Miracle-dz/UniFAR-FTUs huggingface dataset:
TNFAIP8 Deficiency Exacerbates Acute Graft Versus Host Disease in a Murine Model of Allogeneic Hematopoietic Cell Transplantation

Background. Gastrointestinal acute graft-versus-host disease (GVHD) occurring after allogeneic hematopoietic cell transplant is an allo-reactive T cell and inflammatory cytokine driven organ injury with epithelial apoptosis as 1 of its hallmark findings and is associated with significant mortality. Tumor necrosis factor (TNF)-alpha-induced protein 8 (TNFAIP8 or TIPE) acts as a negative mediator of apoptosis via inhibition of caspase-3 activation, promotes cell proliferation and Tipe−/− deficiency is associated with increased inflammation. Methods. To evaluate the role of TIPE in acute GVHD, naive C57BL/6 and Tipe−/− C57BL/6 mice were conditioned with 1000 cGy single dose total body irradiation, followed by transplantation of 10 million bone marrow cells and 20 million splenocytes from either syngeneic C57BL/6 or allogeneic BALB/c donors. Results. Allo TIPE-deficient mice developed exacerbated gut GVHD compared with allo controls and had significantly decreased survival (6 wk overall survival: 85% versus 37%; P < 0.05), higher clinical GVHD scores, more profound weight loss, increased serum proinflammatory cytokines (interleukin-17A, TNF, interleukin-6, and interferon-γ). T-cell infiltration into the ileum was increased; epithelial proliferation was decreased along with significantly higher levels of chemokines KC and monokine induced by gamma interferon. Using bone marrow chimeric experiments, TIPE was found to have a role in both hematopoietic and nonhematopoietic cells. Conclusions. Absence of TIPE results in excessive inflammation and tissue injury after allo-HCT, supporting that TIPE confers immune homeostasis and has tissue-protective function during the development of gut GVHD and may be a potential future target to prevent or treat this complication after allogeneic HCT.
Mutations of RAS genes in endometrial polyps

Endometrial polyps are common, yet the molecular mechanisms underlying their formation and progression remain unclear. We examined gene mutations possibly related to the pathogenesis of endometrial polyps, as well as to their clinical features. Four premenopausal patients with endometrial polyps, who were not under drug treatment, were recruited. Whole exomes of endometrial polyps and peripheral blood lymphocytes were analyzed by next-generation sequencing, and somatic mutations were derived by subtraction. Then, 35 samples of endometrial polyps and 12 samples of atypical polypoid adenomyoma were newly recruited to validate the identified mutations by polymerase chain reaction-reverse sequence specific oligonucleotide method. The mutations were also analyzed in separate stromal and glandular components of the polyps after laser-capture microdissection. Whole exome sequencing revealed that KRAS mutations were the only type of mutation detectable in multiple cases (2/4). Targeted mutation analysis revealed that 16 of 35 samples (45.7%) of endometrial polyps harbored RAS mutations. Mutation-positive cases exhibited a significantly higher number of endometrial polyps (3.25±2.70 vs. 1.74±0.87, P=0.045). Laser-capture microdissection in NRAS-mutated endometrial polyps revealed that both stromal and glandular components harbored RAS mutations. There was no RAS mutation in 12 samples of atypical polypoid adenomyoma. This is the first report demonstrating that pathogenic RAS mutations are frequent in non-treated endometrial polyps. RAS mutations may have an important role in tumorigenesis and in the formation of multiple endometrial polyps.
Sales data as a measure of antibiotics usage: Concepts, examples and discussion of influencing factors

Abstract Monitoring and surveillance of antimicrobial usage in animals is a public health concern and different methods are currently discussed widely in public, science and politics. The objective of the paper is to present the available methods of monitoring and to discuss possible differences in the assessment of the antibiotics treatment. Sales data are expressed as the average amount of substance per animal or kg live weight (e.g. population‐corrected unit, PCU). The number of Defined Daily Doses (nDDDvet) is calculated by extrapolating sales data with average animal weights and defined drug doses to a number of treatments theoretically applied to animals. In contrast, the number of Used Daily Doses (nUDDvet) displays the actual number of treatments which have been applied. As sales data are relatively easily obtained, they are frequently used. However, their results are influenced by the composition of the population and by the dose of the substances. As both may vary strongly between countries, direct comparison of sales data between countries may be misleading. The concept of analysing sales data is shown by exemplarily using the methods in the ESVAC report 2015. The presentation of usage data in terms of nDDDvet or of nUDDvet increases the comparability of the data from different countries or time periods. Furthermore, fluoroquinolones and third‐/fourth‐generation cephalosporins which, among other substances, bare a potential risk for human health, are used at low doses. Hence, their use contributes to a sales reduction while contrasting the guidelines of prudent use. nDDDvet or nUDDvet have the ability to better reflect the treatment frequency and thus to better link antibiotics use to public health concerns. Quantification of antibiotics should assist to focus on prudent use of antimicrobials to reduce the burden of resistant bacteria and, thus, enhance public health, animal health and animal welfare.
Arm movements induced by noninvasive optogenetic stimulation of the motor cortex in the common marmoset

Significance Which brain area drives hand/arm movements after learning or brain injury? When does motor cortical activity generate appropriate hand/arm movements? To address these issues, it is necessary to manipulate motor cortical activity in a controlled manner. Optogenetic tools allow neuronal activity to be manipulated in a variety of animals, but forelimb movements in nonhuman primates have not previously been optogenetically induced or modulated. Here, we improved a method of optogenetic cortical stimulation and induced overt forelimb movements in the common marmoset, a New World monkey. Photostimulation also modulated voluntary forelimb movements, with the modulated movement trajectories depending on the stimulation site and timing. Our results open doors for noninvasive interrogation of motor circuits in behaving nonhuman primates. Optogenetics is now a fundamental tool for investigating the relationship between neuronal activity and behavior. However, its application to the investigation of motor control systems in nonhuman primates is rather limited, because optogenetic stimulation of cortical neurons in nonhuman primates has failed to induce or modulate any hand/arm movements. Here, we used a tetracycline-inducible gene expression system carrying CaMKII promoter and the gene encoding a Channelrhodopsin-2 variant with fast kinetics in the common marmoset, a small New World monkey. In an awake state, forelimb movements could be induced when Channelrhodopsin-2−expressing neurons in the motor cortex were illuminated by blue laser light with a spot diameter of 1 mm or 2 mm through a cranial window without cortical invasion. Forelimb muscles responded 10 ms to 50 ms after photostimulation onset. Long-duration (500 ms) photostimulation induced discrete forelimb movements that could be markerlessly tracked with charge-coupled device cameras and a deep learning algorithm. Long-duration photostimulation mapping revealed that the primary motor cortex is divided into multiple domains that can induce hand and elbow movements in different directions. During performance of a forelimb movement task, movement trajectories were modulated by weak photostimulation, which did not induce visible forelimb movements at rest, around the onset of task-relevant movement. The modulation was biased toward the movement direction induced by the strong photostimulation. Combined with calcium imaging, all-optical interrogation of motor circuits should be possible in behaving marmosets.
Fast and Robust Monocular Visua-Inertial Odometry Using Points and Lines

When the camera moves quickly and the image is blurred or the texture in the scene is missing, the Simultaneous Localization and Mapping (SLAM) algorithm based on point feature experiences difficulty tracking enough effective feature points, and the positioning accuracy and robustness are poor, and even may not work properly. For this problem, we propose a monocular visual odometry algorithm based on the point and line features and combining IMU measurement data. Based on this, an environmental-feature map with geometric information is constructed, and the IMU measurement data is incorporated to provide prior and scale information for the visual localization algorithm. Then, the initial pose estimation is obtained based on the motion estimation of the sparse image alignment, and the feature alignment is further performed to obtain the sub-pixel level feature correlation. Finally, more accurate poses and 3D landmarks are obtained by minimizing the re-projection errors of local map points and lines. The experimental results on EuRoC public datasets show that the proposed algorithm outperforms the Open Keyframe-based Visual-Inertial SLAM (OKVIS-mono) algorithm and Oriented FAST and Rotated BRIEF-SLAM (ORB-SLAM) algorithm, which demonstrates the accuracy and speed of the algorithm.
Intravenous thrombolytic therapy in acute ischemic stroke: The art and science of treatment decision making

Intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) within 3 h of symptom onset is currently approved for treatment of acute ischemic stroke. Those who present within 3 h and have a vascular occlusion and a good CT scan are the ideal candidates for thrombolysis. Clinical trials and phase IV data has shed substantial light on the factors associated with more favorable outcomes with tPA. In the 3-6 h time window, cerebral perfusion information can be used for selection of patients for thrombolytic therapy. In many special circumstances, such as seizure at stroke onset, stroke on awakening, age more than 80 years, and patients with rapidly improving symptoms, the decision to treat depends on expert judgment. Due to the narrow time window, the fear of bleeding complications, and doubts regarding its effectiveness, tPA is still underused. Constant efforts are required to educate the public on the fact that stroke is a treatable emergency.
Comparison of Gene Delivery to the Kidney by Adenovirus, Adeno-associated Virus, and Lentiviral Vectors after Intravenous and Direct Kidney Injections.

There are many kidney diseases that might be addressed by gene therapy. However, gene delivery to kidney cells is inefficient. This is due in part to the fact that the kidney excludes molecules above 50 kDa and that most gene delivery vectors are megaDaltons in mass. We compared the ability of adeno-associated virus (AAV), adenovirus (Ad), and lentiviral (LV) vectors to deliver genes to renal cells. When vectors were delivered by the intravenous (IV) route in mice, weak luciferase activity was observed in the kidney with substantially more in the liver. When gene delivery was observed in the kidney, expression was primarily in the glomerulus. To avoid these limitations, vectors were injected directly into the kidney by retrograde ureteral (RU), and subcapsular (SC) injections in mice. Small AAV vectors transduced the kidney, but also leaked from the organ and mediated higher levels of transduction in off-target tissues. Comparison of AAV2, 6.2, 8, and rh10 vectors by direct kidney injection demonstrated highest delivery by AAV6.2 and 8. Larger Ad and LV vectors transduced kidney cells and mediated less off-target tissue transduction. These data demonstrate the utility of direct kidney injections to circumvent the kidney size exclusion barrier. They also identify the effects of vector size on on-target and off-target transduction. This lays the foundation for the use of different vector platforms for gene therapy of diverse kidney diseases.
Asymmetric Distribution of Gene Trees Can Arise Under Purifying Selection if Differences in Population Size Exist.

Incomplete lineage sorting (ILS) is an important factor that causes gene tree discordance. For gene trees of three species, under neutrality, random mating and the absence of interspecific gene flow, ILS creates a symmetric distribution of gene trees: the gene tree that accords with the species tree has the highest frequency, and the two discordant trees are equally frequent. If the neutral condition is violated, the impact of ILS may change, altering the gene tree distribution. Here, we show that under purifying selection, even assuming that the fitness effect of mutations is constant throughout the species tree, if differences in population size exist among species, asymmetric distributions of gene trees will arise, which is different from the expectation under neutrality. In extremes, one of the discordant trees rather than the concordant tree becomes the most frequent gene tree. In addition, we found that in a real case, the position of Scandentia relative to Primate and Glires, the symmetry in the gene tree distribution can be influenced by the strength of purifying selection. In current phylogenetic inference, the impact of purifying selection on the gene tree distribution is rarely considered by researchers. This study highlights the necessity of considering this impact.
Cranial suture biomechanics in Metoposaurus krasiejowensis (Temnospondyli, Stereospondyli) from the upper Triassic of Poland

Cranial sutures connect adjacent bones of the skull and play an important role in the absorption of stresses that may occur during different activities. The Late Triassic temnospondyl amphibian Metoposaurus krasiejowensis has been extensively studied over the years in terms of skull biomechanics, but without a detailed description of the function of cranial sutures. In the present study, 34 thin sections of cranial sutures were examined in order to determine their histovariability and interpret their biomechanical role in the skull. The histological model was compared with three‐dimensional‐finite element analysis (FEA) simulations of the skull under bilateral and lateral biting as well as skull‐raising loads for maximum and minimum principal stress. Histologically, only two sutural morphologies were recognised in the skull of Metoposaurus: interdigitated sutures (commonly associated with compressive stresses) are dominant along the entire length of the skull roof and palate; tongue‐and‐groove sutures (commonly associated with tensile stresses) are present across the maxilla. FEA shows a much more complex picture of stress type and distribution than predicted by sutures. Common to both methods is a predominance of compressive stresses which act on the skull during biting. The methods predict different stress regimes during biting in the posterior part of the skull: where histological analysis suggests compression, FEA predicts tension. For lateral biting and skull raising, histological and digital reconstructions show similar general patterns but with some variations.
Laser-Patternable Graphene Field Emitters for Plasma Displays

This paper presents a plasma display device (PDD) based on laser-induced graphene nanoribbons (LIGNs), which were directly fabricated on polyimide sheets. Superior field electron emission (FEE) characteristics, viz. a low turn-on field of 0.44 V/μm and a large field enhancement factor of 4578, were achieved for the LIGNs. Utilizing LIGNs as a cathode in a PDD showed excellent plasma illumination characteristics with a prolonged plasma lifetime stability. Moreover, the LIGN cathodes were directly laser-patternable. Such superior plasma illumination performance of LIGN-based PDDs has the potential to make a significant impact on display technology.
A New Approach for Motor Imagery Classification Based on Sorted Blind Source Separation, Continuous Wavelet Transform, and Convolutional Neural Network

Brain-Computer Interfaces (BCI) are systems that allow the interaction of people and devices on the grounds of brain activity. The noninvasive and most viable way to obtain such information is by using electroencephalography (EEG). However, these signals have a low signal-to-noise ratio, as well as a low spatial resolution. This work proposes a new method built from the combination of a Blind Source Separation (BSS) to obtain estimated independent components, a 2D representation of these component signals using the Continuous Wavelet Transform (CWT), and a classification stage using a Convolutional Neural Network (CNN) approach. A criterion based on the spectral correlation with a Movement Related Independent Component (MRIC) is used to sort the estimated sources by BSS, thus reducing the spatial variance. The experimental results of 94.66% using a k-fold cross validation are competitive with techniques recently reported in the state-of-the-art.
Formation of Nanospikes on AISI 420 Martensitic Stainless Steel under Gallium Ion Bombardment

The focused ion beam (FIB) has proven to be an extremely powerful tool for the nanometer-scale machining and patterning of nanostructures. In this work, we experimentally study the behavior of AISI 420 martensitic stainless steel when bombarded by Ga+ ions in a FIB system. The results show the formation of nanometer sized spiky structures. Utilizing the nanospiking effect, we fabricated a single-tip needle with a measured 15.15 nanometer curvature radius and a microneedle with a nanometer sized spiky surface. The nanospikes can be made straight or angled, depending on the incident angle between the sample and the beam. We also show that the nanospiking effect is present in ferritic AISI 430 stainless steel. The weak occurrence of the nanospiking effect in between nano-rough regions (nano-cliffs) was also witnessed for austenitic AISI 316 and martensitic AISI 431 stainless steel samples.
Repurposing peptidomimetic as potential inhibitor of New Delhi metallo-β-lactamases in Gram-negative bacteria.

The emergence, prevalence and rapid spread of New Delhi metallo-β-lactamases (NDMs) in Gram-negative pathogens threaten our traditional regimen to treat bacterial infectious diseases. Discovery of novel NDMs inhibitors offers an alternative approach to restore the carbapenems activity. However, thus far, no clinical inhibitor of NDMs has been approved. In this study, the potential of peptides and analogues as carbapenems adjuvant in NDMs-positive pathogens were investigated. Herein, we successfully found that peptidomimetic 4 (PEP4) is a potential inhibitor of NDM enzymes. PEP4 displayed significant synergistic activity with meropenem against NDM-expression Gram-negative bacteria in vitro. Moreover, PEP4 effectively restored meropenem efficacy in mice infection models infected with NDM-5-positive E. coli. These data demonstrated the high potential of PEP4 as carbapenems adjuvant to address NDMs-positive Gram-negative pathogens.
Surgical Management of Vestibular Schwannoma: Practice Pattern Analysis via NSQIP

Objective: Characterize current perspectives in the surgical management of vestibular schwannoma (VS) to guide otolaryngologists in understanding United States practice patterns. Methods: A retrospective analysis of ACS-NSQIP database was performed to abstract all patients from 2008 to 2016 who underwent VS resection using ICD-9/10 codes 225.1 and D33.3, respectively. The specific surgical approach employed was identified via CPT codes 61520, 61526/61596, and 61591, which represent retrosigmoid (RS), translabyrinthine (TL) and middle cranial fossa (MCF) approaches, respectively. Analyzed outcomes include general surgical complications, total length of stay, and reoperation. Results: A total of 1671 VS cases were identified, 1266 (75.7%) were RS, 292 (17.5%) were TL, and 114 (6.8%) were MCF. The annual number of cases increased over the study period from 15 to 375, which is chiefly attributed to increased institutional participation in ACS-NSQIP. Perioperative variables including BMI (P < .001), ASA class (P = .004), ethnicity (P = .008), operative time (P < .001), and reoperation (P < .001) were found to be statistically significant between cohorts. Increased utilization of RS approach was consistent over the entire study period, with significantly more RS performed than either TL or MCF. Finally, a statistically significant difference with respect to general surgical complication rates was not noted between surgical approaches. Conclusions: There is increased employment of RS approach for the operative management of VS, which likely is the result of increased reliance on both stereotactic radiosurgery and observation as alternative treatment strategies.
Caveolin-1 Regulates P2Y2 Receptor Signaling during Mechanical Injury in Human 1321N1 Astrocytoma

Caveolae-associated protein caveolin-1 (Cav-1) plays key roles in cellular processes such as mechanosensing, receptor coupling to signaling pathways, cell growth, apoptosis, and cancer. In 1321N1 astrocytoma cells Cav-1 interacts with the P2Y2 receptor (P2Y2R) to modulate its downstream signaling. P2Y2R and its signaling machinery also mediate pro-survival actions after mechanical injury. This study determines if Cav-1 knockdown (KD) affects P2Y2R signaling and its pro-survival actions in the 1321N1 astrocytoma cells mechanical injury model system. KD of Cav-1 decreased its expression in 1321N1 cells devoid of or expressing hHAP2Y2R by ~88% and ~85%, respectively. Cav-1 KD had no significant impact on P2Y2R expression. Post-injury densitometric analysis of pERK1/2 and Akt activities in Cav-1-positive 1321N1 cells (devoid of or expressing a hHAP2Y2R) revealed a P2Y2R-dependent temporal increase in both kinases. These temporal increases in pERK1/2 and pAkt were significantly decreased in Cav-1 KD 1321N1 (devoid of or expressing a hHAP2Y2R). Cav-1 KD led to an ~2.0-fold and ~2.4-fold decrease in the magnitude of the hHAP2Y2R-mediated pERK1/2 and pAkt kinases’ activity, respectively. These early-onset hHAP2Y2R-mediated signaling responses in Cav-1-expressing and Cav-1 KD 1321N1 correlated with changes in cell viability (via a resazurin-based method) and apoptosis (via caspase-9 expression). In Cav-1-positive 1321N1 cells, expression of hHAP2Y2R led to a significant increase in cell viability and decreased apoptotic (caspase-9) activity after mechanical injury. In contrast, hHAP2Y2R-elicited changes in viability and apoptotic (caspase-9) activity were decreased after mechanical injury in Cav-1 KD 1321N1 cells expressing hHAP2Y2R. These findings support the importance of Cav-1 in modulating P2Y2R signaling during mechanical injury and its protective actions in a human astrocytoma cell line, whilst shedding light on potential new venues for brain injury or trauma interventions.