Miracle-dz/UniFAR-FTUs huggingface dataset:
Computational Modeling of the Crosstalk Between Macrophage Polarization and Tumor Cell Plasticity in the Tumor Microenvironment

Tumor microenvironments contain multiple cell types interacting among one another via different signaling pathways. Furthermore, both cancer cells and different immune cells can display phenotypic plasticity in response to these communicating signals, thereby leading to complex spatiotemporal patterns that can impact therapeutic response. Here, we investigate the crosstalk between cancer cells and macrophages in a tumor microenvironment through in silico (computational) co-culture models. In particular, we investigate how macrophages of different polarization (M1 vs. M2) can interact with epithelial-mesenchymal plasticity of cancer cells, and conversely, how cancer cells exhibiting different phenotypes (epithelial vs. mesenchymal) can influence the polarization of macrophages. Based on interactions documented in the literature, an interaction network of cancer cells and macrophages is constructed. The steady states of the network are then analyzed. Various interactions were removed or added into the constructed-network to test the functions of those interactions. Also, parameters in the mathematical models were varied to explore their effects on the steady states of the network. In general, the interactions between cancer cells and macrophages can give rise to multiple stable steady-states for a given set of parameters and each steady state is stable against perturbations. Importantly, we show that the system can often reach one type of stable steady states where cancer cells go extinct. Our results may help inform efficient therapeutic strategies.
Developments in Rapid Detection Methods for the Detection of Foodborne Campylobacter in the United States

The accurate and rapid detection of Campylobacter spp. is critical for optimal surveillance throughout poultry processing in the United States. The further development of highly specific and sensitive assays to detect Campylobacter in poultry matrices has tremendous utility and potential for aiding the reduction of foodborne illness. The introduction and development of molecular methods such as polymerase chain reaction (PCR) have enhanced the diagnostic capabilities of the food industry to identify the presence of foodborne pathogens throughout poultry production. Further innovations in various methodologies, such as immune-based typing and detection as well as high throughput analyses, will provide important epidemiological data such as the identification of unique or region-specific Campylobacter. Comparable to traditional microbiology and enrichment techniques, molecular techniques/methods have the potential to have improved sensitivity and specificity, as well as speed of data acquisition. This review will focus on the development and application of rapid molecular methods for identifying and quantifying Campylobacter in U.S. poultry and the emergence of novel methods that are faster and more precise than traditional microbiological techniques.
Transfusion-Transmitted Zika Virus Infection in Pregnant Mice Leads to Broad Tissue Tropism With Severe Placental Damage and Fetal Demise

Zika virus (ZIKV) infection during pregnancy can cause significant problems, particularly congenital Zika syndrome. Nevertheless, the potential deleterious consequences and associated mechanisms of transfusion-transmitted ZIKV infection on pregnant individuals and their fetuses and babies have not been investigated. Here we examined transmissibility of ZIKV through blood transfusion in ZIKV-susceptible pregnant A129 mice. Our data showed that transfused-transmitted ZIKV at the early infection stage led to significant viremia and broad tissue tropism in the pregnant recipient mice, which were not seen in those transfused with ZIKV-positive (ZIKV+) plasma at later infection stages. Importantly, pregnant mice transfused with early-stage, but not later stages, ZIKV+ plasma also exhibited severe placental infection with vascular damage and apoptosis, fetal infection and fetal damage, accompanied by fetal and pup death. Overall, this study suggests that transfusion-related transmission of ZIKV during initial stage of infection, which harbors high plasma viral titers, can cause serious adverse complications in the pregnant recipients and their fetuses and babies.
Pharmacological Blockade of Soluble Epoxide Hydrolase Attenuates the Progression of Congestive Heart Failure Combined With Chronic Kidney Disease: Insights From Studies With Fawn-Hooded Hypertensive Rats

An association between congestive heart failure (CHF) and chronic kidney disease (CKD) results in extremely poor patient survival rates. Previous studies have shown that increasing kidney epoxyeicosatrienoic acids (EETs) by blocking soluble epoxide hydrolase (sEH), an enzyme responsible for EETs degradation, improves the survival rate in CHF induced by aorto-caval fistula (ACF) and attenuates CKD progression. This prompted us to examine if sEH inhibitor treatment would improve the outcome if both experimental conditions are combined. Fawn-hooded hypertensive (FHH) rats, a genetic model showing early CKD development was employed, and CHF was induced by ACF. Treatment with an sEH inhibitor was initiated 4 weeks after ACF creation, in FHH and in fawn-hooded low-pressure (FHL) rats, a control strain without renal damage. The follow-up period was 20 weeks. We found that ACF FHH rats exhibited substantially lower survival rates (all the animals died by week 14) as compared with the 64% survival rate observed in ACF FHL rats. The former group showed pronounced albuminuria (almost 30-fold higher than in FHL) and reduced intrarenal EET concentrations. The sEH inhibitor treatment improved survival rate and distinctly reduced increases in albuminuria in ACF FHH and in ACF FHL rats, however, all the beneficial actions were more pronounced in the hypertensive strain. These data indicate that pharmacological blockade of sEH could be a novel therapeutic approach for the treatment of CHF, particularly under conditions when it is associated with CKD.
Characterizing the Interplay Between Autism Spectrum Disorder and Comorbid Medical Conditions: An Integrative Review

Co-occurring medical disorders and associated physiological abnormalities in individuals with autism spectrum disorder (ASD) may provide insight into causal pathways or underlying biological mechanisms. Here, we review medical conditions that have been repeatedly highlighted as sharing the strongest associations with ASD—epilepsy, sleep, as well as gastrointestinal and immune functioning. We describe within each condition their prevalence, associations with behavior, and evidence for successful treatment. We additionally discuss research aiming to uncover potential aetiological mechanisms. We then consider the potential interaction between each group of conditions and ASD and, based on the available evidence, propose a model that integrates these medical comorbidities in relation to potential shared aetiological mechanisms. Future research should aim to systematically examine the interactions between these physiological systems, rather than considering these in isolation, using robust and sensitive biomarkers across an individual's development. A consideration of the overlap between medical conditions and ASD may aid in defining biological subtypes within ASD and in the development of specific targeted interventions.
Unicellular Cyanobacteria Are Important Components of Phytoplankton Communities in Australia’s Northern Oceanic Ecoregions

The tropical marine environments of northern Australia encompasses a diverse range of geomorphological and oceanographic conditions and high levels of productivity and nitrogen fixation. However, efforts to characterize phytoplankton assemblages in these waters have been restricted to studies using microscopic and pigment analyses, leading to the current consensus that this region is dominated by large diatoms, dinoflagellates, and the marine cyanobacterium Trichodesmium. During an oceanographic transect from the Arafura Sea through the Torres Strait to the Coral Sea, we characterized prokaryotic and eukaryotic phytoplankton communities in surface waters using a combination of flow cytometry and Illumina based 16S and 18S ribosomal RNA amplicon sequencing. Similar to observations in other marine regions around Australian, phytoplankton assemblages throughout this entire region were rich in unicellular picocyanobacterial primary producers while picoeukaryotic phytoplankton formed a consistent, though smaller proportion of the photosynthetic biomass. Major taxonomic groups displayed distinct biogeographic patterns linked to oceanographic and nutrient conditions. Unicellular picocyanobacteria dominated in both flow cytometric abundance and carbon biomass, with members of the Synechococcus genus dominating in the shallower Arafura Sea and Torres Strait where chlorophyll a was relatively higher (averaging 0.4 ± 0.2 mg m-3), and Prochlorococcus dominating in the oligotrophic Coral Sea where chlorophyll a averaged 0.13 ± 0.07 mg m-3. Consistent with previous microscopic and pigment-based observations, we found from sequence analysis that a variety of diatoms (Bacillariophyceae) exhibited high relative abundance in the Arafura Sea and Torres Strait, while dinoflagellates (Dinophyceae) and prymnesiophytes (Prymnesiophyceae) were more abundant in the Coral Sea. Ordination analysis identified temperature, nutrient concentrations and water depth as key drivers of the region’s assemblage composition. This is the first molecular and flow cytometric survey of the abundance and diversity of both prokaryotic and picoeukaryotic phytoplankton in this region, and points to the need to include the picocyanobacterial populations as an essential oceanic variable for sustained monitoring in order to better understand the health of these important coastal waters as global oceans change.
Visual Inhibition Measures Predict Speech-in-Noise Perception Only in People With Low Levels of Education

Inhibition—the ability to suppress goal-irrelevant information—is thought to be an important cognitive skill in many situations, including speech-in-noise (SiN) listening. Both inhibition and SiN perception are thought to worsen with age, but attempts to connect age-related declines in these two abilities have produced mixed results even though a clear positive relationship has generally been hypothesized. We suggest that these inconsistencies may occur because listener-based demographic variables such as educational attainment modulate the relationship between inhibition and SiN perception. We tested this hypothesis with a group of 50 older adults (61–86 years, mean: 69.5) with mild-to-moderate age-related hearing loss (8–53 average dB HL, mean: 25.3 dB HL). Participants performed a visual Stroop task and two SiN tasks. In a Stroop task one stimulus dimension is named while a second, more prepotent dimension is ignored. Results show a clear influence of educational attainment on the relationship of visual Stroop scores to SiN performance, but only for those with lower levels of education. These findings highlight for the first time the importance of considering potentially heterogeneous demographic listener variables when analyzing cognitive tasks and their relationship to SiN perception.
Aging and Strength Training Influence Knee Extensor Intermuscular Coherence During Low- and High-Force Isometric Contractions

Aging is associated with reduced maximum force production and force steadiness during low-force tasks, but both can be improved by training. Intermuscular coherence measures coupling between two peripheral surface electromyography (EMG) signals in the frequency domain. It is thought to represent the presence of common input to alpha-motoneurons, but the functional meaning of intermuscular coherence, particularly regarding aging and training, remain unclear. This study investigated knee extensor intermuscular coherence in previously sedentary young (18–30 years) and older (67–73 years) subjects before and after a 14-week strength training intervention. YOUNG and OLDER groups performed maximum unilateral isometric knee extensions [100% maximum voluntary contraction (MVC)], as well as force steadiness tests at 20 and 70% MVC, pre- and post-training. Intermuscular (i.e., EMG-EMG) coherence analyses were performed for all (three) contraction intensities in vastus lateralis and medialis muscles. Pre-training coefficient of force variation (i.e., force steadiness) and MVC (i.e., maximum torque) were similar between groups. Both groups improved MVC through training, but YOUNG improved more than OLDER (42 ± 27 Nm versus 18 ± 16 Nm, P = 0.022). Force steadiness did not change during 20% MVC trials in either group, but YOUNG demonstrated increased coefficient of force variation during 70% MVC trials (1.28 ± 0.46 to 1.57 ± 0.70, P = 0.01). YOUNG demonstrated greater pre-training coherence during 20% and 70% MVC trials, particularly within the 8–14 Hz (e.g., 20%: 0.105 ± 0.119 versus 0.016 ± 0.009, P = 0.001) and 16–30 Hz (20%: 0.063 ± 0.078 versus 0.012 ± 0.007, P = 0.002) bands, but not during 100% MVC trials. Strength training led to increases in intermuscular coherence within the 40–60 Hz band during 70% MVC trials in YOUNG only, while OLDER decreased within the 8–14 Hz band during 100% MVC trials. Age-related differences in intermuscular coherence were observed between young and older individuals, even when neuromuscular performance levels were similar. The functional significance of intermuscular coherence remains unclear, since coherence within different frequency bands did not explain any of the variance in the regression models for maximum strength or force steadiness during 20 and 70% MVC trials.
The Reliability and Relevance of a Quality of Decision Making Instrument, Quality of Decision-Making Orientation Scheme (QoDoS), for Use During the Lifecycle of Medicines

Introduction: The Quality of Decision-Making Orientation Scheme (QoDoS) was developed to provide organisations involved in submission, approval and reimbursement of new medicines with a tool to improve the quality of their decision-making processes and is considered the most promising tool for such purpose. This study aimed to further establish the measurement properties of the QoDoS by evaluating its reliability (internal consistency and test-retest reliability) and relevance in the target population. Methods: The study participants consisted of 55 individuals recruited from pharmaceutical companies, regulatory and HTA agencies. It was designed as a longitudinal study with participants assessed on two different occasions, at baseline (test 1) and then 7 days later (test 2). Internal consistency reliability was assessed with Cronbach’s alpha and the test-retest reliability was evaluated using the intraclass correlation coefficients (ICC) based on absolute agreement, 2 way mixed-effects model for the four QoDoS domains. The relevance of the QoDoS was evaluated by applying cognitive debriefing using five short feedback questions following test 1. Results: Test 1 was completed by 44 study participants (80% response rate) and test 2 was completed by 32 of the 44 individuals, resulting in a 73% response rate. Cronbach’s alpha coefficient was greater than 0.7 across all the domains for test 1 and test 2, ranging from 0.71 to 0.79, indicating good consistency of responses. For the overall score across all 47 items, the Cronbach’s alpha coefficient was 0.81 for test 1 and 0.86 for test 2, which is rated as very good. The four QoDoS domains showed moderate to strong reproducibility (ICC range: 0.63–0.86). The outcome of the cognitive debriefing from the 43 respondents (98% response rate) confirmed the relevance (95% agreement), language clarity (95%) and completeness of items (86%); the clarity of the scaling (91%) as well as spontaneity of responses (95%). Conclusion: These results provide strong support for the relevance and reliability of the QoDoS, which are key properties for future longitudinal and cross-sectional applications of the instrument when evaluating quality of decision making by those involved in the lifecycle of medicines.
A Comprehensive Analysis of Fibroblast Growth Factor Receptor 2b Signaling on Epithelial Tip Progenitor Cells During Early Mouse Lung Branching Morphogenesis

This study demonstrates that FGF10/FGFR2b signaling on distal epithelial progenitor cells, via ß-catenin/EP300, controls, through a comprehensive set of developmental genes, morphogenesis, and differentiation. Fibroblast growth factor (FGF) 10 signaling through FGF receptor 2b (FGFR2b) is mandatory during early lung development as the deletion of either the ligand or the receptor leads to lung agenesis. However, this drastic phenotype previously hampered characterization of the primary biological activities, immediate downstream targets and mechanisms of action. Through the use of a dominant negative transgenic mouse model (Rosa26rtTA; tet(o)sFgfr2b), we conditionally inhibited FGF10 signaling in vivo in E12.5 embryonic lungs via doxycycline IP injection to pregnant females, and in vitro by culturing control and experimental lungs with doxycycline. The impact on branching morphogenesis 9 h after doxycycline administration was analyzed by morphometry, fluorescence and electron microscopy. Gene arrays at 6 and 9 h following doxycycline administration were carried out. The relationship between FGF10 and ß-catenin signaling was also analyzed through in vitro experiments using IQ1, a pharmacological inhibitor of ß-catenin/EP300 transcriptional activity. Loss of FGF10 signaling did not impact proliferation or survival, but affected both adherens junctions (up-regulation of E-cadherin), and basement membrane organization (increased laminin). Gene arrays identified multiple direct targets of FGF10, including main transcription factors. Immunofluorescence showed a down-regulation of the distal epithelial marker SOX9 and mis-expression distally of the proximal marker SOX2. Staining for the transcriptionally-active form of ß-catenin showed a reduction in experimental vs. control lungs. In vitro experiments using IQ1 phenocopied the impacts of blocking FGF10. This study demonstrates that FGF10/FGFR2b signaling on distal epithelial progenitor cells via ß-catenin/EP300 controls, through a comprehensive set of developmental genes, cell adhesion, and differentiation.
Upregulated Interleukin 21 Receptor Enhances Proliferation and Epithelial-Mesenchymal Transition Process in Benign Prostatic Hyperplasia

Background: Interleukins (ILs) and related chronic inflammation have been found to contribute to the development of benign prostatic hyperplasia (BPH) in recent decades. As a late member of the ILs family, IL-21 receptor (IL-21R) can modulate cell proliferation, however, IL-21R activity in the prostate has not been examined. The current study aimed to elucidate a potential role of IL-21R in the development of BPH. Material and Methods: Human prostate tissues, cell lines and rats were used. QRT-PCR, Western blot, and immunohistochemistry, along with hematoxylin and eosin, Masson's trichrome, and immunofluorescent staining were performed. BPH-1 cells with IL-21R silenced were cultured or co-cultured with macrophages (active THP-1, AcTHP-1). Apoptosis and cell cycle phases were determined via flow cytometry. Epithelial-mesenchymal transition (EMT) processes were also examined. In vivo, rat prostatitis was induced with intraprostatic injected lipopolysaccharide (LPS). Results: IL-21R was highly expressed in human as well as rat prostate, mainly in the epithelial compartment. BPH concomitant with prostatitis significantly upregulated the expression of IL-21R. Knockdown of IL-21R induced cell apoptosis and cycle arrest at G0/G1 phase, and blocked the EMT process in BPH-1 cells. When IL-21R silenced BPH-1 cells were co-cultured with AcTHP-1 cells, these aforementioned processes and IL-21R change were completely reversed. Prostatic hyperplasia was observed with IL-21R upregulated in LPS induced prostatitis rats. More specifically, the expression of apoptosis, cyclin, and EMT proteins in this rat model are altered in a manner consistent with that seen in the cell line model. Conclusions: Our novel data demonstrates the expression and functional activities of IL-21R in the mechanism for development of BPH. IL-21R mainly localized in prostate epithelium and it was upregulated in hyperplastic prostate tissues. IL-21R enhanced proliferation of BPH-1 cells, via inhibiting cell apoptosis, and modulating cell cycles, as well as the EMT process, in response to inflammatory stimuli.
CULTIVO PROTEGIDO: UMA ALTERNATIVA NA PRODUÇÃO ORGÂNICA DE VIDEIRA

O objetivo do trabalho foi avaliar a incidencia e severidade de doencas, assim como, as necessidades de controle fitossanitario que sao impostas pelo cultivo protegido de videira e desta forma, sua viabilidade como cultivo orgânico. O experimento foi realizado no ciclo 2006/07, em Flores da Cunha-RS, em vinhedo de Vitis vinifera ‘Moscato Giallo’, conduzido em “Y”, com e sem cobertura plastica. Em ambas areas, caracterizou-se o microclima. Na area coberta foram aplicados fungicidas somente se necessario, enquanto que na area descoberta foram realizadas aplicacoes por calendario. Durante a floracao e a maturacao, avaliou-se a incidencia e a severidade das principais doencas fungicas de ocorrencia na regiao. Nao houve necessidade de utilizacao de fungicidas no cultivo protegido, o qual evitou o estabelecimento de mildio, e diminuiu a incidencia e severidade de podridoes de cacho, devido a alteracao microclimatica. Portanto, esta tecnologia apresentou-se como uma importante ferramenta na viabilizacao da producao orgânica de uvas.
Arabic community question answering

Abstract We analyze resources and models for Arabic community Question Answering (cQA). In particular, we focus on CQA-MD, our cQA corpus for Arabic in the domain of medical forums. We describe the corpus and the main challenges it poses due to its mix of informal and formal language, and of different Arabic dialects, as well as due to its medical nature. We further present a shared task on cQA at SemEval, the International Workshop on Semantic Evaluation, based on this corpus. We discuss the features and the machine learning approaches used by the teams who participated in the task, with focus on the models that exploit syntactic information using convolutional tree kernels and neural word embeddings. We further analyze and extend the outcome of the SemEval challenge by training a meta-classifier combining the output of several systems. This allows us to compare different features and different learning algorithms in an indirect way. Finally, we analyze the most frequent errors common to all approaches, categorizing them into prototypical cases, and zooming into the way syntactic information in tree kernel approaches can help solve some of the most difficult cases. We believe that our analysis and the lessons learned from the process of corpus creation as well as from the shared task analysis will be helpful for future research on Arabic cQA.
The effect of morphology in named entity recognition with sequence tagging

Abstract This work proposes a sequential tagger for named entity recognition in morphologically rich languages. Several schemes for representing the morphological analysis of a word in the context of named entity recognition are examined. Word representations are formed by concatenating word and character embeddings with the morphological embeddings based on these schemes. The impact of these representations is measured by training and evaluating a sequential tagger composed of a conditional random field layer on top of a bidirectional long short-term memory layer. Experiments with Turkish, Czech, Hungarian, Finnish and Spanish produce the state-of-the-art results for all these languages, indicating that the representation of morphological information improves performance.