatGA VAS; 0-100 scale), fatigue numerical rating scale (NRS; 0 [no fatigue] to 10 [worst imaginable]), and Health Assessment Questionnaire-Disability Index (HAQ-DI; 0-3), up to Week 108. RESULTS IXE-treated patients compared to placebo reported rapid and statistically significant improvement in pain VAS, PatGA, and HAQ-DI as early as Week 1 and this benefit was sustained or increased through Week 108. Fatigue scores improved in IXE-treated patients compared to placebo in both studies; results were statistically significant at Week 24 only in SPIRIT-P2. Improvements in fatigue with IXE were sustained over 2 years. The improvements observed in these patient-reported outcomes (PROs) were consistent in biologic-naive or TNFi-experienced patients. CONCLUSIONS Patients treated with IXE versus PBO achieved significantly greater improvements and showed faster onset of improvements in patient-reported outcomes measuring symptoms and impact of PsA. Responses were sustained over 2 years and were generally consistent regardless of prior TNFi experience.
Extraction, partial characterization and susceptibility to Hg2+ of acid phosphatase from the microalgae Pseudokirchneriella subcapitata

Pseudokirchneriella subcapitata e uma alga verde unicelular amplamente distribuida em corpos d´agua e solos. Devido a sua natureza cosmopolita, seu uso e recomendado por protocolos nacionais e internacionais na realizacao de estudos de ecotoxicidade. A alteracao da atividade de fosfatases por agentes poluentes de origem agricola, como metais pesados, tem sido largamente usada como um biomarcador na avaliacao de risco e biomonitoramento. No presente trabalho foi comparada a extracao da fosfatase acida de P. subcapitata por diferentes metodos e estudada a sua estabilidade, especificidade por substratos, cinetica e efeito do Hg2+ no extrato bruto. O congelamento e descongelamento, associado com ultrassom, foi o metodo que proporcionou maior rendimento de extracao. A enzima, praticamente estavel por armazenamento a -20oC, durante aproximadamente seis meses, demonstrou uma atividade otima em pH 5 e um valor de Km para o p-nitrofenilfostato (pNPP) de 0,27 mM. Alguns substratos naturais foram hidrolisados com uma intensidade semelhante a do substrato sintetico pNPP. Diferentemente dos estudos de exposicao a curto prazo (24 horas), observou-se inibicao da atividade especifica nas culturas expostas durante 7 dias, com um valor de CE50 (concentracao de Hg2+ que promove 50% de decrescimo da atividade especifica) equivalente a 12,63 μM Hg2+.
Quality of Life Impacts of Bright Light Treatment, Fluoxetine, and the Combination in Patients with Nonseasonal Major Depressive Disorder: A Randomized Clinical Trial

Objective: Bright light therapy is increasingly recommended (alone or in combination with antidepressant medication) to treat symptoms of nonseasonal major depressive disorder (MDD). However, little is known about its impacts on quality of life (QoL), a holistic, patient-valued outcome. Methods: This study utilizes secondary outcome data from an 8-week randomized, controlled, double blind trial comparing light monotherapy (n = 32), fluoxetine monotherapy (n = 30), and the combination of these (n = 27) to placebo (n = 30). QoL was assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). Treatment-related differences in QoL improvements were assessed using a repeated measures analysis of variance. The influence of potential predictors of QoL (demographic variables and change in depressive symptoms) were investigated via hierarchical linear regression. Results: Q-LES-Q-SF scores significantly improved across all treatment conditions; however, no significant differences were observed between treatment arms. QoL remained poor relative to community norms by the end of the trial period: Across conditions, 70.6% of participants had significantly impaired QoL at the 8-week assessment. Reduction in depressive scores was a significant predictor of improved QoL, with the final model accounting for 54% of variance in QoL change scores. Conclusion: The findings of this study emphasize that improvement in QoL and reduction in depressive symptoms in MDD, while related, cannot be taken to be synonymous. Adjunctive therapies may be required to address unmet QoL needs in patients with MDD receiving antidepressant or light therapies. Further research is required to explore additional predictors of QoL in order to better refine treatments for MDD.
Ultrasound and Near Infrared Light Dual-triggered Upconversion Zeolite-based Nanocomposite for Hyperthermia Enhanced Multi-modal Melanoma Therapy via a Precise Apoptotic Mechanism.

High reactive oxygen species (ROS) generation efficiency as well as induction of targeted cells apoptosis are recognized as key objective to achieve highly efficient strategy for cancer therapy with minimum side effects of inflammatory reaction. However, it is still of challenge to realize higher therapeutic efficiency with a cell apoptosis model. Herein, we present strong upconversion luminescent biosafe cores derived from Linde Type A (LTA) zeolites and modification with targeted/therapeutic drugs for multi-modal therapy, in which sonodynamic therapy (SDT) combined with photodynamic therapy (PDT) increases therapeutic efficiency especially in deep sites of tumor via producing cytoplasmic ROS and mitochondrial superoxide, photothermal therapy (PTT) enhances PDT effects via higher fluorescence resonance energy transfer (FRET) efficacy attributed to an increased temperature. Furthermore, the transcriptomic analysis reveals that cellular internalization of the nanosystem can lead to tumor ablation via cell apoptosis. We expect the multi-modal therapy based on LTA zeolites drug-nanocarriers could be applied in the cancer therapeutics in the near future.
Immigration – left/right or centre/periphery? A party competition explanation for the integration policies of national minority regions

How do minority regions in multi-national states respond to immigration? Do they use regional decision-making competencies to foster inclusion of immigrants into the sub-state nation, or to tighten the boundaries of belonging exclusively around the minority group? This paper presents first results from a project that explores answers to these questions through comparative case studies of integration policies in the autonomous minority regions of Catalonia (described as inclusive in the literature) and South Tyrol (described as taking a more exclusivist approach). Qualitative content analysis of regional integration bills (the “Integrationsgesetz” in South Tyrol and the “Llei d'acollida” in Catalonia) shows that the policy response differs between regions, but also between the three dimensions of integration policy, the political-legal, the socio-economic and the cultural. The paper hypothesizes that an explanation for the differences can be found in the way parties link the issue of integration to key dimensions of regional party competition. Acknowledgements Parts of this paper have been presented at the “3-Länder-Tagung: Politik der Vielfalt”, 19-21 September, University of Innsbruck, the “GRITIM-UPF Seminar Series”, 28 October 2013, Pompeu Fabra University, and the “Inhouse Seminar” of the EURAC Institute for Minority Rights, 20 February 2014 Bolzano. I thank all those present on either of these occasions for inspiring comments and very helpful suggestions. I am indebted to the Fritz Thyssen Foundation for sponsoring me during my stay in Barcelona and Bolzano.