Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression and role of cocaine-amphetamine regulated transcript (CART) in the proliferation of biliary epithelium

Cholangiocytes, the epithelial cells that line the biliary tree, can proliferate under the stimulation of several factors through both autocrine and paracrine pathways. The cocaine-amphetamine-regulated-transcript (CART) peptide has several physiological functions, and it is widely expressed in several organs. CART increases the survival of hippocampal neurons by upregulating brain-derived neurotrophic factor (BDNF), whose expression has been correlated to the proliferation rate of cholangiocytes. In the present study, we aimed to evaluate the expression of CART and its role in modulating cholangiocyte proliferation in healthy and bile duct ligated (BDL) rats in vivo, as well as in cultured normal rat cholangiocytes (NRC) in vitro. Liver samples from both healthy and BDL (1 week) rats, were analyzed by immunohistochemistry and immunofluorescence for CART, CK19, TrkB and p75NTR BDNF receptors. PCNA staining was used to evaluate the proliferation of the cholangiocytes, whereas TUNEL assay was used to evaluate biliary apoptosis. NRC treated or not with CART were used to confirm the role of CART on cholangiocytes proliferation and the secretion of BDNF. Cholangiocytes proliferation, apoptosis, CART and TrkB expression were increased in BDL rats, compared to control rats. We found a higher expression of TrkB and p75NTR, which could be correlated with the proliferation rate of biliary tree during BDL. The in vitro study demonstrated increased BDNF secretion by NRC after treatment with CART compared with control cells. As previously reported, proliferating cholangiocytes acquire a neuroendocrine phenotype, modulated by several factors, including neurotrophins. Accordingly, CART may play a key role in the remodeling of biliary epithelium during cholestasis by modulating the secretion of BDNF.
Lung and bone metastases patterns in limb osteosarcoma: Surgical treatment of primary site improves overall survival

Osteosarcoma (OS) is one of the most prevalent malignant bone tumors. The proportion of patients with limb OS was relatively high. Lung metastasis (LM) and bone metastasis are the first and second most common metastatic types of OS, respectively. A total of 270 new cases of LM, 55 new cases of bone metastases (BM), and 36 new cases of lung and BM were diagnosed in the surveillance, epidemiology and end results database from 2010 to 2019. Univariate and multivariate logistic regression analyses were used to identify the risk factors for lung and/or BM, and Cox regression analyses were performed to identify the prognostic factors for lung and/or BM. Kaplan–Meier curves and log-rank tests were used to analyze the overall survival of limb OS patients with lung and/or BM. Female sex, telangiectatic OS type, central OS type, T3 stage, N1 stage, BM, surgical treatments, radiotherapy and chemotherapy were significantly correlated with LM. T3 stage, LM, liver metastases, and radiotherapy significantly correlated with BM. The small cell OS type, T2 stage, T3 stage, N1 stage, liver metastases, and radiotherapy were significantly correlated with lung and BM. Among limb OS patients with LM, the mean survival months of older age, black race, N1 stage, BM, brain metastases, no surgery, and no chemotherapy were lower than those of the control group. In limb OS patients with LM and BM, the mean survival months in the no surgery group was lower than in the surgery group. T stage and radiotherapy significantly influence the occurrence of limb OS with lung and/or BM. Surgery at the primary site has been shown to be effective in improving the survival rate of patients with lung and/or BM.
Clinical remission in severe asthma with biologic therapy: an analysis from the UK Severe Asthma Registry

Background Novel biologic therapies have revolutionised the management of severe asthma with more ambitious treatment aims. Here we analyse the definition of clinical remission as a suggested treatment goal and consider the characteristics associated with clinical remission in a large, real-world severe asthma cohort. Methods This was a retrospective analysis of severe asthma patients registered in the UK Severe Asthma Registry (UKSAR) who met strict national access criteria for biologics. Patients had a pre-biologics baseline assessment and annual review. The primary definition of clinical remission applied included Asthma Control Questionnaire (ACQ)-5 <1.5 and no oral corticosteroids for disease control and forced expiratory volume in 1 s above lower limit of normal or no more than 100 mL less than baseline. Results 18.3% of patients achieved the primary definition of remission. The adjusted odds of remission on biologic therapy were 7.44 (95% CI 1.73–31.95)-fold higher in patients with type 2 (T2)-high biomarkers. The adjusted odds of remission were lower in patients who were female (OR 0.61, 95% CI 0.45–0.93), obese (OR 0.49, 95% CI 0.24–0.65) or had ACQ-5 ≥1.5 (OR 0.19, 95% CI 0.12–0.31) pre-biologic therapy. The likelihood of remission reduced by 14% (95% CI 0.76–0.97) for every 10-year increase in disease duration. 12–21% of the cohort attained clinical remission depending on the definition applied; most of those who did not achieve remission failed to meet multiple criteria. Conclusions 18.3% of patients achieved the primary definition of clinical remission. Remission was more likely in T2-high biomarker patients with shorter duration of disease and less comorbidity. Further research on the optimum time to commence biologics in severe asthma is required. Tweetable abstract Analysis of a real-world severe asthma registry shows clinical remission rates of 18%; associated pre-biologic characteristics include male sex, never smoking, BMI <30 kg·m−2, shorter disease duration, T2-high biomarkers and lower symptom burden https://bit.ly/46JLeDb
Application of microfluidic technologies in forensic analysis

The application of microfluidic technology in forensic medicine has steadily expanded over the last two decades due to the favorable features of low cost, rapidity, high throughput, user‐friendliness, contamination‐free, and minimum sample and reagent consumption. In this context, bibliometric methods were adopted to visualize the literature information contained in the Science Citation Index Expanded from 1989 to 2022, focusing on the co‐occurrence analysis of forensic and microfluidic topics. A deep interpretation of the literature was conducted based on co‐occurrence results, in which microfluidic technologies and their applications in forensic medicine, particularly forensic genetics, were elaborated. The purpose of this review is to provide an impartial evaluation of the utilization of microfluidic technology in forensic medicine. Additionally, the challenges and future trends of implementing microfluidic technology in forensic genetics are also addressed.
Everglades virus: an underrecognized disease-causing subtype of Venezuelan equine encephalitis virus endemic to Florida, USA

Everglades virus (EVEV) is subtype II of the Venezuelan equine encephalitis virus (VEEV) complex (Togaviridae: Alphavirus), endemic to Florida, USA. EVEV belongs to a clade that includes both enzootic and epizootic/ epidemic VEEV subtypes. Like other enzootic VEEV subtypes, muroid rodents are important vertebrate hosts for EVEV and certain mosquitoes are important vectors. The hispid cotton rat Sigmodon hispidus and cotton mouse Peromyscus gossypinus are important EVEV hosts, based on natural infection (virus isolation and high seropositivity), host competence (experimental infections), and frequency of contact with the vector. The mosquito Culex (Melanoconion) cecedei is the only confirmed vector of EVEV based upon high natural infection rates, efficient vector competence, and frequent feeding upon muroid rodents. Human disease attributed to EVEV is considered rare. However, cases of meningitis and encephalitis are recorded from multiple sites, separated by 250 km or more. Phylogenetic analyses indicate that EVEV is evolving, possibly due to changes in the mammal community. Mutations in the EVEV genome are of concern, given that epidemic strains of VEEV (subtypes IAB and IC) are derived from enzootic subtype ID, the closest genetic relative of EVEV. Should epizootic mutations arise in EVEV, the abundance of Aedes taeniorhynchus and other epizootic VEEV vectors in southern Florida provides a conducive environment for widespread transmission. Other factors that will likely influence the distribution and frequency of EVEV transmission include the establishment of Culex panocossa in Florida, Everglades restoration, mammal community decline due to the Burmese python, land use alteration by humans, and climate change.
Global transcriptomic analysis of breast cancer and normal mammary epithelial cells infected with Borrelia burgdorferi

Abstract The bacterial spirochete Borrelia burgdorferi, the causative agent of Lyme Disease, can disseminate and colonize various tissues and organs, orchestrating severe clinical symptoms including arthritis, carditis, and neuroborreliosis. Previous research has demonstrated that breast cancer tissues could provide an ideal habitat for diverse populations of bacteria, including B. burgdorferi, which is associated with a poor prognosis. Recently, we demonstrated that infection with B. burgdorferi enhances the invasion and migration of triple-negative MDA-MB-231 cells which represent a type of breast tumor with more aggressive cancer traits. In this study, we hypothesized that infection by B. burgdorferi affects the expression of cancer-associated genes to effectuate breast cancer phenotypes. We applied the high-throughput technique of RNA-sequencing on B. burgdorferi-infected MDA-MB-231 breast cancer and normal-like MCF10A cells to determine the most differentially expressed genes (DEG) upon infection. Overall, 142 DEGs were identified between uninfected and infected samples in MDA-MB-231 while 95 DEGs were found in MCF10A cells. A major trend of the upregulation of C-X-C and C-C motif chemokine family members as well as genes and pathways was associated with infection, inflammation, and cancer. These genes could serve as potential biomarkers for pathogen-related tumorigenesis and cancer progression which could lead to new therapeutic opportunities.
Two social minds in one brain? error-related negativity provides evidence for parallel processing pathways during social evaluation

ABSTRACT Several authors assume that evaluative conditioning (EC) relies on high-level propositional thinking. In contrast, the dual-process perspective proposes two processing pathways, one associative and the other propositional, contributing to EC. Dual-process theorists argue that attitudinal ambiguity resulting from these two pathways’ conflicting evaluations demonstrate the involvement of both automatic and controlled processes in EC. Previously, we suggested that amplitude variations of error-related negativity and error-positivity, two well-researched event-related potentials of performance monitoring, allow for the detection of attitudinal ambiguity at the neural level. The present study utilises self-reported evaluation, categorisation performance, and neural correlates of performance monitoring to explore associative-propositional ambiguity during social attitude formation. Our results show that compared to associative-propositional harmony, attitudinal ambiguity correlates with more neutral subjective evaluations, longer response times, increased error commission, and diminished error-related negativity amplitudes. While our findings align with dual-process models, we aim to offer a propositional interpretation. We discuss dual-process theories in the context of evolutionary psychology, suggesting that associative processes may only represent a small piece of the EC puzzle.
Polyamines and hypusination are important for Clostridioides difficile toxin B (TcdB)-mediated activation of group 3 innate lymphocytes (ILC3s)

ABSTRACT Clostridioides difficile is the most common cause of nosocomial gastrointestinal tract bacterial infections. We lack fully effective reliable treatments for this pathogen, and there is a critical need to better understand how C. difficile interacts with our immune system. Group 3 innate lymphocytes (ILC3s) are rare immune cells localized within mucosal tissues that protect against bacterial infections. Upon activation, ILC3s secrete high levels of the cytokine interleukin-22 (IL-22), which is a critical regulator of tissue responses during infection. C. difficile toxin B (TcdB), the major virulence factor, directly activates ILC3s, resulting in high IL-22 levels. We previously reported that polyamines are important in the activation of ILC3s by the innate cytokine interleukin-23 (IL-23) but did not identify a specific mechanism. In this study, we examine how a pathogen impacts a metabolic pathway important for immune cell function and hypothesized that polyamines are important in TcdB-mediated ILC3 activation. We show that TcdB upregulates the polyamine biosynthesis pathway, and the inhibition of the pathway decreases TcdB-mediated ILC3 activation. Two polyamines, putrescine and spermidine, are involved. Spermidine is the key polyamine in the hypusination of eukaryotic initiation factor 5A (eIF5A), and the inhibition of eIF5A reduced ILC3 activation. Thus, there is potential to leverage polyamines in ILC3s to promote activation of ILC3s during C. difficile infection and other bacterial infections where ILC3s serve a protective role.
User behavior in microblogs with a cultural emphasis

The main objective of this thesis is to carry out a multidisciplinary study of the behavior of microblog users. To that end we first explore several user behavior patterns employing data mining techniques. Then we use social science theories of culture and socio-economic indicators to better understand differences and similarities of user behavior across countries. We found several insights on user behavior such as (i) social link recommendations made by current friends have a large effect on link formation and the accepted recommendations have more longevity than other links; (ii) as users mature, they evolve to adopt microblogs as a news media rather than a social network; (iii) the collective behavior of users from some countries standout, based on certain special characteristics such as conversations, reciprocity, etc.; (iv) national culture determines the temporal patterns with which users post, or the extent to which they mention, follow, recommend and befriend others; and (v) socio-economic and cultural features improve the prediction of communication strength among users from different countries.
Charged nanoporous phosphorene as a water desalination membrane: insights from molecular dynamics

Phosphorene, due to its remarkable properties such as self-passivation, stability, and anti-fouling, makes it a promising material for desalination membranes. Practically, these membranes acquire charges and affect the salt rejection and water flux. In this article, water desalination performance through positively charged (PC), negatively charged (NC), and charged but overall neutral (CN) single-layer nanoporous phosphorene (NPP) membrane of nanopore size ∼41 Å2 is investigated using pressure-driven molecular dynamics simulations. It is observed that the electrostatic interactions due to the distribution of charge around the nanopore edges strongly affect the desalination performance rather than steric hindrance. Overall, with an equivalent magnitude of total applied charge, the water flux through the CN membrane is more than PC and NC membranes. A membrane best suited for desalination performance among the charged NPP membranes is a CN membrane due to its high flux and adequate salt rejection, though it allows the passage of both ions. Comparatively, a PC or NC membrane has lower flux and allows the course of their counter ions respectively. To construe this observation salt ion density maps and molar concentration profiles are further examined. The degree of localization of counter ions around the nanopore edge increases with the increased total applied charge. While no such localization is observed for the CN membranes. PC and NC membranes provide more energetic barriers to co-ions due to strong coulombic repulsions and molecular layering of the adsorbed water, which hinder their transport. This study suggests the design of charged phosphorene membranes to maximize water transport while still maintaining the salt rejection potential.
Improvement in Activities of Daily Living among Danish Centenarians?

Citation for pulished version (APA): Rasmussen, S. H. , Thinggaard, M. , Højgaard, M. B. , Jeune, B. , Christensen, K. , & Andersen-Ranberg, K. (2018). Improvement in Activities of Daily Living among Danish Centenarians? A Comparative Study of Two Centenarian Cohorts Born Twenty Years Apart. The journals of gerontology. Series A, Biological sciences and medical sciences, 73(8), 1125–1131. https://doi.org/10.1093/gerona/glx113
Iron supplementation: A qualitative study on the perception of blood donors, blood collection staff and donor physicians

Iron supplementation is an effective strategy to mitigate donation‐induced iron deficiency in blood donors. However, evidence on the perception of individuals involved in blood donation on iron supplementation as a blood service policy is lacking. This study aimed to evaluate the knowledge and perception of whole blood donors (donors), blood collection staff (collection staff) and donor physicians (physicians) regarding donation‐induced iron loss and iron supplementation.
LRBA signalosomes activate vasopressin‐induced AQP2 trafficking at recycling endosomes

Aquaporin‐2 (AQP2) water channels are proteins that are recycled between intracellular vesicles and the apical plasma membrane in renal collecting ducts. Lipopolysaccharide‐responsive beige‐like anchor protein (LRBA) is a protein kinase A (PKA) anchoring protein that creates compartmentalized PKA signalling responsible for AQP2 phosphorylation. In response to increased plasma osmolality, vasopressin/cyclic adenosine monophosphate (cAMP)/PKA signalling phosphorylates AQP2, promoting AQP2 trafficking into the apical plasma membrane and increasing water reabsorption from urine. However, the molecular mechanisms by which LRBA mediates vasopressin‐induced AQP2 phosphorylation remain unknown. To investigate AQP2 intracellular localization and phosphorylation status in vivo, a density gradient ultracentrifugation technique was combined with an in situ proximity ligation assay, super‐resolution structured illumination microscopy and immunoelectron microscopy. Most of the AQP2 was localized on the recycling endosome in the presence of tolvaptan, a vasopressin type 2 receptor (V2R) antagonist. Desmopressin, a V2R agonist, phosphorylated AQP2, translocating it from the recycling endosome to the apical plasma membrane. In contrast, LRBA was constitutively localized at the recycling endosome. Therefore, LRBA and AQP2 were well colocalized in the absence of vasopressin stimulation. The loss of LRBA/PKA signalling by Lrba knockout impaired vasopressin‐induced AQP2 phosphorylation, resulting in AQP2 retention at the recycling endosome. Defective AQP2 trafficking caused low urinary concentrating ability in Lrba−/− mice. The LRBA‐PKA complex created compartmentalized PKA signalling at the recycling endosome, which facilitated AQP2 phosphorylation in response to vasopressin.
Data-Driven Gradient Regularization for Quasi-Newton Optimization in Iterative Grating Interferometry CT Reconstruction

Grating interferometry CT (GI-CT) is a promising technology that could play an important role in future breast cancer imaging. Thanks to its sensitivity to refraction and small-angle scattering, GI-CT could augment the diagnostic content of conventional absorption-based CT. However, reconstructing GI-CT tomographies is a complex task because of ill problem conditioning and high noise amplitudes. It has previously been shown that combining data-driven regularization with iterative reconstruction is promising for tackling challenging inverse problems in medical imaging. In this work, we present an algorithm that allows seamless combination of data-driven regularization with quasi-Newton solvers, which can better deal with ill-conditioned problems compared to gradient descent-based optimization algorithms. Contrary to most available algorithms, our method applies regularization in the gradient domain rather than in the image domain. This comes with a crucial advantage when applied in conjunction with quasi-Newton solvers: the Hessian is approximated solely based on denoised data. We apply the proposed method, which we call GradReg, to both conventional breast CT and GI-CT and show that both significantly benefit from our approach in terms of dose efficiency. Moreover, our results suggest that thanks to its sharper gradients that carry more high spatial-frequency content, GI-CT can benefit more from GradReg compared to conventional breast CT. Crucially, GradReg can be applied to any image reconstruction task which relies on gradient-based updates.
IMPACT OF TROPOSPHERIC OZONE ON THE EURO

29 The impact of ozone on European vegetation is largely under-investigated, despite huge areas of 30 Europe are exposed to high ozone levels and which are expected to increase in the next future. 31 We studied the potential effects of ozone on photosynthesis and leaf area index as well as the 32 feedback between vegetation and atmospheric chemistry using a land surface model (ORCHIDEE) 33 at high spatial resolution (30 km) coupled with a chemistry transport model (CHIMERE) for the 34 whole year 2002. 35 Our results show that the effect of tropospheric ozone on vegetation leads to a reduction in yearly 36 gross primary production (GPP) of about 22% and a reduction in leaf area index (LAI) of 15-20%. 37 Larger impacts have been found during summer, when ozone reaches higher concentrations. During 38 these months the maximum GPP decrease is up to 4 gC m d, and the maximum LAI reduction is 39 up to 0.7 m/m. 40 Since CHIMERE uses the LAI computed by ORCHIDEE to estimate the biogenic emissions, a LAI 41 reduction may have severe implications on the simulated atmospheric chemistry. We found a large 42 change in ozone precursors that however leads to small changes in tropospheric ozone 43 concentration, while larger changes have been found for surface NO2 concentrations. 44
High-resolution seismic reflection profiling: an aid for resolving the Pleistocene stratigraphy of a buried valley in central Illinois, USA

Abstract High-resolution seismic reflection (HRSR) data acquired over the Pesotum Bedrock Valley in central Illinois, USA, helped construct the seismic stratigraphy of a valley fill and the overlying sediments. Integrating these data with drilling and borehole geophysics allowed us to develop a seismo-stratigraphic classification for sediments on undulating and folded bedrock. Seven seismo-stratigraphic units that overlie the bedrock surface were characterized. Seismic units A and B include glacial sediments of multiple Pleistocene glaciations above the Pesotum Bedrock Valley, which completely mask the feature. Seismic units C–F, the valley fill, primarily include tills and glacial lake sediment deposited during the earliest Pleistocene glaciations and preglacial alluvium and colluvium that is draped over in situ weathered bedrock. The preservation of conformable-lying glacial and preglacial deposits and paucity of sand and gravel in the buried valley strongly indicate that little or no incision by glacial meltwaters has occurred. These observations contrast markedly with interpretations from buried valleys elsewhere in North America and northern Europe where valley fills contain significant deposits of sand and gravel in tunnel valleys. The HRSR data assisted the characterization and analysis of heterogeneous sedimentary sequences over a buried valley where existing subsurface information was limited. The extent of Pleistocene-age glacial lakes is inferred from the lateral continuity of silt and clay units.