PD1+ T-cells correlate with Nerve Fiber Density as a prognostic biomarker in patients with resected perihilar cholangiocarcinoma.

Background & Aims: Perihilar cholangiocarcinoma (pCCA) is a hepatobiliary malignancy. Nerve fiber invasion (NFI) shows cancer invading the nerve and is considered an aggressive feature. Nerve fiber density (NFD) consists of small nerve fibers without cancer invasion and is divided into high NFD (high numbers of small nerve fibers) or low NFD (low numbers of small nerve fibers). We aim to explore differences in immune cell populations and survival. Approach & Results: We applied multiplex immunofluorescence (mIF) on 47 pCCA surgically resected patients and investigated immune cell composition in the tumor microenvironment (TME) of nerve fiber phenotypes (NFI, high and low NFD). Group comparison was performed and overall survival (OS) was assessed. The NFI Region of Interest (ROI) was measured with highest CD68+ macrophage levels among 3 ROIs (NFI compared to tumor free p= 0.016 and to tumor p=0.034) and PD1 expression on CD8 and were more abundant in the tumor rather than NFI ROI (p= 0.004 and p= 0.0029 respectively). NFD compared to NFI, demonstrated co-expression of CD8+PD1+ as well as CD68+PD1+ to be significantly higher in high NFD patients (p= 0.027 and p= 0.044, respectively). The high NFD OS was 92 months median OS (95% CI:41-142), for low NFD 20 months ((95% CI: 4-36) and for NFI 19 months (95% CI 7-33). High NFD OS was significantly better compared to low NFD (p= 0.046) and NFI (p= 0.032). Conclusions: PD1+ T-cells correlate with high NFD as a prognostic biomarker, the biological pathway behind this needs to be investigated.

Structural and Functional Characterization of Four Novel Fibrinogen Mutations in FGB Causing Congenital Fibrinogen Disorder

Congenital fibrinogen disorders are caused by mutations in genes coding for fibrinogen and may lead to various clinical phenotypes. Here, we present a functional and structural analysis of 4 novel variants located in the FGB gene coding for fibrinogen Bβ chain-heterozygous missense BβY416C and BβA68S, homozygous nonsense BβY345*, and heterozygous nonsense BβW403* mutations. The cases were identified by coagulation screening tests and further investigated by various methods. Fibrin polymerization had abnormal development with decreased maximal absorbance in all patients. Plasmin-induced fibrin degradation revealed different lytic phases of BβY416C and BβW403* than those of the control. Fibrinopeptide cleavage measured by reverse phase high pressure liquid chromatography of BβA68S showed impaired release of fibrinopeptide B. Morphological properties, studied through scanning electron microscopy, differed significantly in the fiber thickness of BβY416C, BβA68S, and BβW403*, and in the fiber density of BβY416C and BβW403*. Finally, homology modeling of BβA68S showed that mutation caused negligible alternations in the protein structure. In conclusion, all mutations altered the correct fibrinogen function or structure that led to congenital fibrinogen disorders.

Derivation of Yarn Package Radius Measuring System for Yarn Winding Machines

Decreasing waste materials through recycle has in the recent contributed to sustainable manufacturing in many textile industries for better resource utilization in textile mills. This has been given first priority in manufacturing, processing and finishing operations. Most of the time the yarn manufacturing and proper utilization of this material didn’t give attention in most companies. Especially yarn length variation of packages, weaving beams and copes have very critical impact on those companies which manufacture and utilize yarn products. This variation problem has great impact on their productivity and profitability. This paper describes the application of a new formula in the yarn packaging process and it is accomplished by derivation a new formula that can determine the radius of any package. The formula has integrated the basic characteristics of yarn and fiber including yarn diameter, yarn/ fiber density and mass of the yarn coiled on the cop. Finally we have concluded that package radius is the quadratic function of yarn density and package mass on the cope.

Ubim Fiber (Geonoma baculífera): A Less Known Brazilian Amazon Natural Fiber for Engineering Applications

The production of synthetic materials generally uses non-renewable forms of energy, which are highly polluting. This is driving the search for natural materials that offer properties similar to synthetic ones. In particular, the use of natural lignocellulosic fibers (NLFs) has been investigated since the end of 20th century, and is emerging strongly as an alternative to replace synthetic components and reinforce composite materials for engineering applications. NLFs stand out in general as they are biodegradable, non-polluting, have comparatively less CO2 emission and are more economically viable. Furthermore, they are lighter and cheaper than synthetic fibers, and are a possible replacement as composite reinforcement with similar mechanical properties. In the present work, a less known NLF from the Amazon region, the ubim fiber (Geonoma bacculifera), was for the first time physically characterized by X-ray diffraction (XRD). Fiber density was statistically analyzed by the Weibull method. Using both the geometric method and the Archimedes’ technique, it was found that ubim fiber has one of the lowest densities, 0.70–0.73 g/cm3, for NLFs already reported in the literature. Excluding the porosity, however, the absolute density measured by pycnometry was relatively higher. In addition, the crystallinity index, of 83%, microfibril angle, of 7.42–7.49°, and ubim fiber microstructure of lumen and channel pores were also characterized by scanning electron microscopy. These preliminary results indicate a promising application of ubim fiber as eco-friendly reinforcement of civil construction composite material.

Exploring electrospun nanofibers for physically unclonable functions: a scalable and robust method toward unique identifiers

Optical physical unclonable functions (PUFs) have great potentials in the security identification of Internet of Things. In this work, electrospun nanofibers are proposed as a candidate for a nanoscale, robust, stable and scalable PUF. The dark-field reflectance images of the polymer fibers are quantitatively analyzed by Hough transform. We find that the fiber length and orientation distribution reach an optimal point as the fiber density grows up over 850 in 400 x 400 pixels for a polyvinylpyrrolidone nanofiber based PUF device. Subsequently, we test the robustness and randomness of the PUF pattern by using the fiber amount as an encoding feature, generating a reconstruction success rate over 80% and simultaneously an entropy of 260 bits within a mean size of 4 cm2. A scale-invariant algorithm is adopted to identify the uniqueness of each pattern on a 256-sensor device. Furthermore, thermo-, moisture as well as photostability of the authentication process are systematically investigated by comparing polyacrylonitrile to polyvinylpyrrolidone system.

Spectral theory of approximate lattices in nilpotent Lie groups

We consider approximate lattices in nilpotent Lie groups. With every such approximate lattice one can associate a hull dynamical system and, to every invariant measure of this system, a corresponding unitary representation. Our results concern both the spectral theory of the representation and the topological dynamics of the system. On the spectral side we construct explicit eigenfunctions for a large collection of central characters using weighted periodization against a twisted fiber density function. We construct this density function by establishing a parametric version of the Bombieri–Taylor conjecture and apply our results to locate high-intensity Bragg peaks in the central diffraction of an approximate lattice. On the topological side we show that under some mild regularity conditions the hull of an approximate lattice admits a sequence of continuous horizontal factors, where the final horizontal factor is abelian and each intermediate factor corresponds to a central extension. We apply this to extend theorems of Meyer and Dani–Navada concerning number-theoretic properties of Meyer sets to the nilpotent setting.

Small Fiber Neuropathy in Sarcoidosis

Sarcoidosis (SC) is a granulomatous disease of an unknown origin. The most common SC-related neurological complication is a small fiber neuropathy (SFN) that is often considered to be the result of chronic inflammation and remains significantly understudied. This study aimed to identify the clinical and histological correlates of small fiber neuropathy in sarcoidosis patients. The study was performed in 2018–2019 yy and included 50 patients with pulmonary sarcoidosis (n = 25) and healthy subjects (n = 25). For the clinical verification of the SFN, the “Small Fiber Neuropathy Screening List” (SFN-SL) was used. A punch biopsy of the skin was performed followed by enzyme immunoassay analysis with PGP 9.5 antibodies. Up to 60% of the sarcoidosis patients reported the presence of at least one complaint, and it was possible that these complaints were associated with SFN. The most frequent complaints included dysfunctions of the cardiovascular and musculoskeletal systems and the gastrointestinal tract. A negative, statistically significant correlation between the intraepidermal nerve fiber density (IEND) and SFN-SL score was revealed. In patients with pulmonary sarcoidosis, small fiber neuropathy might develop as a result of systemic immune-mediated inflammation. The most common symptoms of this complication were dysautonomia and mild sensory dysfunction.

Energy-dense dietary patterns high in free sugars and saturated fat and associations with obesity in young adults

Purpose To derive dietary patterns based on dietary energy density (DED), free sugars, SFA, and fiber and investigate association with odds of overweight/obesity in young adults. Methods Cross-sectional data from 625 young Australian adults (18–30 years) were used. Dietary patterns were derived using reduced rank regression based on dietary data from a smartphone food diary using DED, free sugars, SFA, and fiber density as response variables. Multivariable logistic regression was used to investigate associations between dietary patterns and odds of self-reported overweight/obesity (BMI ≥ 25 kg/m2). Results Two dietary patterns were identified (DP1 and DP2). DP-1 was positively correlated with DED, free sugars, and SFA, and inversely correlated with fiber density. It was characterized by higher sugar-sweetened beverages intake and lower vegetable intake, and associated with higher odds of overweight/obesity (OR: 1.22; 95% CI 1.05, 1.42). DP-2 was positively correlated with fiber density and free sugars, and inversely correlated with DED and SFA. It was characterized by higher sugar-sweetened beverages intake and lower non-lean red meat intake, and was not significantly associated with overweight/obesity. Conclusion An energy-dense dietary pattern high in free sugars and SFA and low in fiber was associated with higher odds of obesity in young adults. These findings support dietary interventions that target reductions in energy-dense foods and sugar-sweetened beverages.

The Human SCN10AG1662S Point Mutation Established in Mice Impacts on Mechanical, Heat, and Cool Sensitivity

The voltage-gated sodium channel NAV1.8 is expressed in primary nociceptive neurons and is involved in pain transmission. Mutations in the SCN10A gene (encoding NAV1.8 channel) have been identified in patients with idiopathic painful small fiber neuropathy (SFN) including the SCN10AG1662S gain-of-function mutation. However, the role of this mutation in pain sensation remains unknown. We have generated the first mouse model for the G1662S mutation by using homologous recombination in embryonic stem cells. The corresponding Scn10aG1663S mouse line has been analyzed for Scn10a expression, intraepidermal nerve fiber density (IENFD), and nociception using behavioral tests for thermal and mechanical sensitivity. The Scn10aG1663S mutants had a similar Scn10a expression level in dorsal root ganglia (DRG) to their wild-type littermates and showed normal IENFD in hindpaw skin. Mutant mice were more sensitive to touch than wild types in the von Frey test. In addition, sexual dimorphism was observed for several pain tests, pointing to the relevance of performing the phenotypical assessment in both sexes. Female homozygous mutants tended to be more sensitive to cooling stimuli in the acetone test. For heat sensitivity, male homozygous mutants showed shorter latencies to radiant heat in the Hargreaves test while homozygous females had longer latencies in the tail flick test. In addition, mutant males displayed a shorter reaction latency on the 54°C hot plate. Collectively, Scn10aG1663S mutant mice show a moderate but consistent increased sensitivity in behavioral tests of nociception. This altered nociception found in Scn10aG1663S mice demonstrates that the corresponding G1662 mutation of SCN10A found in SFN patients with pain contributes to their pain symptoms.

Microstructural Tissue Changes in a Rat Model of Mild Traumatic Brain Injury

Our study investigates the potential of diffusion MRI (dMRI), including diffusion tensor imaging (DTI), fixel-based analysis (FBA) and neurite orientation dispersion and density imaging (NODDI), to detect microstructural tissue abnormalities in rats after mild traumatic brain injury (mTBI). The brains of sham-operated and mTBI rats 35 days after lateral fluid percussion injury were imaged ex vivo in a 11.7-T scanner. Voxel-based analyses of DTI-, fixel- and NODDI-based metrics detected extensive tissue changes in directly affected brain areas close to the primary injury, and more importantly, also in distal areas connected to primary injury and indirectly affected by the secondary injury mechanisms. Histology revealed ongoing axonal abnormalities and inflammation, 35 days after the injury, in the brain areas highlighted in the group analyses. Fractional anisotropy (FA), fiber density (FD) and fiber density and fiber bundle cross-section (FDC) showed similar pattern of significant areas throughout the brain; however, FA showed more significant voxels in gray matter areas, while FD and FDC in white matter areas, and orientation dispersion index (ODI) in areas most damage based on histology. Region-of-interest (ROI)-based analyses on dMRI maps and histology in selected brain regions revealed that the changes in MRI parameters could be attributed to both alterations in myelinated fiber bundles and increased cellularity. This study demonstrates that the combination of dMRI methods can provide a more complete insight into the microstructural alterations in white and gray matter after mTBI, which may aid diagnosis and prognosis following a mild brain injury.