Miracle-dz/UniFAR-FTUs huggingface dataset:
Complement receptor C5aR1 blockade reprograms tumor‐associated macrophages and synergizes with anti‐PD‐1 therapy in gastric cancer

In gastric cancer (GC), the therapeutic response of immune checkpoint blockade (ICB) remains suboptimal. Targeting myeloid cell checkpoints might be feasible as adjuvant to current ICB regimens. We sought to evaluate the crucial role of C5aR1+ TAMs in regulating antitumor immunity and the efficacy of combinatorial treatment with antiprogrammed cell death protein‐1 (PD‐1) and C5aR1 blockade. Here, we found that C5aR1 was predominantly expressed on macrophages and high level of C5aR1+ TAMs infiltration could predict poor prognosis and inferior chemotherapeutic response. The flow cytometry (FCM) and single‐cell RNA‐seq (scRNA‐seq) data revealed that C5aR1+ TAMs exhibited immunosuppressive property which might contribute to CD8+ T cell dysfunction. Blockade of C5aR1 could diminish the immunosuppressive function of TAMs and led to reinvigorated CD8+ T cells mediated antitumor immunity. Moreover, using in vitro intervention experiment based on fresh GC surgical specimens, we discovered that C5aR1 blockade exert a synergistic effect when combined with PD‐1 inhibitor for tumor clearance. Our study demonstrated that C5aR1 is a critical myeloid checkpoint and plays a crucial role in regulating the immunosuppressive property of TAMs and CD8+ T cell immune tolerance. C5aR1 blockade reprograms TAMs and reinvigorated the cytotoxicity of CD8+ T cells, thus improving the efficacy of anti‐PD‐1 therapy for tumor eradication in GC.
Free convection in low-temperature gaseous helium

Free convection has been studied in gaseous helium at low temperatures in a cylindrical vessel of aspect ratio (diameterlheight) 2·5. Compared with measurements in fluids at room temperature the present arrangement has the advantages of small size, a short time constant and improved accuracy. As the Rayleigh number was varied from 60 to 2 × 109, the Nusselt number rose from 1 to 69, obeying the relation Nu = 0·173Ra0·2800±0·0005 over the upper four decades of Ra. The critical Rayleigh number was 1630, but the conditions of the experiment did not allow reliable measurements at such low values of Ra. The very high sensitivity within a given experiment showed the presence of several ‘discrete transitions’, which were often step like and not merely a change of gradient as reported by other workers. The largest of these, at Ra = 3 · 105, involved a drop in heat flux of some 6% and was somewhat hysteretic. The temperature fluctuations increased markedly as the step was crossed.
MiR-214 Expression Is Elevated in Chronic Rhinosinusitis Mucosa and Regulates Lipopolysaccharide-Mediated Responses in Undifferentiated Human Nasal Epithelial Cell Culture

Background Chronic rhinosinusitis (CRS) is an inflammatory disorder of the upper airways. MicroRNAs (miRs) are reported to regulate several diverse physiological and pathological processes. Objective This study aimed to evaluate the impact of miR-214 on lipopolysaccharide (LPS)-mediated inflammation, and mucin 5AC (MUC5AC) expression in human nasal epithelial cells. Methods The expression of miR-214 was detected in CRS with polyps (CRSwNP) and CRS without polyps (CRSsNP) tissues. Cells were treated with LPS and a miR-214 inhibitor. The level of miR-214 was detected by quantitative real-time reverse transcriptase-PCR (qRT-PCR). The inflammatory cytokines (IL-6, IL-8, TNF, and IL-1β) and MUC5AC production were determined by qRT-PCR and ELISA. MUC5AC protein level was detected using western blot. Similarly, we determined the relationship between miR-214 and Sirtuin 1 (SIRT1) using the Dual luciferase activity assay. Results miR-214 was increased in CRSwNP and CRSsNP tissues. LPS triggered the expression of miR-214, while miR-214 inhibition diminished the level of miR-214. MiR-214 inhibition prevented LPS-mediated the production of inflammatory cytokines. LPS treatment augmented MUC5AC mRNA, protein levels, and secretion, whereas miR-214 loss inhibited MUC5AC production in the presence of LPS. SIRT1 is a direct target of miR-214. Impairing SIRT1 by siRNA (siSIRT1) or EX527 (a selective SIRT1 inhibitor) reversed the effects of miR-214 inhibitor on inflammation and MUC5AC expression. Furthermore, miR-214 depression inhibited the STAT3/GDF15 pathway via targeting SIRT1. Upregulation of STAT3 or GDF15 partly abolished the anti-inflammatory roles of miR-214 inhibitor. Conclusion Taken together, miR-214 regulates LPS-mediated inflammation and MUC5AC expression via targeting SIRT1, and STAT3/GDF15 may involve in the regulation of miR-214 inhibitor on inflammation and MUC5AC expression.
Natural History of Pediatric Cyclic Vomiting Syndrome: Progression to Dysautonomia

Background: The clinical features of pediatric cyclic vomiting syndrome (CVS) often evolve over time. Many patients develop a constellation of chronic symptoms that suggest autonomic nervous system (ANS) dysfunction during adolescence. We aimed to determine the proportion of children with CVS who develop chronic rather than episodic symptoms consistent with ANS dysfunction. Methods: Retrospective chart review of children ages 0–18 years followed in an outpatient tertiary care CVS center. Patients completed standardized questionnaires at intake and follow-up visits, documenting clinical symptom pattern. Continuous variables are summarized as median [interquartile range (IQR)]. A Mann-Whitney test was used for group comparisons. Results: One hundred subjects were included. A total of 40% developed symptoms of ANS dysfunction (ANS+); 20% were confirmed by comprehensive ANS testing, 11% by orthostatic vital sign abnormalities, and 9% by clinical symptoms. The median (IQR) age at onset of chronic symptoms was 14 (10.02, 15) years. The presence of another disorder of gut-brain interaction (P = 0.018) and a greater number of comorbidities (P = 0.031) were more common in the ANS+ group. ANS+ subjects missed more school days (P= 0.047) and were seen less frequently in the emergency department (P = 0.023). Conclusions: Many children with CVS (40%) develop symptoms consistent with clinical dysautonomia in adolescence. These patients experience more comorbid conditions and a greater impact on school attendance, possibly representing a worsened quality of life as their disease course transitions to daily symptoms. When symptoms of CVS change over time, therapeutic interventions may need to be adjusted and targeted accordingly.
Long Noncoding RNA Expression Independently Predicts Outcome in Pediatric Acute Myeloid Leukemia

PURPOSE Optimized strategies for risk classification are essential to tailor therapy for patients with biologically distinctive disease. Risk classification in pediatric acute myeloid leukemia (pAML) relies on detection of translocations and gene mutations. Long noncoding RNA (lncRNA) transcripts have been shown to associate with and mediate malignant phenotypes in acute myeloid leukemia (AML) but have not been comprehensively evaluated in pAML. METHODS To identify lncRNA transcripts associated with outcomes, we evaluated the annotated lncRNA landscape by transcript sequencing of 1,298 pediatric and 96 adult AML specimens. Upregulated lncRNAs identified in the pAML training set were used to establish a regularized Cox regression model of event-free survival (EFS), yielding a 37 lncRNA signature (lncScore). Discretized lncScores were correlated with initial and postinduction treatment outcomes using Cox proportional hazards models in validation sets. Predictive model performance was compared with standard stratification methods by concordance analysis. RESULTS Training set cases with positive lncScores had 5-year EFS and overall survival rates of 26.7% and 42.7%, respectively, compared with 56.9% and 76.3% with negative lncScores (hazard ratio, 2.48 and 3.16; P < .001). Pediatric validation cohorts and an adult AML group yielded comparable results in magnitude and significance. lncScore remained independently prognostic in multivariable models, including key factors used in preinduction and postinduction risk stratification. Subgroup analysis suggested that lncScores provide additional outcome information in heterogeneous subgroups currently classified as indeterminate risk. Concordance analysis showed that lncScore adds to overall classification accuracy with at least comparable predictive performance to current stratification methods that rely on multiple assays. CONCLUSION Inclusion of the lncScore enhances predictive power of traditional cytogenetic and mutation-defined stratification in pAML with potential, as a single assay, to replace these complex stratification schemes with comparable predictive accuracy.
Sudden arrhythmic death and cardiomyopathy are important causes of sudden cardiac death in the UK: results from a national coronial autopsy database

Sudden cardiac death (SCD) is defined as natural unexpected death in witnessed cases occurring < 1 h and in unwitnessed cases as last seen alive < 24 h. SCD due to ischaemic heart disease (IHD) is frequent in older age groups; in younger people genetic cardiac causes, including channelopathies and cardiomyopathies, are more frequent. This study aimed to present the causes of SCD from a large specialist pathology registry.
Temperature, productivity, and habitat characteristics collectively drive lake food web structure

While many efforts have been devoted to understand variations in food web structure among terrestrial and aquatic ecosystems, the environmental factors influencing food web structure at large spatial scales remain hardly explored. Here, we compiled biodiversity inventories to infer food web structure of 67 French lakes using an allometric niche‐based model and tested how environmental variables (temperature, productivity, and habitat) influence them. By applying a multivariate analysis on 20 metrics of food web topology, we found that food web structural variations are represented by two distinct complementary and independent structural descriptors. The first is related to the overall trophic diversity, whereas the second is related to the vertical structure. Interestingly, the trophic diversity descriptor was mostly explained by habitat size (26.7% of total deviance explained) and habitat complexity (20.1%) followed by productivity (dissolved organic carbon: 16.4%; nitrate: 9.1%) and thermal variations (10.7%). Regarding the vertical structure descriptor, it was mostly explained by water thermal seasonality (39.0% of total deviance explained) and habitat depth (31.9%) followed by habitat complexity (8.5%) and size (5.5%) as well as annual mean temperature (5.6%). Overall, we found that temperature, productivity, and habitat characteristics collectively shape lake food web structure. We also found that intermediate levels of productivity, high levels of temperature (mean and seasonality), as well as large habitats are associated with the largest and most complex food webs. Our findings, therefore, highlight the importance of focusing on these three components especially in the context of global change, as significant structural changes in aquatic food webs could be expected under increased temperature, pollution, and habitat alterations.
NUMERICAL STUDY OF THE EFFECT OF INLET GEOMETRY ON STRATIFICATION IN THERMAL ENERGY STORAGE

A finite difference computer code incorporating two methods of discretization for the advection terms in the flow governing conservation equations has been developed. These methods are the weighted upwind difference scheme (WUDS) and the second-order upwind difference scheme (SOUDS). Application of the code to a stratified thermal storage showed very good agreement between the experimental and the predicted temperature profiles when using SOUDS as opposed to WUDS. Investigation of the effect of inlet geometry on thermal stratification in a thermal storage tank was carried out using the SOUDS method. Results show that the effect of inlet geometry is negligible for Richardson numbers above 10. Thus a performance criterion for stratified thermal storage tanks with different inlet geometries has been established.
ARMA-based time-signature estimator for analyzing resonant structures by the FDTD method

We propose an algorithm for estimation of the optimal "system" parameters of time sequences (TSs) computed by the finite-difference time-domain (FDTD) method, with the goal of accurate representation of the time-signature using low-order models. The FDTD method requires computation of very long time sequences to accurately characterize the slowly decaying transient behavior of resonant structures. Therefore, it becomes critical to investigate methods of reducing the computational time for such objects. Several researchers have argued that the FDTD-TS can be modeled as the impulse response (IR) of an autoregressive moving average (ARMA) transfer function. However, it is known that determination of ARMA parameters by IR matching is a complex nonlinear optimization problem. Hence, many existing methods in EM literature tend to use Prony-based, linear predictor-type spectrum estimation algorithms, which minimize a linearized "equation error" criterion that approximates the true nonlinear model-fitting error criterion. As a result, significantly high model orders are needed by these methods to achieve good corroboration in the frequency domain, especially when a magnitude spectrum has deep nulls or notches. We propose to use a deterministic ARMA approach, which minimizes the true nonlinear criterion iteratively, and attains significantly improved IR fit over Prony's (1795) method using fewer ARMA model parameters. For a given time-sequence of an analyzed circuit, the issues of model order selection and choice of decimation factor are also addressed systematically. The improved performance of the proposed algorithm is demonstrated with transient simulation and signal analysis of microstrip structures which manifest deep nulls in the frequency domain.
The effects of delta‐9‐tetrahydrocannabinol administration in the regulation of female rat sociosexual behaviour

By targeting the endocannabinoid system, delta‐9‐tetrahydrocannabinol (THC) modulates female motivated behaviours, influenced by sex hormones. Both medial preoptic nucleus (MPN) and ventromedial nucleus of the hypothalamus (VMN) are involved in the modulation of female sexual responses. The first triggers proceptivity, whereas the ventrolateral division of the latter (VMNvl) triggers receptivity. These nuclei are modulated by glutamate, which inhibits female receptivity, and GABA, which has a dichotomous action in female sexual motivation. Here, we evaluated the action of THC on the modulation of social and sexual behaviours, on signalling pathways of MPN and VMNvl and how sex hormones influence these parameters. Young ovariectomized female rats, given sex hormones (oestradiol benzoate, EB, and progesterone, P) and THC were used for behavioural testing and for immunofluorescence analyses of vesicular glutamate transporter 2 (VGlut2) and GAD (glutamic acid decarboxylase)67 expression. Results showed that females given EB + P exhibited a higher preference for male partner, as well as higher proceptivity and a higher receptivity than control or females given only EB. Females treated with THC presented similar responses in control or EB + P female rats and even more facilitated behavioural responses in EB females than the ones that did not receive THC. Immunofluorescence results in the MPN exhibited a decreased expression of GAD67 and VGlut2 in EB + THC‐treated female rats. Within VMNvl of EB‐primed rats no changes in the expression of both proteins were observed after THC exposure. This study demonstrates how the possible outcomes of endocannabinoid system instability within hypothalamic neuron connectivity can modify female rat sociosexual behaviour.
Inverse power law potentials about polygonal prisms and in polygonal cavities

Abstract The effects on adsorption of the geometry of the solid may be studied through calculations based on a (distance)−ε (ε> 3) intermolecular potential. This paper establishes the result that the potential due to an infinitely long polygonal homogeneous solid prism, at position r in the plane of its right section, is – . Here ρi = ∣ r − ri ∣, where the ri are the position vectors of the n vertices of the polygon, and θij are the angles r − ri makes with the two sides of the polygon which meet at vertex ri. The g's are exact functions of θij. They are, in general, integrals of associated Legendre functions, but they are elementary for ε an even integer. A similar result holds for the potential within an infinitely long polygonal prismatic cavity. The analysis involves a systematic superposition schema and the concept of a supplementary potential with datum within the solid at infinity. The cases ε = 6 and ε = 4 are treated in detail and illustrative solutions given for the following configurations: semi-infinite laminae, deep rectangular cracks, square prisms, square prismatic cavities and regular n-gonal prismatic cavities.
Wearable Nanocomposite Sensor System for Motion Phenotyping Chronic Low Back Pain: A BACPAC Technology Research Site

Abstract Chronic low back pain (cLBP) is a prevalent and multifactorial ailment. No single treatment has been shown to dramatically improve outcomes for all cLBP patients, and current techniques of linking a patient with their most effective treatment lack validation. It has long been recognized that spinal pathology alters motion. Therefore, one potential method to identify optimal treatments is to evaluate patient movement patterns (ie, motion-based phenotypes). Biomechanists, physical therapists, and surgeons each utilize a variety of tools and techniques to qualitatively assess movement as a critical element in their treatment paradigms. However, objectively characterizing and communicating this information is challenging due to the lack of economical, objective, and accurate clinical tools. In response to that need, we have developed a wearable array of nanocomposite stretch sensors that accurately capture the lumbar spinal kinematics, the SPINE Sense System. Data collected from this device are used to identify movement-based phenotypes and analyze correlations between spinal kinematics and patient-reported outcomes. The purpose of this paper is twofold: first, to describe the design and validity of the SPINE Sense System; and second, to describe the protocol and data analysis toward the application of this equipment to enhance understanding of the relationship between spinal movement patterns and patient metrics, which will facilitate the identification of optimal treatment paradigms for cLBP.
EM Scattering from Complex Targets above a Slightly Rough Surface

A hybrid approach which combines the \four-path" model with a quasi-image method is developed in this paper to deal with the high frequency EM scattering problems of complex targets located above a slightly rough surface. The computation process of the multi- path scatterings in the \four-path" model is greatly simplifled by using the image targets to treat the shadowing efiects and a damped re∞ection coe-cient to correct the scattered fleld of the rough surface. The efiectiveness and e-ciency of this method are verifled by numerical results, which show that the proposed approach can be used to quickly and accurately evaluate the high frequency scattering from complex targets above a slightly rough surface. DOI: 10.2529/PIERS061212012947
On antenna impedances in a cold plasma with a perpendicular static magnetic field

A flat strip antenna is embedded in a magnetoionic medium with its longitudinal axis perpendicular to the static magnetic field. The antenna characteristics differ for antennas oriented with their surfaces parallel and perpendicular to the static magnetic field. In the former case there are no resistance peaks for frequencies near the plasma frequency and the reactance of a short antenna is capacitive for low frequencies. For frequencies near the gyrofrequency the antennas are electrically longer for the parallel orientation of their surfaces. The accuracy of the solutions is illustrated by computing the tangential electric surface fields that are excited by the approximate current distributions used in the impedance computations.
Slowly propagating instabilities in plasmas with Margenau-Davydov electron distribution function

The properties of certain wave modes excited in a weakly ionized plasma placed in an external d.c. electric field are analyzed from the standpoint of the linearized kinetic equation, the electron steady-state distribution function being taken in the form of the extended Margenau–Davydov and, in particular, Druyvesteinian. The presence of absolute stability cones formed by certain propagation directions is found. The corresponding critical values of the electron drift, destabilizing each of the modes considered, is also evaluated for a plasma with a Druyvesteinian distribution.
Overexpression of the pro‐protein convertase furin predicts prognosis and promotes papillary thyroid carcinoma progression and metastasis through RAF/MEK signaling

Furin belongs to the pro‐protein convertases (PCs) family and its aberrant expression has been documented in various types of cancers; however, its role in thyroid cancer remains unclear. We investigated the expression of furin in a large cohort of Middle Eastern papillary thyroid carcinoma (PTC) patient samples and explored its functional role and mechanism in PTC cell lines in vitro and in vivo. Furin overexpression was observed in 44.6% of all PTC cases and was significantly associated with aggressive clinicopathological parameters and poor outcomes. We show that the knockdown of FURIN suppresses tumor growth, proliferation, migration, invasion, spheroid growth, and progression of epithelial‐to‐mesenchymal transition (EMT) in B‐Raf proto‐oncogene, serine/threonine kinase (BRAF) mutant cells, whereas its overexpression in BRAF wild‐type PTC cell lines reversed the effect. FURIN knockdown in the BRAF mutant cell line led to reduced tumor growth and increased apoptosis. Mechanistically, FURIN knockdown led to MEK/ERK pathway suppression in BRAF mutant cells, although inhibition of MEK did not affect furin expression, which suggests that furin acts through the MEK/ERK pathway. Furthermore, our study revealed the synergistic antitumor effect of furin depletion and anti‐MEK inhibitor treatment. Overall, these results indicate that furin is an important prognostic marker in Middle Eastern PTC and that it plays a crucial role in BRAF‐associated MAP/ERK pathway activation and tumorigenesis. Furin inhibition could be a potential therapeutic target for aggressive PTC.