Miracle-dz/UniFAR-FTUs huggingface dataset:
Post-traumatic stress disorder moderates the relationship between trauma exposure and chronic pain

ABSTRACT Background: Trauma exposure and post-traumatic stress disorder (PTSD) are risk factors for chronic pain. Objective: This study investigated how exposure to intentional and non-intentional traumatic events and PTSD are related to pain severity and outcome of treatment in chronic pain patients. Methods: We assessed exposure to potentially traumatizing events, psychiatric diagnosis with structured clinical interview, and pain severity in 63 patients at a secondary multidisciplinary pain clinic at the beginning of treatment, and assessed level of pain at follow up. Exposure to potentially traumatizing events and PTSD were regressed on pain severity at the initial session and at follow up in a set of multiple regression analysis. Results: The participants reported exposure to an average of four potentially traumatizing events, and 32% had PTSD. Exposure to intentional traumatic events and PTSD were significantly associated with more severe pain, and PTSD significantly moderated the relationship between trauma exposure and pain (all p < .05). The treatment programme reduced pain moderately, an effect that was unrelated to trauma exposure and PTSD. Conclusions: Trauma exposure is related to chronic pain in the same pattern as to mental disorders, with intentional trauma being most strongly related to pain severity. PTSD moderated the relationship between trauma exposure and pain. While pain patients with PTSD initially report more pain, they responded equally to specialist pain treatment as persons without PTSD.
Membrane potential and cancer progression

Membrane potential (Vm), the voltage across the plasma membrane, arises because of the presence of different ion channels/transporters with specific ion selectivity and permeability. Vm is a key biophysical signal in non-excitable cells, modulating important cellular activities, such as proliferation and differentiation. Therefore, the multiplicities of various ion channels/transporters expressed on different cells are finely tuned in order to regulate the Vm. It is well-established that cancer cells possess distinct bioelectrical properties. Notably, electrophysiological analyses in many cancer cell types have revealed a depolarized Vm that favors cell proliferation. Ion channels/transporters control cell volume and migration, and emerging data also suggest that the level of Vm has functional roles in cancer cell migration. In addition, hyperpolarization is necessary for stem cell differentiation. For example, both osteogenesis and adipogenesis are hindered in human mesenchymal stem cells (hMSCs) under depolarizing conditions. Therefore, in the context of cancer, membrane depolarization might be important for the emergence and maintenance of cancer stem cells (CSCs), giving rise to sustained tumor growth. This review aims to provide a broad understanding of the Vm as a bioelectrical signal in cancer cells by examining several key types of ion channels that contribute to its regulation. The mechanisms by which Vm regulates cancer cell proliferation, migration, and differentiation will be discussed. In the long term, Vm might be a valuable clinical marker for tumor detection with prognostic value, and could even be artificially modified in order to inhibit tumor growth and metastasis.
Downregulation of Nipah Virus N mRNA Occurs through Interaction between Its 3′ Untranslated Region and hnRNP D

ABSTRACT Nipah virus (NiV) is a nonsegmented, single-stranded, negative-sense RNA virus belonging to the genus Henipavirus, family Paramyxoviridae. NiV causes acute encephalitis and respiratory disease in humans, is associated with high mortality, and poses a threat in southern Asia. The genomes of henipaviruses are about 18,246 nucleotides (nt) long, which is longer than those of other paramyxoviruses (around 15,384 nt). This difference is caused by the noncoding RNA region, particularly the 3′ untranslated region (UTR), which occupies more than half of the noncoding RNA region. To determine the function(s) of the NiV noncoding RNA region, we investigated the effects of NiV 3′ UTRs on reporter gene expression. The NiV N 3′ UTR (nt 1 to 100) demonstrated strong repressor activity associated with hnRNP D protein binding to that region. Mutation of the hnRNP D binding site or knockdown of hnRNP D resulted in increased expression of the NiV N 3′ UTR reporter. Our findings suggest that NiV N expression is repressed by hnRNP D through the NiV N 3′ UTR and demonstrate the involvement of posttranscriptional regulation in the NiV life cycle. To the best of our knowledge, this provides the first report of the functions of the NiV noncoding RNA region.
Vascularized composite allotransplantation: current standards and novel approaches to prevent acute rejection and chronic allograft deterioration

The advent of more potent immunosuppressants led to the first successful human upper extremity transplantation in 1998. At this time, >100 upper extremity transplants, 30 face transplants, and a variety of other vascularized composite allotransplantation (VCA) procedures have been performed around the world. VCA recipients present unique challenges for transplantation. The incidence of acute rejection exceeds 80% in hand and face transplantation and is well documented, whereas reports about antibody‐mediated rejection and chronic rejection remain scarce. Immunosuppression protocols commonly used at US centers are derived from solid organ transplantation protocols. Novel approaches to minimize rejections in VCA may include improved HLA matching and considerations toward cytomegalovirus infection status. New graft preservation techniques may decrease immunogenicity prior to transplant. Novel monitoring methods such as valid biomarkers, ultrasound biomicroscopy, and sentinel flaps may enable earlier diagnosis of rejection. Cell‐based therapies are being explored to achieve immunosuppressive regimen minimization or even tolerance induction. The efficacy of local immunosuppression in clinical VCA remains controversial. In conclusion, although immunosuppressive strategies adapted from SOT have demonstrated good midterm results, focusing on the unique features of VCA grafts may enable additional, more specific treatment strategies in the future and improved long‐term graft outcomes.
Chemical strategies for the covalent modification of filamentous phage

Historically filamentous bacteriophage have been known to be the workhorse of phage display due to their ability to link genotype to phenotype. More recently, the filamentous phage scaffold has proven to be powerful outside the realm of phage display technology in fields such as molecular imaging, cancer research and materials, and vaccine development. The ability of the virion to serve as a platform for a variety of applications heavily relies on the functionalization of the phage coat proteins with a wide variety of functionalities. Genetic modification of the coat proteins has been the most widely used strategy for functionalizing the virion; however, complementary chemical modification strategies can help to diversify the range of materials that can be developed. This review emphasizes the recent advances that have been made in the chemical modification of filamentous phage as well as some of the challenges that are involved in functionalizing the virion.
Ror2/Frizzled Complex Mediates Wnt5a-Induced AP-1 Activation by Regulating Dishevelled Polymerization

ABSTRACT The receptor tyrosine kinase Ror2 acts as a receptor or coreceptor for Wnt5a to mediate Wnt5a-induced activation of the Wnt/JNK pathway and inhibition of the β-catenin-dependent canonical Wnt pathway. However, little is known about how Ror2 cooperates with another receptor component(s) to mediate Wnt5a signaling. We show here that Ror2 regulates Wnt5a-induced polymerization of Dishevelled (Dvl) and that this Ror2-mediated regulation of Dvl is independent of the cytoplasmic region of Ror2. Ror2 can associate with Frizzled7 (Fz7) via its extracellular cysteine-rich domain to form a receptor complex that is required for the regulation of Dvl and activation of the AP-1 promoter after Wnt5a stimulation. Suppressed expression of Fz7 indeed results in the inhibition of Wnt5a-induced polymerization of Dvl and AP-1 activation. Interestingly, both the DIX and the DEP domains of Dvl are indispensable for Dvl polymerization and subsequent AP-1 activation after Wnt5a stimulation. We further show that polymerized Dvl is colocalized with Rac1 and that suppressed expression of Rac1 inhibits Wnt5a-induced AP-1 activation. Collectively, our results indicate that Ror2/Fz receptor complex plays an important role in the Wnt5a/Rac1/AP-1 pathway by regulating the polymerization of Dvl.
Interaction of Botulinum Toxin with the Epithelial Barrier

Botulinum neurotoxin (BoNT) is a protein toxin (~150 kDa), which possesses a metalloprotease activity. Food-borne botulism is manifested when BoNT is absorbed from the digestive tract to the blood stream and enters the peripheral nerves, where the toxin cleaves core proteins of the neuroexocytosis apparatus and elicits the inhibition of neurotransmitter release. The initial obstacle to orally ingested BoNT entering the body is the epithelial barrier of the digestive tract. Recent cell biology and molecular biology studies are beginning to elucidate the mechanism by which this large protein toxin crosses the epithelial barrier. In this review, we provide an overview of the structural features of botulinum toxins (BoNT and BoNT complex) and the interaction of these toxins with the epithelial barrier.
Maximum likelihood estimation in meta‐analytic structural equation modeling

Meta‐analytic structural equation modeling (MASEM) involves fitting models to a common population correlation matrix that is estimated on the basis of correlation coefficients that are reported by a number of independent studies. MASEM typically consist of two stages. The method that has been found to perform best in terms of statistical properties is the two‐stage structural equation modeling, in which maximum likelihood analysis is used to estimate the common correlation matrix in the first stage, and weighted least squares analysis is used to fit structural equation models to the common correlation matrix in the second stage. In the present paper, we propose an alternative method, ML MASEM, that uses ML estimation throughout. In a simulation study, we use both methods and compare chi‐square distributions, bias in parameter estimates, false positive rates, and true positive rates. Both methods appear to yield unbiased parameter estimates and false and true positive rates that are close to the expected values. ML MASEM parameter estimates are found to be significantly less bias than two‐stage structural equation modeling estimates, but the differences are very small. The choice between the two methods may therefore be based on other fundamental or practical arguments. Copyright © 2016 John Wiley & Sons, Ltd.
Evaluation of emerging TSV-enabled main memories on the PARSEC benchmark

This paper evaluates emerging TSV-interconnected memory technologies employed as the main memory of 3D Symmetric MultiProcessing (SMP). As the target architecture, we implemented a typical 3D SMP including L1 and L2 caches together with some tiers of main memory. Besides, we employed DDR3 as a baseline comparison to normalize all results. The experimental results show a tradeoff between energy efficiency and execution time when using six memory technologies executing a set of applications of PARSEC benchmark on Gem5. All evaluated memories reveal significant reductions in energy consumption with some penalization on the execution time. Additionally, HBM shows to be the most promising one, reducing more than five times the energy consumption and giving a small performance boost than DDR3, in general.
The Broiler Breeder Paradox: ethical, genetic and physiological perspectives, and suggestions for solutions

1. Due to intensive selection, broiler chickens became the most efficient meat-producing animals because of their fast growth, supported by a virtually unlimited voluntary feed intake. These characteristics cause many problems in the management of broiler breeder hens because of the negative correlation between muscle growth and reproduction effectiveness. 2. This problem, namely the fast muscle growth versus reproduction health paradox, induces a second paradox, acceptable reproduction and health versus hunger stress and impaired welfare, because broiler breeder hens require dedicated programmes of feed restriction (1) to maximise egg and chick production and (2) to avoid metabolic disorders and mortality in broiler breeders. 3. Given that poultry selection is a global large-scale business and chickens are a prolific species, improvement in profit can only be obtained by selecting on feed conversion and/or for higher breast meat percentage, which will intensify the broiler–breeder paradox. 4. New feeding strategies are being studied, but it is questionable if the paradox can be solved by management tools alone. Because breeding and selection are long-term processes, involving animals, farmers, consumers, industry, environment etc., a more sustainable breeding goal needs to be determined by a multidisciplinary approach and an open debate between several actors in the discussion. 5. Using dwarf broiler breeder hens could be one alternative, because dwarf hens combine relatively good reproductive fitness with ad libitum feeding. Another possibility is to accept lower broiler productivity by assigning economic values to welfare and including integrity traits in an extended breeding goal.
Tungsten Oxide (WO3) Films Prepared by Sol-Gel Spin-Coating Technique

Tungsten oxide (WO3) is a transition metal oxide with a wide range of applications such as displays, rear-view mirrors, electrochromic (EC) smart windows and gas sensors. Many techniques were adopted for the fabrication of WO3, namely magnetron sputtering, spray pyrolysis and sol-gel synthesis techniques. In this work, WO3 films were deposited on indium tin oxide (ITO) coated glasses by sol-gel spin-coating method. The film thickness was varied by depositing different number of layers. The WO3 film thickness and optical transmittance were determined using step profilometer and ultraviolet-visible (UV-Vis) spectrophotometer, respectively. WO3 film thicknesses increased from 38 nm to 606 nmwith increasing number of deposited layers.The optical transmittance of the WO3 films in visible range decreased with increasing film thickness. The optical transmittance were at least 70 % up to 10 deposited layers.WO3is a promising EC material in the application ofEC devices (ECDs). The application of WO3 in the EC devices will be discussed.
Individual and Workplace Factors that Influence Psychiatric Nursing Staff's Participation in Clinical Supervision: A Survey Study and Prospective Longitudinal Registration

This paper reports findings from a survey of 239 psychiatric nursing staff. This study aimed to investigate how often psychiatric nursing staff participates in clinical supervision and any possible associations among individual and workplace factors in relation to participation. The survey findings are followed by a prospective longitudinal registration of participants in clinical supervision. The registration revealed that participation varies considerably and large numbers of the staff may not participate in clinical supervision at all. Characteristics of the workplace, including organisational location, work shift, and work-environmental factors, are related to participation and, consequently, may affect the outcome of clinical supervision.
Extractor codes

We study error-correcting codes for highly noisy channels. For example, every received signal in the channel may originate from some half of the symbols in the alphabet. Our main conceptual contribution is an equivalence between error-correcting codes for such channels and extractors. Our main technical contribution is a new explicit error-correcting code based on Trevisan's extractor that can handle such channels, and even noisier ones. Our new code has polynomial-time encoding and polynomial-time soft-decision decoding. We note that Reed-Solomon codes cannot handle such channels, and our study exposes some limitations on list decoding of Reed-Solomon codes. Another advantage of our equivalence is that when the Johnson bound is restated in terms of extractors, it becomes the well-known Leftover Hash Lemma. This yields a new proof of the Johnson bound which applies to large alphabets and soft decoding. Our explicit codes are useful in several applications. First, they yield algorithms to extract many hardcore bits using few auxiliary random bits. Second, they are the key tool in a recent scheme to compactly store a set of elements in a way that membership in the set can be determined by looking at only one bit of the representation. Finally, they are the basis for the recent construction of high-noise, almost-optimal rate list-decodable codes over large alphabets.
3D bioprinting for tissue engineering: Stem cells in hydrogels

Surgical limitations require alternative methods of repairing and replacing diseased and damaged tissue. Regenerative medicine is a growing area of research with engineered tissues already being used successfully in patients. However, the demand for such tissues greatly outweighs the supply and a fast and accurate method of production is still required. 3D bioprinting offers precision control as well as the ability to incorporate biological cues and cells directly into the material as it is being fabricated. Having precise control over scaffold morphology and chemistry is a significant step towards controlling cellular behaviour, particularly where undifferentiated cells, i.e., stem cells, are used. This level of control in the early stages of tissue development is crucial in building more complex systems that morphologically and functionally mimic in vivo tissue. Here we review 3D printing hydrogel materials for tissue engineering purposes and the incorporation of cells within them. Hydrogels are ideal materials for cell culture. They are structurally similar to native extracellular matrix, have a high nutrient retention capacity, allow cells to migrate and can be formed under mild conditions. The techniques used to produce these materials, as well as their benefits and limitations, are outlined.
PKR Regulates B56α-mediated BCL2 Phosphatase Activity in Acute Lymphoblastic Leukemia-derived REH Cells*

Protein phosphatase 2A (PP2A) is a heterotrimer comprising catalytic, scaffold, and regulatory (B) subunits. There are at least 21 B subunit family members. Thus PP2A is actually a family of enzymes defined by which B subunit is used. The B56 family member B56α is a phosphoprotein that regulates dephosphorylation of BCL2. The stress kinase PKR has been shown to phosphorylate B56α at serine 28 in vitro, but it has been unclear how PKR might regulate the BCL2 phosphatase. In the present study, PKR regulation of B56α in REH cells was examined, because these cells exhibit robust BCL2 phosphatase activity. PKR was found to be basally active in REH cells as would be predicted if the kinase supports B56α-mediated dephosphorylation of BCL2. Suppression of PKR promoted BCL2 phosphorylation with concomitant loss of B56α phosphorylation at serine 28 and inhibition of mitochondrial PP2A activity. PKR supports stress signaling in REH cells, as suppression of PKR promoted chemoresistance to etoposide. Suppression of PKR promoted B56α proteolysis, which could be blocked by a proteasome inhibitor. However, the mechanism by which PKR supports B56α protein does not involve PKR-mediated phosphorylation of the B subunit at serine 28 but may involve eIF2α activation of AKT. Phosphorylation of serine 28 by PKR promotes mitochondrial localization of B56α, because wild-type but not mutant S28A B56α promoted mitochondrial PP2A activity. Cells expressing wild-type B56α but not S28A B56α were sensitized to etoposide. These results suggest that PKR regulates B56α-mediated PP2A signaling in REH cells.
KLF 15 is a positive regulatory factor in the process of myocardial remodeling and angiogenesis induced by pressure overload

Objectives: To elucidate the role of KLF15 on cardiac fibroblast in the dynamic angiogenesis in pressureoverload cardiac remodeling. Methods: Aortic banding was performed in rats to induce pressure-overload and cardiac hypertrophy. Part of the animals has their aorta constriction removed 3 or 6 weeks after the banding surgery. Cardiac function by echocardiography, cardiac tissue morphology and fibrosis, interstitial angiogenesis and KLF15 expression were measured. The effect of KLF15 on cardiac fibroblasts and vascular endothelial cells was determined in vitro using an over-expression system by KLF15 recombinant adenovirus to investigate the role of KLF15 in angiogenesis. Results: Pressure overload led to cardiac dysfunction, myocardial hypertrophy and fibrosis, accompanied with decreased capillary density. These phenotypes were associated with decreased cardiac expression level of KLF5. All cardiac dysfunction and hypertrophy phenotypes were slowed down or reversed by de-banding the constriction at an early stage (3 weeks after banding) together with a normalized cardiac KLF5 level, and partially reversed at a late stage (6 weeks after banding). In vitro over-expressing KLF15 in cardiac fibroblast promoted the formation of budding and tubular structure of endothelial cells in a three-dimensional co-cultures system, providing a potential causational relation between KLF15 and angiogenesis. Conclusion: Pressure-overload induced cardiac hypertrophy led to enhanced vascular angiogenesis which was possibly regulated by KLF15 base on both in vivo and in vitro data. Pressure-overload alleviation resulted in improved cardiac function, and partial reversal of fibrosis and angiogenesis with reversed KLF15 levels.
Troponin as a Biomarker of Cardiac Toxicity

Cardiac troponin (cTn) is a sensitive and specific biomarker for assessing cardiac damage and should be utilized in drug safety assessment. Lactate dehydrogenase and creatine kinase isoenzyme analyses have historically been used in pre-clinical toxicity testing to assess cardiac injury, but since these assays are less sensitive and specific than cTn, isoenzyme analyses, as determined by the manual electrophoretic technique, are no longer warranted. Commercial cTn assays developed for humans do not have the same immunoreactivity and functional sensitivity in the common pre-clinical testing species, so it is important to show that the assay that is chosen is appropriate for the pre-clinical species being assessed. The kinetics of the cTn response depends on the dose and frequency of test article administration as well as the mechanism of the cardiac injury induced by the test article. Cardiac troponin should be used in the assessment of classes of compound that have previously been shown to induce cardiac necrosis or if cardiac necrosis is identified histologically with a novel compound. Next generation high sensitivity cTn assays are being developed and the low levels of cTn detected with these assays may be an early sign of possibly reversible damage to the heart.